Determinants of Small for Gestational Age in Women with Type 2 Diabetes in Pregnancy: Who should get Metformin?

OBJECTIVE

In the MiTy [Metformin in Women with Type 2 Diabetes in Pregnancy] randomized trial of metformin vs placebo added to insulin, we found numerous benefits with metformin but identified an increased proportion of small for gestational age (SGA) infants. We aimed to determine the predictors of SGA in order to individualize care.

RESEARCH DESIGN AND METHODS

Using logistic regression, we assessed baseline maternal characteristics as predictors of SGA. We compared maternal/neonatal outcomes in SGA metformin and placebo groups using t-tests, chi-squared tests or Fisher’s exact tests, as appropriate.  

RESULTS

Of the 502 mothers, 460 infants were eligible for this study. There were 30 infants with SGA in the metformin group (12.9%) and 15 in the placebo group (6.6%) (p=0.026). Among SGA infants, those in the metformin group delivered significantly later than those in the placebo group (37.2 vs 35.3 weeks, p=0.038). In adjusted analyses, the presence of a comorbidity (chronic hypertension and/or nephropathy, OR 3.05 (95%CI1.58-5.81) and metformin use (OR 2.26 (95%CI1.19 to 4.74)) were predictive of SGA. The absolute risk of SGA was much higher in women on metformin with comorbidity compared to women on metformin without comorbidity (25.0% vs 9.8%).

CONCLUSIONS

In this study we observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin. Thus, with the aim of reducing SGA, it is reasonable to be cautious in our use of metformin in those with T2D and chronic hypertension or nephropathy in pregnancy.