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Metformin during pregnancy – Goldilocks principle strikes again!

March 15, 2018 Dr Chee L Khoo

Hyperglycaemia during pregnancy has significant metabolic consequences for the mother, the pregnancy as well as for the offspring’s future health. It is tempting to assume that keeping the glucose lower during pregnancy must be beneficial for both parties. Metformin has been used in women with PCOS, GDM and obesity during pregnancy in an attempt to improve pregnancy and foetal outcomes but this practice is not based on solid scientific evidence.

Metformin passes the placental barrier but we don’t know about possible effects of metformin on growth, metabolism, endocrine and nervous system development in the foetus and cognitive and psychological effects later in life. Studies in women with gestational diabetes on metformin are conflicting – 5 studies found no effect on birth weight, 2 studies found increased birth length while another found shorter and lighter babies with metformin. In pregnant women who are obese and on metformin, two studies did find any effect on birth weight.

In the initial analysis of the PregMet study, women with PCOS, there were no difference in pregnancy complications or newborn data with metformin. However, head size was larger with metformin. They also examined the in utero ultrasound measurements of the foetus at 19 weeks and 32 weeks. Head circumference, length and weight of the newborn were also obtained immediately after delivery.

Overall, there were no difference in HC at 19 weeks but HC was larger at 32 weeks (p= 0.027) and at birth (p=0.007) in the metformin group. When the data were stratified according to maternal prepregnancy weight, they found that HC is increased in the metformin group only in mothers who were overweight (BMI>25). On the other hand birth length was reduced in the metformin group but only in normal weight women but not overweight women. Similarly, birth weight was reduced in the metformin group but only in normal weight mothers. This suggests a growth restrictive effect of metformin in normal weight women with PCOS.

Strangely, metformin exposed girls but not boys, seem to have a larger HC. After adjustment for maternal BMI, the sex difference was lost. Overall, compared with the reference population, the PCOS off-springs were shorter.

More convincing data are needed on the potential of metformin to decrease pregnancy complications before metformin can be recommended in nondiabetic pregnancies. So far, precaution is advised when metformin is prescribed to normal-weight mothers with PCOS without

well-documented indication.

Access abstract here

Reference

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Kollmann M, Klaritsch P, Martins WP, Guenther F, Schneider V, Herzog SA, Craciunas L, Lang U, Obermayer-Pietsch B, Lerchbaum E, Raine-Fenning N. Maternal and neonatal outcomes in pregnant

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Anderson H, Fogel N, Grebe SK, Singh RJ, Taylor RL, Dunaif A. Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J Clin Endocrinol

Metab. 2010;95(5):2180–2186.

Rowan JA, HagueWM,Gao W, Battin MR, Moore MP;MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358(19):2003–2015.

Anna Hjorth-Hansen,Oyvind Salvesen, Liv Guro Engen Hanem, Torbjørn Eggebø, Kjell A . Salvesen, Eszter Vanky,Rønnaug Ødega. Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS. J Clin Endocrinol Metab, February 2018, 103(2):740–747

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