Doctor: Ayesha Siddiqui

Title: Association between maternal origin and severe maternal morbidity : exploring the obesity mediated pathway

Supervisors: Catherine Deneux, Elie Azria

Doctoral school: ED 393 Epidemiology and Biomedical Information Sciences, Université Paris Cité

Date of thesis defense: 05/2021

Jury: Elizabeth F. Howell

Thesis summary:

Severe maternal morbidity (SMM) occurs more frequently than mortality and is a sensitive tool to investigate disease mechanisms, particularly in high-income countries. Maternal origin, race-ethnicity or maternal place of birth (immigrant status), has emerged as an important social factor associated with SMM in high-income countries. The current challenge in maternal health research is to identify causal mechanisms, a first step towards reduction of social disparities. Obesity is a significant health concern among women of reproductive age in most high-income countries and is more prevalent among minority and immigrant women. There is some limited evidence of an association between obesity and SMM. Obesity is therefore a candidate of interest on the causal pathway between maternal origin and SMM. We hypothesized that prepregnancy maternal obesity is associated with SMM and that it mediates the relationship between maternal origin and SMM in two high-income countries – France and the USA. We also postulated that the strength of the mediation effect does not vary by national context. The project was divided into two specific objectives: 1.To test and quantify the association between prepregnancy BMI and SMM. 2.To test the hypothesis through path analysis methods that maternal obesity is an intermediary in the association between maternal origin and SMM. Secondary analyses of existing data were conducted using three data sets with complementary strengths, two in France and one in the USA. We reasoned that a cross-national approach would lead to more robust conclusions and provide insights regarding the importance of context. In both countries we confirmed an association between maternal obesity and SMM. Additionally, in the French data we demonstrated that maternal obesity is specifically associated with SMM that occurs in the antepartum, mostly due to severe hypertensive disorders. The mediation analysis conducted using French data found an 18% indirect effect of prepregnancy obesity in the association between Sub-Saharan African maternal place of birth and severe preeclampsia. In the American data, Black race was strongly associated with global SMM but the obesity-mediated effect represented only 3.2% of the total association. Latina ethnicity was also associated with severe maternal morbidity and the obesity-mediated effect was similarly small: 3.4% of the total association. In a sensitivity analysis we found a higher mediation effect of obesity in the association with Black race and Latina ethnicity (15.3% and 15.2% of the total association, respectively) and SMM cases excluding blood transfusion, consisting largely of SMM due to severe hypertensive disease. Our analyses confirm that maternal prepregnancy obesity is associated with global SMM, and suggest that obesity is a relevant although partial mediator specifically of SMM due to severe hypertensive disease. Our congruent findings in both national settings have significant implications for clinical practice, public health policy, and health disparities research. Our results highlight the need to investigate other mediators of health disparities relating to maternal origin, such as social-structural factors and quality of care.

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