Sex-Specific Differences in Late Preterm Neonatal Outcomes

Abstract

Objective To estimate sex-specific differences in late preterm outcomes and evaluate whether betamethasone modifies this association.

Study Design We conducted a secondary analysis of a multicenter trial of women at risk for late preterm birth randomized to receive betamethasone or placebo. We included women who delivered at 34 to 37 weeks and excluded major fetal anomalies. The primary outcome was severe neonatal morbidity (mechanical ventilation, respiratory distress syndrome, bronchopulmonary dysplasia, sepsis, necrotizing enterocolitis, and intraventricular hemorrhage). Maternal characteristics were compared using chi-square test, t-test, or Mann–Whitney U-test. Multivariable logistic regression estimated the association between sex and morbidity, and likelihood ratio testing assessed for effect modification by betamethasone.

Results Of 2,831 women in the primary trial, 2,331 met the inclusion criteria: 1,236 delivered males and 1,095 delivered females. Betamethasone modified the association between sex and severe morbidity (p = 0.047). Among those who received betamethasone, male sex was associated with higher odds of severe morbidity (adjusted odds ratio: 1.95, 95% confidence interval: 1.25–3.05), compared with female sex. Among those who did not receive betamethasone, there was no significant association between sex and morbidity.

Conclusion Male sex is a risk factor for adverse late preterm outcomes, including severe neonatal morbidity after betamethasone receipt.

Keywords

late preterm - sex differences - preterm birth - betamethasone - respiratory distress syndrome

Note

This study was presented in poster format at the 38th Annual Meeting of the Society for Maternal-Fetal Medicine, Dallas, TX, January 29 to February 3, 2018.

• References

• 1 Martin JA, Hamilton BE, Osterman MJK. , et al. Births: Final data for 2015. National vital statistics report; vol 66, no 1. Hyattsville, MD: National Center for Health Statistics; 2017
• 2 McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol 2008; 111 (01) 35-41
• 3 Papageorgiou AN, Colle E, Farri-Kostopoulos E, Gelfand MM. Incidence of respiratory distress syndrome following antenatal betamethasone: role of sex, type of delivery, and prolonged rupture of membranes. Pediatrics 1981; 67 (05) 614-617
• 4 Tyson JE, Parikh NA, Langer J, Green C, Higgins RD. ; National Institute of Child Health and Human Development Neonatal Research Network. Intensive care for extreme prematurity--moving beyond gestational age. N Engl J Med 2008; 358 (16) 1672-1681
• 5 Kent AL, Wright IM, Abdel-Latif ME. ; New South Wales and Australian Capital Territory Neonatal Intensive Care Units Audit Group. Mortality and adverse neurologic outcomes are greater in preterm male infants. Pediatrics 2012; 129 (01) 124-131
• 6 Binet M-E, Bujold E, Lefebvre F, Tremblay Y, Piedboeuf B. ; Canadian Neonatal Network™. Role of gender in morbidity and mortality of extremely premature neonates. Am J Perinatol 2012; 29 (03) 159-166
• 7 Shim SY, Cho SJ, Kong KA, Park EA. Gestational age-specific sex difference in mortality and morbidities of preterm infants: a nationwide study. Sci Rep 2017; 7 (01) 6161
• 8 Gyamfi-Bannerman C, Thom EA, Blackwell SC. , et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med 2016; 374 (14) 1311-1320
• 9 Marshall SW. Power for tests of interaction: effect of raising the Type I error rate. Epidemiol Perspect Innov 2007; 4: 4
• 10 Peacock JL, Marston L, Marlow N, Calvert SA, Greenough A. Neonatal and infant outcome in boys and girls born very prematurely. Pediatr Res 2012; 71 (03) 305-310
• 11 Månsson J, Fellman V, Stjernqvist K. ; EXPRESS Study Group (authors). Extremely preterm birth affects boys more and socio-economic and neonatal variables pose sex-specific risks. Acta Paediatr 2015; 104 (05) 514-521
• 12 Weng YH, Yang CY, Chiu YW. Neonatal outcomes in relation to sex differences: a national cohort survey in Taiwan. Biol Sex Differ 2015; 6 (01) 30
• 13 Anadkat JS, Kuzniewicz MW, Chaudhari BP, Cole FS, Hamvas A. Increased risk for respiratory distress among white, male, late preterm and term infants. J Perinatol 2012; 32 (10) 780-785
• 14 Kaltofen T, Haase M, Thome UH, Laube M. Male sex is associated with a reduced alveolar epithelial sodium transport. PLoS One 2015; 10 (08) e0136178
• 15 Lazrak A, Samanta A, Venetsanou K, Barbry P, Matalon S. Modification of biophysical properties of lung epithelial Na(+) channels by dexamethasone. Am J Physiol Cell Physiol 2000; 279 (03) C762-C770
• 16 Ishak N, Sozo F, Harding R, De Matteo R. Does lung development differ in male and female fetuses?. Exp Lung Res 2014; 40 (01) 30-39
• 17 Clifton VL. Review: sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta 2010; 31 (Suppl): S33-S39
• 18 Stark MJ, Clifton VL, Wright IMR. Sex-specific differences in peripheral microvascular blood flow in preterm infants. Pediatr Res 2008; 63 (04) 415-419
• 19 Stark MJ, Wright IMR, Clifton VL. Sex-specific alterations in placental 11beta-hydroxysteroid dehydrogenase 2 activity and early postnatal clinical course following antenatal betamethasone. Am J Physiol Regul Integr Comp Physiol 2009; 297 (02) R510-R514