Trends in sex-specific differences in outcomes in extreme preterms: progress or natural barriers?

OBJECTIVE: To examine the differences and trends of outcomes of preterm boys and girls born at <29 weeks' gestation. DESIGN: A retrospective cohort study. SETTING: Data collected by the Canadian Neonatal Network. PATIENTS: Neonates born at <29 weeks' gestation between January 2007 and December 2016. MAIN OUTCOME MEASURES: We examined rate differences in mortality, major morbidities (bronchopulmonary dysplasia, severe brain injury, retinopathy of prematurity, necrotising enterocolitis and late-onset sepsis) and care practices (antenatal steroids, magnesium sulfate, maternal antibiotics, ventilation and surfactant administration) between boys and girls and evaluated trends in these rate differences over the study period. Our primary outcome was a composite of mortality and any one of the five morbidities. RESULTS: Our study included 8219 boys and 6934 girls with median gestational age of 26 (IQR 25-28) weeks. The composite of death or major morbidity was more common in boys (adjusted risk ratio 1.07, 95% CI 1.05 to 1.10) and remained higher in boys over the study period. The gap between boys and girls for mortality, however, decreased over time: the slope for boys was -0.043 (95% CI -0.071 to -0.015) and for girls was -0.012 (95% CI -0.045 to 0.020) (p=0.04). All other morbidities remained higher in boys. Care practices changed at similar rates between the sexes. CONCLUSION: The difference between the mortality rates for boys and girls decreased over the study period but the difference between rates of the major morbidities was unchanged. More research is needed to understand biological differences and outcome disparities.

Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP).

OBJECTIVES: To determine the risk of bronchopulmonary dysplasia (BPD) in subgroups of infants with and without patent ductus arteriosus (PDA) who were randomized to indomethacin prophylaxis or placebo, and to examine whether adverse drug effects on edema formation and oxygenation may explain why indomethacin prophylaxis does not reduce BPD. STUDY DESIGN: We studied 999 extremely low birth weight infants who participated in the Trial of Indomethacin Prophylaxis in Preterms (TIPP) and who survived to a postmenstrual age of 36 weeks. RESULTS: The incidence of BPD in the 2 subgroups of infants with PDA was 52% (55/105) after indomethacin prophylaxis and 56% (137/246) after placebo. In contrast, rates of BPD in the 2 subgroups without a PDA were 43% (170/391) after indomethacin prophylaxis and 30% (78/257) after placebo (P [interaction] = .015). Logistic regression analysis with adjustment for prognostic baseline factors showed that adverse and independent effects of indomethacin prophylaxis on the need for supplemental oxygen and on weight loss by the end of the first week of life may increase the risk of BPD in infants without PDA. CONCLUSIONS: Harmful side effects on oxygenation and edema formation may explain why indomethacin prophylaxis does not prevent BPD even though it reduces PDA.

Reduced bone mineralization in infants fed palm olein-containing formula: a randomized, double-blinded, prospective trial.

OBJECTIVE: Palm and palm olein (PO) oils are used in some infant formula fat blends to match the fatty acid profile of human milk, but their presence has been shown to lower calcium and fat absorption. We aimed to determine if the reported differences in calcium absorption could affect skeletal development by comparing bone mineral accretion in healthy term infants fed a milk-based formula with (PMF) or without PO. METHODS: Whole body bone mineralization was evaluated in healthy term infants fed 1 of 2 coded, commercially available, ready-to-feed infant formulas in a randomized, double-blind, parallel study. Subjects were fed either 1). PMF formula (Enfamil with iron; Mead Johnson Division of Bristol Myers, Evansville, IN; N = 63) containing PO/coconut/soy/high-oleic sunflower oils (45/20/20/15% oil); or 2). milk-based formula without PO (Similac with iron; Ross Products Division Abbott Laboratories, Columbus, OH; N = 65), containing high-oleic safflower/coconut/soy oils (40/30/30% oil) from enrollment by 2 weeks after birth until 6 months. Anthropometrics and formula intake were determined monthly; total body bone mineral content (BMC) and bone mineral density (BMD) were measured at baseline, 3, and 6 months of age using dual energy x-ray absorptiometry. RESULTS: Intent-to-treat analyses indicated no significant differences between feeding groups in weight, length, head circumference, or formula intake throughout the study. BMC and BMD were not different at baseline but repeated measures analyses show that infants fed PMF had significantly lower BMC and BMD at 3 and 6 months. CONCLUSIONS: Healthy term infants fed a formula containing PO as the predominant oil in the fat blend had significantly lower BMC and BMD than those fed a formula without PO. The inclusion of PO in infant formula at levels needed to provide a fatty acid profile similar to that of human milk leads to lower bone mineralization.