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OBJECTIVE: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation. STUDY DESIGN: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks. RESULTS: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003). CONCLUSIONS: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03192839.

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OBJECTIVE: To assess serial secretory activation biomarker concentrations (sodium [Na], potassium [K], Na:K, protein, lactose, and citrate) in mother's own milk (MOM) from breast pump-dependent mothers of preterm infants to determine associations with coming to volume (CTV), defined as producing at least 500 mL/day MOM by day 14 postpartum. STUDY DESIGN: We collected serial MOM samples and pumped MOM volume data for 14 days postpartum in mothers who delivered at <33 weeks of gestation. Regression models and the Mann-Whitney U test were used to evaluate associations. RESULTS: Among 40 mothers, 39 (mean gestational age, 28.8 weeks; 67% overweight/obese; 59% nonwhite) had paired MOM volume and biomarker data; 33% achieved CTV between postpartum days 6 and 14. In univariate models, MOM Na on postpartum day 5 and Na:K on days 3 and 5 were associated with CTV. Mothers achieving CTV were more likely to have postpartum Na:K ≤1 on day 3 (75% vs 25%; P = .06) and ≤0.8 on day 5 (69% vs 10%; P < .01). In a multivariable regression model, day 5 Na:K (1 unit decrease in Na:K: OR, 18.7; 95% CI, 1.13-311.41; P = .049) and maternal prepregnancy body mass index (BMI) (1 unit increase in BMI: OR, 0.88; 95% CI, 0.78-0.99; P = .04) were associated with CTV between postpartum days 6 and 14. CONCLUSIONS: Secretory activation and CTV were compromised in breast pump-dependent mothers with preterm delivery. CTV was predicted by MOM Na level and Na:K. These biomarkers have potential as objective point-of-care measures to detect potentially modifiable lactation problems in a high-risk population.

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OBJECTIVE: To assess the cost-effectiveness of mother's own milk supplemented with donor milk vs mother's own milk supplemented with formula for infants of very low birth weight in the neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective analysis of 319 infants with very low birth weight born before (January 2011-December 2012, mother's own milk + formula, n = 150) and after (April 2013-March 2015, mother's own milk + donor milk, n = 169) a donor milk program was implemented in the NICU. Data were retrieved from a prospectively collected research database, the hospital's electronic medical record, and the hospital's cost accounting system. Costs included feedings and other NICU costs incurred by the hospital. A generalized linear regression model was constructed to evaluate the impact of feeding era on NICU total costs, controlling for neonatal and sociodemographic risk factors and morbidities. An incremental cost-effectiveness ratio was calculated for each morbidity that differed significantly between feeding eras. RESULTS: Infants receiving mother's own milk + donor milk had a lower incidence of necrotizing enterocolitis (NEC) than infants receiving mother's own milk + formula (1.8% vs 6.0%, P = .048). Total (hospital + feeding) median costs (2016 USD) were $169 555 for mother's own milk + donor milk and $185 740 for mother's own milk + formula (P = .331), with median feeding costs of $1317 and $936, respectively (P < .001). Mother's own milk + donor milk was associated with $15 555 lower costs per infant (P = .045) and saved $1812 per percentage point decrease in NEC incidence. CONCLUSIONS: The additional cost of a donor milk program was small compared with the cost of a NICU hospitalization. After its introduction, the NEC incidence was significantly lower with small cost savings per case. We speculate that NICUs with greater NEC rates may have greater cost savings.

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OBJECTIVE: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC). STUDY DESIGN: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition. RESULTS: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001). CONCLUSIONS: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU.

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OBJECTIVE: To identify factors associated with prolonged maternal breast milk (BM) provision in very low birth weight (VLBW) infants. STUDY DESIGN: This was a cohort study of VLBW infants who initially received maternal BM and were born at one of 197 neonatal intensive care units managed by the Pediatrix Medical Group from 2010 to 2012. We used multivariable logistic regression to identify demographic, clinical, and maternal factors associated with provision of maternal BM on day of life (DOL) 30 and at discharge. RESULTS: Median gestational age for all infants was 28 weeks (25th, 75th percentiles: 26, 30), and median maternal age was 28 years (23, 33). Of 8806 infants, 6261 (71%) received maternal BM on DOL 30, and 4003 of 8097 (49%) received maternal BM at discharge to home. Predictors of maternal BM provision at DOL 30 included increased maternal age, white maternal race, absence of history of necrotizing enterocolitis or late-onset sepsis, higher household income, lower education level, lack of donor BM exposure, and lower gestational age. CONCLUSIONS: Our results suggest that maternal-infant demographic and clinical factors and household neighborhood socioeconomic characteristics were associated with provision of maternal BM at 30 postnatal days to VLBW infants. Identification of these factors allows providers to anticipate mothers' needs and develop tailored interventions designed to improve rates of prolonged maternal BM provision and infant outcomes.

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OBJECTIVE: To determine the association between direct costs for the initial neonatal intensive care unit hospitalization and 4 potentially preventable morbidities in a retrospective cohort of very low birth weight (VLBW) infants (birth weight <1500 g). STUDY DESIGN: The sample included 425 VLBW infants born alive between July 2005 and June 2009 at Rush University Medical Center. Morbidities included brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and late-onset sepsis. Clinical and economic data were retrieved from the institution's system-wide data and cost accounting system. A general linear regression model was fit to determine incremental direct costs associated with each morbidity. RESULTS: After controlling for birth weight, gestational age, and sociodemographic characteristics, the presence of brain injury was associated with a $12048 (P = .005) increase in direct costs; necrotizing enterocolitis, with a $15 440 (P = .005) increase; bronchopulmonary dysplasia, with a $31565 (P < .001) increase; and late-onset sepsis, with a $10055 (P < .001) increase. The absolute number of morbidities was also associated with significantly higher costs. CONCLUSION: This study provides collective estimates of the direct costs incurred during neonatal intensive care unit hospitalization for these 4 morbidities in VLBW infants. The incremental costs associated with these morbidities are high, and these data can inform future studies evaluating interventions aimed at preventing or reducing these costly morbidities.

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OBJECTIVE: To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants. STUDY DESIGN: Infants fed their own mothers' milk were randomized to 1 of 3 study groups. Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor human milk if no mother's milk was available. Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother's milk was available. Outcomes included duration of parenteral nutrition, morbidity, and growth. RESULTS: The 3 groups (total n = 207 infants) had similar baseline demographic variables, duration of parenteral nutrition, rates of late-onset sepsis, and growth. The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis (NEC; P = .02) and NEC requiring surgical intervention (P = .007). CONCLUSIONS: For extremely premature infants, an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother's milk-based diet that also includes bovine milk-based products.

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