Influence of Consanguinity and Maternal Education on Risk of Stillbirth and Infant Death in Norway, 1967–1993

Camilla Stoltenberg 1 2 Per Magnus 1 2 Rolv Terje Lie 0 2 Anne Kjersti Daltveit 0 2 Lorentz M. Irgens 0 2 0 Medical Birth Registry of Norway, University of Bergen , Bergen , Norway. Reprint requests to Dr. Camilla Stoltenberg, Section of Epidemi- ology, Department of Population Health Sciences, National Institute of Public Health , P.O. Box 4404 Torshov, 0403 Oslo , Norway 1 National Institute of Public Health , Oslo , Norway 2 Received for publication March 24 , 1997, and accepted for pub- lication February 19, 1998. Abbreviations: AR, attributable risk; Cl, confidence interval; F , coefficient of inbreeding-proportion of autosomal loci predicted from pedigree analysis to be homozygous though inheritance of identical genes from common ancestors; OR , odds ratio To analyze the influence of consanguinity and maternal education on stillbirth and infant death for children born in Norway between 1967 and 1993, the authors studied 7,274 children of ethnic Pakistani origin and 1,431,055 children of Norwegian ethnic origin. Of these children, 31.0% of the Pakistani children and 0.1 % of the Norwegian children had parents who were first cousins. Consanguinity increased the relative risk of stillbirth (odds ratio (OR) = 1.3, 95% confidence interval (Cl) 1.0-1.6) and infant death (OR = 2.4, 95% Cl 2.0-3.0), after adjustment for maternal education, maternal age, parity, and year of birth. In 1985-1993, 29% (95% Cl 13-45) of stillbirths and infant deaths among the Pakistani group were attributable to consanguinity. In the Norwegian group, 17% (95% Cl 13-21) of the deaths were attributable to factors associated with low maternal education, while in the Pakistani group, the corresponding estimate was nonsignificant. The risks of stillbirth and infant death were similar for children with non-consanguineous parents in both populations. This is an important observation considering the differences in socioeconomic status between the two groups. The authors conclude that consanguinity influenced stillbirth and infant death independent of maternal education, and that a large proportion of deaths could be attributed to consanguinity in the Pakistani group due to high frequencies of consanguinity. Am J Epidemiol 1998; 148:452-9. consanguinity; education; ethnic groups; fetal death; genetics; infant death; social class - Consanguinity, defined as marriage between close relatives, increases the risk of stillbirth and infant death (1-3), but the extent to which socioeconomic conditions can account for this association is disputed (2, 4, 5). In 1987, a meta-analysis of studies on prereproductive death (before 20 years of age) and consanguinity (2) concluded that the proportion of deaths attributable to consanguinity was low in all the populations considered. Since the publication of that meta-analysis, it has become clear that the attributable risk of early death due to consanguinity seems to be increasing globally. Consanguinity appears to be more prevalent than was estimated about 10 years ago (6-18), and in many populations where consanguinity is prevalent, the frequency of consanguinity does not decline (6, 18). Several of the populations with high rates of consanguineous marriages now experience decreasing or low rates of mortality due to social and economic development and migration to wealthier countries, and it has been postulated that the relative influence of consanguinity may be larger when mortality rates are low (2). Consanguinity influences stillbirth and infant mortality mainly by increasing the frequency of autosomal recessive diseases (1). In addition, a slight increase in the frequency of diseases with a polygenic etiology is considered to play a role (1). British and Norwegian studies have reported higher mortality rates among children of Pakistani immigrants than in other ethnic groups (19-21). Parental consanguinity has been found to be related to these mortality differences (19, 21), but there has been little attempt to control for the influence of social class, even though it is established that in most populations consanguinity is more prevalent among parents with low socioeconomic status (8, 22-26). The aims of this study were to estimate the risk of stillbirth and infant death in Norway among children whose parents were ethnic Norwegians or ethnic Pakistanis in order to: 1) estimate the relative risks and population attributable risks associated with consanguinity and maternal education within each population group, 2) analyze whether consanguinity is a risk factor for stillbirth and infant death after socioeconomic factors are controlled for, and 3) explore whether consanguinity and differences in socioeconomic factors, such as maternal education, explain risk differences between the two populations. MATERIALS AND METHODS The study population consisted of the 7,494 children who had two parents of ethnic Pakistani origin and the 1,448,766 children who had two parents of ethnic Norwegian origin and who were born in Norway between 1967 and 1993. For simplicity, the two groups will be referred to as "Pakistani" and "Norwegian," regardless of citizenship and that none of the children were immigrants. Births missing information on whether the child was still alive or not by December 31, 1993 (11 births in the Norwegian group), on parental consanguinity (13,153 births; 0.9 percent of the Norwegians, 2.6 percent of the Pakistanis), and on parity (5,773 births; 0.4 percent of the Norwegians and 0.6 percent of the Pakistanis) were excluded. The final sample consisted of 7,274 Pakistani births and 1,431,055 Norwegian births. Information on survival of the child, consanguinity between parents, maternal age, parity, and year of birth was obtained from the Medical Birth Registry of Norway (27), which has collected data on all births from 1967 and onward. Data for parental country of origin and maternal educational level obtained by 1990 were linked to the Birth Registry by Statistics Norway. Maternal educational levels for the total population were obtained from a census conducted in 1990. The categorization and distributions for the variables are shown in table 1. The outcomes were 1) stillbirth ratenumber of stillborn infants with gestational age S 1 6 weeks per 1,000 births, and 2) infant mortalitynumber of deaths in the first year of life per 1,000 live births. Early mortality is the sum of stillbirths and infant deaths per 1,000 births. Parental relations were categorized as "not consanguineous," "first cousins or closer," or "other consanguineous relations." In the Norwegian group, most of the parents assigned to the category with "other consanguineous relations" were related in more distant ways than first cousins, while, in the Pakistani group, most of them were related in an unspecified way (Appendix table). Consanguinity is routinely recorded on a standardized form when the mother undergoes her first pregnancy control, usually before 12 weeks of gestation. Beca (...truncated)