Relationship between maternal thyroid-stimulating hormone (TSH) elevation during pregnancy and low birth weight: A longitudinal study of apparently healthy urban Japanese women at very low risk
Introduction
Maternal thyroid function changes markedly across gestational ages during normal pregnancy, and these changes directly affect fetal development. In the first trimester, a transient surge of human chorionic gonadotropin (hCG) is secreted from the placenta and stimulates the synthesis of the mother's thyroid hormones [1], [2], [3]. As a result, serum concentrations of free triiodothyronine (FT3) and free thyroxine (FT4) are increased in women in early pregnancy [2], [3]. Conversely, thyroid hormones suppress thyroid-stimulating hormone (TSH) release from the mother's pituitary gland via a negative feedback mechanism [4]. Several lines of evidence confirm that maternal thyroid hormones cross the placenta to promote fetal development [5]. The fetal thyroid gland is too immature in the first trimester to supply sufficient thyroid hormones to support development and, thus, must rely on maternal hormones. As pregnancy progresses into the second trimester, thyroid hormone levels gradually return to normal and the TSH concentration subsequently increases to the normal range [6].
Overt hypothyroidism and subclinical hypothyroidism are known risk factors for low birth weight (LBW) [7]. Previous investigations of the impact of hypothyroidism on fetal growth have focused on the first trimester because the fetus can synthesize thyroid hormones independently in the second and third trimesters [8]. Despite this, the fetus may continue to require maternal thyroid hormones to sustain growth in the second and third trimesters [7], [9]. A limited number of longitudinal studies have been conducted in normal pregnant women [10], [11]. The present study investigated whether an increase in maternal TSH levels between the first and third trimesters of a normal pregnancy is a determinant of birth weight. Thyroid function was measured longitudinally in normal pregnant women and the impact of TSH levels on birth weight was compared with that of other risk factors for LBW neonates.
Section snippets
Inclusion and exclusion criteria
This study was designed as a longitudinal observational study of pregnant women from early gestation to delivery. We recruited 191 candidates aged 20 years or older within 1 week before or after the first day of the 12 weeks of gestation from the outpatient obstetric clinic at Juntendo University Hospital, Tokyo, Japan, from December 2010 to December 2011. Based on the patients' medical records and answers to a health status questionnaire, we excluded women with established risk factors for fetal
Participants
By 25 weeks of pregnancy, we excluded 10 of 191 participants from the study because of spontaneous and/or induced abortion (n = 4), intrauterine fetal death (n = 1), and referral to other hospitals (n = 5) (Fig. 1). In another 18 women, we could not collect at least one blood sample at the designated weeks. The final analysis was carried out for 163 participants who had 5 preterm infants after the third blood sampling.
Comparison of normal and low birth weight groups
The average birth weight of all neonates was 3052 g (range, 2032–3984 g), which was
Discussion
The present study indicates that an increase in the maternal TSH concentration between the first and third trimesters is an independent determinant of birth weight in a normal pregnancy. In this study, maternal TSH significantly increased during normal pregnancy (Fig. 2). Furthermore, ∆TSH12–36 W was three-fold higher in the LBW than in the control neonates (Table 2). The multivariate linear regression analysis confirmed that ΔTSH12–36 W was inversely correlated with birth weight after adjusting
Conflict of interest statement
The authors declare that there are no conflicts of interest in this research.
Acknowledgments
This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the promotion of Science; (B), 2011–2012, 23792670 and Grant-in-Aid for Juntendo University project research. This study was supported by the Institute for Environmental and Gender Specific Medicine, Juntendo University. We would like to thank the mother–baby pairs who participated in this study. We are also grateful to the obstetricians and midwives of Juntendo University Hospital and Hiromi Shimauchi
References (31)
- et al.
First- and second-trimester thyroid hormone reference data in pregnant women: a FaSTER (First- and Second-Trimester Evaluation of Risk for aneuploidy) Research Consortium study
Am J Obstet Gynecol
(2008) - et al.
The effect of medications on thyroid function tests
Med Clin North Am
(2012) - et al.
Variation in newborn size according to pregnancy weight change by trimester
Am J Clin Nutr
(2002) - et al.
A study to establish gestation-specific reference intervals for thyroid function tests in normal singleton pregnancy
Eur J Obstet Gynecol Reprod Biol
(2008) - et al.
Transthyretin-thyroid hormone internalization by trophoblasts
Placenta
(2013) - et al.
Secretion and transfer of the thyroid hormone binding protein transthyretin by human placenta
Placenta
(2012) - et al.
Regulation of maternal thyroid during pregnancy
J Clin Endocrinol Metab
(1990) - et al.
Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy
J Endocrinol Invest
(1993) - et al.
Thyroid function in early pregnancy in Japanese healthy women: relation to urinary iodine excretion, emesis, and fetal and child development
J Clin Endocrinol Metab
(2009) - et al.
Carrier-mediated thyroid hormone transport into placenta by placental transthyretin
J Clin Endocrinol Metab
(2009)
The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny
Thyroid
Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China
J Clin Endocrinol Metab
Maternal thyroid hormone parameters during early pregnancy and birth weight: the Generation R study
J Clin Endocrinol Metab
Fetal thyroid hormone level at birth is associated with fetal growth
J Clin Endocrinol Metab
Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women
Eur J Endocrinol
Cited by (0)
- 1
Present address.