Malaria during pregnancy is a major problem in sub-Saharan Africa, affecting an estimated 24 million pregnant women each year [1,2]. In malaria-endemic areas Plasmodium falciparum parasitaemia during pregnancy is associated with anaemia in pregnant women, and low birthweight (LBW) resulting from premature delivery and intrauterine growth retardation (IUGR) [3–5], and LBW is an important risk factors for early infant mortality and morbidity .
During the past two decades, HIV/AIDS has emerged as a major problem in many malaria-endemic areas of sub-Saharan Africa, where an estimated 28 million people are infected with HIV . Africa south of the Sahara accounts for over two-thirds of the world's 40 million HIV-infected individuals, and 80% of the world's HIV-infected women , with HIV prevalence as high as 25–45% among pregnant women [7–14]. Given the wide geographical overlap between HIV and malaria, the epidemic of HIV/AIDS in areas where P. falciparum is endemic has generated serious concern about potential interactions between the two infections [9,11,13,15,16]. Studies among pregnant women in sub-Saharan Africa have shown that HIV-infected women, particularly multigravidae are more likely to be infected with P. falciparum, and to have higher parasite densities than HIV-uninfected women [9, 11,13]. HIV infection thus seems to alter the well-established parity-specific pattern of malaria susceptibility in areas of stable malaria transmission, where in the absence of HIV, primigravidae and, to a lesser extent, secundigravidae are more affected than are other parities [1,3].
Although it is now well established that HIV-infected pregnant women are more susceptible to malaria, little is known of the adverse consequences of dual infection with maternal HIV and malaria on pregnancy outcomes. We report here the effects of dual infections on infant outcomes, including their effect on the two major aetiological pathways of LBW: shortened gestation (preterm delivery; PTD) and IUGR (i.e. small for gestational age; SGA) . Because maternal malaria and HIV infections are associated with an increase in the severity of anaemia, a known risk factor for maternal death and poor infant outcomes [18–21], we also report on the effect of dual infections on maternal anaemia at delivery.
Subjects and methods
This study was conducted at the Nyanza Provincial General Hospital (NPGH) in Kisumu, a city with a population of approximately 300 000 people, located on the shores of Lake Victoria. Malaria transmission is perennial and P. falciparum accounts for 98% of the malaria cases, the remaining 2.0% being caused by Plasmodium malariae and Plasmodium ovale. Chloroquine resistance is widespread, with 75–80% of P. falciparum strains showing a RII/RIII resistance pattern . NPGH is a 400-bed government referral hospital providing healthcare mostly to the local low-income population. On average, approximately 100 pregnant women present each day to the antenatal care (ANC) clinic, 30 of whom do so for their first visit. As part of the ANC package for this hospital, women are tested for syphilis using the rapid plasma reagin card test, (Becton Dickinson, Cockeyville, USA), and those seroreactive for syphilis are treated with 2.4 mU intramascular benzathine penicillin . The study was completed before the introduction of intermittent preventative treatment with sulfadoxine–pyrimethamine as the national policy for the control of malaria in pregnancy.
Enrolment procedures have been described elsewhere . Briefly, healthy pregnant women with no known underlying disease visiting the prenatal clinic service of the NPGH with an uncomplicated singleton pregnancy of at least 32 weeks’ gestation and residing in Kisumu area were invited to participate. After informed consent was obtained, a questionnaire was completed to collect information on socioeconomic status, medical, and obstetric history, and body weight was measured. After the client received counselling about HIV, blood was obtained by finger prick for HIV testing, a malaria thick smear and haemoglobin levels. Post-test counselling, supportive counselling and haematinics were offered to all participating women, and women with symptomatic malaria were treated. All screened women were encouraged to deliver in NPGH. At delivery, blood was again obtained from the mother for a malaria smear and haemoglobin, and a placental blood smear was obtained. Within 24 h of birth, infants were weighed on an electronic balance (Ohaus, Florham Park, NJ, USA), and their gestational age was assessed by trained study assistants using the modified Dubowitz method .
The study protocol was approved by the institutional review boards of the Kenya Medical Research Institute, the Centers for Disease Control and Prevention, Atlanta, Georgia (USA) and the Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Peripheral and placental blood smears were stained with Giemsa and examined for malaria parasites. A thick smear was considered negative if 100 microscopic fields revealed no parasites. Haemoglobin was measured using Hemocue (Mission Viejo, CA, USA.). HIV testing involved two rapid tests: an initial Serostrip HIV-1/2 (Saliva Diagnostic Systems Pte. Ltd., Singapore) and a confirmatory Capillus HIV-1/HIV-2 (Cambridge Diagnostics Ltd., Wicklow, Ireland) on samples that tested positive. Western blot was performed on discordant samples.
An uncomplicated pregnancy was defined as a pregnancy without the presence of hypertension, pre-eclampsia, polyhydramnios, an abnormal presentation of the foetus, a history of a previous caesarean section, haemorrhage, or repeated spontaneous abortions (more than two). Because we were interested in the overall effect of malaria in pregnancy, malaria infection at delivery was defined as any evidence of current malarial infection (post-delivery maternal peripheral parasitaemia or placental parasitaemia, either in the presence of asexual stages or malaria pigment), detected on a thick blood smear. Haemoglobin levels < 11 g/dl of blood and < 8 g/dl were considered anaemia and moderate to severe anaemia, respectively [26,27]. HIV seropositivity was defined as a positive result on both rapid tests; women not reactive with the initial Serostrip HIV-1/2 test were considered to be HIV seronegative. Women who were HIV seronegative and had no malaria at delivery were considered to be uninfected. Women who were HIV seronegative but had malaria at delivery were considered to be infected with malaria alone. Women who were HIV seropositive but had no malaria at delivery were considered to be infected with HIV alone. Women were considered to have dual infection if they were HIV seropositive and had malaria at delivery. Newborns were classified as LBW if they weighed less than 2500 g . PTD was defined as any delivery that occurred before 37 completed weeks of gestation. SGA was defined as a sex-specific birthweight at or below the 10th percentile for the weight-for-gestational-age of an international reference population . For the purpose of this analysis, normal weight-for-gestational-ages were children with birthweights greater than the 10th percentile of the weight-for-gestational-age reference population. An adverse birth outcome was defined as a stillbirth, LBW, PTD or SGA infant, or moderate to severe maternal anaemia at delivery. The rainy season included the months of April, May and June (long rains) and October and November (short rains).
Data analysis and statistical methods
Differences in means were compared using the Student's t test, and differences in proportions were analysed using the chi-square test. Risk ratios (RR) were computed with 95% confidence intervals (CI) to measure the strength of the associations. The relationship between malaria at delivery, maternal HIV infection and demographic and obstetric factors on adverse birth outcomes were investigated by bivariate analysis, and stratified by gravidity (primigravidae versus multigravidae). Adjusted odds ratios (OR) were computed using logistic regression ; models adjusted for maternal weight (< 25th percentile versus ≥ 25th percentile, kg), maternal age (< 20 versus ≥ 20 years), years of education (< 8 versus ≥ 8 years), ethnicity (Luo versus non-Luo), season of delivery (rainy versus dry), hospitalization in current pregnancy, and sex of the child. The models for postpartum anaemia were also adjusted for the type of delivery (caesarean section or assisted delivery versus normal delivery) and the use of haematinics. The covariates were included in the models if they were significantly associated with any of the four outcome measures in the bivariate analyses, or if they were known to be associated with these outcomes based on previous studies. Cigarette smoking, a well-known risk factor for LBW, was not common in this population (reported by less than 1% of the women) and was not included in the analysis. A multiple linear model  was used to assess the effect of HIV, malaria, and dual infection on birthweight, gestational age and maternal haemoglobin. We assessed the interaction between malaria and HIV in separate models, and a statistically significant interaction was evident among anaemic multigravidae. We then repeated the analyses using the infection categories: no infection, HIV alone, malaria alone or dual infection. Analysis was performed using EPI INFO 6.01 (Centers for Disease Control and Prevention, Atlanta, GA, USA) and SAS (Version 6.12, SAS Institute, Cary, NC, USA).
Between June 1996 and March 1999, 5168 women were screened, of whom 75 (1.5%) did not have complete laboratory results. Of the remaining 5093 women, and consistent with patterns of home versus health facility delivery, 2539 (49.9%) delivered at the study hospital. Women with twins (36), and women without malaria result (37) were excluded from the analysis.
Compared with women who were included in the analysis, those who were excluded (i.e. home delivery or incomplete laboratory data) were more likely to be older, to have less than 8 years of education, to be married, to be multigravidae, to be of Luo ethnicity, to reside in the peri-urban rather than the urban area of Kisumu, and to have had moderate-to-severe anaemia in the third trimester. The prevalence of HIV, syphilis and malaria in the third trimester was similar between the two groups (data not shown).
Of the 2466 women included in the analysis, 1169 (47.4%) were primigravidae. Compared with multigravidae, primigravidae women were more likely to be younger [mean age (SD) 18.8 (2.5) versus 24.3 (4.7) years; P < 0.001]. Among the 2466 women, 599 (24.3%) were HIV seropositive and 543 (22.0%) had evidence of malaria infection at delivery. Malaria infection at delivery occurred in 179 out of 599 HIV-seropositive women (29.9%) compared with 364 out of 1867 HIV-seronegative women (19.5%) (RR 1.5; 95% CI 1.3–1.8; P < 0.001), and was more common among primigravidae in whom 323 out of 1169 (27.6%) had malaria at delivery compared with 220 out of 1297 (17.0%) among multigravidae (RR 1.6; 95% CI 1.4–1.9; P < 0.001). Comparing women who had and who did not have malaria at delivery, women who had malaria at delivery were more likely to have had malaria in the third trimester: 45.1% (245/543) versus 11.8% (227/1923) (RR 3.8; 95% CI 3.3–4.5; P < 0.001).
Of the 34 stillbirths, 17 (1.1%) were recorded among 1503 women without HIV and malaria infection, four (1.0%) among 420 women infected with HIV alone, nine (2.5%) among 364 women with malaria alone, and four (2.2%) among 179 women with dual infection. Compared with women without malaria, stillbirths were more common in women with malaria infection at delivery, irrespective of HIV status [1.1% (21/1923) versus 2.4% (13/543); P = 0.02]; stillbirth rates were similar in women with and without HIV infection regardless of malaria infection status [1.3% (8/599) versus 1.4% (26/1867); P = 1.00]. The characteristics of the women studied stratified by outcome of delivery are shown in Table 1. Third trimester anaemia, HIV infection, malaria and dual infection had the strongest association with an adverse birth outcome. Because of the small numbers, all stillborn infants were removed from further analysis, leaving 2432 live singleton infants with maternal HIV and malarial infection status available for analysis.
Adverse birth outcomes in relation to maternal HIV infection and malaria
Birthweight was recorded for 2431 infants (99.9%). The overall mean (SD) birthweight was 3235 g (450), and 113 out of 2431 babies (4.6%) had LBW. An increase in LBW prevalence was seen among firstborns of mothers with HIV alone, malaria alone, or dual infection compared with those with neither infection (P = 0.09, 0.006 and < 0.001, respectively; Table 2). However, no difference was seen in the prevalence of LBW and maternal infection status among multigravidae (P = 0.3, P = 0.4, and P = 1.0, respectively). Women who had parasitaemia in the third trimester and also had malaria at delivery were at a higher risk of delivering an LBW baby, compared with aparasitaemic women in the third trimester who had malaria at delivery [10.5% (25/239) versus 5.5% (16/291), RR 1.9; 95% CI 1.0–3.5; P = 0.04]. In a logistic regression model among the primigravidae, malaria alone and dual infection were associated with a twofold and a 3.5-fold increased risk of LBW (P = 0.006 and P < 0.001) respectively, with no significant effect seen in women with similar status among the multigravidae (P = 0.7 for both groups; Table 3).
In a linear analysis, maternal HIV infection was associated with a 99 g (95% CI 52–145) reduction in mean birthweight among all gravidae (P < 0.001). Among primigravidae, the mean (SD) birthweight of infants of uninfected women was 3186 g (416) (Fig. 1). After adjusting for other covariates in the linear model, this mean (95% CI) birthweight was 40 g (−32 to 112; P = 0.3) lower in primigravidae women with HIV alone, 145 g (82–209; P = 0.001) lower in primigravidae women with malaria alone, and 206 g (115–298; P = 0.001) lower in primigravidae with dual infection. The mean (SD) birthweight of infants of uninfected multigravidae women was 3373 g (447). Maternal HIV alone and dual infection lowered this mean birthweight by 138 g (78–199) and 161 g (63–259), respectively (P < 0.001 for each), but malaria infection alone had no effect (8 g, 95% CI −71–88; P = 0.80).
Gestational age was determined for 2397 infants (98.6%). The mean (SD) gestational age was 38.6 weeks (1.3 weeks) and 160 infants (6.7%) were PTD. Higher rates of PTD were seen with maternal malaria infection (P = 0.027) or dual HIV/malaria infection (P < 0.0001), but only in primigravidae (Table 2).
In a logistic regression model, primigravidae women infected with malaria alone had an increased risk of PTD when compared with uninfected women (P = 0.04), whereas dual-infection in the same group increased the risk of PTD by threefold (P < 0.001); none of the infections had any effect on PTD among the multigravidae (HIV alone P = 0.5, malaria alone P = 0.3 and dual infection P = 0.2, Table 3).
The mean (SD) gestational age of infants of uninfected primigravidae women was 38.6 (1.3) weeks. In a linear model, malaria and dual infection had a minimal, but significant effect of reducing the mean gestational age among primigravidae, but not among multigravidae (data not shown).
Small for gestational age
Overall, the prevalence of SGA was 9.8% (236/2397) and like PTD, the prevalence of SGA was higher among primigravidae with malaria alone (P = 0.008) or primigravidae and multigravidae with dual-infection (P = 0.02) and (P = 0.01), respectively (Table 2). Women who had parasitaemia in the third trimester and also at delivery were at higher risk of delivering an SGA infant compared with aparasitaemic women in the third trimester who had malaria at delivery [18.2% (43/236) versus 11.4% (33/290), RR 1.6; 95% CI 1.1–2.4; P = 0.03], but no effect was observed on prematurity [8.5% (20/236) versus 9.0% (26/290), RR 0.9; 95% CI 0.5–1.7; P = 0.8]. In a logistic regression model, primigravidae women infected with malaria alone (P = 0.008) or both gravidae with dual infection (P = 0.02 for primigravidae and P = 0.05 for multigravidae) were at increased risk of delivering an SGA infant when compared with uninfected women (Table 3).
A haemoglobin level was available for 2173 women (89.4%). The mean (SD) haemoglobin level was 10.5 g/dl (2.4) and 1243 out of 2173 women (57.2%) had anaemia (haemoglobin < 11 g/dl), and 300 women (13.8%) had moderate to severe anaemia (haemoglobin < 8 g/dl). A higher prevalence of moderate to severe anaemia was seen among primigravidae with HIV alone (P = 0.008) and in both gravidae with dual infection (P = 0.003 for primigravidae and P < 0.001 for multigravidae) (Table 2). An interaction term between HIV and malaria was significant among the multigravidae (Table 3). In a logistic regression model, primigravidae with HIV alone had a twofold increased risk of postpartum moderate to severe anaemia (P = 0.007; Table 3), and this risk was more than twofold among dually infected primigravidae and threefold among multigravidae (P = 0.001 and P < 0.001, respectively).
Mean haemoglobin levels, stratified by maternal infection status and gravidity are shown in Fig. 2. The mean (SD) haemoglobin level of uninfected primigravidae was 10.8 g/dl (2.4). After adjusting for other covariates in the multiple linear analysis, this mean (95% CI) haemoglobin level was 0.9 g/dl (0.4–1.3) lower in primigravidae women with HIV alone (P < 0.001), 0.8 g/dl (0.4–1.2) lower in primigravidae women with malaria alone (P < 0.001), and 1.5 g/dl (0.9–2.0) lower in women with dual infection (P < 0.001) (Fig. 2). Among uninfected multigravidae women, the mean (SD) haemoglobin was 10.7 g/dl (2.4). Multiple linear analysis among multigravidae women showed that infection with HIV alone lowered the mean (95% CI) haemoglobin levels by 0.4 g/dl (0.05–0.7; P = 0.03), but malaria alone had no effect (mean reduction 0.4, 95% CI 0.0–0.8; P = 0.1). Dual infection significantly lowered the mean (95% CI) haemoglobin level by 1.3 g/dl (0.7–1.8; P < 0.001) (Fig. 2).
Adverse birth outcomes in relation to single versus dual infection
Compared with women infected with HIV alone, primigravidae with dual infection had an increased risk of delivering an LBW baby (P = 0.04) or a PTD (P = 0.02); multigravidae with dual infection had an increased risk of anaemia (P = 0.002) (Table 3). Similarly, dual infection increased the risk of maternal anaemia among the primigravidae (P = 0.03) and multigravidae (P = 0.01) over the risk caused by infection with malaria alone (Table 3).
The overall prevalence of LBW was low in this study population, and multigravidae overall had a higher mean birthweight than primigravidae. Compared with uninfected women (with no malaria or HIV), maternal HIV infection was associated with a 99 g reduction in mean birthweight, which is consistent with findings from other studies in the region [32,33], although this reduction did not translate into a greater risk of LBW in either gravidae. Neither PTD nor SGA was associated with HIV infection alone, a finding consistent with a Ugandan study among asymptomatic HIV-seropositive women , but in contrast to findings from Kinshasa, Zaire . The latter study included women with symptomatic HIV infection, and a significantly higher prevalence of PTD and LBW was reported among infants in that study .
Infection with HIV alone nearly doubled the risk of postpartum moderate to severe anaemia in primigravidae, and was associated with a reduction in mean haemoglobin levels in multigravidae, consistent with a previous report . Postpartum haemorrhage has been found to be associated with HIV infection , and could have lowered the postpartum haemoglobin levels in our study. However, this pregnancy outcome was reported in less than 1% of our study population, and could not be further evaluated in the study. In addition, the time between delivery and taking blood for haemoglobin estimation could affect the maternal postpartum haemoglobin levels because of volume redistribution resulting from the effects of labour. However, the blood sample for haemoglobin estimation in this study was taken soon after delivery in a consistent manner for all the women in the four groups. The observed trend in Fig. 2 is therefore probably a true trend reflecting the direct effect of HIV  or its co-infection with malaria on postpartum anaemia.
As expected, maternal malaria infection identified at delivery was associated with a reduction in the mean birthweight, resulting from a combination of reduced gestational age and an increased risk of IUGR among the primigravidae . Women who had parasitaemia during the third trimester and also had malaria at delivery had an increased risk of both LBW and SGA, when compared with women with malaria at delivery but no detectable parasitaemia in the third trimester. This finding reflects the effect of chronic malaria infection on fetal growth.
When compared with uninfected women, dual infection among primigravidae was associated with a threefold increased risk of LBW, almost a threefold increased risk of prematurity, and approximately a twofold increased risk of SGA. In addition, dual infection more than doubled the risk of moderate to severe anaemia (haemoglobin < 8 g/dl) in both primigravidae and multigravidae. A comparison of dually infected women with women infected with HIV alone showed that the risks of LBW and prematurity among primigravidae, and moderate to severe anaemia among multigravidae were exacerbated by co-existent malaria. Similarly, when compared with women infected with malaria alone, dual infection substantially increased the risk of moderate to severe anaemia over and above that among primigravidae and multigravidae women infected with malaria alone. We are currently also investigating whether children born to women dually infected with HIV and placental malaria are more likely to be infected with HIV, as a result of the increased transmission of HIV from mother to infant in the presence of placental infections with P. falciparum, as was postulated in a study from Malawi .
This study has several limitations and may not be fully generalizable to other populations. In our study population, only 4.6% of the infants were LBW, compared with 15.0% reported by a previous study from the same hospital . This is likely to have resulted from the different entry criteria used in the current study: as opposed to the previous study, which included all women attending for delivery at our study hospital, women in the current study were eligible for screening only if they had no known underlying disease, had attained a gestational age of 32 weeks or more, and had had an uncomplicated pregnancy. Therefore, this study sample is not representative of the overall ANC population in this hospital, and represents a selection of otherwise ‘healthy’ women. Because of the study design, we only collected data on women who had met the inclusion criteria, and no pre-enrolment data were documented at the recruitment stage for women who were not eligible for enrolment. Because we only included women with a gestational age of 32 weeks or greater, the effects of HIV and malaria infection on the early events of pregnancy outcome, such as abortions and very premature delivery, could not be evaluated. In addition, the number of perinatal deaths in our study was small (2.0%; n = 2466), probably due to the same reasons noted above.
This study demonstrates that women with dual infection are at a particular risk of adverse birth outcomes. In areas with a moderate or high prevalence of HIV and malaria, all pregnant women should be the focus of malaria control efforts to improve birth outcomes. It is important to assess whether treatments for anaemia that have proved to be beneficial in HIV-seronegative pregnant women offer the same benefits in HIV-seropositive women.
The authors would like to thank the project staff at the ANC, labour ward, counsellors, laboratory technicians and computer data entry staff for assisting in many ways to realize this work. They also thank Dr Kevin DeCock for his valuable comments on the manuscript; and Dr John Odondi, the Medical Superintendent, and health workers from the Nyanza Provincial General Hospital for their cooperation in the study. Special thanks go to all the pregnant women who participated in this study, and the Director of the Kenya Medical Research Institute for his permission to publish this work.
Sponsorship: Supported by the United States Agency for International Development (grant numbers AOT0483-PH1-2171 and HRN-A-00-04-00010-02) and the Netherlands Foundation for the Advancement of Tropical Research, the Hague, the Netherlands (J.G.A., A.M.vE. and F.O.tK.).
1.McGregor IA. Epidemiology, malaria and pregnancy. Am J Trop Med Hyg
2.Phillips-Howard PA. Epidemiological and control issues related to malaria in pregnancy. Ann Trop Med Parasitol
1999, 93 (Suppl.)
3.Brabin BJ. An analysis of malaria in pregnancy in Africa. Bull WHO
4.McGregor IA, Wilson ME, Billewicz WZ. 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
5.Redd SC, Wirima JJ, Steketee RW. Risk factors for anemia in young children in rural Malawi. Am J Trop Med Hyg
6.McCormick MC. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med
7.UNAIDS/WHO (2001). Global HIV/AIDS epidemic update.
Geneva: UNAIDS; December 2001.
8.Allen S, de Perre P, Serufilira A, Lepage P, Carael M, DeClercq A, et al
. Human immunodeficiency virus and malaria in representative sample of childbearing women in Kigali, Rwanda. J Infect Dis
9.Steketee RW, Wirima JJ, Bloland PB, Chilima B, Mermin JH, Chitsulo L, Breman JG. Impairment of pregnant women's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus infection in Malawi. Am J Trop Med Hyg
10.Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Russell WB, Broadhead RL. An evaluation of the effects of intermittent sulfadoxine–pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi. Ann Trop Med Parasitol
11.Parise ME, Ayisi JG, Nahlen BL, Schultz LJ, Roberts JM, Misore A, et al
. Efficacy of sulfadoxine–pyrimethamine for prevention of placental malaria in an area of Kenya with high prevalence of malaria and human immunodeficiency virus infection. Am J Trop Med Hyg
12.Brabin L, Verhoeff FH, Kazembe P, Brabin BJ, Chimsuku L, Broadhead R. Improving antenatal care for pregnant adolescents in Southern Malawi. Acta Obstet Gynecol Scand
13.Verhoeff FH, Brabin BJ, Hart CA, Chimsuku L, Kazembe P, Broadhead RL. Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control. Trop Med Intern Hlth
14.Weiss HA, De Cock KM. The global epidemiology of HIV/AIDS. Trop Med Intern Hlth
15.Whitworth J, Morgan D, Quigley M, Smith A, Mayanja B, Eotu H, et al
. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet
16.French N, Nakiyingi J, Lugada E, Watera C, Whitworth JA, Gilks CF. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS
17.Villar J, Belizan JM. The relative contribution of prematurity and fetal growth retardation to low birth weight in developing and developed societies. Am J Obstet Gynecol
18.Brabin BJ. The risks and severity of malaria in pregnant women
. UNDP/World Bank/WHO programme for Research and Training in Tropical Diseases Research (TDR)
. Applied Field Research in Malaria Reports No. 1; 1991.
19.McDermott JM, Slutsker L, Steketee RW, Wirima JJ, Breman JG, Heymann DL. Prospective assessment of mortality among a cohort of pregnant women in rural Malawi. Am J Trop Med Hyg
20.Moore RD. Human immunodeficiency virus infection, anemia, and survival. Clin Infect Dis
21.van Eijk A, Ayisi J, ter Kuile FO, Misore A, Otieno JA, Kolczak MS, et al
. Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenyan. Am J Trop Med Hyg
22.Bloland PB, Lackritz EM, Kazembe PN, Were JB, Steketee R, Campbell CC. Beyond chloroquine: implications of drug resistance for evaluating malaria therapy efficacy and treatment policy in Africa. J Infect Dis
23.Ministry of Health. Clinical guidelines for diagnosis and treatment of common hospital conditions in Kenya
. Nairobi, Kenya: Government of Kenya, Ministry of Health; 1994.
24.Ayisi JG, van Eijk A, ter Kuile FO, Kolczak MS, Otieno JA, Misore AO, et al
. Risk factors for HIV infection among asymptomatic pregnant women attending an antenatal clinic in western Kenya. Int J STD AIDS
25.Ballard JL, Novak KK, Driver M. A simplified score for assessment of fetal maturation of newly born infants. J Pediatr
26.World Health Organization. Prevention and management of severe anaemia in pregnancy.
(WHO/FHE/MSM/93.5). Geneva: World Health Organization, 1993.
27.Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Broadhead RL. An analysis of the determinants of anaemia in pregnant women in rural Malawi – a basis for action. Ann Trop Med Parasitol
28.World Health Organization. Development of indicators for monitoring progress towards health for all by the year 2000.
(Health for all series, Vol. 4). Geneva: World Health Organization; 1981.
29.Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, Tashiro M. Fetal growth and perinatal viability in California. Obstet Gynecol
30.Kleinbaum DG. Logistic regression: a self-learning text.
Dietz M, Gail M, Krickeberg K, Singer B (editors). New York: Springer-Verlag; 1994. 282282 pp.
31.Kleinbaum DG, Kupper LL, Muller KE. Confounding and interaction in regression.
In: Applied regression analysis and other multivariable methods
, 2nd ed. Payne M (editor). Belmont, California: Duxbury Press; 1994. pp. 163–180.
32.Braddick MR, Kreiss JD, Embree JE, Datta P, Ndinya-Achola JO, Pamba H, et al
. Impact of maternal HIV infection on obstetrical and early neonatal outcome. AIDS
33.Mmiro F, Ndugwa C, Guay L, Hom D, Ball P, Mugisha NK, et al
. Effect of human immunodeficiency virus-1 infection on the outcome of pregnancy in Ugandan women. Pediatr AIDS HIV Infect Fetus Adolesc
34.Ryder RW, Nsa W, Hassig SE, Behets F, Rayfield M, Ekungola B, et al
. Perinatal transmission of human immunodeficiency virus type 1 (HIV) to infants of seropositive women in Zaire. N Engl J Med
35.Leroy V, Ladner J, Nyiraziraje M, De Clercq A, Bazubagira A, Van de Perre P, et al
. Effect of HIV-1 infection on pregnancy outcome in women in Kigali, Rwanda, 1992–1994. Pregnancy and HIV Study Group. AIDS
36.Van Den Broek NR, White SA, Neilson JP. The relationship between asymptomatic human immunodeficiency virus infection and prevalence and severity of anaemia in pregnant women. Am J Trop Hyg
37.Steketee RW, Wirima JJ, Hightower AW, Slutsker L, Heymann DL, Breman JG. The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi. Am J Trop Med Hyg
38.Bloland PB, Wirima JJ, Steketee RW, Chilima B, Hightower A, Breman JG. Maternal HIV infection and infant mortality in Malawi: evidence for increased mortality due to placental malaria infection. AIDS
39.Were EO, Karanja JK. Low birth weight at the Nyanza General Hospital Kisumu, Kenya. East Afr Med J