Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands2School of Public Health and Community Development, Maseno University, Maseno, Kenya.
Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands3KIT Biomedical Research, Royal Tropical Institute, Amsterdam, the Netherlands.
JAMA. 2015 Sep 8;314(10):1009-20. doi: 10.1001/jama.2015.9496.
Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden.
To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes.
DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given.
Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum.
Primary outcome was maternal Plasmodium infection at birth. Predefined secondary outcomes were birth weight and gestational age at delivery, intrauterine growth, and maternal and infant iron status at 1 month after birth.
Among the 470 participating women, 40 women (22 iron, 18 placebo) were lost to follow-up or excluded at birth; 12 mothers were lost to follow-up postpartum (5 iron, 7 placebo). At baseline, 190 of 318 women (59.7%) were iron-deficient. In intention-to-treat analysis, comparison of women who received iron vs placebo, respectively, yielded the following results at birth: Plasmodium infection risk: 50.9% vs 52.1% (crude difference, -1.2%, 95% CI, -11.8% to 9.5%; P = .83); birth weight: 3202 g vs 3053 g (crude difference, 150 g, 95% CI, 56 to 244; P = .002); birth-weight-for-gestational-age z score: 0.52 vs 0.31 (crude difference, 0.21, 95% CI, -0.11 to 0.52; P = .20); and at 1 month after birth: maternal hemoglobin concentration: 12.89 g/dL vs 11.99 g/dL (crude difference, 0.90 g/dL, 95% CI, 0.61 to 1.19; P < .001); geometric mean maternal plasma ferritin concentration: 32.1 µg/L vs 14.4 µg/L (crude difference, 123.4%, 95% CI, 85.5% to 169.1%; P < .001); geometric mean neonatal plasma ferritin concentration: 163.0 µg/L vs 138.7 µg/L (crude difference, 17.5%, 95% CI, 2.4% to 34.8%; P = .02). Serious adverse events were reported for 9 and 12 women who received iron and placebo, respectively. There was no evidence that intervention effects on Plasmodium infection risk were modified by intermittent preventive treatment use.
Among rural Kenyan women with singleton pregnancies, administration of daily iron supplementation, compared with administration of placebo, resulted in no significant differences in overall maternal Plasmodium infection risk. Iron supplementation led to increased birth weight.
clinicaltrials.gov Identifier: NCT01308112.
贫血影响大多数非洲孕妇，主要是由于缺铁，但产前铁补充剂的健康益处不确定，并且可能会增加疟疾负担。
测量产前铁补充对产妇疟原虫感染风险、产妇铁状况和新生儿结局的影响。
设计、设置和参与者：2011 年 10 月至 2013 年 4 月，在肯尼亚农村地区进行的一项随机安慰剂对照试验，参与者为 470 名年龄在 15 至 45 岁之间、怀有单胎妊娠、孕龄 13 至 23 周、血红蛋白浓度为 9 g/dL 或更高的女性。所有女性在干预期间通过面粉强化剂每天摄入 5.7 毫克铁，并且给予常规间歇性预防治疗疟疾。
从随机分组到产后 1 个月，每天口服补充 60 毫克元素铁（富马酸亚铁，n = 237 名女性）或安慰剂（n = 233 名）。
主要结局是出生时产妇疟原虫感染。预先定义的次要结局是出生体重和分娩时的孕龄、宫内生长和产后 1 个月时产妇和婴儿的铁状况。
在 470 名参与的女性中，有 40 名女性（22 名铁剂，18 名安慰剂）失访或在分娩时被排除；产后有 12 名母亲失访（5 名铁剂，7 名安慰剂）。在基线时，190 名女性中有 318 名（59.7%）患有缺铁症。在意向治疗分析中，与安慰剂相比，分别接受铁剂和安慰剂的女性在出生时的结果如下：疟原虫感染风险：50.9%对 52.1%（粗差，-1.2%，95%CI，-11.8%至 9.5%；P = 0.83）；出生体重：3202 g 对 3053 g（粗差，150 g，95%CI，56 至 244；P = 0.002）；出生体重与胎龄的 z 评分：0.52 对 0.31（粗差，0.21，95%CI，-0.11 至 0.52；P = 0.20）；产后 1 个月时：产妇血红蛋白浓度：12.89 g/dL 对 11.99 g/dL（粗差，0.90 g/dL，95%CI，0.61 至 1.19；P < 0.001）；几何均数产妇血浆铁蛋白浓度：32.1 µg/L 对 14.4 µg/L（粗差，123.4%，95%CI，85.5%至 169.1%；P < 0.001）；几何均数新生儿血浆铁蛋白浓度：163.0 µg/L 对 138.7 µg/L（粗差，17.5%，95%CI，2.4%至 34.8%；P = 0.02）。接受铁剂和安慰剂的女性分别有 9 人和 12 人报告了严重不良事件。没有证据表明干预对疟原虫感染风险的影响因间歇性预防治疗的使用而改变。
在肯尼亚农村的怀有单胎妊娠的女性中，与安慰剂相比，给予铁补充剂并没有显著降低产妇整体疟原虫感染风险。铁补充剂会导致出生体重增加。
clinicaltrials.gov 标识符：NCT01308112。
