Research Article: Malaria, malnutrition, and birthweight: A meta-analysis using individual participant data

Date Published: August 8, 2017

Publisher: Public Library of Science

Author(s): Jordan E. Cates, Holger W. Unger, Valerie Briand, Nadine Fievet, Innocent Valea, Halidou Tinto, Umberto D’Alessandro, Sarah H. Landis, Seth Adu-Afarwuah, Kathryn G. Dewey, Feiko O. ter Kuile, Meghna Desai, Stephanie Dellicour, Peter Ouma, Julie Gutman, Martina Oneko, Laurence Slutsker, Dianne J. Terlouw, Simon Kariuki, John Ayisi, Mwayiwawo Madanitsa, Victor Mwapasa, Per Ashorn, Kenneth Maleta, Ivo Mueller, Danielle Stanisic, Christentze Schmiegelow, John P. A. Lusingu, Anna Maria van Eijk, Melissa Bauserman, Linda Adair, Stephen R. Cole, Daniel Westreich, Steven Meshnick, Stephen Rogerson, Lorenz von Seidlein

Abstract: BackgroundFour studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population.Methods and findingsWe evaluated the interaction between maternal malaria infection and maternal anthropometric status on the risk of LBW using pooled data from 14,633 pregnancies from 13 studies (6 cohort studies and 7 randomized controlled trials) conducted in Africa and the Western Pacific from 1996–2015. Studies were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability of treatment-weighted linear and log-binomial regression models and pooled using a random-effects model. The adjusted risk of delivering a baby with LBW was 8.8% among women with malaria infection at antenatal enrollment compared to 7.7% among uninfected women (adjusted risk ratio [aRR] 1.14 [95% confidence interval (CI): 0.91, 1.42]; N = 13,613), 10.5% among women with malaria infection at delivery compared to 7.9% among uninfected women (aRR 1.32 [95% CI: 1.08, 1.62]; N = 11,826), and 15.3% among women with low mid-upper arm circumference (MUAC <23 cm) at enrollment compared to 9.5% among women with MUAC ≥ 23 cm (aRR 1.60 [95% CI: 1.36, 1.87]; N = 9,008). The risk of delivering a baby with LBW was 17.8% among women with both malaria infection and low MUAC at enrollment compared to 8.4% among uninfected women with MUAC ≥ 23 cm (joint aRR 2.13 [95% CI: 1.21, 3.73]; N = 8,152). There was no evidence of synergism (i.e., excess risk due to interaction) between malaria infection and MUAC on the multiplicative (p = 0.5) or additive scale (p = 0.9). Results were similar using body mass index (BMI) as an anthropometric indicator of nutritional status. Meta-regression results indicated that there may be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies.ConclusionsPregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only 1 risk factor or none, but malaria and malnutrition do not act synergistically.

Partial Text: Annually, over 20 million infants are born low birthweight (LBW; <2,500 g), predominantly in low- and middle-income countries (LMICs) [1]. LBW can have negative impacts on neonatal mortality and childhood neurological, metabolic, and physical development [2]. The World Health Organization (WHO) has set a Global Nutrition Target of 30% reduction in LBW by 2025 [1]. Using a convenience sample approach, a total of 18 studies were considered for inclusion by the time of our inclusion cutoff date (1 January 2016), of which 13 were included in the pooled analysis (Fig 1). We excluded 5 studies: 2 studies did not assess malaria at antenatal enrollment [42,43], 1 study had data that were not yet available for inclusion [44], 1 recruited women comparatively late in pregnancy [10], and 1 had not directly measured the number of sulfadoxine-pyrimethamine (SP) doses given for IPTp [45]. Following the cutoff date, 5 further studies were identified, of which 4 could be eligible with a collective sample size of 3,528 pregnant women (S3 Table) [46–50]. Using the large M3 initiative dataset, we found that pregnant women who were both infected with malaria and malnourished were at greater risk of LBW and reduced mean BW compared to their uninfected, well-nourished counterparts, but there was overall no convincing evidence of synergism, i.e., excess risk due to interaction. This finding was consistent for both time points of malaria diagnosis (at enrollment and delivery) and both definitions of malnutrition (MUAC and BMI). This suggests that malaria infection and malnutrition largely act independently to influence fetal growth and gestational length. Source: http://doi.org/10.1371/journal.pmed.1002373

 

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