Adverse pregnancy outcomes tied to elevated TSH levels

Women with elevated prepregnancy thyroid-stimulating hormone levels may have an increased risk for adverse pregnancy outcomes, study data from China show.

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Hui Pan, MD, of the department of endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in China, and colleagues evaluated data from the National Prepregnancy Checkups Project on 184,611 Chinese women who became pregnant to determine the relationship between maternal preconception TSH levels and pregnancy outcomes. Within 6 months before pregnancy, participants had TSH measured and researchers divided them into groups according to TSH level: 0.48 mIU/L to 2.49 mIU/L (72%), 2.5 mIU/L to 4.28 mIU/L (24%) and 4.29 mIU/L to 10 mIU/L (4%).

Overall, 9,049 participants experienced a pregnancy loss and 183,923 had a singleton birth. Mean maternal age at delivery was 25.3 years, and median TSH was 1.85 mIU/L at the examination before pregnancy. Mean gestational age of infants was 39.2 weeks, and mean birth weight was 3,311 g.

Incidence of adverse perinatal maternal and infantile adverse events was 28.6%, specifically the incidence of cesarean section was highest (38.1%), followed by operative vaginal delivery (4.8%), preterm birth (4.7%), spontaneous abortion (2.5%), stillbirth (0.3%) and postterm birth (0.2%). Incidence of adverse effects on infant birth weight were as follows: 11.1% for small for gestational age, 11.9% for large for gestational age, 4.9% for low birth weight and 5.8% for macrosomia.

The first trimester specific upper limit was TSH 2.5 mIU/L; nonpregnant reference upper limit was 4.29 mIU/L.

The risks for spontaneous abortion (adjusted OR = 1.1; 95% CI, 1.03-1.18), preterm birth (adjusted OR = 1.09; 95% CI, 1.04-1.15), early preterm birth (adjusted OR = 1.16; 95% CI, 1.05-1.27), late preterm birth (adjusted OR = 1.07; 95% CI, 1-1.13) and operative vaginal delivery (adjusted OR = 1.15; 95% CI, 1.09-1.21) were increased among the upper limit group (TSH, 2.5-4.29 mIU/L) compared with the reference group (TSH, 0.48-2.5 mIU/L). Associations were also found between the high TSH group (4.29-10 mIU/L) and spontaneous abortion (adjusted OR = 1.15; 95% CI, 1.1-1.22), stillbirth (adjusted OR = 1.58; 95% CI, 1.1-2.28), preterm birth (adjusted OR = 1.2; 95% CI, 1.08-1.34), early preterm birth (adjusted OR = 1.34; 95% CI, 1.1-1.62), late preterm birth (adjusted OR = 1.15; 95% CI, 1.01-1.3), cesarean section delivery (adjusted OR = 1.15; 95% CI, 1.1-1.22) and large for gestation age infants (adjusted OR = 1.12; 95% CI, 1.04-1.21).

“Preconception high TSH levels were associated with a small but significant increased risk of overall adverse events, including preterm birth, [cesarean section] delivery, and [large for gestational age] infants, even within normal nonpregnant range,” the researchers wrote. “TSH < 2.5 mIU/L is more suitable for the assessment of women planning a pregnancy in China, but one should not make a hasty decision to initiate treatment at this point without repeating TSH measurement and checking [thyroid antibody] status. Prospective randomized controlled trials examining the role of levothyroxine supplement in mildly hypothyroid prepregnant women are warranted in the future.” – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.

Perspective

PERSPECTIVE

Tim Korevaar

Inadequate thyroid function during early pregnancy is associated with various adverse maternal and fetal outcomes. Specifically, during early pregnancy, thyroid physiology undergoes major changes, and placental development, as well as the fetus, are dependent on maternal thyroid hormones. Therefore, if we wish to optimally treat women with a suboptimal thyroid function, we have to identify high-risk women as early as possible. Unfortunately, this can prove difficult as was illustrated in the recent study (Casey BM, et al. N Engl J Med. 2017; doi:10.1056/NEJMoa1606205). A prepregnancy thyroid function test could prove valuable to identify high-risk women. Unfortunately, there are very few data on the effects of pregestational thyroid function and the risk for adverse pregnancy outcomes.
This large study from China therefore adds important new data. The researchers showed that high prepregnancy TSH concentrations are associated with a higher risk for spontaneous abortion, preterm birth, stillbirth and children large for gestational age. Unfortunately, the authors measured only TSH concentrations and not FT4 or TPO-antibody concentrations. Thyroid autoimmunity is associated with similar outcomes, and some, but not all, studies have also found that low FT4 concentrations are associated with higher risks. Although the authors had a massive dataset, they investigated associations only by splitting up the data in a rather random manner — it would have been interesting to investigate from which TSH concentration these risks actually started to become higher. By doing so, the definition of pregestational high TSH as a risk factor for adverse pregnancy outcomes could be identified much more specifically. Future studies are needed to investigate whether prepregnancy TSH is a marker for early pregnancy thyroid function and whether that is the underlying mechanism of the associations of the current paper.

Tim Korevaar, MD, MSc
Erasmus University Medical Center in Rotterdam, Netherlands

Disclosure: Korevaar reports no relevant financial disclosures.

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Source:

Chen S, et al. Clin Endocrinol. 2017;doi:10.1111/cen.13329.