PubMed · 8195728
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L M Cousins. 1994. GDM screening.. https://pubmed.ncbi.nlm.nih.gov/8195728/
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Gestational diabetes mellitus (GDM) is associated with adverse metabolic outcomes and may also be related to postpartum breast and lactation disorders. Observational studies are susceptible to confounding and reverse causation. We used a 2-sample Mendelian randomization design to examine the association between genetic liability to GDM and other disorders of the breast and lactation associated with childbirth. Genetic liability to GDM was associated with higher odds of a composite phenotype of breast and lactation disorders associated with childbirth. Replication using independent samples and more specific clinical outcomes is required. Summary statistics for GDM and the FinnGen outcome "other disorders of breast and lactation associated with childbirth" were obtained from the Integrative Epidemiology Unit open genome-wide association study resource. single nucleotide polymorphisms associated with GDM (P < 5 × 10-6) were clumped (R2 < 0.001) within 10,000 kb. The inverse-variance weighted method was the primary analysis; Mendelian randomization-Egger, weighted median, simple mode, and weighted mode analyses were complementary methods. Heterogeneity, directional horizontal pleiotropy, leave-one-out, and Steiger directionality analyses were performed. Nineteen single nucleotide polymorphisms were retained; F statistics ranged from 21.08 to 288.04. Genetic liability to GDM was associated with higher odds of the outcome in the inverse-variance weighted analysis (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.08-2.09; P = .0165). The weighted median (OR, 1.76; 95% CI, 1.09-2.84; P = .0216) and weighted mode estimates (OR, 1.98; 95% CI, 1.21-3.26; P = .0148) were directionally consistent. There was no statistical evidence of heterogeneity or directional horizontal pleiotropy. The Steiger test supported the direction from GDM to the outcome (P = 1.30 × 10-11).
There are very few publications on the possible relationship between maternal diabetes and infants presenting heterotaxia-asymmetry defects. In mice, there is a relationship between maternal diabetes and heterotaxia, although this is influenced by the fetal genotype. An epidemiological analysis of heterotaxia-asymmetry in children born to diabetic mothers (diabetes mellitus or gestational diabetes) is presented here. The analysis is based in the case-control study of the ECEMC database. However, due to the very small sample size for each type of study of heterotaxia-asymmetry alterations, up to 10 control infants for each case were selected. Although the sample size is small, the results suggest that only maternal diabetes mellitus significantly increases the risk for transposition of great vessels (OR=61.87; CI:7.36-519.82), and transposition of viscera (OR=24.82; CI;1.84-335.44).
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