New research has found that babies whose mothers received treatment with metformin, a medication commonly used to treat diabetes in pregnancy, had a lower birthweight but faster postnatal growth than babies whose mothers had their diabetes treated with insulin.
These results suggest there could be long term risks to the health of the offspring of mothers treated with this widely used drug, taken by around one in 100 pregnant women in the UK.
Researchers based at the University of Cambridge and the Rosie Hospital, Cambridge University Hospitals, say that while treating diabetes during pregnancy is important for both the mother and her baby’s health, these results indicate that metformin could increase the risk of these babies developing metabolic problems in later life.
Gestational diabetes, a form of diabetes that arises in pregnancy, is becoming increasingly common globally. Currently in the UK, gestational diabetes affects at least one in 20 pregnancies. If not well managed, gestational diabetes is associated with an increased risk of birth complications, including emergency Caesarean section and stillbirth. However, most gestational diabetes doesn’t need medication and can be managed with diet and lifestyle advice alone. Women who need medication to control their diabetes are offered either insulin injections or metformin tablets.
Professor Susan Ozanne from the Wellcome Trust-Medical Research Council Institute of Metabolic Science at the University of Cambridge and her team carried out a systematic review and meta-analysis of 28 studies that included almost 4000 women. The results are published in the open access journal PLOS Medicine.
The researchers found that babies whose mothers were treated with metformin weighed on average 108g less at birth than those whose mothers were treated with insulin. However, by 18–24 months, metformin-exposed infants were 0.44kg heavier than insulin-exposed infants and had a higher BMI (increased by 0.8 kg/m2) by mid-childhood (5–9 years).
While there are few long-term follow up studies in relation to the effects of metformin treatment during pregnancy, previous research has shown that children who are born small and then undergo ‘catch-up growth’ after birth are at increased risk of developing cardiovascular disease and type 2 diabetes later in life.
Professor Ozanne said: “It is important to diagnose and treat gestational diabetes for the benefit of both mother and baby and many women can manage their condition simply by making changes to diet and lifestyle.
“The two main treatments – metformin and insulin – both have their own benefits and drawbacks and we have to consider that during pregnancy there are two patients – the mother and the baby. Our study showed that children exposed to metformin in the womb were born at significantly lower birth weights compared to babies whose mother’s took insulin, but then grew faster in infancy and were significantly heavier in childhood.
“We don’t know enough yet about the long-term risks to the health of these children, so it’s important that there are more studies to explore this in depth and to help fine-tune treatments. We know that metformin crosses the placenta, while insulin doesn’t, so it is likely that the drug acts on the placenta or foetal tissue.”
The researchers caution that pregnant mothers should not change their treatment.
Co-lead author Dr Catherine Aiken, from the Department of Obstetrics and Gynaecology at the Rosie Hospital and the University of Cambridge, said: “While our study shows that metformin is associated with alterations in the baby’s growth, we know that untreated gestational diabetes has significant adverse effects for the baby, so it’s very important that pregnant mums receive treatment.
“Mothers should not stop taking metformin – it is still an important drug. If they have any concerns about their treatment, they should speak to their medical team about their options.”