The challenges of heterogeneity in gestational age and birthweight inclusion criteria for research synthesis on very preterm birth and childhood cognition: An umbrella review and meta-regression analysis

Background: Meta-analyses of studies on very preterm (VPT) birth and childhood cognition select primary studies using gestational age inclusion criteria only, while others also include birthweight criteria. The consequences of this choice are unknown.

Objective: The objective of this study was to describe the gestational age (GA) and birthweight (BW) criteria used in studies of VPT birth and cognition and to investigate whether meta-analysis results differ based on these criteria.

Data sources: Five systematic reviews on VPT birth and childhood IQ.

Study selection and data extraction: Country, birth years, GA-BW selection criteria and participant IQ were extracted from 156 studies representing 103 birth cohorts.

Synthesis: Pooled standardised mean differences (SMD) in IQ between children born VPT and term-born controls were estimated by sub-group based on GA-BW criteria (GA, BW and GA-BW combined) and degree of preterm birth-low birthweight combinations: extremely preterm (EPT, <28 weeks) and extremely low BW (ELBW, <1000 g); VPT (<32 weeks) and very low BW (VLBW, <1500 g); and moderately MPT (<34 weeks) and moderately low BW (MLBW, <1800 g).

Results: Cohorts used 27 distinct GA-BW inclusion criteria. Most common criteria were BW <1500 g (24 cohorts), BW <1000 g (12), GA <32 weeks (12) and GA <33 weeks (12); 23 studies used GA-BW combinations. BW-only criteria were more frequent in North America than Europe (63% versus 24%) and for cohorts before than after 1990 (67% vs 26%). Pooled SMD in IQ varied: SMD_EPT/ELBW -0.94, 95% confidence interval [CI] -1.07, -0.82; SMD_VPT/VLBW -0.78, 95% CI -0.85, -0.71; SMD_MPT/MLBW -0.68, 95% CI -0.79, -0.57; however, there was no difference in SMD across cohorts using BW compared to GA criteria after adjustment on risk group.

Conclusions: These findings support the inclusion of studies using GA and/or BW criteria in meta-analyses on VPT birth and cognition to increase the geographical and temporal generalisability of the results and to allow investigation of the impact of the heterogeneous inclusion criteria in this literature on outcomes.