Small for date preterm infants and risk of higher blood pressure in later life: A systematic review and meta-analysis

Abstract

Background: Historical reports suggest that infants born small for gestational age (SGA) are at increased risk for high blood pressure (BP) at older ages after adjustment for later age body size. Such adjustment may be inappropriate since adiposity is a known cause of cardiovascular and metabolic disease.

Objectives: To assess the association between SGA births and later BP among preterm births, considering potential background confounders and over-adjustment for later body size.

Methods: A database search of studies up to October 2022 included MEDLINE, EMBASE and CINAHL. Studies were included if they reported BP (systolic [SBP] or diastolic [DBP]) (outcomes) for participants born preterm with SGA (exposure) or non-SGA births. All screening, extraction steps, and risk of bias (using the Risk of Bias In Non-randomised Studies of Interventions [ROBINS-I] tool) were conducted in duplicate by two reviewers. Data were pooled in meta-analysis using random-effects models. We explored potential sources of heterogeneity.

Results: We found no meaningful difference in later BP between preterm infants with and without SGA status at birth. Meta-analysis of 25 studies showed that preterm SGA, compared to preterm non-SGA, was not associated with higher BP at age 2 and older with mean differences for SBP 0.01 mmHg (95% CI -0.10, 0.12, I² = 59.8%, n = 20,462) and DBP 0.01 mm Hg (95% CI -0.10, 0.12), 22 studies, (I² = 53.0%, n = 20,182). Adjustment for current weight did not alter the results, which could be due to the lack of differences in later weight status in most of the included studies. The included studies were rated to be at risk of bias due to potential residual confounding, with a low risk of bias in other domains.

Conclusions: Evidence indicates that preterm infants born SGA are not at increased risk of developing higher BP as children or as adults as compared to non-SGA preterm infants.

Keywords: birth; birthweight, blood pressure; growth; infant; preterm infant; risk adjustment; small for gestational age; weight.