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Background: Malaria in pregnancy (MiP) is a major cause of fetal growth restriction and low birth weight in endemic areas of sub-Saharan Africa. Understanding of the impact of MiP on infant growth and infant risk of malaria or morbidity is poorly characterized. The objective of this study was to describe the impact of MIP on subsequent infant growth, malaria and morbidity. Methods: Between 2006 and 2009, 82 % (832/1018) of pregnant women with live-born singletons and ultrasound determined gestational age were enrolled in a prospective cohort with active weekly screening and treatment for malaria. Infants were followed monthly for growth and morbidity and received active monthly screening and treatment for malaria during their first year of life. Multivariate analyses were performed to analyse the association between malaria exposure during pregnancy and infants’ growth, malaria infections, diarrhoea episodes and acute respiratory infections. Results: Median time of infant follow-up was 12 months and infants born to a mother who had MiP were at increased risk of impaired height and weight gain (-2.71 cm, 95 % CI -4.17 to -1.25 and -0.42 kg, 95 % CI -0.76 to -0.08 at 12 months for >1 MiP compared to no MiP) and of malaria infection (relative risk 10.42, 95 % CI 2.64-41.10 for infants born to mothers with placental malaria). The risks of infant growth restriction and infant malaria infection were maximal when maternal malaria occurred in the 12 weeks prior to delivery. Recurrent MiP was also associated with acute respiratory infection (RR 1.96, 95 % CI 1.25-3.06) and diarrhoea during infancy (RR 1.93, 95 % CI 1.02-3.66). Conclusion: This study shows that despite frequent active screening and prompt treatment of MiP, impaired growth and an increased risk of malaria and non-malaria infections can be observed in the infants. Effective preventive measures in pregnancy remain a research priority. This study was registered with ClinicalTrials.gov, number NCT00495508.
This mother–baby cohort study was conducted in Mbarara district, southwestern Uganda. This predominantly rural area lies at an altitude of about 1500 m above sea level and has a tropical climate with a bimodal rainfall pattern averaging 1200 mm per annum in September–January and March–May. Malaria transmission was considered as mesoendemic although significant heterogeneity has been observed recently [25, 26]. The study design was a prospective cohort of 1218 pregnant women of estimated GA ≥13 weeks with a nested clinical trial conducted between October 2006 and May 2009, in which 304 pregnant women were enrolled [27]. All women with a positive blood smear were invited to participate in a study comparing the efficacy and tolerance of artemether–lumefantrine (AL) with oral quinine for the treatment of uncomplicated falciparum malaria of whom 304 met the criteria and consented [27]. Newborns of mothers enrolled in the cohort were included in a birth cohort and actively followed until 12 months. Only live-born singletons with accurate GA estimation were included in this analysis. At enrolment, a comprehensive assessment of the mothers was performed that included the collection of information on their demographic, socioeconomic, medical and obstetric characteristics, a clinical and obstetric examination, an ultrasound evaluation, blood smear and haemoglobin measurements. An estimation of GA by ultrasound for foetal biometry using biparietal diameter and femur length was performed between 16 and 22 weeks of pregnancy [28]. After the initial assessment, mothers were followed every week. Malaria infection was systematically screened using a Paracheck Pf® (Orchid, Goa, India) rapid diagnostic test (RDT) and confirmed with a blood smear test. Women in the cohort received standard supervised IPT with two doses of sulfadoxine-pyrimethamine (SP) given at intervals of one month or more during the second and third trimesters as recommended by national guidelines. IPT was not given to the women who receive anti-malarial treatment (quinine or AL). All treatments were provided free-of-charge. At delivery, blood smears were obtained from the mother, the placenta, cord and from the newborn to verify the presence of malaria infection. Newborns were weighed to the nearest 10 g using a SECA mechanical type scale and received an initial standardized physical examination by a medical officer. Length was measured using a Stadiometer. After the initial evaluation, infants were seen every month or more frequently if required until 12 months. At each visit, anthropometric characteristics were measured once, malaria infection was screened with a Paracheck® RDT and treated with AL, and a medical examination by a paediatrician was performed. Morbidity definitions in infancy were based on national guidelines [29]. Thick and thin blood smears were prepared and stained with Giemsa. Parasitaemia was calculated by counting parasites against 200 white blood cells. Placenta smears were taken by incising a fresh placenta on the maternal surface halfway between the cord and the periphery. HIV testing and treatment was proposed for all women and performed according to the national guidelines. Small-for-GA (SGA) was defined as a birth weight less than the 10th percentile of sex-specific birth weight-for-GA [30]. Peripheral malaria infection was defined as the occurrence of a positive peripheral blood smear or rapid diagnostic test. Placental malaria was defined as the detection of any parasite in a placental blood smear by microscopy. The change in weight and height between birth and 12 months (weight and height gain) were analysed using a linear model. Missing data at 12 months because of irregular visit schedules (n = 150/794) were imputed and confidence intervals were adapted using Rubin’s formula [31, 32]. The other outcomes considered in this analysis were the time to the first malaria infection in infancy (defined by a positive RDT), the time to first diarrhoea episode and the time to first acute respiratory infection. Their association with the explanatory variables was assessed with a Poisson model [33, 34]. Two categories of explanatory variables were considered in the analysis: This study was powered to assess the primary outcome and not for this secondary analysis. All analyses were performed using the open source statistical software R [36]. The study was approved by the institutional review boards of Mbarara University of Science and Technology, Uganda National Council for Science and Technology, and France’s “Comité de protection des personnes—Ile-de-France XI”. This study was registered with ClinicalTrials.gov, number {“type”:”clinical-trial”,”attrs”:{“text”:”NCT00495508″,”term_id”:”NCT00495508″}}NCT00495508. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
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