Impact of Preconception Cardiometabolic and Thyroid Dysfunction on Preterm Birth

Public Health/Epidemiology

Committee: 
Catherine L. Haggerty, Department of Epidemiology (advisor)
Janet M. Catov, Departments of Epidemiology and Obstetrics, Gynecology & Reproductive Sciences
Gong Tang, Department of Biostatistics
Emma Barinas-Mitchell, Department of Epidemiology
Maisa Feghali, Department of Obstetrics, Gynecology & Reproductive Sciences

Abstract: 

Background  Cardiometabolic markers such as blood pressure and other clinical factors such as thyroid dysfunction during pregnancy have been associated with preterm birth but less is known about the impact of preconception health factors.  Research is needed to determine the effect of preconception health on preterm birth among reproductive-age women.

Objective  This dissertation is comprised of three papers with the following objectives:  1) To conduct a systematic review to assess the quality and breath of current literature on preconception cardiometabolic markers and risk of preterm birth (Manuscript 1).  The purpose of this systematic review was to identify gaps in the literature that can serve to inform future research.  2) To evaluate the association between thyroid dysfunction and risk of preterm birth in reproductive-age women (Manuscript 2).  3) To determine the trajectory of blood pressure changes from the period prior to conception through pregnancy and its association with the risk of preterm birth (Manuscript 3).

Methods  For the systematic review, we conducted a search in PubMed (including Medline with In-Process & Other Non-Indexed Citations), PubmMed Central (PMC), Embase, and ClinicalTrials.gov to identify original research articles published between 1950 and July 2020.  We included articles that included analyses of preconception lipids, glucose, or blood pressure, and preterm birth.  For Manuscripts 2 and 3, women from the Longitudinal Indian Family hEalth Study (LIFE; n=539; mean age 21.60±2.83) who were recruited preconception and had measures both on the exposures of interest (blood pressure and thyroid hormones) and outcome of interest (preterm birth) were included.  For Manuscript 2, we used multivariable logistic models to assess the association between preconception thyroid dysfunction and risk of preterm birth.  Additionally, we assessed mediation by hypertensive disorders of pregnancy between thyroid dysfunction and preterm birth.  For Manuscript 3, we modeled blood pressure trajectories over time (preconception, first and third trimesters, and postpartum) and used mixed-effects models with splines to assess the longitudinal change over time in blood pressure among women experiencing preterm birth versus those delivering at full-term.  Additionally, we used logistic regression and generalized additive models at three time points (preconception, first and third trimesters) to assess the association between blood pressure and risk of preterm birth.

Results  The systematic review showed considerable heterogeneity in the assessment of the exposures and none of the studies assessed all cardiometabolic markers of interest.  Given the sparsity of the studies, we were unable to draw meaningful conclusions regarding the risk of these markers prior to conception and their association with preterm birth.  The second manuscript showed that preconception hyperthyroidism increases the risk of preterm birth, after adjusting for maternal age at conception, pre-pregnancy BMI, time between pre-pregnancy thyroid measurement and conception, education level, and hypertensive disorders of pregnancy.  However, were not able to conclude that thyroid dysfunction and risk of preterm birth is mediated by hypertensive disorders of pregnancy.  In the third manuscript, we showed that blood pressure trajectories change over time as a woman transitions from preconception to pregnancy to postpartum.  We were not able to determine an association between blood pressure increase during preconception, first or third trimesters and increased odds of preterm birth.

Conclusions  Our systematic review highlights the need for additional studies assessing preconception measures so that future healthcare recommendations can be formulated.  Our data suggest that women diagnosed with hyperthyroidism during the preconception period may have a higher risk of preterm birth in a subsequent pregnancy.  The period prior to conception may be a critical window to identify women at risk for preterm birth who may benefit from interventions to address abnormal thyroid function.  Additionally, our data indicate that the level of change in blood pressure and rate of that change is different among women with preterm births compared to women with term births.  Sufficiently powered studies with more time points are needed to better understand blood pressure trajectories before and during the course of pregnancy in association with the risk of preterm birth.