1 UR 24 (Epidemiology and Prevention Unit), Institut de Recherche pour le Développement (IRD, formerly named ORSTOM), BP 64501, 34394 Montpellier Cedex 5, France
2 US 009 (Niakhar Population and Health Unit), IRD, BP 1386, Dakar, Senegal
3 Bandim Health Project, Danish Epidemiology Science Centre, Bissau, Guinea-Bissau
Correspondence: KB Simondon, Centre IRD, BP 64501, 34394 Montpellier Cedex 5, France. E-mail: kirsten.simondon{at}mpl.ird.fr
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Abstract |
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Methods A cohort of 9192 subjects born 19622001 with prospectively collected dates of birth and death was analysed. MR by season of birth (JulyDecember/JanuaryJune) was estimated using Cox's proportional hazards analysis. The nutritional status of non-pregnant women was analysed at monthly intervals 19901996.
Results MR by season of birth was slightly greater than 1 during infancy, and close to 1 from 15 years and from 514.5 years. From 14.5 years old the MR was 0.77 (95% CI: 0.47, 1.25, P = 0.29), compared with 0.53 (95% CI: 0.28, 1.02, P = 0.056) from 20 years and 0.33 (95% CI: 0.09, 1.25, P = 0.10) from 25 years. The weight of women varied strongly by season: means were 3.03.9 kg lower at the end of the rainy season (SeptemberNovember) than during the dry season (FebruaryMay, P < 0.001 for each year).
Conclusions This study found no increased risk of death among young adults born during the hungry season in a rural West African area despite large seasonal variations in women's nutritional status. The strongly increased risk in adult Gambians is probably not explained by fetal undernutrition.
Accepted 26 June 2003
A recent study in the Gambia has shown a strong relationship between risk of death (mainly due to infectious diseases) in young adults and their season of birth (mortality ratio [MR] = 3.7 from 14.5 years old and MR = 10.3 from 25 years old, with an excess risk for those born JulyDecember).1 Season of birth was used as a proxy for fetal undernutrition. Indeed, birthweight varies strongly with season in the Gambia,2 as does women's weight3 and pregnancy weight gain.2 Furthermore, in a randomized trial comparing intervention and control villages, maternal food supplementation increased the birthweight by 201 g in the rainy season (JuneOctober), compared with 94 g in the dry season (NovemberMay).2
Since most of these premature deaths were from infections, the authors suggested that maternal malnutrition during the hungry season might have deleterious long-lasting effects on the immune status of the fetus. Thus, the fetal origins of disease hypothesis, first proposed by Barker and co-authors,4 may not be limited to chronic (cardiovascular) disease; rather, fetal malnutrition might also programme a major risk of infectious disease among adults.
Other factors (malaria, aflatoxin) were also considered by the authors, but were considered less likely causes than undernutrition.1
Demographic surveillance conducted by the Institut de Recherche pour le Développement (IRD, formerly named ORSTOM) in a rural area of Senegal since late 1962 offered the opportunity of examining the relationship between season of birth and risk of early adult death in another West African setting. The geographical proximity of this area to the Gambia, with similar strong seasonal variations in nutritional status5 and in malaria,6,7 makes this comparison particularly interesting.
The objectives of the present report were to provide further evidence for seasonal variation in women's weight, and to examine the impact of season of birth on the risk of death among children and young adults in this rural Senegalese area.
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Population and Methods |
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Childhood morbidity and mortality from vaccine-preventable diseases have decreased sharply since the onset of immunization programmes in the 1980s, in particular for measles,10 pertussis,11 and neonatal tetanus.12 However, outbreaks of meningitis and cholera13 still occur. Young adults also die from maternal mortality (ratio: 516 per 100 000),14 tuberculosis, and hepatocarcinoma (A Diallo, unpublished observations).
The incidence of disease varies strongly with season. Meningitis, measles, and pertussis peak during the dry season (FebruaryMay), while malaria almost exclusively occurs at the end of the rainy season.7
The demographic surveillance system
In October 1962, the first demographic survey in the area was launched in eight villages, the Ngayokhem zone (5000 inhabitants).15,16 A continuous follow-up of this population has been maintained ever since. In 1983, 22 additional villages were included in the demographic surveillance to form the Niakhar zone, including 30 villages.
From 1963 to 1983, censuses were organized at yearly intervals, generally in the dry season (February). However, no census was conducted in 1967, 1975, 1976, or 1979.15,16 Demographic surveillance was performed twice yearly from 1983 to 1986, weekly from 1987 to 1997 and at 3-month intervals since March 1997.
At each census, experienced demographic field workers, through visits to all compounds, noted the occurrence and date of all births, deaths, marriages, divorces, and out- and immigration which had occurred since the preceding visit. The field workers referred to all residents by name to ensure completeness of new events.16
This surveillance conforms to the Helsinki Declaration and has received approval from the national Senegalese authorities.
Assessment of dates of births
The dates of births which had occurred since the preceding visit were obtained through interviews with mothers using a local calendar of events. Season and specific agricultural activities were important guidelines for this procedure. Systematic registration of pregnancies enabled the monitoring of outcomes, thus facilitating the registration of birth dates.
From 1983 on, the date of registration of birth dates by fieldworkers was also entered into the database. Mean duration between occurrence and registration of births was 3.8 months from 1983 to 1986, 0.3 months from 1987 to 1997, and 2.0 months thereafter.
Cohorts selected for the analysis
Two cohorts with prospective follow-up were selected: the Ngayokhem cohort and the Niakhar cohort. The Ngayokhem cohort consisted of subjects born 19622001 in the eight villages followed since 1962 (n = 9192). Among them, 4095 were born prior to 1983. The rate of missing month of birth for this period was 0.9%.
The Niakhar cohort was comprised of the 22 823 children born in the 30 villages 19832001. Thus, the 5097 subjects born 19832001 in the Ngayokhem zone were included in both cohorts. No subjects had missing information on date of birth.
All subjects born alive and within the study area until March 2001 were included.
Survival analysis
The Cox model was used for survival analysis. The Niakhar cohort was chosen to assess MR by season of birth for infants (01 year), 15 year olds, and 514.5 year old children. The Ngayokhem cohort with the longer follow-up was used to estimate MR from 14.5, 20, and 25 years of age.
Subjects were entered at fixed ages (birth, 1, 5, 14.5, 20, or 25 years) and contributed to the analysis until 31 December 2001, upper limit of age range (when relevant), emigration, or death, whichever came first. Subjects were allowed to re-enter the cohort after migration if they resettled in the area.
Season of birth was defined as in the study by Moore et al.,1 i.e. post-harvest season JanuaryJune and hungry season JulyDecember.
Gender was not related to season of birth, and no interaction was found between gender and season of birth in relation to mortality. Gender was therefore excluded from the final analyses. Prior to the use of the Cox model, we tested the proportionality of mortality rates by season of birth for each age interval under study.
Dbase files (Version 4.0) were extracted from the central database and analysed using Epiinfo and S+ (version 1995).
Monitoring of nutritional status of women
From 1990 to 1996, nutritional status of women was assessed during vaccination sessions for their infants, organized by IRD in the three dispensaries of the area during the first week of each month.17 Women were weighed using a Seca 769 electronic scale precise to the nearest 100 g. Attendance rates were about 80%, each woman attended up to four times (at about 2, 4, 6, and 9 months postpartum) per infant, and the mean number of women per session was 311.
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Results |
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Survival curves by season of birth are shown in Figure 4. Subjects born JulyDecember showed no tendency towards poorer survival during adolescence or adulthood. From 2737 years, survival seemed less favourable for those born January June, but at age 37 the survival curves again crossed over (Figure 4).
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Discussion |
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During the first year of life only, Senegalese children born in the hungry season had a higher risk of death. However, the difference was moderate (MR = 1.18), and due to the close relationship between season of birth, season of death, and age at death (which is closely related to risk of death during infancy), the relative effects of prenatal and postnatal season on mortality cannot be differentiated for infants. In the Keneba area, infants born FebruaryApril and particularly MayJuly also had lower risks of death.18
Between 1 and 5 years of age, season of birth was not linked to risk of death in Senegal, despite considerable statistical power (2243 deaths). Similar results were reported in a smaller study in a rural Gambian area distinct from Keneba.19
One limitation of our study was the fact that duration of follow-up for adults was shorter than in the study by Moore et al.,1 i.e. up to 39 years compared with 48 in the Gambia. However, the relative risk of death associated with birth in the hungry season in the Keneba area was so high (more than tenfold from 25 years old)1 that if a similar tendency indeed existed in Senegal, it would have been detected even with a shorter follow-up.
The statistical power for detecting an increased mortality risk among births in the hungry season from 14.5 years old was greater in our study because it included more deaths in the group of post-harvest births (37 versus 12 for the Gambia). The smallest increased MR that we would have been able to detect with 95% statistical power and significance of 5% was below 2, while it was above 2.5 for the Gambian study.20
The quality of date of birth is critical, since lack of specificity and misclassification would bias results towards similarity of risk between groups.21 Cohorts were defined with this in mind by selecting only subjects with prospective assessment of dates of birth. From 1962 to 1983, when demographic visits were performed less frequently, the rate of missing month of birth was very small (<1%). The date-of-births were estimated by interviews with the mothers using calendars of local events. Therefore, for 19621983 the estimation would have a precision of ±1 month. However, misclassification of season of birth, as defined here, is probably insignificant and cannot explain the absence of a relationship of mortality risk with season of birth.
Considering the completeness of death registration, data are highly reliable, except for infants born 19621982. Indeed, infants who are born and die between two censuses may be omitted by their families when censuses are conducted at yearly intervals or less.8 Furthermore, a bias related to season of birth cannot be ruled out, since censuses were usually conducted at the beginning of the post-harvest season (in February), so that infants born in the post-harvest season who later died were perhaps more likely to be omitted. However, the MR for infancy was computed for the period 19832001 when follow-up visits were conducted at 6-month intervals or less, and was unchanged when computed only for subjects born 19872001 (MR = 1.18, 95% CI: 1.06, 1.31, P = 0.002). For the Ngayokhem cohort of subjects born 19622001, the MR was slightly greater (MR = 1.23, 95% CI: 1.09, 1.39; P < 0.001).
Our inability to replicate the Gambian results could have several different explanations. First, season of birth may be related to risk of death only in the Gambia. Indeed, a prospective population follow-up from 1978 to 2000 in peri-urban Bissau, Guinea-Bissau,22 160 km south of Keneba, found a lower risk of death among subjects born during the hungry season. Prospective follow-up of 1457 children born 19722000 conducted at annual or bi-annual intervals from 1978 to 2000, yielded 23 deaths (excluding 3 deaths due to bombs) during 5249 person-years. Cox's survival analysis provided an MR by season of birth, from 15 years old, of 0.36 (95% CI: 0.13, 0.99). Adjusting for gender provided a MR of 0.37 (95% CI: 0.13, 1.04).
Limitations to these data were that subjects were, at most, 22 years old at the end of follow-up, that the study area was peri-urban, presumably with less seasonal variation in nutritional status than in agricultural societies; and that for those born 19721977 birth dates were determined retrospectively in 1978, using a local seasonal calendar. The better survival of Guineans born during the hungry season may have occurred by chance, especially since the age range (1522 years) was different from that during which Senegalese adults, born in the hungry season, tended to die less frequently (2737 years).
A second possibility is that the phenomenon responsible for differences in survival in the Gambia was present in Senegal in the 1940s and 1950s as well, but had disappeared prior to 1962. Unfortunately, Senegalese adults born in the 1950s could not be included in the present analysis because their birth dates, collected by the recall method in 1962, were not considered precise.
Finally, this phenomenon may no longer exist in the Gambia. Indeed, a recent study revealed no evidence of immunodeficiency in 610 year old children born JulyDecember in the Keneba area.23 Thus, the increasing MR with increasing age in the Gambia would be a cohort effect (i.e. the relationship exists only in older generations) rather than an age effect.24 In this case, fetal undernutrition cannot be the causal factor. Indeed, strong seasonal variations in nutritional status were still present in the 1980s (maternal weight) and in the 1990s (birthweight).
Which other causal factors could be considered? Moore et al.1 discussed maternal malaria during pregnancy, fetal, or postnatal exposure to aflatoxin (peak in AprilMay) and postnatal exposure to gastrointestinal rotavirus infection (epidemics in January), but argued that the timing of these seasonal factors did not correlate well with that of high-risk births.1 Conversely, the timings of maternal weight loss (MayOctober/November) and of lower than average birthweights (JuneDecember) are very similar,2 and closely mimic the pattern of death by season of birth.1 Hence, birthweight is mainly affected by maternal undernutrition during the last months of fetal life, and thus, this could thus also be the case for immunocompetence.
The results of our study support the hypothesis that malaria and aflatoxin do not explain the Gambian finding. Indeed, malaria is intensely transmitted from September to November in Niakhar,6 and exposure to aflatoxin is common in the Sine-Saloum region during the dry season.25 With regard to rotavirus infection, a peak in the prevalence of diarrhoea in January February has also been described for infants in Niakhar,5 and rotavirus infection in infants in Guinea-Bissau, south of Senegal, occurs almost exclusively from January to March.26
In conclusion, longitudinally collected data on birth and death over a long period of time are rare in developing countries. The prospectively collected Senegalese data presented here do not replicate the Gambian finding of an increased adult mortality risk for subjects born during the hungry season, strongly suggesting that their poor survival is not explained by either maternal undernutrition, malaria, or aflatoxin exposure.
KEY MESSAGES
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Acknowledgments |
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References |
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