Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study

Abstract

Background: During early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks' gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction.

Methods: Data were analysed from 548 antenatal visits after 20 weeks' gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction.

Results: There were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia.

Conclusions: Early pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk of intrauterine growth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy.

Figure 1

Time plot of mean uterine and umbilical artery resistance index against gestational age. Population average smoothed trend line (in black) (n = 128, with 544 visits). Kinshasa, Democratic Republic of Congo, 2005–2006. A. Uterine artery resistance index against gestational age in weeks. B. Umbilical artery resistance index against gestational age in weeks.

Figure 2

Population average growth curves for uterine artery resistance index by early pregnancy malaria parasitaemia exposure. Kinshasa, Democratic Republic of Congo, 2005–2006. A. The unadjusted effect of early pregnancy malaria parasitaemia on mean uterine artery resistance index (n = 547 visits). B. The adjusted effect of early pregnancy malaria parasitaemia on mean uterine artery resistance index by maternal mid-upper arm circumference (MUAC). Model adjusted for gravidity and foetal sex; product interaction term (early pregnancy malaria parasitaemia * low MUAC) -2LL test p = 0.026, with 1 df (n = 544 visits). The overall standard deviation for uterine artery resistance index was 0.089.

Figure 3

Population average growth curves for umbilical artery resistance index by early pregnancy malaria parasitaemia exposure. Kinshasa, Democratic Republic of Congo, 2005–2006. A. The unadjusted effect of early pregnancy malaria parasitaemia on umbilical artery resistance index (n = 547 visits). B. The adjusted effect of early pregnancy malaria parasitaemia on umbilical artery resistance index by gravidity. Model adjusted for foetal sex and low education; interaction terms: (early pregnancy malaria parasitaemia * gestational age in weeks) -2LL test p = 0.025; (early pregnancy malaria parasitaemia * primigravidae) -2LL test p = 0.025, with 1 df (n = 540 visits). The overall standard deviation for UA RI was 0.089.