Jamie M. Robertson is an Instructor
in Surgery at Harvard Medical
School and the Direction of
Innovation in Surgical Innovation
in the Department of Surgery
at Brigham and Women’s
Hospital. She leads efforts within
the surgery department to
develop curricula and assessments
to support medical students,
residents, fellows and faculty.
Her academic focus is on
non-technical skills among
teams. She co-leads the Brigham
and Women’s Operating Room
Training with Simulation program,
which has trained more than 100 teams of surgeons, anesthesiologists
and nurses. Dr. Robertson completed her undergraduate education
at Seattle University before earning her MPH in Behavioral and
Community Health Sciences and PhD in Epidemiology from the University
of Pittsburgh Graduate School of Public Health.
Background Consanguineous marriage (CM) has been linked to spontaneous abortion (SAB), although studies have largely been cross-sectional and likely underestimated early loss. We aimed to determine the relationships between CM and SAB in a prospective pregnancy cohort study in Telangana State, India. +
Methods Data from 661 participants aged 15–35 years in the Longitudinal Indian Family hEalth (LIFE) study actively followed for pregnancy and pregnancy loss were analyzed. SAB was classified as early (< 8) or late (8–22) weeks gestation. We used logistic regression to model the relationships between CM, defined by first-cousin marriage, and SAB, adjusted for maternal age.
Results Women in CM were at a modestly increased risk of any ( ORadj 1.15, 95% CI 0.69, 1.91) and early ( ORadj 2.03, 95% CI 0.85, 4.83) SAB compared to women in non-CM, although results were not statistically significant. There was no relationship between CM and late SAB. Conclusion Among couples in southern India, there was a modest increase in early but not late SAB among CMs which may be explained by the expected influence of chromosomal abnormalities and lethal homozygous recessive disease on early loss. Pre- and Peri-marital Health Counseling that addresses this risk may be warranted.
Keywords : Consanguineous marriage · Cousin marriage · Spontaneous abortion · India · Pregnancy loss
Background The prevalence of consanguineous marriage (CM), the union between two individuals who are related as second cousins or closer [1], varies globally with rates as low as 5% in the USA, Western Europe, and Australia [2] and up to 70% in regions such as the Middle East [3]. In India, rates differ depending on the geographic region within the country in addition to the size, diversity and divergent attitudes toward CM [4]. Rates vary from 1–10% in northern states to 20–60% in southern India [5]. Although proportions have declined overall since the early 1990s [4], rates remain high in Telangana State, with over 40% of women reporting being in a related marriage [6]. Globally, and in India, first-cousin marriages are the most common form of consanguineous relationships, comprising roughly 20–30% [2].
Marriage between related individuals has been shown to result in a number of adverse outcomes among offspring. Several studies have reported an increased risk of death among offspring of consanguineous couples [7, 8]. The most commonly studied and well-known association with CM is congenital anomalies. Offspring of related individuals are more likely to have rare autosomal recessive conditions that are uncommon in offspring of non-consanguineous couples [2, 9]. Absolute risk varies by population and outcome and has been found to be 1.7–2.8% higher for the children of first cousins than for those from non-related couples [2].
CM may also result in a spontaneous abortion (SAB) [10–12], a common outcome occurring in 15–20% of all clinically recognized pregnancies [13, 14]. Chromosomal abnormalities are implicated in roughly 50% of early losses, yet early pregnancies and pregnancy losses are often missed in cross-sectional studies and studies that recruit women later in the first trimester [13]. Studies of SAB are methodologically challenging, as early miscarriages often occur before women are aware of the pregnancy, increasing the likelihood of misclassification and missed identification of cases. For this reason, most studies looking at the association between CM and SAB have been cross-sectional in nature and derived from survey data, and results from these studies have been conflicting [10–12, 15–18].
To address these research gaps, we conducted a prospective pregnancy cohort study in Telangana which utilized active identification of early pregnancies as well as SABs, providing data on SABs that might be missed using cross-sectional and self-report data. In addition, southern India, especially the state of Telangana, is understudied in terms of both CM and birth outcomes. This paper aims to explore the association between first-cousin marriages and SAB in this region to provide an evidence base for medical professionals and women looking to conceive.
CM is common in many parts of the world, including South India. Our results showed an increase in the risk of early SAB among women in consanguineous versus unrelated marriage independent of maternal age, although results were of borderline statistical significance. On the other hand, we did not find that CM increased the odds of later gestation SAB. This pattern may reflect the greater influence of chromosomal abnormalities and lethal homozygous recessive disease in early SAB [21], as many early SABs are the result of chromosomal abnormalities, whereas late SABs may be more influenced by environmental exposures [22, 23]. In fact, chromosomal abnormalities are much more common in consanguineous relationships, which may suggest that recessive genetic mutations inherited from a common ancestor can lead to adverse prenatal outcomes [24].
Other studies on the risk of SAB among consanguineous couples in India have reported mixed results. A study in Tamil Nadu reported a significant increase in SAB [12], while others conducted in various regions of South India, excluding Telangana State, have shown insignificant [16–18] or mixed results [11]. All of these studies may have missed capturing early SABs that might go unnoticed in non-planning populations with little access to healthcare. Further, these studies did not distinguish between early and late SABs. In addition, diverse geographical and ethnic groups in India have different marriage customs and levels of overall relatedness. The effects of CM within one region may not be indicative of the risk in another. The results of this study along with previous research demonstrate a need for larger prospective studies that are able to identify early pregnancies and losses among a variety of populations.
Our study has a number of notable strengths. First, to our knowledge this is the first prospective pregnancy cohort study in this region to actively follow women for pregnancy and pregnancy loss, allowing us to examine predictors of accurately measured SAB, including CM. Despite the high rate of CM in Telangana, information on the degree of relatedness of couples in the area and the impact on pregnancies has not been previously reported. Our study also has limitations. First, women were asked to self-report their consanguineal kinship to their husband. No information on ancestral relationship between the couple was available in this study. Some couples may be more related than measured in the current analysis. Future studies using blood samples may be able to determine the true degree of relatedness among participants. Second, approximately a quarter of SABs were identified as occurring early, and models of CM and SAB may have been underpowered. Still, our study identified a trend for an increased risk of early SAB and no increased risk of late SAB, which was in line with a priori hypotheses. Additional prospective studies including sufficient numbers of early and late SABs in a variety of regions and ethnic groups are needed to replicate our findings. Finally, there may be misclassification of the outcome variable. SABs were ascertained through staff follow-up and participant self-report, but several days or weeks may have passed between the actual loss and when the women became aware of the loss. For those who were near the cutoff of 22 weeks of gestation, they may have been classified as having had a stillbirth. To determine whether this was a potential problem in our analysis, a single fetal death variable consisting of both SABs and still births (n = 117) was used in subsequent analysis. Overall, this change had did not change the conclusion (Table SI).
We demonstrated an increased risk of pregnancy loss, particularly early SAB, among women in a region of India with high rates of CM, suggesting that efforts to counsel reproductive aged women and married couples may be warranted [25]. As evidence suggests that prenatal morbidity and mortality rates increase due to intrafamilial marriages [25–27], pre-marital Health Counseling (PMHC) is a growing trend among nations where CM rates are high. Our study provides additional findings for evidenced-based counseling of populations at risk. Both pre-marital counseling and perimarital counseling on the risk of SAB may help healthcare providers better counsel patients who are experiencing recurrent miscarriages.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s13224- 021- 01498-7.
Funding This project was supported by SHARE INDIA Research Foundation and their fundraising efforts and by the Fogarty International Center of the National Institutes of Health training program under Award Number D43 TW 009078.
Conflicts of interest The investigators have no conflicts of interest.
Informed Consent Informed consent was obtained for all participants in the study.
Ethics approval All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 1964 Helsinki Declaration of and its later amendments or comparable ethical standards. This study was a population based prospective study and was approved by the Institutional Review Board of the MediCiti Institute of Medical Sciences (MIMS) hospital and was conducted within the tenets of the Declaration of Helsinki.
