Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy

Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A

doi:10.1210/jc.2010-0340

The Journal of Clinical Endocrinology and Metabolism, 95(9), E44-E48, 2010

Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy

Roberto Negro , Alan Schwartz , Andrea Tinelli

Author affiliations (4)

Ospedale Vito Fazzi ROR
University of Chicago Medical Center ROR
Touro University California ROR
Casa di Cura Città di Roma ROR

DOI10.1210/jc.2010-0340 PMID20534758

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Abstract

Context

The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter.

Objective

The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter.

Design

The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups based on their initial TSH: group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4), and group B, TSH level between 2.5 and 5.0 mIU/liter.

Setting

The study was conducted at two ambulatory clinics of community hospitals in southern Italy.

Patients

A total of 4123 women were evaluated.

Intervention

There was no intervention.

Main Outcome Measures

The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured.

Results

The rate of pregnancy loss was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively, P = 0.006). There was no difference in the rate of preterm delivery between the two groups.

Conclusions

The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.

Topics

pregnancy/early-pregnancy/miscarriage birth-and-delivery/birth-outcomes/maternal-morbidity diagnostics/hormone-testing/serum-panels

TSH 2.5 to 5.0 pregnancy loss first trimester, thyroid antibody negative subclinical hypothyroidism miscarriage, Negro Stagnaro-Green TSH upper limit pregnancy, redefining normal TSH first trimester pregnancy, thyroid peroxidase antibody negative women pregnancy outcomes, subclinical hypothyroidism preterm delivery pregnancy loss, TSH upper limit 2.5 mIU first trimester evidence, prospective trial levothyroxine pregnancy thyroid screening, elevated TSH spontaneous abortion risk antibody negative, thyroid function early pregnancy miscarriage rate

PMID 20534758 20534758 DOI 10.1210/jc.2010-0340 10.1210/jc.2010-0340 Negro et al. 2010, Negro 2010

Cite this article

Negro, R., Schwartz, A., Gismondi, R., Tinelli, A., Mangieri, T., & Stagnaro-Green, A. (2010). Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. The Journal of clinical endocrinology and metabolism, 95(9), E44-E48. https://doi.org/10.1210/jc.2010-0340

Keywords

Abortion, Spontaneous/blood/epidemiology/etiology/immunology, Adult, Case-Control Studies, Embryo Loss/blood/epidemiology/etiology/immunology, Female, Humans, Immunoglobulins, Thyroid-Stimulating/blood, Incidence, Osmolar Concentration, Parity/physiology, Pregnancy, Pregnancy Trimester, First/blood/immunology, Reference Values, Thyrotropin/analysis/blood, Young Adult, Immunoglobulins, Thyroid-Stimulating, Thyrotropin

Hormone Testing · Serum Panels

Significance of dynamically monitoring serum estrogen and β-human chorionic gonadotropin in early pregnancy assessment

Li Y et al., 2021 Journal of clinical laboratory analysis

Spontaneous abortion occurs in 15% ~ 25% of clinical pregnancy. β-human chorionic gonadotropin (β-HCG) and progesterone (P) have been widely used in early pregnancy assessment, but their clinical significances are still controversial. Estradiol (E2) has not been used as widely as β-HCG and P, and its value in predicting pregnancy outcome is unclear. In this retrospective study, two hundred early pregnancy women were divided into two groups according to their early pregnancy outcomes: the ongoing pregnancy group and inevitable abortion group. Serum E2 and β-HCG levels and their growth rates were compared weekly. Estradiol and β-HCG of the ongoing pregnancy group were significantly higher than that of the inevitable abortion group from the 5th to 10th week of pregnancy. Taking 489.5 pg/mL in the 5th and 6th week, 590.5 pg/mL in the 7th week, and 614.5 pg/mL in the 8th week as cutoff levels of E2, the sensitivity and specificity for E2 to predict bad pregnancy outcome were 91.7% and 41.5%, 82.9% and 71.1%, 84.8% and 84.7%, 75.0% and 95.7%, respectively (P < .05). Both E2 and β-HCG increased much more rapidly in the ongoing pregnancy group. 80% of the normal pregnancy women showed continuously increasing E2 level. Meanwhile, the inevitable abortion group presented E2 variation types as slow increase or fluctuation, continuous decline, and sudden drop, which account for 54.0%, 34.0%, and 12.0%, respectively. Low values and low growth rates of E2 and β-HCG probably indicate bad pregnancy outcomes.

Hormone Testing · Serum Panels

Antimüllerian hormone and pregnancy loss from the Effects of Aspirin in Gestation and Reproduction trial

Zarek SM et al., 2016 Fertil Steril Open Access

To evaluate if antimüllerian hormone (AMH) is associated with pregnancy loss. Prospective cohort study within a block-randomized, double-blind, placebo-controlled trial of low-dose aspirin. Not applicable. PATIENT(S): Women (n = 1,228) were of ages 18-40 years with a history of one to two pregnancy losses and were actively attempting pregnancy without fertility treatment. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Pregnancy loss. RESULT(S): Relative risks (and 95% confidence interval [CIs]) of human chorionic gonadotropin (hCG)-detected and clinical pregnancy loss were assessed with the use of log binomial models with robust variance and inverse probability weights adjusted for age, race, body mass index, income, trial treatment assignment, parity, number of previous losses, and time since most recent loss. AMH levels were defined as: low (<1.00 ng/mL; n = 124), normal (referent; 1.00-3.5 ng/mL; n = 595), and high (>3.5 ng/mL; n = 483). Of the 1,202 women with baseline AMH data, 19 (17.3%) with low AMH experienced a clinical loss, compared with 61 (11.4%) with normal AMH and 50 (11.8%) with high AMH levels. Low or high AMH levels, compared with normal AMH, were not associated with clinical loss. Results for hCG-detected pregnancy loss mirrored those of clinical loss. CONCLUSION(S): AMH values were not associated with hCG-detected or clinical pregnancy loss in unassisted conceptions in women with a history of one to two previous losses. Our data do not support routine AMH testing for prediction of pregnancy loss. Clinical NCT00467363.

Hormone Testing · Serum Panels

Abnormal thyroid function parameters in the second trimester of pregnancy are associated with breech presentation at term: a nested cohort study

Vissenberg R et al., 2016 Eur J Obstet Gynecol Reprod Biol

Thyroid dysfunction has been described as a possible risk factor for having an abnormal fetal position at birth. In this study we aim to determine the association between thyroid function in early pregnancy and breech presentation at term. We used data from the Amsterdam Born Children and their Development (ABCD) cohort. 3347 pregnant women were included between January 2003 and March 2004 in Amsterdam, the Netherlands. Thyroid function tests were performed between 5 and 37 weeks gestational age (median 12.9 weeks). The main outcome measure was the association between thyroid function in early pregnancy and breech presentation at term. Univariate and multivariate analysis were performed to determine the association between thyroid function and breech presentation. Increased TSH in pregnancy, defined as thyroid stimulating hormone (TSH) >97.5th percentile (>3.53mIU/L), was associated with a higher risk for breech presentation at term (aOR 2.32, CI 1.1-4.8, p=0.02) compared to euthyroidism (TSH between 2.5th and 97.5th percentile). After exclusion of overt hypothyroidism and hyperthyroidism the aOR was 2.34 (CI 1.1-5.0, p=0.03). Trimester specific analysis showed a significant association of increased TSH levels (>3.68mIU/L) in the second trimester with breech presentation (aOR 3.7, CI 1.7-7.8, p=0.001). In the second trimester low free thyroxine (FT4) <2.5th percentile (<6.7pmol/L) was also associated with breech presentation (aOR 2.5, CI 1.0-6.3, p=0.04). Increased TSH and decreased FT4 in the second trimester of pregnancy are associated with an increased risk for breech presentation at term. The association of abnormal thyroid parameters in the first of third trimester is still unclear.

Luteal Phase · Luteal Phase Deficiency

Luteal phase estradiol and pregnancy outcome in gonadotropin releasing hormone agonist/human menopausal gonadotropin-treated gamete intrafallopian transfer cycles

Molo MW et al., 1995 J Reprod Med

To correlate luteal estradiol (E2) levels with pregnancy outcome, 36 consecutive conceptions resulting from gamete intrafallopian transfer in gonadotropin releasing hormone agonist/human menopausal gonadotropin (GnRH-a/hMG) cycles were analyzed. GnRH-a was initiated during the preceding luteal phase. HMG was adjusted individually. Human chorionic gonadotropin (hCG), 5,000 IU, was administered when E2 was > 500 pg/mL and the leading follicle > 17 mm (day 0). The luteal phase was supported by (1) hCG, 1,500 IU in three doses from day 5 and (2) progesterone (P) from day 7. E2 and P levels were analyzed in three groups of normally progressing pregnancy (NPP), abortion (AB) and preclinical abortion (PAB). No significant differences in mean E2 levels were seen between the groups from day 0 through day 5 after hCG. Midluteal E2 levels were significantly different between the groups (P < .05). Late luteal E2 values were significantly higher for NPP than for either AB or PAB (P < .05). There were no significant differences in luteal P values between the NPP, AB and PAB groups. Decreased luteal E2 appears to be associated with early pregnancy wastage; this may be due to inadequate endometrial support.

Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy

Abstract

Topics

Cite this article

Keywords

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Significance of dynamically monitoring serum estrogen and β-human chorionic gonadotropin in early pregnancy assessment

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