MODULES

M8.1.1
1. Respiratory Problems; ENT &
Eye Problems
Antenatal care
2. Child & Adolescent; GI Problems

3. Chronic Disease Management,

Haematology, Oncology, & 1. INTRODUCTORY COMMENTS (M8.1.1R1) … 2
Palliative Care

4. Elder Care; Mental Health 2. PRECONCEPTION HEALTH CARE

(M8.1.1R2) ........................................................... 3
5. Health Promotion & Disease
Prevention; Skin Problems & STI
3. ROUTINE ANTENATAL CARE (M8.1.1R3) ..... 11
6. Work Related Health; Renal,
Urological, & Endocrine
Problems 4. COMMON QUESTIONS PATIENTS ASK
(M8.1.1R4) ……………………………………. 18
7. Women’s Health (Gynae);
Emergent Problems & Acute
Medicine 5. ANTENATAL TESTING & PRENATAL
SCREENING (M8.1.1R5) ………………………. 23
8. Women’s Health (Obst); Neuro-
muscular Disorders
6. USE OF ULTRASOUND IN PREGNANCY
8.1 WOMEN’S HEALTH (M8.1.1R6) ……………………………………. 29
(OBSTETRICS)

7. DRUG USE IN PREGNANCY (M8.1.1R7) ……. 33

8.1.1 - Antenatal care

8.1.2 - Medical disorders of 8. CASE STUDIES (M8.1.1CS) ...………………… 38

pregnancy

8.1.3 - Complications in pregnancy

8.1.4 - Postnatal care

8.2 NEUROMUSCULO
SKELETAL PROBLEMS

8.2.1 - Acute musculoskeletal

problems

8.2.2 - Chronic musculoskeletal

problems

8.2.3 - Acute neurological problems

8.2.4 - Chronic neurological

problems

College of Family Physicians Singapore THE INSTITUTE OF FAMILY MEDICINE

College of Medicine Bldg
College of Family Physicians Singapore
16 College Road #01-02
Singapore 169854 FAMILY MEDICINE TRAINING
Tel: 6223 0606 Fax: 6222 0204 PROGRAMME (FMTP)
Email: contact@cfps.org.sg © College of Family Physicians Singapore.
Website: http://www.cfps.org.sg All Rights Reserved 2014
 M8.1.1R1
INTRODUCTORY COMMENTS

INTRODUCTION

The chief objective of antenatal care is to ensure good pregnancy outcome. Women should be counselled
on five aspects: genetic risks; screening for infectious diseases; avoidance of environmental toxins such
as cigarette smoke, alcohol, solvents and pesticides; chronic disease control; and lifestyle: exercise,
obesity, nutritional adequacy and caution in the use of medications in pregnancy. One important goal is to
recognize the women who have high risk pregnancies and to triage these to appropriate care.

Antenatal care practices are being rationalized and it is useful to be updated on the pros and cons of
proposed changes. NICE (National Institute of Clinical Excellence) guidelines released in 2003 advised
fewer visits and also earlier first visits. There is an advocacy for the shift of prenatal screening from
second trimester to first trimester.

Symptoms of pregnancy, routine antenatal assessment, advice on ultrasound in assessing foetal growth
and well-being; and advice on when the patient should be referred to the specialist for further
management are common reasons for encounter with the primary care doctor.

LEARNING OBJECTIVES

At the end of this study unit the course participant should be able to describe:
1. the principles of preconception health care.
2. routine antenatal care.
3. common symptoms of pregnancy and their management.
4. the investigations used during antenatal care for diagnosis and monitoring.
5. commonly used drugs that a pregnant patient may need to use and those that should be avoided.

CASE STUDIES

The case studies will focus on the principles of antenatal care.

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 M8.1.1R2
PRECONCEPTION HEALTH CARE

INTRODUCTION

Preconception care refers to interventions that aim to identify and modify biomedical, behavioural,
environmental and social risks to a woman's health or pregnancy outcome through prevention and
management. Preconception evaluation and counselling provide an opportunity to inform women about
fertility/pregnancy issues, identify some of the risks of pregnancy for the mother and foetus, educate them
about these risks, and institute appropriate interventions, when possible, before conception.

A case for preconception health care counselling can be made. Many women have their first visit for
prenatal care at eight weeks of pregnancy or later, yet the period of time before the first prenatal visit
carries the most risk to fetal development. A survey of patients in a family practice residency clinic
showed that 52 percent of 136 women with a negative pregnancy test had a medical risk that could
adversely affect a future pregnancy (Jack et al, 1995; Brundage, 2002).

Optimizing the health of the mother before conception is important for improving pregnancy outcome.
This is particularly true for certain populations of women, such as those with medical disorders (eg,
diabetes mellitus, phenylketonuria), nutritional deficiencies (eg, folate), and exposure to toxins or
teratogens (eg, cigarettes, alcohol, warfarin, isotretinoin), in whom preconception care has been shown to
reduce neonatal morbidity and mortality.

Preconception care can be an essential part of primary and preventive care, rather than an isolated visit.
Preconception assessment could be offered to women who request pregnancy testing and family planning
advice. Preconception issues could also be addressed during work physicals and at follow-up visits for
patients with chronic diseases (Swan & Apgar, 1995; Brundage, 2002). Other potential opportunities for
preconception counselling include visits for premarital examination and testing; evaluation for sexually
transmitted disease or vaginal infection; and anytime a woman of childbearing age presents for a periodic
health examination.Written materials on preconception health care could be made available in waiting
and examination rooms.

Family planning is an essential component of preconception care and allows optimal opportunity for
health promotion and preventive care. Primary care clinicians should consider asking all patients of
reproductive age about intention to become pregnant and providing contraceptive counseling tailored to
patients' intentions, specific characteristics and medical conditions.

For primary care physicians, caring for a woman of reproductive age should include identifying health
risks to her and her future children, and implementing interventions to reduce these risks. General issues
in preconception care include (Farahi, 2013; Brundage, 2002):

 Genetic risk counselling

 Nutritional considerations
 Lifestyle modification
 Infectious disease control
 Environmental toxin risk avoidance
 Chronic disease control

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GENETIC RISK COUNSELLING

The physician should screen for personal or family history of congenital anomalies or genetic disorders.
Couples should be referred for genetic counseling when risk factors are identified, and carrier testing
provided when appropriate to determine risk to future pregnancy e.g. in conditions such as thalassemia.

Many women are postponing child bearing until after age 35 years, which poses a higher risk of medical
problems during pregnancy and chromosomal abnormalities in the foetus. Older couples should be
counselled about genetic risks and the availability of antenatal testing (amniocentesis and chorionic
villous sampling), which may not be options if the first visit for prenatal care is delayed. The risk of
infertility also increases with age, rising to 20 percent in couples older than 35 years (Brundage, 2002).

NUTRITIONAL CONSIDERATIONS

Folic Acid
The neural tube closes between 18 and 26 days after conception so folic acid supplementation after the
diagnosis of pregnancy is usually too late to reduce the risk of neural tube defects (Sackey, 2014). Folic
acid supplementation of 400 mcg daily started before pregnancy and continued until six to 12 weeks
postconception reduces the rate of neural tube defects by nearly 75%. One study showed that women
receiving preconception counseling from their primary care physicians are five times more likely to take
folic acid before conception. (Farahi, 2013)

Women taking folic acid antagonists or who have carried a fetus affected by a neural tube defect or other
birth defects linked with folic acid deficiency (e.g., oral facial cleft, structural heart disease, limb defect,
urinary tract anomaly, hydrocephalus) should take 4 to 5 mg of folic acid daily starting three months
before conception and continuing until 12 weeks postconception. Women with certain health risks (e.g.,
epilepsy, insulin-dependent diabetes mellitus, obesity with a body mass index greater than 35 kg per m2,
family history of a neural tube defect) should also take this higher dosage. (Farahi, 2013)

Overweight
Women who are overweight or obese are at risk of diabetes, gestational diabetes, and hypertension. These
conditions are associated with adverse pregnancy outcomes, including macrosomia, shoulder dystocia,
operative delivery, congenital anomalies, intrauterine growth restriction, spontaneous abortion, stillbirth,
preeclampsia, and eclampsia.

Women who are overweight or obese are more likely to have difficulty with conception because of
insulin resistance and oligomenorrhea. Weight loss and medications can improve these symptoms, as well
as fertility. (Farahi, 2013)

Underweight
Low pre-pregnancy weight (BMI less than 18.5 kg per m2) is associated with preterm birth and low birth
weight. Low body weight is also associated with nutrient deficiencies, osteoporosis, amenorrhea,
infertility, and arrhythmias. Infants whose mothers had low pre-pregnancy body weight are at higher risk
of gastroschisis. Women with low BMI should be assessed for eating disorders and counseled about how
being underweight can affect their health and pregnancy. (Farahi, 2013)

Diet and Supplements

Vegetarians who consume eggs or dairy products usually have no nutritional deficiency; however, strict
vegans may have deficiencies in amino acids, zinc, calcium, iron, and vitamins D and B12. Such patients
may need to be referred to a nutritionist who can recommend proper food selection and supplementation.
Milk intolerance may result in calcium deficiency. These women may be able to tolerate yogurt or cooked
cheese. They can also benefit from using lactose-reduced milk, lactase tablets, or calcium supplements
(Brundage, 2002).

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Megavitamins, nonessential dietary supplements, and herbal preparations should be discontinued, given
that the risk to the fetus from such substances has generally not been evaluated (Sackey, 2014).
Overdoses of vitamin A, vitamin D, and caffeine may be toxic. Vitamin A is teratogenic in dosages of
20,000 to 50,000 IU per day. The FDA recommends a limit of 3,000 IU per day. Dosages of vitamin D
greater than 1,600 to 2,000 IU per day may cause foetal hypercalcemia and growth retardation. Women
should not exceed total dosages of 400 IU per day of vitamin D alone or combined in calcium
supplements or multiple vitamins (Brundage, 2002). It may be prudent for women who are attempting to
conceive or who are pregnant to limit caffeine consumption to less than 200 to 300 mg per day (two cups
of coffee or six glasses of tea or soda). Higher amounts of caffeine may be associated with increased rates
of abortion and low birth weight (Klebanoff et al, 1999; Brundage, 2002).

Common mineral deficiencies in women of childbearing age include iron and calcium (40 percent of
menstruating women have deficient iron stores). A daily prenatal vitamin containing 30 mg of elemental
iron is sufficient when combined with a diet that includes meats and other foods high in iron. Before
conception, women need 1,200 mg of calcium per day, or the equivalent of a quart of milk or fortified
orange juice, or six servings of fortified bread or cereals (Brundage, 2002).

Patients should be counseled about avoiding mercury exposure by not consuming large fish (e.g., shark,
swordfish, tilefish, king mackerel) and limiting other fish intake (Farahi, 2013). Only cooked fish should
be eaten (Sackey, 2014).

LIFESTYLE MODIFICATIONS

Exercise
Regular moderate exercise is generally beneficial and has not been found to increase the risk of low birth
weight or other problems. In the first trimester, hyperthermia related to hot tub use has been associated
with increases in congenital anomalies. Pregnant women should limit vigorous exercise to avoid an
increase in core body temperature above 38°C (100.4°F). They should be adequately hydrated, wear loose
clothing, and avoid extreme environmental temperatures. (Brundage, 2002)

Smoking
Smoking increases the risk of miscarriage, low birth weight, perinatal mortality, and attention-deficit
disorder in the child. Smoking should be screened for and patients counseled about the effect of smoking
on pregnancies and child health. Smoking cessation treatment should be provided when needed. The
physician can recommend behavioural techniques, support groups, and family help. Pharmacotherapy
(nicotine replacement therapy and bupropion) may be helpful. If the patient cannot stop smoking, the
physician should help her set a goal to decrease her number of cigarettes to fewer than 10 per day,
because many of the adverse effects are dose-related.

Alcohol
Alcohol abuse can cause mental retardation, malformation, growth retardation, miscarriage, and
behavioural disorders in infants (Brundage, 2002). There are no data to establish a safe threshold for
alcohol consumption during pregnancy, thus the safest course of action is to abstain entirely. Patients with
alcohol dependence should be treated through interventional counselling, usually by referral to a
treatment program.

Substance abuse
Women using illegal drugs such as cocaine, marijuana, or heroin will need help quitting before
pregnancy. Cocaine use is associated with miscarriage, prematurity, growth retardation, and congenital
defects. Marijuana can cause prematurity and jitteriness in the neonate. Use of heroin may lead to
intrauterine growth restriction, hyperactivity, and severe neonatal withdrawal syndrome. Even a single
teaching session about how drug use affects the foetus, along with reinforcement at subsequent visits,
usually helps women who occasionally use drugs. Women who use drugs daily should be referred to a
substance abuse treatment program. Periodic urine drug testing may help to encourage abstinence.
Women who use heroin should be referred to a supervised withdrawal program to be completed before
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conception. A methadone maintenance program is an alternative if the patient is unable to complete the
withdrawal. (Brundage, 2002)

Psychosocial Factors
Domestic violence is reportedly underdiagnosed, and the incidence escalates during pregnancy.
Physicians should routinely ask about domestic violence using non-judgmental questions. Validating the
woman's concerns and providing a supportive physician-patient relationship are key factors in helping
women to leave a violent relationship (Brundage, 2002). The patient's safety should be evaluated, and
referral to appropriate resources provided.

A couple's readiness for children and the availability of sufficient financial resources should be discussed.
Physicians may choose to discuss the effect of pregnancy on the mother's work income. If she has a job
that requires prolonged standing, will she be able to transfer to a more sedentary job in the last trimester
of pregnancy? How will the family handle the loss of her income if she develops complications that
require her to take time off? The couple should be advised to learn about their employers' policies
regarding parental leave benefits as well as the maternity coverage of their health insurance plan
(Brundage, 2002).

INFECTIOUS DISEASE CONTROL

Infectious disease control in preconception care involves screening, treating, immunisation and
counselling.

Sexually Transmitted Infections (STI)

Preconception testing for human immunodeficiency virus (HIV) is important for those at risk. Patients
should be counseled about the risk of vertical transmission of HIV and that treatment reduces this risk.
Screening for syphilis should also be performed for high-risk women. Earlier treatment of HIV and
syphilis decreases the risk of transmission to the foetus. Other STIs which may require screening and
treatment in women at risk include chlamydia, gonorrhoea and herpes simplex virus infection.

Tuberculosis
High-risk women should be screened and women with active and latent disease treated before pregnancy.

Hepatitis B
Women who have not received the hepatitis B vaccine should be considered for immunization before
pregnancy. Serologic testing of hepatitis B should be done prior to vaccination as some women may have
a positive titre due to prior subclinical disease. This can also identify carriers or infected persons who will
benefit from follow-up and treatment. Chronic carriers should be counseled about prevention of vertical
transmission. (Farahi, 2013).

Measles, Mumps, Rubella, Varicella

Screening for immunity can be carried out and all nonimmune women who are not pregnant should be
recommended vaccination. Patients should be counseled to avoid pregnancy for three months after
vaccination (one month for varicella). (Farahi, 2013)

Influenza
Influenza vaccination is recommended for women who will be pregnant during influenza season and
women at risk of influenza-related complications. Influenza is particularly morbid in pregnant women, as
it increases the risk of serious medical complications and hospitalization.

Toxoplasmosis, CMV & Parvovirus B19

Toxoplasmosis, cytomegalovirus (CMV), and parvovirus B19 (fifth disease) may cause congenital
infections if the mother becomes infected during pregnancy. Currently, no immunizations are available
for these infections. Toxoplasmosis is a parasite commonly found in raw meat or cat faeces. New owners
of cats that go outside the house are most at risk. Women should be counselled to avoid contact with cat
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faeces in litter boxes, wear gloves while gardening, and avoid eating raw or undercooked meat. CMV
exposure is especially risky for child care and health care workers. Persons at risk should wash their
hands frequently and use gloves to prevent transmission. Parvovirus B19 is transmitted by prolonged
close contact with small children who have the disease in household or child care settings. (Brundage,
2002)

ENVIRONMENTAL TOXIN RISK AVOIDANCE

Adverse reproductive and developmental outcomes from exposure to toxic agents include: abnormal
sperm, menstrual disorders, infertility, spontaneous abortion, stillbirth or infant death, low birth weight,
congenital malformations, developmental delays, and childhood cancer.

The fetus is more susceptible to environmental toxins than adults. Table 1 shows the environmental toxin
risks to be avoided. Exposures to hazardous substances at work need to be avoided. Ionizing radiation,
including that from exposure to radiography and radioactive materials, is associated with genetic damage
when delivered at high levels to the developing embryo. In the home, pregnant women should avoid
prolonged exposure to pesticides and to solvents such as paint thinners and strippers (Gjerdingen &
Fontane, 1991; Brundage, 2002). Microwaves, ultrasound, and radio waves are nonionizing and safe.

Endocrine disruptors are chemicals that mimic or disrupt the action of naturally occurring hormones.
Some of these substances have estrogenic effects or anti-androgenic effects, and may have effects on
reproductive and developmental outcomes in human and wildlife populations. Studies are in progress
looking at the effects of contaminants that leach from plastics such as bisphenol A and phthalates,
commonly found in many consumer products. (Goldman, 2014)

TABLE 1. ENVIRONMENTAL TOXIN RISK AVOIDANCE

Metals
 Lead -- result in abnormal sperm, menstrual disorders, miscarriages, stillbirths, mental retardation. Sources: Solder, lead
pipes, batteries, paints, ceramics, smelter emissions
 Mercury -- result in impaired foetal motor and mental development. Sources: Thermometers, mirror coating, dyes, inks,
pesticides, dental fillings, fish from contaminated waters
Solvents
 Trichloroethylene, chloroform, benzene, toluene -- result in birth defects. Sources: Dry cleaning fluids, degreasers, paint
strippers, drug and electronics industries
Plastics
 Vinyl chloride -- result in decreased fertility, chromosomal aberrations, miscarriages, stillbirths, birth defects. Sources:
Plastic manufacturing
Pollutants
 Polychlorinated biphenyl, polybrominated biphenyl -- result in low birth weight, stillbirths. Sources: Pesticides; carbonless
copy paper; rubber, chemicals, and electronics industries; fire retardants; food chain
Pesticides
 2,4,5-T and 2,4-D organophosphates – result in birth defects, miscarriages, low birth weight. Sources: Farm, home, and
garden insect sprays; wood treatment
Gases
 Carbon monoxide -- result in low birth weight, stillbirths. Sources: Auto exhaust, furnaces, kerosene heaters, cigarette
smoke
 Anaesthetic gases – result in decreased fertility, miscarriages, and birth defects. Sources: Dental offices, operating
rooms, chemicals industries
Radiation
 Radiographs, radioactive materials -- result in sterility, birth defects. Sources: Medical and dental offices, electronics
industries
Source: Cefalo RC, Moos MK. Preconceptional health promotion. In: Cefalo RC, Moos MK, eds. Preconceptional health care: a
practical guide. 2d ed. St. Louis: Mosby, 1995:41-2; Brundage, 2002.

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CHRONIC DISEASE CONTROL

Medications
Women should be assessed for the use of teratogenic medications. As an example, isotretinoin, used in
the treatment of acne, should be avoided as it is associated with miscarriage and birth defects.

Women with chronic diseases should switch to safer medications when possible, and use the fewest
medications at the lowest dosages needed to control the disease.

Diabetes Mellitus
Women whose diabetes is poorly controlled (defined as glycosylated hemoglobin [HbA1C] levels higher
than 8.4 percent) have a 32 percent rate of spontaneous abortion and a sevenfold increased risk of severe
foetal anomalies compared with women who have good control. Intensive diabetic management starting
before conception decreases the risk of abortions and congenital anomalies and lessen complications of
pregnancy (Brundage, 2002).

Insulin has long been the drug of choice for women with type 1 and type 2 diabetes mellitus during
pregnancy. Research on the use of glyburide (Micronase) in patients with gestational diabetes shows
promise for a future role of oral agents in women with pre-existing diabetes (Langer et al, 2000;
Brundage 2002). Table 2 lists the goals of the preconception visit for women who have diabetes.

TABLE 2. PRECONCEPTION CARE FOR WOMEN WITH DIABETES MELLITUS

 Use contraception until excellent glucose control is achieved
 Train in self-monitoring and balancing food intake, exercise, and insulin
 Transition to insulin (type 2 diabetes)
 Give the patient specific goals: Fasting glucose, 60 to 100 mg per dL (3.3 to 5.6 mmol per L); Two-hour postprandial
glucose, 100 to 120 mg per dL (5.6 to 6.7 mmol per L); HbA1C within normal range for local laboratory
 Identify, evaluate, and treat: Hypertension; Nephropathy; Retinopathy; Thyroid disease; Hyperlipidemia
 Counsel on risks of pregnancy, requirement for increased visits, and close monitoring
 Evaluate for relative contraindications to pregnancy: Blood urea nitrogen greater than 30 mg per dL (10.7 mmol per L);
Creatinine clearance less than 30 mL per minute (0.5 mL per second); Coronary artery disease

Source: Brundage, 2002; Information from Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of
diabetes, congenital malformations, and spontaneous abortions. Diabetes Care 1996;19:514-41, and American Diabetes
Association. Preconception care of women with diabetes. Diabetes Care Jan 2003;26:Suppl 1;S91-S93. HbA1C = glycosylated
hemoglobin.

Hypertension
Chronic hypertension in pregnancy is associated with higher rates of preterm birth, placental abruption,
intrauterine growth restriction, preeclampsia, and fetal death. Women with chronic hypertension are at
risk of worsening hypertension and end-organ damage, and 25% of women with hypertension develop
superimposed preeclampsia during pregnancy. Women with long-standing hypertension who are planning
pregnancy should be assessed for retinopathy, renal disease, and ventricular hypertrophy. (Farahi, 2013)

Caring for women of reproductive age with hypertension should include educating them about the risks of
hypertension during pregnancy and that their medication regimen may need to be changed before
conception. Methyldopa (Aldomet) and calcium channel blockers are commonly used during pregnancy.
Drugs to be avoided during pregnancy are angiotensin-converting enzyme inhibitors, angiotensin II
receptor antagonists, and thiazide diuretics, which are associated with congenital defects (Brundage,
2002).

Epilepsy
Children of mothers with epilepsy have a 4 to 8 percent risk of congenital anomalies, which may be
caused by anticonvulsant medication or may be related to an increased genetic risk (Brundage, 2002).

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Preconception counselling should include optimizing seizure control, prescribing folic acid supplements
(4 mg of folic acid daily should be initiated at least one month before conception and continued in the
first trimester), and offering referral to a genetic counsellor if required.

Many major antiepileptic drugs (e.g., valproate, phenytoin, carbamazepine, phenobarbital) are teratogenic
(Farahi, 2013). Rates of congenital anomalies are related to higher doses and polytherapy (Farahi, 2013).
Physicians should aim to use the best single agent for the seizure type at the lowest protective level. There
is no single drug of choice. The older agents are classified as FDA pregnancy risk category D, and the
newer agents are poorly studied (Brundage, 2002). Because there are no clear data indicating that any
drug is without risk in pregnancy, patients planning pregnancy should be managed on the most effective
antiepileptic drug for their seizures. As an exception, valproate should be avoided if an alternate effective
antiepileptic drug regimen can be found, as results suggest a trend toward higher teratogenicity with
valproate than with other antiepileptic drugs (Schachter, 2013).

If the patient has been seizure-free for two years or longer, drug discontinuation with a long taper period
(three months) may be successful (Brundage, 2002).

Thromboembolism
Women who have a personal or family history of venous thromboembolism should be offered testing for
thrombophilia before pregnancy. Women with a history of a deep venous thrombosis (DVT) have a 7 to
12 percent risk of recurrence during pregnancy. Heparin (in regular or low-molecular-weight form) is
indicated for prophylaxis and should be started as early in pregnancy as possible. Women receiving
warfarin as maintenance therapy for DVT should be switched to heparin before conception, because
warfarin is teratogenic. (Brundage, 2002)

Thyroid Disease
Thyroid disease can significantly impact pregnancy outcomes. Hypothyroidism affects 2.5% of women of
reproductive age, and even more have subclinical disease. Many patients with hypothyroidism are
inadequately treated. Hypothyroidism in the first trimester is associated with cognitive impairment in
children. Hypothyroidism (clinical and subclinical) in pregnant women increases the risk of preterm birth,
low birth weight, placental abruption, and fetal death.

Women who are adequately treated before pregnancy and those diagnosed and treated early in pregnancy
have no increased risk of perinatal morbidity. It is essential to monitor women on thyroid replacement
therapy and educate them about its impact on pregnancy. During pregnancy, thyroid replacement dosages
typically need to be increased by four to six weeks' gestation, possibly by 30% or more. Routine
screening for subclinical hypothyroidism is not recommended; however, women with risk factors and
symptoms of thyroid diseases should be screened, and subclinical hypothyroidism should be treated.

Hyperthyroidism can result in significant maternal and neonatal morbidity, and outcomes correlate with
disease control. Guidelines recommend achieving euthyroidism before pregnancy. (Farahi, 2013)

Asthma
Women with poorly controlled asthma before pregnancy are more likely to experience worsening
symptoms during pregnancy. Poorly controlled asthma poses risks to the fetus, such as neonatal hypoxia,
intrauterine growth restriction, preterm birth, low birth weight, and fetal and neonatal death.
Preconception care should focus on optimizing asthma control with medications, and identifying and
reducing exposure to allergens. Patients should be counseled on smoking cessation and avoidance of
secondhand smoke exposure. (Farahi, 2013)

Inhaled corticosteroids and beta agonists are preferred. Use of oral corticosteroids in the first trimester is
associated with reduced birth weight, increased risk of oral cleft, and higher rates of preeclampsia.
Inhaled corticosteroids are recommended for preventive treatment and may avoid the need for oral
treatment. When oral corticosteroids are indicated for treatment of severe asthma, the risk of uncontrolled
severe asthma to the mother and fetus is greater than the risk of oral corticosteroids. (Farahi, 2013)

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Depression & Anxiety
Screening for depression and anxiety disorders is recommended. About 10 percent of pregnant women
have depression. Patients should be counselled about the risks of untreated depression during pregnancy,
as well as the risks of treatment. Tricyclic antidepressants and selective serotonin reuptake inhibitors have
generally not been shown to cause any teratogenic effects and may be used before conception (Brundage,
2002). Several studies have, however, reported an association between paroxetine exposure and
cardiovascular defects. These findings remain controversial and await confirmation by other studies
(Shaila Misri, 2013). Withdrawal syndromes can occur in neonates whose mothers are treated with
tricyclic antidepressants and selective serotonin reuptake inhibitors near the time of delivery.

Maternal use of benzodiazepines has been associated with a withdrawal syndrome in the newborn
(Brundage, 2002). Also, pooled data from case-control studies show that exposure to benzodiazepines in
early pregnancy may increase the risk of major malformations and oral cleft. Benzodiazepines should be
avoided in pregnancy (MOH CPG, 2011).

Reference
1. Brundage SC. Preconception health care. Am Fam Physician 2002;65:2507-14,2521-2
2. Farahi N et al. Recommendations for Preconception Counseling and Care. Am Fam Physician. 2013 Oct 15;
88(8):499-506
3. Sackey JA. The preconception office visit. UpToDate. 2014
4. Rose H Goldman. Occupational and environmental risks to reproduction in females. UpToDate. 2014
5. Steven C Schachter. Management of epilepsy and pregnancy. UpToDate. 2013
6. Shaila Misri et al. Depression in pregnant women: Management. UpToDate. 2013
7. Diana Rodriguez-Thompson. Smoking and pregnancy. UpToDate. 2013
8. Tan Thiam Chye et al. Practical Obstetrics and Gynaecology Handbook for the General Practitioner. 2006
9. Tao Le et al. First Aid in Family Medicine Boards. McGraw Hill: New York. 2008
10. MOH Clinical Practice Guidelines 2011. Bipolar Disorder. 2011

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 M8.1.1R3
ROUTINE ANTENATAL CARE

INTRODUCTION

Aims Of Antenatal Care

The Aims of Antenatal Care are:
 To provide advice, reassurance, education and support for the pregnant woman and her family
 To deal with the minor ailments of pregnancy
 To detect, prevent, and manage any factors which may adversely affect the health of the mother and
her baby
 To provide an on-going screening program
 To identify the high risk pregnancy and to direct this to appropriate management.

Shared Antenatal Care

One purpose of shared antenatal care is to reduce the burden on overcrowded antenatal clinics. There are
other advantages.

The advantages of GP care

 First line of contact
 Good knowledge of the patient's medical history, and dynamics of her family. Hence he or she is in a
better position to know the antenatal patient’s needs

The advantages of OG specialist care

 Good knowledge in that area of obstetrics care
 Access to tertiary level investigations e.g. ultrasound scans
 Access to tertiary level medical supports e.g. high risk pregnancy consultation, and neonatal support

In Singapore, the shared antenatal care programme is variable in practice. There may be a place to work
towards such a system of care but this will depend on the collaboration of participating family physicians
and obstetricians.

Example of workable programme

The Australian Family Physician reports (Gunn J, 2003) that successful shared care programmes operate
in most states and territories in Australia. The Geelong programme launched in 1999 has:
 Formalized accreditation processes
 Increased communication between hospital staff and family physicians
 Introduced a patient held medical record
 Introduced written guidelines and protocols, and
 Addressed many issues in the process of care.

THE ROLE OF GP IN ANTENATAL CARE

These include:
 Diagnosis of pregnancy
 Assessment of risk factors
 Basic investigations
 Counselling
 Dating of the pregnancy
 Extrapolation of antenatal follow up plan
 Follow up
 Obstetric referral

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Diagnosis of Pregnancy
Amenorrhea is the cardinal sign of early pregnancy. However, many women present with symptoms of
pregnancy even before they have noticed any abnormality in their menstrual cycle. Common symptoms
include breast tenderness, fatigue, and nausea or vomiting. Signs on physical examination in the early
first trimester include Chadwick’s sign (blue cervix) or Goodell’s sign (cervical softening) and uterine
enlargement.

Definitive diagnosis of pregnancy is made by urine qualitative hCG assay (approximately 98% sensitive 7
days after implantation), serum quantitative beta-hCG assay (sensitive 4-5 days after implantation), or
pelvic ultrasound ( a gestational sac is usually visible at 4.5 to 5 weeks after the last menstrual period).

The presence of vaginal bleeding or pelvic/abdominal pain would warrant an immediate referral to
exclude ectopic pregnancy or spontaneous/incomplete/missed abortion.

Assessment of Risk Factors

The aim of a formal risk scoring system in pregnancy is to permit the classification of women into
different categories so that appropriate individual management strategies can be implemented.

The risk profile is gleaned from

 General risk factors
 Past obstetric history
 Past medical, surgical, gynaecological history
 Family history
 Problems arising in current pregnancy
 Examination findings
 Investigations

History
The history at the first visit should include:
 Symptoms – in the current pregnancy, if any. Check for abnormal bleeding, pelvic or abdominal pain,
hormone therapy and recent illness with rash.
 Confirmation of pregnancy – check if pregnancy test has been done (see above: diagnosis of
pregnancy).
 Menstrual history – check for regularity and duration of cycles. The estimated date of delivery (EDD)
can be calculated (see below: dating of pregnancy).
 Medical History – diabetes mellitus, hypertension, heart disease, bronchial asthma, thyrotoxicosis,
epilepsy, other medical conditions, and any medications prescribed.
 Obstetric History – number of pregnancies, number of living children, abortions, stillbirth, problems
during past pregnancies and deliveries (large baby, or preterm delivery), birth weight.
 Gynaecological History – cervical smear, contraception
 Family History – multiple pregnancy, diabetes mellitus, hypertension, thalassemia, Down’s
syndrome, congenital problems.
 Social History – socio-economic status, occupation of the woman and her spouse.
 Habits – smoking, alcohol intake and drug abuse, exposure to toxic substances or radiation.

Physical Examination
The physical examination at the first visit should include:
 Height – a very short patient (<1.5 m) is at risk for cephalo-pelvic disproportion.
 Weight – useful as baseline reading to assess weight gain later in pregnancy.
 Blood pressure, heart and lungs, thyroid.
 Breasts – retracted or inverted nipples, breast lumps.
 Abdomen – scars of previous operations, masses.

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 Vaginal examination (recommended at first trimester but not routine) – speculum examination where
necessary; bimanual examination for uterine size and pelvic masses. This may be replaced by an
ultrasound examination.

Investigations (more details in M8.1.1R5):

Basic investigations at the first visit include:
 Full blood count (with indices): Hb, MCV, MCH, PBF.
The four indices constitute the first stage thalassaemia screening. A low or normal Hb, low MCV,
low MCH and a PBF showing microcytic, hypochromic red blood cells, fragmented target cells and
poikilocytosis suggest a thalassaemia trait or iron deficiency anaemia. Do Hb electrophoresis and
serum ferritin to differentiate between the two.
 ABO/Rh blood group
 Hepatitis B status: Hepatitis B Surface Antigen (Hbs Ag) and Antibody to Hepatitis B Surface
Antigen (Anti-Hbs Ag); Hepatitis B "e" Antigen (Hbe Ag) if HbsAg positive.
 Assessment of rubella and varicella immunity (eg, documented verification of infection by a health
care provider, documented vaccination, or laboratory evidence of immunity)
 VDRL
 HIV
 Urine FEME – protein, sugar and WBCs
 Urine culture - screen for asymptomatic bacteriuria (see M8.1.2R6)

Other tests include:

 A first trimester pelvic ultrasound scan for dating and to confirm foetal number and viability, and
location of the pregnancy (to exclude ectopic pregnancy).
 A diabetic mother may require HbAIC / blood glucose profile
 A mother with SLE may require ANA/Anti DNA/ESR/C3,C4 complement levels/renal function test
 Screening for gestational diabetes mellitus: women at high risk for GDM should undergo OGTT as
early in pregnancy as feasible (see M8.1.2R4)
 All pregnant women at any age should be offered Down syndrome screening e,g. combined test: first
trimester screening test for Down syndrome which consists of sonographic measurement of fetal
nuchal translucency and maternal serum assessment of beta-hCG and pregnancy-associated plasma
protein-A (PAPP-A) (see M8.1.1R5)
 Mothers older than 35 years at EDD require genetic counselling and option of amniocentesis or other
tests
 A mother with or suspected of thyroid disease requires a thyroid function test
 Other investigations where relevant: testing for toxoplasmosis / cytomegalovirus / parvovirus /
hepatitis C / herpes simplex; chlamydia / gonorrhoea screening in women at risk; genetic carrier
testing if indicated
 Pap smear
 Other tests as indicated by the mother’s risk factors, history and examination

The following tests may be ordered in the later stages of pregnancy:

 Ultrasound scan at 18-22 weeks for fetal abnormalities (see M8.1.1R6)
 Ultrasound scan at 28-34 weeks to assess growth, amniotic fluid index, presentation and placental
location (see M8.1.1R6)
 Doppler studies are indicated if intrauterine growth restriction is suspected
 Screening for diabetes in the second trimester (see M8.1.2R4)
 Maternal serum screening for neural tube defects and Down syndrome in second trimester (see
M8.1.1R5)
 Screening for group B beta-hemolytic streptococcus (GBS) colonization with swabs of both the lower
vagina and rectum at 35 to 37 weeks of gestation

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Counselling
GPs can provide 2 types of counselling.

General Counselling
 Overview of antenatal care and follow-up
 Patient can be advised on healthy lifestyles and a balanced dietary intake.
 Patients should be advised on cigarette and alcohol consumption and drug use.
 Advice on appropriate exercise and rest.
 First time mothers-to-be need to know what to do when membranes rupture and labour begins,
strategies to manage pain, as well as the value of labour support.
 Discussion of breastfeeding
 Discussion of antenatal exercises
 Health education on pregnancy and infant care
 Health education on parenting
 Arrangements for follow-up
 If a high-risk pregnancy, assess and refer when necessary

Specific Counselling
Patient should be counselled specifically with regards to their risk factors, for example:
 Dietary counselling for gestational diabetes mellitus.
 Educating patients on symptoms and signs of pre-eclampsia.
 Smokers should stop.
 Genetic counselling and testing in couples with a family history of genetic disorders, who did not
receive it before conception.
 Prenatal serum marker screening can be offered to screen for trisomies and/or neural tube defects.
 Genetic counselling for Down syndrome for mothers older than 35 years at EDD

Dating of the pregnancy

Dating is important. Correct gestational age is especially important in interpretation of antenatal tests and
management of preterm labour, IUGR and post dates. The GP is often the first contact with a pregnant
woman and is therefore in the best position for gestation estimation. Dating can be done by inquiring
about regularity of menses and the LMP. However, up to 40% of women can be wrong with their dates.
Hence, more objective methods like early first trimester ultrasound scan should be performed.

The estimated date of delivery (EDD) can be established by several methods:

 EDD is calculated by adding 7 days and 9 months to the first day of the last normal menstrual period
for the patient with 28-day cycles. For cycles longer than 28 days, add the difference to the EDD. For
cycles shorter than 28 days, subtract the difference from the EDD.
 Uterine size
 The presence of fetal heart tones on Doppler ultrasound (audible after 9-12 weeks)
 The presence of fetal movement (felt by the mother by 16-20 weeks)
 Pelvic ultrasound (the most reliable method): most accurate from first trimester dating scan. The
ultrasound scan can also confirm fetal number and viability, and location of the pregnancy (exclude
ectopic pregnancy).

Antenatal Follow Up Plan

This should be decided at the first consultation.

General plan
In an uncomplicated case, the future management plan may include:
 Routine blood and urine tests
 An early dating scan in first trimester
 A screening scan at 18-20 weeks gestation
 Referral to obstetrician for review, preferably at least 2 times before term at: 20 weeks gestation after
the screening scan, 34 weeks gestation for review of antenatal progress
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Specific plan
 Genetic counselling and option of amniocentesis or other tests for all women reaching or older than
35 years at EDD or those with past obstetric history of foetal abnormality
 Screening for gestational diabetes mellitus in high risk patient at first visit (see M8.1.2R4).
 A growth scan at 28-34 weeks gestation for pregnancies at high risk of foetal growth restriction (see
M8.1.1R6)
 All high risk obstetric patients should be referred for tertiary level of care at as early in gestation as
possible.

First visit
All women should be encouraged to seek antenatal care as early in the pregnancy as possible. At the first
visit, the following should be done:
 Diagnosis of pregnancy; assessment of risk factors; history and physical examination (see sections
above)
 If a high risk pregnancy, assess and refer where necessary
 Basic investigations (see section above)
 General and specific counselling (see section above)
 Dating of pregnancy (see section above)
 Arrangements for follow-up.

Follow up tasks and frequency

The main aim of follow up is to detect any risk factors that may arise in the course of pregnancy.

For low risk antenatal patients, at each visit the following are done:
 Short history is sought of events that have happened since the last antenatal visit
 Detailed evaluation of any complaints
 Physical examination of the patient and baby
 Weight and blood pressure is measured and compared with the previous reading
 Routine urine labstix test for glucose and protein
 Palpation of the abdomen and measurements of the fundal height above the pubic symphysis are done
with special attention at:
 28-32 weeks - identification of intrauterine growth retardation;
 32-36 weeks - identification of malpresentation.
 See Figure 1 for fundal heights corresponding to gestation (Thein, 1997)
 Foetal heart sounds are checked
 Assessment of fetal activity
 Screen for gestational diabetes (see section M8.1.2R4)

FIGURE 1. ESTIMATION OF FUNDAL HEIGHT

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The frequency of follow up visits varies. Generally, for uncomplicated pregnancies, if the first visit is in
the first trimester, subsequent visits will be once every 4 weeks till 28 weeks gestation, followed by once
every 2 weeks till 36 weeks gestation and weekly till delivery.

Shared Care Scheme

For a low risk pregnancy, a suggested shared care scheme is:

First half of pregnancy

 1st visit and 4 weekly interval thereafter

Second half of pregnancy

 Refer for screening scan by 20 weeks at tertiary centres; refer for growth scan at 28-34 weeks if foetal
growth restriction suspected
 20 weeks and 34 weeks onwards by specialist
 24, 28, 30 and 32 weeks by GP

The patient can be referred to the obstetrician after 32-34 weeks for the follow up and delivery. The
patient can also be sent back to the GP for post-delivery counselling on breastfeeding and contraception
4-6 weeks after delivery.

Obstetrician Referral
Refer the patient for opinion or co-management of incidental problems. GP and obstetrician should strive
to work in tandem for the good of the patient, her baby and her family. If in doubt, refer.

All patients belonging to high risk group should be referred early to the specialist. Some suggested
guidelines for referral of antenatal patients to hospitals are shown in Table 1.

TABLE 1. SUGGESTED GUIDELINES FOR REFERRAL OF ANTENATAL PATIENTS

Medical/surgical indication
Anaemia (Hb<9gm/dl); Diabetes mellitus; Hypertension; Cardiac disease; Nephritis, recurrent urinary infections;
Thyrotoxicosis; Tuberculosis; Psychiatric disease; Pelvic fracture
Past obstetric history
 Maternal factor: Primary or secondary infertility; Recurrent spontaneous abortions; Genital or uterine abnormality;
Uterine rupture; Myomectomy; Cervical incompetence; Severe preeclampsia or eclampsia; Preterm labour
 Foetal factor: Intrauterine death, still born or neonatal death; Low birth weight (less than 2270g); Large babies (over
4000 g); Previous baby with genetic disorder; Rhesus incompatibility
Present pregnancy
Primigravida below 15 or over 35 years of age; Uterus smaller or larger than dates; Polyhydramnios, oligohydramnios;
Multiple pregnancy; Pre-eclampsia; Threatened abortion; Antepartum haemorrhage; Premature rupture of membranes;
Absent or decreased foetal movements
At 32 weeks
Malpresentation; Unstable lie
Source: Thein, 1997

SHOULD THERE BE FEWER ANTENATAL CHECK UPS?

This question has been raised since the 1980s. The National Institute for Clinical Excellence (NICE) has
published a guideline for England and Wales which was released in late October 2003 recommending 10
appointments during first pregnancies and 7 during subsequent pregnancies, rather than the current
average of around 14 described above.

In that guideline, it advised earlier first visit, at around 8 weeks instead of 12 weeks. It also recommends
that all women should be given ultrasonography at 10 to 13 weeks to estimate when their baby is due,
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instead of having the date estimated from the date of their last period. This should improve the accuracy
of pregnancy staging and reduce the number of women whose labour is inappropriately induced at 41
weeks. The guideline is the first major change to the basic pattern of antenatal care since the 1920s and is
based on a review of all relevant evidence (Mayor, 2003). However, up to the present there is still limited
data as to what constitutes the optimal number and frequency of antenatal visits, or the optimal content of
those visits (Lockwood, 2013).

A meta-analysis reported in the Cochrane Database found that:

 Reducing the number of antenatal visits did not lead to increased adverse outcomes for mothers or
infants.
 Women were less satisfied with the reduced-visit schedule.
 Caregiver continuity during the antenatal period was related to reduced intervention in labour and
increased maternal satisfaction.
 Care from midwives, family physicians and obstetricians were equally effective; but there was
slightly greater satisfaction with care from midwives and family physicians.

References
1. Lombardo M & Golding G.Shared antenatal care. Aust Fam Physician 2003 Mar;32(3):133-9
2. Zolotor AJ et al. Update on Prenatal Care. American Fam Physician February 1 2014 Vol. 89 Number 3
3. Charles J Lockwood et al. Initial prenatal assessment and first trimester prenatal care. UpToDate. 2014
4. Charles J Lockwood et al. Prenatal care (second and third trimesters). UpToDate. 2013
5. Mackenzie AP et al. Prenatal assessment of gestational age. UpToDate. 2013
6. Bastian LA et al. Clinical manifestations and diagnosis of early pregnancy. UpToDate. 2014
7. Mayor S. NICE guidance recommends fewer but earlier antenatal check ups. BMJ 2003 (1 Nov);327:1009
8. Myint Myint Thein. Antenatal Care in: Handbook for Primary Care Doctors, 1997
9. O’Brien GD, Robinson HP & Warren P. The 18 to 20 week obstetrical scan. Med J Aust, 19 April
1993;158:567. A joint statement from the Australian Society for Ultrasound in Medicine, the Royal Australian
College of Obstetricians and Gynaecologists and the Royal Australian College of Radiologists.
10. Kirkham C. Evidence-based Prenatal Care: Part 1. AmFP 2005 April;71(7):1307-16
11. Tan Thiam Chye et al. Practical Obstetrics and Gynaecology Handbook for the General Practitioner. 2006
12. Tao Le et al. First Aid in Family Medicine Boards. McGraw Hill: New York. 2008

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 M8.1.1R4
COMMON QUESTIONS PATIENTS ASK

INTRODUCTION

Pregnant women often ask their family physicians questions about the safety of medications and the risks
that may be associated with their daily activities.

Common Medications
Cough and cold medications are among the drugs most commonly used during pregnancy.
Chlorpheniramine and diphenhydramine have mostly reassuring pregnancy data and should be considered
the preferred antihistamines in pregnancy. The newer antihistamines eg fexofenadine, cetirizine, and
loratadine have no published human pregnancy data and should not be used as first line agents in
pregnancy. The lack of efficacy of cough medicines eg codeine, dextromethorphan and guaifenisin
suggests their use is not justifiable in pregnancy for the common cold especially given questions about
the safety of some of these agents in pregnancy. Neonatal withdrawal has been reported in babies born
both to addicted and non-addicted women who took codeine in the days prior to delivery. Codeine
ingestion near the time of labour can produce respiratory depression in the newborn.

It should be noted that simple reassurance about the self-limited nature of the common cold is the best
treatment for many pregnant women.

In addition to cough and cold preparations, analgesics are often used in pregnancy. The extensive use of
acetaminophen (paracetamol) by pregnant women combined with the paucity of documented adverse
effects has served to make this medication the pain reliever and antipyretic of choice during pregnancy
when short-term drug therapy is indicated. However, it may be prudent to caution women to avoid
prolonged use of acetaminophen wherever possible.

Acetylsalicylic acid (aspirin), ibuprofen and naproxen should be used cautiously during pregnancy
because of the association of nonsteroidal anti-inflammatory agents (NSAIDs) with adverse effects on
foetal renal function and transient narrowing of the ductus arteriosus. Furthermore, aspirin has been noted
to increase maternal and neonatal blood loss following delivery, even when the medication is
discontinued up to three weeks before delivery.

While low-dose aspirin therapy is being used more frequently to prevent preeclampsia and low birth
weight, acetaminophen is the analgesic that poses the least risk to the mother and the foetus. Only when
acetaminophen is contraindicated should aspirin and NSAIDs be used for pain relief.

Fiber laxatives and over-the-counter antacids are other types of medications frequently used during
pregnancy. Because fiber laxatives are not systemically absorbed, they do not increase risks during
pregnancy. Antacids also pose little risk to the developing foetus, but these agents may bind iron in the
gastrointestinal tract. Thus, excessive use of antacids during pregnancy could contribute to iron-
deficiency anaemia. Ideally, pregnant women should minimize their intake of antacids by avoiding foods
and beverages that may exacerbate heartburn, by discontinuing smoking and by eating small, frequent
meals.

Antibiotics. Antibiotics with a good safety profile in pregnant women include the cephalosporins,
penicillins, erythromycin (except the estolate), azithromycin, and clindamycin. Aminoglycosides are
relatively safe, but carry a risk of fetal (and maternal) ototoxicity and nephrotoxicity. Although
erythromycin and azithromycin have good safety profiles, clarithromycin, another macrolide, has
produced adverse pregnancy outcome in animal studies at low-order multiples of human doses; human
experience is very limited but has not suggested an increase in congenital anomalies in exposed
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pregnancies, but an increased risk of miscarriage has been reported, possibly related to the underlying
maternal disease.

Doxycycline is avoided during pregnancy because other tetracyclines have been associated with transient
suppression of bone growth and with staining of developing teeth, but available data do not show
teratogenic effects from doxycycline. Fluoroquinolones are generally avoided during pregnancy and
lactation because they are toxic to developing cartilage in experimental animal studies. However, neither
adverse effects on cartilage nor an increase in congenital malformations from use during human
pregnancy has been documented.

Trimethoprim is generally avoided in the first trimester because it is a folic acid antagonist, has caused
abnormal embryo development in experimental animals, and some case control studies have reported a
possible association with a variety of birth defects. However, it is not a proven teratogen in humans.
Additional evaluation of the safety of trimethoprim in human pregnancy is needed. The safest course is to
avoid using trimethoprim in the first trimester if another antibiotic that is safe and effective is available. If
exposure does occur, patients should be advised of the baseline risk of birth defects in the population and
the possibility of a low, but unproven increase in risk of birth defects after exposure to trimethoprim.

Studies have reported statistically significant associations between a variety of birth defects and use of
sulfonamides or nitrofurantoin, and a statistically significant association between nitrofurantoin use and
cardiac defects. Although these findings should be interpreted with caution because the studies were
retrospective, the safest course is to avoid using nitrofurantoin or sulfonamides in the first trimester if
another antibiotic that is safe and effective is available.

Sulfonamides compete with bilirubin for albumin binding sites and theoretically may increase the risk of
kernicterus at low bilirubin levels. For this reason, these drugs are avoided near delivery if another
antibiotic is available. (Lockwood, 2014)

Dental Procedures
Pregnancy increases the risk for developing gingivitis and periodontitis. The increased susceptibility is
due to the increase in estrogen and progesterone during pregnancy. An increase in gingivitis frequently
appears between the second and eighth months of pregnancy. Studies have shown a correlation between
periodontal disease and preterm labour. Morning sickness and general malaise in the first trimester can
also result in poor oral health, increasing the susceptibility of the woman to caries. Food cravings during
pregnancy may result in higher or more frequent sugar intake, thus increasing the risk of developing
caries. Hence, good dental hygiene is recommended in pregnancy. (Tan, 2006)

To maintain good oral hygiene, advice should be given to the pregnant woman to brush after each meal,
floss at least once a day and use an anti-plaque mouth rinse. Also, she should visit the dentist regularly at
least every 6 monthly for cleaning. While regular check-ups and cleaning are highly recommended during
pregnancy, major dental procedures (e.g. wisdom tooth removal, bleaching) that are not urgent should be
postponed till after delivery of the baby. As the first trimester is the most critical period of the baby’s
development, dental treatment, if necessary, is best performed in the second trimester to minimize any
potential risks. Treatment in the third trimester is not recommended due to the unfavourable supine
position of the pregnant woman that may impede cardiac venous return. (Tan, 2006)

The major concerns of women who need dental care during pregnancy are exposure to anaesthetic agents
and diagnostic radiographs. Because of low systemic absorption, local anaesthetics used in appropriate
amounts are acceptable in pregnancy. Nitrous oxide is also acceptable for sedation, but it is less desirable
than local anaesthesia because it is systemically absorbed and crosses the placenta. However, nitrous
oxide is not a known teratogen.

The risk of foetal malformation from diagnostic dental radiographs in an appropriately shielded patient is
extremely low. However, dental radiographs should be obtained only when necessary and leaded aprons
should always be used for shielding.

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Caffeine
Heavy caffeine consumption during pregnancy may cause caffeine withdrawal in newborns. Infants with
caffeine withdrawal have feeding difficulties, vomiting, excessive crying, irritability and poor sleep
patterns. Because neonates metabolize caffeine poorly, the half-life of caffeine in the neonate is about
four days. This prolonged half-life may cause withdrawal symptoms to persist for days to weeks.

It may be prudent for women who are attempting to conceive or who are pregnant to limit caffeine
consumption to less than 200 to 300 mg per day (two cups of coffee). Higher amounts of caffeine may be
associated with increased rates of abortion and low birth weight (Brundage, 2002). Pregnant patients
should also be informed about sources of caffeine other than coffee, including tea, colas, chocolate and
over-the-counter drugs.

Aspartame
Pregnant women often ask whether they should curtail their consumption of beverages and foods
sweetened with aspartame (NutraSweet). There have been no reported studies of adverse foetal or
maternal effects from aspartame, either in laboratory animals or humans.

Hair Care Products & Cosmetics

The concern about exposure to hair dye and hair straightening agents is that there may be absorption of
chemicals into the bloodstream at the time of use. However, most chemicals are cleared from the
bloodstream fairly quickly. Unfortunately, there have been only very few studies on the use of such
products during pregnancy to quantify the risk of hair dye to a developing foetus. While no one can
provide data about timing and safety, avoid dyeing or rebonding the hair once a woman has conceived.
Perming hair during the second and third trimesters of pregnancy is a safe procedure and can make caring
for hair less time consuming and easier. There are no studies to indicate that perming hair during
pregnancy is detrimental to the foetus. (Tan, 2006)

No data are available to determine whether an association exists between hair spray or shampoos and
adverse outcomes of pregnancy. Therefore, no firm statement can be made concerning the risks of using
these products during pregnancy.

Little information is available regarding the risks to the foetus from cosmetics (including facial make-up
and nail polish), perfumes, soaps, lotions and antiperspirants or deodorants. Considering the widespread
use of these products during pregnancy, an association with one particular product would be difficult to
find.

Video Display Terminals

Many pregnant women are employed in clerical, sales or administrative positions that require the use of
video display terminals. Studies have not demonstrated a convincing association between miscarriage,
low birth weight or birth defects and the use of video display terminals.

House Paint
Pregnant women may have an occupational exposure to paint, or they may be exposed to paint at home.
Most studies that suggest an association between paint exposure and adverse pregnancy outcomes are
either case reports or retrospective studies that deal with chronic occupational exposure to fumes. The
data from these studies are insufficient to show a cause-and-effect relationship between paint exposure
and foetal harm. However, because oil based paints and paint thinners contain a number of aromatic
organic solvents, exposure to these products should be limited or avoided, particularly during the first
trimester of pregnancy.

Brief exposure to water-based paints and similar compounds in a well-ventilated area should not pose a
significant risk to the foetus. Pregnant women should be reminded to use all paints as directed by the
manufacturer. For example, paints labelled for outdoor use should not be used indoors.

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Insecticides
Most insecticides are very lipid-soluble, and they are readily absorbed, even with limited exposure. In
general, pregnant women probably should not apply pesticides in the home or in the garden. In particular,
they should avoid the use of fumigants. Pesticides should be applied by someone other than the pregnant
woman. Products such as insecticide strips and flea collars should also be avoided, since these products
may pose some increased risk during pregnancy.

Seat Belt Use

Maternal trauma is the leading non-obstetric cause of foetal death. A study of 441 pregnant women
involved in motor vehicle accidents showed that maternity mortality increased sixfold and foetal
mortality increased fivefold in cases where the woman was ejected from the automobile (Crosby and
Castiloe, 1971). Consequently, the use of seat belts is recommended to decrease maternal foetal trauma in
the event of a motor vehicle accident.

Use of a conventional lap belt alone has been implicated as a causative agent of uteroplacental accidents
and foetal injuries. The best protection is provided by the diagonal shoulder strap with a lap belt (i.e. a
threepoint restraint). The diagonal strap should pass over the shoulder and across the chest between the
breasts. The lap strap should lie across the upper thighs. Thus, the straps should be above and below the
"bump" of pregnancy and not over it. Use of the three-point restraint distributes the energy of the impact
over the chest wall and the pelvis.

Air Travel during Pregnancy

Flying is not contraindicated in an uncomplicated pregnancy. Domestic travel is usually permitted until
36 weeks of gestation, whereas international travel may be curtailed after 32 weeks of pregnancy. This is
due to the risk of preterm labour. (Tan, 2006)

Traveling should be done mostly in the second trimester when the pregnant woman feels more
comfortable and the risks of miscarriage and preterm labour are lower. It is important to take deep vein
thrombosis (DVT) precautions, such as getting a seat with more leg room, interval walking along the
aisles or toilet breaks, leg massages or wearing thrombosis deterrent stockings. Prevent dehydration in the
plane by taking enough fluids orally and avoiding alcohol. Avoid travel to countries that would require
immunisation in pregnancy. (Tan, 2006)

Carrying Heavy Loads during Pregnancy

It is common to hear that it is unsafe to lift heavy things during pregnancy. However, the risk of injury is
usually directed at the mother and not the baby. The increase in the level of hormones during pregnancy
causes the ligaments to soften, which leads to joints that may be less stable. Also, the centre of gravity of
a pregnant mother has shifted, which puts more stress on her back. These two factors make the mother
more susceptible to injury when lifting heavy things. (Tan, 2006)

Some FAQs for the medical practitioner to answer

Should I do things differently now I am pregnant?

 Go for regular check-ups.
 Cautious use of medications (prescription & OTC).
 Avoid alcohol & cigarette use.
 Avoid cats, raw foods (toxoplasmosis risk)
 Avoid hot tubs & saunas in 1st trimester (maternal heat exposure may be associated with neural tube
defects).

How much weight do I need to gain?

 BMI <18.5 kg/m2 (underweight)* — weight gain 12.5 to 18.0 kg
 BMI 18.5 to 24.9 kg/m2 (normal weight)* — weight gain 11.5 to 16.0 kg
 BMI 25.0 to 29.9 kg/m2 (overweight)* — weight gain 7.0 to 11.5 kg
 BMI ≥30.0 kg/m2 (obese)* — weight gain 5 to 9.0 kg

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*WHO International classification of BMI

What should my diet be like?

 Balanced diet, extra 300 Kcal/day.
 Fully cooked food.
 3 to 4 servings of dairy products.
 Limit caffeine to no more than 2 cups of coffee a day.
 Sweeteners are fine.

Do I need vitamins?
 Folate 0.4 mg/day for the first twelve weeks.
 Iron, calcium supplements may be needed by some women.

Can I exercise?
 Yes. 20 minutes of moderate exercise thrice a week recommended unless there are medical reasons.
However, avoid activities at high risk for injury/contact sports (Tan, 2006).
 Don’t overdo it.
 Drink lots of water.

Is it safe to have sex?

 For most women, yes.
 However, sex is best avoided if there are signs of threatened abortion or if there is presence of low
lying placenta or premature contractions (Tan, 2006)

References
1. Hueston WJ & Eilers G. Common questions patients ask during pregnancy. Am Family Physician May 1, 1995;
51(6):1465-1469.
2. Pregnancy: Keeping Yourself and Your Baby Healthy. Am FP 2005 April; 71(7):1321-2
3. Tan Thiam Chye et al. Practical Obstetrics and Gynaecology Handbook for the General Practitioner. 2006
4. Charles J Lockwood et al. Initial prenatal assessment and first trimester prenatal care. UpToDate. 2014
5. Lucia Larson et al. Treatment of respiratory infections in pregnant women. UpToDate. 2014
6. Jonathan Gillen-Goldstein et al. Nutrition in pregnancy. UpToDate. 2013
7. Hugh Silk et al. Oral Health During Pregnancy. Am Fam Physician. 2008 Apr 15;77(8):1139-1144

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 M8.1.1R5
ANTENATAL TESTING & PRENATAL SCREENING

INTRODUCTION

The usual profile of antenatal tests done at the first visit has been described in section M8.1.1R3.

Other tests are performed as indicated:

 Chromosome studies may be done late in the first trimester (cellular material obtained from chorionic
villus sampling) or early in second trimester (cellular material obtained from amniocentesis). The
new development is the use of non-invasive tests in the first trimester (first trimester ultrasound for
nuchal translucency plus first trimester maternal serum biochemistry – free beta-HCG and PAPP-A))
for the screening of Down syndrome; for second trimester screening, the most effective and safe
method is the quadruple test.
 The 20 weeks anomaly scan is now a fairly routine test in the second trimester.
 Screening for diabetes is also routine in the second trimester.
 Monitoring for placenta praevia and intrauterine foetal growth retardation is done with ultrasound in
the third trimester.

HUMAN HCG

Detection of human chorionic gonadotropin (hCG) in blood or urine is the basis of all pregnancy tests.
Human chorionic gonadotrophin (HCG) is a glycoprotein produced by the trophoblast shortly after
implantation. Its level depends on the stage of pregnancy:
 Eleven days after the luteinizing hormone (LH) peak (which immediately precedes ovulation), HCG
should be detectable in all normal pregnancies by either urine or serum testing.
 It reaches a concentration of about 100 IU/L at the time of the missed menses and rises to a peak of
between 60 000 and 100 000 IU/L approximately 8-10 weeks after the last menstrual period. At term
the HCG level is from one third to half of the peak level.
 In a viable intrauterine pregnancy, the serum HCG will double approximately every 48 hours up to
about the 8th week. There is a prolonged doubling time in abnormal intrauterine and ectopic
pregnancies. Serial quantitative estimations of serum HCG are useful to determine the viability of a
pregnancy in a patient with an early established pregnancy who is bleeding vaginally.

In clinical practice, the most sensitive method for detecting hCG in early pregnancy is a serum pregnancy
test. Qualitative serum pregnancy tests typically detect hCG levels of 5 to 10 IU/L, while a high
sensitivity, quantitative serum beta-hCG assay can measure hCG values as low as 1 to 2 IU/L. In contrast,
the urine pregnancy test is less sensitive, detecting hCG beginning at a level of 20 to 50 IU/L. (Bastian,
2014)

FULL BLOOD COUNT AND SMEAR

The total blood volume increases by up to 45% and reaches its maximum volume at about 34 weeks of
pregnancy. This expansion of the plasma volume despite an increase of 20-40% in red cell mass, causes
the haemoglobin to fall to between 10 g/dL and 12 g/dL. It reaches its lowest level at about 34 weeks,
thereafter rising by about 0.5 g/dL (range of Hb at term 10.4-14.8 g/dL). The non pregnant haematocrit of
0.40 – 0.42 falls, due to haemodilution, to a minimum of 0.31-0.34. The mean corpuscular volume
(MCV) falls in early pregnancy but increases in the later half of pregnancy.

The World Health Organization defines anemia in pregnant women as haemoglobin < 110 g/L (11 g/dL)
or hematocrit < 0.33 L/L (33 percent). Women with haemoglobin values below these levels can be
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considered anaemic and should undergo a standard evaluation (complete blood count, review of
peripheral smear, reticulocyte count, serum Fe/TIBC, ferritin, and Hb electrophoresis as indicated). If the
evaluation is negative, a haemoglobin as low as 10 g/dL can be attributed to physiologic anaemia since a
wide variety of factors affects the normal level of haemoglobin in a specific individual. (Bauer, 2013)

The white cell count (WCC) tends to rise in pregnancy due to an increase in polymorphonuclear
leucocytes, the mean count being about 9000. The blood of normal pregnant women may contain up to
3% myelocytes or metamyelocytes.

Platelets may vary between 150 and 400 X 103/L in pregnancy. Falling numbers of platelets in association
with severe pre-eclampsia heralds the impending onset of disseminated intravascular coagulation.

The morphology of red blood cells indicates the type of anaemia - microcytic suggests iron deficiency or
thalassaemia while macrocytic suggests folate deficiency, or rarely vitamin B12 deficiency.

Haemoglobin and full blood count and smear should be done at presentation and again between 28 and 36
weeks.

BLOOD GROUP AND ANTIBODIES

It is important to determine the patient's blood group, and check for the presence of red cell antibodies. If
the patient is rhesus (Rh) negative, she should be referred to tertiary care for further management. Rh
negative women who deliver an Rh positive baby or who are otherwise exposed to Rh positive red blood
cells are at risk of developing anti-Rh antibodies. Rh positive fetuses/neonates of these mothers are at risk
of developing hemolytic disease of the fetus and newborn, which can be lethal or associated with serious
morbidity.

For pregnancies at risk, usually the indirect Coombs' test is repeated at close intervals (as close as 2
weekly if indicated) up to delivery. The Neubauer haemocytometer is used to identify the presence and
quantity of foetal cells in the maternal circulation. This should be done on all rhesus-negative women
after events such as placental abruption, severe pre-eclamptic toxaemia, unexplained foetal death and at
delivery.

Treatment includes giving prophylactic antenatal anti-D immunoglobulin at 28 and 34 weeks, as well as
postnatally if mother is not iso-immunised (i.e. Rh antibody negative). Anti-D immunoglobulin should
also be given for sensitizing events such as antepartum haemorrhage, abdominal trauma or post-
procedure such as amniocentesis if partner is Rh positive. (Tan, 2006)

COMPLICATED PREGNANCIES

The following may be indicated:

 Serum uric acid. This tends to rise progressively during the evolution of pre-eclamptic toxaemia
(PET).
 Liver function tests (LFTs). These become elevated in severe pre-eclamptic toxaemia: an aspartate
amino-transferase (AST) over 40 suggests liver damage, while alkaline phosphatase (which normally
rises in pregnancy) and serum gamma glutamyl-transaminase (GGT) tend to rise first, and lactate
dehydrogenase (LDH) post-delivery (LDH over 600 indicates severe disease). LFTs are also
necessary if active hepatitis is suspected.
 Proteinuria occurs in PET and increases markedly as the disease becomes more severe.

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MATERNAL INFECTIONS

Syphilis Serology
Syphilis, yaws and pinta are all caused by treponemes that are indistinguishable morphologically and
serologically. Syphilis continues to be a problematic issue in many parts of the world. It is necessary to
follow up all babies born to women who have positive serological tests for syphilis. Risk factors include
multiple sexual partners, or a history of sexually transmitted diseases.

All patients should be screened by serological tests (VDRL, RPR). If the serological tests are positive the
more specific treponemal tests such as Treponema pallidum haemagglutination antibody (TPHA) or
fluorescent treponemal antibody (FTA) tests are used.

Rubella Status
The serum rubella antibody level should be checked in all women when they attend for their first
antenatal visit. If nonimmune, the patient should be counseled to avoid exposure to individuals with
rubella and receive postpartum immunization. After immunization, they should be retested 6-8 weeks
later to ensure that they have seroconverted.

Pregnant women with a record of vaccination who develop a rash during pregnancy should be
investigated further because of the possibility of vaccine failure. Infection with rubella will produce a
typical primary antibody response with IgG seroconversion and a high concentration of rubella specific
IgM which persists for up to 8 weeks.

Hepatitis B Virus Antigen (HbsAg)

The presence of HBsAg in serum indicates infectious serum. It may disappear with resolution of acute
hepatitis but on the other hand it may persist in the serum indefinitely after the resolution of acute
hepatitis, and indicates a chronic carrier state. If active hepatitis is suspected in the pregnant woman, then
further serological tests and liver function tests should be done.

Neonates born to HBsAg positive women (chronic carriers) should receive hepatitis B immunoglobulin
and HBV vaccine at birth.

HIV
Universal HIV testing of pregnant women early in each pregnancy using an 'opt-out' approach is
generally recommended.

INVASIVE TESTS

Laparoscopy
If an ectopic pregnancy is suspected on clinical or ultrasonographic grounds, or if other pelvic pathology
is suspected or has been demonstrated, then one should proceed to laparoscopy for confirmation of the
diagnosis. Definitive treatment can be performed at the same time.

Chorionic Villous Sampling

Chorionic villous sampling (CVS) is usually performed from 11 weeks gestation, and is done under
ultrasound control, with the needle passed into the placenta, either per abdomen or per vagina. Between 5
and 30 mg of villi are usually required, which are then subjected to either cytogenetic analysis that gives a
result in 48 hours, or long term culture that takes about 10 days. These methods involve a direct and
indirect karyotype analysis. CVS carries a risk of miscarriage of up to 2%.

Amniocentesis
This is a technique to enable foetal chromosomes to be studied in pregnancy to discover chromosomal
disorders, such as trisomy 18 or 21. The procedure can also be used for other tests, such as rhesus disease
monitoring and for measurement of alpha-fetoprotein (AFP) to screen for spina bifida. It is performed at
approximately 16 weeks gestation, by placing a needle through the abdominal wall under ultrasound
control, to obtain a sample of liquor amnii, which is used to culture foetal cells. This may take up to 2-3
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weeks. Interphase fluorescence in situ hybridization (FISH) provides a limited karyotype within 24 to 48
hours, but only detects aneuploidy of chromosomes 13, 18, 21, X, and Y, which are the most common
causes of aneuploidy. Irrevocable actions (eg, pregnancy termination) should not be undertaken based on
FISH results alone because rare false positives occur. Amniocentesis carries up to a 1% risk of
miscarriage.

MATERNAL SERUM TESTING

Screening for Down Syndrome

Down syndrome is the most common chromosome abnormality among live births and the most frequent
form of intellectual disability caused by a demonstrable chromosomal aberration. Couples may wish to
prevent birth of an affected infant, or want the opportunity to plan for the birth of an affected child. 30%
of affected foetuses are carried by 9% of pregnant mothers who are over 35 years of age. These women
would normally be offered amniocentesis or CVS on the grounds of maternal age. The other 70% are
carried by 91% of women who are in the younger age group who in the past would not be routinely
screened.

Presently it is recommended to offer all pregnant women prenatal screening for Down syndrome,
regardless of age. However, it should be noted that screening tests are not diagnostic tests. A negative
screening test result means the patient's risk of having a baby with Down syndrome is less than a specific
cut-off level; it does not exclude the possibility of Down syndrome. Also, most positive results are
associated with a normal pregnancy outcome. After a positive screening test, it is helpful to have the
parents meet with an obstetrician/genetic counsellor to inform them of their diagnostic and management
options, including information about the natural history of Down syndrome. Foetal karyotype
determination is offered for definitive diagnosis. In the first trimester, karyotype is obtained by CVS. In
the second trimester, amniocentesis is performed to obtain amniocytes for chromosomal analysis.

In 2007, the American College of Obstetricians and Gynecologists (ACOG) recommended that (1) all
women be offered aneuploidy screening before 20 weeks of gestation and that (2) all women should have
the option of invasive testing, regardless of maternal age. ACOG also stated that a prenatal diagnostic
procedure for fetal karyotype, rather than serum screening, should be considered in women of any age at
high risk of Down syndrome or other fetal aneuploidies. (Messerlian, 2013)

Table 1 shows the antenatal screening methods for Down syndrome.

Table 1. Glossary of Down syndrome screening terms

Nuchal translucency (NT) measurement
The width of the translucent space at the back of the fetal neck determined by ultrasound.
Combined test
First trimester test based on sonographic and maternal serum measurements: NT, β-human chorionic gonadotropin (β-hCG:
free or total), and pregnancy-associated plasma protein-A (PAPP-A), together with maternal age.
Triple test
Second trimester test based on measurement of maternal serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and β-
hCG (free or total), together with maternal age.
Quadruple test
Second trimester test based on measurement of maternal serum AFP, uE3, β-hCG, and inhibin-A, together with maternal age.
Integrated test (full)
The integration of measurements performed during the first and second trimesters into a single test result. Typically, the
integrated test refers to the integration of NT and PAPP-A measurements in the first trimester with the quadruple test markers
in the second trimester, together with maternal age.
Serum integrated test
A variation of the integrated test using maternal serum markers only: PAPP-A in the first trimester and the quadruple markers in
the second trimester, together with maternal age.
Source: Messerlian, 2013

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Choice of Screening Test (Messerlian, 2013)
The choice of screening tests depends largely on the timing of presentation of the patient, her preferences,
and availability.

The first trimester combined test is the best option for women whose most important goal is to obtain
their estimate of risk of Down syndrome early in pregnancy (alpha-fetoprotein is still recommended in the
second trimester for detection of neural tube defects). This test is done between 9 and 13 weeks of
gestation, and consists of three markers:
 Maternal serum beta human chorionic gonadotropin (beta-hCG)
 Maternal serum pregnancy-associated plasma protein-A (PAPP-A)
 Ultrasound measurement of nuchal translucency (NT)

These three markers together with maternal age provide a patient-specific risk. The combined test detects
approximately 85 percent of Down syndrome (ie, detection rate [DR] = sensitivity = 85 percent) with a
false positive rate (FPR) of 5 percent. It can also detect trisomy 18.

The combined test performs slightly better than the second trimester quadruple test (ie, the DR is higher
and/or the FPR is lower). The quadruple test is the best available screening test for women who present
for prenatal care in the second trimester, and has supplanted the single, double, and triple tests formerly
used for this purpose. At 15 to 18 weeks of gestation (but as late as 22 weeks), the serum markers AFP,
uE3, hCG, and inhibin A are measured in maternal serum. Maternal serum AFP and uE3 levels are, on
average, reduced by 25 to 30 percent in pregnancies affected by Down syndrome, and hCG and inhibin A
levels are, on average, twice as high as those in unaffected pregnancies.

The full integrated test uses markers measured in both the first and second trimesters to provide a single
estimate of risk for Down syndrome pregnancy. It has the highest detection rate for Down syndrome and
the lowest false positive rate, achieving an 85 percent DR at a 1 percent FPR. In the first trimester, a
serum sample is assayed for PAPP-A between 9 and 13 weeks and an ultrasound measurement of NT,
along with estimation of gestational age by crown-rump length, is performed between 10 and 13 weeks.
The information is kept on file until a second trimester serum sample is drawn and the quadruple test
markers are run (AFP, unconjugated estriol, inhibin A, beta-hCG). The six marker values are used,
together with maternal age, to calculate a single risk for Down syndrome. The integrated test can also
detect trisomy 18 and includes screening for open neural tube defects.

The serum integrated test has the highest detection rate for any test in which nuchal translucency
measurement is not used, and provides an option to patients in areas where expertise in measurement of
nuchal translucency is not available.

New test: Maternal plasma-based tests for cell-free DNA (circulating, free maternal and fetal DNA in
maternal plasma) use next generation genomic sequencing to detect trisomy 21, 18, and possibly 13, after
10 weeks of gestation. It can be used as a primary screening option for women at increased risk of fetal
aneuploidy or as a secondary Down syndrome screening test in women who are screen-positive by any
current primary screening test. This test has very high sensitivity and specificity, leading to a significant
reduction in the number of women falsely identified as high risk after primary screening. However, it is
not a diagnostic test; confirmation of positive results by an invasive test is still needed.

Screening for Neural Tube Defects

Raised maternal serum alpha-fetoprotein (AFP) at 16 weeks enables detection of most foetuses with open
spina bifida. It must be combined with ultrasonography, as it is also raised in twin pregnancies and a
variety of other open foetal abnormalities, such as anencephaly, exomphalos and foetal death.

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References
1. Wald NJ et al. First and second trimester antenatal screening for Down’s syndrome: the results of the serum,
urine and ultrasound screening study (SURUSS). Health Technol Assess 2003:7(11).
2. McLennan A. Advances in prenatal screening. Aust Fam Physician, Mar 2003:32(3): 107-12.
3. Cornerford JA. Antenatal care. Which tests and when. Aust Fam Physician 1997;26(3):229-237.
4. Kenneth A Bauer. Hematologic changes in pregnancy. UpToDate 2013
5. Tan Thiam Chye et al. Practical Obstetrics and Gynaecology Handbook for the General Practitioner. 2006
6. Geralyn M Messerlian et al. Overview of prenatal screening and diagnosis of Down syndrome. UpToDate 2013
7. Geralyn M Messerlian et al. First trimester combined test and integrated tests for screening for Down syndrome
and trisomy 18. UpToDate 2013
8. Geralyn M Messerlian et al. Second trimester maternal serum screening for Down syndrome. UpToDate 2013
9. Bastian LA et al. Clinical manifestations and diagnosis of early pregnancy. UpToDate. 2014
10. Charles J Lockwood et al. Initial prenatal assessment and first trimester prenatal care. UpToDate. 2014
11. Ghidini A. Diagnostic amniocentesis. UpToDate 2013
12. Moise KJ. Overview of Rhesus (Rh) alloimmunization in pregnancy. UpToDate 2013
13. Moise KJ. Management of pregnancy complicated by Rhesus (Rh) alloimmunization. UpToDate. 2014

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 M8.1.1R6
THE USE OF ULTRASOUND IN PREGNANCY

INTRODUCTION

Ultrasound as a diagnostic medical imaging test became available during the 1970s. Early images showed
the outline of the foetus and measurements allowed the gestational age to be estimated. Foetal heart
movements were recorded, placental site and amniotic fluid volume were assessed. The crown rump
length (CRL), allowing an estimate of gestational age, was first published by Dr Hugh Robinson in 1975
and proved to be the most accurate method of assessing gestational age. With rapid development in
technology resulting in increasing clarity of images, real time imaging, duplex, colour and power
Doppler, ultrasound has been established as a most important non-invasive diagnostic test. The sound
waves that are used in diagnostic ultrasound have not demonstrated any harmful effects (O’Brien et al,
1993).

LIMITATIONS

However, there are limitations. Obesity, abdominal scarring and bowel gas will all reduce detail in the
images. Transvaginal scans generally provide better detail due to the higher frequency transducer and its
near proximity to the pelvic organs. However, details of an enlarged uterus or mass may be limited by the
smaller field of view (O’Brien et al, 1993). At present, no evidence directly links improved foetal
outcomes with routine ultrasound screening.

RATIONALE FOR ROUTINE SCREENING PRENATAL ULTRASOUND

Most countries offer at least one mid-trimester ultrasound examination as part of standard prenatal care,
although worldwide obstetric practice varies. In the United States, the American College of Obstetricians
and Gynecologists (ACOG) supports the use of ultrasound when there is a specific medical indication and
advises against nonmedical use of prenatal ultrasonography (eg, to accommodate parental curiosity about
fetal sex or parental desire to view and/or obtain an image of the fetus). ACOG also stated that the
benefits and limitations of ultrasonography should be discussed with all patients, and performance of the
procedure is reasonable in patients who request it. (Sfakianaki, 2014)

Compared to no prenatal ultrasound examination or ultrasound examination in selected patients, routine

ultrasound examination improves:
 Estimation of gestational age
 Identification of multiple gestation
 Identification of congenital anomalies

However, the benefit of such prenatal sonographic screening on neonatal outcomes remains unproven.

INDICATIONS IN THE SYMPTOMATIC PATIENT

Patients with suspected foetal death, premature rupture of the membranes and antepartum haemorrhage
will generally require a scan at presentation. Continuing, failed or ectopic pregnancy may be diagnosed.
A patient with a complete abortion will not generally require curettage (O’Brien et al, 1993).

There are non-obstetric indications for ultrasound scans in pregnancy. Maternal renal disease, biliary
problems, suspected deep venous thrombosis, abdominal pain and suspected complicated ovarian cyst are
not uncommon indications and in many patients ultrasound will replace radiographic examinations. The
latter should be avoided during pregnancy, wherever possible (O’Brien et al, 1993).
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ULTRASOUND SCREENING FOR FOETAL ABNORMALITIES

The UK Royal College of Obstetricians and Gynaecologists (RCOG) recommends a two-stage scan
programme: an initial scan performed at booking and the second at or around 20 weeks' gestation
(RCOG, 2000).

The Early Pregnancy Scan

The first scan in early pregnancy, referred to as a booking scan, is undertaken ideally before 15 weeks.
The purpose of this scan should be to establish:
 gestational age accurately
 viability
 foetal number, and in multiple pregnancies the chorionicity/ amnionicity
 presence of gross foetal abnormalities
 location of pregnancy, to exclude ectopic pregnancy

Randomised studies (Nielson JP, 1999;RCOG, 2000) suggest that at least one routine scan in pregnancy
to confirm gestational age confers benefit, especially in reducing the need for intervention for post-
maturity. If serum testing is to be used as a method of screening for Down syndrome, accurate knowledge
of gestational age is essential (Wald et al, 1992;RCOG 2000).

Before 13 weeks, gestational age can be accurately assessed from the measurement of crown rump length.
However, from 13 weeks crown rump length should not be used because the foetus becomes increasingly
flexed making the measurement unreliable. As an alternative, bi-parietal diameter and/or head
circumference should be used; some units include femur length measurement. The early scan can usually
be performed abdominally but, on occasion, a vaginal scan is necessary.

As far as scanning for nuchal translucency is concerned, current evidence suggests that this is an effective
way of determining babies at risk of Down syndrome and is best performed between 10-14 weeks.
Extensive research has now established that screening by nuchal translucency can detect about 80% of
affected foetuses for a screen positive rate of 5%. The combination of nuchal translucency and maternal
serum free ß-hCG and PAPP-A improves the detection to 90%. Preliminary data suggests that together
with the examination of the foetal nasal bone, the detection rate increases to 97% (Spencer at al,
1999;McLennan, 2003). At this time, the role for foetal nasal bone imaging is still unclear. In experienced
hands, it may be a useful adjunct to screening, especially when other studies show a borderline or high
risk of Down syndrome. (Benacerraf, 2013)

Ample evidence has accumulated that routine early ultrasound examination results in more accurate
assessment of the EDD than LMP dating or physical examination. Routine early ultrasound is beneficial
in an unselected population because of better estimation of gestational age resulting in significantly
reduced frequency of labour induction for post-term pregnancy, reduction in diagnosis of fetal growth
restriction, and reduction in use of tocolysis. In addition, first trimester ultrasound examination can lead
to earlier detection of clinically unsuspected foetal malformations (including aneuploidies) and earlier
detection of multiple pregnancy, although these effects have not been shown to improve ultimate foetal
outcome. (Sfakianaki et al, 2014)

Improvements in technology, increasing experience, and refinements in visualization should make the
detection of anomalies in the first trimester more efficient at a time when termination of pregnancy is
possible and private. (Sfakianaki et al, 2014)

The “20 week” Anomaly Scan

In units in which a booking scan is not performed, the "20 week" scan provides dating information and
diagnosis of multiple pregnancy. The majority of non-viable pregnancies will be lost before the scan at
twenty weeks.

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The twenty week anomaly scan is to reassure the woman that her baby appears to have no obvious
structural abnormalities. Lack of explicitness about which structures have been examined may lead to
confusion. The literature provides a range of detection rates and therefore individual units should provide
their own figures to inform women undergoing the "20 week" scan. Recent data (Boyd et al, 1998;
RCOG, 2000) from one unit (Oxford, UK) would suggest that about 50% of significant abnormalities will
be identified by a screening scan.

The value of identifying foetal abnormalities at this stage is that it offers parents options. Some, probably
the majority, for serious lesions, will elect to terminate the pregnancy. Those couples who choose to
continue the pregnancy have the opportunity to prepare themselves through discussions with health care
personnel and self-help groups, whilst attendants can ensure appropriate care during pregnancy and
following delivery (RCOG, 2000).

If one screening ultrasound examination is performed, the American College of Obstetricians and
Gynecologists (ACOG) recommends that the optimal timing is at 18 to 20 weeks of gestation. This allows
for good visualization of anatomy and is early enough to allow completion of prenatal diagnostic
procedures (eg, fetal karyotype, additional imaging studies) while legal termination of pregnancy is
possible, if desired. The ultrasound examination should be carried out by an experienced practitioner.
(Sfakianaki et al, 2014)

The objectives of the anomaly ultrasound examination should be made as explicit as possible to women
and their partners to enable them to opt for, or opt out of, having a scan. For example, women who do not
wish to be informed of a risk of aneuploidy may consider not having a scan at all.

Facts Patients Should Know

 An ultrasound scan is a medical diagnostic test. It is a complex detailed examination that is exacting
for the technician.
 An unexpected serious finding may be present, for example, foetal death or a serious abnormality.
The abnormality may be lethal (e.g. anencephaly), or very serious (e.g. spina bifida).
 The outcome may be uncertain, for example, mild cerebral ventriculomegaly may be a normal variant
or the early stage of developing hydrocephalus. Further tests and follow up will be required and the
immediate prognosis for the foetus will not be certain.
 A normal 20 week scan does not guarantee a normal liveborn infant. Some abnormalities are not
present at 20 weeks and develop later, e.g. hydranencephaly, some diaphragmatic herniae,
sacrococcygeal teratoma or hydronephrosis.
 Foetal sex is not always seen.
 A moderately full bladder is often desirable for an abdomino-pelvic scan. An internal or transvaginal
scan is frequently suggested to better visualise the pelvis. The probe is usually smaller than the
speculum used for a "Pap test".

The minimum standard for a "20 week" anomaly scan

Gestational age can be established by measurement of bi-parietal diameter, head circumference and femur
length. The inclusion of abdominal circumference would be optional.

Foetal Normality
 Head shape + internal structures: cavum pellucidum, cerebellum, ventricular size at atrium (<10 mm)
 Spine: longitudinal and transverse
 Abdominal shape and content at level of stomach
 Abdominal shape and content at level of kidneys and umbilicus
 Renal pelvis (<5 mm AP measurement)
 Longitudinal axis - abdominal-thoracic appearance (diaphragm/bladder)
 Thorax at level of 4 chamber cardiac view
 Arms - three bones and hand (not counting fingers)
 Legs - three bones and foot (not counting toes)

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The optimal standard for the "20 week" anomaly scan
If resources allow, the following could be added to the list of features above:
 Cardiac outflow tracts
 Face and lips

It is likely that the "optimal scan" will only improve the detection of cardiac abnormalities and clefts.
However, ensuring the outflow tracts are intact takes additional time and may require the woman to return
for a further check in 15% of cases; an additional 9% may need another visit. Also, more skill is required.
Not all centres can therefore offer these features (RCOG, 2000).

The 3rd trimester ultrasound scan

An ultrasound scan may be done at 28-34 weeks of gestation to ensure that foetal biometry and amniotic
fluid index (AFI) are within normal range and to check presentation and placental location. However,
routine use of ultrasound screening examination in the third trimester is not supported by available data.
Although early identification of growth-restricted foetuses allows for closer surveillance and earlier
intervention in case of decompensation, the use of ultrasound in the third trimester to screen for fetal
growth disturbance in low risk women has not been effective for reliably detecting these foetuses or
improving outcome. (Lockwood et al, 2013) However, a third trimester ultrasound scan is indicated in
pregnancies at risk of, or when there is suspicion of, suboptimal foetal growth.

Doppler Ultrasound Screening

The application of Doppler to obstetrical ultrasound provides information on function in addition to form.
Doppler velocimetry of the fetal circulation is used to assess vascular impedance, especially in the setting
of suspected growth restriction. Multiple trials have evaluated the use of Doppler ultrasound as a
screening tool in low risk women. These have consistently found neither maternal nor foetal benefit,
which is in contrast to the proven benefit in high-risk pregnancies. (Sfakianaki et al, 2014)

Advanced techniques
Additional clinical techniques are used selectively to provide further evaluation of uncertain findings on
real time grey scale two dimensional sonography (Shipp, 2013):

Three-dimensional sonography. Three-dimensional sonography refers to a two-dimensional static

display of three-dimensional data. Special probes and software are needed to acquire and render the
images. Although not a new technique, the indications for its use have not been well-defined. The use of
three-dimensional technology can reduce scanning time while maintaining adequate visualization of the
foetus in obstetrical ultrasound. Surface rendering of the foetus with three-dimensional sonography can
better demonstrate abnormalities previously detected with two-dimensional sonography, especially facial
abnormalities and neural tube defects. Foetal central nervous system three-dimensional data sets can be
examined remotely to diagnose foetal brain malformations.

Four-dimensional sonography. Four-dimensional sonography refers to three-dimensional images that

can be viewed in real-time. It is also called dynamic three-dimensional sonography. It has been used to
study the foetal heart, foetal movement, and foetal behavioural states.

References
1. RCOG. Supplement to Ultrasound Screening for Foetal Abnormalities. July 2000.URL:
http://www.rcog.org.uk (accessed 11 January 2014)
2. O'Brien GD, Robinson HP, Warren P. The 18 to 20 week obstetrical scan. A joint statement from the
Australasian Society for Ultrasound in Medicine, the Royal Australian College of Obstetricians and
Gynaecologists and the Royal Australasian College of Radiologists. Med J Aust. 1993 Apr 19;158(8):567-70
(Historically, a landmark paper).
3. Anna K Sfakianaki et al. Routine prenatal ultrasonography as a screening tool. UpToDate. 2014
4. Beryl R Benacerraf. Sonographic findings associated with fetal aneuploidy. UpToDate. 2013
5. Thomas D Shipp. Ultrasound examination in obstetrics and gynecology. UpToDate. 2013
6. Charles J Lockwood et al. Prenatal care (second and third trimesters). UpToDate. 2013

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 M8.1.1R7
DRUG USE IN PREGNANCY

INTRODUCTION

In pregnancy, drugs should be prescribed only if the expected benefit to the mother is thought to be
greater than the risk to the foetus, and all drugs should be avoided if possible during the first trimester.

Drugs which have been extensively used in pregnancy and appear to be usually safe should be prescribed
in preference to new or untried drugs; and the smallest effective dose should be used. Few drugs have
been shown conclusively to be teratogenic in man but no drug is safe beyond all doubt in early
pregnancy. Therefore, it is prudent to minimize the number of medications taken, limit use of medication
to situations where the benefit clearly outweighs the risk, choose medications with the best safety profile,
and use them at the lowest dose and for the shortest duration that is effective (Lockwood, 2014).

During the first trimester, drugs may produce congenital malformations (teratogenesis), and the period of
greatest risk is from the third to the eleventh week of pregnancy. During the second and third trimesters,
drugs may affect the growth and functional development of the foetus or have toxic effects on foetal
tissues; and drugs given shortly before term or during labour may have adverse effects on labour or on the
neonate after delivery.

Some medications commonly used in pregnancy have been covered in M8.1.1R4. Table 1 shows the
definitions and management strategies from the US Food and Drug Administration categories for drugs
taken during pregnancy. Table 2 shows a list of known teratogens in humans.

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 TABLE 1. FDA PREGNANCY RISK CATEGORIES

CATEGORY DEFINITION MANAGEMENT STRATEGY

Adequate and well-controlled studies in pregnant Because studies are not able to rule out the possibility of
A women have failed to demonstrate a risk to the foetus in harm, (name of drug) should be used during pregnancy only
the first trimester of pregnancy. if clearly indicated.
Animal reproduction studies have failed to demonstrate Because the studies of humans cannot rule out the
a risk to the foetus, but there are no adequate and well- possibility of harm, (name of drug) should be used during
controlled studies of pregnant women. Or animal pregnancy only if clearly needed.
B
studies demonstrate a risk, and adequate and well-
controlled studies in pregnant women have not been
done during the first trimester.
Animal reproduction studies have shown an adverse (Name of drug) should be given to pregnant women only if
effect on the foetus, but there are no adequate and well- clearly needed.
controlled studies of humans. The benefits from the use
C of the drug in pregnant women might be acceptable
despite its potential risks. Or animal studies have not
been conducted and there are no adequate and well-
controlled studies of humans.
There is positive evidence of human foetal risk based If this drug is used during pregnancy, or if the patient
on adverse reaction data from investigational or becomes pregnant while taking this drug, the patient should
D marketing experience or studies of humans, but the be apprised of the potential hazard to the foetus.
potential benefits from the use of the drug in pregnant
women might be acceptable despite its potential risks.
Studies in animals or humans have demonstrated foetal (Name of drug) is contraindicated in women who are or
abnormalities or there is positive evidence of foetal risk might become pregnant. If this drug is used during
based on adverse reaction reports from investigational pregnancy, or if the patient becomes pregnant while taking
X
or marketing experience, or both. The risk involved in this drug, the patient should be apprised of the potential
the use of the drug in pregnant women clearly hazard to the foetus.
outweighs any possible benefits.
Source: Law R et al, 2010.

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 TABLE 11. SELECTED AGENTS WITH POTENTIAL ADVERSE FETAL EFFECTS
Reproductive toxin
Aminopterin, methotrexate
Androgens
Angiotensin-converting
enzyme inhibitors and
angiotensin receptor blockers
Antidepressants
Antituberculous therapy
Caffeine
Chorionic villous sampling
(<10 weeks)
Cobalt in hematemic
multivitamins
Cocaine
Corticosteroids
Cyclophosphamide and other
chemotherapeutic agents
and immunosuppressive
agents (e.g, cyclosporine,
leflunomide)
Diethylstilbestrol
Ethyl alcohol
Ionizing radiation
Insulin shock therapy
Lithium therapy
Minoxidil
Methimazole
Methylene blue intra-amniotic
instillation
Misoprostol
Mycophenolate mofetil
Penicillamine (D-
penicillamine)
Progestin therapy
Alleged effects
Growth retardation, microcephaly, meningomyelocele, mental retardation, hydrocephalus, and
cleft palate
Masculinization of the developing female fetus can occur from androgens and high doses of
some male-derived progestins.
Fetal hypotension syndrome in second and third trimester resulting in fetal kidney
hypoperfusion and anuria, oligohydramnios, pulmonary hypoplasia, and cranial bone
hypoplasia. Heart defects from 1st trimester exposure.
Recent publications have implicated some of the SSRIs administered in the last trimester with
postnatal neurobehavioral effects that are transient and whose long-term effects have not
been determined. First-trimester exposures to some SSRIs have been reported to increase the
risk of some congenital malformations, predominantly congenital heart disease. The results
have not been consistent, but warnings have been issued.
Isoniazid and paraaminosalicylic acid have an increased risk for some CNS abnormalities.
Moderate caffeine exposure is not associated with birth defects; high exposures are
associated with an increased risk of abortion but the data are inconsistent.
Vascular disruption malformations (i.e., limb-reduction defects).
Fetal goiter.
Vascular disruptive type malformations in very low incidence; pregnancy loss.
High exposures administered systemically have a low risk for cleft palate in some studies, but
the epidemiologic studies are not consistent.
Many chemotherapeutic agents used to treat cancer have a theoretical risk for producing
malformations in the fetus when administered to pregnant women, especially because most of
these drugs are teratogenic in animals, but the clinical data are not consistent. Many of these
drugs have not been shown to be teratogenic, but the numbers of cases in the studies are
small. Caution is the byword.
Administration during pregnancy produces genital abnormalities, adenosis, and clear cell
adenocarcinoma of vagina in adolescents. The last has a risk of 1:1000 to 1:10,000, but the
other effects, such as adenosis, can be quite high.
Fetal alcohol syndrome consists of microcephaly, mental retardation, growth retardation,
typical facial dysmorphogenesis, abnormal ears, small palpebral fissures.
Radiation exposure above a threshold of 20 rad (0.2 Gy) can increase the risk for some fetal
effects such as microcephaly or growth retardation, but the threshold for mental retardation is
higher.
Insulin shock therapy, when administered to pregnant women, resulted in microcephaly,
mental retardation.
Chronic usage for the treatment of manic depressive illness has an increased risk for Ebstein's
anomaly and other malformations, but the risk seems to be very low.
This drug's promotion of hair growth was discovered because administration during pregnancy
resulted in hirsutism in newborns.
Aplasia cutis has been reported to be increased in mothers administered this drug during
pregnancy*.
Fetal intestinal atresia, hemolytic anemia, and jaundice in neonatal period. This procedure is
no longer used to identify one twin.
A low incidence of vascular disruptive phenomenon, such as limb-reduction defects and
Mobius syndrome, has been reported in pregnancies in which this drug was used to induce an
abortion.
1st trimester exposure associated with miscarriage, abnormalities of the ear, distal limbs,
heart, esophagus, kidney, and cleft lip/palate.
This drug results in the physical effects referred to as "lathyrism," the results of poisoning by
the seeds of the genus Lathyrus. It causes collagen disruption, cutis laxa, and hyperflexibility
of joints. The condition seems to be reversible, and the risk is low.
Very high doses of androgen hormone-derived progestins can produce masculinization. Many
drugs with progestational activity do not have masculinizing potential. None of these drugs
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 have the potential for producing nongenital malformations.
Propylthiouracil This drug and other antithyroid medications administered during pregnancy can result in an
infant born with a goiter.
Radioactive isotopes Tissue- and organ-specific damage depends on the radioisotope element and distribution (ie,
high doses of Iodine-131 administered to a pregnant woman can cause fetal thyroid
hypoplasia after the eighth week of development).
Retinoids Systemic retinoic acid, isotretinoin, and etretinate can cause increased risk of CNS,
cardioaortic, ear, and clefting defects such as microtia, anotia, thymic aplasia, other branchial
arch and aortic arch abnormalities, and certain congenital heart malformations.
Retinoids, topical Topical administration is very unlikely to have teratogenic potential, because teratogenic
serum levels cannot be attained by topical exposure to retinoids.
Streptomycin Streptomycin and a group of ototoxic drugs can affect the eighth nerve and interfere with
hearing; it is a relatively low-risk phenomenon. Children are less sensitive than adults to the
ototoxic effects of these drugs.
Sulfa drugs and vitamin K These drugs can produce hemolysis in some subpopulations of fetuses.
Tetracycline This drug produces bone and teeth staining, it does not increase the risk of any other
malformations.
Thalidomide This drug results in an increased incidence of deafness, anotia, preaxial limb-reduction
defects, phocomelia, ventricular septal defects, and gastrointestinal atresias. The susceptible
period is from the twenty-second to the thirty-sixth day after conception.
Trimethoprim This drug was used frequently to treat urinary tract infections and has been linked to an
increased incidence of neural tube defects. The risk is not high, but it is biologically plausible
because of the drug's effect on lowering folic acid levels, which has resulted in neurologic
symptoms in adults taking this drug.
Vitamin A The malformations reported with the retinoids have been reported with very high doses of
vitamin A (retinol). Dosages to produce birth defects would have to be in excess of 25,000 to
50,000 units/d.
Warfarin and warfarin Early exposure during pregnancy can result in nasal hypoplasia, stippling of secondary
derivatives epiphysis, intrauterine growth restriction. Central nervous system malformations can occur in
late pregnancy exposure because of bleeding.

Anticonvulsants

Phenytoin Increases risk of fetal hydantoin syndrome, consisting of facial dysmorphology, cleft palate,
ventricular septal defect, and growth and mental retardation.
Trimethadione and Increases the risk of characteristic facial dysmorphology, mental retardation, V-shaped
paramethadione eyebrows, low-set ears with anteriorly folded helix, high-arched palate, irregular teeth, CNS
anomalies, and severe developmental delay.
Valproic acid Increases the risk of spina bifida, facial dysmorphology, autism, atrial septal defect, cleft
palate, hypospadias, polydactyly, and craniosynostosis.
Carbamazepine Increases the risk facial dysmorphology, neural tube defects, cardiovascular defects, and
urinary tract defects.

Chemicals

Carbon monoxide poisoning Central nervous system damage has been reported with very high exposures, but the risk
seems to be low*.
Lead Very high exposures can cause pregnancy loss; intrauterine teratogenesis is not established at
very low exposures below 20 microgram/percent in the serum of pregnant mothers.
Gasoline addiction Facial dysmorphology, mental retardation
embryopathy
Methyl mercury Minamata disease consists of cerebral palsy, microcephaly, mental retardation, blindness, and
cerebellum hypoplasia. Other epidemics have occurred from adulteration of wheat with
mercurycontaining chemicals that are used to prevent grain spoilage. Present environmental
levels of mercury are unlikely to represent a teratogenic risk, but reducing or limiting the
consumption of carnivorous fish has been suggested to avoid exceeding the maximum
permissible exposure recommended by the Environmental Protection Agency, an exposure
level far below the level at which the toxic effects of mercury are seen.
Polychlorinated biphenyls Poisoning has occurred from adulteration of food products ("Cola-colored babies," CNS
effects, pigmentation of gums, nails, teeth, and groin; hypoplastic deformed nails; intrauterine

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 growth retardation; abnormal skull calcification). The threshold exposure has not been
determined, but it is unlikely to be teratogenic at the present environmental exposures.
Toluene addiction Facial dysmorphology, mental retardation
embryopathy

Embryonic and fetal infections

Cytomegalovirus infection Retinopathy, CNS calcification, microcephaly, mental retardation

Rubella Deafness, congenital heart disease, microcephaly, cataracts, mental retardation
Herpes simplex Fetal infection, liver disease, death
HIV Perinatal HIV infection
Parvovirus infection, B19 Stillbirth, hydrops
Syphilis Maculopapular rash, hepatosplenomegaly, deformed nails, osteochondritis at joints of
extremities, congenital neurosyphilis, abnormal epiphyses, chorioretinitis
Toxoplasmosis Hydrocephaly, microphthalmia, chorioretinitis, mental retardation
Varicella zoster Skin and muscle defects; intrauterine growth retardation; limb reduction defects, CNS damage
(very low increased risk)
Venezuelan equine Hydranencephaly; microphthalmia; destructive CNS lesions; luxation of hip
encephalitis

Maternal disease states

Corticosteroid-secreting
endocrinopathy
Iodine deficiency
Intrauterine problems of
constraint and vascular
disruption
Maternal androgen
endocrinopathy (adrenal
tumors)
Maternal diabetes with poor
glycemic control
Maternal folic acid in reduced
amounts
Maternal phenylketonuria
Maternal starvation
Tobacco smoking
Zinc deficiency*
CNS: central nervous system.
* Controversial.
Mothers who have Cushing's disease can have infants with hyperadrenocortism, but anatomic
malformations do not seem to be increased.
Can result in embryonic goiter and mental retardation.
These defects are more common in multiple-birth pregnancies, pregnancies with anatomic
defects of the uterus, placental emboli, or amniotic bands. Possible birth defects include club
feet, limb-reduction defects, aplasia cutis, cranial asymmetry, external ear malformations,
midline closure defects, cleft palate and muscle aplasia, cleft lip, omphalocele, and
encephalocele).
Masculinization of female fetuses
Increases the risk of a wide variety of congenital anomalies; cardiac abnormalites are most
common.
An increased incidence of neural tube defects.
Abortion, microcephaly, and mental retardation; very high risk in untreated patients.
Intrauterine growth restriction, abortion, neural tube defects (Dutch famine experience)
Abortion, intrauterine growth restriction, stillbirth
Neural tube defects*

Source: Lockwood, 2014. Reproduced with permission from: Brent, RL. How does a physician avoid prescribing drugs and
medical procedures that have reproductive and developmental risks? Clin Perinatol 2007; 34:233. Copyright © 2007 Elsevier.
Updated July 15, 2010 Gerald Briggs, B.Pharm.

Reference
1. Law R et al. FDA pregnancy risk categories and the CPS: do they help or are they a hindrance? Can Fam
Physician. 2010 Mar;56(3):239-41.
2. Charles J Lockwood et al. Initial prenatal assessment and first trimester prenatal care. UpToDate. 2014

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 M8.1.1CS
CASE STUDIES

ANTENATAL CARE & DRUG USE IN PREGNANCY

M8.1.1CS.1

A 17-year-old patient sees you for antenatal care. She is not sure of her dates and says that her last
menses was three months ago. She has nausea which is worse in the morning.

Questions
Q1. What questions would be relevant to ask her in relation to the antenatal care in this patient?
Q2. How would you attempt to determine the gestational age of her pregnancy?
Q3. How would you manage her complaints? What antiemetics would you avoid?

M8.1.1CS.2

Madam T is expecting her third child. She is now 18 weeks by dates and attending a routine antenatal
clinic. Her first two pregnancies were uneventful and the two children are aged 4 years and 2 years. Her
usual doctor, your partner is away and he has asked you to look after her during his absence. The patient
is a patient on the shared care programme with a private obstetrician.

Questions
Q1. Discuss the antenatal care that she would need at this stage of her pregnancy.
Q2. What problems of pregnancy may arise at this stage of pregnancy?

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