Study Title:

Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes

Study Abstract

Objectives To summarise evidence on the associations of maternal anaemia and prenatal iron use with maternal haematological and adverse pregnancy outcomes; and to evaluate potential exposure-response relations of dose of iron, duration of use, and haemoglobin concentration in prenatal period with pregnancy outcomes.

Design Systematic review and meta-analysis

Data sources Searches of PubMed and Embase for studies published up to May 2012 and references of review articles.

Study selection criteria Randomised trials of prenatal iron use and prospective cohort studies of prenatal anaemia; cross sectional and case-control studies were excluded.

Results 48 randomised trials (17 793 women) and 44 cohort studies (1 851 682 women) were included. Iron use increased maternal mean haemoglobin concentration by 4.59 (95% confidence interval 3.72 to 5.46) g/L compared with controls and significantly reduced the risk of anaemia (relative risk 0.50, 0.42 to 0.59), iron deficiency (0.59, 0.46 to 0.79), iron deficiency anaemia (0.40, 0.26 to 0.60), and low birth weight (0.81, 0.71 to 0.93). The effect of iron on preterm birth was not significant (relative risk 0.84, 0.68 to 1.03). Analysis of cohort studies showed a significantly higher risk of low birth weight (adjusted odds ratio 1.29, 1.09 to 1.53) and preterm birth (1.21, 1.13 to 1.30) with anaemia in the first or second trimester. Exposure-response analysis indicated that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was 0.88 (0.84 to 0.92) (P for linear trend<0.001). Birth weight increased by 15.1 (6.0 to 24.2) g (P for linear trend=0.005) and risk of low birth weight decreased by 3% (relative risk 0.97, 0.95 to 0.98) for every 10 mg increase in dose/day (P for linear trend<0.001). Duration of use was not significantly associated with the outcomes after adjustment for dose. Furthermore, for each 1 g/L increase in mean haemoglobin, birth weight increased by 14.0 (6.8 to 21.8) g (P for linear trend=0.002), however, mean haemoglobin was not associated with the risk of low birth weight and preterm birth. No evidence of a significant effect on duration of gestation, small for gestational age births, and birth length was noted.

Conclusions Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.

From press release:

Taking iron daily during pregnancy is associated with a significant increase in birth weight and a reduction in risk of low birth weight, finds a study published on bmj.com today.

The effects were seen for iron doses up to 66 mg per day. The World Health Organization currently recommends a dose of 60 mg per day for pregnant women.

Iron deficiency is the most widespread nutritional deficiency in the world. It is the most common cause of anaemia during pregnancy, especially in low and middle income countries, affecting an estimated 32 million pregnant women globally in 2011.

Studies suggest an association between prenatal anaemia and risk of premature (preterm) birth, but evidence on other birth outcomes is inconsistent. The effect of prenatal iron use on adverse birth outcomes is also unclear.

So researchers in the UK and US analysed the results of over 90 studies (a mix of randomised trials and cohort studies) of prenatal iron use and prenatal anaemia, involving nearly two million women.

Iron use increased a mother’s average haemoglobin levels compared with controls and significantly reduced the risk of anaemia.

There was no reduction in risk of preterm birth as a result of iron use. However analysis of cohort studies showed a significantly higher risk of low birth weight and preterm birth with anaemia in the first or second trimester of pregnancy.

Further analysis indicated that for every 10 mg increase in iron dose per day (up to 66 mg per day), risk of maternal anaemia was 12% lower, birth weight increased by 15 g and risk of low birth weight decreased by 3%.

No differences were seen in duration of iron use after adjusting for dose.

“Our findings suggest that use of iron in women during pregnancy may be used as a preventive strategy to improve maternal haematological status and birth weight,” say the authors. They call for “rigorous evaluation of the effectiveness of existing antenatal care programmes in high burden countries to identify gaps in policy and programme implementation.”

And they say future research should explore “feasible strategies of iron delivery” as well as “evaluation of the effectiveness of other strategies, such as fortification and dietary diversification.”

Study Information

Batool A Haider, Ibironke Olofin, Molin Wang, Donna Spiegelman, Majid Ezzati, Wafaie W Fawzi
Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis
British Medical Journal
2013 June
Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA

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