Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis.

BMJ. 2013 Jun 21;346:f3443. doi: 10.1136/bmj.f3443.
Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW; Nutrition Impact
Model Study Group (anaemia).

Comment in
    BMJ. 2013;347:f4399.

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
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.

PMCID: PMC3689887
PMID: 23794316  [PubMed - indexed for MEDLINE]