Long-Term Endocrine and Metabolic Outcomes in Early Term Born Offspring: A Systematic Review and Meta-Analysis

Abstract

Childhood endocrine and metabolic morbidity is a major global public health concern, with rising prevalence. Prematurity clearly impacts the long-term risk for such morbidity. We sought to systematically review the literature and evaluate whether early-term deliveries (370/7-386/7 weeks of gestation) impact the long-term endocrine and metabolic health of offspring up to the age of 18 years, as compared to offspring born at full term or later. This systematic review and meta-analysis was conducted according to the PRISMA guidelines and was registered in PROSPERO. We searched Medline, Embase, and relevant reference lists up to November 8th, 2020, including observational studies addressing the association. Two independent reviewers extracted data and assessed risk of bias. Pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) and heterogeneity were determined. Publication bias was assessed by Funnel plots with Eggers regression line and contours, and sensitivity analyses were performed using Baujat plots. Seven studies were included following a screen of over 5000 abstracts. Five studies were scored high quality according to the Newcastle-Ottawa Quality Assessment Scale. Early term delivery significantly increased the risk of total endocrine and metabolic morbidity in the offspring (OR=1.12, 95%CI=1.08, 1.17) as compared to full term delivery (Figure 1). The increased endocrine morbidity was mainly attributed to childhood diabetes (OR=1.14, 95%CI=1.09, 1.19) (Figure 2). Compared with full term born offspring, early term delivery poses a significant risk for long-term pediatric endocrine and metabolic morbidity. This association may be due to lack of full maturity of the hormonal axis in early term born children.