背景:首次怀孕前补充铁可以通过减少母亲贫血来改善母亲和婴儿的未来健康。铁补充剂可以,然而,增加疟疾感染,特别是在最容易感染的primigravidae中。其他利用铁的病原体的致病性也可能增加,引起炎症,导致不良分娩结局的风险增加。本文报告了布基纳法索在疟疾高流行地区进行的一项安全性试验得出的预先指定的二次分娩结局。该试验的主要结果调查了长期每周补充铁对非孕妇和孕妇的疟疾和生殖道感染的影响。
方法:双盲,随机对照试验。未产,主要是青春期女性,单独随机分组,每周接受60毫克元素铁和2.8毫克叶酸,或单独2.8毫克叶酸,继续为那些怀孕的人进行第一次产前检查。次要结果是超声测孕龄,胎儿生长,胎盘疟疾,绒毛膜羊膜炎和铁生物标志物。评估了季节性影响。分析是有意治疗。
结果:1959年妇女发生了478次怀孕:258/980名妇女分配了铁和叶酸,220/979名妇女仅分配了叶酸。首次产前检查时的疟疾患病率为53%(铁)和55%(对照)。铁组的平均出生体重较低111g(95%CI9:213g,P=0.033)。平均胎龄分别为264天(铁)和269天(对照)(P=0.012),37周为27.5%,而对照组为13.9%(adjRR=2.22;95%CI1.39-3.61),P<0.001)。三分之一的婴儿受到生长限制,但不同试验组的发病率没有差异.一半的胎盘有过去疟疾感染的证据。C-反应蛋白>5mg/l在出生前<37周时更常见(adjRR=2.06,95%CI1.04-4.10,P=0.034)。雨季早产发生率在铁臂中为约50%,在对照组中为<20%(P=0.001)。绒毛膜羊膜炎患病率在旱季达到高峰(P=0.046),各试验组没有差异(P=0.14)。
结论:在疟疾流行地区,对未产妇女长期每周补铁与首次妊娠早产风险较高相关。试用注册NCT01210040。2010年9月27日在Clinicaltrials.gov注册。
BACKGROUND: Iron supplementation before a first pregnancy may improve the future health of mother and baby by reducing maternal anaemia. Iron supplementation could, however, increase malaria infections, notably in primigravidae who are most susceptible. The pathogenicity of other iron-utilizing pathogens could also increase, causing inflammation leading to increased risk of adverse birth outcomes. This paper reports pre-specified secondary birth outcomes from a safety
trial in Burkina Faso in an area of high malaria endemicity. Primary outcomes from that
trial had investigated effects of long-term weekly iron supplementation on malaria and genital tract infections in non-pregnant and pregnant women.
METHODS: A double-blind, randomized controlled
trial. Nulliparous, mainly adolescent women, were individually randomized periconceptionally to receive weekly either 60 mg elemental iron and 2.8 mg folic acid, or 2.8 mg folic acid alone, continuing up to the first antenatal visit for those becoming pregnant. Secondary outcomes were ultrasound-dated gestational age, fetal growth, placental malaria, chorioamnionitis and iron biomarkers. Seasonal effects were assessed. Analysis was by intention to treat.
RESULTS: 478 pregnancies occurred to 1959 women: 258/980 women assigned iron and folic acid and 220/979 women assigned folic acid alone. Malaria prevalence at the first antenatal visit was 53% (iron) and 55% (controls). Mean birthweight was 111 g lower in the iron group (95% CI 9:213 g, P = 0.033). Mean gestational ages were 264 days (iron) and 269 days (controls) (P = 0.012), with 27.5% under 37 weeks compared to 13.9% in controls (adjRR = 2.22; 95% CI 1.39-3.61) P < 0.001). One-third of babies were growth restricted, but incidence did not differ by
trial arm. Half of placentae had evidence of past malaria infection. C-reactive protein > 5 mg/l was more common prior to births < 37 weeks (adjRR = 2.06, 95% CI 1.04-4.10, P = 0.034). Preterm birth incidence during the rainy season was ~ 50% in the iron arm and < 20% in controls (P = 0.001). Chorioamnionitis prevalence peaked in the dry season (P = 0.046), with no difference by trial arm (P = 0.14).
CONCLUSIONS: Long-term weekly iron supplementation given to nulliparous women in a malaria endemic area was associated with higher risk of preterm birth in their first pregnancy.
Trial Registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010.