Effect of zinc supplementation on pregnancy and infant outcomes: a systematic review.

Poor maternal zinc status has been associated with foetal loss, congenital malformations, intra-uterine growth retardation, reduced birth weight, prolonged labour and preterm or post-term deliveries. A meta-analysis completed in 2007 showed that maternal zinc supplementation resulted in a small but significant reduction in preterm birth. The purposes of this analysis are to update that previous review and expand the scope of assessment to include maternal, infant and child health outcomes. Electronic searches were carried out to identify peer-reviewed, randomised controlled trials where daily zinc supplementation was given for at least one trimester of pregnancy. The co-authors applied the study selection criteria, assessed trial quality and abstracted data. A total of 20 independent intervention trials involving more than 11,000 births were identified. The 20 trials took place across five continents between 1977 and 2008. Most studies assessed the zinc effect against a background of other micronutrient supplements, but five were placebo-controlled trials of zinc alone. The provided dose of supplemental zinc ranged from 5 to 50 mg/day. Only the risk of preterm birth reached statistical significance (summary relative risk 0.86 [95% confidence interval 0.75, 0.99]). There was no evidence that supplemental zinc affected any parameter of foetal growth (risk of low birth weight, birth weight, length at birth or head circumference at birth). Six of the 20 trials were graded as high quality. The evidence that maternal zinc supplementation lowers the risk of preterm birth was graded low; evidence for a positive effect on other foetal outcomes was graded as very low. The effect of zinc supplementation on preterm birth, if causal, might reflect a reduction in maternal infection, a primary cause of prematurity. While further study would be needed to explore this possibility in detail, the overall public health benefit of zinc supplementation in pregnancy appears limited.