Tim I M Korevaar1,2,3, Eric A P Steegers4, Layal Chaker2,3, Marco Medici1,2,3, Vincent W V Jaddoe1,5,6, Theo J Visser2,3, Yolanda B de Rijke3,7, Robin P Peeters2,3. 1. The Generation R Study Group, Erasmus Medical Center and/or Sophia Children's Hospital, 3015 GE Rotterdam, The Netherlands. 2. Department of Internal Medicine, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands. 3. Academic Center for Thyroid Diseases, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands. 4. Department of Obstetrics and Gynecology, Erasmus Medical Center and/or Sophia Children's Hospital, 3015 GE Rotterdam, The Netherlands. 5. Department of Pediatrics, Erasmus Medical Center and/or Sophia Children's Hospital, 3015 GE Rotterdam, The Netherlands. 6. Department of Epidemiology, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands. 7. Department of Clinical Chemistry, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands.
Abstract
Context: Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Design, Setting, and Participants: Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Results: Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. Conclusion: In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy.
Context:Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Design, Setting, and Participants: Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Results:Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. Conclusion: In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy.
Authors: T I M Korevaar; Arash Derakhshan; Peter N Taylor; Marcel Meima; Liangmiao Chen; Sofie Bliddal; David M Carty; Margreet Meems; Bijay Vaidya; Beverley Shields; Farkhanda Ghafoor; Polina V Popova; Lorena Mosso; Emily Oken; Eila Suvanto; Aya Hisada; Jun Yoshinaga; Suzanne J Brown; Judit Bassols; Juha Auvinen; Wichor M Bramer; Abel López-Bermejo; Colin Dayan; Laura Boucai; Marina Vafeiadi; Elena N Grineva; Alexandra S Tkachuck; Victor J M Pop; T G Vrijkotte; M Guxens; L Chatzi; J Sunyer; A Jiménez-Zabala; I Riaño; M Murcia; X Lu; S Mukhtar; C Delles; U Feldt-Rasmussen; S M Nelson; E K Alexander; L Chaker; T Männistö; J P Walsh; E N Pearce; E A P Steegers; R P Peeters Journal: JAMA Date: 2019-08-20 Impact factor: 56.272