Miscarriage, Stillbirth Rates Higher With Mild Thyroid Dysfunction

Nancy A. Melville

June 24, 2012

June 24, 2012 (Houston, Texas) — In women with even mild thyroid dysfunction during early pregnancy, rates for miscarriage are double those of women with normal levels, and the risk for stillbirth is as much as 7 times greater, according to research presented here at ENDO 2012: the Endocrine Society 94th Annual Meeting.

Hypothyroidism has been linked to an increased risk for miscarriage, stillbirth, and low birth weight; however, the level of risk among pregnant women who have only subclinical hypothyroidism has remained uncertain.

In an effort to gain a better understanding of the risk, a research team led by author Jubbin Jagan Jacob, MD, of Christian Medical College and Hospital, Ludhiana, Punjab, India, evaluated 1000 pregnant women in their first trimester of pregnancy who were part of a larger project involving routine thyroid screening during early pregnancy.

The women were divided into 2 groups — those with first-trimester thyroid-stimulating hormone (TSH) levels of 2.5 mIU/L or lower, and those with TSH levels greater than 2.5 mIU/L but less than or equivalent to 4 mIU/L, which the researchers considered as indicating mild hypothyroid dysfunction.

Data were available on 533 women in the group with normal thyroid function and 263 women with TSH levels between 2.5 and 4 mIU/L.

The results showed that those with mild hypothyroid dysfunction had a significant increase in early (≤ 20 weeks' gestation) losses compared with those with normal function (8.4% vs 4.1%; P < .001) as well as late (> 20 weeks' gestation) losses (4.2% vs .6% P < .001).

The combined pregnancy losses for the mild thyroid dysfunction and normal function groups were 12.5% and 4.7%, respectively (P < .001; odds ratio [OR], 2.9; 95% confidence interval [CI], 1.6 - 5.0).

The overall odds of preterm delivery before 37 weeks in the mild thyroid dysfunction group compared with the normal function group was 2.02 (95% CI, 1.1 - 3.7).

No other significant differences were seen between the 2 groups in 11 other maternal outcomes.

The neonates born to women with mild thyroid dysfunction were more likely to be of low birth weight compared with the neonates of women with normal thyroid function (24.2% vs 16.6%; P = .01; OR, 1.6; 95% CI, 1.1 - 2.3); they were also more likely to be small for gestational age (18.6% vs 10.7%; P < .001; OR, 1.9; 95% CI, 1.2 - 2.9) and to have neonatal hyperbilirubinemia (12.1% vs 7.5%; P = .04).

Although previous research has associated mild thyroid dysfunction with pregnancy problems, Dr. Jacob said the researchers did not expect to see such dramatic stillbirth rates.

"There has been good evidence that miscarriage rates increase with mild thyroid dysfunction, especially with patients with thyroid antibody positivity, which indicates autoimmunity," he told Medscape Medical News.

"So we were not really surprised to see the increase in miscarriages; however, the increase in stillbirth rates was surprising."

Although the findings would seem to underscore the need to screen all pregnant women for abnormal thyroid levels in the first trimester, the complexities of thyroid disorders introduce a host of uncertainties, Dr. Jacob added.

"The main argument against [first-trimester testing] is that mild thyroid dysfunction manifested by a slightly elevated TSH may not necessarily imply that the thyroid dysfunction is the trigger for the increased fetal losses," he said.

"Instead, it could just be a marker for autoimmunity or micronutrient deficiency, like, for example, selenium."

"So the proof of its relevance would only be more clinically appropriate when we can demonstrate that thyroid testing and early treatment would improve outcomes."

Session moderator Stephen R. Hammes, MD, PhD, the Louis S. Wolk Distinguished Professor of Medicine and chief of the Division of Endocrinology and Metabolism at the University of Rochester Medical Center in New York, agreed that drawing conclusions on the basis of TSH levels can be tricky.

"TSH [levels] can vary from draw to draw, and in addition, we don't really know that higher TSH causes fetal loss. We only know that the 2 are associated with each other," said Dr. Hammes.

"Until you do a prospective study where you treat the higher patients with thyroid hormone, then you don't know for sure that the hypothyroid state is causing fetal loss."

Dr. Hammes noted that it is also important to consider that the study was conducted at only 1 center and that the participants were of the same ethnicity.

"Still, overall, this study is intriguing, as it suggests that thyroid status, even if seemingly normal, might have important effects on pregnancy outcome," he told Medscape Medical News. "It clearly suggests that larger prospective treatment studies should be considered.

"But given how common hypothyroidism is in women, I am a big fan of checking thyroid levels in pregnant women."

The study received funding from Christian Medical College and Hospital. The authors have disclosed no relevant financial relationships.

ENDO 2012: The Endocrine Society 94th Annual Meeting. Abstract Oro4-1. Presented June 23, 2012.


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