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

https://doi.org/10.1016/j.earlhumdev.2014.12.014Get rights and content

Highlights

  • Maternal thyroid hormones and TSH were measured during normal pregnancy.

  • These hormones were compared between low birth weight (LBW) and normal groups.

  • An increase in maternal TSH in third trimesters was larger in LBW than in normal groups.

  • An increase in maternal TSH is an independent determinant of newborn LBW.

Abstract

Objective

Thyroid hormones cross the placenta and promote fetal development and growth. The present study investigated whether an increase in maternal thyroid-stimulating hormone (TSH) concentration between the first and third trimesters is a determinant of birth weight during normal pregnancy.

Methods

Maternal thyroid hormones and TSH were longitudinally measured at 12, 25, and 36 weeks of pregnancy in 163 healthy pregnant women. Low birth weight (LBW) was defined as less than 2500 g. ∆TSH12–36 W was calculated as the difference in TSH concentrations between 12 and 36 weeks of pregnancy.

Results

Of the 163 neonates, 10 (6.1%) were LBW neonates. Free triiodothyronine and free thyroxine levels were similar at all gestational ages in the normal birth weight (Normal) and LBW groups. However, the median ∆TSH12–36 W value was higher in the LBW than the Normal group (1.67 vs. 0.54 mIU/L, P = 0.008). Multivariate linear regression analysis showed that ∆TSH12–36 was inversely correlated with birth weight (β =  0.179, P = 0.008).

Conclusion

An increase in maternal TSH concentration between the first and third trimesters is an independent determinant of birth weight in normal pregnancy.

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)

  • D. Glinoer et al.

    The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny

    Thyroid

    (2000)
  • P.Y. Su et al.

    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

    (2011)
  • M. Medici et al.

    Maternal thyroid hormone parameters during early pregnancy and birth weight: the Generation R study

    J Clin Endocrinol Metab

    (2013)
  • B.M. Shields et al.

    Fetal thyroid hormone level at birth is associated with fetal growth

    J Clin Endocrinol Metab

    (2011)
  • M. Boas et al.

    Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women

    Eur J Endocrinol

    (2009)
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