Elsevier

The Lancet

Volume 360, Issue 9329, 27 July 2002, Pages 290-294
The Lancet

Articles
Zinc supplementation during pregnancy and effects on mental development and behaviour of infants: a follow-up study

https://doi.org/10.1016/S0140-6736(02)09551-XGet rights and content

Summary

Background

Zinc deficiency is widely prevalent in developing countries. Zinc supplements given to Bangladeshi pregnant women have been shown to reduce infants' infectious disease morbidity. We assessed these infants at age 13 months to establish the effect of antenatal zinc supplementation on infant development and behaviour.

Methods

The study originally consisted of 559 pregnant women who were randomly allocated to zinc (30 mg daily) or placebo (cellulose) from 4 months' gestation to delivery. The effect of zinc supplementation on pregnancy outcome and on infant growth and morbidity in the first 6 months was assessed. We then randomly selected a subsample of 168 infants from 383 who completed the study at 6 months. When babies in this subsample reached age 13 months, we assessed mental development with Bayley scales of infant development-II, rated behaviour on a modified version of Wolke's scales, and measured weight and height.

Findings

When we controlled for differences between tested and non-tested participants, infants in the placebo group had higher scores on mental development index (regression coefficient=3·3, SE 1·6, 95% Cl 0·2–6·5, p=0·04) and psychomotor development index (5·1, 2·4, 0·2–9·9, p=0·04) than those in the zinc-supplemented group. Zinc supplementation had no significant effect on behaviour or growth. The children's nutritional status was poor, and weight-for-age at testing was strongly related to developmental levels, which accounted for some of the treatment effect.

Interpretation

Prenatal supplementation with zinc alone in poor women from Bangladesh does not seem to confer benefit on infants' mental development. Such treatment should be considered with caution.

Introduction

Zinc deficiency is widely prevalent in the developing world, where diets contain low levels of animal protein and high fibre and phytate. Zinc supplementation improves growth1 and reduces morbidity2 in zinc-deficient children, and there is some evidence that it improves children's development, but findings are inconsistent.3 Pregnant women are also thought to be at high risk of zinc deficiency because of an increased physiological requirement.4 Some investigators have noted that maternal zinc intake or plasma zinc concentration is positively related to pregnancy outcome, whereas others have failed to show an association.5, 6 Trials during pregnancy have had inconsistent findings about the effects of zinc supplementation on birthweight and length of gestation.7

Does zinc deficiency in pregnancy adversely affect the mental development of offspring? Results of studies in animals have shown that severe zinc deficiency during pregnancy affects brain development8 and behaviour of offspring.9 In an observational study of pregnant women in Egypt, maternal intake of fibre and phytate, which are inhibitors of zinc absorption, was negatively related to infants' motor development.10 Furthermore, maternal intake of foods from animal sources was a significant predictor of the newborn baby's speed of encoding information.11 The investigators suggested that zinc bioavailability might play a part in this relation. Fetal neurobehavioural development improves when zinc is added to iron and folate supplement during pregnancy.12 However, we are unaware of any trial to assess the effect of zinc supplementation in pregnancy on subsequent mental and motor development of offspring.

In 1997, pregnant Bangladeshi women took part in a randomised controlled trial to examine the effect of zinc supplementation from the fourth month of pregnancy to term, on the outcome of pregnancy13 and subsequent growth and morbidity of the infants in the first 6 months of life.14 There was no benefit with regard to birthweight or gestational age at birth, but low birthweight infants whose mothers received zinc supplements had a reduced rate of infections. We took the opportunity presented in that study to examine the effect of prenatal zinc supplementation on development. We postulated that zinc supplementation of pregnant women would benefit the psychomotor and mental development and behaviour of their offspring.

Section snippets

Methods

The study was done in slum areas of Dhaka, which are characterised by high population density, poor housing, multifamily latrines and water sources, poor sewerage and drainage facilities, and irregular rubbish collection. The study was approved by the research and ethical review committees of International Centre for Diarrhocal Disease Research, Bangladesh (ICDDR, B). Prior informed consent was obtained from the parents of the children.

Results

The figure shows the trial profile. Of 240 randomly selected infants, four had died before our study began, one had epilepsy and was excluded, five refused to come for further assessment, and eight were ill and by the time they recovered had exceeded the age required by the selection criteria for testing. Another 54 infants could not be found. We therefore located a total of 168 children from our subset of 240 (zinc=83, placebo=85).

We compared the characteristics at enrolment of the mothers of

Discussion

We have shown that zinc supplementation of pregnant women was associated with lower Bayley scores in their infants than in the placebo group. The difference remained significant when we controlled for differences between tested and non-tested participants, and between treatment groups. The deficit was small, about a third of 1 SD. Children of zinc-treated mothers were also less cooperative during the test and fussier than the placebo group, but this difference disappeared when we controlled for

References (30)

  • KO O'Brien et al.

    Influence of prenatal iron and zinc supplements on supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant Peruvian women

    Am J Clin Nutr

    (1999)
  • SM Grantham-McGregor

    A review of studies of the effect of severe malnutrition on mental development

    J Nutr

    (1995)
  • KH Brown et al.

    Effect of zinc supplementation on children's growth: a meta-analysis of intervention trials

    Bibl Nutr Dieta

    (1998)
  • MM Black

    Zinc deficiency and child development

    Am J Clin Nutr

    (1998)
  • LE Caulfield et al.

    Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival

    Am J Clin Nutr

    (1998)
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