Aim-To determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer. Methods-One hundred and eighty materno-neonatal pairs from a Malawian population were assessed. Cord and maternal serum samples were tested for total serum IgG antibody titres using nephelometry, and for specific IgG antibody titres to Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme linked immunsorbent assay (ELISA). Results-Multiple regression analyses showed that placental malaria was associated with a decrease in placental IgG antibody transfer to S pneumoniae and measles to 82% and 81%, respectively. Maternal HIV infection was associated with a reduction in IgG antibody transfer to S pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S pneumoniae and measles IgG antibody transfer reduction to 86% and 87%, respectively. No eVect was seen with tetanus toxoid antibody transfer. Conclusion-The combined influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia seems to be linked to the low transplacental antibody transfer observed in the Malawian population.

Summaryobjectives 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.method Descriptive cross-sectional analysis of P. falciparum prevalence in pregnant women at first antenatal visit and of women at delivery who had received two sulphadoxine-pyrimethamine treatments for malaria. HIV status was assessed in 621 women who attended for antenatal care and for delivery at two rural hospitals in southern Malawi in 1993-94. Information was collected on maternal age, parity and gestational age. Prevalence of P. falciparum was measured at first antenatal visit and delivery. Women were given two routine treatment doses of sulphadoxine-pyrimethamine (SP), at first antenatal visit and between 28 and 34 weeks gestation, conforming to Malawi government policy on antimalarial control during pregnancy.results Prevalence of HIV infection was 25.6% and all infections were HIV type-1. In primigravidae malaria prevalence at recruitment was 56.3% in HIV-infected and 36.5% in HIV-uninfected women (P ϭ 0.04). The corresponding figures for multigravidae were 23.8% and 11.0%, respectively (P Ͻ 0.01). HIVinfected primigravidae had increased malaria prevalence at all gestational ages. Peak parasite prevalence occurred earlier in gestation in HIV-infected primigravidae (16-19 weeks if HIV-infected; 20-23 weeks if HIV-uninfected). The relative risk for parasitaemia in HIV-infected compared to HIV-uninfected women was significantly increased in three of five parity groups, including the two highest ones (parity Ͼ3), indicating parity-specific immunity to malaria was impaired. Malaria prevalence at delivery remained high in HIV-infected women despite prior routine treatment with sulphadoxine-pyrimethamine in pregnancy. There was no significant difference in parasite prevalence at delivery between women who did or did not use sulphadoxine-pyrimethamine.conclusions HIV infection is associated with a significant increase in malaria prevalence in pregnant women of all parities with the effect apparent from early in gestation. Two treatment doses of sulphadoxine-pyrimethamine were inadequate to clear parasitaemia in many women by the time of delivery and this occurred independently of HIV status and despite high sensitivity to SP in this area. There is a need to undertake longitudinal studies to determine the incidence of P. falciparum infection in HIV-infected and uninfected pregnant women and to reassess the frequency and timing of sulphadoxine-pyrimethamine treatment doses in these women. Late pregnancy re-infections with P. falciparum probably explain the high parasite prevalence at delivery following sulphadoxinepyrimethamine treatment at 28-34 weeks gestation. keywords pregnancy, malaria, HIV, antimalarial control, sulphadoxine-pyrimethamine correspondence Professor B.J. Brabin,

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Objective: (1) To describe the sex-speci®c, 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 (modi®ed Ballard). Sex-speci®c 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. Signi®cantly 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 gadl) at ®rst 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-speci®c 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.

The prevalence of infants born with low cord haemoglobin (fetal anaemia) is high in areas where malaria and iron deficiency anaemia in pregnancy are common. The objective of the present study was to determine risk factors for fetal anaemia in an area of high malaria transmission in southern Malawi. A case control study was undertaken with fetal anaemia defined as cord haemoglobin (Hb) < 12.5 g/dl. Between March 1993 and July 1994, pregnant women attending the study hospitals for the first time in that pregnancy were enrolled. Data on socio-economic status, anthropometry, previous obstetric history and current pregnancy were collected. Malaria parasitaemia, Hb levels and iron status were measured in maternal blood at recruitment and delivery and in umbilical venous blood. Fetal anaemia occurred in 23.4% of babies. Mean (SD) cord Hb was 13.6 g/dl (1.83). Factors associated with fetal anaemia were: birth in the rainy season [adjusted odds ratio (AOR) 2.33, 95% CI 1.73-3.14], pre-term delivery (AOR 1.60, 1.03-2.49), infant Hb < 14 g/dl at 24 hours (AOR 2.35, 1.20-4.59), maternal Hb at delivery < 8 g/dl (AOR 1.61, 1.10-2.42) or <11 g/dl (AOR 1.60, 1.10-2.31). A higher prevalence of fetal anaemia occurred with increasing peripheral Plasmodium falciparum parasite density (p=0.03) and geometric mean placental parasite densities were higher in babies with fetal anaemia than in those without (3331 vs 2152 parasites/microl, p=0.07). Interventions should aim to reduce fetal anaemia by improving malaria and anaemia control in pregnancy and by addressing the determinants of pre-term delivery.

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.

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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.