a Institut National de la Santé et de la Recherche Médicale. Unité 149 Recherches Epidémiologiques en Santé Périnatale et Santé des Femmes, Paris, France.
b Burkina Faso: Ouedraogo C, Sondo B, Testa J, Koné B; Ivory Coast: Barbé T, Berche T, Bohoussou MK, Eono P, Koffi AS, Ortiz P, Portal JL, Tano-Bian A, Touré-Coulibally K, Welffens-Ekra C, Zadi F; Mali: Decam C, Doucouré-Diallo A, Duponchel JL, Huguet D, Prual A; Mauritania: Cunin P, Ould El Joud D; Niger: Alfari D, Mounkaila N, Vangeenderhuysen C; Senegal: de Bernis L, Bouillin D, Dompnier JP, Gueye A; Ministère de la Coopération, France: Laure JM, Leloup M.
Marie-Hélène Bouvier-Colle, INSERM U149, 123 Boulevard de Port-Royal, 75014 Paris, France. E-mail: bouvier-colle{at}cochin.inserm.fr
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Abstract |
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Methods Data came from a prospective population-based study (the MOMA survey) that collected information about 20 326 pregnant women in seven areas, primarily urban, in West Africa.
Results There were 19 870 singleton births. The stillbirth rate was 25.9 per 1000 total births (95% CI: 23.728.1). In the crude analysis, after adjustment and consideration of prevalence, the principal risk factors for late stillbirth were: late antenatal or intrapartum vaginal bleeding, intrapartum hypertension, dystocia, and infection. Other risk factors were: maternal height (<150 cm), maternal age (>35 years), previous stillbirths, hypertension at the 8-month antenatal visit and number of antenatal visits (<2).
Conclusions The principal risk factors for late stillbirth observed in our study could be detected only in the late antenatal and intrapartum period. These results highlight the potential benefits of partograph use. They need to be confirmed by studies incorporating continuous intrapartum fetal monitoring.
Keywords Developing countries, West Africa, fetal death, epidemiology, multivariate analysis
Accepted 17 December 2001
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Introduction |
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In developing countries, methodological issues have limited or made controversial the results of the principal studies of risk factors for stillbirth.613,1723 Voorhoeve et al.6 have demonstrated the substantial recruitment bias in hospital-based studies.812,1721 Moreover, these studies are unable to take into consideration the real prevalence of risk factors in the population. On the other hand, some population-based studies have failed to analyse intrapartum risk factors22 or limited their analysis to antepartum fetal deaths.23 The three population-based studies that did consider risk factors detectable in antenatal visits and during labour unfortunately did not use statistical analysis to identify the risk factors that were significant.6,7,13
The present work is a part of a prospective populationbased inquiry in six West African countries (the MOMA study). It tested the hypothesis that the late antenatal and intrapartum risk factors for perinatal mortality that we have identified in West Africa are also risk factors for stillbirth. This study also allowed us to compare the potential contribution of antenatal care and monitoring during labour in their detection.
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Methods |
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Ethics
Every woman provided oral informed consent to study participation. The study was designed to avoid any interference with local health care and medical structures. When investigators detected unknown risk factors or conditions, they advised the women to consult their usual health provider.
Specific methods for this analysis
Definition of early and late stillbirths
A stillbirth was defined as a product of conception weighing 500 g or with a gestational age >22 weeks without evidence of life at birth. Early and late stillbirths were distinguished clinically: early stillbirths were those for which active movements or heart sounds were absent at the 8-month antenatal visit, and late stillbirths were those that occurred after this visit.
Patient selection
The present study analyses only singleton births. Multiple pregnancies will be analysed separately to comply with international standardization recommendations28 and because they represent a special risk factor for stillbirth.18,29,30 Except for the calculation of overall stillbirth rates, the early stillbirths were excluded from analysis, to avoid studying variables that were collected after the death of the fetus.
Potentially viable fetuses
In developing countries, the main perinatal problem is not, as it is in industrialized nations, saving very low birthweight or premature or malformed neonates. For that reason, we have paid particular attention to the sub-group of fetuses that should not have died. We defined a potentially viable fetus as one weighing >2500 g, with a gestational age >36 weeks and no major malformations on clinical examination at birth. Within this group of potentially viable fetuses, we compared the late stillbirths and the live births. The study of this sub-group also allowed us to take into consideration potential confounding factors (e.g. prematurity and low birthweight) that are highly related to intrapartum risk factors (e.g. non-cephalic presentation, which is more frequent in pre-term births).
Statistical analysis
All analyses used either SAS (SAS Institute Inc., Cary, NC, USA) or BMDP (BMDP Statistical Software Inc., Los Angeles, CA, USA) software. Potential risk factors for late stillbirth were selected from all available variables if their prevalence in the study population was >0.5% and the rate of missing data was <15%. We performed a univariate analysis to determine the association between 29 simple clinical variables and late stillbirth and used logistic regression to examine the modifications after adjustment for study site. The Breslow-Day test assessed the potential interaction between the study site and the other risk factors. Subsequent multivariate analysis also used logistic regression (backward stepwise procedure). If the P-value of the Breslow-Day test was <0.05, an interaction term was included. The study site was forced into all regressions. The population-attributable risks were calculated from the adjusted odds ratios (OR) and the proportion of cases exposed to the risk factor.31
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Results |
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The overall maternal mortality rate was 311 per 100 000 live births, and the perinatal mortality rate 41.8 per 1000 total births. Further details have been reported elsewhere.16,27 Stillbirths accounted for 62% of the overall perinatal deaths (range 5571). The overall stillbirth rate was 25.9 per 1000 total births (95% CI: 23.728.1) and ranged from 19.6 in Niamey to 33.9 in Abidjan (Table 1). Eleven mothers of stillborns died: two before labour, two during labour, and seven after delivery. Of the 513 stillbirths, 18 (3.5%) were early, and 495 (96.5%) late. The following analysis is based on 19 296 live births and 495 late stillbirths.
Univariate analysis
A significant association was found with only two of the social, economic, and anthropometric risk factors: shortness (<150 cm) and age (35 years) (Table 2
). No significant association was found with educational level (low), occupation (none), absence of a partner (i.e. widow, unmarried, or divorced), absence of a co-wife, or lameness. Of the risk factors related to obstetric history and status, grand multiparity (>6), previous stillbirth, previous postnatal death, more than three previous miscarriages and previous caesarean section were significantly associated with stillbirth (Table 3
). No significant association was found with nulliparity, short interval between births (<18 months) or undesired pregnancy. Of the risk factors detectable at the 8-month antenatal visit, subsequent stillbirth was fairly significantly associated with vaginal bleeding at examination (OR = 3.4, 95% CI: 1.86.5). Further significant associations were also found with one or no antenatal visits, self-reported absence of malaria chemoprophylaxis, absence of tetanus immunization during this pregnancy, and hypertension (as defined by WHO32) (Table 4
). No significant association was found with self-reported absence of iron supplementation.
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The adjusted population-attributable risks reveal that the three principal risk factors were intrapartum oxytocin administration (12%), non-cephalic presentation (11%), and prolonged labour (9%).
Results among potentially viable fetuses
At birth, the weight, gestational age, and presence of malformations were known for 85.6% of the 19 296 live births and 495 late stillbirths. Of the live births, 86.5% met the criteria defining a potentially viable fetus, and, of the late stillbirths, 55.8%. The associations between intrapartum risk factors and late stillbirths in this subgroup were in the same range as, or stronger than, those observed in the overall population (Table 6).
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Discussion |
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Because confounding factors such as prematurity or low birthweight might have caused the association between some of the intrapartum risk factors and late stillbirth, we performed a sub-group analysis of potentially viable fetuses to take these factors into account. The associations in this subgroup were still in the same range as or stronger than those for the overall population.
Intrapartum oxytocin administration was an important risk factor for stillbirth. This association remained strong after an overall adjustment for factors including prolonged labour, which is a major confounder. Oxytocin administration must be accompanied by close monitoring of fetal tolerance as suggested by Ellis et al.33 Prospective trials should reassess the safety of oxytocin in situations where this monitoring is not available, as is the case in most developing countries. Finally, non-cephalic presentation was a strong and frequent risk factor for stillbirth, even among full-term fetuses. This association, like the others involving intrapartum risk factors, may indicate sub-optimal intrapartum monitoring and care. One explanation for this inadequate intrapartum monitoring is that the partograph, a graphic record of the progress of labour, is not used in the study areas.
Internal validity
Approximately 5.8% of the 21 557 pregnant women counted in the census were not included in the study because they refused to participate or were lost to follow-up. It was not possible to determine the vital status at birth of 61 (0.3%) of the included singleton pregnancies, and we cannot be sure that the results were not biased by these missing data. There was not, however, any significant difference between the distribution of risk factors among the 61 women whose pregnancy outcome was unknown and the others (data not shown). We therefore assume that the potential bias is small.
The exhaustiveness of the study was assessed from local birth registers or a new door-to-door census at the end of the study period or both, depending on study site. We concluded that we had enrolled up to 93.9% of non-early-aborted pregnancies. As we enrolled women during the second trimester, we may have missed many late abortions or very early stillbirths. Accordingly, we have probably substantially underestimated the percentage of early stillbirths and the overall stillbirth rate. This selection bias, however, is presentand essentially inescapablein all studies of stillbirths in developing countries. It does not modify the relations observed with late stillbirths.
Because of missing birthweight data, potential viability could not be determined for 40.6% of the late stillbirths. It is likely that many premature or growth-restricted stillbirths were not weighed. The selection bias may therefore have been less important among the potentially viable stillbirths, although this cannot be demonstrated. The relations observed between intrapartum risk factors and potentially viable stillbirths should thus be interpreted with caution.
We took several steps to avoid introducing any bias when we pooled data from the different study sites. Crude OR were compared with OR adjusted for sites; they did not differ. All regressions were adjusted for site, and the heterogeneity between sites was also taken into consideration.
The variables that we studied were primarily clinical signs, rather than risk factors in the strict sense of the term. Accordingly, a directly causal interpretation of the adjusted population-attributable risks is inappropriate; these risks simply reflect a combination of the level of association and the prevalence of the signs among patients.
External validity
The stillbirth rate we observed was in the same range (1356) as those reported in other developing countries over the past 20 years.613,1723 The strong associations between late stillbirths and intrapartum risk factors are consistent with those from previous studies in Brazil,17 India,7,19 Nepal10,13 and Zambia.21 The particularly adverse role of non-cephalic presentation and prolonged labour was also emphasized in these studies. The less important but still significant relations with short stature,20,22 maternal age,6,17,18,21 previous stillbirth,7,17,20 late antenatal vaginal bleeding,17,21 and minimal if any antenatal visits7,17,19,21 are also consistent with previous findings. Similarly, others have also found that stillbirth is not significantly associated with socio-economic status,17,20 schooling,17 marital status,6 short period between children17 or undesired pregnancy.17
Other issues
An initial question raised by our findings is whether the intrapartum clinical signs we examined are predictive of an ongoing stillbirth or simply associated with an already dead fetus. A definitive answer would necessitate continuous fetal monitoring. Although this may be feasible in hospital-based studies in developing countries,34 it was not compatible with the observational population-based design of our study. Two points support the hypothesis that these risk factors are predictive. First, other studies in developing countries indicate that an important portion of stillbirths occur during labour. Kunzel et al., in a survey of 3548 pregnancies in three countries in West Africa, found that 60% of the stillbirths were intrapartum deaths.35 In their population-based study of 10 527 pregnancies in Jamaica, Ashley et al. found approximately 56% of the stillbirths to be intrapartum deaths.36 Second, as Ellis et al.10 demonstrated in Nepal, intrapartum risk factors are related to both fetal death and neonatal encephalopathy; this indicates that these factors precede stillbirth rather than following it.
A second question necessarily follows: if these intrapartum clinical signs are predictive of stillbirth, what if any intervention could be helpful? Our results cannot answer this question. We think, however, that implementation of a definition of high risk based principally on late antenatal clinical and labour monitoring could be helpful. The elements in our definition of high risk are not very different from those used in the WHO partograph.37 Its introduction in four hospitals in Southeast Asia was associated with a 38% decline in intrapartum stillbirths. Similar results were obtained in a rural area of Gabon.38 Women with late antenatal vaginal bleeding and intrapartum risk factors should be referred promptly to structures where optimal care is available.
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Conclusion |
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KEY MESSAGES
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Acknowledgments |
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References |
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