Vitamin A supplementation during pregnancy for maternal and newborn health outcomes

Vitamin A is a fat-soluble vitamin derived from the retinoids retinal and retinoic acid, found in liver, kidney, eggs, and dairy produce. Carotenoids are converted to vitamin A in the liver, where vitamin A is stored; beta-carotene is found in dark or yellow vegetables and carrots. Low dietary fat intake or intestinal infections may interfere with the absorption of vitamin A. Natural retinoids are required for a wide range of biological processes including vision, immune function, bone metabolism and haematopoiesis. In pregnancy, extra vitamin A may be  required. Currently, the WHO and other international agencies recommend routine vitamin A supplementation during pregnancy or at any time during lactation in areas with endemic vitamin A deficiency (where night blindness occurs).

The principal forms used as nutritional supplements are vitamin A palmitate (retinyl palmitate) and vitamin A acetate (retinyl acetate) but carotenoids (most commonly beta-carotene) and retinoids (retinol, retinal, retinoic acid) can also be used as nutritional supplements. Signs of vitamin A deficiency include night blindness, dryness of the conjunctiva and cornea and a diminished ability to fight infections, especially respiratory and gastroenteric infections.

Findings of this review do not suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. There is, however, good evidence that antenatal vitamin A supplementation reduces maternal anaemia in women who live in areas where Vitamin A deficiency is common or who are HIV-positive. The available evidence suggests a reduction in maternal infection but these data are not of a high quality and further trials would be needed to confirm or refute this.

We included 16 randomised trials where vitamin A was commenced pre-pregnancy or during pregnancy and in some cases continued into the postnatal period. Seven trials were conducted in Africa, five in Indonesia and one each in India, Nepal, UK and USA. The trials were conducted in populations considered to be vitamin A deficient except for the trials in the USA and UK.

Vitamin A supplementation did not reduce the risk of maternal mortality, perinatal and newborn mortality, stillbirth, preterm birth, low birthweight or newborn anaemia. The risk of maternal anaemia, infection and night blindness was reduced. In one study, for women who were HIV-positive, the addition of vitamin A to supplements of iron and folate did result in fewer low birthweight babies (less than 2.5 kg at birth). The trials published so far did not report any side effects, adverse events or congenital malformations. The dose of vitamin A given, in combination with additional micronutrients and the duration of supplementation differed in the trials and varied between 5000 IU and 10,000 IU for daily doses, around 200,000 IU vitamin A for weekly supplementation and 200,000 IU vitamin A at time of delivery.

 

Authors' conclusions: 

The pooled results of two large trials in Nepal and Ghana (with almost 95,000 women) do not currently suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. However the populations studied were probably different with regard to baseline vitamin A status and there were problems with follow-up of women. There is good evidence that antenatal vitamin A supplementation reduces maternal anaemia for women who live in areas where vitamin A deficiency is common or who are HIV-positive. In addition the available evidence suggests a reduction in maternal infection, but these data are not of a high quality.

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Background: 

The World Health Organization recommends routine vitamin A supplementation during pregnancy or lactation in areas with endemic vitamin A deficiency (where night blindness occurs), based on the expectation that supplementation will improve maternal and newborn outcomes including mortality, morbidity and prevention of anaemia or infection.  

Objectives: 

To review the effects of supplementation of vitamin A, or one of its derivatives, during pregnancy, alone or in combination with other vitamins and micronutrients, on maternal and newborn clinical outcomes.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 July 2010).

Selection criteria: 

All randomised or quasi-randomised trials, including cluster-randomised trials, evaluating the effect of vitamin A supplementation in pregnant women.

Data collection and analysis: 

Two review authors independently assessed all studies for inclusion and resolved any disagreement through discussion with a third person. We used pre-prepared data extraction sheets.

Main results: 

We examined 88 reports of 31 trials, published between 1931 and 2010, for inclusion in this review. We included 16 trials, excluded 14, and one is awaiting assessment.

Overall when trial results are pooled, Vitamin A supplementation does not affect the risk of maternal mortality (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.55 to 1.10, 3 studies, Nepal, Ghana,UK ), perinatal mortality, neonatal mortality, stillbirth, neonatal anaemia, preterm birth or the risk of having a low birthweight baby. Vitamin A supplementation reduces the risk of maternal night blindness (risk ratio (RR) 0.70, 95% CI 0.60 to 0.82, 1 trial Nepal). In vitamin A deficient populations and HIV-positive women, vitamin A supplementation reduces maternal anaemia (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.43 to 0.94, 3 trials, Indonesia, Nepal,Tanzania ). There is evidence that vitamin A supplements may reduce maternal clinical infection (RR 0.37, 95% CI 0.18 to 0.77, 3 trials, South Africa, Nepal and UK).

In HIV-positive women vitamin A supplementation given with other micronutrients was associated with fewer low birthweight babies (< 2.5 kg) in the supplemented group in one study (RR 0.67, CI 0.47 to 0.96).