ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: JAMA Pediatr 2019; 173(5):493–494.

This double-blind, randomized controlled trial, in 345 US women who smoked cigarettes during pregnancy, showed that high (4 mg/day) versus standard dose (0.8 mg/day) folic acid increased mean birth weight by 140 grams, had a 31% lower risk of having a SGA baby, and a 35% lower risk of fetal growth restriction.

It is well known that smoking during pregnancy reduces fetal growth and birth weight, by roughly 200 grams; offspring subsequently show rapid ‘catch-up’ weight gain during infancy leading to higher risk of overweight and obesity during childhood (1). While there may be various possible mechanisms, here the authors tested a hypothesis based on observational evidence of lower serum folate levels in smokers. The findings are clear – high dose of folic acid (similar to the dose that some recommend to obese women for prevention of neural tube defects) prevented most of the birth weight reduction normally seen in infants of maternal smokers. This is the first such trial, the protective effect on SGA did not quite reach statistical significance, and confirmation in larger samples is needed. However, the apparent large effect sizes are highly promising for a new and safe way to improve the health of such babies.

But is it controversial to find a way to allow mothers to smoke more safely? Could this be seen as encouraging mothers not to stop smoking in pregnancy? The same issue applies to use of medical therapies to prevent co-morbidities of obesity. Of course we should encourage lifestyle behaviour change, and in this trial both study arms received smoking cessation counselling. But we should also aim to understand the mechanisms that link unhealthy lifestyles to disease and use this information to improve preventive strategies.

Reference: 1. Ong KK, Preece MA, Emmett PM, Ahmed ML, Dunger DB. Size at birth and early childhood growth in relation to maternal smoking, parity and infant breast-feeding: longitudinal birth cohort study and analysis. Pediatric Research 2002;52:863–7.