Associations of maternal cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1(CDKAL1) gene variants with adverse pregnancy outcome in Chinese women

TL;DR

This study finds that certain genetic variants in the CDKAL1 gene in Chinese women are linked to higher risks of adverse pregnancy outcomes like low birth weight and macrosomia, even after accounting for gestational diabetes.

Contribution

The study identifies CDKAL1 gene variants as independent risk factors for adverse pregnancy outcomes in Chinese women, beyond the influence of gestational diabetes.

Findings

CDKAL1 genetic marker was associated with increased risk of adverse pregnancy outcome (OR: 2.51).

The marker was significantly linked to low birth weight (OR: 19.80) and macrosomia (OR: 2.40).

The association remained significant after adjusting for gestational diabetes mellitus.

Abstract

To test associations of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene variants with the risk of adverse pregnancy outcome in Chinese women and whether the association was mediated by occurrence of gestational diabetes mellitus.

We organized a 1:1 age-matched study nested within a prospective cohort of pregnant women (207 pairs) established in urban Tianjin. Adverse pregnancy outcome was defined as a composite outcome of preterm birth, low birth weight or macrosomia. Logistic regression analyses were used to estimate associations of CDKAL1 gene variants with adverse pregnancy outcome and its components. The CDKAL1 genetic marker was defined as encompassing any of the identified susceptibility variants for adverse pregnancy outcome.

The CDKAL1 genetic marker was associated with the risk of adverse pregnancy outcome (OR: 2.51, 95%CI: 1.47, 4.28), low birth weight (OR: 19.80, 95%CI: 2.15, 182) and macrosomia (OR: 2.40, 95%CI: 1.17, 4.93), but not with preterm birth (P = 0.105) after adjusting for traditional risk factors. Further adjusting for gestational diabetes mellitus, the CDKAL1 genetic marker remained significantly associated with adverse pregnancy outcome, and the OR (95%CI) was 2.52 (1.48, 4.30).

The maternal CDKAL1 gene variants were associated with increased risk of adverse pregnancy outcome, low birth weight and macrosomia, independent of gestational diabetes mellitus. CDKAL1 gene might be a useful marker for identification of individuals at a particularly high risk of adverse pregnancy outcome in early pregnancy.

The online version contains supplementary material available at 10.1186/s12884-025-07418-1.

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