Gender variations in neonatal and early infant mortality in India and Pakistan: a secondary analysis from the Global Network Maternal Newborn Health Registry

Abstract

Background To determine the gender differences in neonatal mortality, stillbirths, and perinatal mortality in south Asia using the Global Network data from the Maternal Newborn Health Registry. Methods This study is a secondary analysis of prospectively collected data from the three south Asian sites of the Global Network. The maternal and neonatal demographic, clinical characteristics, rates of stillbirths, early neonatal mortality (1–7 days), late neonatal mortality (8–28 days), mortality between 29–42 days and the number of infants hospitalized after birth were compared between the male and female infants. Results Between 2010 and 2018, 297,509 births [154,790 males (52.03%) and 142,719 females (47.97%)] from two Indian sites and one Pakistani site were included in the analysis [288,859 live births (97.1%) and 8,648 stillbirths (2.9%)]. The neonatal mortality rate was significantly higher in male infants (33.2/1,000 live births) compared to their female counterparts (27.4/1,000, p < 0.001). The rates of stillbirths (31.0 vs. 26.9/1000 births) and early neonatal mortality (27.1 vs 21.6/1000 live births) were also higher in males. However, there were no significant differences in late neonatal mortality (6.3 vs. 5.9/1000 live births) and mortality between 29–42 days (2.1 vs. 1.9/1000 live births) between the two groups. More male infants were hospitalized within 42 days after birth (1.8/1000 vs. 1.3/1000 live births, p < 0.001) than females. Conclusion The risks of stillbirths, and early neonatal mortality were higher among male infants than their female counterparts. However, there was no gender difference in mortality after 7 days of age. Our results highlight the importance of stratifying neonatal mortality into early and late neonatal period to better understand the impact of gender on neonatal mortality. The information from this study will help in developing strategies and identifying measures that can reduce differences in sex-specific mortality.

Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

“…Male COVID-19 patients are three times more likely to require admission to intensive care units and have higher odds of death than females ( 84 ). This male-biased vulnerability to maternal SARS-CoV-2 infection mirrors the male-biased risk of mortality and morbidity across the perinatal period ( 1 – 3 ). Our findings of sexually dimorphic placental innate immune responses to infection, coupled with sex differences in transfer of maternal humoral immunity, may provide insight into increased vulnerability of male infants to morbidity and mortality.…”

Sex Differences Are Here to Stay: Relevance to Prenatal Care

“…A few studies report no sex differences in the rates of stillbirth [71,104], while one study found female excess in stillbirths without any observed demographic or obstetric differences by sex at diagnosis [109]. In addition, a study of infant mortality in India and Pakistan, where the probable causes for stillbirth were similar in both male and female groups, revealed a significantly higher rate of male stillbirths and an increased risk for early perinatal mortality among male infants [107].…”

“…Male fetal sex has been recognized as one of the most prevalent risk factors for stillbirth [102]. A heightened male risk of perinatal morbidity and mortality is well reported in the literature [71,[103][104][105][106], and a higher frequency of stillbirth among males has also been described [106][107][108]. However, nuances exist regarding male risk of stillbirth; for instance, one study noted that while male fetuses were at an increased risk of stillbirth, the association diminished with increasing birth weight quintile [103].…”

Sexually dimorphic placental responses to maternal SARS-CoV-2 infection

“…Mortality and morbidity risk during the perinatal period and infancy is significantly higher in males than in females (1)(2)(3)(4). The underlying susceptibility of males may relate to evolutionary differences that occur throughout pregnancy and in the perinatal period, but the precise mechanistic differences that lead to this differential female survival benefit is not completely understood.…”