Author(s)

Pompilio Torremante¹, Wolf Kirschner², Rainer Muche³, Felix Flock⁴

¹Practice for Gynecology and Obstetrics, Ochsenhausen, Germany.
²Institute for Research, Consultation and Evaluation, Berlin, Germany.
³Institute for Biometry and Epidemiology, University of Ulm, Ulm, Germany.
⁴Department of Obstetrics and Gynecology at the Medical Centre of Memmingen, Memmingen, Germany.

Hypothyroidism, defined as thyrotropin (TSH) above and free thyroxine (fT4) serum level below the reference rage, as well as hyperthyroidism, defined as suppressed TSH and elevated thyroid hormones exceeding the upper limit of the reference range, may have major impacts on fertility and pregnancy outcome. Ideally, euthyroidism, defined as TSH and fT4 in the reference range, should be established and preserved during pregnancy prior to gestation. High estrogen levels during pregnancy stimulate the synthesis of maternal thyroxine-binding-globulin (TBG) in the liver, increasing TBG serum concentration by 2 - 3 fold compared to the initial value and affecting thus maternal fT4 serum level. As a consequence, maternal thyroid function adapts by increasing synthesis and secretion of thyroxine. TBG-induced elevation of serum thyroxine either total or free in the absence of hyperthyroidism is defined as euthyroid hyperthyroxinemia. Since TBG concentration declines first after delivery, pregnancy-induced euthyroid hyperthyroxinemia constitutes a physiological metabolic state. Depending on functional capacity, maternal thyroid may exhaust, resulting in hypothyroxinemia, which increases the risk of fetal neurodevelopmental impairment and preterm birth. The study aims to determine whether L-Thyroxine (L-T4) replacement, sustaining pregnancy-induced maternal euthyroid hyperthyroxinemia during the whole pregnancy by keeping fT4 level in the high normal reference range might reduce preterm birth rate. Preterm birth rate of women with singleton gestation and L-T4-induced high normal fT4 level constituting the study group (n = 918) was compared with the preterm birth rate of women with singleton gestation (n = 6414) who completed a questionnaire concerning L-T4 administration during pregnancy. Two groups were formed. In group A we compared the preterm birth rate between women with L-T4-induced high normal fT4 level and a control group without L-T4 administration during pregnancy. In group B we compared the preterm birth rate of women already receiving L-T4 prior to conception, maintaining dosage to keep fT4 level in the high normal reference range during gestation to a control group with L-T4 intake during pregnancy. The preterm birth rates in group A declined by 51% (p = 0.01) and in group B by 87% (p = 0.001) in multiparous women, while in primiparous the preterm birth rate was similar between study and the control group. Sustaining a high normal fT4 level during pregnancy with L-T4 may significantly reduce preterm birth rate in multiparous women.

Preterm Birth, Euthyroid Hyperthyroxinemia, Thyroid, Pregnancy

Torremante, P. , Kirschner, W. , Muche, R. and Flock, F. (2017) Maternal Euthyroid Hyperthyroxinemia May Reduce Preterm Birth Rate in Multiparous Women. Open Journal of Obstetrics and Gynecology, 7, 623-638. doi: 10.4236/ojog.2017.76065.