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Original Investigation
May 26, 2020

Association of Intrauterine Growth Restriction and Small for Gestational Age Status With Childhood Cognitive Outcomes: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Developmental Psychology and Socialization, University of Padova, Padova, Italy
  • 2Centre for the Developing Brain, King's College London School of Bioengineering & Imaging Sciences, London, United Kingdom
  • 3Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
  • 4Department of Women’s and Children’s Health, University of Padova, Padova, Italy
JAMA Pediatr. 2020;174(8):772-781. doi:10.1001/jamapediatrics.2020.1097
Key Points

Question  Do preterm and term-born neonates with intrauterine growth restriction and small for gestational age have worse childhood cognitive outcomes than those born appropriate for gestational age?

Findings  In this systematic review and meta-analysis of 89 samples from 60 studies including 52 822 children (aged 1-12 years), compared with children born appropriate for gestational age, children who had intrauterine growth restriction and who were small for gestational age had significantly lower cognitive scores.

Meaning  The findings suggest that preventive strategies should be directed to pregnancies and deliveries of fetuses and neonates with intrauterine growth restriction and that pediatric follow-up care should be tailored to address the potential cognitive problems in children who were born with intrauterine growth restriction and were small for gestational age.


Importance  The magnitude of the association of intrauterine growth restriction (IUGR) and small for gestational age (SGA) status with cognitive outcomes in preterm and term-born children has not been established.

Objective  To examine cognitive outcomes of preterm and term-born children who had IUGR and were SGA compared with children who were appropriate for gestational age (AGA) during the first 12 years of life.

Data Sources  For this systematic review and meta-analysis, the Scopus, PubMed, Web of Science, Science Direct, PsycInfo, and ERIC databases were searched for English-language, peer-reviewed literature published between January 1, 2000, and February 20, 2020. The following Medical Subject Heading terms for IUGR and SGA and cognitive outcomes were used: intrauterine growth restriction, intrauterine growth retardation, small for gestational age AND neurodevelopment, neurodevelopmental outcome, developmental outcomes, and cognitive development.

Study Selection  Inclusion criteria were assessment of cognitive outcomes (full-scale IQ or a cognitive subscale), inclusion of an AGA group as comparison group, and inclusion of gestational age at birth and completion of cognitive assessment up to 12 years of age.

Data Extraction and Synthesis  The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed. Data were double screened for full-text articles, and a subset were independently coded by 2 authors. Standardized mean differences (SMDs) and odd ratios from individual studies were pooled by applying random-effects models.

Main Outcomes and Measures  Cognitive outcomes, defined as mental, cognitive, or IQ scores, estimated with standardized practitioner-based cognitive tests or as borderline intellectual impairment (BII), defined as mental, cognitive, or IQ scores at least 1 SD below the mean cognitive score.

Results  In this study of 89 samples from 60 studies including 52 822 children, children who had IUGR and were SGA had significantly poorer cognitive outcomes (eg, cognitive scores and BII) than children with AGA in childhood. For cognitive scores, associations are consistent for preterm (SMD, −0.27; 95% CI, −0.38 to −0.17) and term-born children (SMD, −0.39; 95% CI, −0.50 to −0.28), with higher effect sizes reported for term-born IUGR and AGA group comparisons (SMD, –0.58; 95% CI, –0.82 to –0.35). Analyses on BII revealed a significantly increased risk in the preterm children who had IUGR and were SGA (odds ratio, 1.57; 95% CI, 1.40-1.77) compared with the children with AGA.

Conclusions and Relevance  Growth vulnerabilities assessed antenatally (IUGR) and at the time of birth (SGA) are significantly associated with lower childhood cognitive outcomes in preterm and term-born children compared with children with AGA. These findings highlight the need to develop interventions that boost cognitive functions in these high-risk groups.

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