Neonatal and infant mortality associated with spina bifida: A systematic review and meta-analysis

PLoS One. 2021 May 12;16(5):e0250098. doi: 10.1371/journal.pone.0250098. eCollection 2021.


Objectives: A systematic review was conducted in high-income country settings to analyse: (i) spina bifida neonatal and IMRs over time, and (ii) clinical and socio-demographic factors associated with mortality in the first year after birth in infants affected by spina bifida.

Data sources: PubMed, Embase, Ovid, Web of Science, CINAHL, Scopus and the Cochrane Library were searched from 1st January, 1990 to 31st August, 2020 to review evidence.

Study selection: Population-based studies that provided data for spina bifida infant mortality and case fatality according to clinical and socio-demographical characteristics were included. Studies were excluded if they were conducted solely in tertiary centres. Spina bifida occulta or syndromal spina bifida were excluded where possible.

Data extraction and synthesis: Independent reviewers extracted data and assessed their quality using MOOSE guideline. Pooled mortality estimates were calculated using random-effects (+/- fixed effects) models meta-analyses. Heterogeneity between studies was assessed using the Cochrane Q test and I2 statistics. Meta-regression was performed to examine the impact of year of birth cohort on spina bifida infant mortality.

Results: Twenty studies met the full inclusion criteria with a total study population of over 30 million liveborn infants and approximately 12,000 spina bifida-affected infants. Significant declines in spina bifida associated infant and neonatal mortality rates (e.g. 4.76% decrease in IMR per 100, 000 live births per year) and case fatality (e.g. 2.70% decrease in infant case fatality per year) were consistently observed over time. Preterm birth (RR 4.45; 2.30-8.60) and low birthweight (RR 4.77; 2.67-8.55) are the strongest risk factors associated with increased spina bifida infant case fatality.

Significance: Significant declines in spina bifida associated infant/neonatal mortality and case fatality were consistently observed, advances in treatment and mandatory folic acid food fortification both likely play an important role. Particular attention is warranted from clinicians caring for preterm and low birthweight babies affected by spina bifida.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Female
  • Humans
  • Infant
  • Infant Mortality
  • Infant, Newborn
  • Pregnancy
  • Premature Birth
  • Spinal Dysraphism / mortality*