Steven J. Gross

Nutritional composition of milk produced by mothers delivering preterm.

The nutritional composition of milk obtained during the first month postpartum from 33 mothers delivering preterm and 18 mothers delivering at term was determined. Milk produced by mothers delivering preterm contained significantly higher concentrations of protein, sodium, and chloride, and significantly lower concentrations of lactose than milk produced by mothers delivering at term. The caloric concentration of milk produced by the two groups of mothers was similar, as were the concentrations of potassium, calcium, phosphorus, and magnesium. PT milk appears to approximate more closely the nutritional needs of the preterm infant than does other breast milk.

Elevated IgA concentration in milk produced by mothers delivered of preterm infants.

Concentrations of immunoglobulins G, M, and A were measured by double-antibody radioimmunoassay in morning milk samples collected during the first month postpartum from 35 mothers delivered of preterm infants and 14 mothers delivered of term infants. Mean concentrations of IgG (1.8 to 2.8 mg/gm protein) and IgM (2.8 to 11.7 mg/gm protein) were similar in milk from both groups of mothers. In contrast, IgA was present in significantly higher concentrations throughout the first month postpartum in milk from mothers delivered of preterm infants than in milk from those giving birth at term ( P P P

Follow-up at 15 Years of Preterm Infants From a Controlled Trial of Moderately Early Dexamethasone for the Prevention of Chronic Lung Disease

Objective. Postnatal dexamethasone treatment of ventilator-dependent preterm infants results in rapid improvement in lung function and reduction in chronic lung disease. However, limited data are available on long-term outcomes after such therapy. We studied growth, neurodevelopmental, and pulmonary outcomes at adolescence in children who had participated in a double-blind, placebo-controlled trial of dexamethasone beginning at 2 weeks of age for the prevention of chronic lung disease. Methods. Thirty-six infants (birth weight ≤1250 g and gestational age ≤30 weeks) who were dependent on mechanical ventilation at 2 weeks of age received a 42-day course of dexamethasone, an 18-day course of dexamethasone, or saline placebo. Twenty-two children survived to 15 years (69% of the 42-day dexamethasone group, 67% of the 18-day dexamethasone group and 45% of the control group), and all were evaluated. Intact survival was defined as survival with normal neurologic examination, IQ >70, and receiving education in the regular classroom. Results. There were no differences among groups for growth or incidence of neurologic abnormalities. The mean IQ for the 42-day dexamethasone group was 85 ± 10 compared with 60 ± 20 for the 18-day dexamethasone group and 73 ± 23 for the control group. All children in the 42-day dexamethasone group were receiving education in the regular classroom compared with only 50% of the 18-day dexamethasone group and 40% of the control group. As a result, intact survival was significantly greater for the 42-day dexamethasone group (69%) than for either the 18-day dexamethasone group (25%) or the control group (18%). Pulmonary function was significantly better for the 42-day dexamethasone group compared with the 18-day dexamethasone group (eg, forced expiratory volume in 1 second: 90 ± 16 vs 71 ± 15% predicted, respectively). Conclusion. A 42-day course of dexamethasone therapy beginning at 2 weeks of age in preterm infants who are at high risk for severe chronic lung disease was associated with improved long-term neurodevelopmental outcome. Although additional research is needed to establish the optimal steroid preparation, dosage, and duration of therapy, these data support the view that moderately early (beginning at 1-2 weeks) corticosteroid treatment is advantageous for a select group of ventilator-dependent preterm infants.

Growth, Efficacy, and Safety of Feeding an Iron-Fortified Human Milk Fortifier

Objective. Survival rates for preterm infants who weigh between 501 and 1500 g at birth have continued to improve over time. In response to this continuing decrease in birth weight of surviving preterm infants, Enfamil Human Milk Fortifier has recently been reformulated to meet the nutritional requirements of these smaller, more rapidly growing infants. It now provides an increased protein level of 1.1 g/58 kJ, a decreased carbohydrate level of 0.2 g/58 kJ, and a combined linoleic and α-linolenic fatty acid content of 157 mg/58 kJ. As these very small preterm infants have an increased requirement for dietary iron, the fortifier has been supplemented with 1.44 mg/58 kJ of iron, an amount of iron similar to that provided in a typical iron-fortified term infant formula. An iron-fortified product obviates the need for administration of an iron supplement, a hyperosmolar-inducing intervention. The purpose of this prospective, double-blind, randomized, controlled study was to evaluate growth, safety, and efficacy in a population of very low birth weight (VLBW) preterm infants who received human milk fortified with either the reformulated iron-fortified powdered human milk fortifier test product (HMF-T) or a powdered commercially available human milk fortifier control product (HMF-C). Methods. Infants who weighed ≤1500 g, had a gestational age ≤33 weeks postmenstrual age, and had an enteral intake of at least 100 mL/kg per day of unfortified human milk were stratified by gender and birth weight and randomized to receive HMF-T or HMF-C product from study day 1 to study day 28, hospital discharge, or the termination of human milk feedings, whichever came first. Unless medically indicated, investigators were not to administer iron supplements from study days 1 to 14. Infants were assessed serially for growth; enteral and parenteral intake; serum chemistry and hematologic values; clinical histories, including the administration of blood transfusions; feeding tolerance; respiratory outcomes; and morbidities, including adverse events. Results. Of the 181 participating infants in this study, 96 received HMF-T and 85 received HMF-C. At randomization, there were no significant differences in infant characteristics between the fortifier groups. The percentage of participants who remained in the study for 28 days was similar between fortifier groups (57% HMF-T, 46% HMF-C). For both fortifier groups, the most frequent reasons for discontinuing the study before study day 28 were unavailability of human milk and hospital discharge. Rate of weight gain was similar between the fortifier groups (17.5 ± 0.53 g/kg per day for HMF-T and 17.3 ± 0.59 g/kg per day for HMF-C). Mean achieved weight, length, and head circumference were comparable between groups across the 28-day study period. Total protein intake from enteral and parenteral nutrition was significantly greater for the HMF-T fortifier group; however, this difference did not result in any difference in growth between the 2 fortifier groups. An analysis of the growth and energy intake data of a subset of the intent-to-treat population who adhered more strictly to the study feeding protocol yielded results similar to those seen for the intent-to-treat population. There were no clinically significant differences in the results of laboratory studies between the groups at study days 0, 14, and 28. Anemia of prematurity was prevalent in both study groups; by study day 28, median hematocrit levels were 27.0% (interquartile range [IQR]: 24.0%–29.6%) for the HMF-T group and 26.0% (IQR: 24.0%–31.0%) for the HMF-C group. Median ferritin levels were 77.0 ng/mL (IQR: 37-155 ng/ml) for HMF-T and 92.0 ng/mL (IQR: 33-110 ng/mL) for HMF-C. There were no significant differences between the study fortifier groups in regard to the receipt of medically indicated iron supplements on or before study day 14 or in the administration of blood transfusions before study day 0 or from study days 0 through 14. However, from study day 15 to study day 28, fewer HMF-T infants (n = 12) required a blood transfusion than did HMF-C infants (n = 20). Although the higher levels of iron in the HMF-T fortifier (1.44 mg vs 0.35 mg for HMF-C per 4 packets of powdered fortifier) did not prevent anemia per se, it did reduce the frequency of one of the most serious outcomes of anemia: the need for a blood transfusion. There was no statistically significant difference between fortifier groups in regard to feeding tolerance. Rates of suspected sepsis (26% HMF-T vs 31% HMF-C) and confirmed sepsis (5% HMF-T, 7% HMF-C) were low as were the rates of suspected necrotizing enterocolitis (NEC; 6% HMF-T and 5% HMF-C) and confirmed Bells stage 2 or more NEC (1% HMF-T and 1% HMF-C). There were no statistically significant differences between the study fortifier groups in regard to the incidence of confirmed and suspected sepsis and NEC. Conclusion. Both human milk fortifiers studied are safe, are well tolerated, and facilitate comparable good growth; however, using the iron-fortified product may reduce the need for blood transfusions in VLBW infants. The similar low rates of suspected and confirmed NEC and sepsis seen in both fortifier groups in this study refutes the premise that the inclusion of iron in fortifiers will increase the incidence of sepsis and NEC. Indeed, the incidence for NEC and sepsis for both groups in this study was lower than is reported for VLBW infants and similar to that seen for infants who are fed human milk.

Controlled study of treatment for disseminated intravascular coagulation in the neonate

Thirty-three neonates with disseminated intravascular coagulation were assigned randomly to one of three treatment groups: (1) exchange transfusion, (2) administration of fresh-frozen plasma and platelets, and (3) control (no therapy directed specifically at the coagulopathy). The three groups were comparable for degree of abnormality in initial coagulation studies and underlying pathologic processes. Shock was a common accompaniment of DIC and occurred in 85% of all infants. In all cases, underlying disease states and shock were treated aggressively. Resolution of DIC and survival were not different in the three treatment groups. Outcome of DIC was dependent on the success of treatment of the underlying pathologic process and aggressive supportive care, including restoration of blood pressure, but was not altered by therapy specifically directed at the coagulopathy.

Vitamin E status in preterm infants fed human milk or infant formula

Vitamin E status was assessed in 36 infants with birth weights less than 1500 gm who were assigned randomly to receive one of three sources of nutrition: milk obtained from mothers of preterm infants (preterm milk), mature human milk, or infant formula. Infants in each dietary group were further assigned randomly to receive iron supplementation (2 mg/kg/day) beginning at 2 weeks or to receive no iron supplementation. All infants received a standard multivitamin, providing 4.1 mg alpha-tocopherol daily. Serum vitamin E concentrations at 6 weeks were significantly related both to type of milk (P less than 0.0001) and to iron supplementation (P less than 0.05). Infants fed preterm milk had significantly higher serum vitamin E levels than did infants fed mature human milk, and both groups had significantly higher levels than did those fed formula. Ratios of serum vitamin E/total lipid were also significantly greater for infants fed human milks than for those fed formula. The addition of iron to all three diets resulted in significantly lower serum vitamin E levels at 6 weeks (P less than 0.05); however, only in the group fed formula was there evidence of vitamin E deficiency. Preterm milk with routine multivitamin supplementation uniformly resulted in vitamin E sufficiency in VLBW infants whether or not iron was administered.

Cingulate sulcus development in preterm infants

ABSTRACT: Cranial ultrasounds performed during the first 3 d of life on 211 infants of 24 to 40 wk gestational age were examined to determine the in utero development of the cingulate sulcus. The sulcus was identified between 24 and 28 wk of gestational age as fragmented echoes in the region between the thalamus and the anterior fontanelle. Over the next several weeks, these fragments coalesced into a single linear echo. Branches then appeared off of the primary cingulate sulcus, increasing in number until a complex pattern of branching was noted near term gestation. This maturational sequence was similar to postnatal cortical development determined from serial ultrasounds performed on 144 infants who were ≤ 32 wk of gestational age at birth. The timing of postconceptional cingulate sulcus development was independent of gestational age at birth. However, severe brain insult, defined as intraventricular hemorrhage complicated by ventriculomegaly or intraparenchymal extension or periventricular leukomalacia, was associated with significant delays in all stages of cingulate sulcus development. Cranial ultrasound examinations in preterm infants allow a noninvasive means of staging qualitative brain development during the early postnatal period.

Normative early head growth in very-low-birth-weight infants.

Normative head growth curves were developed from serial weekly measurements of head circumference in 50 infants with birth weights less than 1500 gm who had good neurodevelopmental outcome at 2 years of age (assessed by neurologic examination and by the Bayley Mental Developmental Scale). Forty-one of the infants with good outcome were normocephalic at birth; after head shrinkage during the first week of life, increments in head circumference averaged 0.49 cm during the second week, 0.79 cm during the third week, and 0.95 cm per week thereafter. Nine infants with good outcome were microcephalic at birth; these infants had no head shrinkage during the first week of life and had a significantly greater mean weekly increment in head circumference of 0.98 cm (P less than 0.008). In contrast, 10 normocephalic and seven microcephalic infants with poor outcome had significantly less postnatal head growth (P less than 0.02 and p less than 0.001, respectively). Head growth curves developed from measurements in infants with documented good short-term developmental outcome are the most appropriate standards for head growth for very-low-birth-weight infants.

86 PROSPECTIVE RANDOMIZED CONTROLLED TRIAL OF CONVENTIONAL TREATMENT OR TRANSPORT FOR ECMO IN INFANTS WITH SEVERE PERSISTENT PULMONARY HYPERTENSION (PPHN): TWO YEAR FOLLOW UP

28 of 31 ECMO eligible infants born July, 1988 to March, 1992 with severe PPHN were assigned randomly when oxygenation index (OI) was ≥ 40 for four hours to be transported for ECMO (n=15, birthweight 3601 ± 622 g; OI 63 ± 28) or to receive conventional therapy at our center (n=13, birthweight 3403 ± 640 g; OI 60 ± 28). Fourteen of the 15 infants (93%) transported for ECMO survived to hospital discharge (including 3 who did not receive ECMO), while 7 of 13 (54%) conventionally treated infants survived (p<05). One ECMO infant died after hospital discharge at age 3 months of SIDS. Outcome for the survivors (mean ± SD):ECMO salvaged sicker neonates (mean OI at study entry for ECMO survivors was 60 ± 21 vs 44 ± 5 for conventionally treated survivors); nevertheless, transport for ECMO was not associated with worse neurodevelopmental outcome at 2 years. These data support the use of ECMO in term infants with severe respiratory distress.

THE EFFECT OF VITAMIN E ON RED CELL HEMOLYSIS AND BILIRUBINEMIA

The life span of the term infant’s erythrocytes is approximately two-thirds that of the erythrocytes of normal adults.’ The red cells of premature infants have an even shorter life span than do the red cells of term infants.’ The mechanisms responsible for this accelerated senescence are unknown. Premature infants, at birth, are deficient in vitamin E. Deficiency of vitamin E, a naturally occurring antiperoxidant, can produce a shortening of red cell life span.3 The purpose of this investigation was to determine if the presence of vitamin E deficiency in the premature infant during the first week of life played a contributory role in the shortened red cell survival. In addition, since hyperbilirubinemia is, in part, secondary to red cell breakdown, we examined the influence of early vitamin E supplementation on bilirubinemia in preterm infants.