# The Role of Selenium During Gestation in the Development of Fetal Congenital Anomalies: A Systematic Review

## TL;DR

This systematic review examines how selenium during pregnancy may influence the risk of fetal congenital anomalies, finding mixed associations with specific types of defects.

## Contribution

The study systematically reviews the relationship between selenium exposure during gestation and congenital anomalies, highlighting gaps in current evidence.

## Key findings

- Higher selenium levels were linked to increased risk of urinary tract anomalies but decreased risk of heart defects and neural tube defects.
- Selenium exposure showed no significant effect on overall congenital anomalies, abdominal or limb anomalies, chromosomal anomalies, or fetal alcohol syndrome.
- The evidence is limited by observational study designs and potential confounding factors like gestational age.

## Abstract

Background/Objectives: During intrauterine development, cell proliferation, differentiation, and apoptosis are strictly regulated for organogenesis to be ensured; disruption of these processes, e.g., by oxidative stress, may lead to congenital anomalies. This systematic review aimed to examine the role of selenium (Se), an important antioxidant, during gestation in the development of congenital anomalies. Methods: To identify relevant original research studies in English, PubMed, Embase, and Cochrane Library were systematically searched up to December 2025. A qualitative synthesis, quality appraisal, and assessment of predefined sources of bias and heterogeneity were performed. Results: 2743 titles and abstracts were screened, 473 full texts assessed, and 31 papers included. Selenium exposure did not affect the risk of all/any congenital anomalies (n = 20,815), abdominal (n = 89,273) and limb anomalies (n = 551,547), chromosomal anomalies (n = 1242), or fetal alcohol syndrome (n = 41). Higher concentrations of Se were associated with increased risk for urinary tract anomalies (n = 2150), but decreased risk for congenital heart defects (n = 1807), neural tube defects (max n = 12,188), and orofacial clefts (max n = 1155). Conclusions: Available scientific evidence arises from observational studies and is prone to confounding mainly by gestational age, while only one randomized controlled trial has been identified. Given the major contribution of congenital anomalies to neonatal morbidity, mortality, and long-term impairment of quality of life, well-designed prospective studies are required to establish scientific consensus, define optimal maternal Se levels during pregnancy, and provide evidence-based recommendations for Se supplementation during pregnancy.