Update on pediatric nutrition: Breastfeeding, infant nutrition, and growth

Jill Fulhan, MPH, RD, LDN, IBCLC, Sharon Collier, MEd, RD, LDN, and Christopher Duggan, MD, MPH

Recent studies continue to point out the critical nature of a patients nutritional status in helping to determine important health outcomes in pediatrics. We review recent data concerning the composition of breast milk and its adequacy to support infant growth in the first six months of life, as well as trials that support breastfeeding as an important method to delay or reduce the incidence of atopic diseases such as eczema, allergies, and asthma. Studies have also been published that show how physician education and training about breastfeeding can be optimized. Studies showing how nutritional status is measured (using standard anthropometric techniques as well as more modern measures of basal metabolic rate) are highlighted, as well as the role of micronutrient supplementation of patients with the human immunodeficiency virus infection and diarrheal diseases. Curr
Opin Pediatr 2003, 15:323332 2003 Lippincott Williams & Wilkins.

Pediatricians are familiar with the importance of nutritional status of children and associated health outcomes. This past year a number of studies have been published that more clearly make this link, as well as provide the practitioner with vital information in the areas of breastfeeding, nutritional counseling, nutritional assessment, and micronutrient therapies.

Exclusive breastfeeding for the term infant

In the 1997 policy statement Breastfeeding and the Use of Human Milk [1], the American Academy of Pediatrics recommended exclusive breastfeeding (no other complementary food) for approximately the first 6 months of life. Breastfeeding should then continue along with complementary foods for the next 6 months, and afterward for as long as is mutually desired by mother and baby. The World Health Organization (WHO) has also recommended exclusive breastfeeding until age 6 months, with continued breastfeeding until at least 2 years of age. Recent studies have addressed the adequacy of exclusive breastfeeding for 6 months for all populations, especially regarding infant growth and micronutrient adequacy. A recent review by WHO [2] assessed certain nutrients in breast milk that are affected by maternal diet and those that can be growth or developmentally limiting in the breastfed infant. In the analysis, several factors were considered, including the combined effects of endogenous and exogenous stores of certain nutrients to meet infant requirements, the ongoing research defining infant nutrient requirements, and the use of specific outcomes (eg, growth, immune response and neurodevelopment) to evaluate the adequacy of breast milk. Highlights from this report follow. The volume of breast milk a healthy individual mother is able to produce is based on her infants requirements for energy and protein. Average breast milk intake of infants at 6 months ( 854 g/d in well-nourished populations) has been shown to meet energy requirements and is thought to meet protein requirements for growth. Relatively few study populations who exclusively breastfeed until this time are available, however, because of high attrition rates before 6 months based on cultural, sociological, or economic conditions. Several interventions, including community-based breastfeeding promotion, have been
323

Clinical Nutrition Service, Division of Gastroenterology and Nutrition, Childrens Hospital, Boston; Harvard Medical School, Boston, Massachusetts, USA Correspondence to Christopher Duggan, MD, MPH, Childrens Hospital, Harvard Medical School, Clinical Nutrition Service, Division of Gastroenterology and Nutrition, 300 Longwood Avenue, Boston, MA 02115; e-mail: christopher.duggan@tch.harvard.edu Current Opinion in Pediatrics 2003, 15:323332 Abbreviations BMI CHD HIV NICU ORS WHO body mass index coronary heart disease human immunodeficiency virus neonatal intensive care unit oral rehydration solutions World Health Organization

ISSN 10408703 2003 Lippincott Williams & Wilkins

324 Office pediatrics

shown to increase rates of exclusive breastfeeding, which may allow further testing in this area. Breast milk concentrations of vitamins A and B6 are highly dependent on maternal stores. Therefore, in wellnourished populations, breast milk contains sufficient amounts of each to meet infant needs for 6 months. However, in populations where maternal vitamin A or B6 status may be suboptimal, a need exists for either supplementation of mothers, infants, or both, or provision of complementary foods rich in these nutrients. Infants depend on exogenous sources of vitamin D or sunlight for bone health, as the amount of vitamin D alone in breast milk is small. In geographic areas where exposure to sunlight is minimized or is limited because of cultural factors, infant supplementation with vitamin D is needed. Calcium availability in breast milk is independent of mothers diet and is fairly constant throughout lactation. Calcium needs are met during the first 6 months with exclusive breastfeeding. Iron and zinc nutriture in infants is dependent on both the endogenous stores of infants and the amount they receive through their diet. Iron supplementation of the mother does not increase breast milk iron concentration, so if iron is not received from complementary foods or additional supplements after stores diminish, infants are at risk of anemia after 6 months. In populations where maternal zinc stores are low and infants are born with inadequate stores, breastfed infants may be at risk of zinc deficiency with exclusive breastfeeding to 6 months. Recent studies have confirmed that pureed meat is an excellent source of well-absorbed dietary zinc for breastfed infants [3]. Also from the WHO, the Report of the Expert Consultation on the Optimal Duration of Exclusive Breastfeeding [4] stated that the recommendation of exclusive breastfeeding to 6 months, with introduction of complementary foods thereafter, applies to populations and is not meant to be a universal prescription. To prevent potential problems in populations where infants may be at risk, the following factors were recommended to be addressed: (1) the nutritional status of pregnant and lactating mothers; (2) the micronutrient status of infants living in areas with high prevalence of deficiencies such as iron, zinc, and vitamin A; and (3) the routine primary healthcare of individual infants, including assessment of growth and of clinical signs of micronutrient deficiencies. Also recommended was the need for appropriate complementary foods that are prepared in a safe manner. Research continues to be needed in many areas, including long-term growth status of exclusively breastfed infants, diarrheal morbidity, neuromotor development, changes in maternal weight, breast milk composition and its production by mothers with low body mass index (BMI) (<18.5), lactational amenorrhea, evaluation of complementary food around the world and its potential for

supplementation, and the needs of infants born smallfor-gestational age. In 2002, the WHO Working Group on the Growth Reference Protocol and the WHO Task Force on Methods for the Natural Regulation of Fertility reported findings [5] on growth of exclusively and predominantly breastfed healthy infants in seven different countries, with respect to the introduction of complementary foods. They found that although significant, differences in growth were small and likely not biologically important, based on the timing, type, or frequency of food given between 4 and 6 months of age. These infants were full-term, living in healthy environments without major economic constraints, and had low rates of illness. Although not applicable to infants living in poor conditions, no risk or benefit to starting complementary feeds at 4 months or waiting until 6 months was seen for healthy, term infants regarding growth. Thus, recent policy statements from WHO and others continue to support the importance of mothers exclusively breastfeeding their infants for 4 to 6 months, and to continue breastfeeding for 12 months or longer. Whereas the decision about length of breastfeeding is ultimately a personal one, pediatricians should remain knowledgeable about this field to counsel their families appropriately. Although the precise timing of exclusive breastfeeding (4 to 6 vs strictly 6 months) can continue to be debated, policy statements for populations should be acknowledged to be different than individual recommendations.

Physician knowledge and support of breastfeeding

Whereas most decisions regarding the chosen method of infant feeding may be made before the pediatrician meets their new patient, the role of the pediatrician in supporting the breastfeeding mother and infant can be crucial to the continuation of breastfeeding, especially in the first weeks postpartum. Adequate breastfeeding education, however, has not yet become a requirement for physicians in training, nor are educational opportunities with hands-on skill training abundant for established pediatricians. Lack of sufficient support or mixed messages about establishing an adequate milk supply, especially for new mothers, can lead to premature weaning from breastfeeding. The role of healthcare providers offering support for mothers giving birth to their first or second child was prospectively studied by Humenick et al. in two regions of the United States with low rates of breastfeeding [6]. Of 233 mothers who intended to breastfeed and had received information or advice about breastfeeding in the first 20 weeks postpartum, discussions were limited. When they did happen, it was most often with physicians

Breastfeeding, infant nutrition, and growth Fulhan et al. 325

(53%); conversations with nurses (27%) and lactation consultants (21%) occurred less often. The messages received from the healthcare provider was rated by mothers as strongly or mildly positive (encouragement to continue breastfeeding); mixed (continue breastfeeding and give human milk substitutes or food); or negative (encouragement to give human milk substitutes and not continue breastfeeding). Physicians, however, gave strongly or mildly positive advice only 68% of the time versus lactation consultants who gave positive advice 98% of the time. Most negatively affected were the primiparous mothers who received negative encouragement, with most (86%) of these mothers having a subsequent decline in breastfeeding. Surprisingly, 75% of mothers reported having had no conversations about breastfeeding with a healthcare professional during the second week postpartum (as breast milk supply continues to be established). The authors note that primiparous mothers may be a group for which early, positive encouragement for continued breastfeeding by health professionals may have the most positive effect for their first infant as well as future offspring. Factors also affecting duration of breastfeeding were assessed prospectively by McLeod et al. in New Zealand [7]. At 20 to 24 weeks gestation, 74% of 490 women planned to breastfeed, whereas another 23% planned to breastfeed partially. By 6 to10 weeks postpartum, these numbers were realized, with 67% fully breastfeeding and 22% partially breastfeeding. Of those women who had discontinued breastfeeding, 83% would have preferred to have breastfed longer. After controlling for maternal education and socioeconomic status, women who were not fully breastfeeding at 4 months tended more often to smoke cigarettes, experience problems breastfeeding, give baby a pacifier, or return to work or study, compared with women who continued to breastfeed. Women who had stopped breastfeeding altogether reported reasons such as a hungry or unsettled baby, milk running out, a need to return to work, or a perception that baby was old enough to stop. This study not only identifies factors that account for shorter duration of intended breastfeeding, but points out that many of these factors can be addressed and resolved via enhanced prenatal education and assistance with common problems while establishing breastfeeding. Health professionals, including pediatricians, are uniquely positioned to learn the skills needed to support mothers in establishing a healthy breastfeeding relationship and avoiding premature weaning. In the United States, Philadelphia-area hospital breastfeeding policies were reviewed by Kovach [8]. While significant improvements were made since first assessed in 1994, several areas were rated as only partially implemented and, therefore, needed the greatest attention. These areas included the training of healthcare staff (including physicians) in skills necessary to assist breast-

feeding mothers and infants, the reduction of formula supplements provided to breastfeeding babies, and an emphasis on more rooming-in of mothers and babies. A significant increase was seen in the number of educational programs offered for both physicians and nurses, but the education in hospital was brief, only 1 to 3 hours versus the 18 hours of formal training recommended by the Baby Friendly Hospital Initiative [9]. Longer formal training programs were offered for nurses, but often at outlying community or breastfeeding centers. The authors note that improvement in healthcare professional training in breastfeeding management skills continues to be a goal of Philadelphia hospitals, to comply with the Ten Steps to Successful Breastfeeding [10] (Table 1). When 1602 members of the American Academy of Pediatrics were randomly surveyed, significant gaps were found in breastfeeding education and confidence in giving accurate breastfeeding information to mothers. Schanler et al. [11] reported that, although most pediatricians recommended breastfeeding in general, many did so against current recommendations. For instance, discontinuing breastfeeding was often suggested in situations where effective remedies to actually improve breastfeeding exist (eg, mastitis, sore nipples, and infant jaundice). Most pediatricians were unaware of the Baby Friendly Hospital Initiative or the Ten Steps to Successful Breastfeeding, and many did not know their hospitals breastfeeding policy or if one even existed. The Academy thus recognized a need for increased breastfeeding education in several areas for pediatricians, so that clear and accurate recommendations and messages are conveyed to patients in support of the initiation and duration of breastfeeding. Hillenbrand and Larsen [12] designed an interactive multimedia educational program for pediatric residents, and assessed changes in the residents knowledge, skills, and confidence in addressing breastfeeding concerns. Pre- and postintervention questionnaires were administered and answered by 49 pediatric residents. Residents attended educational opportunities, including readings, lectures, group discussions, role-playing exercises, demonstrations, and panel discussions with breastfeeding mothers. To assess changes in behavior regarding skills learned, phone interviews with mothers who received breastfeeding counseling in the first month postpartum were conducted before and after the intervention. The percent of correct answers obtained from residents about breastfeeding benefits and treatment for common problems increased from 69% to 80% after the intervention. Significant knowledge increases were seen in advice given to mothers concerning low milk supply (P = 0.049); maternal infections, including mastitis (P = 0.002) or abscess (P = 0.044); and maternal medications (P < 0.001). Interestingly, no increase in maternal satisfaction regarding residents behaviors was noted, although an increase

326 Office pediatrics Table 1. 10 steps to successful breastfeeding Every facility or agency providing maternity services and care of newborn infants should 1. Have a written breastfeeding policy that is routinely communicated to all health care staff 2. Train all health care staff in skills necessary to implement this policy 3. Inform all pregnant women about the benefits and management of breastfeeding 4. Help mother initiate breastfeeding within one half hour of birth 5. Show mothers how to breastfeed and how to maintain lactation even if they are separated from their infants 6. Give newborn infants no food or drink other than breastmilk unless medically indicated 7. Practice rooming-in; ie, allow mothers and infants to remain together 24 h/d 8. Encourage breastfeeding on demand 9. Give no artificial teats or pacifiers to breastfeeding infants 10. Foster the establishment of breastfeeding support groups and refer mothers to them on discharge from the hospital or clinic Adapted from [49].

fore, breastfeeding with the avoidance of milk other than breast milk until after 4 months of age was noted to protect against asthma and atopy later in childhood. More recently, Oddy et al. [14] evaluated the same cohort to ascertain the relation between presence of maternal asthma, infant feeding, and the risk of asthma in childhood. The definition of a childs current asthma at 6 years of age included diagnosis by a physician and wheeze in the last year. The presence of atopy was noted with a positive skin prick test. Maternal age and education, age that solids were introduced, pet exposure, and family income were controlled for in the analysis. Although the presence of maternal asthma, the childs atopic status, and the cessation of exclusive breastfeeding before 4 months of age were significantly related to current asthma in the child, no evidence indicated any association between breastfeeding and maternal asthma status, as had been reported earlier [15]. The authors, therefore, recommend that an infant with or without maternal history of asthma should be breastfed exclusively for at least 4 months. Sears et al. [16], in contrast, recently studied a cohort of 1037 children who were born between April 1972 and March 1973 to assess the relation of breastfeeding and development of asthma and atopy. Subjects were assessed every 2 to 5 years between the ages of 9 and 26 years with questionnaires, pulmonary function tests, bronchial challenge, and allergy skin tests. History of breastfeeding was recorded by maternal interviews when the children were 3 years of age and were verified from available clinic records. Importantly, breastfed infants were not necessarily exclusively breastfed; many newborns received a nightly formula feed (prepared from dried cows milk powder) while in the hospital so that mothers were allowed to sleep. Children who were breastfed were more likely to be firstborn, from parents of higher socioeconomic status, born to nonsmoking mothers, and have a sheepskin on their bed in infancy, than those who were not breastfed. After controlling for socioeconomic status, birth order, sheepskin use in infancy, and maternal smoking, asthma and atopy outcomes in children and young adults all remained highly significantly associated with partial breastfeeding over 4 weeks, compared with infants who were not breastfed. The failure of this study to find a protective effect of breastfeeding may result from several features, including the low rate of exclusive breastfeeding, as seen by the practice of providing cows milk formula to neonates in the 1970s. Kull et al. [17] prospectively studied the effect of breastfeeding on the development of allergic disease in children to 2 years of age. A cohort of 4089 infants born in Sweden between February 1994 and November 1996 were followed. When controlling for multiple possible

in confidence in providing lactation help was reported by residents. The authors suggest that similar multimedia educational programs be instituted among larger physician groups.

Breastfeeding and allergic disease

Provision of breast milk has been shown to reduce the risk of otitis media, lower respiratory infection and necrotizing enterocolitis, and protect against insulindependent diabetes mellitus, Crohn disease, and ulcerative colitis [1]. Its beneficial role in the delay or prevention of asthma (one of the leading causes of admission to hospital for children) and atopy has been demonstrated repeatedly, although some evidence is conflicting. The individual roles of exclusive breastfeeding (no milk other than mothers milk) and duration of breastfeeding may be cause for different findings. Through the Western Australian Pregnancy Cohort, Oddy et al. [13] prospectively studied 2187 infants to determine whether exclusive breastfeeding or the duration of breastfeeding had a protective effect on the risk of asthma and atopy at 6 years of age. Parents completed questionnaires regarding the general health of their child at birth, 1 year, and 6 years of age. A diary of the childs health was kept during the first year. Exposure to breastfeeding was analyzed with respect to length of exclusive breastfeeding and total duration of breastfeeding. After controlling for factors including childs gender, gestational age, smoking in the household, and childcare or playgroup attendance, multiple logistic regression analyses showed that the inclusion of milk other than mothers milk was positively associated with physician diagnosis of asthma, wheezing, disturbed sleep from wheezing, and positive skin prick test to at least one of four allergens. The age of diagnosis of asthma and age at first wheeze both occurred earlier in the childs life if exclusive breastfeeding ended before 4 months of age. There-

Breastfeeding, infant nutrition, and growth Fulhan et al. 327

factors (eg, gender, heredity for allergic disease, mothers age, maternal smoking, and year of construction of the homeall significant risk factors for asthma and suspected allergic rhinitis), results showed that infants who were exclusively breastfed for 4 or more months had less asthma (7.7% vs 12%), less atopic dermatitis (25% vs 27%), and less suspected allergic rhinitis (6.5% vs 9%) by age 2 years, than those infants not exclusively breastfed. Exclusive breastfeeding also reduced the occurrence of multiple allergic disease (5.8% vs 9.2%) during the first 2 years of life. Partial breastfeeding for 6 or more months provided a significant risk reduction for asthma (7.7% vs 12%). The authors, therefore, suggest a protective effect of exclusive breastfeeding against allergic disease through the first 2 years of life. Dell and To [18] studied data from 2184 subjects enrolled in the Canadian National Longitudinal Survey of Children and Youth from 1994 to 1995. Duration of breastfeeding was stratified to none to less than 2 months, 2 to 6 months, 7 to 9 months, and more than 9 months. Exclusive breastfeeding and the introduction of complementary foods were not measured. In an unadjusted analysis, the duration of breastfeeding, male gender, parental asthma history, prenatal and postnatal smoking, prematurity, and low birthweight were all risk factors for asthma. After adjusting for smoking, prematurity, low birthweight, low maternal education, and low income, breastfeeding for longer than 9 months provided a protective effect for prevention of asthma and wheeze. A positive dose-response effect for breastfeeding was also observed. These authors note that, although the protective effect of increased breastfeeding duration and delay of asthma was observed to 2 years of age and that the effect thereafter may diminish, breastfeeding is still an important preventive measure against morbidity related to asthma in young children. Therefore, exclusive breastfeeding for at least the first 4 months of life should be promoted and supported to reduce or delay the risk of asthma and other atopic diseases, as well as to offer the many nutritional and immunologic benefits that breast milk provides.

United States (US), because of concerns about the 1977 charts and the availability of recent, comprehensive data and improved statistical smoothing procedure. The major differences between the 2000 CDC growth charts and the 1977 NCHS charts includes (1) inclusion of breastfed infants proportional to the distribution in US population during the past 30 years; (2) wider representation of a cross section of children living in the US between 1971 and 1994 (vs primarily white, middle-class infants); (3) expansion to include up to 20 years of age; (4) BMI percentile curves for 2 to 20 years; and (5) using one data source to decrease the disjunction between recumbent length and stature when changing from the infant (0 to 36 months) to the older child growth chart. The new 2000 CDC growth charts should be used by all ambulatory pediatricians for routine monitoring of growth for all children from infancy through adolescence in the United States. As critical as it is to have reliable tools to assess growth, it is just as important to take accurate measurements to plot on the growth chart. Corkins et al. [20] compared two different methods of measuring length in a recent study. Subjects were 25 infants and toddlers admitted to an inpatient facility who required nutrition intervention by a dietitian. Two recumbent length measurements were obtained: one using a tape measure performed by the admitting nurse and then one using a length board by a registered dietitian with an assistant. The tape measurement was performed by placing the infant on a paper barrier, marking the places of the head and foot, and measuring the distance between the two marks. The recommended technique for length board measurement was followed by the dietitian and assistant. A second length board measurement was obtained within 24 hours of admission by a second dietitian unaware of the first measurement. Excellent agreement was seen between the measurements of the two dietitians, and each produced consistent individual measurements. The difference between tape and length board measurements averaged 1.7 cm and, when plotted on the NCHS growth chart, resulted in a change of length percentile in 12 of the 25 patients and a change in weight for length percentile in 13 patients. An inaccurate length could potentially alter medical care. Because BMI is based on weight and length, an inaccurate length could under- or overestimate overweight status. The weight for length parameter is often used to assess if aggressive nutritional intervention is warranted. Length is also used to calculate body surface area, which determines chemotherapy and other drug dosages. Therefore, to obtain the most accurate length, a length board should be used and measurements obtained by trained healthcare providers. Although this study used registered dieticians, most practices can successfully employ clinical nursing assistants with proper training.

Growth assessment
A fundamental aspect of pediatric nutrition is the assessment of body growth. It is essential that the tools used to assess growth are accurate and valid. One of the most used and basic tools is the age- and gender-specific National Center for Health Statistics (NCHS) growth charts. Growth charts are used to assess the nutritional and health status of children, to monitor individual growth, and also for research efforts to calculate prevalence estimates and z scores, compare populations, monitor trends, evaluate interventions, and define nutritional outcomes [19]. In May 2000, the Centers for Disease Control (CDC) released revised NCHS growth charts for use in the

328 Office pediatrics

Nutrition and prematurity

Determination of optimal growth encompasses many areas, including genetic, social, economic, environmental, and nutritional factors. An added factor can be medical diagnosis and the specific disease. Premature infants are at special risk of growth failure; 97% of infants with a birthweight of less than 1500 g are discharged with weights less than the tenth percentile for corrected gestational age [21]. Genetic factors, severity of illness, clinical practices, and medical complications can all influence growth. Growth is an important health outcome because it can have an impact on length of stay, hospital costs, as well as cognitive development. A study performed by Olsen et al. [22] compared the differences in overall practice and weight growth velocity of premature infants at six different level III Neonatal Intensive Care Unit (NICU) sites in New England. The investigators evaluated (1) medical practice and complications (temperature control, respiratory support, insulin use, postnatal steroid use, infections, incidence of necrotizing enterocolitis, patent ductus arteriosus; (2) baseline newborn characteristics (<30 weeks gestation, birthweight, small for gestational age, race, gender, multiple gestation, Apgar score, illness severity, and maternal characteristics, including prenatal steroid use and prenatal care); (3) weight gain; and (4) nutritional intake, parenteral or enteral. Growth velocity (g/kg/d) was the primary outcome. Significant variability in growth rates and energy and protein intake were seen among the six NICU. For example, by day 14, energy intake ranged from 78 to 111 kcal/kg/d among the six sites. Differences in nutritional intake (in conjunction with NICU site, case mix and medical factors) could explain 53% of the overall variance in growth velocities. Other factors significantly associated with a higher growth velocity were lower severity of illness scores, African-American race, single parity, prenatal exposure to steroids, less exposure to postnatal steroids, and protein intake. Enteral nutrition recommendations for premature infants range from 120 to 165 kcal/kg/d and 3 to 4 g protein/kg/d, with the upper end recommended for smaller, younger infants. This study clearly demonstrates a wide variability in the nutritional management of premature infants, and points out how these practices, more than any underlying characteristics of the infants themselves, affect growth.

these outcomes are a consequence of persisting physiologic and metabolic changes that cause slow growth in utero (poor nutrition in utero changing blood pressure and glucose tolerance) or postnatal adaptation in growth. In addition, genetics play an important role in determining fetal growth and disease. One recent cohort study [25] evaluated young British adults for whom detailed longitudinal data on childhood growth rates had been collected. Mean birthweight (3.43 kg for males; 3.31 kg for females) was slightly lower than local published standards. Mean systolic blood pressures as adults were lower by approximately 7 mm Hg for men and 11 mm Hg for women, compared with a nationally representative sample of similarly aged adults. As anticipated, blood pressure increased with adult BMI. The highest systolic pressures were observed in adults who had been light at birth but who had gained relatively large amounts of weight between 1 and 5 years of age. Weight gain within the first year of life was not associated with adult systolic blood pressure. The correlation of lower birthweight with higher blood pressure was found to be independent of postnatal growth, adult BMI, or other lifestyle factors, suggesting that at least part of the risk of hypertension is determined in fetal life. Possible mechanisms occurring in utero that may have an impact on blood pressure include the structural development of resistance arteries, programming of hormone levels, and nephron development. A similar study [26] in Helsinki assessed the association between early growth and CHD in a cohort of 4630 men. They saw less risk of CHD with increased birthweight and ponderal index (weight divided by length3). Also less risk of CHD was seen with increasing weight, height, and BMI at 1 year of age. Small body size at this age predicted CHD independent of BMI. Two different scenarios were associated with CHD: (1) low birthweight followed by rapid weight gain in childhood, and (2) failure of infant growth followed by persisting thinness during childhood. Both were associated with short stature in childhood. The authors speculated that infants who are thin at birth lack muscle, a deficiency that will persist throughout life because the critical period for muscle growth is around 30 weeks in utero and little cell replication occurs after birth. If a high BMI is developed in childhood, this will disproportionately be fat. The development of insulin resistance, therefore, can be associated with this high amount of fat mass. A study done in Iceland by Gunnarsdottir et al. [27] also evaluated the association between birthweight and the occurrence of CHD. The population in Iceland is relatively genetically homogenous, with higher birthweight and lower incidence of CHD than those of other Scandinavian countries. The authors reviewed the birth records of 4775 subjects. A nonsignificant trend was noted

Long-term effects of fetal and infant nutrition

Evidence continues to accumulate about the importance of infant nutrition and later diseases of so-called adult onset [23, 24]. Epidemiologic studies have demonstrated that low birthweight is associated with a number of important diseases, including coronary heart disease (CHD) in adults, insulin resistance, and others. It is not clear if

Breastfeeding, infant nutrition, and growth Fulhan et al. 329

toward a decreased risk of CHD with higher birthweight. Men who were born short (<50.5 cm) and who became tall as adults were shown to have a higher incidence of myocardial infarction or to die of CHD than were other men. Because linear growth, unlike weight growth, proceeds steadily throughout gestation, birth length may reflect nutritional factors operating throughout gestation, rather than at a specific time during pregnancy. Iceland has a lower prevalence of type 2 diabetes mellitus than seen in other Scandinavian countries, despite its higher prevalence of obesity. The high birthweight of Icelanders may protect them from disease related to impaired fetal growth. By reducing the incidence of low birthweight infants, it may be possible to lower the incidence of type 2 diabetes mellitus worldwide and, therefore, lower the prevalence, morbidity, and mortality rate of CHD.

ports. The apparent protective effect of breastfeeding has been noted [31] and possible causative factors have been hypothesized to include the macronutrient content of breast milk, the inclusion of certain growth factors, and the ability of the breastfed infant to better regulate energy intake. Toschke et al. [32] studied the impact of breastfeeding on the occurrence of overweight and obesity on children ages 6 to 14 years. Data regarding breastfeeding, educational level, parental BMI, maternal smoking, TV watching, siblings, physical activity, fruit consumption, and birthweight were analyzed and anthropometric evaluation of 33,768 school-aged children were completed. In this study, overweight defined as BMI above 90th percentile and obese as more than the 97th percentile of local norms. Breastfeeding was common in the Czech Republic from 1976 to 1985: 90.7% of infants were ever breastfed and only 9.3% were never breastfed. The final results showed a lower prevalence of overweight and obesity in children 6 to 14 years of age who had been breastfed, compared with those not breastfed, as infants (9.3% vs 12.4% and 3.2% versus 4.4%, respectively). Length of breastfeeding was inversely correlated with the prevalence of overweight. Encouraging breastfeeding may benefit the child further into adulthood by helping to reduce the risk of overweight and obesity and, therefore, decreasing the risk of developing CHD.

Obesity
Obesity and its related risk of development of CHD has been noted as an increasingly prevalent health problem; obesity now affects 30% of the US adult population [28]. Over the past four decades, the prevalence rose from 4% to 11% in children 6 to 11 years of age. A similar increase of 5% to 11% was observed in those 12 to 19 years of age [29]. Ogden et al. [30] studied the prevalence of overweight in US children and adolescents using data obtained from National Health and Nutrition Examination Survey 19992000. The study included 4722 children from birth through 19 years of age. Overweight was defined as >95%ile of the gender-specific BMI for age. The prevalence of overweight was found to be 15.5% among those 12 to 19 years of age, 15.3% among those 6 to 11 years of age, and 10.4% among children 2 to 5 years of age, compared with 10.5%, 11.3%, and 7.2%, respectively, in the period 19881994. The prevalence of overweight among non-Hispanic black and MexicanAmerican adolescents increased more than 10% between the periods 19881994 and 19992000. The treatment of obesity is extremely difficult. Diets have a high failure rate and the surgical options for morbid obesity are expensive, not without risks, and not well studied in children. Therefore, emphasis should be placed on prevention of overweight, starting with young children. Factors contributing to the growing incidence of overweight can be related to large portion sizes, consumption of high fat, energy dense fast foods, and sedentary lifestyle with television viewing and computer use. The most effective preventive intervention is likely a combination of parental involvement (to determine diet and physical activity practices) and school-based programs (to help reduce sedentary behavior, as well as some dietary modifications). The effect of infant nutrition and the development of obesity later in life has been the subject of several re-

Nutritional needs of sick infants and children

Overweight, of course, is not the only form of malnutrition common in pediatric patients; the burden of infectious and other diseases places an increased demand on infants and children that, if not met, can lead to significant undernutrition. Several papers published recently have addressed this possibility and extended our knowledge of how acute or chronic illness can have an impact on a childs nutritional status. These included studies in infants and children with sepsis, diarrhea, and the human immunodeficiency virus (HIV) infection.
Studies of energy expenditure

Infants are especially susceptible to the adverse effects of illness on nutritional status because of (1) low body reserves of fat, protein, and glycogen; (2) higher basal metabolic rate and increased energy demands for growth, and (3) increased incidence of infectious and inflammatory stress. A recent technologic development has allowed nutrition researchers to more fully evaluate the energy needs of infants in a noninvasive manner. The technique, using a whole body indirect calorimeter called the Enhanced Metabolic Testing Activity Chamber, relies on the fact that energy expenditure can be calculated from measurements of oxygen consumption and carbon dioxide production. This particular device circulates room air to the baby in the testing chamber,

330 Office pediatrics

allows parents or other caregivers to have physical access to the infants during the test, and measures how physically active the subject is. Studying 50 healthy infants with the device during rest and sleep for 4- to 6-hour periods, Duro et al. compared the predictive equation from these results with those from other equations in the literature [33]. They found that the predictive equation derived from data obtained with this device led to much lower predictions of energy expenditure than those from more standard equations. Should this technology be validated in more infants, it is possible that our understanding of normative nutritional intake will be altered. Another example of energy expenditure studies was the recent publication of data concerning whether infants with sepsis have higher energy expenditure [34]. Although it would seem likely that oxygen consumption (a prime determinant of resting energy expenditure) is elevated in patients with serious bacterial infections, previous data had yielded inconclusive results. These investigators measured resting energy expenditure in 10 fullterm infants with sepsis, defined as (1) clinical signs of infection, including tachycardia, bradycardia, tachypnea, feeding intolerance, lethargy, irritability, and others; (2) elevated IL-6 and IL-8; (3) positive blood cultures; and (4) abnormal white blood cell count. Compared with seven healthy infants matched for birthweight and gestational age, the oxygen consumption and energy expenditure measurements of septic infants was 15% to 20% higher. Not surprisingly, these septic infants also had poorer weight gain (19 vs 33 g/d) than did the healthy infants during the 7-day study. These investigators, who also recently published data on the increased energy expenditure of premature infants treated with caffeine [35], therefore, have used important new technology to quantify the nutritional repercussions of a common occurrence, namely infection. As always, the guide for nutritional adequacy for the practitioner will be adequate weight gain over time, but the technologic advances such as these and other measures of nutrient requirements and body composition allow pediatricians to more precisely prescribe the nutritional management of their patients.
Zinc studies

et al. [37] randomly assigned nearly 1800 Nepalese children with acute diarrhea to either zinc (three times the RDA), vitamin A plus zinc, placebo (all distributed in a blinded fashion by a field worker), or zinc (given in an open-labeled fashion by the parent). All children were also treated with oral rehydration solutions (ORS). The risk of diarrhea lasting for more than 7 days after enrollment was 43% to 47% lower in the groups receiving zinc, and no added benefit was seen with additional vitamin A, compared with the placebo group. Bhandari et al. [38] reported that daily ingestion of zinc (two times the RDA) by infants and children living in urban India was associated with a substantial reduction in subsequent diarrhea incidence, especially severe or prolonged episodes. Finally, Bahl et al. evaluated the efficacy and safety of a zinc-fortified ORS (40 mg/L) among 1219 children with acute diarrhea [39]. The intake of ORS was not different across the groups. Compared with zinc syrup given at a dose of 15 to 30 mg/d, zinc-fortified ORS did not increase plasma zinc concentration. Clinical outcomes in the zincfortified ORS, however, were modestly improved compared with the control group who received standard ORS only. For instance, the total number of stools was lower in the zinc-ORS group (RR 0.83; 95% CI, 0.71 to 0.96) compared with the control group. No significant effect was seen on diarrheal duration or risk of prolonged diarrhea. Therefore, these studies confirm that zinc has an important role to play in improving outcomes in children with diarrheal diseases [40, 41], still one of the worlds most important causes of child morbidity and mortality [42]. Although many of these studies were performed in children from poor countries, it seems likely that improved forms of ORS will be transferred to the United States and other industrialized settings, a phenomenon that some have termed a reverse transfer of technology [43].
Nutrition and human immunodeficiency virus infection

Other nutritional management decisions are needed when the office-based practitioner is faced with children with a variety of common illnesses, including diarrhea, HIV infection, and others. As noted in our last review of the nutrition literature in this journal [36], zinc is becoming an increasingly appreciated micronutrient in human health and disease. Several studies published this last year continue to emphasize its importance. For instance, at least three trials of supplementary zinc showed impressive reductions in the occurrence and severity of diarrheal diseases in children receiving supplement. Strand

Malnutrition has long been known to afflict pediatric patients with HIV infection and to be a common indicator of serious morbidities and mortality [4446]. Two recent articles have shed light on the impact of medical and nutritional therapy for children with HIV infection. In one study, researchers in The Netherlands examined the impact of highly active antiretroviral therapy in children with HIV on clinical, virologic, and nutritional outcomes. Pediatric patients aged 0.4 to 16 years with HIV infection (N = 24) were enrolled in the study, and many had significant growth failure on admission (mean weight for age z score 0.74, mean height for age z score 1.22). After initiation of this antiretroviral therapy strong positive correlations were noted between changes in CD4+ T-cell z scores and changes in weight for age z scores (r values between 0.408 and 0.693). Among the patients

Breastfeeding, infant nutrition, and growth Fulhan et al. 331

who had a significant virologic response to highly active antiretroviral therapy, significant improvements were seen in both weight and height z scores, up to the 2 years of follow-up. In contrast, those who did not have a virologic response did not exhibit significant nutritional improvements. In the second trial [47], researchers noted among HIVinfected infants that vitamin A supplementation resulted in significant increases in body length (average increment 2.8 cm over 4 months of follow-up) compared with placebo. This study also pointed out that periodic vitamin A supplementation was associated with improved growth outcomes among children with a high incidence of malaria, persistent diarrhea, and dysentery. Further trials of nutrient supplementation among vulnerable populations such as these are warranted, and promising data are accruing concerning nutritional regimens and vertical transmission of HIV infection [48].

Humenick SS, Hill PD, Spiegelberg PL: Breastfeeding and health professional encouragement. J Human Lact 1998, 14:305310.

7 McLeod D, Pullon S, Cookson T: Factors influencing continuation of breastfeeding in a cohort of women. J Hum Lact 2002, 18:335343. This study prospectively addresses the influence of womens experiences in preparing for and establishing breastfeeding with their duration of breastfeeding. Factors including prenatal education and skills to address common problems of breastfeeding initiation can be addressed to reduce the chance of premature weaning. Kovach AC: A 5-year follow-up study of hospital breastfeeding policies in the Philadelphia area: a comparison with the Ten Steps. J Hum Lact 2002, 18:144154. Areas within the Ten Steps to Successful Breastfeeding, as identified by UNICEF and WHO in the Baby-Friendly Hospital Initiative (BFHI), which need the greatest attention in Philadelphia area hospitals are breastfeeding education of healthcare professionals and mothers, prenatal and postdischarge outreach to mothers, and the restriction of infant supplementation. 8 9 United Nations Childrens Fund: UNICEF Guidelines: Baby Friendly Hospital Initiative. Washington: US committee for the United Nations International Childrens Emergency Fund; 1992. World Health Organization: Innocenti Declaration: On the Protection, Promotion, and Support of Breastfeeding. Geneva: World Health Organization; 1990. Schanler RJ, OConnor KG, Lawrence RA: Pediatricians practices and attitudes regarding breastfeeding promotion. Pediatrics 1999,103:E35.

10

11 12

Conclusions
We have reviewed a series of studies that add to the growing literature linking the in utero and postnatal environment with important health outcomes in later life. The role of nutrition in these outcomes will likely be clarified over time, so the implications to the practicing physician include continued efforts to reduce the incidence of low birthweight, encourage exclusive breastfeeding early in infancy (especially in families with atopic histories), and encourage accurate measurement of nutritional and anthropometric status. Recent findings about the efficacy of micronutrient supplementation, especially in nutritionally vulnerable populations such as those with HIV infection, malaria, and persistent diarrhea, are encouraging.

Hillenbrand KM, Larsen PG: Effect of educational intervention about breastfeeding on the knowledge, confidence, and behaviors of pediatric resident physicians. Pediatrics 2002,110. Available at http://www.pediatrics. org/cgi/content/full/110/5/e59. Accessed January 15, 2003. The details of a four-part breastfeeding education intervention are described along with its effect on the knowledge, confidence, and behaviors of residents in pediatrics. 13 Oddy WH, Holt PG, Sly PD, et al.: Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ 1999, 319:815819.

14 Oddy WH, Peat JK, de Klerk NH: Maternal asthma, infant feeding, and the risk of asthma in childhood. J Allergy Clin Immunol 2002, 110:6567. Prospective cohort study of 2602 children found maternal asthma not to be a risk factor for childhood asthma when infants were exclusively breastfed for at least 4 months. 15 Wright AL, Holberg CJ, Taussig LM, et al.: Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood. Thorax 2001, 56:192197.

16

Sears MR, Greene JM, Willan AR, et al.: Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002, 360:901907. This study of infants partially breastfed for more than 4 weeks, versus not breastfed, does not show a protective effect for atopy and asthma. 17 Kull I, Wickman M, Lilja G, et al.: Breast feeding and allergic diseases in infantsa prospective birth cohort study. Arch Dis Child 2002, 87:478481. This study of 4089 infants shows the potential for exclusive breastfeeding to have a preventive effect on the early development of single and multiple allergic disease. 18 Dell S, To T: Breastfeeding and asthma in young children. Findings from a population-based study. Arch Pediatr Adolesc Med 2001, 155:12611265. Ogden CL, Kuczmarski RJ, Flegal KM, et al.: Centers for Disease Control and prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 2002, 109:4560. Corkins MR, Lewis P, Cruse W, et al.: Accuracy of infant admission lengths. Pediatrics 2002, 109;11081111. Lemons JA, Bauer CR, Oh W, et al.: Very low birth weight outcomes of the National Institute of Child Health and Human Development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics 2001, 107: e1. Available at: www.pediatrics. org/cgi/content/full/107/1/e1. Accessed January 15, 2003.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as: Of special interest Of outstanding interest 1 2 American Academy of Pediatric: Work Group on Breastfeeding. Breastfeeding and the Use of Human Milk. Pediatrics 1997, 100:10351039.

19

Butte NF, Lopez-Alarcon MG, Garza C: Nutrient adequacy of exclusive breastfeeding for the term infant during the first six months of life. Geneva: World Health Organization, 2002. Authors review of 235 studies of exclusive breastfeeding of term infants, with specific regard to micronutrient adequacy of breast milk, gathered for a WHO expert consultation on the optimal duration of exclusive breastfeeding. Jalla S, Westcott JE, Steirn M, et al.: Zinc absorption and exchangeable zinc pool sizes in breast-fed infants fed meat or cereal as first complementary food. J Pediatr Gastroenterol Nutr 2002, 34:3541. Stable isotope study that demonstrated pureed meat as an excellent source of dietary zinc among infants 7 months of age. 3 4 5 Report of the expert consultation of the optimal duration of exclusive breastfeeding. Geneva: World Health Organization, 2830 March 2001, c. 2002.

20 21

WHO Working Group on the Growth Reference Protocol and the WHO Task Force on Methods for the Natural Regulation of Fertility: Growth of health infants and the timing, type, and frequency for complementary foods. Am J Clin Nutr 2002, 76:62027. Authors detail an international, longitudinal study of healthy, term infants in favorable conditions, and their receipt of complementary foods with breastfeeding.

22 Olsen IE, Richardson DK, Schmid CH, et al.: Intersite differences in weight growth velocity of extremely premature infants. Pediatr 2002;110:112532. Overall medical practices and growth outcomes of extremely premature infants were compared among six level III NICUs in New England. Significant variability in growth rates and energy and protein intake were observed among the sites. Differences in nutritional intake in conjunction with NICU site, case mix and medical factors could explain 53% of the overall variance in growth velocities. The authors concluded that increasing nutritional intake to the recommended range of 120 to 165 kcal/kg/d and 3 to 4 g protein/kg/d might increase growth velocity of extremely premature infants to more closely approximate intrauterine growth rates.

332 Office pediatrics

23 24 25 Barker D: Mothers, babies and disease in later life. London: BMJ Publishing Group; 1994. Barker D: Growth in utero and coronary heart disease. Nutr Rev 1996, 54:S1S7 Law CM, Shiell AW, Newsome CA, et al.: Fetal, infant, and childhood growth and adult blood pressure. A longitudinal study from birth to 22 years of age. Circulation 2002, 105:10881092. Eriksson JG, Forsen T, Tuomilehto J, et al.: Early growth and coronary heart disease in later life: longitudinal study. BMJ 2001, 322:949953. Gunnarsdottir I, Birgisdottir BE, Thorsdottir I, et al.: Size at birth and coronary artery disease in a population with high birth weight. Am J Clin Nutr 2002, 76:12901294. Flegal KM, Carroll, MD, Ogden CL, et al.: Prevalence and trends in obesity among US adults, 19992000. JAMA 2002, 288:17231727. Prevalence of overweight among children and adolescents: United States, 19992000. http://www.cdc.gov/nchs/products/pubs/pubd/hestats/overwght99.htm. Accessed February 7, 2003. 34 35 Bauer J, Hentschel R, Linderkamp O: Effect of sepsis syndrome on neonatal oxygen consumption and energy expenditure. Pediatrics 2002, 110:e69. Bauer J, Maier K, Linderkamp O, et al.: Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea. Pediatrics 2001, 107:660663. Oken E, Duggan C: Update on micronutrients: iron and zinc. Curr Op Pediatr 2002, 14:350353. Strand TA, Chandyo RK, Bahl R, et al. Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children. Pediatrics 2002,109:898 903.. Bhandari N, Bahl R, Taneja S, et al.: Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomized controlled trial in an urban slum. BMJ 2002, 324:1358. Bahl R, Bhandari N, Saksena M, et al.: Efficacy of zinc-fortified oral rehydration solution in 6- to 35-month-old children with acute diarrhea. J Pediatr 2002, 141:677682. Zinc Investigators Collaborative Group: Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000, 72:1516 1522. Zinc Investigators Collaborative Group: Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. J Pediatr 1999, 135:689697. Victora CG, Bryce J, Fontaine O, et al.: Reducing deaths from diarrhea through oral rehydration therapy. Bull World Health Organ 2000, 78:1246 1255. Santosham M: Oral rehydration therapy: reverse transfer of technology. Arch Pediatr Adolesc Med 2002, 156:11771179. Thea DM, St. Louis ME, Atido U, et al.: A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants. N Engl J Med 1993, 329:1696 1702. Ball CS: Global issues in pediatric nutrition: AIDS Nutr 1998, 14:767770. Mulligan K, Bloch AS: Energy expenditure and protein metabolism in human immunodeficiency virus infection and cancer cachexia. Semin Oncol 1998, 25:8291. Villamor E, Mbise R, Spiegelman D, et al.: Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth. Pediatrics 2002, 109:E6. Dreyfuss ML, Fawzi WW: Micronutrients and vertical transmission of HIV-1. Am J Clin Nutr 2002, 75:959970. World Health Organization and UNICEF: Protecting, promoting, and supporting breastfeeding: the special role of maternity services. Geneva: World Health Organization, 1989.

36 37

26 27

38

28 29

39

40

30

Ogden CL, Flegal KM, Carroll MD, et al.: Prevalence and trends in overweight among US children and adolescents, 1999 2000. JAMA 2002, 288:172832. The prevalence of overweight (defined as BMI equal to or greater than 95%) in US children and adolescents was found to be 15.5% among those 12 to 19 years of age, 15.3% among those 6 to 11 years of age, and 10.4% among those 2 to 5 years of age in the period 19992000, compared with 10.5%, 11.3%, and 7.2%, respectively, in 19881994. A 10% increase was observed among non-Hispanic black and Mexican-American adolescents during this same time period. Interventions may need to involve both family- and school-based programs to help modify diet and physical activity practices, to help reduce the increasing prevalence of overweight in US children. 31 Gillman MW, Rifas-Shiman SL, Camargo Jr CA, et al.: Risk of overweight among adolescents who were breast fed as infants. JAMA 2001, 285:2461 2467.

41

42

43 44

45 46

32

Toschke AM, Vignerova J, Lhotska L, et al.: Overweight and obesity in 6- to 14-year-old Czech children in 1991: protective effect of breast-feeding. J Pediatr 2002, 141:764769. The impact of breastfeeding in infancy on overweight and obesity in children ages 6 to 14 years was studied in the Czech Republic. Breastfeeding was common, with 90.7% of infants ever breastfed and only 9.3% never breastfed. Prevalence of overweight was lower in breastfed children (9.3% vs 12.4%) in never breastfed children. Prevalence of obesity was 3.2% in breast fed versus 4.4% in those not breastfed. Length of time breastfeeding was inversely correlated to prevalence of overweight but not to obesity. 33 Duro D, Rising R, Cole C, et al.: New equations for calculating the components of energy expenditure in infants. J Pediatr 2002, 140:534539.

47

48 49