Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.

Area of Science:

• Reproductive biology
• Human genetics
• Endocrinology

Background:

• Observational studies link higher maternal cortisol to lower offspring birth weight.
• Potential residual confounding in observational studies necessitates further investigation.

Purpose of the Study:

• To investigate the causal relationship between maternal circulating cortisol levels and offspring birth weight using Mendelian Randomisation.
• To address potential confounding factors present in previous observational research.

Main Methods:

• Two-sample Mendelian Randomisation (MR) employed using genetic variants associated with morning plasma cortisol.
• Utilized genome-wide association study (GWAS) data from large cohorts (up to N=406,063) for maternal cortisol and offspring birth weight.
• Performed sensitivity analyses, including linkage disequilibrium adjustment and pleiotropy testing.

Main Results:

• Maternal cortisol levels showed an estimated association with lower birth weight (e.g., -50 grams per 1 SD increase in cortisol).
• Alternative analyses yielded similar results, supporting the primary finding.
• Evidence of pleiotropy and a weaker effect on pregnancy cortisol were noted, indicating potential biases.

Conclusions:

• Findings suggest a causal effect of higher maternal morning plasma cortisol on reduced offspring birth weight.
• Further research with more genetic instruments is needed to refine estimates and address potential biases.