| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
BRIEF REPORT |
Department of Endocrinology (B.S., A.H., B.K., A.T.H., B.V.), Peninsula Medical School, Royal Devon and Exeter Hospital, Exeter EX2 5DW, United Kingdom; and Department of Endocrinology (M.B., R.W.B.), James Cook University Hospital, Middlesbrough TS4 3BW, United Kingdom
Address all correspondence and requests for reprints to: Dr. B. Vaidya, Department of Endocrinology, Royal Devon, Exeter Hospital, Exeter EX2 5DW, United Kingdom. E-mail: bijay.vaidya{at}pms.ac.uk.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Aim: Our aim was to examine whether smoking is associated with changes in thyroid function of pregnant women and their fetus.
Subjects and Methods: We examined the relationship between smoking and thyroid function (serum TSH, free T4, and free T3) in two independent cohorts of pregnant women without a history of thyroid disorder or an overt biochemical thyroid dysfunction: 1) first-trimester cohort (median gestation 9 wk) (n = 1428) and 2) third-trimester cohort (gestation 28 wk) (n = 927). We also analyzed the relationship between maternal smoking and thyroid hormone levels in cord serum of 618 full-term babies born to the women in the third-trimester cohort.
Results: In smokers compared with nonsmokers, median serum TSH was lower (first-trimester cohort: 1.02 vs. 1.17 mIU/liter, P = 0.001; third-trimester cohort: 1.72 vs. 1.90 mIU/liter, P = 0.037), and median serum FT3 was higher (first-trimester cohort: 5.1 vs. 4.9 pmol/liter, P < 0.0001; third-trimester cohort: 4.4 vs. 4.1 pmol/liter, P < 0.0001). In both cohorts, serum FT4 in smokers and nonsmokers were similar. The prevalence of anti-thyroperoxidase antibodies was also similar in smokers and nonsmokers in both cohorts. Cord serum TSH of babies born to smokers was lower than of those born to nonsmokers (6.7 vs. 8.1 mIU/liter, P = 0.009).
Conclusions: Cigarette smoking is associated with changes in maternal thyroid function throughout the pregnancy and in fetal thyroid function as measured in cord blood samples.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
We analyzed the relationship between smoking and thyroid hormone levels in two independent cohorts of pregnant women: one during the first trimester and one at the beginning of the third trimester.
Middlesbrough cohort
In 2002–2003, TSH, free T4 (FT4), and FT3 was analyzed in 1466 pregnant women without known thyroid disorders during their first antenatal check-up (13). At the time of sampling, with a questionnaire, women were asked how many cigarettes they smoked a day, within different categories (Table 1
), and whether they stopped smoking within the past 12 months.
|
Exeter cohort
Women were recruited from 1999–2004 as part of the Exeter Family Study of Child Health (14). Blood samples were taken at 28 wk gestation, when women were asked by the research midwife whether they smoked and, if so, how many a day, within different categories (Table 1
). The women were also given a questionnaire to fill in which asked whether they had ever smoked and, if so, how many they smoked 1 month before their pregnancy and within the first 3 months of their pregnancy.
TSH, FT4, FT3, and anti-TPO were analyzed in stored serum samples of 1001 women without known thyroid disorders. We excluded women with overt biochemical hypothyroidism (n = 9) and hyperthyroidism (n = 1). Smoking data were missing in 41 women. Therefore, 927 women were included in the analysis. Results of anti-TPO were available in 924 (99.7%). TSH, FT4, and FT3 levels in cord serum samples of 618 full-term babies born to these women were also available.
Socioeconomic status in both cohorts was assessed by Townsend scores based on post codes (15). The local research ethics committees approved the study, and all participants gave informed written consent.
Analysis of thyroid function and thyroid antibodies
Serum TSH, FT4, and FT3 were analyzed in both cohorts using the electrochemiluminescent immunoassay, run on the Modular E170 Analyzer (Roche, Burgess Hill, United Kingdom). The manufacturers’ reference ranges were as follows: Middlesbrough, TSH 0.27–4.2 mIU/liter, FT4 12–23 pmol/liter, and FT3 4–7.8 pmol/liter; Exeter, TSH 0.35–4.5 mIU/liter, FT4 11–24 pmol/liter, and FT3 3.9–6.8 pmol/liter. In Middlesbrough, anti-TPO was analyzed by a manual semiquantitative microtiter plate agglutination method (Fujirebio Inc., Tokyo, Japan). A reactive pattern detected at a final dilution of 1 in 1600 or greater was considered positive. In Exeter, anti-TPO was analyzed using the competitive immunoassay (Roche), and a concentration above 34 kIU/liter was considered positive.
Statistical analyses
Maternal TSH results were not normally distributed despite various transformations of the data. Therefore, analysis was carried out using nonparametric statistics. For consistency, maternal FT3 and FT4 results were also analyzed using nonparametric statistics. Comparisons in thyroid function tests between smokers and nonsmokers were carried out using Mann-Whitney U tests. Regression analysis was used to examine associations between smoking and thyroid function tests while adjusting for parity and socioeconomic status, and residuals were checked for normality. Cord TSH and FT3 concentrations were also positively skewed, but log transformation of the data approximated normal distribution. ANOVA was used to examine associations between maternal smoking and cord thyroid function tests, while adjusting for confounders such as gestational age, low Apgar score, and mode of delivery (cesarean, assisted delivery, or normal vaginal birth, added to the ANOVA as dummy variables).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Demographic characteristics of the pregnant women are shown in Table 1. The prevalence of smokers was higher in the Middlesbrough cohort (P < 0.0001). Among the nonsmokers, 248 of 1022 in the Middlesbrough cohort and 134 of 794 in the Exeter cohort had stopped smoking during the pregnancy (previous smokers).
Effect of smoking during pregnancy on maternal thyroid function
In both cohorts, maternal TSH concentrations were lower in smokers than in nonsmokers, and FT3 concentrations were higher (Table 2). There was no association between smoking and FT4 concentrations. Removing those with subclinical hypo- or hyperthyroidism made little difference to the results, although in the Exeter cohort, the difference in the TSH concentrations was no longer statistically significant (P = 0.055). Similarly, removing those who had no anti-TPO status made no difference to the results. In both cohorts, the prevalence of anti-TPO-positive women was similar among smokers and nonsmokers, although median anti-TPO concentration was higher in smokers in the Exeter cohort (Table 2).
|
). TSH concentrations remained lower in the smokers; however, the difference between the smokers and nonsmokers was reduced, and the result was significant only in the Middlesbrough cohort.
|
We analyzed, within the nonsmoker groups, whether thyroid hormone levels in women who stopped smoking only during the pregnancy (previous smokers) were different from those in women who did not smoke at all (long-term nonsmokers). In both cohorts, there were no differences in the thyroid function results between previous smokers and long-term nonsmokers, except FT4 concentrations were reduced in previous smokers in the Middlesbrough cohort (P = 0.007) (supplemental Table 2). In the Exeter cohort, we found no differences in thyroid function tests between those who ceased smoking in the first 12 wk with those who had never smoked (data not shown).
When examining number of cigarettes smoked per day, we found no effects of a dose response on TSH, FT4, or FT3 concentrations (data not shown).
Effect of paternal smoking on maternal thyroid function
Paternal smoking status was available only in the Exeter cohort. To explore the effect of passive smoking, we compared those families where neither parent smoked (n = 590) and those where only the father smoked (n = 160). There was no significant difference in maternal TSH or FT4 concentrations between those families where neither parent smoked and those where only the father smoked, but FT3 concentrations were slightly higher in the latter [median (interquartile range): 4.10 pmol/liter (3.85–4.43) vs. 4.17 pmol/liter (3.91–4.55); P = 0.049].
Effect of maternal smoking on fetal thyroid function
TSH in cord serum samples of babies born to women who smoked during pregnancy was lower than of those born to nonsmokers (P = 0.008) (Table 2).
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
There are several possible mechanisms by which smoking may affect thyroid hormone levels. First, nicotine or other constituents in cigarette smoke may stimulate thyroid hormone secretion either directly or through sympathetic activation. However, nicotine infusion in rats did not show any effect on T4, T3, and TSH levels (16). Second, thiocyanate (a toxin in the cigarette smoke) may cause intrathyroidal iodine depletion predisposing to increased thyroid nodularity and autonomous thyroid hormone secretion (7). Third, smoking has been shown to be associated with a reduced prevalence of anti-TPO, suggesting that low TSH levels in smokers reflect a decreased prevalence of autoimmune hypothyroidism (8). However, we found similar prevalence of anti-TPO in smokers and nonsmokers in our two cohorts (Table 2), and the influence of smoking on thyroid hormone levels were persistent when only anti-TPO-negative women were analyzed (Table 3). Finally, smoking may alter thyroid hormone levels through its effect on deiodinase activity. Nicotine has been shown to increase type 2 deiodinase activity in cultured rat brain glial cells (17). Our finding of raised FT3 (and not FT4) among smokers may be explained by the increased type 2 deiodinase activity associated with smoking and suggests that this smoking-related change in thyroid function is more likely to be a peripheral phenomenon than thyroid stimulation.
In both cohorts, we found that women who stopped smoking during the pregnancy (previous smokers) had thyroid hormone levels similar to nonsmokers. Similarly, in the Exeter cohort, women who stopped smoking in the first 12 wk of pregnancy had thyroid hormone levels similar to nonsmokers. Consistent with these findings, a study in the general population has shown that smoking cessation is associated with a reversal of smoking-related changes in thyroid hormone levels (10). Together, these findings suggest that the smoking-related changes in thyroid hormone levels are rapidly reversible in both nonpregnant and pregnant individuals.
This study shows, for the first time, that smoking during pregnancy is also associated with changes in fetal thyroid function as measured in cord blood at the time of delivery. Cord serum TSH of babies born to women who smoked during pregnancy was lower than those born to nonsmoker mothers. Previous studies did not find a correlation between maternal smoking and cord thyroid function (18, 19, 20), but the studies were smaller and were not sufficiently powered to detect the size of change in our study. We did not find an association between maternal smoking and cord serum FT3. A possible explanation for this finding is that the mild influence of smoking on FT3 (possibly mediated by an increased type 2 deiodinase activity) is counterbalanced by very active placental type 3 deiodinase enzyme (1). One limitation of our study was that we did not corroborate smoking status using laboratory tests; however, a recent study of pregnant women has shown that self-reported smoking information is reliable (21).
There is increasing evidence that even mild abnormalities in maternal thyroid hormone levels during pregnancy are associated with both maternal and fetal adverse outcomes (1). Therefore, finding of factors, such as smoking, which may modulate thyroid hormone levels in pregnancy is important. Although, the magnitude of effect of smoking on thyroid function in our study was small, the smoking-related changes in the thyroid function extended to the fetus, suggesting these changes could have a biological impact on the fetus. Further studies are needed to analyze whether the changes in the maternal and fetal thyroid function associated with maternal smoking results in any adverse pregnancy outcomes.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Disclosure Statement: The authors have nothing to disclose.
First Published Online November 18, 2008
Abbreviations: Anti-TPO, Anti-thyroperoxidase antibodies; FT4, free T4.
Received February 19, 2008.
Accepted October 14, 2008.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  M. Boas, J. L. Forman, A. Juul, U. Feldt-Rasmussen, N. E. Skakkebaek, L. Hilsted, M. Chellakooty, T. Larsen, J. F. Larsen, J. H Petersen, et al. Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women Eur. J. Endocrinol., December 1, 2009; 161(6): 903 - 910. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
