Does higher early neonatal mortality in boys reverse over the neonatal period? A pooled analysis from three trials of Nepal

Seema Subedi, Joanne Katz, Daniel Joseph Erchick, Andrea Verhulst, Subarna K Khatry, Luke C Mullany, James M Tielsch, Steven C LeClerq, Parul Christian, Keith P West, Michel Guillot, Seema Subedi, Joanne Katz, Daniel Joseph Erchick, Andrea Verhulst, Subarna K Khatry, Luke C Mullany, James M Tielsch, Steven C LeClerq, Parul Christian, Keith P West, Michel Guillot

Abstract

Objectives: Neonatal mortality is generally 20% higher in boys than girls due to biological phenomena. Only a few studies have examined more finely categorised age patterns of neonatal mortality by sex, especially in the first few days of life. The objective of this study is to examine sex differentials in neonatal mortality by detailed ages in a low-income setting.

Design: This is a secondary observational analysis of data.

Setting: Rural Sarlahi district, Nepal.

Participants: Neonates born between 1999 and 2017 in three randomised controlled trials.

Outcome measures: We calculated study-specific and pooled mortality rates for boys and girls by ages (0-1, 1-3, 3-7, 7-14, 14-21 and 21-28 days) and estimated HR using Cox proportional hazards models for male versus female mortality for treatment and control groups together (n=59 729).

Results: Neonatal mortality was higher in boys than girls in individual studies: 44.2 vs 39.7 in boys and girls in 1999-2000; 30.0 vs 29.6 in 2002-2006; 33.4 vs 29.4 in 2010-2017; and 33.0 vs 30.2 in the pooled data analysis. Pooled data found that early neonatal mortality (HR=1.17; 95% CI: 1.06 to 1.30) was significantly higher in boys than girls. All individual datasets showed a reversal in mortality by sex after the third week of life. In the fourth week, a reversal was observed, with mortality in girls 2.43 times higher than boys (HR=0.41; 95% CI: 0.31 to 0.79).

Conclusions: Boys had higher mortality in the first week followed by no sex difference in weeks 2 and 3 and a reversal in risk in week 4, with girls dying at more than twice the rate of boys. This may be a result of gender discrimination and social norms in this setting. Interventions to reduce gender discrimination at the household level may reduce female neonatal mortality.

Trial registration number: NCT00115271, NCT00109616, NCT01177111.

Keywords: Community child health; EPIDEMIOLOGY; NEONATOLOGY.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Sex difference in probability of dying for individual studies: NNIPS-3, CHX and NOMS (from left to right). CHX, Chlorhexidine Study; NNIPS, Nepal Nutrition Intervention Project Sarlahi; NOMS, Nepal Oil Massage Study,
Figure 2
Figure 2
Sex difference in probability of dying for pooled analysis, Nepal 1999–2017.

References

    1. Elsmén E, Steen M, Hellström-Westas L. Sex and gender differences in newborn infants: why are boys at increased risk? The Journal of Men's Health & Gender 2004;1:303–11. 10.1016/j.jmhg.2004.09.010
    1. Drevenstedt GL, Crimmins EM, Vasunilashorn S, et al. . The rise and fall of excess male infant mortality. Proc Natl Acad Sci U S A 2008;105:5016–21. 10.1073/pnas.0800221105
    1. Nathanson CA. Sex differences in mortality. Annu Rev Sociol 1984;10:191–213. 10.1146/annurev.so.10.080184.001203
    1. Hammoud EI. Studies in fetal and infant mortality. II. differentials in mortality by sex and race. Am J Public Health Nations Health 1965;55:1152–63. 10.2105/AJPH.55.8.1152
    1. Waldron I. Patterns and causes of excess female mortality among children in developing countries. World Health Stat Q 1987;40:194–210. 1987.
    1. Gove WR, Carpenter GR. The fundamental connection between nature and nurture: a review of the evidence. Free Press, 1982.
    1. Aghai ZH, Goudar SS, Patel A, et al. . Gender variations in neonatal and early infant mortality in India and Pakistan: a secondary analysis from the global network maternal newborn health registry. Reprod Health 2020;17:1–11. 10.1186/s12978-020-01028-0
    1. Hou L, Wang X, Li G, et al. . Cross sectional study in China: fetal gender has adverse perinatal outcomes in mainland China. BMC Pregnancy Childbirth 2014;14:372. 10.1186/s12884-014-0372-4
    1. Aibar L, Puertas A, Valverde M, et al. . Fetal sex and perinatal outcomes. J Perinat Med 2012;40:271–6. 10.1515/jpm-2011-0137
    1. Simchen MJ, Weisz B, Zilberberg E, et al. . Male disadvantage for neonatal complications of term infants, especially in small-for-gestational age neonates. J Matern Fetal Neonatal Med 2014;27:839–43. 10.3109/14767058.2013.845658
    1. Klein SL. Hormones and mating system affect sex and species differences in immune function among vertebrates. Behav Processes 2000;51:149–66. 10.1016/S0376-6357(00)00125-X
    1. Klein SL, Marson AL, Scott AL, et al. . Neonatal sex steroids affect responses to Seoul virus infection in male but not female Norway rats. Brain Behav Immun 2002;16:736–46. 10.1016/S0889-1591(02)00026-0
    1. Klein SL. Hormonal and immunological mechanisms mediating sex differences in parasite infection. Parasite Immunol 2004;26:247–64. 10.1111/j.0141-9838.2004.00710.x
    1. Mishra SK, Ram B, Singh A, et al. . Birth order, stage of infancy and infant mortality in India. J Biosoc Sci 2018;50:604–25. 10.1017/S0021932017000487
    1. Chowdhury R, Taneja S, Mazumder S, et al. . Gender differences in infant survival: a secondary data analysis in rural North India. BMJ Open 2017;7:e014179. 10.1136/bmjopen-2016-014179
    1. Yorita KL, Holman RC, Sejvar JJ, et al. . Infectious disease hospitalizations among infants in the United States. Pediatrics 2008;121:244–52. 10.1542/peds.2007-1392
    1. Elsmén E, Hansen Pupp I, Hellström-Westas L. Preterm male infants need more initial respiratory and circulatory support than female infants. Acta Paediatr 2004;93:529–33. 10.1080/08035250410024998
    1. Baqui AH, Darmstadt GL, Williams EK, et al. . Rates, timing and causes of neonatal deaths in rural India: implications for neonatal health programmes. Bull World Health Organ 2006;84:706–13. 10.2471/BLT.05.026443
    1. Rosenstock S, Katz J, Mullany LC, et al. . Sex differences in neonatal mortality in Sarlahi, Nepal: the role of biology and environment. J Epidemiol Community Health 2013;67:986–91. 10.1136/jech-2013-202646
    1. Zhao D, Zou L, Lei X, et al. . Gender differences in infant mortality and neonatal morbidity in mixed-gender twins. Sci Rep 2017;7:1–6. 10.1038/s41598-017-08951-6
    1. Garenne M. Sex differences in health indicators among children in African DHS surveys. J Biosoc Sci 2003;35:601–14. 10.1017/S0021932003006047
    1. Titaley CR, Dibley MJ, Agho K, et al. . Determinants of neonatal mortality in Indonesia. BMC Public Health 2008;8:232. 10.1186/1471-2458-8-232
    1. Jehan I, Harris H, Salat S, et al. . Neonatal mortality, risk factors and causes: a prospective population-based cohort study in urban Pakistan. Bull World Health Organ 2009;87:130–8. 10.2471/BLT.08.050963
    1. Katz J, West KP, Khatry SK, et al. . Risk factors for early infant mortality in Sarlahi district, Nepal. Bull World Health Organ 2003;81:717–25.
    1. Nielsen BB, Liljestrand J, Hedegaard M, et al. . Reproductive pattern, perinatal mortality, and sex preference in rural Tamil Nadu, South India: community based, cross sectional study. BMJ 1997;314:1521. 10.1136/bmj.314.7093.1521
    1. Willis JR. Perceived neonatal morbidities and healthcare utilization for neonatal health in rural Uttar Pradesh, India: effects of a behavior-change communication intervention. ProQuest, 2007.
    1. Pandey A, Sengupta PG, Mondal SK, et al. . Gender differences in healthcare-seeking during common illnesses in a rural community of West Bengal, India. J Health Popul Nutr 2002;20:306–11. 10.3329/jhpn.v20i4.168
    1. Howlader AA, Bhuiyan MU. Mothers' health-seeking behaviour and infant and child mortality in Bangladesh. Asia Pac Popul J 1999;14:1–11. 10.18356/43e95f41-en
    1. Christian P, West KP, Khatry SK, et al. . Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. Am J Clin Nutr 2003;78:1194–202. 10.1093/ajcn/78.6.1194
    1. Tielsch JM, Darmstadt GL, Mullany LC, et al. . Impact of newborn skin-cleansing with chlorhexidine on neonatal mortality in southern Nepal: a community-based, cluster-randomized trial. Pediatrics 2007;119:e330–40. 10.1542/peds.2006-1192
    1. Rosenstock S, Katz J, Mullany LC, et al. . Sex differences in morbidity and care-seeking during the neonatal period in rural southern Nepal. J Health Popul Nutr 2015;33:1–10. 10.1186/s41043-015-0014-0
    1. Cleland J, Verall J, Vasessen M. Sex of children and their influence on reproductive behavior. world fertility survey comparative studies; 1983.
    1. Ministry of Health - MOH/Nepal, New ERA/Nepal, ICF . Nepal Demographic and Health Survey 2016; 2017.
    1. Budlender D, Moussié R. Making Care Visible Women’s Unpaid Care Work in Nepal, Nigeria, Uganda and Kenya, 2013.
    1. Nanda P, Gautam A, Verma R, International Center for Research on Women (ICRW) New Dehli . Study on gender masculinity and son preference in Nepal and Vietnam; 2012.
    1. Ismail SA, McCullough A, Guo S, et al. . Gender-Related differences in care-seeking behaviour for newborns: a systematic review of the evidence in South Asia. BMJ Glob Health 2019;4:e001309. 10.1136/bmjgh-2018-001309
    1. UNICEF . Boys and girls in the life cycle; 2011.
    1. Family Health Division of the Department of Health Services of the Ministry of Health/Nepal, New ERA/Nepal, Macro O . Nepal demographic and health survey 2001; 2002.
    1. Paudel D, Thapa A, Shedain PR, Paudel B. Trends and determinants of neonatal mortality in Nepal: further analysis of the Nepal demographic and health surveys, 2001-2011; 2013. and.
    1. National Planning Commission . Sustainable development goals 2016–2030: national (preliminary) report. Kathmandu: National Planning Commission, 2015.
    1. Brinda EM, Rajkumar AP, Enemark U. Association between gender inequality index and child mortality rates: a cross-national study of 138 countries. BMC Public Health 2015;15:97–3. 10.1186/s12889-015-1449-3
    1. Dandona R, Kumar GA, Bhattacharya D, et al. . Distinct mortality patterns at 0–2 days versus the remaining neonatal period: results from population-based assessment in the Indian state of Bihar. BMC Med 2019;17:1–19. 10.1186/s12916-019-1372-z
    1. Sankar MJ, Natarajan CK, Das RR, et al. . When do newborns die? A systematic review of timing of overall and cause-specific neonatal deaths in developing countries. J Perinatol 2016;36 Suppl 1:S1–11. 10.1038/jp.2016.27
    1. Peelen MJCS, Kazemier BM, Ravelli ACJ, et al. . Impact of fetal gender on the risk of preterm birth, a national cohort study. Acta Obstet Gynecol Scand 2016;95:1034–41. 10.1111/aogs.12929
    1. Zeitlin J, Ancel P-Y, Larroque B, et al. . Fetal sex and indicated very preterm birth: results of the EPIPAGE study. Am J Obstet Gynecol 2004;190:1322–5. 10.1016/j.ajog.2003.10.703
    1. Lao TT, Sahota DS, Suen SSH, et al. . The impact of fetal gender on preterm birth in a southern Chinese population. J Matern Fetal Neonatal Med 2011;24:1440–3. 10.3109/14767058.2011.589872

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