TY - JOUR T1 - Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study JF - BMJ Open Diabetes Research & Care JO - BMJ Open Diab Res Care DO - 10.1136/bmjdrc-2021-002363 VL - 10 IS - 1 SP - e002363 AU - Kerstin M G Brand AU - Laura Saarelainen AU - Jaak Sonajalg AU - Emmanuelle Boutmy AU - Caroline Foch AU - Marja Vääräsmäki AU - Laure Morin-Papunen AU - Judith Schlachter AU - CLUE Study Group AU - Katja M Hakkarainen AU - Pasi Korhonen Y1 - 2022/01/01 UR - http://drc.bmj.com/content/10/1/e002363.abstract N2 - Introduction This study aimed to investigate if maternal pregnancy exposure to metformin is associated with increased risk of long-term and short-term adverse outcomes in the child.Research design and methods This register-based cohort study from Finland included singleton children born 2004–2016 with maternal pregnancy exposure to metformin or insulin (excluding maternal type 1 diabetes): metformin only (n=3967), insulin only (n=5273) and combination treatment (metformin and insulin; n=889). The primary outcomes were long-term offspring obesity, hypoglycemia, hyperglycemia, diabetes, hypertension, polycystic ovary syndrome, and challenges in motor–social development. In a sensitivity analysis, the primary outcomes were investigated only among children with maternal gestational diabetes. Secondary outcomes were adverse outcomes at birth. Analyses were conducted using inverse- probability of treatment weighting (IPTW), with insulin as reference.Results  Exposure to metformin or combination treatment versus insulin was not associated with increased risk of long-term outcomes in the main or sensitivity analyses. Among the secondary outcomes, increased risk of small for gestational age (SGA) was observed for metformin (IPTW-weighted OR 1.65, 95% CI 1.16 to 2.34); increased risk of large for gestational age, preterm birth and hypoglycemia was observed for combination treatment. No increased risk was observed for neonatal mortality, hyperglycemia, or major congenital anomalies.Conclusions This study found no increased long-term risk associated with pregnancy exposure to metformin (alone or in combination with insulin), compared with insulin. The increased risk of SGA associated with metformin versus insulin suggests caution in pregnancies with at-risk fetal undernutrition. The increased risks of adverse outcomes at birth associated with combination treatment may reflect confounding by indication or severity.All data relevant to the study are included in the article or uploaded as supplementary information. Study documents are available at ENCePP with EU PAS Register Number EUPAS19686. ER -