Neural tube defect

Background
Neural tube defects (NTD) occur because of a defect in the neurulation process. Since the
anterior and posterior neuropores close last, they are the most vulnerable to defects.
Consequently, a majority of NTDs arise in these areas.

NTDs can be classified, based on embryological considerations and the presence or absence of
exposed neural tissue, as open or closed types.

• Open NTDs frequently involve the entire CNS (eg, associated hydrocephalus, Chiari II
malformation) and are due to failure of primary neurulation. Neural tissue is exposed
with associated cerebrospinal fluid (CSF) leakage.
• Closed NTDs are localized and confined to the spine (brain rarely affected) and result
from a defect in secondary neurulation. Neural tissue is not exposed and the defect is
fully epithelialized, although the skin covering the defect may be dysplastic.

Cranial presentations include the following:

• Anencephaly
• Encephalocele (meningocele or meningomyelocele)
• Craniorachischisis totalis
• Congenital dermal sinus

Spinal presentations include the following:

• Spina bifida aperta (cystica)

• Myelomeningocele
• Meningocele
• Myeloschisis
• Congenital dermal sinus
• Lipomatous malformations (lipomyelomeningoceles)
• Split-cord malformations
• Diastematomyelia
• Diplomyelia
• Caudal agenesis

For more information on the classification of neural tube defects, see eMedicine article Spinal
Dysraphism/Myelomeningocele.

Pathophysiology
Two distinct processes appear to be involved in the formation of the neural tube: primary
neurulation and secondary neurulation (ie, canalization). The neural plate and the notochord are
formed during early embryonic development. The neural groove develops by the third
gestational week. Subsequently, the neural folds form bilaterally.

Primary neurulation
 • The neural folds elevate, approximate each other, and start closing, thus forming the
neural tube.
• The point of initial closure occurs at the caudal rhombencephalon or cranial spinal cord.
• The cutaneous ectoderm fuses first, followed by the neuroectoderm.
• The cranial neuropore closes during the fourth gestational week. The last area to close is
the commissural plate.
• The caudal neuropore closes between T11 and S2.
• Parallel to this process, the cutaneous ectoderm separates from the neuroectoderm to
form the overlying skin, while the lateral mesoderm migrates between the 2 ectodermal
layers to form the posterior vertebral arches.

Secondary neurulation (canalization)

• This comprises further neural development occurring caudal to the caudal neuropore after
the termination of primary neurulation.
• This process includes formation of the filum terminale and conus medullaris from a
poorly differentiated cell mass of the medial eminence.
• Because of differential growth between the vertebral column and the spinal cord, the
conus becomes more rostral during later development.

Open NTDs have been suggested to result from defective primary neurulation while defective
secondary neurulation gives rise to closed NTDs. However, this issue is not settled. Another
possible explanation is that open NTDs (spina bifida in particular) result from defects in either
primary or secondary neurulation, depending on their site being cranial or caudal to the posterior
neuropore (ie, upper and lower spina bifida, respectively).

Frequency
United States

• The incidence of NTDs declined 50% between 1970 and 1989 (0.6-1.3 cases per 1000
live births) in the United States.
• During this period, the proportion of spina bifida cases increased relative to anencephaly.
• The race ratio of whites to other races for isolated NTDs decreased and the risk of
isolated NTDs in female infants also decreased.
• The highest incidence is in Appalachia (1 case per 1000 live births).
• Incidence is higher in the eastern United States than on the West Coast.

International

• NTDs are among the most common birth defects.

• They exhibit a marked geographical variation, with the incidence higher in Great Britain
and lower in Japan.
• In white populations, the lowest birth incidence was noted in mainland Europe and the
highest in Great Britain (especially Ireland).
• Currently, the highest reported incidence is in Northern China (3.7 cases per 1000 live
births).
 • Indian and Eastern Mediterranean populations (with the exception of Israeli Jews) also
have relatively high incidences of NTDs. However, unlike the Western white
populations, anencephaly is more common than spina bifida.

Mortality/Morbidity

• Anencephaly is incompatible with life.

o No differentiated supratentorial neural tissue is present, and the brain stem
consists of nests of poorly differentiated neural elements.
o The brain stem is believed by some to be not sufficiently developed to be
responsible for the temporary brainstem reflexes that are observed. Some have
implicated the upper cervical cord as the seat of these functions.
o The survival of these newborns is limited to a few hours (rarely >2 d).
o In an earlier policy statement, the American Medical Association recommended
that organs could be harvested from anencephalic infants even before the
traditional criteria of death are met. However, the statement has since been
revoked.
• Other NTDs may give rise to progressive neurological deterioration, which may present
early after birth or later in life.
o The neurological deficits may be due to accompanying hydrocephalus, a Chiari II
malformation, tethering of the cord, cystic mass, or fibrous band compressing the
neural elements.
o Another possible complication is meningitis (infectious or chemical), especially in
open NTDs.
o The average recurrence risk of NTDs for parents with one affected child has been
estimated to be about 5%, and that for monozygotic twins about 20%. Recurrence
risks are higher in populations with a higher birth incidence.
• The most common NTD compatible with life is myelomeningocele (see Media files 1-2).
o Its incidence is 1 case in 1,200-1,400 live births. It is a disease affecting 6,000-
11,000 newborns in the United States each year.
o Paralysis, bladder and bowel incontinence, and hydrocephalus are the most
common clinical complications. Severe mental retardation is present in 10-15% of
these patients.
o Despite aggressive medical care, 10-15% of these children die prior to reaching
the first grade. However, most children with isolated myelomeningocele (without
major anomalies of other organs) survive to adulthood, and life expectancy is
nearly normal.
o Sixty percent have normal intelligence, although of these, 60% have some
learning disability (math and problem solving being particularly difficult).
 Attention deficit disorder without hyperactivity also has been described in
these children.
 Hydrocephalus is present in 85% but bears little relationship to
intelligence.
 About 80% are socially continent (although many require clean
intermittent catheterization).
Race

• In studies done before the availability of prenatal screening and prophylactic vitamin
supplementation, birth incidence of both spina bifida and anencephaly was reported to be
higher in the European white population than in the black population.
• In North America, the risk of NTDs was found to be highest in the Hispanic population
(more than 3-fold higher than that for non-Hispanic whites).
• Migration studies in the white migrant population showed a prevalence of NTDs that
corresponded more closely to the risk of the place to which they had migrated, as
opposed to the place of their origin.
o In contrast, similar studies in descendants of the black and Asian migrant
populations in Europe and North America showed prevalences not substantially
higher than those of their parent countries.
o These variations are consistent with the theory that NTDs are a phenotypically
heterogeneous group of malformations with multifactorial inheritance in some
cases and single gene defects in others.

Sex

• Anencephaly has a female preponderance, especially among premature births, with a

female-to-male ratio of 3:1.
• Other NTDs above the thoracolumbar junction show a mild female preponderance.
• No such gender difference has been noted in more distal forms of spina bifida.

Age

• Open NTDs are readily visible at birth, with the majority being discovered during
pregnancy.
• Closed NTDs may remain undetected for years, even decades, especially in the absence
of cutaneous markers.

Clinical
History

• Most open NTDs are readily apparent at the time of birth.

• Closed NTDs have a variable presentation.
o The most common presentation of a closed NTD is an obvious abnormality along
the spine such as a fluid-filled cystic mass, area of hypopigmentation or
hyperpigmentation, cutis aplasia, congenital dermal sinus, capillary
telangiectasia/hemangioma, hairy patch (hypertrichosis), skin appendages, or
asymmetrical gluteal cleft.
 Common to all these patients is a fully epithelialized lesion and no visible
neural tissue.
 A closed NTD can present without a cutaneous marker.
 o The second most common reason for seeking medical attention is asymmetry of
the legs and/or feet. One calf can be thinner, with a smaller foot on the same side,
higher arch, and hammering or clawing of the toes.
o Other children exhibit progressive spinal deformities such as scoliosis.
o Some children present with a picture of progressive neurological deficits that may
include weakness in one distal lower extremity, sensory loss in the same
distribution, and bladder or bowel dysfunction.
o Low back pain also can occur, sometimes without neurological deficit. Pain is
more common in older children or adolescents.
o Adults can present with the sudden onset of pain, motor and sensory loss, and
bladder dysfunction after an acute trauma (eg, fall, motor vehicle accident,
placement in lithotomy position). The reason for such presentation may be related
to tethering of the cord (the distal end of the spinal cord is fixed in position).
Mechanical forces associated with motion may produce compression and/or
vascular insufficiency.
o A patient with a closed NTD such as a congenital dermal sinus with an intraspinal
dermoid cyst or a neurenteric cyst can present with symptoms of spinal cord
compression due to enlargement of the mass.
o A patient with a dermal sinus also can present with bacterial meningitis or spinal
abscess.
o Neurenteric or dermoid cysts also can present with repeated bouts of aseptic
meningitis due to leaking of the contents into the spinal subarachnoid space.

Physical
A complete neurological assessment of the newborn with an open NTD should be performed to
document the many possible structural and neurological problems. This provides a baseline for
future comparison.

• Particularly important aspects of the evaluation are measurement of head circumference,

assessment of general vigor (especially cry and sucking), upper extremity motor function,
anal sphincter, and urinary stream, as well as thorough motor and sensory examination of
the lower extremities and trunk.
• Usually the level of sensory dysfunction is slightly greater than the dysfunction detected
on the motor examination.
• Motor examination involves observation of muscle bulk, spontaneous active movements,
movements in response to stimulation, as well as assessment of muscle tone by palpation.
• Further information regarding the level of neurological dysfunction can be obtained from
evaluation of hip and foot deformities. If the disparity in segmental level between the 2
sides is more than 1 level, an occult neurological problem must be suspected (eg,
hemimyelia).
• The spine should be examined carefully, with determination of the size and site of the
lesion.
o The shape of the defect, size of the placode, and health and laxity of the
surrounding skin and soft tissue should be noted carefully.
o The presence of early spinal deformity (eg, kyphosis) also should be assessed.
Causes

• Several genetic and environmental factors have been implicated in the pathogenesis of
NTDs.
o A slight female predominance, and the higher incidence in certain ethnic groups
and in the offspring of consanguineous marriages, have suggested a genetic basis
for NTDs.
o Chromosomal abnormalities (trisomy 13, 18, 21) also have been associated with
NTDs.
o Concordance between monozygotic twins is low. Thus, genetic abnormalities are
more likely to predispose to environmental factors.
• Possible environmental factors include geographic location, season of conception,
socioeconomic class, maternal diabetes, maternal age, zinc and folate deficiencies,
maternal alcohol abuse, maternal use of valproate, and intrauterine hyperthermia.
• Marked seasonal trends in the birth incidence of NTDs have been reported. Anencephaly
and spina bifida tend to occur more frequently in spring conceptions (anencephaly
peaking in early spring and spina bifida in late spring). This is especially true in areas
where the risk is high; however, most US studies failed to demonstrate such variations.
• Since encephaloceles do not exhibit geographic, gender, or ethnic variations, some have
proposed that they occur after the completion of neurulation.
Neural tube defects (NTDs) are one of the most common birth defects, occurring in
approximately one in 1,000[1] live births in the United States. An NTD is an opening in the spinal
cord or brain that occurs very early in human development. In about the 3rd or 4th weeks of
pregnancy, specialized cells on the dorsal side of the fetus begin to fuse and form the neural tube.
When the neural tube does not close completely, an NTD develops.

Types of NTDs

There are two types of NTDs: open, which are more common, and closed. Open NTDs occur
when the brain and/or spinal cord are exposed at birth through a defect in the skull or vertebrae
(back bones). Examples of open NTDs
are anencephaly, encephaloceles, hydranencephaly, iniencephaly, schizencephaly,and spina
bifida. Rarer types of NTDs are called closed NTDs. Closed NTDs occur when the spinal defect
is covered by skin. Common examples of closed NTDs
are lipomyelomeningocele, lipomeningocele, and tethered cord.
[edit]Anencephaly
Anencephaly (without brain) is a neural tube defect that occurs when the head end of the neural
tube fails to close, usually during the 23rd and 26th days of pregnancy, resulting in an absence of
a major portion of the brain and skull. Infants born with this condition are born without the main
part of the forebrain-the largest part of the cerebrum. Infants born with this condition are usually
blind, deaf and unconscious. The lack of a functioning cerebrum will ensure that the infant will
never gain consciousness. Infants are either stillborn or usually die within a few hours or days
after birth.
[edit]Encephaloceles
Encephaloceles are a neural tube defect that characterize by sac-like protrusion of the brain
though through the opening in the skull. The defect is caused by the incomplete closure of the
cranium during development.
[edit]Hydranencephaly
Hydranencephaly is a condition in which the cerebral hemispheres are missing and instead filled
with sacs filled with cerebrospinal fluid.
[edit]Iniencephaly
This is a rare neural tube defect that results in extreme bending of the head to the spine. The
diagnosis can usually be made on antenatal ultrasound scanning but if not will undoubtedly be
made immediately after birth because the head is bent backwards and the face looks upwards.
Usually the neck is absent. The skin of the face connects directly to the chest and the scalp
connect to the upper back. The infant usually will not survive more than a few hours.
[edit]Spina Bifida
Spina Bifida is further divided into two subclasses, Spina Bifida Cystica and Spina Bifida
Occulta.
[edit]Spina Bifida Cystica
This includes meningocele and myelomeningocele. Meningocele is less severe and is
characterized by herniation of the meninges, but not the spinal cord, through the opening in the
spinal canal. Myeolomeningocele involves herniation of the meninges as well as the spinal cord
through the opening.[2]
[edit]Spina Bifida Occulta
In this type of neural tube defect, the meninges do not herniate through the opening in the spinal
canal.[2]
[edit]Causes

Neural tube defects are cause by multiple genes and environmental factors which are not
completely understood.[3] Although more than 200 genes are known to cause NTDs in mice, the
cause of NTDs in human is still poorly understood.[4] The failure to identify a single gene factor
suggests that the major causes of human NTDs are from the summation of genetic,
environmental and nutritional factors.[5] [6] Research has shown that women with folic
acid deficiencies also have a higher chance of having a child with a neural tube defect, but this is
only one factor. Taking folic acid does not completely negate the risk of neural tube problems,
but it does significantly reduce the risk. Folic acid deficiency leads to hyper-
homocysteinemia,which in turn results in neural tube defects.[7]
[edit]Folic acid pathway

Folic acid and vitamin B12 are very important in reducing the occurrences of NTDs. [8] Folate is
required for production and maintenance of new cells., for DNA synthesis and RNA synthesis.
Folate is needed to carry one carbon groups for methylation and nucleic acid synthesis. Vitamin
B12 is also an important receptor in the folic acid biopathway such that studies have shown
deficiency in vitamin B12 contributes to risk of NTDs as well. [9]

[edit]Other Causes
Other potential causes can include folate antimetabolites (such as methotrexate), maternal
diabetes, maternal obesity, mycotoxins in contaminated corn meal, arsenic, and hyperthermia in
early development[10].[11][12] Studies have shown that both maternal cigarette smoking and
maternal exposure to secondhand smoke increased the risk for neural tube defects in offspring. A
mechanism by which maternal exposure to cigarette smoke could increase NTD risk in offspring
is suggested by several studies which show an association between cigarette smoking and
homocysteine levels. The study suggests that cigarette smoke including secondhand exposure is
not only hazardous to the mother but may also interfere with neural tube closure in the
developing embryo.[13]
[edit]Detection

Tests for neural tube defects include ultrasound examination and measurement of maternal serum
alpha-fetoprotein(MSAFP). Amniotic fluid alpha-fetoprotein(AFAFP) and amniotic fluid
acetylcholinesterase(AFAChE) tests are also used to confirming if ultrasound screening indicates
a positive risk.[14] Often, these defects are apparent at birth, but occult defects may be not
diagnosed until much later in life. An elevated MSAFP measured at 16-18 weeks gestation is a
good predictor of neural tube defects.
[edit]Prevention

In 1996, the United States Food and Drug Administration published regulations requiring the
addition of folic acid to enriched breads, cereals, flour and other grain products. [15]It is important
to note that during the first four weeks of pregnancy (when most women do not even realize that
they are pregnant), adequate folic intake is essential for proper operation of
the neurulation process. Therefore, women who could become pregnant are advised to eat foods
fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the
risks of serious birth defects. [16][17][18] In Canada, mandatory fortification of selected foods with
folic acid has been shown to reduce the incidence of neural tube defects by 46%[19].

Women who could become pregnant are advised to get 400 micrograms of folic acid daily.
Women who are pregnant should receive 1.0 mg daily, and women who have previously given
birth to a child with a neural tube defect should get 4.0 mg daily.[20]
[edit]Treatment

Treatments of NTDs depends on the severity of the complication. No treatment is available for
anencephaly because the infants usually do not survive more than few hours. Aggressive surgical
management has improved survival and functions of infants with spina bifida and meningoceles
and mild myelomeningoceles. The success of surgery often depends on the amount of brain
tissue involved in the encephalocele. The goal of treatment for NTDs is to allow the individual to
achieve the highest level of function and independence.

Note !!! co-related po un apgar and ballard po ahhh tignan lng po kng magagamit mo po
un tlg ….
Newborn screening is the process of testing newborn babies for
treatable genetic, endocrinologic, metabolic and hematologic diseases.[1][2] Newborn screening
has been adopted by most countries around the world, though the lists of screened diseases vary
widely, anywhere from 1 disorder to more than 100 disorders.

Disease qualification

Common considerations in determining whether to screen for disorders:

1. A disease that can be missed clinically at birth

2. A high enough frequency in the population
3. A delay in diagnosis will induce irreversible damages to the baby
4. A simple and reasonably reliable test exists
5. A treatment or intervention that makes a difference if the disease is detected early

[edit]Newborn screening in the United States

The following tests are mandated (required to be performed on every newborn born in the state)
in most of the United States. According to the U.S. Centers for Disease Control, approximately
3,000 babies with severe disorders are identified in the United States each year using newborn
screening programs at current testing rates. States vary, and not all tests are required in every
state, and a few states mandate more than this. The first test to be universally mandated across
the U.S. was the Guthrie test for phenylketonuria (PKU), and in many areas and hospitals, the
newborn blood test is often erroneously referred to as a "PKU test", even though all states now
universally test for congenital hypothyroidism, galactosemia, and increasing numbers of other
diseases as well.

 Endocrine disorders: Congenital adrenal hyperplasia (CAH), Congenital hypothyroidism

 Blood cell disorders: sickle-cell disease (SS)
 Inborn errors of carbohydrate metabolism: Galactosemia
 Inborn errors of amino acid metabolism: Phenylketonuria (PKU), Maple syrup urine
disease (MSUD), Homocystinuria
 Inborn errors of organic acid metabolism: Biotinidase deficiency

For a recent state-by-state list, see U.S. National Newborn Screening and Genetics Resource
Center. According to this resource, the only tests mandated in every state are the following:
  CH - Congenital hypothyroidism
 H-HPE - Benign hyperphenylalaninemia
 PKU -- Phenylketonuria/hyperphenylalaninemia
 HEAR - Hearing
 GALT - Transferase deficient galactosemia

[edit]Usual procedures and responses to positive results

Heel blood on a filter paper card for the newborn screening

In nearly all of the United States, the newborn screening program is a division of the state health
department. State law mandates collecting a sample by pricking the heel of a newborn baby to
get enough blood (typically, two to three drops) to fill a few circles on filter paper labeled with
names of infant, parent, hospital, and primary physician. It is usually specified that the sample be
obtained on the second or third day of life, after protein-containing feedings (i.e., breast
milk or formula) have started, and the postnatal TSH surge subsided. Every hospital in the state
as well as independent midwivessupervising home deliveries are required to collect the papers
and mail each batch each day to the central laboratory.

The state health department agency in charge of screening will either run a laboratory or contract
with a laboratory to run the mandated screening tests on the filter paper samples. The goal is to
report the results within a short period of time. If screens are normal, a paper report is sent to the
submitting hospital and parents rarely hear about it.

If an abnormality occurs, employees of the agency, usually nurses, begin to try to reach the
physician, hospital, and/or nursery by telephone. They are persistent until they can arrange an
evaluation of the infant by an appropriate specialist physician (depending on the disease). The
specialist will attempt to confirm the diagnosis by repeating the tests by a different method or
laboratory, or by performing other corroboratory or disproving tests. The confirmatory test varies
depending on the initial screen, and can include enzyme assays, DNA testing or MS/MS.
Depending on the likelihood of the diagnosis and the risk of delay, the specialist will initiate
treatment and provide information to the family. Performance of the program is reviewed
regularly and strenuous efforts are made to maintain a system that catches every infant with these
diagnoses. Guidelines for newborn screening and follow up have been published by
the American Academy of Pediatrics.[3]
[edit]Recommended target conditions and disorders
The following list includes most of the disorders detected by the expanded or supplemental
newborn screening by mass spectrometry. This expanded screening is not yet universally
mandated by most states, but may be privately purchased by parents or hospitals at a cost of
approximately US$80. The same can also be purchased from other countries like Germany,
Austria, Spain and India where more than 100 disorders are being tested based on a urine
sample of the newborn. Perhaps one in 5,000 infants will be positive for one of the metabolic
tests below (excluding the congenital infections).
[edit]Core panel
The following conditions and disorders were recommended as "core panel" by the 2005 report of
the American College of Medical Genetics (ACMG).[4] The incidences reported below are
from their report, pages 143-307, though the rates may vary in different populations.
(WARNING: The file is a very large PDF.)

Blood cell disorders

 Sickle cell anemia (Hb SS) > 1 in 5,000; among African-Americans 1 in 400
 Sickle-cell disease (Hb S/C) > 1 in 25,000
 Hb S/Beta-Thalassemia (Hb S/Th) > 1 in 50,000

Inborn errors of amino acid metabolism

 Tyrosinemia I (TYR I) < 1 in 100,000

 Argininosuccinic aciduria (ASA) < 1 in 100,000
 Citrullinemia (CIT) < 1 in 100,000
 Phenylketonuria (PKU) > 1 in 25,000
 Maple syrup urine disease (MSUD) < 1 in 100,000
 Homocystinuria (HCY) < 1 in 100,000

Inborn errors of organic acid metabolism

 Glutaric acidemia type I (GA I) > 1 in 75,000

 Hydroxymethylglutaryl lyase deficiency (HMG) < 1 in 100,000
  Isovaleric acidemia (IVA) < 1 in 100,000
 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC) > 1 in 75,000
 Methylmalonyl-CoA mutase deficiency (MUT) > 1 in 75,000
 Methylmalonic aciduria, cblA and cblB forms (MMA, Cbl A,B) < 1 in 100,000
 Beta-ketothiolase deficiency (BKT) < 1 in 100,000
 Propionic acidemia (PROP) > 1 in 75,000
 Multiple-CoA carboxylase deficiency (MCD) < 1 in 100,000

Inborn errors of fatty acid metabolism

 Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) > 1 in 75,000

 Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) > 1 in 25,000
 Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) > 1 in 75,000
 Trifunctional protein deficiency (TFP) < 1 in 100,000
 Carnitine uptake defect (CUD) < 1 in 100,000

Miscellaneous multisystem diseases

 Cystic fibrosis (CF) > 1 in 5,000

 Congenital hypothyroidism (CH) > 1 in 5,000
 Biotinidase deficiency (BIOT) > 1 in 75,000
 Congenital adrenal hyperplasia (CAH) > 1 in 25,000
 Classical galactosemia (GALT) > 1 in 50,000

Newborn screening by other methods than blood testing

 Congenital deafness (HEAR) > 1 in 5,000

[edit]Secondary targets
The following disorders are additional conditions that may be detected by screening. Many[4] are
listed as "secondary targets" by the 2005 report ACMG. Some states are now screening for more
than 50 congenital conditions. Many of these are rare and unfamiliar to pediatricians and other
primary health care professionals.[4]

Blood cell disorders

 Variant hemoglobinopathies (including Hb E)[4]

  Glucose-6-phosphate dehydrogenase deficiency (G6PD)

Inborn errors of amino acid metabolism

 Tyrosinemia II[4]
 Argininemia[4]
 Benign hyperphenylalaninemia
 Defects of biopterin cofactor biosynthesis[4]
 Defects of biopterin cofactor regeneration[4]
 Tyrosinemia III[4]
 Hypermethioninemia[4]
 Citrullinemia type II[4]

Inborn errors of organic acid metabolism

 Methylmalonic acidemia (Cbl C,D)[4]

 Malonic acidemia[4]
 2-Methyl 3-hydroxy butyric aciduria[4]
 Isobutyryl-CoA dehydrogenase deficiency[4]
 2-Methylbutyryl-CoA dehydrogenase deficiency [4]
 3-Methylglutaconyl-CoA hydratase deficiency[4]
 Glutaric acidemia type II
 HHH syndrome (Hyperammonemia, hyperornithinemia, homocitrullinuria syndrome)
 Beta-methyl crotonyl carboxylase deficiency
 Adenosylcobalamin synthesis defects

Inborn errors of fatty acid metabolism

 Medium/short-chain L-3-hydroxy acyl-CoA dehydrogenase deficiency[4]

 Medium-chain ketoacyl-CoA thiolase deficiency[4]
 Dienoyl-CoA reductase deficiency[4]
 Glutaric acidemia type II[4]
 Carnitine palmityl transferase deficiency type 1[4]
 Carnitine palmityl transferase deficiency type 2[4]
  Short-chain acyl-CoA dehydrogenase deficiency (SCAD)[4]
 Carnitine/acylcarnitine Translocase Deficiency (Translocase)[4]
 Short-chain hydroxy Acyl-CoA dehydrogenase deficiency (SCHAD)
 Long-chain acyl-CoA dehydrogenase deficiency (LCAD)
 Multiple acyl-CoA dehydrogenase deficiency (MADD)

Congenital infections

 TORCH complex (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes

simplex, Syphilis etc.), if there are indicative symptoms or mothers who may have been
exposed[5]
 HIV

Miscellaneous multisystem diseases

 Galactokinase deficiency[4]
 Galactose epimerase deficiency[4]
 Maternal vitamin B12 deficiency

Newborn Screening Program in the Philippines

The following tests are mandated in the R.A. 9288 or Newborn Screening program of
2004.Newborn screening is available in practicing health institutions (hospitals, lying-ins, Rural
Health Units and Health Centers) with cooperation with DOH. If babies are delivered at home,
babies may be brought to the nearest institution offering newborn screening. However, now there
is also a simple method by which the Newborn Screening can be made possible even at home.
The urine sample of newborn can be absorbed on filter paper and sent to laboratories which may
run the test. The reports are simple enough to be understood by the parents. A negative screen
mean that the result of the test is normal and the baby is not suffering from any of the disorders
being screened. In case of a positive screen, the NBS nurse coordinator will immediately inform
the coordinator of the institution where the sample was collected for recall of patients for
confirmatory testing. Babies with positive results should be referred at once to the nearest
hospital or specialist for confirmatory test and further management. Should there be no specialist
in the area, the NBS secretariat office will assist its attending physician. Disorders Screened:
Heel Prick Method for the newborn screening

 CH (Congenital hypothyroidism) - is a condition of thyroid hormone deficiency present

at birth. Approximately 1 in 4000 newborn infants has a severe deficiency of thyroid
function, while even more have mild or partial degrees. If untreated for several months after
birth, severe congenital hypothyroidism can lead to growth failure and permanent mental
retardation. Treatment consists of a daily dose of thyroid hormone (thyroxine) by mouth.
Because the treatment is simple, effective, and inexpensive, nearly all of the developed world
practices newborn screening to detect and treat congenital hypothyroidism in the first weeks
of life.
 CAH (Congenital adrenal hyperplasia) - refers to any of several autosomal recessive
diseases resulting from mutations of genes for enzymes mediating the biochemical steps of
production of cortisol from cholesterol by the adrenal glands (steroidogenesis). Most of these
conditions involve excessive or deficient production of sex steroids and can alter
development of primary or secondary sex characteristics in some affected infants, children,
or adults. Approximately 95% of cases of CAH are due to 21-hydroxylase deficiency.
 GAL (Galactosemia) - is a rare genetic metabolic disorder which affects an individual's
ability to properly metabolize the sugar galactose. Lactose in food (such as dairy products) is
broken down by the body into glucose and galactose. In individuals with galactosemia, the
enzymes needed for further metabolism of galactose are severely diminished or missing
entirely, leading to toxic levels of galactose to build up in the blood, resulting in
hepatomegaly (an enlarged liver), cirrhosis, renal failure, cataracts, and brain damage.
Without treatment, mortality in infants with galactosemia is about 75%.
 PKU (Phenylketonuria) - is an autosomal recessive genetic disorder characterized by a
deficiency in the enzyme phenylalanine hydroxylase (PAH). This enzyme is necessary to
metabolize the amino acid phenylalanine to the amino acid tyrosine. When PAH is deficient,
phenylalanine accumulates and is converted into phenylpyruvate (also known as
phenylketone), which is detected in the urine. PAH is found on chromosome number 12.Left
untreated, this condition can cause problems with brain development, leading to progressive
 mental retardation and seizures. However, PKU is one of the few genetic diseases that can be
controlled by diet. A diet low in phenylalanine and high in tyrosine can be a very effective
treatment. There is no cure. Damage done is irreversible so early detection is crucial.
 G6PD Deficiency - is an X-linked recessive hereditary disease characterized by
abnormally low levels of the glucose-6-phosphate dehydrogenase enzyme (abbreviated
G6PD or G6PDH). It is a metabolic enzyme involved in the pentose phosphate pathway,
especially important in red blood cell metabolism.

Newborn screening results are available within three weeks after the NBS Lab receives and tests
the samples sent by the institutions. However the time period is too long a wait to know a
disorder since the damage may already have started. There are few laboratories which give
results with in 24 to 48 hours from receipt of samples. Results are released by NBS Lab to the
institutions and are released to your attending birth attendants or physicians.Parents may seek the
results from the institutions where samples are collected. Christian Nieto,Emilio Aguinaldo
College-Manila
[edit]Expanded screening and controversies
With the development of tandem mass spectrometry in the early 1990s and now the
revolutionary GC/MS based technology with assisted analytic program, the number of detectable
diseases quickly grew, especially in the categories of fatty acid oxidation disorders and organic
acidoses. Screening tests for the disorders listed below (and an increasing number of others) are
now available, though not universally mandated. There is considerable variability from state to
state, and sometimes from hospital to hospital within a state, on disease that are screened. To
make matters more confusing, some hospitals routinely obtain supplemental screening (most of
the tests below) on all infants even if not mandated by the state or requested by parents. In recent
years in the United States, expanded newborn screening with tandem mass spectrometry has
become a profitable commercial venture. Ahead with this trend, now GC/MS based screening for
even more number of disorders has become a bigger success. The obvious advantage being a
urine sample absorbed on a filter paper, which can easily be transported to remote laboratories,
even if situated in different country. Though the debate is on about the number of disorders to be
tested, parents choose the tests for 'peace of mind'.

Newborn screening tests have become a subject of political controversy in the last decade. Two
California babies, Zachary Wyvill and Zachary Black, were both born with Glutaric acidemia
type I. Wyvill's birth hospital only tested for the four diseases mandated by state law, while
Black was born at a hospital that was participating in an expanded testing pilot program. Black's
disease was treated with diet and vitamins; Wyvill's disease went undetected for over six months,
and during that time the damage from the enzyme deficiency became irreversible. Birth-defects
lobbyists pushing for broader and more universal standards for newborn testing cite this as an
example of how much of an impact testing can have.

Instituting MS/MS screening often requires a sizable up front expenditure. When states choose to
run their own programs the initial costs for equipment, training and new staff can be significant.
Moreover, MS/MS gives only the screening result and not the confirmatory result. The same has
to be further done by higher technologies or procedure like GC/MS, Enzyme Assays or DNA
Tests. This in effect adds more cost burden and makes physicians lose precious time. To avoid at
least a portion of the up front costs, some states such as Mississippi have chosen to contract with
private labs for expanded screening. Others have chosen to form Regional Partnerships sharing
both costs and resources. But for many states, screening is an integrated part of the department of
health which can not or will not be easily replaced. Thus the initial expenditures can be difficult
for states with tight budgets to justify. Screening fees have also increased in recent years as
health care costs rise and more states add MS/MS screening to their programs. (See Report of
Summation of Fees Charged for Newborn Screening, 2001–2005) Dollars spent for these
programs may reduce resources available to other potentially lifesaving programs. It has been
recommended that one disorder, Short Chain Acyl-coenzyme A Dehydrogenase Deficiency, or
SCAD, be eliminated from screening programs, due to a "spurious association between SCAD
and symptoms. [6] However, recent studies suggest that expanded screening is cost effective
(see ACMG report page 94-95 and articles published in Pediatrics [7]'[8]. Advocates are quick to
point out studies such as these when trying to convince state legislatures to mandate expanded
screening.

Expanded newborn screening is also opposed by among some health care providers who are
concerned that effective follow-up and treatment may not be available, that false
positive screening tests may cause harm, and issues of informed consent[9].

Controversy has also erupted in some countries over collection and storge of blood or DNA
samples by government agencies during the routine newborn blood screen. It was revealed that
in Texas the state had collected and stored blood and DNA samples on millions of newborns
without the parents knowledge or consent. These samples were then used by the state for genetic
experiments and to setup a database to catalog all of the samples/newborns. [10]

Apgar scoring
The Apgar score was devised in 1952 by Dr. Virginia Apgar as a simple and repeatable method
to quickly and summarily assess the health of newbornchildren immediately after birth.[1]
[2]
Apgar was an anesthesiologist who developed the score in order to ascertain the effects
of obstetric anesthesia on babies.

The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale
from zero to two, then summing up the five values thus obtained. The resulting Apgar score
ranges from zero to 10. The five criteria (Appearance, Pulse, Grimace, Activity, Respiration) are
used as a mnemoniclearning aid.
Criteria

The five criteria of the Apgar score:

Component of
Score of 0 Score of 1 Score of 2
acronym

blue at extremities no cyanosis

Skin blue or pale all
body pink body and Appearance
color/Complexion over
(acrocyanosis) extremities pink

Pulse rate 0 <100 ≥100 Pulse

no response to grimace/feeble cry cry or pull away

Reflex irritability Grimace
stimulation when stimulated when stimulated

flexed arms and legs

Muscle tone none some flexion Activity
that resist extension

weak, irregular,
Breathing absent strong, lusty cry Respiration
gasping

[edit]Interpretation of scores
Mind map showing summery for the Apgar score

The test is generally done at one and five minutes after birth, and may be repeated later if the
score is and remains low. Scores 3 and below are generally regarded as critically low, 4 to 6
fairly low, and 7 to 10 generally normal.

A low score on the one-minute test may show that the neonate requires medical attention[3] but is
not necessarily an indication that there will be long-term problems, particularly if there is an
improvement by the stage of the five-minute test. If the Apgar score remains below 3 at later
times such as 10, 15, or 30 minutes, there is a risk that the child will suffer longer-
term neurological damage. There is also a small but significant increase of the risk of cerebral
palsy. However, the purpose of the Apgar test is to determine quickly whether a newborn needs
immediate medical care; it was not designed to make long-term predictions on a child's health.[1]

A score of 10 is uncommon due to the prevalence of transient cyanosis, and is not substantially
different from a score of 9. Transient cyanosis is common, particularly in babies born at high
altitude. A study comparing babies born in Peru near sea level with babies born at very high
altitude (4340 m) found a significant difference in the first but not the second Apgar score.
Oxygen saturation (see Pulse oximetry) also was lower at high altitude.[4]
[edit]Acronym

Some ten years after the initial publication, the acronym APGAR was coined in the US as
a mnemonic learning aid: Appearance (skin color), Pulse (heart rate), Grimace (reflex
irritability), Activity (muscle tone), and Respiration. The same acronym is used in German
(Atmung, Puls, Grundtonus, Aussehen, Reflexe), Spanish
(Apariencia, Pulso, Gesticulación, Actividad, Respiración) and French
(Apparence, Pouls, Grimace, Activité, Respiration) although the letters have different meanings.

Another such backformation attempting to make Apgar an acronym is American Pediatric

Gross Assessment Record. The test, however, is named for Dr. Apgar,
making Apgar an eponymous backronym.

The test has also been reformulated with a different mnemonic, How Ready Is This Child, but
the criteria are the same: Heart rate, Respiratory effort, Irritabililty, Tone, and Color.

Ballard maturational

The Ballard Maturational Assessment, Ballard Score, or Ballard Scale is a commonly used
technique of gestational age assessment. It assigns a score to various criteria, the sum of all of
which is then extrapolated to the gestational age of the baby. These criteria are divided
into Physical and Neurological criteria. This scoring allows for the estimation of age in the
range of 26 weeks-44 weeks. The New Ballard Score is an extension of the above to include
extremely pre-term babies i.e. up to 20 weeks.

The scoring relies on the intra-uterine changes that the fetus undergoes during its maturation.
Whereas the neurological criteria depend mainly upon muscle tone, the physical ones rely on
anatomical changes. The neonate (less than 28 days of age) is in a state of
physiological hypertonia. This tone increases throughout the fetal growth period, meaning a
more premature baby would have lesser muscle tone.
The Physical criteria

These are:

1. Skin
2. Ear/Eye
3. Lanugo Hair
4. Plantar Surface
5. Breast bud
6. Genitals

[edit]The Neurological criteria

 1. Posture
2. Square Window
3. Arm Recoil
4. Popliteal Angle
5. Scarf sign
6. Heel to Ear

[edit]Scoring

Each of the above criteria are scored from 0 through 5, in the original Ballard Score. The scores
were then ranged from 5 to 50, with the corresponding gestational ages being 26 weeks and 44
weeks. An increase in the score by 5, increases the age by 2 weeks. The New Ballard Score
allows scores of -1 for the criteria, hence making negative scores possible. The possible scores
then range from -10 to 50, the gestational range extending up to 20 weeks. (A simple formula to
come directly to the age from the Ballard Score is Age=(2*score+120) /5)

4th stage of labor (Recovery stage)

The "fourth stage of labor" is a term used in two different senses:

 It can refer to the immediate puerperium,[11] or the hours immediately after delivery of the
placenta.[12]

 It can be used in a more metaphorical sense to describe the weeks following delivery.[13]

[edit]Afterwards
Further information: Postnatal

Many cultures feature initiation rites for newborns, such as naming ceremonies, baptism, and
others.
Mothers are often allowed a period where they are relieved of their normal duties to recover from
childbirth. The length of this period varies. In many countries, taking time off from work to care
for a newborn is called "maternity leave" or "parental leave" and can vary from a few days to
several months.
[edit]Being born in the caul
When the amniotic sac has not ruptured during labour or pushing, the infant can be born with the
membranes intact. This is referred to as "being born in the caul." The caul is harmless and its
membranes are easily broken and wiped away. In medieval times, and in some cultures still
today, a caul was seen as a sign of good fortune for the baby, even giving the child psychic gifts
such asclairvoyance, and in some cultures was seen as protection against drowning. The caul was
often impressed onto paper and stored away as an heirloom for the child. With the advent of
modern interventive obstetrics, artificial rupture of the membranes has become common, so
babies are rarely born in the caul.

This stage is really more about getting back to normal than anything else. Your blood pressure,
temperature and heart rate will stabilize in much the same way a marathon runners does: a little
at a time during the hour after the placenta is delivered. Contractions will cease. Your uterus will
harden, doing its job to tighten around the blood vessels that had supplied the placenta and your
baby with nutrients. Your midwife or doctor will keep an eye on you, make sure the entire
placenta was expelled and take a look at the umbilical cord. If you had an episiotomy, this is
when you'll get a few sutures

Your medical person will make sure you didn't suffer any tears in delivery and will repair them if
you did. You probably won't be paying much attention, since once your baby is checked out for
health and admired for his or her beauty, wiped down, weighed and identified, you will most
likely be spending this time getting to know each other. The fourth stage is typically the time
parents spend counting fingers and toes and wondering at the fact that their newborn is much
more gorgeous than anyone else's could ever be. And that's just the way it should be.