Maternal malaria and preterm birth linked to higher infant malaria risk

Maternal malaria and preterm birth linked to higher infant malaria risk | Image Credit: © jarun011 - © jarun011 - stock.adobe.com.

Data published in JAMA Network Open has highlighted variations in the link between preterm delivery (PTD) and hazard of malaria based on maternal gravidity and infection history during pregnancy.¹

Malaria disease is most common in children aged under 5 years.² Additionally, acquired immunity toward malaria may lessen in women during pregnancy, making infection more likely.¹ Adverse outcomes such as PTD, small for gestational age neonate, stillbirth, and early neonatal death are more likely in women with pregnancy malaria (PM).

“Several studies have reported that PM modifies the risk of malaria infection in infants. In a longitudinal study in Tanzania, PM at delivery was associated with a shorter time to first infection in offspring,” wrote investigators.

Methods of malaria detection

The study was conducted to determine the impact of child susceptibility to malaria on the link between PM and PTD. Participants included pregnant women aged 15 to 45 years between November 23, 2010, and December 9, 2014, without chronic or debilitating disease.

At enrollment, investigators collected patient blood samples to screen for malaria. Most of the study population underwent transonographic examinations to determine gestational age. Offspring follow-up occurred until 5 years of age and included monthly visits during the malaria transmission season and every 2 months during the dry season.

During visits, children underwent clinical examination and blood smear microscopy for malaria diagnosis. The presence of parasites in the sample or detected in DNA by nested polymerase chain reaction analysis indicated maternal infection, while offspring infection was based on fever and parasites detected by blood smear microscopy.

Cases of severe malaria were also reported, defined as parasite detection alongside either coma, 2 or more convulsions in 24 hours, prostration, hemoglobin level under 6 mg/dL, or respiratory distress. Investigators defined PTD as viable birth under 37-weeks’ gestation.

Rates of offspring infection

There were 1687 mother-child dyads included in the final analysis, with a mean maternal age of 24.2 years. Of mothers, 66.9% presented with infection during pregnancy and 5.7% underwent PTD. Birth during the malaria transmission season was reported in 45.3% of offspring.

Infection with P falciparum was reported in 46% of offspring by the age of 1 year, and 83% by the age of 3 years. In offspring of PM-positive mothers, the median time to infection was 49.9 weeks, vs 80.9 weeks in offspring of PM-negative mothers.

A 1.56-fold increased risk of instantaneous first P falciparum infection was reported in offspring of PM-positive mothers vs PM-negative mothers. In subanalyses stratified by gravidity, the odds of infection were increased in offspring of PM-positive mothers of all gravidities.

Children born to PM-positive vs PM-negative primigravid women presented with a significantly increased risk of first malaria infection, with an adjusted hazard ratio (aHR) of 1.86. Increased risks were also found for offspring of secundigravid and multigravida women, with aHRs of 1.40 and 1.54, respectively.

Role of preterm delivery

PTD was linked to a 1.12-fold increased risk of infection vs full-term birth. While this was not a significant association, the risk from PTD in multigravida women vs full-term was increased 1.76-fold, indicating statistical significance.

Overall, the data indicated increased child susceptibility to malaria in early life from maternal infection during pregnancy. Additionally, the link for PTD with susceptibility was only found in offspring of uninfected multigravid women.

“The parity-dependent response to PTD remains to be further explored in a larger study sample with monitoring for immune cell profiles,” wrote investigators.

References

1. Barry A, Dang L, Sidibe Y, et al. Preterm birth and malaria susceptibility in offspring of uninfected multigravid women. JAMA Netw Open. 2025;8(9):e2532179. doi:10.1001/jamanetworkopen.2025.32179
2. Gonçalves BPFM, Duffy PE. Malaria pathogenesis. In: Gaur DCC, Chauhan VS, eds.Advances in Malaria Research. John Wiley & Sons Inc; 2017:427-464.