Late Preterm Birth and the Risk of Cardiometabolic Disease

Cardiovascular disease rates have substantially increased worldwide, with a near doubling of prevalence, from 271 million to 523 million people, reported between 1990 and 2019. Cardiovascular disease remains the leading cause of adult death around the world and, in some areas, an increase has occurred among younger age groups, suggesting that the aging population is not the only factor in the increasing prevalence.¹ Identifying those at high risk of cardiometabolic disease and developing interventions to prevent or delay disease onset will reduce the high burden of disease on health care systems. Meta-analyses^2,3 have found that low birth weight and preterm gestational age are associated with increased risk of cardiometabolic syndrome, but these analyses have been limited by the inclusion of studies with self-reported questionnaires regarding birth weight and gestational age as well as inconsistent definitions of low birth weight. Most population-based studies have focused on cardiometabolic outcomes in adults who were born extremely preterm (<28 weeks’ gestation) or very preterm (<32 weeks’ gestation). However, several studies,^4-6 including the study by Yoshida-Montezuma et al⁴ elsewhere in JAMA Network Open, have attempted to assess cardiometabolic risk among those born late preterm (34-36 weeks’ gestation).

The retrospective cohort study by Yoshida-Montezuma et al⁴ reports an association of late preterm birth (34-36 weeks’ gestation) and moderately preterm birth (<34 weeks’ gestation) with cardiometabolic risk (CMR) score during childhood. The study is novel for its assessment of the association between late preterm gestational age and childhood CMR score.⁴

Yoshida-Montezuma et al⁴ statistically isolate late preterm birth from common fetal and maternal variables. Extremes of in utero growth associated with being born both small and large for gestational age as well as maternal factors, including diabetes, hypertension, and thromboembolism, may influence the decision to induce preterm labor. However, these variables may also be independently associated with increased risk of cardiometabolic disease later in life.

In fact, the authors⁴ report those born late preterm were more likely to have older mothers with non-European ethnicity and lower family income. The mothers of infants born late preterm were also more likely to have pregnancies complicated by diabetes, hypertension, and preeclampsia or eclampsia. The statistical analyses controlled for potential in utero and maternal confounding variables. A total of 1742 children with CMR data were matched to their birth data. The public health registers of Ontario, Canada, which were used to collect maternal and newborn data, were audited against medical records and found to have greater than 90% agreement. Additional disease registries were used to identify diabetes and hypertension in mothers, further limiting the potential for error and allowing the authors to control for these potential confounding variables in the analyses. Compared with full-term birth (≥39 weeks’ gestation), both late preterm and moderately preterm birth were associated with a higher mean CMR score at ages 3 to 12 years. As a continuous variable, each additional week of gestational age was associated with a lower mean CMR score.⁴

The CMR score may better identify potential risk of disease through multiple measures rather than assessment of individual risk factors; however, standardization of CMR scores during childhood remains a substantial challenge. Kamel et al⁷ performed a review of publications from 2007 to 2016, noting wide variability in components of the CMR score, with some studies including as few as 3 variables and others as many as 11 variables. Yoshida-Montezuma et al⁴ used The Applied Research Group for Kids (TARGet Kids!) data set, which included the 5 most common components of the CMR score reported in the review,⁷ waist circumference z score, log triglyceride level, glucose level, systolic blood pressure, and inverse high-density lipoprotein cholesterol level. Standardizing and validating CMR scores would strengthen future studies and allow for analyses to be conducted across studies.

The findings of the Yoshida-Montezuma et al⁴ study highlight the importance of gestational age, including late preterm birth, as an independent risk factor for future cardiometabolic disease. A similar cohort study⁵ from northern Finland also controlled for maternal risk factors and noted an association between late preterm delivery and the development of metabolic syndrome in adults. Another recent publication⁶ of a Swedish national cohort that controlled for gestational weight and multiple parental factors noted that late preterm delivery was associated with increased risk of hemorrhagic and ischemic stroke in adults aged 18 to 43 years. All of these studies^4-6 emphasize the need to optimize maternal health and prevent preterm deliveries, even when they occur relatively late in gestation. The studies are limited by their lack of ethnically diverse populations, and additional studies are needed to confirm the significance of late preterm birth across all populations.

When reporting late preterm birth as an independent risk factor for future cardiometabolic disease, Yoshida-Montezuma et al⁴ note the potential to impact long-term health among this group of patients. Future controlled studies are necessary to understand whether early screening and therapeutic interventions directed at those born late preterm have the ability to reduce the risk and burden of cardiometabolic disease.

Published: May 27, 2022. doi:10.1001/jamanetworkopen.2022.14385

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Iacono L et al. JAMA Network Open.

Corresponding Author: Molly O. Regelmann, MD, Division of Pediatric Endocrinology and Diabetes, The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, 3415 Bainbridge Ave, Bronx, NY 10467 (moregelm@montefiore.org).

Conflict of Interest Disclosures: None reported.