BACKGROUND Low birth weight (LBW) and preterm birth (PTB) are major contributors to infant mortality and chronic childhood morbidity. Understanding factors that contribute to or protect against these adverse birth outcomes is an important global health priority. Anaemia and iron deficiency are common in malaria-endemic regions, but there are concerns regarding the value of iron supplementation among pregnant women in malaria-endemic areas due to reports that iron supplementation may increase the risk of malaria. There is a lack of evidence on the impact of iron deficiency on pregnancy outcomes in malaria-endemic regions. METHODS We determined iron deficiency in a cohort of 279 pregnant women in a malaria-endemic area of Papua New Guinea. Associations with birth weight, LBW and PTB were estimated using linear and logistic regression. A causal model using sequential mediation analyses was constructed to assess the association between iron deficiency and LBW, either independently or mediated through malaria and/or anaemia. RESULTS Iron deficiency in pregnant women was common (71% at enrolment) and associated with higher mean birth weights (230 g; 95% confidence interval, CI 118, 514; p < 0.001), and reduced odds of LBW (adjusted odds ratio, aOR = 0.32; 95% CI 0.16, 0.64; p = 0.001) and PTB (aOR = 0.57; 95% CI 0.30, 1.09; p = 0.089). Magnitudes of effect were greatest in primigravidae (birth weight 351 g; 95% CI 188, 514; p < 0.001; LBW aOR 0.26; 95% CI 0.10, 0.66; p = 0.005; PTB aOR = 0.39, 95% CI 0.16, 0.97; p = 0.042). Sequential mediation analyses indicated that the protective association of iron deficiency on LBW was mainly mediated through mechanisms independent of malaria or anaemia. CONCLUSIONS Iron deficiency was associated with substantially reduced odds of LBW predominantly through malaria-independent protective mechanisms, which has substantial implications for understanding risks for poor pregnancy outcomes and evaluating the benefit of iron supplementation in pregnancy. This study is the first longitudinal study to demonstrate a temporal relationship between antenatal iron deficiency and improved birth outcomes. These findings suggest that iron supplementation needs to be integrated with other strategies to prevent or treat infections and undernutrition in pregnancy to achieve substantial improvements in birth outcomes.

中文翻译：

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在一项纵向队列研究中，妊娠期间铁缺乏症与疟疾流行地区不良出生结局的风险降低相关。

背景技术低出生体重（LBW）和早产（PTB）是婴儿死亡率和儿童慢性发病的主要因素。了解促成或预防这些不良分娩结果的因素是全球卫生的重要重点。贫血和缺铁在疟疾流行地区很普遍，但是由于有报道称补铁可能增加患疟疾的风险，因此在疟疾流行地区孕妇对补铁的价值存在担忧。缺乏铁缺乏对疟疾流行地区妊娠结局的影响的证据。方法我们在巴布亚新几内亚的疟疾流行地区的279名孕妇中确定了铁缺乏症。使用线性和逻辑回归来估计出生体重，LBW和PTB的相关性。构建了使用顺序介导分析的因果模型，以独立或通过疟疾和/或贫血介导来评估铁缺乏与LBW之间的关联。结果孕妇铁缺乏症很普遍（入学时为71％），并且与平均出生体重较高（230克； 95％置信区间，CI 118、514； p <0.001）相关，LBW的几率降低（调整后的几率， aOR = 0.32; 95％CI 0.16，0.64; p = 0.001）和PTB（aOR = 0.57; 95％CI 0.30，1.09; p = 0.089）。初产妇的影响最大（出生体重351 g; 95％CI 188，514; p <0.001; LBW aOR 0.26; 95％CI 0.10，0.66; p = 0.005; PTB aOR = 0.39，95％CI 0.16，0.97 ； p = 0.042）。顺序调解分析表明，铁缺乏对LBW的保护性关联主要是通过与疟疾或贫血无关的机制介导的。结论铁缺乏主要通过与疟疾无关的保护机制，大大降低了LBW几率，这对于理解不良妊娠结局的风险和评估妊娠补充铁的益处具有重大意义。这项研究是首次纵向研究，以证明产前铁缺乏与改善出生结局之间存在时间关系。这些发现表明，补充铁需要与其他预防或治疗感染和营养不良的策略相结合，以实现出生结局的显着改善。结论铁缺乏主要通过与疟疾无关的保护机制，大大降低了LBW几率，这对于理解不良妊娠结局的风险和评估妊娠补充铁的益处具有重大意义。这项研究是第一个纵向研究，以证明产前铁缺乏与改善出生结局之间存在时间关系。这些发现表明，补充铁需要与其他策略结合起来，以预防或治疗妊娠期感染和营养不良，以实现出生结局的实质性改善。结论铁缺乏主要通过与疟疾无关的保护机制，大大降低了LBW几率，这对于理解不良妊娠结局的风险和评估妊娠补充铁的益处具有重大意义。这项研究是首次纵向研究，以证明产前铁缺乏与改善出生结局之间存在时间关系。这些发现表明，补充铁需要与其他策略结合起来，以预防或治疗妊娠期感染和营养不良，以实现出生结局的实质性改善。这对于理解不良妊娠结局的风险以及评估孕期补充铁的益处具有重大意义。这项研究是首次纵向研究，以证明产前铁缺乏与改善出生结局之间存在时间关系。这些发现表明，补充铁需要与其他策略结合起来，以预防或治疗妊娠期感染和营养不良，以实现出生结局的实质性改善。这对于理解不良妊娠结局的风险以及评估孕期补充铁的益处具有重大意义。这项研究是第一个纵向研究，以证明产前铁缺乏与改善出生结局之间存在时间关系。这些发现表明，补充铁需要与其他预防或治疗感染和营养不良的策略相结合，以实现出生结局的显着改善。