Under-5 mortality decreased with increasing age of the mother, was lower in those whose fathers were traders or salaried workers compared with subsistence farmers or casual labourers, decreased with increased levels of maternal education, was slightly lower in those born in later years and was highest in the far north of the district. After adjustment for these factors, the impact on survival of having an HIV-positive mother increased slightly (Table 4). There was no evidence that the effect of HIV status of the mother varied depending on these risk factors.
Restriction of group 4 to children born after, or ≤ 6 months before, the baseline filter paper collection (the restriction made for children born to HIV-positive mothers), and restriction of group 4 to children of mothers who were certainly HIV-negative at the time of the child's birth, made little difference to the estimates of the HRs (not shown). Inclusion of the 34 children said to be alive or to have died outside the district, but for whom the informant was not a relative, also made little difference to the results.
Nineteen children of HIV-positive mothers and 15 children of HIV-negative mothers experienced the death or terminal illness of their mother before age 10 years. The figure of 19 appears low and reflects the fact that 18/88 (20%) of children born to HIV-positive mothers died more than 1 year before their mother's death. Among infants born to HIV-positive mothers, mortality was higher among those whose mother had died or who was terminally ill (three deaths among eight children) compared with those whose mother was alive and not terminally ill (HR 2.7, 95% CI 0.8–9.2). Mortality between 1 and 5 years was also increased slightly for those who experienced their mother's death or terminal illness (two deaths among 12 children; HR 1.7, 95% CI 0.4–7.6). There were no deaths among children born to HIV-negative mothers who died or were terminally ill, but only one such terminal illness occurred during the first year of the child's life.
Eight children of HIV-positive mothers and 27 children of HIV-negative mothers experienced the death or terminal illness of their father before age 10 years. Among infants born to HIV-positive mothers, mortality was 25% for children whose father died or was terminally ill (one death among four children) compared with 27% for children whose father was alive and not terminally ill. The corresponding percentages for those born to HIV-negative mothers were 0% (no deaths in four children) and 11%. Five children born to an HIV-positive mother and 19 children born to an HIV-negative mother were aged 1–5 years during the period from 1 year prior to 1 year after their father's death, and none died during that period. Only one child with an HIV-positive mother experienced the death of both parents.
Of the childhood deaths, 54% (114/212) were caused by acute febrile illnesses; this proportion did not vary by maternal HIV status (P = 0.8). A verbal postmortem result classified as AIDS/TB–AIDS was found for 16% (6/38) of dead children in group 1, 15% (4/26) in group 2, 0% (0/28) in group 3 and 4% (5/118) in group 4 (P = 0.03 comparing group 1 and group 4).
Given a prevalence of HIV infection in pregnant women of 10%, 18% (95% CI, 10–26) of deaths in children before their fifth birthday can be attributed to HIV in this population.
None of the children in the study who were seen in the follow-up met the WHO Pediatric AIDS Case Definition  and the symptom review did not reveal a high prevalence of morbidity among surviving children. Children of HIV-positive mothers were more likely to be reported as ‘not well’ at the time of interview [group 1, 3/32 (9%); group 2, 9/78 (12%); group 3, 3/89 (3%); group 4, 24/554 (4%); P = 0.03], but this was not reinforced by specific symptoms or reported health care usage.
Children aged < 10 years were generally stunted [Z-scores were less than −2 for 46% (238/512) for height-for-age]. They were, on average, wasted, although only 3% (15/511) had a Z-score of less than −2 for weight-for-height. The proportion of children aged 10–14 years whose body mass index was below the 15th centile was 41% (109/263) . All indices were normally distributed.
Differences in anthropometric measurements between children in groups 1 and 4, and differences by orphanhood, were small and not statistically significant (Table 5; results for body mass index not shown), both on crude analysis and after adjustment for other risk factors. There was no evidence that the impact of the mother's HIV status or orphanhood varied depending on other examined risk factors, although the power of these analyses was low.
It was not possible to compare double, maternal and paternal orphans because of sample size constraints. Most orphanhood was from paternal mortality: of orphans aged < 5 years, one was a double orphan, three were maternal and eight were paternal orphans. The corresponding figures for children aged 5–9 years were four, four and 34.
Under-5 child mortality is much higher in children born to HIV-positive mothers than in those born to HIV-negative mothers. Assuming around 35% vertical transmission , and given the degree of uncertainty in our mortality estimates, our findings are consistent with the increase in mortality being largely confined to children who were themselves HIV infected. Other studies have found that HIV-negative children of HIV-positive mothers have similar mortality rates to children of HIV-negative mothers [1,16,26]. However, the borderline evidence for an increased mortality rate in those born to HIV-negative mothers for whom there was later evidence of HIV positivity in a parent (group 3) suggests that parental HIV infection may have an indirect effect on child mortality.
The lack of evidence for higher mortality rates after 5 years among children born to HIV-positive mothers compared with those born to HIV-negative mothers probably reflects the low power of the analysis in this age group, since some HIV-positive children are expected to survive beyond 5 years .
The mortality rates observed at 1–2 years were higher than those reported in most other studies [1,2,10–14,27]. This reflects the relatively high child mortality rates reported in Malawi compared with other countries (State of the World's Children, UNICEF, http://www.unicef.org).
HIV seropositivity in this population at the time of the filter paper collection was associated with higher levels of education and with occupations other than subsistence farming . After adjustment for these and other sociodemographic factors, the HR for the association of maternal HIV status and child mortality was slightly increased, indicating that the true impact of HIV was larger than the crude mortality rates suggest. Most other studies have not adjusted for socioeconomic status and so may have underestimated the impact of HIV [8,10,12,16,28,29].
Maternal mortality was associated with child mortality among HIV-positive mothers but not among HIV-negative mothers. The association among HIV-positive mothers may reflect the fact that mothers with more advanced disease are more likely to transmit HIV to their children . Furthermore, among infants with vertically acquired HIV infection, the rate of progression depends on the severity of disease in the mother at the time of delivery [27,30]. Both severe illness and death of the mother could be expected to increase infant and child mortality through problems in child care , but this needs to be distinguished from the increase in risk of HIV, and of rapid progression if HIV positive. The extended family has almost certainly helped to mitigate the impact of parental death [32,33].
It has been suggested that paternal mortality could have greater socioeconomic impact than maternal mortality . This may be influenced by the traditional practice of widow-inheritance by the deceased husband's brother in this population. Neither in our study, in a patrilineal society, nor in another Malawian study in a matrilineal society  was there evidence that the father's death influenced child survival, but both analyses had low power.
Our findings suggest that, in this part of Africa, verbal postmortems are neither sensitive nor specific in identifying whether a childhood death is caused by HIV. This is consistent with two other studies in Malawi [16,28].
We found little evidence of differences in child morbidity according to either mother's HIV status or orphanhood. This is surprising. Children of parents who have been ill or who have died from AIDS have been found to be at high risk of malnutrition in several African countries [5,6,34]. However, these studies also show that the risks are setting dependent.
Our findings are consistent with a study in Lusaka, Zambia that compared children living in households known to be affected by HIV/AIDS with a control group living in households that were not known to be affected by HIV/AIDS; this study found no difference in stunting or weight . They are also consistent with a study of children aged < 3 years in Blantyre, Malawi, which found no differences in morbidity between HIV-negative children of HIV-positive mothers and children of HIV-negative mothers . A study of children aged < 5 years old in Kagera, Tanzania found no evidence that adult mortality affected child wasting  but suggested that orphanhood was associated with stunting, and that the effect of paternal orphanhood on stunting was greater in poorer households.
The study design has several important strengths: identification of ‘index’ individuals was based on a total population survey, HIV-positive and HIV-negative index individuals were closely matched, and the follow-up period is long. However, the retrospective nature of the study has drawbacks. Maternal HIV status at the time of delivery was unknown for a considerable proportion of mothers, and the study relied on recall for children's birth and death dates. Recall was probably less accurate when the child and/or the mother had died or was absent. After controlling for mother's age when last ‘known about', the total number of children reported for mothers living outside Karonga was lower than for mothers living in Karonga. However, the proportion of children who had died was similar in the two groups, suggesting there was no selective under-reporting of dead children for mothers no longer resident in the district.
We were unable to assess the impact of parental morbidity on child mortality and morbidity, since individuals were seen only at baseline and at the 10-year follow-up. However, the lack of evidence for an impact of parental death on child mortality and physical well-being suggests that parental morbidity is unlikely to have had a substantial effect.
The correlation between weight-for-height and mid-upper-arm-circumference in these data (0.57 and 0.68 for children aged < 5 years and 5–9 years, respectively) was moderately strong, suggesting that the anthropometric data are reliable and that our findings have internal validity. However, children who are no longer resident in the district may have been more severely affected by HIV/AIDS, in which case the findings will have underestimated the impact on morbidity.
The HIV status of the children in our study was not known, so the direct (vertical transmission of HIV infection) and indirect impacts of HIV in the mother could not be unambiguously distinguished. However, knowledge of child mortality according to maternal HIV status, rather than child HIV status, is valuable for projections of child mortality in Africa. This is because maternal HIV prevalence is widely available through antenatal clinic surveillance, whereas children's HIV status is usually unknown. Estimates of child mortality based on maternal HIV status now will provide a baseline against which the impact of interventions can be judged.
Mortality among children under 5 years of age is much higher in children born to HIV-positive mothers than in those born to HIV-negative mothers, and approximately 18% of mortality in this population is attributable to HIV. Most of the excess is attributable to vertical transmission of HIV.
The lack of evidence for excess morbidity in surviving children born to HIV-positive mothers suggests that, at least in terms of physical well-being and for children who have remained in the district, the extended family has not discriminated against children whose parents have been ill or have died from HIV/AIDS. However, it would be wrong to infer that the HIV epidemic has had little impact on surviving children's physical well-being. Traditional coping mechanisms based on the extended family appear to have diluted the impact on individuals, but the impact at the level of the community could still be considerable. It is also likely that pressures will increase in the near future, as the HIV epidemic matures and adult mortality rises .
We thank the Government of the Republic of Malawi for their interest in and support of the project and the Malawi Health Sciences Research Committee of the Malawi Ministry of Health and Population for permission to conduct the study and present these data. We thank Dr Jörg Pönnighaus for organizing and implementing the original field surveys that made this study possible. We thank Drs Stephen Graham, Frank Mwaungulu and Nicola Hargreaves for reviewing the verbal postmortem data. We thank Prof Andrew Prentice for comments on an earlier version.
Sponsorship: Until 1996 the Karonga Prevention Study was funded primarily by LEPRA (the British Leprosy Relief Association) and ILEP (the International Federation of Anti-Leprosy Organizations) with contributions from the WHO/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases. Since 1996, the Wellcome Trust has been the principal funder. BN was supported by the British High Commission in Malawi. JRG was partially supported by the British Department for International Development.
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Keywords:© 2003 Lippincott Williams & Wilkins, Inc.
HIV; child mortality; child morbidity; Africa; orphanhood