Barry Amadou, Dang Lauren, Sidibe Youssoufa, Issiaka Djibrilla, Gaoussou Santara, Hu Zonghui, Dicko Yahia, Mahamar Almahamoudou, Attaher Oumar, Diarra Bacary S, Keita Sekouba, Dicko Alassane, Duffy Patrick E, Fried Michal
Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
JAMA Netw Open. 2025 Sep 2;8(9):e2532179. doi: 10.1001/jamanetworkopen.2025.32179.
Pregnancy malaria (PM) is associated with adverse pregnancy outcomes such as stillbirth, early neonatal death, preterm delivery (PTD), and low birthweight. PM also increases the risk of malaria infection in infants. However, it is unknown whether PTD modifies the risk of malaria infection during early childhood.
To investigate the association of PM and PTD with child susceptibility to malaria infection and disease.
DESIGN, SETTING, AND PARTICIPANTS: Pregnant women were enrolled between November 23, 2010, and December 9, 2014, into an observational longitudinal cohort study of mother-child pairs in Ouélessébougou, Mali, an area of high seasonal malaria transmission. Follow-up was completed through pregnancy. Children were enrolled at birth and followed up from January 21, 2011, to July 31, 2016, for as long as 5 years with monthly clinical visits during the malaria transmission season and every 2 months during the dry season. Data were analyzed from November 4, 2024, to July 15, 2025.
PM and PTD.
Study end points included Plasmodium falciparum infection, clinical malaria, and severe malaria infections. Malaria diagnosis and clinical data were collected during scheduled examinations and unscheduled sick visits. Cox proportional hazards models were used to analyze whether hazards of first malaria infection and first clinical malaria infection were associated with PM and PTD. Associations between the incidence rate of parasitemia and risk factors (eg, maternal infection history, PTD) were estimated using negative binomial models. Cox proportional hazards and negative binomial models with an interaction term among PTD, pregnancy malaria, and gravidity were used to evaluate associations within strata of the 3 covariates.
In 1679 children included in adjusted models (848 female [50.5%] and 831 male [49.5%]), 760 (45.3%) were born during the malaria transmission season and 96 (5.7%) were born preterm. Children were followed up for a mean (SD) of 25.8 (16.1) months. PM was associated with an increased hazard of first malaria infection and first clinical malaria infection in children of women of all gravidities, while PTD (vs full-term delivery) was associated with increased hazard of first malaria infection (hazard ratio, 1.76; 95% CI, 1.05-2.95; P = .03) in offspring of multigravid women only. Further, the hazard ratio of first parasitemia for preterm compared with full-term offspring was 2.17 (95% CI, 1.25-3.75; P = .006) and 3.63 (95% CI, 1.90-5.93; P < .001) in offspring of uninfected secundigravida and multigravida women, respectively. The parasitemia infection incidence rate ratio for PTD was 2.74 (95% CI, 1.80-4.18) in offspring of uninfected multigravida women.
In this cohort study of young children, the association between PTD and the hazard of malaria varied based on maternal gravidity and maternal infection history during pregnancy. This information could be used to evaluate the health effects of active monitoring of P falciparum infection or adherence to malaria chemoprevention in children born preterm.
妊娠疟疾（PM）与不良妊娠结局相关，如死产、早期新生儿死亡、早产（PTD）和低出生体重。PM还会增加婴儿感染疟疾的风险。然而，尚不清楚早产是否会改变幼儿期疟疾感染的风险。
研究妊娠疟疾和早产与儿童对疟疾感染及疾病易感性之间的关联。
设计、地点和参与者：2010年11月23日至2014年12月9日期间，招募了孕妇，对马里韦莱塞布古的母婴对进行观察性纵向队列研究，该地区季节性疟疾传播率高。随访贯穿整个孕期。儿童在出生时入组，从2011年1月21日至2016年7月31日进行随访，长达5年，在疟疾传播季节每月进行临床访视，旱季每2个月进行一次访视。数据分析时间为2024年11月4日至2025年7月15日。
妊娠疟疾和早产。
研究终点包括恶性疟原虫感染、临床疟疾和严重疟疾感染。在定期检查和不定期就诊时收集疟疾诊断和临床数据。使用Cox比例风险模型分析首次疟疾感染和首次临床疟疾感染的风险是否与妊娠疟疾和早产相关。使用负二项模型估计寄生虫血症发病率与危险因素（如母亲感染史、早产）之间的关联。使用带有早产、妊娠疟疾和妊娠次数交互项的Cox比例风险模型和负二项模型评估这3个协变量分层内的关联。
在纳入调整模型的1679名儿童中（848名女性[50.5%]和831名男性[49.5%]），760名（45.3%）在疟疾传播季节出生，96名（5.7%）早产。儿童的平均（标准差）随访时间为25.8（16.1）个月。妊娠疟疾与所有妊娠次数女性的子女首次疟疾感染和首次临床疟疾感染风险增加相关，而仅多产妇的子女中，早产（与足月分娩相比）与首次疟疾感染风险增加相关（风险比，1.76；95%置信区间，1.05 - 2.95；P = 0.03）。此外，未感染的经产妇和多产妇的子女中，早产与足月产相比首次寄生虫血症的风险比分别为2.17（95%置信区间，1.25 - 3.75；P = 0.006）和3.63（95%置信区间，1.90 - 5.93；P < 0.001）。未感染的多产妇子女中早产的寄生虫血症感染发病率比为2.74（95%置信区间，1.80 - 4.18）。
在这项针对幼儿的队列研究中，早产与疟疾风险之间的关联因母亲妊娠次数和孕期母亲感染史而异。这些信息可用于评估对早产儿童积极监测恶性疟原虫感染或坚持疟疾化学预防的健康效果。
