Free thyroxine during early pregnancy and risk for gestational diabetes

James E. Haddow, Wendy Y. Craig, Louis M. Neveux, Glenn E. Palomaki, Geralyn Lambert-Messerlian, Fergal D. Malone, Mary E. D'Alton, K. Welch, R. Denchy, F. Porter, M. Belfort, B. Oshiro, L. Cannon, K. Nelson, C. Loucks, A. Yoshimura, D. Luthy, S. Coe, D. Schmidt, J. Esler & 28 others G. Hankins, G. Saade, J. Lee, K. Eddleman, Y. Kharbutli, Irwin R. Merkatz, S. Carter, J. Hobbins, L. Schultz, M. Paidas, J. Borsuk, B. Isquith, B. Berlin, C. Duquette, Rhode Island, R. Baughman, J. Hanson, F. De La Cruz, T. Tripp, D. Emig, L. Sullivan, J. Bestwick, A. Abuhamad, J. Copel, J. Goldberg, J. Haddow, A. Hogg, M. Mennuti

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester) and 15-18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI1.37-3.09] (unadjusted); and 1.89 [95% CI1.26-2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted) and 1.11 [95% CI 0.74-1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related lowfT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.

Original languageEnglish (US)
Article numbere0149065
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

gestational diabetes
Gestational Diabetes
Second Pregnancy Trimester
Medical problems
thyroxine
Thyroxine
pregnancy
First Pregnancy Trimester
Pregnancy
Weights and Measures
odds ratio
risk assessment
Iodide Peroxidase
Odds Ratio
Mothers
thyrotropin
Triiodothyronine
triiodothyronine
Thyrotropin
thyroid hormones

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Haddow, J. E., Craig, W. Y., Neveux, L. M., Palomaki, G. E., Lambert-Messerlian, G., Malone, F. D., ... Mennuti, M. (2016). Free thyroxine during early pregnancy and risk for gestational diabetes. PLoS One, 11(2), [e0149065]. https://doi.org/10.1371/journal.pone.0149065

Free thyroxine during early pregnancy and risk for gestational diabetes. / Haddow, James E.; Craig, Wendy Y.; Neveux, Louis M.; Palomaki, Glenn E.; Lambert-Messerlian, Geralyn; Malone, Fergal D.; D'Alton, Mary E.; Welch, K.; Denchy, R.; Porter, F.; Belfort, M.; Oshiro, B.; Cannon, L.; Nelson, K.; Loucks, C.; Yoshimura, A.; Luthy, D.; Coe, S.; Schmidt, D.; Esler, J.; Hankins, G.; Saade, G.; Lee, J.; Eddleman, K.; Kharbutli, Y.; Merkatz, Irwin R.; Carter, S.; Hobbins, J.; Schultz, L.; Paidas, M.; Borsuk, J.; Isquith, B.; Berlin, B.; Duquette, C.; Island, Rhode; Baughman, R.; Hanson, J.; De La Cruz, F.; Tripp, T.; Emig, D.; Sullivan, L.; Bestwick, J.; Abuhamad, A.; Copel, J.; Goldberg, J.; Haddow, J.; Hogg, A.; Mennuti, M.

In: PLoS One, Vol. 11, No. 2, e0149065, 01.02.2016.

Research output: Contribution to journalArticle

Haddow, JE, Craig, WY, Neveux, LM, Palomaki, GE, Lambert-Messerlian, G, Malone, FD, D'Alton, ME, Welch, K, Denchy, R, Porter, F, Belfort, M, Oshiro, B, Cannon, L, Nelson, K, Loucks, C, Yoshimura, A, Luthy, D, Coe, S, Schmidt, D, Esler, J, Hankins, G, Saade, G, Lee, J, Eddleman, K, Kharbutli, Y, Merkatz, IR, Carter, S, Hobbins, J, Schultz, L, Paidas, M, Borsuk, J, Isquith, B, Berlin, B, Duquette, C, Island, R, Baughman, R, Hanson, J, De La Cruz, F, Tripp, T, Emig, D, Sullivan, L, Bestwick, J, Abuhamad, A, Copel, J, Goldberg, J, Haddow, J, Hogg, A & Mennuti, M 2016, 'Free thyroxine during early pregnancy and risk for gestational diabetes', PLoS One, vol. 11, no. 2, e0149065. https://doi.org/10.1371/journal.pone.0149065
Haddow JE, Craig WY, Neveux LM, Palomaki GE, Lambert-Messerlian G, Malone FD et al. Free thyroxine during early pregnancy and risk for gestational diabetes. PLoS One. 2016 Feb 1;11(2). e0149065. https://doi.org/10.1371/journal.pone.0149065
Haddow, James E. ; Craig, Wendy Y. ; Neveux, Louis M. ; Palomaki, Glenn E. ; Lambert-Messerlian, Geralyn ; Malone, Fergal D. ; D'Alton, Mary E. ; Welch, K. ; Denchy, R. ; Porter, F. ; Belfort, M. ; Oshiro, B. ; Cannon, L. ; Nelson, K. ; Loucks, C. ; Yoshimura, A. ; Luthy, D. ; Coe, S. ; Schmidt, D. ; Esler, J. ; Hankins, G. ; Saade, G. ; Lee, J. ; Eddleman, K. ; Kharbutli, Y. ; Merkatz, Irwin R. ; Carter, S. ; Hobbins, J. ; Schultz, L. ; Paidas, M. ; Borsuk, J. ; Isquith, B. ; Berlin, B. ; Duquette, C. ; Island, Rhode ; Baughman, R. ; Hanson, J. ; De La Cruz, F. ; Tripp, T. ; Emig, D. ; Sullivan, L. ; Bestwick, J. ; Abuhamad, A. ; Copel, J. ; Goldberg, J. ; Haddow, J. ; Hogg, A. ; Mennuti, M. / Free thyroxine during early pregnancy and risk for gestational diabetes. In: PLoS One. 2016 ; Vol. 11, No. 2.
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AU - Haddow, James E.

AU - Craig, Wendy Y.

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AU - Malone, Fergal D.

AU - D'Alton, Mary E.

AU - Welch, K.

AU - Denchy, R.

AU - Porter, F.

AU - Belfort, M.

AU - Oshiro, B.

AU - Cannon, L.

AU - Nelson, K.

AU - Loucks, C.

AU - Yoshimura, A.

AU - Luthy, D.

AU - Coe, S.

AU - Schmidt, D.

AU - Esler, J.

AU - Hankins, G.

AU - Saade, G.

AU - Lee, J.

AU - Eddleman, K.

AU - Kharbutli, Y.

AU - Merkatz, Irwin R.

AU - Carter, S.

AU - Hobbins, J.

AU - Schultz, L.

AU - Paidas, M.

AU - Borsuk, J.

AU - Isquith, B.

AU - Berlin, B.

AU - Duquette, C.

AU - Island, Rhode

AU - Baughman, R.

AU - Hanson, J.

AU - De La Cruz, F.

AU - Tripp, T.

AU - Emig, D.

AU - Sullivan, L.

AU - Bestwick, J.

AU - Abuhamad, A.

AU - Copel, J.

AU - Goldberg, J.

AU - Haddow, J.

AU - Hogg, A.

AU - Mennuti, M.

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N2 - Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester) and 15-18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI1.37-3.09] (unadjusted); and 1.89 [95% CI1.26-2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted) and 1.11 [95% CI 0.74-1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related lowfT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.

AB - Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester) and 15-18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI1.37-3.09] (unadjusted); and 1.89 [95% CI1.26-2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted) and 1.11 [95% CI 0.74-1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related lowfT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.

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