Researchers say infections during pregnancy may be a protective factor for the development of allergic diseases in children, rather than a risk factor.
Children exposed to metformin in utero were nearly five times more likely to develop allergies by the age of eight, according to Norwegian researchers.
They also had higher rates of eczema (35% vs 18%) than children who were not exposed, although asthma rates were similar across both groups.
However, for the mothers, metformin treatment was associated with 10% fewer infections during pregnancy (OR = 0.68).
This was particularly noticeable in viral infections such as respiratory tract infections, which occurred in 26% of the treatment group and 33% in the placebo group.
Bacterial, fungal, and postpartum infections, as well as antibiotic use, were similar across the groups.
The findings came from post hoc analyses of two randomised controlled trials of pregnant women with PCOS, along with a follow-up study of their offspring in Norway, Sweden and Iceland.
More than 600 women were equally randomised to 1700-2000 mg of daily metformin or placebo from the first trimester to delivery. Nearly 150 of their offspring were included.
Nearly a fifth of children exposed to metformin in utero developed allergies between birth and follow-up, compared to only 4% of the placebo-exposed offspring.
The increased rates of allergies and eczema were independent of maternal BMI, offspring BMI z-score, birthweight and maternal infections.
Metformin does cross the placenta, but teratogenicity has not been reported, the researchers explained.
However, they said that exposed offspring have previously been shown to have lower birth weight and larger head circumference at birth, and increased BMI and weight at long-term follow-ups, than offspring exposed to placebo or insulin in utero.
Researchers said this was the first study showing that metformin reduces infections during pregnancy in women with PCOS, but that the findings were supported by similar effects in other populations.
Related
Women with PCOS are more susceptible to infections, a known mediator of preterm birth, and prior research has shown that maternal metformin treatment may reduce the risk of preterm birth.
The RCTs were prospective, randomized, double-blind multicentre trials of pregnant women with PCOS conducted between 2005-2009 and 2012-2017, with a follow-up of a similar trial from 2000-2003 that included clinical examination of offspring at around eight years of age.
Researchers noted that the trials adhered to good clinical practice, with strict randomisation and masking procedures, large sample sizes and longitudinal design.
However, the studies were not originally designed to investigate a link between metformin and infection or allergic diseases.
Parents reported whether their child had been diagnosed with asthma or eczema, which was not verified through testing at follow-up. Allergy data were based on antihistamine treatment history rather than systematic surveys, and subtype information was not available.
Infections during pregnancy were self-reported and categorised by the most likely pathogen based on symptoms and treatment, rather than via laboratory testing.
Previous research has shown that the PCOS inflammatory state persists in pregnancy and that metformin induces a broad maternal immune mobilisation.
Researchers said they were tempted to speculate that this mobilisation could protect against infection during pregnancy but that the study design didn’t allow for that conclusion to be drawn.
What the study did confirm, however, was the need for caution when considering metformin treatment during pregnancy.
