Metformin exposure in pregnancy poses no risk of SGA, LGA in infants

Exposure to metformin in utero does not appear to put infants at risk of being small for gestational age (SGA) or being large for gestational age (LGA) as compared with nonexposure, a study has found.

This Finnish population register-based cohort study included singleton children who were born during 2004–2016. These included 3,964 children who were exposed to metformin in utero and 82,675 who were nonexposed. Researchers conducted additional analyses in a subcohort that restricted the metformin cohort to children of mothers with gestational diabetes (GDM; n=2,361).

The median gestational age at birth was 39.4 weeks in the metformin cohort and 39.9 weeks in the naïve cohort. Median maternal age at delivery was 32 years in the metformin cohort and 31 years in the naïve cohort, while the respective median maternal prepregnancy body mass index median was 29.7 kg/m² and 26.9 kg/m², respectively.

SGA was reported in 2.3 percent of the children in the metformin cohort, 2.0 percent in the naïve cohort, and 2.2 percent in the metformin-GDM subcohort. Metformin exposure was not associated with increased SGA risk in the main analysis (treatment weighted odds ratio [wOR], 0.97, 95 percent confidence interval [CI], 0.73–1.27) and in the metformin-GDM subcohort analysis (wOR, 1.01, 95 percent CI, 0.75–1.37).

LGA was documented in 4.0 percent of the children in the metformin cohort, 4.1 percent in the naïve cohort, and 4.7 percent in the metformin-GDM subcohort. Likewise, metformin exposure did not contribute to an increased LGA risk in the main analyses (wOR, 0.91, 95 percent CI, 0.75–1.11) and in the metformin-GDM subcohort analysis (wOR, 0.72, 95 percent CI, 0.56–0.92).

The null effect of metformin on SGA risk is consistent with findings from studies using metformin in nondiabetic pregnancies. However, there are pieces of evidence reporting lower birth weight and increased SGA birth risk in GDM pregnancies exposed to metformin vs insulin.

As such, the researchers caution the use of metformin in view of emerging growth restriction in utero. They called for additional studies to elucidate the interplay of intrauterine hyperglycaemia and pharmacological treatments.