Zinc supplementation for improving pregnancy and infant outcome

What is the issue?

In low- and middle-income countries, many women have poor diets and are deficient in key micronutrients that are required for good health. This is especially concerning during pregnancy, when energy and nutrient needs are greater for both the mother and the growing baby. Zinc plays a critical role in normal growth and development. Deficiency in zinc could lead to adverse health outcomes, such as being born too soon or too small.

This is an update of a review first published in 1997 and subsequently updated in 2007, 2012 and 2015.

Why is this important?

Although severe zinc deficiency is rare, it is estimated that mild-to-moderate deficiency is common in several regions of the world. Studies of human pregnancy and zinc supplementation, including those from low- and middle-income countries, have failed to document a consistent beneficial effect on fetal growth, length of gestation, and early newborn survival.

What evidence did we find?

We searched for studies in July 2020. This updated review now includes 25 randomised controlled trials, involving over 18,000 women and their babies. We found that zinc supplementation in pregnancy may make little to no difference in reducing the risk of preterm births, stillbirths, or deaths around the time of birth, when compared to no zinc supplementation or placebo. Zinc supplementation may make little or no difference to the birthweight of babies, and probably makes little or no difference to the number of babies born either with a low birthweight or small for their gestational age, when compared with no zinc supplementation, or with giving a placebo. We cannot be sure whether zinc supplementation reduces death in newborns, because the certainty of the evidence is very low.

What does this mean?

There is not enough evidence that zinc supplementation during pregnancy results in better outcomes for women and their babies. Finding ways to improve women's overall nutritional status, particularly in low-income areas, will do more to improve the health of mothers and babies than supplementing pregnant women with zinc alone. This should be an urgent research priority for the future.

Authors' conclusions: 

There is not enough evidence that zinc supplementation during pregnancy results in improvements in maternal or neonatal outcomes. Future research to address ways of improving the overall nutritional status of pregnant women, particularly in low-income regions, and not looking at zinc in isolation, should be an urgent priority.

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Background: 

It has been suggested that low serum zinc levels may be associated with suboptimal outcomes of pregnancy, such as prolonged labour, atonic postpartum haemorrhage, pregnancy-induced hypertension, preterm labour and post-term pregnancies, although these associations have not yet been established. This is an update of a review first published in 1997 and subsequently updated in 2007, 2012 and 2015.

Objectives: 

1. To compare the effects on maternal, fetal, neonatal and infant outcomes in healthy pregnant women receiving zinc supplementation versus no zinc supplementation, or placebo.
2. To assess the above outcomes in a subgroup analysis reviewing studies performed in women who are, or are likely to be, zinc-deficient.

Search strategy: 

For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 July 2020), and reference lists of retrieved studies.

Selection criteria: 

Randomised trials of zinc supplementation versus no zinc supplementation or placebo administration during pregnancy, earlier than 27 weeks' gestation. We excluded quasi-randomised controlled trials. We intended to include studies presented only as abstracts, if they provided enough information or, if necessary, by contacting authors to analyse them against our criteria; we did not find any such studies.

Data collection and analysis: 

Three review authors applied the study selection criteria, assessed trial quality and extracted data. When necessary, we contacted study authors for additional information. We assessed the certainty of the evidence using GRADE.

Main results: 

For this update, we included 25 randomised controlled trials (RCTs) involving over 18,000 women and their babies. The overall risk of bias was low in half of the studies. The evidence suggests that zinc supplementation may result in little or no difference in reducing preterm births (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.74 to 1.03; 21 studies, 9851 participants; low-certainty evidence). Further, zinc supplementation may make little or no difference in reducing the risk of stillbirth (RR 1.22, 95% CI 0.80 to 1.88; 7 studies, 3295 participants; low-certainty evidence), or perinatal deaths (RR 1.10, 95% CI 0.81 to 1.51; 2 studies, 2489 participants; low-certainty evidence). It is unclear whether zinc supplementation reduces neonatal death, because the certainty of the evidence is very low. Finally, for other birth outcomes, zinc supplementation may make little or no difference to mean birthweight (MD 13.83, 95% CI -15.81 to 43.46; 22 studies, 7977 participants; low-certainty evidence), and probably makes little or no difference in reducing the risk of low birthweight (RR 0.94, 95% CI 0.79 to 1.13; 17 studies, 7399 participants; moderate-certainty evidence) and small-for-gestational age babies when compared to placebo or no zinc supplementation (RR 1.02, 95% CI 0.92 to 1.12; 9 studies, 5330 participants; moderate-certainty evidence). We did not conduct subgroup analyses, as very few studies used normal zinc populations.

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