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    Terminology applied to fetal and infant intervals and events.40 wk = weeks; d = days; yr = year.

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    Perinatal mortality rate (PMR) by human development index (HDI) as a function of the malaria endemicity (55 studies in non-endemic countries and 34 in endemic countries; there are four missing values for the HDI). Adj. = adjusted; CI = confidence interval.

  • View in gallery

    Effect of placental malaria on pregnancy outcome (stillbirths) by random effects meta-analysis. The sizes of the squares are directly proportional to the amount of information each study contributes to the meta-analysis. The diamond represents the effect of placental malaria in all studies, with the vertical axis of the diamond indicating the odds ratio (OR) and the span (horizontal axis) indicating the 95% confidence interval (CI).

  • 1

    WHO/FRH/MSM/96.7, 1996 Perinatal Mortality: A Listing of Available Information. Maternal Health and Safe Motherhood Program. Geneva: World Health Organization.

  • 2

    Weiner R, Ronsmans C, Dorman E, Jilo H, Muhoro A, Shulman C, 2003. Labour complications remain the most important risk factors for perinatal mortality in rural Kenya. Bull World Health Organ 81 :561–566.

    • Search Google Scholar
    • Export Citation
  • 3

    Shulman CE, Dorman EK, 2003. Reducing childhood mortality in poor countries—Importance and prevention of malaria in pregnancy. Trans R Soc Trop Med Hyg 97 :30–35.

    • Search Google Scholar
    • Export Citation
  • 4

    McGregor IA, Wilson ME, Billewicz WZ, 1983. Malaria infection of the placenta in The Gambia, west Africa; its incidence and relationship to stillbirth, birthweight and placental weight. Trans R Soc Trop Med Hyg 77 :232–244.

    • Search Google Scholar
    • Export Citation
  • 5

    Brabin BJ, 1983. An analysis of malaria in pregnancy in Africa. Bull World Health Organ 61 :1005–1016.

  • 6

    Nosten F, McGready R, Simpson JA, Thwai KL, Balkan S, Cho T, 1999. Effects of Plasmodium vivax malaria in pregnancy. Lancet 354 :546–549.

    • Search Google Scholar
    • Export Citation
  • 7

    Blacklock DB, Gordon RM, 1925. Malaria infection as it occurs in late pregnancy; its relationship to labour and early infancy. Ann Trop Med Parasitol 19 :327–365.

    • Search Google Scholar
    • Export Citation
  • 8

    Bruce-Chwatt LJ, 1952. Malaria in African infants and children in southern Nigeria. Ann Trop Med Parasitol 46 :173–200.

  • 9

    Archibald HM, 1956. The influence of malaria infection of the placenta on the incidence of prematurity. Bull World Health Organ 15 :842–845.

    • Search Google Scholar
    • Export Citation
  • 10

    Spitz AJW, 1959. Malaria infection of the placenta and its influence on the incidence of prematurity in eastern Nigeria. Bull World Health Organ 21 :242–244.

    • Search Google Scholar
    • Export Citation
  • 11

    McLaren DS, Ward PG, 1962. Malaria infection of the placenta and foetal nutrition. East Afr Med J 39 :182–189.

  • 12

    Jelliffe EFP, 1968. Low birth weight and malarial infection of the placenta. Bull World Health Organ 38 :69–78.

  • 13

    Reinhardt MC, Ambroise-Thomas P, Cavallo-Serra R, Meylan C, Gautier R, 1978. Malaria at delivery in Abidjan. Helv Paediatr Acta 33 :65–84.

    • Search Google Scholar
    • Export Citation
  • 14

    Connor DSH, 1958. Malaria and prematurity in the western region of Nigeria. BMJ 2 :877–878.

  • 15

    Newman RD, Parise ME, Slutsker L, Nahlen B, Steketee RW, 2003. Safety, efficacy and determinants of effectiveness of antimalarial drugs during pregnancy: implications for prevention programmes in Plasmodium falciparum-endemic sub-Saharan Africa. Trop Med Int Health 8 :488–506.

    • Search Google Scholar
    • Export Citation
  • 16

    Kramer MS, 1987. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ 65 :663–737.

  • 17

    McCormick M-C, 1985. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med 312 :82–90.

  • 18

    Murphy SC, Breman JG, 2001. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 64 :57–67.

    • Search Google Scholar
    • Export Citation
  • 19

    Steketee RW, Nahlen BL, Parise ME, Menendez C, 2001. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 64 :28–35.

    • Search Google Scholar
    • Export Citation
  • 20

    Bruce-Chwatt LJ, 1983. Malaria and pregnancy. BMJ 286 :63–76.

  • 21

    Greenwood AM, Menendez C, Todd J, Greenwood BM, 1994. The distribution of birth weights in Gambian women who received malaria chemoprophylaxis during their first pregnancy and in control women. Trans R Soc Trop Med Hyg 88 :311–312.

    • Search Google Scholar
    • Export Citation
  • 22

    Menendez C, Todd J, Alonso PL, Francis N, Lulat S, Ceesay S, 1994. The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria. Trans R Soc Trop Med Hyg 88 :590–593.

    • Search Google Scholar
    • Export Citation
  • 23

    UNDP, Rapport Mondial sur le Dévelopement Humain 2002, 2003. Electronic citation.

  • 24

    Snow RW, Craig M, Deichmann U, Marsh K, 1999. Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population. Bull World Health Organ 77 :624–640.

    • Search Google Scholar
    • Export Citation
  • 25

    Nyirjesy P, Kavasya T, Axelrod P, Fischer PR, 1993. Malaria during pregnancy: neonatal morbidity and mortality and the efficacy of chloroquine chemoprophylaxis. Clin Infect Dis 16 :127–132.

    • Search Google Scholar
    • Export Citation
  • 26

    Cohn LD, Becker BJ, 2003. How meta-analysis increases statistical power. Psychol Methods 8 :243–253.

  • 27

    Higgins JP, Thompson SG, 2002. Quantifying heterogeneity in a meta-analysis. Stat Med 21 :1539–1558.

  • 28

    Tabutin D, Eliwo A, 1980. Socio-economic and cultural differentials in the mortality of sub-Saharan Africa. van de Walle E, Pison G, Sala-Diakanda M, eds. Mortality and Society in Sub-Saharan Africa. Oxford, United Kingdom: Clarendon Press, 35–61.

  • 29

    D’Alessandro U, Langerock P, Bennett S, Francis N, Cham K, Greenwood BM, 1996. The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia. Trans R Soc Trop Med Hyg 90 :487–492.

    • Search Google Scholar
    • Export Citation
  • 30

    Sachs J, 2003. Economic Analyses Indicate that the Burden of Malaria is Great. Economics of Malaria Executive Summary. Cambridge: Center for International Development, Harvard University and London: London School of Hygiene and Tropical Medicine.

  • 31

    Barros F-C, Victora C-G, Vaughan J-P, Estanislau H-J, 1987. Perinatal mortality in southern Brazil: a population-based study of 7,392 births. Bull World Health Organ 65 :95–104.

    • Search Google Scholar
    • Export Citation
  • 32

    Guildea ZE, Fone DL, Dunstan FD, Sibert JR, Cartlidge PH, 2001. Social deprivation and the causes of stillbirth and infant mortality. Arch Dis Child 84 :307–310.

    • Search Google Scholar
    • Export Citation
  • 33

    Naidu J, Moodley M, Adhikari R, Ramsaroop N, Morar OO, Dunmoye S, 2001. Clinico-pathological study of causes of perinatal mortality in a developing country. J Obstet Gynaecol 21 :443–447.

    • Search Google Scholar
    • Export Citation
  • 34

    Richardus JH, Graafmans WC, Verloove-Vanhoorick SP, Mack-enbach JP; The Euronatal Audit Panel; The Euronatal Working Group, 2003. Differences in perinatal mortality and suboptimal care between 10 European regions: results of an international audit. BJOG 11 :97–102.

    • Search Google Scholar
    • Export Citation
  • 35

    Menon R, 1972. Pregnancy and malaria. Med J Mal 27 :115–119.

  • 36

    van Hung L, 1951. Paludisme et grossesse à Saïgon. Rev Pal Med Trop 83 :75.

  • 37

    Nosten F, 1991. Malaria during pregnancy in an area of unstable endemicity. Trans R Soc Trop Med Hyg 85 :424–429.

  • 38

    Schwetz J, Peel E, 1934. Congenital malaria and placental infections amongst the Negroes of central Africa. Trans R Soc Trop Med Hyg 28 :167–174.

    • Search Google Scholar
    • Export Citation
  • 39

    Peel E, van Hoof L, 1948. Le paludisme à la maternité indigène de Léopoldville. Ann Soc Belg Med Trop 28 :413–420.

  • 40

    Steketee RW, Wirima JJ, Slutsker L, Breman JG, Heymann DL, 1996. Comparability of treatment groups and risk factors for parasitemia at the first antenatal clinic visit in a study of malaria treatment and prevention in pregnancy in rural Malawi. Am J Trop Med Hyg 55 (Suppl 1):17–23.

    • Search Google Scholar
    • Export Citation
  • 41

    Garner P, Gulmezoglu AM, 2003. Drugs for preventing malaria-related illness in pregnant women and death in the newborn. Cochrane Data System Rev 1: CD000169.

    • Search Google Scholar
    • Export Citation
  • 42

    Anagnos D, Lanoie LO, Palmieri JR, 1986. Effects of placental malaria on mothers and neonates from Zaire. Z Parasitol 72 :57–64.

  • 43

    Geelhoed DW, Visser LE, Addae V, Asare K, Schagen van Leeuwen JH, van Roosmalen J, 2001. Malaria prophylaxis and the reduction of anemia at childbirth. Int J Gynaecol Obstet 74 :133–138.

    • Search Google Scholar
    • Export Citation
  • 44

    Lefait JF, Seixas J, Tavora Tavira L, Alves F, Alves A, 1999. Infection palustre à la maternité de Bissau (Guinée-Bissau), parasitémie maternelle, placentaire et néonatale en début de saison des pluies. Med Afr Noire 46 :93–98.

    • Search Google Scholar
    • Export Citation
  • 45

    Voorhoeve AM, Muller AS, W’oigo H, 1979. Machakos Project Studies: agents affecting health of mother and child in a rural area of Kenya. XVI. The outcome of pregnancy. Trop Geogr Med 31 :607–627.

    • Search Google Scholar
    • Export Citation
  • 46

    Kulmala T, Vaahtera M, Ndekha M, Koivisto AM, Cullinan T, Salin ML, Ashorn P, 2000. The importance of preterm births for peri- and neonatal mortality in rural Malawi. Paediatr Perinat Epidemiol 14 :219–226.

    • Search Google Scholar
    • Export Citation
  • 47

    McDermott JM, Steketee R, Wirima J, 1996. Perinatal mortality in rural Malawi. Bull World Health Organ 74 :165–171.

  • 48

    Sule-Odu AO, Ogunledun A, Olatunji AO, 2002. Impact of asymptomatic maternal malaria parasitaemia at parturition on perinatal outcome. J Obstet Gynaecol 22 :25–28.

    • Search Google Scholar
    • Export Citation
  • 49

    Lamikanra OT, 1993. A study of malaria parasitaemia in pregnant women, placentae, cord blood and newborn babies in Lagos, Nigeria. West Afr J Med 12 :213–217.

    • Search Google Scholar
    • Export Citation
  • 50

    Hodges M, Williams RA, 1998. Registered infant and under-five deaths in Freetown, Sierra Leone from 1987–1991 and a comparison with 1969–1979. West Afr J Med 17 :95–98.

    • Search Google Scholar
    • Export Citation
  • 51

    Woodruff AW, Adamson EA, El Suni A, Maughan TS, Kaku M, Bundru N, 1983. Infants in Juba, southern Sudan: the first six months of life. Lancet 2 :262–264.

    • Search Google Scholar
    • Export Citation
  • 52

    Jamieson DJ, Meikle SF, Hillis SD, Mtsuko D, Mawji S, Duerr A, 2000. An evaluation of poor pregnancy outcomes among Burundian refugees in Tanzania. JAMA 283 :397–402.

    • Search Google Scholar
    • Export Citation
  • 53

    Matteelli A, Donato F, Shein A, 1996. Malarial infection and birthweight in urban Zanzibar, Tanzania. Ann Trop Med Parasitol 90 :125–134.

    • Search Google Scholar
    • Export Citation
  • 54

    Walraven GE, Mkanje RJ, van Roosmalen J, van Dongen PW, Dolmans WM, 1994. Comparison of perinatal outcome in rural Tanzania as obtained from a prospective community-based survey and hospital data. Trop Geogr Med 46 :11–13.

    • Search Google Scholar
    • Export Citation
  • 55

    Okoko BJ, Ota MO, Yamuah LK, Idiong D, Mkpanam SN, Avieka A, Banya WA, Osinusi K, 2002. Influence of placental malaria infection on foetal outcome in the Gambia: twenty years after Ian Mcgregor. J Health Popul Nutr 20 :4–11.

    • Search Google Scholar
    • Export Citation
  • 56

    Greenwood AM, Greenwood BM, Bradley AK, Williams K, Shenton FC, Tulloch S, Byass P, Oldfield FSJ, 1987. A prospective survey of the outcome of pregnancy in a rural area of the Gambia. Bull World Health Organ 65 :635–643.

    • Search Google Scholar
    • Export Citation
  • 57

    Ndyomugyenyi R, Magnussen P, 2001. Malaria morbidity, mortality and pregnancy outcome in areas with different levels of malaria transmission in Uganda: a hospital record- based study. Trans R Soc Trop Med Hyg 95 :463–468.

    • Search Google Scholar
    • Export Citation
  • 58

    Kasumba IN, Nalunkuma AJ, Mujuzi G, Kitaka FS, Byaruhanga R, Okong P, Egwang TG, 2000. Low birthweight associated with maternal anaemia and Plasmodium falciparum infection during pregnancy, in a peri-urban/urban area of low endemicity in Uganda. Ann Trop Med Parasitol 94 :7–13.

    • Search Google Scholar
    • Export Citation
  • 59

    Kalenga MK, Mutach K, Nsungula K, Kabyla I, Odimba FK, 1992. Epidemiological considerations on the deliveries of stillbirths in the maternity unit of Gecamines Sendwe of Lubum-bashi (Zaire). Rev Fr Gynecol Obstet 87 :26–29.

    • Search Google Scholar
    • Export Citation
  • 60

    Singh N, Mehra RK, Srivastava N, 2001. Malaria during pregnancy and infancy, in an area of intense malaria transmission in central India. Ann Trop Med Parasitol 95 :19–29.

    • Search Google Scholar
    • Export Citation
  • 61

    McGready R, Cho T, Keo NK, Thwai KL, Villegas L, Looaree-suwan S, White NJ, Nosten F, 2001. Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum.Clin Infect Dis 33 :2009–2016.

    • Search Google Scholar
    • Export Citation
  • 62

    Nosten F, Vincenti M, Simpson J, Yei P, Thwai KL, de Vries A, Chongsuphajaisiddhi T, White NJ, 1999. The effects of meflo-quine treatment in pregnancy. Clin Infect Dis 28 :808–815.

    • Search Google Scholar
    • Export Citation
  • 63

    Amoa AB, Klufio CA, Moro M, Kariwiga G, Mola G, 1998. A case-control study of stillbirths at the Port Moresby General Hospital. P N G Med J 41 :126–136.

    • Search Google Scholar
    • Export Citation
  • 64

    Mola G, Permezel M, Amoa AB, Klufio CA, 1999. Anaemia and perinatal outcome in Port Moresby. Aust N Z J Obstet Gynaecol 39 :31–34.

  • 65

    Das LK, 2000. Malaria during pregnancy and its effects on foetus in a tribal area of Koraput District, Orissa. Indian J Malariol 37 :11–17.

    • Search Google Scholar
    • Export Citation
  • 66

    Carles G, Bousquet F, Raynal P, Peneau C, Mignot V, Arbeille P, 1998. Pregnancy and malaria. Study of 143 cases in French Guyana. J Gynecol Obstet Biol Reprod (Paris) 27 :798–805.

    • Search Google Scholar
    • Export Citation
  • 67

    Luxemburger C, McGready R, Kham A, 2001. Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission. Am J Epidemiol 154 :459–465.

    • Search Google Scholar
    • Export Citation
  • 68

    Philippe E, Gass R, Gendrel D, Zinsou RD, Walter P, Ivanoff B, Lasalle Y, Blot P, 1984. The placenta of premature and hypotrophic Gabonese infants. J Gynecol Obstet Biol Reprod (Paris) 13 :515–519.

    • Search Google Scholar
    • Export Citation
  • 69

    Paksoy N, 1986. The incidence of placental malaria in Vanuatu in the south Pacific. Trans R Soc Trop Med Hyg 80 :174–175.

  • 70

    Taha T el-T, Gray RH, 1993. Malaria and perinatal mortality in central Sudan. Am J Epidemiol 138 :563–568.

  • 71

    Osman NB, Folgosa E, Gonzales C, Bergstrom S, 1995. Genital infections in the aetiology of late fetal death: an incident case-referent study. J Trop Pediatr 41 :258–266.

    • Search Google Scholar
    • Export Citation
  • 72

    Newman RD, Hailemariam A, Jimma D, Degifie A, Kebede D, Rietveld AE, Nahlen BL, Barnwell JW, Steketee RW, Parise ME, 2003. Burden of malaria during pregnancy in areas of stable and unstable transmission in Ethiopia during a nonepidemic year. J Infect Dis 187 :1765–1772.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

THE CONTRIBUTION OF MALARIA IN PREGNANCY TO PERINATAL MORTALITY

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  • 1 Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium

The link between malaria and perinatal mortality was explored by systematically reviewing 117 studies published between 1948 and 2002. The mean perinatal mortality rate was higher in malaria endemic countries (61.1/1,000, 95% confidence interval [CI] = 52.1–70.1) than in non-endemic countries (25.8/1,000, 95% CI = 21.1–30.6). Similarly, the fetal mortality rate was higher in endemic countries (40.1/1,000, 95% CI = 32.1–48.0) than in non-endemic countries (20.0/1,000, 95% CI = 13.2–26.8) countries. Considering that perinatal mortality is an important indicator of obstetric care quality and socioeconomic development, further analysis was restricted to countries with a human development index between 500 and 800. In this category, the perinatal mortality rate was also significantly higher in endemic countries (50.5/1,000, 95% CI = 35.5–65.5) than in non-endemic countries (30.0/1,000, 95% CI = 25.7–34.3). In some publications, the occurrence of placental malaria and stillbirth was available. Placental malaria was significantly associated with a higher risk for stillbirth, regardless of parity (odds ratio = 2.19, 95% CI = 1.49–3.22, P < 0.001). Despite the limitations involved in this kind of review, all information found indicates that in endemic countries, malaria is an important determinant of perinatal mortality. Preventive measures such as intermittent preventive treatment or insecticide-treated bed nets could substantially reduce perinatal mortality and fetal wastage.

INTRODUCTION

Perinatal mortality is an important indicator of obstetric care quality and socioeconomic development.1 Not surprisingly, the highest perinatal mortality rates (PMRs) are found in developing countries, particularly in Africa. Few studies have simultaneously considered intra-partum morbidity, sociodemographic factors, and diseases such as infection with human immunodeficiency virus, malaria, and malnutrition as risk factors for perinatal mortality. The proportion of perinatal deaths attributable to them is not well known.2 It is widely recognized that malaria has a negative effect on the outcome of pregnancy. Pregnant women with little or no pre-existing immunity are at high risk of cerebral malaria, hypoglycemia, pulmonary edema, and severe hemolytic anemia, and fetal and perinatal loss can be as high as 60–70%.3–6 The link between malaria and perinatal morbidity/mortality is less clear in areas with stable endemic malaria where pregnant women have acquired immunity. Malaria infection can cause maternal anemia, low birth weight (LBW), and possibly abortion and stillbirth.7 The mean birth weight of infants born by mothers with placental malaria is reduced by 55–310 grams.8–15 Low birth weight is more frequent in primigravidae with placental malaria compared with those without placental malaria (Kortmann HF, 1972. Malaria and Pregnancy. MD Thesis. Utrecht, The Netherlands: Drukkerij Elinkwijk).9,10,14 Placental malaria is responsible for up to 35% of preventable LBW in malaria-endemic areas.16 In malaria-endemic African countries, at least 13% of all infant deaths can be attributed to LBW resulting in 62,000–363,000 infant deaths per year.17,18 A recent review analyzing the malaria population attributable risk for anemia (3–15%), LBW (8–14%), and infant mortality (3–8%) estimated that each year between 75,000 and 200,000 infant deaths are associated with malaria infection in pregnancy.19 Perinatal mortality caused by malaria is estimated to be 25–80/1,000/year, although several studies have failed to show a clear and significant relationship.20–22 The aim of this report is to determine the contribution of malaria to perinatal mortality by systematically reviewing relevant published data.

METHODS

Case definition.

The definition of perinatal mortality and stillbirth used in this review is that recommended by the World Health Organization (WHO) Maternal Health and Safe Motherhood Program (WHO/FRH/MSM/96.7) and is based on the International Classification of Diseases, revision 10 (ICD-10). Fetal death is defined as death prior to the complete expulsion or extraction of the product of conception, irrespective of the duration of pregnancy. Fetal mortality rate (FMR) is the number of fetal deaths in a year divided by the total number of life births and fetal deaths in a year × 1,000. Stillbirth (late fetal death) is defined as death of a fetus of ≥28 weeks gestation. Early neonatal death is the death of an infant within the first seven days of life. Perinatal deaths include late fetal and early neonatal deaths. The PMR is the number of perinatal deaths divided by the number live births in a year × 1,000 (Figure 1).

Since the PMR is clearly linked to poverty and might confound the relationship between malaria and PMR/FMR, we used the Human Development Index (HDI) as an indicator. The HDI is a summary of three components: long and healthy life, knowledge, and a decent standard of living. It is computed by combining a life expectancy index, an education index based on the adult literacy rate and the combined primary, secondary, and tertiary education gross enrollment ratio, and the Gross Domestic Product (GDP) index based on the GDP per capita.23 The HDI is stratified into three categories following the United Nations Development Program classification: low (HDI < 500), medium (500 ≤ HDI < 800), and high (HDI ≥ 800) human development.

Malaria-endemic areas are defined as areas with significant annual transmission, be it seasonal or perennial. Epidemic areas are defined as areas prone to distinct inter-annual variation, in some years with no transmission taking place at all.24 When available in the recorded studies, the percentage of mothers infected with malaria (peripheral blood smear positive, placental blood smear positive) was used as a proxy marker of malaria endemicity. Placenta results are more sensitive than peripheral blood for detecting maternal infection, and are more accurate in predicting fetal morbidity.25 Values of malaria prevalence in Africa were obtained from the Mapping Malaria Risks in Africa database (http://www.mara.org.za).

Data sources.

A literature search for data on perinatal mortality rate and stillbirth in developed and developing countries was undertaken. MEDLINE, CAB HEALTH, and Cochrane reviews were searched with combinations of the following keywords: perinatal mortality, stillbirth, pregnancy, developing countries, developed countries, malaria, and placenta. Theses known through professional contacts or found in the Institute of Tropical Medicine (Antwerp, Belgium) database were searched with the same keywords. Information on stillbirth outcome in relation to placental malaria was also searched. Reference lists of collected articles were checked for additional references. All data were categorized by location, source (hospital or community), parity, PMR, and stillbirth rate (FMR). Most studies included only singleton births (a few did not make a difference) and were usually not stratified and/or analyzed by parity.

For the meta-analysis quantifying the risk of delivering a stillbirth associated with placental malaria, a study was included if it had a clearly stated diagnostic method for detecting placental malaria. It should have also reported either the relative risks (or odds ratios) of stillbirth according to placental malaria or the raw data to allow these to be computed.

Statistical analysis.

Two types of analysis (STATA version 8.0; Stata Corp., College Station, TX) were done: an ecologic and a meta-analysis. The PMR and FMR were computed against HDI in malaria-endemic countries and in non-endemic countries. Malaria endemicity and HDI were used as continuous and categorical variables. Correlation coefficients were calculated for the continuous variables. We also compared the HDI and PMR/FMR as a continuous variable between malaria-endemic countries and non-endemic countries. Mean PMR/FMR were compared between the different categories (low, medium, and high HDI; endemic and non-endemic malaria). The relationship between FMR and the prevalence of placental malaria was explored by using data from publications where both variables were reported.

Studies that reported the risk of stillbirths in women (all parities) with a positive and a negative placental blood smear were used for the meta-analysis. The random effects meta-analysis model was used to calculate pooled odd ratios (ORs) and 95% confidence intervals (CIs). A random effects model was used as it assumes a different underlying effect for each study.26,27

RESULTS

For the ecologic analysis, 117 studies published between 1948 and 2002 were found. The PMR and/or FMR were obtained mostly from hospital records. The mean PMR was higher in 36 studies from endemic countries (61.1/1,000, 95% CI = 52.1–70.1) than in 59 studies from non-endemic countries (25.8/1,000, 95% CI = 21.1–30.6). Similarly, the FMR was higher in 40 studies from endemic countries (40.1/1,000, 95% CI = 32.1–48.0) than in 42 studies from non-endemic countries (20/1,000, 95% CI = 13.2–26.8). When plotting PMR against HDI, PMR increased with decreasing HDI, and the highest values were found in countries with the lowest HDI (Figure 2). However, considering that few non-endemic countries had HDI values <500 and no endemic country had an HDI value >800, a meaningful comparison was possible only for countries with an HDI between 500 and 800. In this category, the PMR was significantly higher in endemic countries (50.5, 1,000, 95% CI = 35.5–65.5) than in non-endemic countries (30/1,000, 95% CI = 25.7–34.3). In endemic countries, no obvious linear trend between PMR and parasite prevalence was found.

Twenty-five publications from Africa published between 1948 and 2002 and where malaria was specifically reported as a cause of perinatal death and/or stillbirth were found. Approximately two-thirds (68%) were based on hospital data and approximately half (48%) were from urban areas. The PMR ranged from 24/1,000 to 137/1,000, the FMR ranged from 2.3/1,000 to 111/1,000, and placental malaria ranged from 6% to 64% (Table 1). Within the African continent, no significant differences between the different regions (all of them belonging to low HDI countries) was found.

Eleven additional studies from others continents and published between 1951 and 2000 were found. We analyzed these separately because the study conditions were different from those in Africa. Three of them reported perinatal mortality and stillbirth during an epidemic and were excluded from analysis. More than two-thirds (75%) of these publications were based on hospital data and were from rural areas. The PMR was mentioned in only two studies, the FMR ranged from 12/1,000 to 27/1,000, and placental malaria (blood smear) ranged from 4% to 55% (Table 2). The association between FMR and the prevalence of placental infection was not significant (R = 0.59, P = 0.12). The association between PMR and placental malaria could not be explored because there were few data available.

Meta-analysis.

Nine studies filled the criteria and corresponded to 11 records (Table 3). Placental malaria was significantly associated with a higher risk for stillbirth regardless of parity (OR = 2.19, 95% CI = 1.49–3.22; P < 0.001) (Figure 3).

DISCUSSION

The link between socioeconomic variables and childhood or infant mortality is well known and any attempt of investigating the contribution of malaria to perinatal mortality should take this into account.28 The HDI, a summary estimate of several factors such as the life expectancy, education, and the GDP, was used as a rough measure of the socioeconomic status at the country level. Not surprisingly, the PMR and FMR were strongly correlated with HDI. Moreover, most of the malaria-endemic countries had an HDI <800 and many of them clustered around the lowest HDI values. This means that despite the higher values for the PMR and FMR in developing countries, it is extremely difficult to attribute this difference to the presence of malaria. We have tried to circumvent this problem by analyzing only countries with an HDI between 500 and 800 and found that the PMR was significantly higher in endemic countries than in non-endemic countries. Again, these results should be taken with caution for several reasons. First, the HDI reflects the present socioeconomic situation while the PMR and FMR data have been extracted from articles published over the past 50 years. Therefore, the HDI might not reflect the national economic development at the time the data were collected. Second, most of the publications reported data from hospital records and this might have introduced an important bias in the estimation of the PMR and FMR. Indeed, in many endemic countries, a large proportion of women does not deliver in hospitals, but rather in peripheral health centers or, more commonly, at home.29 Therefore, the actual PMR and FMR are probably higher because a large percentage of perinatal deaths or stillbirths goes unreported. This is more likely to be true in countries with the lowest HDI, which are also those with the highest PMR values, than in countries with a medium or high HDI, since access to health care is probably lower. Therefore, the PMR difference between endemic and non-endemic countries might be even larger. Moreover, malaria is a major obstacle to overall economic development; during the period 1965–1990, endemic countries had a growth penalty of more than 1% per year (compared with countries without malaria), even after considering the effects of economic policy and other factors influencing economic growth. The annual growth loss by malaria has been estimated as high as 1.3% points per year.30 The PMR and FMR are often linked to the quality of clinical care31,32 and of obstetric and neonatal services in tropical33 as well as in European countries.34 If one considers that health care quality is often linked to economic development,34 malaria might also have an indirect effect on the PMR by slowing economic development and consequently reducing the provision of health services of acceptable quality.

We were unable to find any obvious trend between malaria prevalence and PMR. This is understandable when one considers that most of the publications reporting PMR values did not have any estimation of malaria prevalence, and that these had to be extracted from other studies done in the same country, but not necessarily in the same location, and during the same period. However, a meta-analysis (at individual level) showed that the stillbirth rate was strongly associated with placental malaria in endemic areas. The relationship between malaria and fetal loss has been described in low endemic or epidemic-prone areas,35–38 but this is far from clear in highly endemic areas.3,8,39 Therefore, we analyzed the individual risk of delivering a stillbirth according to the presence of placental malaria. A tendency of having a higher risk of delivering stillborn babies in women with placental malaria had been reported in all studies included in our meta-analysis, but in several of them such a link was not statistically significant. However, when pooled together, the risk of stillbirth was significantly higher in women with placental malaria. Several limitations ought to be mentioned. First, most of the data included in the meta-analysis came from hospital-based studies, i.e., from a selected group of women who decided to deliver in the hospital for a variety of reasons. These women might have had access to preventive measures, such as chemoprophylaxis, that would have decreased the risk of stillbirths. This would underestimate the impact of malaria on perinatal mortality. Alternatively, if one considers that women delivering at the health facilities might represent high-risk pregnancies, primigravidae for example, the impact of malaria on perinatal mortality might be overestimated. Community-based studies collecting information from all pregnant women would have given a better estimation and overcome selection bias, but they are extremely difficult to carry out. Second, in our analysis parity was not taken into account. Stratification by parity might have shown a stronger effect in primigravidae compared with the other pregnant women because they are more vulnerable to malaria infection and placental malaria.40 Moreover, most studies relied on the result of the placental smear whose sensitivity is low compared with placenta histopathology.3 A more reliable method of assessing placental infection such as the histopathologic examination might have changed the results, although the delivery of a stillborn baby is probably linked to an active malaria infection that can also be detected by a placental smear.

In conclusion, despite the major limitations involved in this kind of review, all the information found indicates that in endemic countries, malaria is an important determinant of perinatal mortality. In the middle income countries (HDI between 500 and 800), a meaningful comparison was possible and we found that the PMR was significantly higher in endemic countries than in non-endemic countries. A meta-analysis of nine studies showed that placental malaria was associated with a more then two-fold risk for stillbirth, regardless of parity. This is consistent with the findings of a recent Cochrane review showing that malaria chemoprophylaxis significantly reduces PMN in primi- and secundigravidae.41 Preventive measures such as intermittent preventive treatment or insecticide-treated bed nets could substantially decrease perinatal mortality and fetal wastage.3

Table 1

Malaria reported as a cause of perinatal death (including stillbirths) in Africa*

CountryYearData sourceStudy siteNo. of birthsPG (%)LBW (%)PDPMR (%)PM (%)StillbirthsFMR (%)Reference
* PG = primigravidae; LBW = low birth weight; PD = perinatal deaths; PMR = perinatal mortality rate; PM = placental malaria; FMR = fetal mortality rate; H = hospital; U = urban; R = rural; C = community; RC = refugee camp; HC = health center. Countries appearing more than once with the same reference number indicate that data from more than one study location are reported in the same publication.
Central African Republic1986H1016476942
Democratic Republic of the Congo1948HU40327686039
Ghana2001HR5,88733204247243
Guinée-Bissau1997HU2022926142110444
Kenya1975–1976CR2,24620105470.2673045
Malawi1995–1996CR7962415526530364546
Malawi1987–1989HR2,06336181115421652947
Nigeria2002HU5642725162848
Nigeria1986HU1052011665749
Sierra Léone1987–1991HU68,883173,280482,5643950
Sudan1983CU21394252451
Tanzania1997–1998RCRC6792261314652
Tanzania1989–1990HU440255211253
Tanzania1989–1991CR427102968122854
Tanzania1989–1990HU3,17415304962457762
The Gambia1997HR313312443137523511155
The Gambia1966–1972HU2,9274412474
The Gambia1966–1972HCR3,5002627794
The Gambia1982–1983CR65849758233556
The Gambia1991–1992CR462100138233275729
Uganda1997–1998HR3,212401434632057
Uganda1997–1998HR2,779435811926957
Uganda1998HU53729117234358
Zaire1989–1990HR29725107243341325
Zaire1980–1984HU49,68134181,5353159
Table 2

Malaria reported as a cause of perinatal death (including stillbirths) outside Africa*

CountryYearData sourceStudy siteNo. of birthsPG (%)LBW (%)PDPMRMalaria deaths (%)P.f. (%)StillbirthsFMRReference
* PG = primigravidae; LBW = low birth weight; PD = perinatal deaths; PMR = perinatal mortality rate; P.f. = Plasmodium falciparum infection; FMR = fetal mortality rate; C = community; R = rural; H = hospital; U = urban.
† Only P. falciparum positive were selected.
India1997–1998CR274285551860
Thailand1992–2000HR3863019100†71861
Thailand1991–1994HR3,587241531611962
Papua New Guinea1987–1992HU22,405104271963
Papua New Guinea1995–1997HU153152264
India2000CR20920838631262965
French Guyana1992–1995HR3,7883922114451266
Thailand1993–1996HR1,5671637432767
Table 3

Placental malaria and stillbirths (all hospital studies)*

CountryYearStillbirths† (PM/N)Live births (PM/N)OR95% CIReference
* PM/N = placenta malaria/total number of stillbirths or live births; OR = odds ratio; CI = confidence interval. Countries that appear twice with the same study references indicates that within the study discreet and different distinct study sites have been analyzed.
†Stillbirths with known causes, such as cephalopelvic disproportion or uterine rupture, were excluded from the analysis.
‡Cases and controls matched by age and parity.
§Fresh and macerated stillbirths.
Sierra Leone192510/1451/1444.561.36–15.277
The Gambia198322/138330/2,7891.410.88–2.264
The Gambia198382/276866/3,2241.150.88–1.514
Gabon19841/152/521.790.15–21.1768
Gabon19844/771/2413.190.70–14.6368
Vanuatu19862/58/17614.02.04–95.9469
Sudan199353/151185/6201.270.87–1.8570
Mozambique‡199511/587/581.710.61–4.7671
Ethiopia20030/212/18372
Ethiopia20034/2617/8078.452.63–27.1972
The Gambia§200225/35135/2782.651.23–5.7255
Uganda20005/2334/5143.921.37–11.2158
Figure 1.
Figure 1.

Terminology applied to fetal and infant intervals and events.40 wk = weeks; d = days; yr = year.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 71, 2_suppl; 10.4269/ajtmh.2004.71.35

Figure 2.
Figure 2.

Perinatal mortality rate (PMR) by human development index (HDI) as a function of the malaria endemicity (55 studies in non-endemic countries and 34 in endemic countries; there are four missing values for the HDI). Adj. = adjusted; CI = confidence interval.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 71, 2_suppl; 10.4269/ajtmh.2004.71.35

Figure 3.
Figure 3.

Effect of placental malaria on pregnancy outcome (stillbirths) by random effects meta-analysis. The sizes of the squares are directly proportional to the amount of information each study contributes to the meta-analysis. The diamond represents the effect of placental malaria in all studies, with the vertical axis of the diamond indicating the odds ratio (OR) and the span (horizontal axis) indicating the 95% confidence interval (CI).

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 71, 2_suppl; 10.4269/ajtmh.2004.71.35

Authors’ address: Jean-Pierre van Geertruyden, Florence Thomas, Annette Erhart, and Umberto D’Alessandro, Department of Parasitology, Prince Leopold Institute of Tropical Medicine Nationalestraat 155, B-2000 Antwerp, Belgium, Telephone: 32-3-247-6354, Fax: 32-3-247-6362, E-mail: udalessandro@itg.be.

Acknowledgments: We thank Professor Bernard Brabin for his useful comments during the preparation of the manuscript.

Financial support: This work received financial support from the European Commission Research Directorate (contract no: PREMA-EU 84 150).

REFERENCES

  • 1

    WHO/FRH/MSM/96.7, 1996 Perinatal Mortality: A Listing of Available Information. Maternal Health and Safe Motherhood Program. Geneva: World Health Organization.

  • 2

    Weiner R, Ronsmans C, Dorman E, Jilo H, Muhoro A, Shulman C, 2003. Labour complications remain the most important risk factors for perinatal mortality in rural Kenya. Bull World Health Organ 81 :561–566.

    • Search Google Scholar
    • Export Citation
  • 3

    Shulman CE, Dorman EK, 2003. Reducing childhood mortality in poor countries—Importance and prevention of malaria in pregnancy. Trans R Soc Trop Med Hyg 97 :30–35.

    • Search Google Scholar
    • Export Citation
  • 4

    McGregor IA, Wilson ME, Billewicz WZ, 1983. Malaria infection of the placenta in The Gambia, west Africa; its incidence and relationship to stillbirth, birthweight and placental weight. Trans R Soc Trop Med Hyg 77 :232–244.

    • Search Google Scholar
    • Export Citation
  • 5

    Brabin BJ, 1983. An analysis of malaria in pregnancy in Africa. Bull World Health Organ 61 :1005–1016.

  • 6

    Nosten F, McGready R, Simpson JA, Thwai KL, Balkan S, Cho T, 1999. Effects of Plasmodium vivax malaria in pregnancy. Lancet 354 :546–549.

    • Search Google Scholar
    • Export Citation
  • 7

    Blacklock DB, Gordon RM, 1925. Malaria infection as it occurs in late pregnancy; its relationship to labour and early infancy. Ann Trop Med Parasitol 19 :327–365.

    • Search Google Scholar
    • Export Citation
  • 8

    Bruce-Chwatt LJ, 1952. Malaria in African infants and children in southern Nigeria. Ann Trop Med Parasitol 46 :173–200.

  • 9

    Archibald HM, 1956. The influence of malaria infection of the placenta on the incidence of prematurity. Bull World Health Organ 15 :842–845.

    • Search Google Scholar
    • Export Citation
  • 10

    Spitz AJW, 1959. Malaria infection of the placenta and its influence on the incidence of prematurity in eastern Nigeria. Bull World Health Organ 21 :242–244.

    • Search Google Scholar
    • Export Citation
  • 11

    McLaren DS, Ward PG, 1962. Malaria infection of the placenta and foetal nutrition. East Afr Med J 39 :182–189.

  • 12

    Jelliffe EFP, 1968. Low birth weight and malarial infection of the placenta. Bull World Health Organ 38 :69–78.

  • 13

    Reinhardt MC, Ambroise-Thomas P, Cavallo-Serra R, Meylan C, Gautier R, 1978. Malaria at delivery in Abidjan. Helv Paediatr Acta 33 :65–84.

    • Search Google Scholar
    • Export Citation
  • 14

    Connor DSH, 1958. Malaria and prematurity in the western region of Nigeria. BMJ 2 :877–878.

  • 15

    Newman RD, Parise ME, Slutsker L, Nahlen B, Steketee RW, 2003. Safety, efficacy and determinants of effectiveness of antimalarial drugs during pregnancy: implications for prevention programmes in Plasmodium falciparum-endemic sub-Saharan Africa. Trop Med Int Health 8 :488–506.

    • Search Google Scholar
    • Export Citation
  • 16

    Kramer MS, 1987. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ 65 :663–737.

  • 17

    McCormick M-C, 1985. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med 312 :82–90.

  • 18

    Murphy SC, Breman JG, 2001. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 64 :57–67.

    • Search Google Scholar
    • Export Citation
  • 19

    Steketee RW, Nahlen BL, Parise ME, Menendez C, 2001. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 64 :28–35.

    • Search Google Scholar
    • Export Citation
  • 20

    Bruce-Chwatt LJ, 1983. Malaria and pregnancy. BMJ 286 :63–76.

  • 21

    Greenwood AM, Menendez C, Todd J, Greenwood BM, 1994. The distribution of birth weights in Gambian women who received malaria chemoprophylaxis during their first pregnancy and in control women. Trans R Soc Trop Med Hyg 88 :311–312.

    • Search Google Scholar
    • Export Citation
  • 22

    Menendez C, Todd J, Alonso PL, Francis N, Lulat S, Ceesay S, 1994. The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria. Trans R Soc Trop Med Hyg 88 :590–593.

    • Search Google Scholar
    • Export Citation
  • 23

    UNDP, Rapport Mondial sur le Dévelopement Humain 2002, 2003. Electronic citation.

  • 24

    Snow RW, Craig M, Deichmann U, Marsh K, 1999. Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population. Bull World Health Organ 77 :624–640.

    • Search Google Scholar
    • Export Citation
  • 25

    Nyirjesy P, Kavasya T, Axelrod P, Fischer PR, 1993. Malaria during pregnancy: neonatal morbidity and mortality and the efficacy of chloroquine chemoprophylaxis. Clin Infect Dis 16 :127–132.

    • Search Google Scholar
    • Export Citation
  • 26

    Cohn LD, Becker BJ, 2003. How meta-analysis increases statistical power. Psychol Methods 8 :243–253.

  • 27

    Higgins JP, Thompson SG, 2002. Quantifying heterogeneity in a meta-analysis. Stat Med 21 :1539–1558.

  • 28

    Tabutin D, Eliwo A, 1980. Socio-economic and cultural differentials in the mortality of sub-Saharan Africa. van de Walle E, Pison G, Sala-Diakanda M, eds. Mortality and Society in Sub-Saharan Africa. Oxford, United Kingdom: Clarendon Press, 35–61.

  • 29

    D’Alessandro U, Langerock P, Bennett S, Francis N, Cham K, Greenwood BM, 1996. The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia. Trans R Soc Trop Med Hyg 90 :487–492.

    • Search Google Scholar
    • Export Citation
  • 30

    Sachs J, 2003. Economic Analyses Indicate that the Burden of Malaria is Great. Economics of Malaria Executive Summary. Cambridge: Center for International Development, Harvard University and London: London School of Hygiene and Tropical Medicine.

  • 31

    Barros F-C, Victora C-G, Vaughan J-P, Estanislau H-J, 1987. Perinatal mortality in southern Brazil: a population-based study of 7,392 births. Bull World Health Organ 65 :95–104.

    • Search Google Scholar
    • Export Citation
  • 32

    Guildea ZE, Fone DL, Dunstan FD, Sibert JR, Cartlidge PH, 2001. Social deprivation and the causes of stillbirth and infant mortality. Arch Dis Child 84 :307–310.

    • Search Google Scholar
    • Export Citation
  • 33

    Naidu J, Moodley M, Adhikari R, Ramsaroop N, Morar OO, Dunmoye S, 2001. Clinico-pathological study of causes of perinatal mortality in a developing country. J Obstet Gynaecol 21 :443–447.

    • Search Google Scholar
    • Export Citation
  • 34

    Richardus JH, Graafmans WC, Verloove-Vanhoorick SP, Mack-enbach JP; The Euronatal Audit Panel; The Euronatal Working Group, 2003. Differences in perinatal mortality and suboptimal care between 10 European regions: results of an international audit. BJOG 11 :97–102.

    • Search Google Scholar
    • Export Citation
  • 35

    Menon R, 1972. Pregnancy and malaria. Med J Mal 27 :115–119.

  • 36

    van Hung L, 1951. Paludisme et grossesse à Saïgon. Rev Pal Med Trop 83 :75.

  • 37

    Nosten F, 1991. Malaria during pregnancy in an area of unstable endemicity. Trans R Soc Trop Med Hyg 85 :424–429.

  • 38

    Schwetz J, Peel E, 1934. Congenital malaria and placental infections amongst the Negroes of central Africa. Trans R Soc Trop Med Hyg 28 :167–174.

    • Search Google Scholar
    • Export Citation
  • 39

    Peel E, van Hoof L, 1948. Le paludisme à la maternité indigène de Léopoldville. Ann Soc Belg Med Trop 28 :413–420.

  • 40

    Steketee RW, Wirima JJ, Slutsker L, Breman JG, Heymann DL, 1996. Comparability of treatment groups and risk factors for parasitemia at the first antenatal clinic visit in a study of malaria treatment and prevention in pregnancy in rural Malawi. Am J Trop Med Hyg 55 (Suppl 1):17–23.

    • Search Google Scholar
    • Export Citation
  • 41

    Garner P, Gulmezoglu AM, 2003. Drugs for preventing malaria-related illness in pregnant women and death in the newborn. Cochrane Data System Rev 1: CD000169.

    • Search Google Scholar
    • Export Citation
  • 42

    Anagnos D, Lanoie LO, Palmieri JR, 1986. Effects of placental malaria on mothers and neonates from Zaire. Z Parasitol 72 :57–64.

  • 43

    Geelhoed DW, Visser LE, Addae V, Asare K, Schagen van Leeuwen JH, van Roosmalen J, 2001. Malaria prophylaxis and the reduction of anemia at childbirth. Int J Gynaecol Obstet 74 :133–138.

    • Search Google Scholar
    • Export Citation
  • 44

    Lefait JF, Seixas J, Tavora Tavira L, Alves F, Alves A, 1999. Infection palustre à la maternité de Bissau (Guinée-Bissau), parasitémie maternelle, placentaire et néonatale en début de saison des pluies. Med Afr Noire 46 :93–98.

    • Search Google Scholar
    • Export Citation
  • 45

    Voorhoeve AM, Muller AS, W’oigo H, 1979. Machakos Project Studies: agents affecting health of mother and child in a rural area of Kenya. XVI. The outcome of pregnancy. Trop Geogr Med 31 :607–627.

    • Search Google Scholar
    • Export Citation
  • 46

    Kulmala T, Vaahtera M, Ndekha M, Koivisto AM, Cullinan T, Salin ML, Ashorn P, 2000. The importance of preterm births for peri- and neonatal mortality in rural Malawi. Paediatr Perinat Epidemiol 14 :219–226.

    • Search Google Scholar
    • Export Citation
  • 47

    McDermott JM, Steketee R, Wirima J, 1996. Perinatal mortality in rural Malawi. Bull World Health Organ 74 :165–171.

  • 48

    Sule-Odu AO, Ogunledun A, Olatunji AO, 2002. Impact of asymptomatic maternal malaria parasitaemia at parturition on perinatal outcome. J Obstet Gynaecol 22 :25–28.

    • Search Google Scholar
    • Export Citation
  • 49

    Lamikanra OT, 1993. A study of malaria parasitaemia in pregnant women, placentae, cord blood and newborn babies in Lagos, Nigeria. West Afr J Med 12 :213–217.

    • Search Google Scholar
    • Export Citation
  • 50

    Hodges M, Williams RA, 1998. Registered infant and under-five deaths in Freetown, Sierra Leone from 1987–1991 and a comparison with 1969–1979. West Afr J Med 17 :95–98.

    • Search Google Scholar
    • Export Citation
  • 51

    Woodruff AW, Adamson EA, El Suni A, Maughan TS, Kaku M, Bundru N, 1983. Infants in Juba, southern Sudan: the first six months of life. Lancet 2 :262–264.

    • Search Google Scholar
    • Export Citation
  • 52

    Jamieson DJ, Meikle SF, Hillis SD, Mtsuko D, Mawji S, Duerr A, 2000. An evaluation of poor pregnancy outcomes among Burundian refugees in Tanzania. JAMA 283 :397–402.

    • Search Google Scholar
    • Export Citation
  • 53

    Matteelli A, Donato F, Shein A, 1996. Malarial infection and birthweight in urban Zanzibar, Tanzania. Ann Trop Med Parasitol 90 :125–134.

    • Search Google Scholar
    • Export Citation
  • 54

    Walraven GE, Mkanje RJ, van Roosmalen J, van Dongen PW, Dolmans WM, 1994. Comparison of perinatal outcome in rural Tanzania as obtained from a prospective community-based survey and hospital data. Trop Geogr Med 46 :11–13.

    • Search Google Scholar
    • Export Citation
  • 55

    Okoko BJ, Ota MO, Yamuah LK, Idiong D, Mkpanam SN, Avieka A, Banya WA, Osinusi K, 2002. Influence of placental malaria infection on foetal outcome in the Gambia: twenty years after Ian Mcgregor. J Health Popul Nutr 20 :4–11.

    • Search Google Scholar
    • Export Citation
  • 56

    Greenwood AM, Greenwood BM, Bradley AK, Williams K, Shenton FC, Tulloch S, Byass P, Oldfield FSJ, 1987. A prospective survey of the outcome of pregnancy in a rural area of the Gambia. Bull World Health Organ 65 :635–643.

    • Search Google Scholar
    • Export Citation
  • 57

    Ndyomugyenyi R, Magnussen P, 2001. Malaria morbidity, mortality and pregnancy outcome in areas with different levels of malaria transmission in Uganda: a hospital record- based study. Trans R Soc Trop Med Hyg 95 :463–468.

    • Search Google Scholar
    • Export Citation
  • 58

    Kasumba IN, Nalunkuma AJ, Mujuzi G, Kitaka FS, Byaruhanga R, Okong P, Egwang TG, 2000. Low birthweight associated with maternal anaemia and Plasmodium falciparum infection during pregnancy, in a peri-urban/urban area of low endemicity in Uganda. Ann Trop Med Parasitol 94 :7–13.

    • Search Google Scholar
    • Export Citation
  • 59

    Kalenga MK, Mutach K, Nsungula K, Kabyla I, Odimba FK, 1992. Epidemiological considerations on the deliveries of stillbirths in the maternity unit of Gecamines Sendwe of Lubum-bashi (Zaire). Rev Fr Gynecol Obstet 87 :26–29.

    • Search Google Scholar
    • Export Citation
  • 60

    Singh N, Mehra RK, Srivastava N, 2001. Malaria during pregnancy and infancy, in an area of intense malaria transmission in central India. Ann Trop Med Parasitol 95 :19–29.

    • Search Google Scholar
    • Export Citation
  • 61

    McGready R, Cho T, Keo NK, Thwai KL, Villegas L, Looaree-suwan S, White NJ, Nosten F, 2001. Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum.Clin Infect Dis 33 :2009–2016.

    • Search Google Scholar
    • Export Citation
  • 62

    Nosten F, Vincenti M, Simpson J, Yei P, Thwai KL, de Vries A, Chongsuphajaisiddhi T, White NJ, 1999. The effects of meflo-quine treatment in pregnancy. Clin Infect Dis 28 :808–815.

    • Search Google Scholar
    • Export Citation
  • 63

    Amoa AB, Klufio CA, Moro M, Kariwiga G, Mola G, 1998. A case-control study of stillbirths at the Port Moresby General Hospital. P N G Med J 41 :126–136.

    • Search Google Scholar
    • Export Citation
  • 64

    Mola G, Permezel M, Amoa AB, Klufio CA, 1999. Anaemia and perinatal outcome in Port Moresby. Aust N Z J Obstet Gynaecol 39 :31–34.

  • 65

    Das LK, 2000. Malaria during pregnancy and its effects on foetus in a tribal area of Koraput District, Orissa. Indian J Malariol 37 :11–17.

    • Search Google Scholar
    • Export Citation
  • 66

    Carles G, Bousquet F, Raynal P, Peneau C, Mignot V, Arbeille P, 1998. Pregnancy and malaria. Study of 143 cases in French Guyana. J Gynecol Obstet Biol Reprod (Paris) 27 :798–805.

    • Search Google Scholar
    • Export Citation
  • 67

    Luxemburger C, McGready R, Kham A, 2001. Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission. Am J Epidemiol 154 :459–465.

    • Search Google Scholar
    • Export Citation
  • 68

    Philippe E, Gass R, Gendrel D, Zinsou RD, Walter P, Ivanoff B, Lasalle Y, Blot P, 1984. The placenta of premature and hypotrophic Gabonese infants. J Gynecol Obstet Biol Reprod (Paris) 13 :515–519.

    • Search Google Scholar
    • Export Citation
  • 69

    Paksoy N, 1986. The incidence of placental malaria in Vanuatu in the south Pacific. Trans R Soc Trop Med Hyg 80 :174–175.

  • 70

    Taha T el-T, Gray RH, 1993. Malaria and perinatal mortality in central Sudan. Am J Epidemiol 138 :563–568.

  • 71

    Osman NB, Folgosa E, Gonzales C, Bergstrom S, 1995. Genital infections in the aetiology of late fetal death: an incident case-referent study. J Trop Pediatr 41 :258–266.

    • Search Google Scholar
    • Export Citation
  • 72

    Newman RD, Hailemariam A, Jimma D, Degifie A, Kebede D, Rietveld AE, Nahlen BL, Barnwell JW, Steketee RW, Parise ME, 2003. Burden of malaria during pregnancy in areas of stable and unstable transmission in Ethiopia during a nonepidemic year. J Infect Dis 187 :1765–1772.

    • Search Google Scholar
    • Export Citation
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