The quality of evidence is downgraded by study quality (unclear allocation concealment, blinding, incomplete outcome data, and selective reporting).
A Cochrane review [Abstract] 1 included 44 studies with a total of 43 274 subjects. 23 studies were conducted in countries that in 2011 had some malaria risk in parts of the country. There were significant heterogeneity across most prespecified outcomes. There was no clear difference in low birthweight babies (RR 0.84; 95% CI 0.69 to 1.03; 11 trials, n=17 613, low quality evidence) with iron supplements compared to controls. They appeared to deliver slightly heavier babies (mean difference (MD) 23g; 95% CI -3.02 to 50.51; 15 trials, n=18 590), but this was non-significant. There were no clear differences between groups for neonatal death or congenital anomalies. Maternal anaemia at term was reduced (RR 0.30; 95% C) 0.19 to 0.46; 14 trials, n=2199, low quality evidence). Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130 g/L during pregnancy, and at term.
A systematic review 2 included 12 supplementation trials. On the basis of 11 trials, routine maternal iron supplementation had inconsistent effects on rates of cesarean delivery, small size for gestational age, and low birthweight and no effect on maternal quality of life, gestational age, Apgar scores, preterm birth, or infant mortality. Maternal hematologic indices were improved, although not all were statistically significant. Less iron deficiency anemia at term was found (RR 0.29, 95% CI 0.17 to 0.49; 4 trials). Maternal iron supplementation did not affect infant iron status at 6 months. Harms were inconsistently reported.
A meta-analysis 3 investigated the association of iron biomarkers and dietary iron exposure with gestational diabetes mellitus (GDM). 33 studies (n=44 110) published in 2001-2017 were included. The standardized mean differences (SMD) in women who had GDM compared to pregnant women without were 0.25 µg/dL (95% CI 0.001 to 0.50) for iron, 1.54 ng/mL (0.56 to 2.53) for ferritin, 1.05% (0.02 to 2.08) for transferrin saturation, and 0.81 g/dL (0.40 to 1.22) for hemoglobin. Adjusted odds ratio for GDM were 1.58 (95% CI 1.20 to 2.08) for ferritin, 1.30 (1.01 to 1.67) for hemoglobin, and 1.48 (1.29 to 1.69) for dietary heme intake.
A case-control study 4 of 350 GDM cases and 349 non-GDM controls was conducted in participants from the Danish National Birth Cohort. Blood was collected at a mean ± SD gestational age of 9.4 ± 3.2 wk. Plasma biomarkers of iron stores, including ferritin and soluble transferrin receptor (sTfR), were measured. Logistic regression was used to estimate the OR of GDM associated with quintiles of plasma biomarkers of body iron stores, controlling for maternal age, family history of diabetes, exercise in pregnancy, parity, and prepregnancy body mass index (BMI).Plasma concentrations of both ferritin and sTfR in early pregnancy were significantly higher in GDM cases than in controls [means ± SDs: 80.6 ± 56.0 compared with 71.8 ± 50.1 μg/L (P = 0.03) and 1.5 ± 0.7 compared with 1.4 ± 0.6 mg/L (P = 0.002) for ferritin and sTfR, respectively]. Ferritin was positively and significantly associated with GDM risk even after adjustment for major risk factors of GDM, including prepregnancy BMI. ORs across increasing quintiles of ferritin were 1.00 (reference), 1.25 (95% CI 0.70 to 2.22), 1.89 (95% CI 1.06 to 3.37), 0.82 (95% CI 0.46 to 1.48), and 2.34 (95% CI 1.30 to 4.21) (P-linear trend = 0.02).
An overview of systematic reviews 5 summarized the evidence concerning oral iron-based interventions compared to placebo or no iron-based interventions to prevent critical outcomes in pregnancy or treat critical outcomes in the postpartum phase. Compared to placebo/no treatment, iron-based therapies reduced maternal anemia at term by 59% (RR 0.41, 95% CI 0.23 to 0.73; 7 trials, I² = 86%; moderate-quality evidence) and maternal iron deficiency anemia by 67% (RR 0.33, 95% CI 0.16 to 0.69; 7 trials, I² = 49%). There was no evidence of difference between iron-based therapies vs control in terms of side effects (RR 1.42, 95% CI 0.91 to 2.21), preterm delivery (13 studies: RR 0.93, 95% CI 0.84 to 1.03; low-quality evidence), low birthweight (RR 0.94, 95% CI 0.79 to 1.13; low-quality evidence) and infant mortality (RR 0.93, 0.72 to 1.20; low-quality evidence).
Date of latest search: 12 September 2019
Primary/Secondary Keywords