Francine H. Verhoeff

Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control.

Summary objectives  To examine in pregnant women the relationship between HIV infection and malaria prevalence and to determine, in relation to HIV infection, the effectiveness of sulphadoxine‐pyrimethamine in clearing P. falciparum infection.

An evaluation of the effects of intermittent sulfadoxine-pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi

The prevalence of infection with malarial parasites and the incidence of anaemia and delivery of infants with low birthweight (LBW) were investigated in 575 Malawian mothers who received one, two or three doses of sulfadoxine-pyrimethamine (SP) during pregnancy. All the subjects were enrolled at their first antenatal visit and all delivered at hospital. The prevalence of Plasmodium falciparum infection at first antenatal visit was 35.3% in primigravidae and 13.6% in multigravidae (P < 0.001). Mean haemoglobin concentration was significantly lower in primigravidae than in multigravidae (8.8 v. 9.5 g/dl; P < 0.001). Of the 233 women tested for HIV infection, 18.8% of the primigravidae and 23.7% of the multigravidae were seropositive. At delivery, there was no significant difference in parasite prevalence in peripheral or placental blood between women who had received one or two antenatal doses of SP. The multigravidae who had received two doses of SP had higher mean haemoglobin concentrations than those who had received just one (P = 0.009) [this difference was not seen in the primigravidae (P = 0.92)]. However, linear regression analysis indicated that the haematinic supplements given to the subjects contributed more to this increase in haemoglobin concentration than the SP. The mean birthweights were higher, and incidence of LBW lower in babies born to primi-and multi-gravidae who had received two or three doses of SP treatment than those seen in babies born to women who had had just one dose (P < 0.03 for each). The odds ratio for LBW in primigravidae compared with multigravidae decreased from 3.2 to 1.0 as the number of SP doses increased from one to three. The benefit of three doses (compared with none) was equivalent to the population-attributable risk of LBW in primigravidae being reduced from 34.6% to 0%. Subjects who were seropositive for HIV were twice as likely to give birth to LBW babies as the other subjects. The use of SP was not associated with maternal side-effects or perinatal complications. The present results indicate that multiple doses of SP taken during pregnancy will lead to a highly significant reduction in the incidence of LBW in infants born to primigravidae, even if the women have HIV infections. This reduction is observable even when parasite prevalence at delivery is high because of re-infections in late pregnancy; reduction in parasite prevalence earlier in pregnancy, as the result of SP treatment, leads to improved foetal growth.

Antimalarial Drugs in Pregnancy: A Review

In this review we examine the available information on the safety of antimalarials in pregnancy, from both animal and human studies. The antimalarials that can be used in pregnancy include (1) chloroquine, (2) amodiaquine, (3) quinine, (4) azithromycin, (5) sulfadoxine-pyrimethamine, (6) mefloquine, (7) dapsone-chlorproguanil, (8) artemisinin derivatives, (9) atovaquone-proguanil and (10) lumefantrine. Antimalarial drugs that should not be used in pregnancy including (1) halofantrine, (2) tetracycline/doxycycline, and (3) primaquine. There are few studies in humans on the pharmacokinetics, safety and efficacy of antimalarials in pregnancy. This is because pregnant women are systematically excluded from clinical trials. The absence of adequate safety data, especially in the first trimester, is an important obstacle to developing treatment strategies. The pharmacokinetics of most antimalarial drugs are also modified in pregnancy and dosages will need to be adapted. Other factors, including HIV status, drug interactions with antiretrovirals, the influence of haematinics and host genetic polymorphisms may influence safety and efficacy. For these reasons there is an urgent need to assess the safety and efficacy of antimalarial treatments in pregnancy, including artemisinin based combination therapies.

An analysis of intra-uterine growth retardation in rural Malawi.

Objective: (1) To describe the sex-specific, birth weight distribution by gestational age of babies born in a malaria endemic, rural area with high maternal HIV prevalence; (2) to assess the contribution of maternal health, nutritional status and obstetric history on intra-uterine growth retardation (IUGR) and prematurity.Methods: Information was collected on all women attending antenatal services in two hospitals in Chikwawa District, Malawi, and at delivery if at the hospital facilities. New-borns were weighed and gestational age was assessed through post-natal examination (modified Ballard). Sex-specific growth curves were calculated using the LMS method and compared with international reference curves.Results: A total of 1423 live-born singleton babies were enrolled; 14.9% had a birth weight <2500 g, 17.3% were premature (<37 weeks) and 20.3% had IUGR. A fall-off in Malawian growth percentile values occurred between 34 and 37 weeks gestation. Significantly associated with increased IUGR risk were primiparity relative risk (RR) 1.9; 95% CI 1.4–2.6), short maternal stature (RR 1.6; 95% CI 1.0–2.4), anaemia (Hb<8 g/dl) at first antenatal visit (RR 1.6; 95% CI 1.2–2.2) and malaria at delivery (RR 1.4; 95% CI 1.0–1.9). Prematurity risk was associated with primiparity (RR 1.7; 95% CI 1.3–2.4), number of antenatal visits (RR 2.2; 95% CI 1.6–2.9) and arm circumference <23 cm (RR 1.9; 95% CI 1.4–2.5). HIV infection was not associated with IUGR or prematurity.Conclusion: The birth-weight-for-gestational-age, sex-specific growth curves should facilitate improved growth monitoring of new-borns in African areas where low birth weight and IUGR are common. The prevention of IUGR requires improved malaria control, possibly until late in pregnancy, and reduction of anaemia.European Journal of Clinical Nutrition (2001) 55, 682–689

Breast and Complementary Feeding Practices in Relation to Morbidity and Growth in Malawian Infants

Objectives:The objective of this study was to compare growth, morbidity incidence and risk factors for undernutrition between infants receiving complementary feeding early, before 3 months of age, with those receiving complementary foods after 3 months in a poor rural Malawian community.Methods:A cohort of babies was enrolled at birth for follow-up to 12 months of age. Weight, length, morbidity and feeding patterns were recorded at 4 weekly intervals from birth to 52 weeks.Results:Mean age at introduction of water was 2.5 months (range 0–11.8), complementary foods 3.4 months (range, 1.0–10.7) and solids 4.5 months (range 1.2–13.8). Over 40% of infants had received complementary foods by 2 months and 65% by 3 months. The proportion of exclusively breast-fed infants, which included those receiving supplemental water, was 13% at 4 months, 6.3% at 5 months and 1.5% at 6 months. Infants with early complementary feeding had lower weight for age at 3 and 6 months (P<0.05), and at 9 months (P=0.07) and at 2 months they were approximately 200 g lighter. Early complementary feeding was significantly associated with increased risk for respiratory infection (P<0.05), and marginally increased risk for eye infection and episodes of malaria. Maternal illiteracy was associated with early complementary feeding (OR=2.1, 95% CI 1.3, 3.2), while later complementary feeding was associated with reduced infant morbidity and improved growth.Conclusion:Breast-feeding promotion programmes should target illiterate women. Greater emphasis is required to improve complementary feeding practices.

Seroprevalence of hepatitis B and C and HIV in Malawian pregnant women

OBJECTIVES to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV-negative pregnant women from rural Malawi. METHODS descriptive study using serum samples collected between 1993-1995 in the Shire valley in rural Malawi. Fifty HIV-positive and 100 HIV-negative samples were selected randomly from 153 HIV-positive and 443 HIV-negative women delivering in the hospital. RESULTS evidence of HBV and HCV infection was found in 71.7 and 16.5% of women, respectively. Chronic carriage of HBV (HBsAg positive) is high (13%) and in agreement with prevalences reported from highly endemic areas. Exposure to HBV and HCV probably occurred well before adulthood as the prevalence of anti-HBc antibody was high in young mothers <20 years of age (22/27; 81%). CONCLUSION HBV and HCV infections are highly endemic in rural Malawi. There was no statistical evidence to suggest that HIV positivity was associated with an increased prevalence of HBV or HCV markers. Infection with HBV or HCV was not statistically associated.

Malaria in pregnancy and its consequences for the infant in rural Malawi.

Maternal malaria and anaemia, pregnancy and infant outcomes are reviewed among a cohort of mothers and their babies living in Chikwawa district, southern Malawi. Overall, 4104 women were screened at first antenatal visit and 1523 at delivery. Factors independently associated with moderately severe anaemia (MSA; < 8 g haemoglobin/dl) in primigravidae were malaria (relative risk = 1.9; 95% confidence interval = 1.6-2.3) and iron deficiency (relative risk = 4.2; 95% confidence interval = 3.5-5.0). Only iron deficiency was associated with MSA in multigravidae. After controlling for antimalarial use, parasitaemia was observed in 56.3% of the HIV-infected primigravidae and 36.5% of the non-infected (P = 0.04). The corresponding figures for multigravidae were 23.8% and 11.0%, respectively (P = 0.002). Over 33% of the infants born alive to primigravidae were of low birthweight (LBW; < 2500 g), and 23.3% of all newborns had foetal anaemia (< 12.5 g haemoglobin/dl cord blood). LBW was significantly associated in primigravidae with pre-term delivery, placental malaria and frequency of treatment with sulfadoxine-pyrimethamine (SP), and in multigravidae with pre-term delivery, adolescence, short stature and MSA. LBW was significantly reduced with a second SP treatment in primigravidae, and with iron-folate supplementation in multigravidae. Mean haemoglobin concentrations were significantly lower in the infant who had been LBW babies than in the others, and significantly associated with parity, peripheral parasitaemia at delivery and placental malaria. At 1 year post-delivery, life status was known for 364 (80.7%) of the 451 infants enrolled in the follow-up study. Independent risk factors for post-neonatal mortality were maternal HIV infection, LBW, and iron deficiency at delivery. This study identifies priorities for improving the health of pregnant women and their babies in this rural area of Malawi.

Changes in haemoglobin levels in infants in Malawi: effect of low birth weight and fetal anaemia.

Objectives: To examine the effect of low birth weight (LBW) and fetal anaemia (FA) on haemoglobin (Hb) patterns in infancy. To study the additional contribution of other risk factors known at birth. To examine the effect of iron supplementation during infancy on Hb levels. Methods: A stratified cohort of infants in Malawi (83 with LBW (< 2500 g), 111 with FA (cord Hb < 125 g/l), 31 with both LBW and FA, and 176 controls) was followed during infancy. Hb levels were measured at about 2, 4, 6, 9, and 12 months of age. Repeated measures models were used to describe the changes in Hb levels over time. Results: The mean Hb concentration in the control group was 95.5 g/l (95% confidence interval (CI) 92.5 to 98.5) at 2 months, 86.9 g/l (95% CI 84.4 to 89.4) at 9 months, and 898 g/l (95% CI 874 to 92.2) at 12 months. Differences between LBW infants and controls increased over time (difference at 12 months: 5.5 g/l (95% CI 1.3 to 9.7)). Infants with FA had borderline significantly lower Hb at 2 months (p = 0.07), but at 6 months their levels were similar to those of controls. The LBW infants and those with FA had the lowest Hb levels (difference from controls at 12 months 7.9 g/l). Parity, placental and maternal malaria at delivery, and sex significantly affected Hb levels after adjustment for LBW and FA. After iron supplementation, Hb significantly increased. Conclusions: Antimalarial control and iron supplementation throughout pregnancy should be increased to reduce the incidence of infant anaemia and improve child development and survival.

Urban malaria and anaemia in children: a cross-sectional survey in two cities of Ghana.

Objective  To describe the epidemiology of urban malaria, an emerging problem in sub‐Saharan Africa.

Improving antenatal care for pregnant adolescents in southern Malawi.

BACKGROUND This paper considers why antenatal care (ANC) programs for adolescents may need to be improved in areas where a high proportion of first pregnancies are to young girls. DESIGN Descriptive data on the characteristics of 615 adolescents (aged 10-19 years) who attended for a first antenatal care visit at two rural hospitals in southern Malawi are given. For the 41.5% who came for a supervised delivery, details of their pregnancy care and delivery outcome are provided. The Chi-square test is used for determining significant differences between age and parity groups and logistic regression for an analysis of low birthweight. RESULTS Fifty-two percent of girls were nulliparous, 24.5% were < or =16 years and 73.3% were illiterate. Prevalence of anemia, malaria and HIV infection was high. Girls who were nulliparous, illiterate, made early antenatal care visits or gave a history of stillbirth or abortion were less likely to attend for delivery. Few primiparae required an assisted vaginal delivery or cesarean section but primiparae had more adverse birth outcomes. Forty percent of primiparae <17 years gave birth to low birthweight babies as did 28.3% of multiparae. In a logistic regression (all adolescents) low birthweight was correlated with literacy (p=0.03) and number of antenatal care visits (p=0.01). CONCLUSIONS Pregnancy morbidity and adverse birth outcomes were common in spite of antenatal care attendance. This partly reflects poor management of malaria during pregnancy. In areas like Malawi, where childbearing starts early, girls in their first pregnancy need good quality care and careful monitoring if problems are not to be perpetuated to a second pregnancy. Many girls start pregnancy with HIV and schistosomal infections which indicates the need for programs before girls become pregnant.