Associations Between Hyperthyroidism and Adverse Obstetric and Neonatal Outcomes

A Study of a Population Database Including Almost 17,000 Women With Hyperthyroidism

Ranit Hizkiyahu; Ahmad Badeghiesh; Haitham Baghlaf; Michael H. Dahan

Disclosures

Clin Endocrinol. 2022;97(3):347-354. 

In This Article

Abstract and Introduction

Abstract

Objective: Large population-based studies on maternal hyperthyroidism's effect on antepartum, intrapartum, and neonatal complications are few. Most of these studies were small or did not evaluate a broad scope of possible complications. Therefore, a large population-based cohort study was conducted to study the associations between maternal hyperthyroidism and pregnancy and perinatal complications.

Design: This is a retrospective population-based cohort study utilizing data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample over 11 years from 2004 to 2014.

Patients: 16,984 deliveries to women with hyperthyroidism and 9,079,804 deliveries to mothers who did not suffer of hyperthyroidism.

Methods: A cohort of all deliveries between 2004 and 2014 inclusively was created. Within this group, all deliveries to women with hyperthyroidism were the study group (n = 16,984) and the remaining deliveries were categorized as nonhyperthyroidism births and comprised the reference group (n = 9,079,804). The main outcome measures were pregnancy and perinatal complications.

Results: Maternal hyperthyroidism was associated with several pregnancy and perinatal complications, including increased risks of gestational hypertension (adjusted odds ratio [aOR]: 1.236, 95% confidence interval [CI]: 1.045–1.462, p = .013) and preeclampsia (aOR: 1.190, 95% CI: 1.006–1.408, p = .042). These patients are more likely to experience preterm premature rupture of membranes (aOR: 1.322, 95% CI: 1.007–1.735, p = .044), preterm delivery (aOR: 1.287 95% CI: 1.132–1.465, p < .001), placental previa (aOR: 1.527, 95% CI: 1.082–2.155, p = .016), and suffer from venous thromboembolism (aOR: 2.894, 95% CI: 1.293–6.475, p = .010).

As for neonatal outcomes, small for gestational age and stillbirth were more likely to occur in the offspring of women with hyperthyroidism (aOR: 1.688, 95% CI: 1.437–1.984, p < .001 and aOR: 1.647, 95% CI: 1.109–2.447, p = .013, respectively).

Conclusions: Women with hyperthyroidism are more likely to experience pregnancy, delivery, and neonatal complications. We found an association between hyperthyroidism and hypertensive disorders, preterm delivery, and intrauterine fetal death.

Introduction

Hyperthyroidism in reproductive-age women is usually attributed to Graves' disease,[1] an autoimmune disease that is characterized by excessive production of thyroid hormone by the thyroid gland and the creation of thyroid stimulating hormone (TSH)-receptor autoantibodies.[2] Clinical hyperthyroidism complicates 0.1%–0.4% of pregnancies and is attributed to the high levels of the human chorionic gonadotropin stimulating the TSH receptor or to Graves' disease.[3] The influence of Graves' disease on pregnancy outcomes has been described for more than 100 years. A report from the early 1900s describes increased risks of maternal death, abortion, and preterm delivery for pregnant women who suffered from Graves' disease.[4] The American Thyroid Association guidelines cite an association between hyperthyroidism during pregnancy and various adverse maternal and neonatal outcomes.[5] These guidelines noted that poorly controlled disease was more dangerous than the illness, which was under control, and has been associated with miscarriage, preterm delivery, gestational hypertension, thyroid storm, and congestive heart failure.[5–10] These guidelines also noted that the fetuses in mothers with hyperthyroidism are at increased risks of intrauterine growth restriction, low birth weight, fetal and neonatal hyperthyroidism, and intrauterine death.[5,10] In a review by Andersen and Andersen,[11] fetal exposure to high levels of thyroid hormones was also reported to have an influence later in life, in a process called "fetal programming." In a meta-analysis from 2020 that included 29 studies, epilepsy and neurodevelopmental disorders in the offspring were associated with maternal hyperthyroidism.[12]

Several population-based studies have investigated the association between maternal hyperthyroidism and pregnancy complications.[13–16] The two larger ones investigated outcomes in a Danish population. The earlier Andersen study focused on preterm delivery and small for gestational age babies in more than 21,000 hyperthyroid women during pregnancy or first diagnosed up to 2 years postpartum. Most women in this study were diagnosed with hyperthyroidism in the 2-year period following delivery (15,980 out of 21,623).[16] The second study compared pregnancy loss in diabetic and hyperthyroidism mothers combined. However, patients were included again if the hyperthyroid diagnosis was made up to 2 years after their pregnancy. Therefore, it is not clear whether they suffered from hyperthyroidism during their pregnancy, nor the role of diabetes versus hyperthyroidism on the pregnancy complications.[14] Several other small population-based studies exist in the literature, which focused either on abortion/stillbirth alone,[15] or involved only 2144 hyperthyroid women.[13] It should be notable that all these studies were performed in the Nordic Countries.

The aim of our study, therefore, was to assess the prevalence of a variety of adverse pregnancy and delivery-associated maternal and neonatal outcomes in women with hyperthyroidism, in a large American database.

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