Effects of size at birth on health, growth and developmental outcomes in children up to age 18: an umbrella review

Abstract

Background: Size at birth, an indicator of intrauterine growth, has been studied extensively in relation to subsequent health, growth and developmental outcomes. Our umbrella review synthesises evidence from systematic reviews and meta-analyses on the effects of size at birth on subsequent health, growth and development in children and adolescents up to age 18, and identifies gaps.

Methods: We searched five databases from inception to mid-July 2021 to identify eligible systematic reviews and meta-analyses. For each meta-analysis, we extracted data on the exposures and outcomes measured and the strength of the association.

Findings: We screened 16 641 articles and identified 302 systematic reviews. The literature operationalised size at birth (birth weight and/or gestation) in 12 ways. There were 1041 meta-analyses of associations between size at birth and 67 outcomes. Thirteen outcomes had no meta-analysis.Small size at birth was examined for 50 outcomes and was associated with over half of these (32 of 50); continuous/post-term/large size at birth was examined for 35 outcomes and was consistently associated with 11 of the 35 outcomes. Seventy-three meta-analyses (in 11 reviews) compared risks by size for gestational age (GA), stratified by preterm and term. Prematurity mechanisms were the key aetiologies linked to mortality and cognitive development, while intrauterine growth restriction (IUGR), manifesting as small for GA, was primarily linked to underweight and stunting.

Interpretation: Future reviews should use methodologically sound comparators to further understand aetiological mechanisms linking IUGR and prematurity to subsequent outcomes. Future research should focus on understudied exposures (large size at birth and size at birth stratified by gestation), gaps in outcomes (specifically those without reviews or meta-analysis and stratified by age group of children) and neglected populations.

Prospero registration number: CRD42021268843.

Keywords: Child Development; Child Health; Growth; Mental health; Mortality.

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart for study selection.

Figure 2. Themes and subthemes identified in 302 reviews.

Figure 3. Summary of the associations presented in online supplemental table 1a–g. BW, birth weight; ELBW, extremely low birth weight; EPT, extremely preterm; GA, gestational age; HBW, high birth weight; LBW, low birth weight; LGA, large for gestational age; PT, preterm; SGA, small for gestational age; VLBW, very low birth weight; VPT, very preterm.