David H. Adamkin

Postnatal Glucose Homeostasis in Late-Preterm and Term Infants

This report provides a practical guide and algorithm for the screening and subsequent management of neonatal hypoglycemia. Current evidence does not support a specific concentration of glucose that can discriminate normal from abnormal or can potentially result in acute or chronic irreversible neurologic damage. Early identification of the at-risk infant and institution of prophylactic measures to prevent neonatal hypoglycemia are recommended as a pragmatic approach despite the absence of a consistent definition of hypoglycemia in the literature.

Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula

Background In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice. Objective To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding. Methods The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750–1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050–3,300 kJ/L, 22–24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) ≥ 50% energy from human milk before hospital discharge (≥ 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119). Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants. This absolute difference persisted until 6 months CA. PFF-T infants were also longer (1.0–1.5 cm) and had larger head circumferences (0.3–1.1 cm) than both PHM-T and ≥ 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed ≥ 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model). Conclusion Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age

BACKGROUND The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants

Objective:Dietary carotenoids (lutein, lycopene and β-carotene) may be important in preventing or ameliorating prematurity complications. Little is known about carotenoid status or effects of supplementation.Study Design:This randomized controlled multicenter trial compared plasma carotenoid levels among preterm infants (n=203, <33 weeks gestational age) fed diets with and without added lutein, lycopene and β-carotene with human milk (HM)-fed term infants. We assessed safety and health.Result:Plasma carotenoid levels were higher in the supplemented group at all time points (P<0.0001) and were similar to those of term HM-fed infants. Supplemented infants had lower plasma C-reactive protein (P<0.001). Plasma lutein levels correlated with the full field electroretinogram-saturated response amplitude in rod photoreceptors (r=0.361, P=0.05). The supplemented group also showed greater rod photoreceptor sensitivity (least squares means 6.1 vs 4.1; P<0.05).Conclusion:Carotenoid supplementation for preterm infants raises plasma concentrations to those observed in HM-fed term infants. Carotenoid supplementation may decrease inflammation. Our results point to protective effects of lutein on preterm retina health and maturation.

Postnatal malnutrition of extremely low birth-weight infants with catch-up growth postdischarge.

Objective: To assess nutritional intakes and subsequent growth of extremely low birth-weight (BW) infants.Study Design: Chart review of 69 extremely low BW infants stratified into two groups by BW: ≤750 g (group 1; n=27) or 751 to 1000 g (group 2; n=42). Dietary intakes, weights, and head circumferences (HC) were collected through discharge and at 1 month postdischarge. The differences between goals and intakes were calculated weekly during hospitalization. Descriptive comparisons were made between growth parameters at birth, discharge, and follow-up.Results: Total energy and protein deficits were inversely related to BW. Both groups exhibited extrauterine growth retardation while hospitalized. After discharge, the rates of weight gain and HC growth increased, leading to some growth recovery at follow-up.Conclusions: Existing feeding methods resulted in sizeable deficits in energy and protein, particularly for the smallest infants. Changing current practices to limit these deficits is essential to improving postnatal growth.

Prediction of Extrauterine Growth Retardation (EUGR) in VVLBW Infants

BACKGROUND:Long-term growth failure in very very low birth weight (VVLBW) infants is a common complication of extreme prematurity. Critical illnesses create challenges to adequate nutriture.PURPOSE:To identify predictors of extrauterine growth retardation (EUGR) in VVLBW infants and to evaluate their nutritional intake and subsequent growth.STUDY DESIGN: A 4-year retrospective chart review of 221 infants ≤1000 g birth weight and ≤29 weeks gestational age who were admitted within 24 hours of birth, were free of major congenital anomalies and survived at least 7 days. Daily intakes and anthropomorphic data were collected and analyzed. Significant events during hospitalization were documented.RESULTS: Mean energy and protein intakes during hospitalization did not reach recommendations of 120 kcal/kg/d and 3.0 g/kg/day. In utero growth rates could not be consistently reached or sustained. As expected, BW (as measured by BW percentile score) was highly predictive of EUGR (p<0.001). When the independent effect of other predictors of EUGR was considered, only days of total parenteral nutrition (p<0.001) and HC percentile at return to birth weight (p<0.001) made a significant contribution to the prediction of EUGR, once the effect of BW was taken into account.

Early amino acids and the metabolic response of ELBW infants (≤ 1000 g) in three time periods

Objective:To evaluate early amino-acid (AA) administration in extremely low birth weight (ELBW) infants over three time periods, beginning with the initiation of this strategy.Study design:This was a retrospective study of ELBW infants between 2000 and 2007. Nutritional intake and laboratory results were monitored during the first 5 days of life. Growth rates and complications were followed until discharge.Result:Infants were similar in birth weight (BW), gestational age (GA) and severity of illness. The age at initiation of AA decreased significantly over time. Age at weight nadir, return to BW and percent postnatal weight loss decreased in epoch 3. There were modest increases in blood urea nitrogen (BUN), but no significant metabolic disturbances were observed. Cholestasis was more prevalent in epoch 2.Conclusion:AA administration within the first hours of life appears to be safe and beneficial for ELBW infants. Absent signs of renal dysfunction, a modest rise in BUN is consistent with the neonates utilization of AAs for energy.

Hidden Morbidity With “Successful” Early Discharge

OBJECTIVE: This study was conducted to determine if early postnatal discharge (EDC; ≤48 hours) in well newborns had an effect on the rate of hospital readmission within the first week after hospital discharge when compared to infants who remained >48 hours after birth (later discharge, LDC).STUDY DESIGN: This was a retrospective medical chart review. Charts of infants born between January 1994 and December 1998, discharged as “well newborns” and treated subsequently at a primary childrens hospital within 7 days of neonatal discharge, were reviewed. Infants were categorized by length of neonatal hospital stay, level of medical intervention (emergency department treatment or hospital admission), and final diagnosis.RESULTS: There was a significant increase in hospital readmission rate for LDC infants when compared to EDC infants. When considering jaundice alone as an admitting diagnosis, EDC infants were admitted at a higher rate than LDC infants and with higher serum bilirubin concentrations. Readmitted, jaundiced infants had been almost always breast-fed.CONCLUSION: Overall, EDC of well newborns appears to be a safe and reasonable practice. However, the risk for severe jaundice is an unresolved issue that requires a discharge strategy and early follow-up to prevent serious morbidity.

A retrospective analysis of the effect of human milk on prevention of necrotizing enterocolitis and postnatal growth

Objective:The objective of this study is to determine whether the use of donor human milk (DHM) in very low birth weight (VLBW, ⩽1500 g) neonates in a large neonatal intensive care unit (NICU) affected the rate of necrotizing enterocolitis (NEC) or impacted growth.Study Design:This was a retrospective chart review of 550 VLBW neonates following the introduction of DHM as the preferred diet if maternal breast milk (MBM) was not available. Demographics, growth parameters, incidence of NEC or death and days of DHM or MBM were extracted from charts.Result:Compared with infants who received human milk (HM) on fewer than 50% of hospital days, neonates who received HM on ⩾50% of hospital days had equivalent growth outcomes but lower rates of NEC (NEC 3.4 vs 13.5%, P<0.001) and mortality (1.0 vs 4.2%, P=0.017). Growth and NEC rates were inversely correlated with the duration of exposure to HM.Conclusion:HM should always be the diet of choice in preterm infants. DHM is a safe alternative, if MBM is not available. Although the use of HM is associated with lower rates of NEC, growth rates were significantly lower in infants with significant HM intake. The decline in growth rates following the introduction of DHM should draw attention to optimize fortification of all HM feedings.

Pragmatic Approach to In-Hospital Nutrition in High-Risk Neonates

Extremely low birth weight infants may experience periods of moderate to severe undernutrition during the acute phase of their respiratory problems. This undernutrition contributes to early growth deficits in these patients and may have long-lasting effects, including poor neurodevelopmental outcome. Early postnatal intravenous amino-acid administration and early enteral feeding strategies will minimize the interruption of nutrient intake that occurs with premature birth. These two strategies will prevent intracellular energy failure, allow the administration of more non-protein energy, as well as enhance overall nutritional health, as evidenced by less postnatal weight loss and earlier return to birth weight, and improved overall postnatal growth and outcome.