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).
The association between maternal diabetes mellitus and congenital defects has been well documented. However, few data exist on the potential teratogenic effect of gestational diabetes (GD). We analyzed 19,577 consecutive infants with malformations of unknown cause and compared the offspring of mothers with GD with those of nondiabetic mothers. The children with each of 20 types of selected anomalies among the two groups were used to calculate the odds ratio (OR). Because we used as a reference group for each congenital defect the rest of malformed infants, the value of the OR gives us the specificity between the association of GD and each congenital defect. Our analysis strongly supports the suggestion that GD is a significant risk for holoprosencephaly, upper/lower spine/rib, and renal and urinary system anomalies. GD is a heterogeneous disorder, which includes previously unrecognized and newly diagnosed nongestational diabetes mellitus (DM). Thus, it is possible that the teratogenic effect is related to latent DM. However, because it is not possible at this time to differentiate between these situations, pregnancies complicated by GD should be considered at risk for congenital anomalies. Prenatal ultrasound examination should be aimed particularly at the detection of abnormalities of the central nervous system, the renal and urinary system, and the spine/rib developmental field.
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