Am J Perinatol 2018; 35(08): 707-715
DOI: 10.1055/s-0037-1608876
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Sex Difference in Mortality for Premature and Low Birth Weight Neonates: A Systematic Review

Huy Duc Vu
1   College of Medicine and Dentistry, James Cook University, Queensland, Australia
2   Neonatal Unit, The Townsville Hospital, Queensland, Australia
,
Corrine Dickinson
1   College of Medicine and Dentistry, James Cook University, Queensland, Australia
2   Neonatal Unit, The Townsville Hospital, Queensland, Australia
,
Yogavijayan Kandasamy
1   College of Medicine and Dentistry, James Cook University, Queensland, Australia
2   Neonatal Unit, The Townsville Hospital, Queensland, Australia
› Author Affiliations
Further Information

Publication History

15 March 2017

19 October 2017

Publication Date:
14 December 2017 (online)

Abstract

Objective Advances in neonatology have made possible the survival of neonates with lower gestational ages and birth weights. Nevertheless, findings remain of a sex difference in mortality for premature and low birth weight (LBW) neonates with male sex often associated with poorer outcome (the “male disadvantage”). Through literature review, this article will seek clarification of the existing evidence regarding the association between sex and mortality at discharge from neonatal intensive care units (NICUs) for premature and LBW neonates.

Methods A systematic review was conducted in Medline and Google Scholar with subsequent search of study reference lists.

Results The database search yielded 349 articles and an additional 11 were identified from study reference lists. A final 32 studies were reviewed. Of these, 26 studies demonstrated worse male mortality outcome and 6 studies reported no sex difference in mortality.

Conclusion The majority of reviewed studies found poorer male mortality outcome. A small number of studies maintained a null association between sex and mortality. This indicates male premature and LBW neonates experience higher risk of mortality by discharge compared with females, an observation which may inform clinical decision making in the NICU.

 
  • References

  • 1 Fanaroff AA, Hack M, Walsh MC. The NICHD neonatal research network: changes in practice and outcomes during the first 15 years. Semin Perinatol 2003; 27 (04) 281-287
  • 2 Rüegger C, Hegglin M, Adams M, Bucher HU. ; Swiss Neonatal Network. Population based trends in mortality, morbidity and treatment for very preterm- and very low birth weight infants over 12 years. BMC Pediatr 2012; 12: 17
  • 3 Stoll BJ, Hansen NI, Bell EF. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA 2015; 314 (10) 1039-1051
  • 4 Berger TM, Steurer MA, Woerner A, Meyer-Schiffer P, Adams M. ; Swiss Neonatal Network. Trends and centre-to-centre variability in survival rates of very preterm infants (<32 weeks) over a 10-year-period in Switzerland. Arch Dis Child Fetal Neonatal Ed 2012; 97 (05) F323-F328
  • 5 Bolisetty S, Legge N, Bajuk B, Lui K. ; New South Wales and the Australian Capital Territory Neonatal Intensive Care Units' Data Collection. Preterm infant outcomes in New South Wales and the Australian Capital Territory. J Paediatr Child Health 2015; 51 (07) 713-721
  • 6 Grisaru-Granovsky S, Reichman B, Lerner-Geva L. , et al; Israel Neonatal Network. Population-based trends in mortality and neonatal morbidities among singleton, very preterm, very low birth weight infants over 16 years. Early Hum Dev 2014; 90 (12) 821-827
  • 7 Shah PS, Sankaran K, Aziz K. , et al; Canadian Neonatal Network. Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern?. J Perinatol 2012; 32 (02) 132-138
  • 8 Ingemarsson I. Gender aspects of preterm birth. BJOG 2003; 110 (Suppl 20): 34-38
  • 9 Naeye RL, Burt LS, Wright DL, Blanc WA, Tatter D. Neonatal mortality, the male disadvantage. Pediatrics 1971; 48 (06) 902-906
  • 10 Hoffman EL, Bennett FC. Birth weight less than 800 grams: changing outcomes and influences of gender and gestation number. Pediatrics 1990; 86 (01) 27-34
  • 11 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
  • 12 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
  • 13 Ray B, Platt MP. Mortality of twin and singleton livebirths under 30 weeks' gestation: a population-based study. Arch Dis Child Fetal Neonatal Ed 2009; 94 (02) F140-F143
  • 14 Jennische M, Sedin G. Gender differences in outcome after neonatal intensive care: speech and language skills are less influenced in boys than in girls at 6.5 years. Acta Paediatr 2003; 92 (03) 364-378
  • 15 Spinillo A, Capuzzo E, Nicola S, Colonna L, Iasci A, Zara C. Interaction between fetal gender and risk factors for fetal growth retardation. Am J Obstet Gynecol 1994; 171 (05) 1273-1277
  • 16 Moher D, Liberati A, Tetzlaff J, Altman DG. ; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535
  • 17 Oxford Centre for Evidence-Based Medicine. Levels of Evidence. March, 2009 http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ . Accessed March 2, 2017
  • 18 Bacak SJ, Baptiste-Roberts K, Amon E, Ireland B, Leet T. Risk factors for neonatal mortality among extremely-low-birth-weight infants. Am J Obstet Gynecol 2005; 192 (03) 862-867
  • 19 Bansal S, Arora A, Bansal S, Gupta M, Singh P. Pattern of morbidity and mortality in preterm newborns in a tertiary care teaching hospital. JEMDS 2015; 4 (69) 11976-11981
  • 20 Battin M, Ling EW, Whitfield MF, Mackinnon M, Effer SB. Has the outcome for extremely low gestational age (ELGA) infants improved following recent advances in neonatal intensive care?. Am J Perinatol 1998; 15 (08) 469-477
  • 21 Deulofeut R, Dudell G, Sola A. Treatment-by-gender effect when aiming to avoid hyperoxia in preterm infants in the NICU. Acta Paediatr 2007; 96 (07) 990-994
  • 22 El-Metwally D, Vohr B, Tucker R. Survival and neonatal morbidity at the limits of viability in the mid 1990s: 22 to 25 weeks. J Pediatr 2000; 137 (05) 616-622
  • 23 Hoekstra RE, Ferrara TB, Couser RJ, Payne NR, Connett JE. Survival and long-term neurodevelopmental outcome of extremely premature infants born at 23-26 weeks' gestational age at a tertiary center. Pediatrics 2004; 113 (1 Pt 1): e1-e6
  • 24 Holtrop PC, Ertzbischoff LM, Roberts CL, Batton DG, Lorenz RP. Survival and short-term outcome in newborns of 23 to 25 weeks' gestation. Am J Obstet Gynecol 1994; 170 (5 Pt 1): 1266-1270
  • 25 Itabashi K, Horiuchi T, Kusuda S. , et al. Mortality rates for extremely low birth weight infants born in Japan in 2005. Pediatrics 2009; 123 (02) 445-450
  • 26 Jones HP, Karuri S, Cronin CMG. , et al; Canadian Neonatal Network. Actuarial survival of a large Canadian cohort of preterm infants. BMC Pediatr 2005; 5: 40
  • 27 Kugelman A, Bader D, Lerner-Geva L. , et al. Poor outcomes at discharge among extremely premature infants: a national population-based study. Arch Pediatr Adolesc Med 2012; 166 (06) 543-550
  • 28 La Pine TR, Jackson JC, Bennett FC. Outcome of infants weighing less than 800 grams at birth: 15 years' experience. Pediatrics 1995; 96 (3 Pt 1): 479-483
  • 29 Lee HC, Green C, Hintz SR. , et al. Prediction of death for extremely premature infants in a population-based cohort. Pediatrics 2010; 126 (03) e644-e650
  • 30 Lucey JF, Rowan CA, Shiono P. , et al. Fetal infants: the fate of 4172 infants with birth weights of 401 to 500 grams--the Vermont Oxford Network experience (1996-2000). Pediatrics 2004; 113 (06) 1559-1566
  • 31 Olugbuyi O, Samms-Vaughan M, Trotman H. Mortality of very-low-birth-weight infants in Jamaica. Trop Doct 2006; 36 (03) 169-171
  • 32 Serenius F, Ewald U, Farooqi A, Holmgren PÅ, Håkansson S, Sedin G. Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish tertiary care centres. Part 2: infant survival. Acta Paediatr 2004; 93 (08) 1081-1089
  • 33 Shankaran S, Fanaroff AA, Wright LL. , et al. Risk factors for early death among extremely low-birth-weight infants. Am J Obstet Gynecol 2002; 186 (04) 796-802
  • 34 Shinwell ES, Reichman B, Lerner-Geva L, Boyko V, Blickstein I. ; Israel Neonatal Network. “Masculinizing” effect on respiratory morbidity in girls from unlike-sex preterm twins: a possible transchorionic paracrine effect. Pediatrics 2007; 120 (03) e447-e453
  • 35 Stevenson DK, Verter J, Fanaroff AA. , et al. Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage. Arch Dis Child Fetal Neonatal Ed 2000; 83 (03) F182-F185
  • 36 Stevenson DK, Wright LL, Lemons JA. , et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1993 through December 1994. Am J Obstet Gynecol 1998; 179 (6 Pt 1): 1632-1639
  • 37 Synnes AR, Ling EW, Whitfield MF. , et al. Perinatal outcomes of a large cohort of extremely low gestational age infants (twenty-three to twenty-eight completed weeks of gestation). J Pediatr 1994; 125 (6 Pt 1): 952-960
  • 38 Tioseco JA, Aly H, Essers J, Patel K, El-Mohandes AA. Male sex and intraventricular hemorrhage. Pediatr Crit Care Med 2006; 7 (01) 40-44
  • 39 Tyson JE, Younes N, Verter J, Wright LL. ; National Institute of Child Health and Human Development Neonatal Research Network. Viability, morbidity, and resource use among newborns of 501- to 800-g birth weight. JAMA 1996; 276 (20) 1645-1651
  • 40 Upadhyay K, Pourcyrous M, Dhanireddy R, Talati AJ. Outcomes of neonates with birth weight. ⩽500 g: a 20-year experience. J Perinatol 2015; 35 (09) 768-772
  • 41 Vanhaesebrouck P, Allegaert K, Bottu J. , et al; Extremely Preterm Infants in Belgium Study Group. The EPIBEL study: outcomes to discharge from hospital for extremely preterm infants in Belgium. Pediatrics 2004; 114 (03) 663-675
  • 42 Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics 2000; 106 (04) 659-671
  • 43 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
  • 44 Chye JK, Lim CT. Very low birth weight infants--mortality and predictive risk factors. Singapore Med J 1999; 40 (09) 565-570
  • 45 Neubauer V, Griesmaier E, Ralser E, Kiechl-Kohlendorfer U. The effect of sex on outcome of preterm infants - a population-based survey. Acta Paediatr 2012; 101 (09) 906-911
  • 46 WHO. UNICEF. Low birthweight: country, regional and global estimates. Switzerland: UNICEF; 2004
  • 47 Bennett FC, Robinson NM, Sells CJ. Growth and development of infants weighing less than 800 grams at birth. Pediatrics 1983; 71 (03) 319-323
  • 48 Stark MJ, Clifton VL, Wright IM. Sex-specific differences in peripheral microvascular blood flow in preterm infants. Pediatr Res 2008; 63 (04) 415-419
  • 49 Adamson IY, Bakowska J, McMillan E, King GM. Accelerated fetal lung maturation by estrogen is associated with an epithelial-fibroblast interaction. In Vitro Cell Dev Biol 1990; 26 (08) 784-790
  • 50 Baenziger O, Jaggi JL, Mueller AC. , et al. Cerebral blood flow in preterm infants affected by sex, mechanical ventilation, and intrauterine growth. Pediatr Neurol 1994; 11 (04) 319-324
  • 51 Catlin EA, Powell SM, Manganaro TF. , et al. Sex-specific fetal lung development and müllerian inhibiting substance. Am Rev Respir Dis 1990; 141 (02) 466-470
  • 52 Davis M, Emory E. Sex differences in neonatal stress reactivity. Child Dev 1995; 66 (01) 14-27
  • 53 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 (04) 529-533
  • 54 Greenough A, Lagercrantz H, Pool J, Dahlin I. Plasma catecholamine levels in preterm infants. Effect of birth asphyxia and Apgar score. Acta Paediatr Scand 1987; 76 (01) 54-59
  • 55 Hanley K, Rassner U, Jiang Y. , et al. Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat. Acceleration by estrogen and delay by testosterone. J Clin Invest 1996; 97 (11) 2576-2584
  • 56 Henderson-Smart DJ, Hutchinson JL, Donoghue DA, Evans NJ, Simpson JM, Wright I. ; Australian and New Zealand Neonatal Network. Prenatal predictors of chronic lung disease in very preterm infants. Arch Dis Child Fetal Neonatal Ed 2006; 91 (01) F40-F45
  • 57 Khoury MJ, Marks JS, McCarthy BJ, Zaro SM. Factors affecting the sex differential in neonatal mortality: the role of respiratory distress syndrome. Am J Obstet Gynecol 1985; 151 (06) 777-782
  • 58 Allen MC, Donohue PK, Dusman AE. The limit of viability--neonatal outcome of infants born at 22 to 25 weeks' gestation. N Engl J Med 1993; 329 (22) 1597-1601
  • 59 Parikh NA, Arnold C, Langer J, Tyson JE. Evidence-based treatment decisions for extremely preterm newborns. Pediatrics 2010; 125 (04) 813-816
  • 60 Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR. Neurologic and developmental disability after extremely preterm birth. EPICure Study Group. N Engl J Med 2000; 343 (06) 378-384
  • 61 Tudehope D, Papadimos E, Gibbons K. Twelve-year review of neonatal deaths in the delivery room in a perinatal tertiary centre. J Paediatr Child Health 2013; 49 (01) E40-E45
  • 62 Doron MW, Veness-Meehan KA, Margolis LH, Holoman EM, Stiles AD. Delivery room resuscitation decisions for extremely premature infants. Pediatrics 1998; 102 (3 Pt 1): 574-582
  • 63 Singh J, Fanaroff J, Andrews B. , et al. Resuscitation in the “gray zone” of viability: determining physician preferences and predicting infant outcomes. Pediatrics 2007; 120 (03) 519-526
  • 64 Eriksson L, Haglund B, Ewald U, Odlind V, Kieler H. Short and long-term effects of antenatal corticosteroids assessed in a cohort of 7,827 children born preterm. Acta Obstet Gynecol Scand 2009; 88 (08) 933-938
  • 65 Gargus RA, Vohr BR, Tyson JE. , et al. Unimpaired outcomes for extremely low birth weight infants at 18 to 22 months. Pediatrics 2009; 124 (01) 112-121