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Meta-Analysis
. 2021 Aug 1;175(8):e211058.
doi: 10.1001/jamapediatrics.2021.1058. Epub 2021 Aug 2.

Association of Very Preterm Birth or Very Low Birth Weight With Intelligence in Adulthood: An Individual Participant Data Meta-analysis

Robert Eves  1 , Marina Mendonça  1 , Nicole Baumann  1 , Yanyan Ni  1 , Brian A Darlow  2 , John Horwood  3 , Lianne J Woodward  4 , Lex W Doyle  5   6   7 , Jeanie Cheong  5   6   7 , Peter J Anderson  7   8 , Peter Bartmann  9 , Neil Marlow  10 , Samantha Johnson  11 , Eero Kajantie  12   13   14   15 , Petteri Hovi  12   15 , Chiara Nosarti  16   17 , Marit S Indredavik  14 , Kari-Anne I Evensen  14   18   19 , Katri Räikkönen  20 , Kati Heinonen  20   21 , Jennifer Zeitlin  22 , Dieter Wolke  1   23
Affiliations
Meta-Analysis

Association of Very Preterm Birth or Very Low Birth Weight With Intelligence in Adulthood: An Individual Participant Data Meta-analysis

Robert Eves et al. JAMA Pediatr. .

Abstract

Importance: Birth before 32 weeks' gestation (very preterm [VPT]) and birth weight below 1500 g (very low birth weight [VLBW]) have been associated with lower cognitive performance in childhood. However, there are few investigations of the association of neonatal morbidities and maternal educational levels with the adult cognitive performance of individuals born VPT or VLBW (VPT/VLBW).

Objective: To assess differences in adult IQ between VPT/VLBW and term-born individuals and to examine the association of adult IQ with cohort factors, neonatal morbidities, and maternal educational level among VPT/VLBW participants.

Data sources: Systematic review of published data from PubMed and meta-analysis of individual participant data (IPD) of cohorts from 2 consortia (Research on European Children and Adults Born Preterm [RECAP] and Adults Born Preterm International Collaboration [APIC]).

Study selection: The meta-analysis included prospective longitudinal cohort studies that assessed the full-scale IQ of adults born VPT or VLBW and respective control groups comprising term-born adults.

Data extraction and synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for analyses of individual participant data and identified 8 studies that provided data from 2135 adults (1068 VPT/VLBW and 1067 term-born participants) born between 1978 and 1995. Meta-analyses of IPD were performed using a 1-stage approach, treating VPT birth or VLBW and cohort as random effects.

Main outcomes and measures: Full-scale IQ scores were converted to z scores within each cohort using the combined SD of VPT/VLBW participants and a control group of term-born participants, with scores centered on the mean of the control group.

Results: A total of 426 records were identified and screened. After exclusions, 13 studies were included in the aggregate meta-analysis. The IPD meta-analysis included 8 of the 9 RECAP and APIC cohorts with adult IQ data. The mean (SD) age among the 8 IPD cohorts was 24.6 (4.3) years, and 1163 participants (54.5%) were women. In unadjusted analyses, VPT/VLBW participants had mean adult IQ scores that were 0.78 SD (95% CI, -0.90 to -0.66 SD) lower than term-born participants, equivalent to a difference of 12 IQ points. Among VPT/VLBW participants, lower gestational age (score difference per week of gestation, 0.11; 95% CI, 0.07-0.14), lower birth weight z scores (score difference per 1.0 SD, 0.21; 95% CI, 0.14-0.28), the presence of neonatal bronchopulmonary dysplasia (score difference, -0.16; 95% CI, -0.30 to -0.02) or any grade of intraventricular hemorrhage (score difference, -0.19; 95% CI, -0.33 to -0.05), and lower maternal educational level (score difference, 0.26; 95% CI, 0.17-0.35) were all significantly associated with lower IQ scores in adulthood.

Conclusions and relevance: In this IPD meta-analysis, lower gestational age, lower weight for gestational age, neonatal morbidities, and lower maternal educational levels were all important risk factors associated with lower IQ among young adults born VPT or VLBW.

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Conflict of interest statement

Conflict of Interest Disclosures: Mr Horwood reported receiving grants from the Health Research Council of New Zealand and the National Institutes of Health during the conduct of the study and grants from Cure Kids (New Zealand) and the National Health and Medical Research Council (Australia) as well as personal fees from the University of Otago at Christchurch outside the submitted work. Dr Doyle reported receiving grants from the Centres of Research Excellence, National Health and Medical Research Council (Australia), during the conduct of the study. Dr Anderson reported receiving grants from the National Health and Medical Research Council (Australia) during the conduct of the study. Dr Marlow reported receiving consulting fees from Novartis, RSM Consulting, and Takeda Pharmaceutical outside the submitted work. Dr Kajantie reported receiving grants from the Academy of Finland, the Finnish Foundation for Pediatric Research, the Signe and Ane Gyllenberg Foundation, and the Sigrid Juselius Foundation during the conduct of the study and grants from the Finnish Diabetes Research Foundation, the Finnish Foundation for Cardiovascular Research, the Juho Vainio Foundation, and the Novo Nordisk Foundation outside the submitted work. Dr Wolke reported receiving funding from the New Opportunities for Research Funding Agency Co-operation in Europe, Dynamics of Inequality Across the Life-course Program outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Studies Included in the Independent Participant Data (IPD) and Aggregate Meta-analyses
APIC indicates Adults Born Preterm International Collaboration; RECAP, Research on European Children and Adults Born Preterm; and VPT/VLBW, very preterm or very low birth weight.
Figure 2.
Figure 2.. Aggregate Meta-analysis Comparing IQ Performance in Independent Participant Data (IPD) vs Non-IPD Cohorts of Adults Who Were Born Very Preterm or With Very Low Birth Weight
Diamonds represent pooled estimates from either the IPD or non-IPD subgroup analysis or from all cohorts; diamond size indicates the 95% CI for the pooled estimate. The arrow indicates that the lower 95% CI (1.54) for the Linsell et al EPICure study is further than the axis limit of 1.5. Horizontal lines represent the 95% CIs of the estimates for each cohort. Box size represents the weighting given to the study. SMD indicates standardized mean difference.
See this image and copyright information in PMC

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