TRANSACTIONS OF THE ROYALSOCIETY OF TROPICALMEDICINEAND HYGIENE(1992)86, 48-85
Malaria
chemoprophylaxis,
A. M. Greenwood, J. R. M. Armstrong, Laboratories, Fajara, Banjul, The Gambia
birth weight
483
and child survival
P. Byass, R. W. Snow and B. M. Greenwood
Medical Research Council
Abstract
Study of the effects of malaria chemoprophylaxis given during pregnancy on birthweight and investigation of the influence of birthweight on child survival suggestthat, in a rural area of The Gambia, chemoprophylaxis given during pregnancy might reduce infant mortality by about one-fifth in the children of primigravidae but by less than 5% in the children of multigravidae. In malaria endemic areas,primigravidae should be protected against malaria not only for their own sakebut also for that of their infants. Introduction
When malaria occurs during pregnancy the placenta may be infected heavily with malaria parasites and its function impaired (BRABIN, 1983; WATKINSON & RUSHTON, 1983; MCGREGOR, 1984). In consequence, babies born to mothers with an infected placenta have~alower mean birth weight than control infants (BRABIN. 1983: MCGREGOR,1954). Primigravidae are iarticulatly sus: ceptible to malaria during pregnancy and, in endemic areas, malaria is an important cause of low birth weight among the infants of this group of women. Chemoprophylaxis given during pregnancy can increasemean birth weight, especially in primigravidae and in grand multigravidae (MORLEY, 1978; HAMILTON et al., 1972; GREENWOOD et al., 1989). For this reason, chemoprophylaxis is generally recommended for pregnant women resident in malaria endemic areas. During a study undertaken in The Gambia in which pregnant women were given chemoprophylaxis with Maloprim@ by traditional birth attendants (TBAs), we found that the mean birth weight of infants born to primigravidae who had received chemoprophylaxis was 156 g higher than the mean birthweight of infants born to mothers who had received placebo (GREENWOOD et al., 1989).; a much more modest effect was found in multigravidae. Both stillbirths and neonatal deaths were less frequent among the babies of women who had received chemoprophylaxis than among the babies of the controls but the number of deaths in each group was small and the differences in mortality rates between groups were not statistically significant. Therefore, we have studied the effects of birth weight on the survival of a larger group of infants born to women resident in the same community in which the chemoprophylaxis trial was undertaken and used these data to estimate the likely effects of chemoprophylaxis given during pregnancy on child survival. Subjects and Methods
The study was undertaken in a group of 41 villages near the town of Farafenni on the north bank of the river Gambia, approximately 120 km from the coast. The characteristics of this study areahave been described previouslv (GREENWOOD et al.. 1987al. In this communitv. over 90% of deliveries occur at home. During the period of the study 16 of the study villages (primaryhealth care (PHC) villages) had a TBA who assisted with annroximate1465%of’deliveries in the village. Nearly ail*pregnant women resident in the 16 PHC villages were included in a study of the effects of chemoprophylaxis on the outcome of pregnancy that we have described previously (GREENWOODet al., 1989). In this study, women were randomly assigned to receive either Maloprim@ (pyrimethamine+dapsone) or placebo which was given fortnightly by TBAs from the time that a woman first reported her pregnancy. The mean number of doses of medication received was 5, so that most mothers received chemoprophylaxis only during the last trimester of pregnancy. Address for correspondence: Dr A. M. Greenwood, MRC Laboratories, Fajara, Banjul, The Gambia.
Each woman was visited as soon as possible after delivery by a field worker employed by the Medical Research Council (MRC) and her newborn baby was weighed. Becauseof problems of distance and communication it was not possible for many weights to be recorded within 24 h of birth but. in 83% of cases. this was achieved within a week of birth. Deaths of children born to study women were recorded by village reporters and MRC field staff (GREENWOODet al.. 1987b1. During the first Z‘years of the study; 902 infants were weighed once during the first week of life and a curve constructed of mean weight by day from birth (available from the authors on request). Weight fell during the first few days of life to reach a nadir of 96% of birthweight at day 34. Subsequently, mean weight began to rise, returning to near birthweight by day 5-6. This curve was used to calculate an estimated birth weight for the majority of infants who were not seen within the first 24 h of life. Results
During a 3 year period, 1778 women resident in the study area delivered a single, live-born child; 1468(83%) of infants were weighed during the first week of life. Ap: proximately one-third of the mothers of these children lived in PHC villages and had received chemoprophylaxis during pregnancy, one-third lived in PHC villages and had received placebo, and one-third lived in smaller non-PHC villages. Thirty-nine of the infants who had been weighed during the first week of life died during the neonatal period (neonatal death rate 27 per 1000live births) and a further 41 died during the remainder of the first year of life (infant mortality rate 54 per 1000live births). Both the neonatal and infant mortality rates were considerably higher in the 310 children who were not weighed (139 and 158 per 1000live births respectively). The relationship between estimated birth weight and survival during the first year of life is shown in the Figure. There was little difference in survival between groups of children with estimated birth weights over 2000 g but both neonatal and infant mortality rates were
under1.5
1 s1.9
2.0-2.4
Estimated
2.5-2.9
30:3.4
wer3.4
birth weight (kg)
Figure. Neonataland infant mortality ratesclassifiedby birth weightin 1468single,live-bornGambianinfants.Figuresabovethe barsindicate thenumberoflive births.
484 birthweight, are underestimated in analyses of birth increased substantially in infants with a birth weight weight. Omission of some of these early deaths from our below 2000 e. Thus. the relative risks for neonatal and analyses is likely to have led to an underestimate of the for infant deiths among infants with an estimated birth incidence of low birth weight in the population as a weight of less than 2O@l g compared with those with a whole. birth weight of 2500 g;or more were 23 (95% confidence Many studies undertaken in industrialized countries interval (CI) 13, 42) aid 12 (95% CI 8, i8) respectively. have demonstrated the imuortant effect of birthweight on For those with a birth weight of 2000-2500 g the correchild survival (MCCORMICK, 1985). This effect is-likely sponding figures were 2.1 (95% CI 0.6, 6.7) and 0.8 to be equally important in developing countries where (95% CI 0.3, 2.6). Among the women whose parity was newborn babies are exposed to many hazards, but this known the proportion of deaths associatedwith low birth has been documented in community studies on only a weight (
Malaria
chemoprophylaxis,
A. M. Greenwood, J. R. M. Armstrong, Laboratories, Fajara, Banjul, The Gambia
birth weight
483
and child survival
P. Byass, R. W. Snow and B. M. Greenwood
Medical Research Council
Abstract
Study of the effects of malaria chemoprophylaxis given during pregnancy on birthweight and investigation of the influence of birthweight on child survival suggestthat, in a rural area of The Gambia, chemoprophylaxis given during pregnancy might reduce infant mortality by about one-fifth in the children of primigravidae but by less than 5% in the children of multigravidae. In malaria endemic areas,primigravidae should be protected against malaria not only for their own sakebut also for that of their infants. Introduction
When malaria occurs during pregnancy the placenta may be infected heavily with malaria parasites and its function impaired (BRABIN, 1983; WATKINSON & RUSHTON, 1983; MCGREGOR, 1984). In consequence, babies born to mothers with an infected placenta have~alower mean birth weight than control infants (BRABIN. 1983: MCGREGOR,1954). Primigravidae are iarticulatly sus: ceptible to malaria during pregnancy and, in endemic areas, malaria is an important cause of low birth weight among the infants of this group of women. Chemoprophylaxis given during pregnancy can increasemean birth weight, especially in primigravidae and in grand multigravidae (MORLEY, 1978; HAMILTON et al., 1972; GREENWOOD et al., 1989). For this reason, chemoprophylaxis is generally recommended for pregnant women resident in malaria endemic areas. During a study undertaken in The Gambia in which pregnant women were given chemoprophylaxis with Maloprim@ by traditional birth attendants (TBAs), we found that the mean birth weight of infants born to primigravidae who had received chemoprophylaxis was 156 g higher than the mean birthweight of infants born to mothers who had received placebo (GREENWOOD et al., 1989).; a much more modest effect was found in multigravidae. Both stillbirths and neonatal deaths were less frequent among the babies of women who had received chemoprophylaxis than among the babies of the controls but the number of deaths in each group was small and the differences in mortality rates between groups were not statistically significant. Therefore, we have studied the effects of birth weight on the survival of a larger group of infants born to women resident in the same community in which the chemoprophylaxis trial was undertaken and used these data to estimate the likely effects of chemoprophylaxis given during pregnancy on child survival. Subjects and Methods
The study was undertaken in a group of 41 villages near the town of Farafenni on the north bank of the river Gambia, approximately 120 km from the coast. The characteristics of this study areahave been described previouslv (GREENWOOD et al.. 1987al. In this communitv. over 90% of deliveries occur at home. During the period of the study 16 of the study villages (primaryhealth care (PHC) villages) had a TBA who assisted with annroximate1465%of’deliveries in the village. Nearly ail*pregnant women resident in the 16 PHC villages were included in a study of the effects of chemoprophylaxis on the outcome of pregnancy that we have described previously (GREENWOODet al., 1989). In this study, women were randomly assigned to receive either Maloprim@ (pyrimethamine+dapsone) or placebo which was given fortnightly by TBAs from the time that a woman first reported her pregnancy. The mean number of doses of medication received was 5, so that most mothers received chemoprophylaxis only during the last trimester of pregnancy. Address for correspondence: Dr A. M. Greenwood, MRC Laboratories, Fajara, Banjul, The Gambia.
Each woman was visited as soon as possible after delivery by a field worker employed by the Medical Research Council (MRC) and her newborn baby was weighed. Becauseof problems of distance and communication it was not possible for many weights to be recorded within 24 h of birth but. in 83% of cases. this was achieved within a week of birth. Deaths of children born to study women were recorded by village reporters and MRC field staff (GREENWOODet al.. 1987b1. During the first Z‘years of the study; 902 infants were weighed once during the first week of life and a curve constructed of mean weight by day from birth (available from the authors on request). Weight fell during the first few days of life to reach a nadir of 96% of birthweight at day 34. Subsequently, mean weight began to rise, returning to near birthweight by day 5-6. This curve was used to calculate an estimated birth weight for the majority of infants who were not seen within the first 24 h of life. Results
During a 3 year period, 1778 women resident in the study area delivered a single, live-born child; 1468(83%) of infants were weighed during the first week of life. Ap: proximately one-third of the mothers of these children lived in PHC villages and had received chemoprophylaxis during pregnancy, one-third lived in PHC villages and had received placebo, and one-third lived in smaller non-PHC villages. Thirty-nine of the infants who had been weighed during the first week of life died during the neonatal period (neonatal death rate 27 per 1000live births) and a further 41 died during the remainder of the first year of life (infant mortality rate 54 per 1000live births). Both the neonatal and infant mortality rates were considerably higher in the 310 children who were not weighed (139 and 158 per 1000live births respectively). The relationship between estimated birth weight and survival during the first year of life is shown in the Figure. There was little difference in survival between groups of children with estimated birth weights over 2000 g but both neonatal and infant mortality rates were
under1.5
1 s1.9
2.0-2.4
Estimated
2.5-2.9
30:3.4
wer3.4
birth weight (kg)
Figure. Neonataland infant mortality ratesclassifiedby birth weightin 1468single,live-bornGambianinfants.Figuresabovethe barsindicate thenumberoflive births.
484 birthweight, are underestimated in analyses of birth increased substantially in infants with a birth weight weight. Omission of some of these early deaths from our below 2000 e. Thus. the relative risks for neonatal and analyses is likely to have led to an underestimate of the for infant deiths among infants with an estimated birth incidence of low birth weight in the population as a weight of less than 2O@l g compared with those with a whole. birth weight of 2500 g;or more were 23 (95% confidence Many studies undertaken in industrialized countries interval (CI) 13, 42) aid 12 (95% CI 8, i8) respectively. have demonstrated the imuortant effect of birthweight on For those with a birth weight of 2000-2500 g the correchild survival (MCCORMICK, 1985). This effect is-likely sponding figures were 2.1 (95% CI 0.6, 6.7) and 0.8 to be equally important in developing countries where (95% CI 0.3, 2.6). Among the women whose parity was newborn babies are exposed to many hazards, but this known the proportion of deaths associatedwith low birth has been documented in community studies on only a weight (
