Influence of the number and timing of malaria episodes during pregnancy on prematurity and small for gestational age in an area of low malaria transmission

Background: Most evidence on the association between malaria in pregnancy and adverse pregnancy outcomes focuses on falciparum malaria detected at birth. We assessed the association between the number and timing of falciparum and vivax malaria episodes during pregnancy on small for gestational age (SGA) and preterm birth. Methods: We analysed observational data collected from antenatal clinics on the Thailand-Myanmar border (1986 to 2015). We assessed the effects of the total number of malaria episodes in pregnancy on SGA, and the effects of malaria in pregnancy on SGA, very preterm birth, and late preterm birth, by the gestation time of malaria detection and treatment using logistic regression models with time-dependent malaria variables (monthly intervals). WHO definitions of very preterm birth (≥28 and <32), late preterm birth (≥32 and <37) weeks and international SGA standards were used. Results: Of 50,060 pregnant women followed, 8221 (16%) had malaria during their pregnancy. Of the 50,060 newborns, 10148 (20%) were SGA, 540 (1%) were very preterm, 4331 (9%) were late preterm. The rates of falciparum and vivax malaria were highest at 6 and 5 weeks’ gestation, respectively. The odds of SGA increased linearly by 1.15-fold (95% CI: 1.10, 1.20) and 1.25-fold (1.20, 1.30) per episode of falciparum and vivax malaria, respectively. Falciparum malaria at any gestation period after 12-16 weeks, and vivax malaria after 20-24 weeks, were associated with SGA (falciparum OR range: 1.19 to 1.49 [p range: <0.001 to 0.047]; vivax OR range: 1.25 to 1.48 [p range: <0.001 to 0.011]). Falciparum malaria at any gestation period after 24-28 weeks was associated with either very or late preterm birth (OR range: 1.44 to 2.53; p range: <0.001 to 0.001). Vivax malaria at 24-28 weeks was associated with very preterm birth (OR: 1.79 [1.11, 2.90]), and vivax malaria at 28-32 weeks was associated with late preterm birth (OR: 1.23 [1.01, 1.50]). Many of these associations held for asymptomatic malaria. Conclusions: Protection against malaria should be started as early as possible in pregnancy. Only malaria control and elimination efforts in the general population can avert the adverse consequences associated with treated asymptomatic malaria in pregnancy.