Metformin exposure in first trimester does not increase risk of congenital anomalies

“Pulmonary valve atresia has not been previously described after exposure to metformin during pregnancy,” they added “Although our findings are reassuring regarding the risk of congenital anomaly, further surveillance is recommended to increase the sample size and to follow up the pulmonary valve atresia signal in an independent dataset,” researchers said. “The long-term outcomes among babies who have been exposed to metformin in utero are also of interest.” https://specialty.mims.com/topic/metformin-exposure-in-first-trimester-does-not-increase-risk-of-congenital-anomalies?channel=obstetrics-gynaecology&elq_mid=45437&elq_cid=35614 MIMS - Obstetrics ang Gynaecology

No evidence exists proving that metformin exposure during the first trimester of pregnancy heightens the risk of all major congenital anomalies combined, reports a study. In addition, the significant association with an increased risk of pulmonary valve atresia may be no more than a chance finding.

Of the babies included in the analysis, 168 affected with congenital anomaly (141 nongenetic and 27 genetic) were exposed to metformin (3.3 per 1,000 births). There was no evidence for a higher proportion of exposure to metformin during the first trimester among babies with all nongenetic anomalies combined vs genetic controls (adjusted odds ratio [aOR], 0.84; 95 percent CI, 0.55–1.30). [BMJ 2018;361:k2477]

The only significant association was for pulmonary valve atresia (aOR, 3.54; 1.05–12.00, compared with nongenetic controls; aOR, 2.86; 0.79–10.30, compared with genetic controls).

“Given the rise in exposure to metformin during pregnancy, our findings are particularly timely,” researchers said. [Obstet Gynecol 2013;121:106-114; PLoS One2016;11:e0155737]

“Our large international, population-based database, with 168 cases of congenital anomaly exposed to metformin, from an estimated 6,245 exposed pregnancies in Europe, represents more than five times the number of metformin exposures previously available in the literature,” they added. [Hum Reprod Update 2014;20:656-669; Fertil Steril 2006;86:658-663; Int J Reprod Biomed (Yazd) 2017;15:461-470; Br J Clin Pharmacol 2018;84:568-578]

Results regarding the risk of all nongenetic congenital anomalies combined support those of previous studies. [Hum Reprod Update 2014;20:656-669; Fertil Steril2006;86:658-663; Int J Reprod Biomed (Yazd) 2017;15:461-470; Br J Clin Pharmacol2018;84:568-578]

However, teratogens appear to elevate the risk of specific, rather than all, congenital anomalies, which is why focusing on specific anomalies is crucial. [N Engl J Med2003;349:2556-2559]

Furthermore, the signal found for pulmonary valve atresia, which has been previously linked to maternal diabetes, might suggest some residual confounding by indication or might have occurred by chance, according to researchers. [Birth Defects Res A Clin Mol Teratol 2012;94:134-140]

“Pulmonary valve atresia has not been previously described after exposure to metformin during pregnancy,” they added. [Hum Reprod Update 2014;20:656-669;Fertil Steril 2006;86:658-663; Br J Clin Pharmacol 2018;84:568-578]

In the present study, researchers obtained data from 11 EUROmediCAT European congenital anomaly registries surveying 1,892,482 births in Europe between 2006 and 2013. A total of 50,167 babies with congenital anomaly (41,242 nongenetic and 8,925 genetic), including live births, foetal deaths from 20 weeks’ gestation and terminations of pregnancy for foetal anomaly, were analysed.

“Although our findings are reassuring regarding the risk of congenital anomaly, further surveillance is recommended to increase the sample size and to follow up the pulmonary valve atresia signal in an independent dataset,” researchers said. “The long-term outcomes among babies who have been exposed to metformin in utero are also of interest.”