Skip to main content
Top
Published in: Malaria Journal 1/2016

Open Access 01-12-2016 | Research

Timing of malaria in pregnancy and impact on infant growth and morbidity: a cohort study in Uganda

Authors: Pierre De Beaudrap, Eleanor Turyakira, Carolyn Nabasumba, Benon Tumwebaze, Patrice Piola, Yap Boum II, Rose McGready

Published in: Malaria Journal | Issue 1/2016

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
2.
go back to reference Menendez C, Ordi J, Ismail MR, Ventura PJ, Aponte JJ, Kahigwa E, et al. The impact of placental malaria on gestational age and birth weight. J Infect Dis. 2000;181:1740–5.CrossRefPubMed Menendez C, Ordi J, Ismail MR, Ventura PJ, Aponte JJ, Kahigwa E, et al. The impact of placental malaria on gestational age and birth weight. J Infect Dis. 2000;181:1740–5.CrossRefPubMed
3.
go back to reference Luxemburger C, McGready R, Kham A, Morison L, Cho T, Chongsuphajaisiddhi T, et al. Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission. Am J Epidemiol. 2001;154:459–65.CrossRefPubMed Luxemburger C, McGready R, Kham A, Morison L, Cho T, Chongsuphajaisiddhi T, et al. Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission. Am J Epidemiol. 2001;154:459–65.CrossRefPubMed
4.
go back to reference Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, et al. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007;7:93–104.CrossRefPubMed Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, et al. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007;7:93–104.CrossRefPubMed
5.
go back to reference Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg. 2001;64:28–35.PubMed Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg. 2001;64:28–35.PubMed
6.
go back to reference Kalanda BF, van Buuren S, Verhoeff FH, Brabin BJ. Catch-up growth in Malawian babies, a longitudinal study of normal and low birthweight babies born in a malarious endemic area. Early Hum Dev. 2005;81:841–50.CrossRefPubMed Kalanda BF, van Buuren S, Verhoeff FH, Brabin BJ. Catch-up growth in Malawian babies, a longitudinal study of normal and low birthweight babies born in a malarious endemic area. Early Hum Dev. 2005;81:841–50.CrossRefPubMed
7.
go back to reference Walther B, Miles DJ, Crozier S, Waight P, Palmero MS, Ojuola O, et al. Placental malaria is associated with reduced early life weight development of affected children independent of low birth weight. Malar J. 2010;9:16.PubMedCentralCrossRefPubMed Walther B, Miles DJ, Crozier S, Waight P, Palmero MS, Ojuola O, et al. Placental malaria is associated with reduced early life weight development of affected children independent of low birth weight. Malar J. 2010;9:16.PubMedCentralCrossRefPubMed
8.
go back to reference Le Hesran JY, Cot M, Personne P, Fievet N, Dubois B, Beyeme M, et al. Maternal placental infection with Plasmodium falciparum and malaria morbidity during the first 2 years of life. Am J Epidemiol. 1997;146:826–31.CrossRefPubMed Le Hesran JY, Cot M, Personne P, Fievet N, Dubois B, Beyeme M, et al. Maternal placental infection with Plasmodium falciparum and malaria morbidity during the first 2 years of life. Am J Epidemiol. 1997;146:826–31.CrossRefPubMed
9.
go back to reference Schwarz NG, Adegnika AA, Breitling LP, Gabor J, Agnandji ST, Newman RD, et al. Placental malaria increases malaria risk in the first 30 months of life. Clin Infect Dis. 2008;47:1017–25.CrossRefPubMed Schwarz NG, Adegnika AA, Breitling LP, Gabor J, Agnandji ST, Newman RD, et al. Placental malaria increases malaria risk in the first 30 months of life. Clin Infect Dis. 2008;47:1017–25.CrossRefPubMed
10.
go back to reference Le Port A, Watier L, Cottrell G, Ouedraogo S, Dechavanne C, Pierrat C, et al. Infections in infants during the first 12 months of life: role of placental malaria and environmental factors. PLoS ONE. 2011;6:e27516.PubMedCentralCrossRefPubMed Le Port A, Watier L, Cottrell G, Ouedraogo S, Dechavanne C, Pierrat C, et al. Infections in infants during the first 12 months of life: role of placental malaria and environmental factors. PLoS ONE. 2011;6:e27516.PubMedCentralCrossRefPubMed
11.
go back to reference Mutabingwa TK, Bolla MC, Li JL, Domingo GJ, Li X, Fried M, et al. Maternal malaria and gravidity interact to modify infant susceptibility to malaria. PLoS Med. 2005;2:e407.PubMedCentralCrossRefPubMed Mutabingwa TK, Bolla MC, Li JL, Domingo GJ, Li X, Fried M, et al. Maternal malaria and gravidity interact to modify infant susceptibility to malaria. PLoS Med. 2005;2:e407.PubMedCentralCrossRefPubMed
12.
go back to reference Asante KP, Owusu-Agyei S, Cairns M, Dodoo D, Boamah EA, Gyasi R, et al. Placental malaria and the risk of malaria in infants in a high malaria transmission area in ghana: a prospective cohort study. J Infect Dis. 2013;208:1504–13.PubMedCentralCrossRefPubMed Asante KP, Owusu-Agyei S, Cairns M, Dodoo D, Boamah EA, Gyasi R, et al. Placental malaria and the risk of malaria in infants in a high malaria transmission area in ghana: a prospective cohort study. J Infect Dis. 2013;208:1504–13.PubMedCentralCrossRefPubMed
13.
go back to reference Bardaji A, Sigauque B, Sanz S, Maixenchs M, Ordi J, Aponte JJ, et al. Impact of malaria at the end of pregnancy on infant mortality and morbidity. J Infect Dis. 2011;203:691–9.PubMedCentralCrossRefPubMed Bardaji A, Sigauque B, Sanz S, Maixenchs M, Ordi J, Aponte JJ, et al. Impact of malaria at the end of pregnancy on infant mortality and morbidity. J Infect Dis. 2011;203:691–9.PubMedCentralCrossRefPubMed
14.
go back to reference Borgella S, Fievet N, Huynh BT, Ibitokou S, Hounguevou G, Affedjou J, et al. Impact of pregnancy-associated malaria on infant malaria infection in southern Benin. PLoS ONE. 2013;8:e80624.PubMedCentralCrossRefPubMed Borgella S, Fievet N, Huynh BT, Ibitokou S, Hounguevou G, Affedjou J, et al. Impact of pregnancy-associated malaria on infant malaria infection in southern Benin. PLoS ONE. 2013;8:e80624.PubMedCentralCrossRefPubMed
15.
go back to reference Rachas A, Le Port A, Cottrell G, Guerra J, Choudat I, Bouscaillou J, et al. Placental malaria is associated with increased risk of nonmalaria infection during the first 18 months of life in a Beninese population. Clin Infect Dis. 2012;55:672–8.CrossRefPubMed Rachas A, Le Port A, Cottrell G, Guerra J, Choudat I, Bouscaillou J, et al. Placental malaria is associated with increased risk of nonmalaria infection during the first 18 months of life in a Beninese population. Clin Infect Dis. 2012;55:672–8.CrossRefPubMed
16.
go back to reference McCormick MC. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med. 1985;312:82–90.CrossRefPubMed McCormick MC. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med. 1985;312:82–90.CrossRefPubMed
17.
go back to reference McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med. 1999;340:1234–8.CrossRefPubMed McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med. 1999;340:1234–8.CrossRefPubMed
18.
go back to reference Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Broadhead RL. Malaria in pregnancy and its consequences for the infant in rural Malawi. Ann Trop Med Parasitol. 1999;93(Suppl 1):S25–33.CrossRefPubMed Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Broadhead RL. Malaria in pregnancy and its consequences for the infant in rural Malawi. Ann Trop Med Parasitol. 1999;93(Suppl 1):S25–33.CrossRefPubMed
19.
go back to reference Katz J, Lee AC, Kozuki N, Lawn JE, Cousens S, Blencowe H, et al. Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis. Lancet. 2013;382:417–25.PubMedCentralCrossRefPubMed Katz J, Lee AC, Kozuki N, Lawn JE, Cousens S, Blencowe H, et al. Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis. Lancet. 2013;382:417–25.PubMedCentralCrossRefPubMed
20.
go back to reference Racicot K, Kwon JY, Aldo P, Silasi M, Mor G. Understanding the complexity of the immune system during pregnancy. Am J Reprod Immunol. 2014;72:107–16.CrossRefPubMed Racicot K, Kwon JY, Aldo P, Silasi M, Mor G. Understanding the complexity of the immune system during pregnancy. Am J Reprod Immunol. 2014;72:107–16.CrossRefPubMed
21.
go back to reference Cot M, Le Hesran JY, Staalsoe T, Fievet N, Hviid L, Deloron P. Maternally transmitted antibodies to pregnancy-associated variant antigens on the surface of erythrocytes infected with Plasmodium falciparum: relation to child susceptibility to malaria. Am J Epidemiol. 2003;157:203–9.CrossRefPubMed Cot M, Le Hesran JY, Staalsoe T, Fievet N, Hviid L, Deloron P. Maternally transmitted antibodies to pregnancy-associated variant antigens on the surface of erythrocytes infected with Plasmodium falciparum: relation to child susceptibility to malaria. Am J Epidemiol. 2003;157:203–9.CrossRefPubMed
22.
go back to reference Malhotra I, Dent A, Mungai P, Wamachi A, Ouma JH, Narum DL, et al. Can prenatal malaria exposure produce an immune tolerant phenotype? A prospective birth cohort study in Kenya. PLoS Med. 2009;6:e1000116.PubMedCentralCrossRefPubMed Malhotra I, Dent A, Mungai P, Wamachi A, Ouma JH, Narum DL, et al. Can prenatal malaria exposure produce an immune tolerant phenotype? A prospective birth cohort study in Kenya. PLoS Med. 2009;6:e1000116.PubMedCentralCrossRefPubMed
23.
go back to reference Thompson KM, Simons EA, Badizadegan K, Reef SE, Cooper LZ. Characterization of the risks of adverse outcomes following rubella infection in pregnancy. Risk Anal. 2014. doi:10.1111/risa.12264. Thompson KM, Simons EA, Badizadegan K, Reef SE, Cooper LZ. Characterization of the risks of adverse outcomes following rubella infection in pregnancy. Risk Anal. 2014. doi:10.​1111/​risa.​12264.
24.
go back to reference De Beaudrap P, Turyakira E, White LJ, Nabasumba C, Tumwebaze B, Muehlenbachs A, et al. Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment. Malar J. 2013;12:139.PubMedCentralCrossRefPubMed De Beaudrap P, Turyakira E, White LJ, Nabasumba C, Tumwebaze B, Muehlenbachs A, et al. Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment. Malar J. 2013;12:139.PubMedCentralCrossRefPubMed
25.
go back to reference De Beaudrap P, Nabasumba C, Grandesso F, Turyakira E, Schramm B, Boum Y II, et al. Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda. Malar J. 2011;10:132.PubMedCentralCrossRefPubMed De Beaudrap P, Nabasumba C, Grandesso F, Turyakira E, Schramm B, Boum Y II, et al. Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda. Malar J. 2011;10:132.PubMedCentralCrossRefPubMed
26.
go back to reference Ojuka P, Boum Y 2nd, Denoeud-Ndam L, Nabasumba C, Muller Y, Okia M, et al. Early biting and insecticide resistance in the malaria vector Anopheles might compromise the effectiveness of vector control intervention in Southwestern Uganda. Malar J. 2015;14:148.PubMedCentralCrossRefPubMed Ojuka P, Boum Y 2nd, Denoeud-Ndam L, Nabasumba C, Muller Y, Okia M, et al. Early biting and insecticide resistance in the malaria vector Anopheles might compromise the effectiveness of vector control intervention in Southwestern Uganda. Malar J. 2015;14:148.PubMedCentralCrossRefPubMed
27.
go back to reference Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, et al. Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2010;10:762–9.CrossRefPubMed Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, et al. Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2010;10:762–9.CrossRefPubMed
28.
go back to reference Verburg BO, Steegers EA, De Ridder M, Snijders RJ, Smith E, Hofman A, et al. New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study. Ultrasound Obstet Gynecol. 2008;31:388–96.CrossRefPubMed Verburg BO, Steegers EA, De Ridder M, Snijders RJ, Smith E, Hofman A, et al. New charts for ultrasound dating of pregnancy and assessment of fetal growth: longitudinal data from a population-based cohort study. Ultrasound Obstet Gynecol. 2008;31:388–96.CrossRefPubMed
29.
go back to reference Uganda Ministry of Health. Integrated community case management of childhood malaria, pneumonia and diarrhoea. Kampala: Uganda Ministry of Health; 2010. Uganda Ministry of Health. Integrated community case management of childhood malaria, pneumonia and diarrhoea. Kampala: Uganda Ministry of Health; 2010.
30.
go back to reference Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino E, Altman DG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014;384:857–68.CrossRefPubMed Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino E, Altman DG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014;384:857–68.CrossRefPubMed
31.
go back to reference Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 2009. Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 2009.
32.
go back to reference Beath KJ. Infant growth modelling using a shape invariant model with random effects. Stat Med. 2007;26:2547–64.CrossRefPubMed Beath KJ. Infant growth modelling using a shape invariant model with random effects. Stat Med. 2007;26:2547–64.CrossRefPubMed
33.
go back to reference Laird N, Oliver D. Covariance analysis of censored survival data using log-linear analysis techniques. J Am Stat Assoc. 1981;76:231–40.CrossRef Laird N, Oliver D. Covariance analysis of censored survival data using log-linear analysis techniques. J Am Stat Assoc. 1981;76:231–40.CrossRef
34.
go back to reference Holford T. The analysis of rates and of survivorship using log-linear models. Biometrics. 1980;36:299–305.CrossRefPubMed Holford T. The analysis of rates and of survivorship using log-linear models. Biometrics. 1980;36:299–305.CrossRefPubMed
35.
go back to reference Carroll RJ. Measurement error in nonlinear models: a modern perspective. Boca Raton: Chapman & Hall/CRC; 2006.CrossRef Carroll RJ. Measurement error in nonlinear models: a modern perspective. Boca Raton: Chapman & Hall/CRC; 2006.CrossRef
36.
go back to reference R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2009. R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2009.
37.
go back to reference Huynh BT, Fievet N, Gbaguidi G, Dechavanne S, Borgella S, Guezo-Mevo B, et al. Influence of the timing of malaria infection during pregnancy on birth weight and on maternal anemia in Benin. Am J Trop Med Hyg. 2011;85:214–20.PubMedCentralCrossRefPubMed Huynh BT, Fievet N, Gbaguidi G, Dechavanne S, Borgella S, Guezo-Mevo B, et al. Influence of the timing of malaria infection during pregnancy on birth weight and on maternal anemia in Benin. Am J Trop Med Hyg. 2011;85:214–20.PubMedCentralCrossRefPubMed
38.
go back to reference McGready R, Lee SJ, Wiladphaingern J, Ashley EA, Rijken MJ, Boel M, et al. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis. 2012;12:388–96.PubMedCentralCrossRefPubMed McGready R, Lee SJ, Wiladphaingern J, Ashley EA, Rijken MJ, Boel M, et al. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis. 2012;12:388–96.PubMedCentralCrossRefPubMed
39.
go back to reference Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009;200:1509–17.CrossRefPubMed Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009;200:1509–17.CrossRefPubMed
40.
go back to reference Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H, Group WHOCHER. Global estimate of the incidence of clinical pneumonia among children under five years of age. Bull World Health Organ. 2004;82:895–903.PubMedCentralPubMed Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H, Group WHOCHER. Global estimate of the incidence of clinical pneumonia among children under five years of age. Bull World Health Organ. 2004;82:895–903.PubMedCentralPubMed
41.
go back to reference Selwyn BJ. The epidemiology of acute respiratory tract infection in young children: comparison of findings from several developing countries. Coordinated Data Group of BOSTID Researchers. Rev Infect Dis. 1990;12(Suppl 8):S870–88.CrossRefPubMed Selwyn BJ. The epidemiology of acute respiratory tract infection in young children: comparison of findings from several developing countries. Coordinated Data Group of BOSTID Researchers. Rev Infect Dis. 1990;12(Suppl 8):S870–88.CrossRefPubMed
42.
go back to reference Moya-Alvarez V, Abellana R, Cot M. Pregnancy-associated malaria and malaria in infants: an old problem with present consequences. Malar J. 2014;13:271.PubMedCentralCrossRefPubMed Moya-Alvarez V, Abellana R, Cot M. Pregnancy-associated malaria and malaria in infants: an old problem with present consequences. Malar J. 2014;13:271.PubMedCentralCrossRefPubMed
43.
go back to reference Cole SR, Chu H, Greenland S. Multiple-imputation for measurement-error correction. Int J Epidemiol. 2006;35:1074–81.CrossRefPubMed Cole SR, Chu H, Greenland S. Multiple-imputation for measurement-error correction. Int J Epidemiol. 2006;35:1074–81.CrossRefPubMed
Metadata
Title
Timing of malaria in pregnancy and impact on infant growth and morbidity: a cohort study in Uganda
Authors
Pierre De Beaudrap
Eleanor Turyakira
Carolyn Nabasumba
Benon Tumwebaze
Patrice Piola
Yap Boum II
Rose McGready
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2016
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-016-1135-7

Other articles of this Issue 1/2016

Malaria Journal 1/2016 Go to the issue