Thyroid disorders in pregnancy: Frequency and association with selected diseases and obstetrical complications in Tunisian women

doi:10.1016/j.clinbiochem.2008.05.002

Clinical Biochemistry

Volume 41, Issue 12, August 2008, Pages 927-931

https://doi.org/10.1016/j.clinbiochem.2008.05.002 Get rights and content

Abstract

Objective

To determine the prevalence of thyroid disorders (TDs) and identify groups at risk for TDs in Tunisian pregnant women.

Methods

Thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase antibodies (TPO-Ab) were determined in 1519 pregnant women. Thyroid disorder was defined as hyperthyroidism (TSH ≤ 0.10 mIU/L) or hypothyroidism (TSH > 4.5 mIU/L), and/or positive TPO-Ab (> 12 IU/L).

Results

TDs were observed in 147 women (9.7%). The prevalence was 6.5%, 3.2% and 1.3% for positive anti-TPO, hypothyroidism and hyperthyroidism, respectively. According to a trimester of gestation (first, second, and third, respectively), the prevalence decreases for positive TPO-Ab (7.7%, 7.5% and 4.7%) and for hyperthyroidism (2.7%, 0.7% and 0.5%), but increases for hypothyroidism (2.2%, 3.3% and 3.7%). TDs were more frequent in women with non-thyroid autoimmune disease [25% vs 9.6%; odds ratio (OR), 95% confidence interval (95% CI), 3.16 (1.01–11.8); p = 0.05]. Women with positive TPO-Ab showed higher prevalence of non-thyroid autoimmune disease [25% vs 6.4%; OR (95% CI), 4.90 (1.31–18.4); p = 0.04] and a trend toward increase of past gestational hypertension (p = 0.09), late abortion (p = 0.09), and fetal death (p = 0.09). Hypothyroidism was more frequent in women with non-thyroid autoimmune disease and those with past pregnancy loss.

Conclusions

TDs are common in Tunisian pregnant women and are associated with autoimmune diseases and poor gestational outcomes. These data support the benefit of thyroid testing in pregnant women, especially those with these conditions.

Introduction

Pregnancy is associated with physiological changes in thyroid function resulting from a combination of several factors specific for the pregnant state [1], [2]. These changes, in turn, may result in thyroid disorders (TDs). TDs during pregnancy have been associated with adverse health outcomes for both the mother and child, including increased risk of miscarriage, gestational hypertension, low birth weight and fetal death [3], [4], [5], [6], [7], [8]. In addition, mild maternal thyroid insufficiency has been associated with delayed neuropsychological development in neonate and child [9], [10], [11], and the presence of anti-thyroid antibodies may result in increased risk of miscarriage, gestational diabetes mellitus, postpartum thyroiditis and depression, permanent hypothyroidism and impaired child development [12], [13], [14], [15], [16], [17].

In Tunisia, thyroid diseases are rather frequent in clinical practice, mainly in menopausal women. However, the precise prevalence of TDs in Tunisian women of reproductive age and pregnant women is unknown. TDs are often undiagnosed, and often remain occult for long periods of time. Even overt forms may be unrecognized during gestation because several symptoms and signs of TDs are common in pregnant women. Further, pregnancy complications such as miscarriage, gestational hypertension and low birth weight occur frequently and often remain of undetermined origin. For these reasons, and in the absence of a consensus for universal screening of TDs in pregnant women, we undertook this study in order to determine the prevalence of TDs in Tunisian pregnant women, and to recognize among them groups at risk for thyroid diseases.

Section snippets

Study design

This cross-sectional study included consecutive pregnant women who presented for prenatal care at the Centre of Maternity and Neonatology of Tunis between July and December 2004 (n = 1548). Almost all participants were from the Tunis region, which is considered marginally iodine sufficient [18], [19]. All women underwent routine prenatal laboratory evaluation, including serology for rubella and toxoplasmosis, and/or glycaemia. With the informed consent of each woman and approval of the Rabta

Results

TDs were observed in 147 pregnant women (9.7%). Positive TPO-Ab was noted in 99 women (6.5%), hypothyroidism in 48 women (3.2%) and hyperthyroidism in 10 women (1.3%). Distribution of subjects according to thyroid function and TPO-Ab status, and values of plasma TSH concentrations in different groups, are shown in Table 1. Prevalence by trimesters (first, second, and third, respectively) was: TDs 11.0%, 10.0% and 8.4%; positive TPO-Ab 7.7%, 7.5% and 4.7%; hypothyroidism 2.2%, 3.3% and 3.7%; and

Discussion

Our data show that TDs, mainly positive TPO-Ab and hypothyroidism, are common in Tunisian pregnant women. The prevalence of TDs, hyperthyroidism and positive TPO-Ab decreases, and the prevalence of hypothyroidism increases through gestation. Hypothyroidism was observed in 3.2%, which is higher than the prevalence of 2.2% to 2.5% reported in European and American pregnant women [4], [8], [13], [21], [22]. In this study, hypothyroidism was often mild (TSH between 5 and 10 mIU/L in 2.9% of women).

Acknowledgments

The authors are indebted to Abbott Diagnostics for providing regents for TSH and TPO-Ab assays. We gratefully acknowledge Dr. Frank Quinn for helpful advice in the preparation of this manuscript.

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Autoimmune thyroid disease, one of the main risk factors for hypothyroidism, is associated with adverse pregnancy outcomes. The burden of autoimmune thyroid disease in pregnancy and its association with thyroid function among normotensive pregnant women and pregnant women with hypertension in South Africa are not known.
This study aimed to establish the magnitude of thyroid peroxidase autoantibodies in pregnancy in the Eastern Cape of South Africa and its relationship with iodine nutrition status and preeclampsia.
Overall, 60 randomly selected normotensive pregnant controls at term and 120 pregnant participants with preeclampsia in the third trimester of pregnancy going to the Mthatha Regional Hospital and the Nelson Mandela Academic Hospital in the Eastern Cape Province who had complete data on thyroid peroxidase antibody titers, urinary iodine concentrations, serum thyroid-stimulating hormones, and free triiodothyronine, free thyroxine, and thyroglobulin levels were enrolled in this unmatched case-control study.
The cases and controls had similar mean chronological age (23.8 vs 24.0 years), body mass index (29.4 vs 28.8 kg/m²), and median parity (both 1) (P>.05). The controls had a higher mean gestational age than participants with preeclampsia (38.5 vs 33.7 weeks, respectively; P<.001). Both participants with preeclampsia and normotensive participants had median thyroid peroxidase antibody levels consistent with a negative thyroid autoimmune status. Participants with preeclampsia had higher but nonstatistically significant median thyroid peroxidase antibody (2.14 vs 1.77 IU/L), thyroglobulin (25.9 vs 21.3 µg/L), and thyroid-stimulating hormone (2.4 vs 2.3 mIU/L) levels (P>.05) and significantly lower median urinary iodine concentration (123.4 vs 188.6 µg/L), free thyroxine (13.2 vs 14.1 pmol/L), and free triiodothyronine (4.3 vs 4.6 pmol/L) levels (P<.05) than normotensive controls. Thyroid peroxidase antibodies were positively correlated with thyroglobulin, urinary iodine concentration, and thyroid-stimulating hormone.
In the rural Eastern Cape of South Africa, pregnant women in the third trimester of pregnancy have thyroid peroxidase antibody titers that show negative thyroid autoimmune status. Insufficient iodine intake, other than thyroid autoimmune disease, seems to be the underlying cause of the lower free triiodothyronine and free thyroxine levels observed among women with preeclampsia.
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Table 3 includes descriptions of each study, including their definitions of RPL as well as thyroid autoimmunity, thyroid status, and results. Fourteen of the 26 studies showed a statistically significant association between thyroid autoimmunity and RPL (26–36, 46, 47, 49), whereas 12 studies showed no association (21, 37–45, 48, 50). Meta-analysis of the 17 studies that provided data comparing the prevalence of thyroid autoimmunity in a cohort of women with RPL to those without RPL revealed a statistically significant association between thyroid autoimmunity and RPL (OR 1.94; 95% CI, 1.43–2.64) (26, 29,31–33, 35–39, 42, 47, 48, 50, 51).
To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves outcomes.
Systematic review and meta-analysis.
University obstetrics and gynecology departments.
Women with RPL and overt/subclinical hypothyroidism, and/or thyroid autoimmunity.
None.
Associations between RPL and overt/subclinical hypothyroidism and/or thyroid autoimmunity and any effects of treatment.
After our review of articles from PubMed, EMBASE, Web of Science, and CENTRAL, we found two interventional studies in which levothyroxine did not improve the subsequent live-birth rate in women with subclinical hypothyroidism with or without thyroid antibodies. A meta-analysis of five studies revealed the prevalence of subclinical hypothyroidism in RPL to be 12.9% (95% confidence interval [CI], 0%–35.2%). A meta-analysis of 17 studies revealed a statistically significant association between RPL and thyroid autoimmunity (odds ratio 1.94; 95% CI, 1.43–2.64). However, a randomized study suggested that levothyroxine does not benefit euthyroid women with thyroid autoimmunity.
Based on the limited observational studies available, no association exists between RPL and subclinical hypothyroidism, nor does levothyroxine improve subsequent pregnancy outcomes. An association exists between RPL and thyroid autoimmunity, but levothyroxine does not improve subsequent pregnancy outcomes. Women with RPL should be screened/treated for overt thyroid disease but not thyroid autoimmunity. Thyroid antibody screening is not supported by the published studies, and further randomized studies are needed. No recommendation regarding the treatment of subclinical hypothyroidism can be made at this time; prospective and randomized studies are urgently needed.
Hipotiroidismo subclínico y autoinmunidad tiroidea en pérdida gestacional recurrente: una revisión sistemática y meta-análisis
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departamentos universitarios de Obstetricia y Ginecología.
Mujeres con RPL e hipotiroidismo clínico o subclínico y/o autoinmunidad tiroidea.
ninguna.
Asociaciones entre RPL e hipotiroidismo clínico o subclínico y/o autoinmunidad tiroidea y algún efecto de su tratamiento.
después de revisar artículos de PubMed, EMBASE, Web of Science y CENTRAL, encontramos dos estudios de intervención en los cuales la levotiroxina no mejoró la tasa de recién nacido vivo en mujeres con hipotiroidismo subclínico con o sin anticuerpos tiroideos. Un meta-análisis de 5 estudios reveló que la prevalencia de hipotiroidismo subclínico en RPL era del 12,9% (95% intervalo de confianza (CI), 0%-35.2%). Un meta-análisis de 17 estudios reveló una asociación estadísticamente significativa entre RPL y autoinmunidad tiroidea (odds ratio 1.94; 95% CI, 1.43-2.64). Sin embargo, un estudio aleatorizado sugirió que la levotiroxina no beneficia a mujeres eutiroideas con autoinmunidad tiroidea.
basado en los estudios observacionales disponibles, no existe asociación entre RPL e hipotiroidismo subclínico, ni la levotiroxina mejora los resultados de la gestación subsecuente. Existe una asociación entre RPL y autoinmunidad tiroidea, pero la levotiroxina no mejora los resultados de la gestación subsecuente. Las mujeres con RPL deben ser valoradas y tratadas por enfermedad tiroidea clínica pero no por autoinmunidad tiroidea. El screening de anticuerpos anti tiroideos no se justifica en los estudios publicados y se necesitan más estudios aleatorizados. No pueden hacerse recomendaciones respecto al tratamiento de hipotiroidismo subclínico en este momento; se necesitan de forma urgente, estudios prospectivos aleatorizados.
Autoimmune thyroid disease during pregnancy
2018, The Lancet Diabetes and Endocrinology
Citation Excerpt :
The prevalences of thyroglobulin and thyroperoxidase antibody positivity in women who are aged 20–29 years are 9·2% and 11·3%; in those aged 30–39 years they are 14·5% and 14·2%; and in those aged 40–49 years old, they are 16·4% and 18·0%, respectively.16 In the general population of pregnant women, the prevalence of thyroperoxidase antibody positivity ranges from 5% to 14%, and that of thyroglobulin antibodies from 3% to 18%.11,13,14,17–24 However, the differences between assays and cutoffs used in various studies could contribute to the differences in the reported prevalence of thyroid antibodies, and differences in antibody associations with pregnancy outcomes.
Understanding of changes in thyroid function and the consequences of thyroid disease during pregnancy has rapidly grown in the past two decades, and revised American Thyroid Association guidelines on this topic were published in 2017. This Review explores the association between thyroid autoimmunity and complications during and after pregnancy. Thyroid autoimmunity refers to the presence of antibodies to thyroperoxidase or thyroglobulin, or thyroid-stimulating hormone receptor antibodies (TRAbs), or a combination of these, and is present in up to 18% of pregnant women. Thyroid antibodies in pregnant women with normal functioning thyroids (ie, euthyroid) have been associated with several complications, including miscarriage and premature delivery. Treatments to improve pregnancy outcomes are being studied. Whether thyroid antibodies are associated with infertility and assisted reproductive technology outcomes is unclear; although, treatment with low doses of levothyroxine, which is usually used to treat hypothyroidism, can be considered in such situations. Additionally, thyroid antibodies have been associated with other neonatal and maternal complications. All these associations require confirmation in larger prospective studies, and their pathogenic mechanisms need to be better understood. Post-partum thyroiditis is substantially more frequent in women who have thyroid antibodies during pregnancy than in those who do not have thyroid antibodies; however, whether treatment can prevent post-partum thyroiditis in women who are or have been antibody positive is unknown. Finally, TRAbs cross the placenta from the mother to the fetus and can cause fetal or neonatal hyperthyroidism. Therefore, women who are positive for TRAbs during pregnancy should be monitored.
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In a Tunisian prospective study cohort involving 147 women with thyroid disorders, they found a higher prevalence for positive anti-thyroid peroxidase antibodies (TPO-Ab) (6.5%), than hypothyroidism (3.2%) and hyperthyroidism (1.3%). That subgroup was also associated with a higher prevalence of non-thyroid autoimmune disease and a trend toward increase of past gestational hypertension, late abortion and fetal death [155]. Hyperthyroidism occurs in 1 to 2 of every 1000 pregnant women, and the most common cause is Graves' disease (80% to 85%).
The impact on fetal outcome in women with autoimmune diseases is a result of a several conditions. Fetal success depends on early immunological changes in the mother, which rely in modifications of the innate and adaptative immune system, inducing tolerance to the semi-allogenic fetus. Others crucial factors are maternal disease activity, severity of organ damage, circulating antibodies, and drug treatment. Although fetal outcome is becoming better still it has a worse prognosis in comparison with healthy women. Diseases like antiphospholipid syndrome, systemic lupus erythematosus and vasculitis have the higher risk while rheumatoid arthritis and spondiloarthopaties the least. In the majority of the diseases the risk of poor fetal outcome directly correlates with the activity of disease. While there are no pathognomonic autoantibodies for fetal outcome, antiphospholipid and anti-thyroid antibodies have been implicated in unsuccessful pregnancies and anti-Ro and, to a lesser extent, anti-La antibodies may result in neonatal lupus syndrome congenital heart block. There is increasingly the hope that fetal outcome will be good if the disease is well controlled prior to pregnancy, and with a specialized interdisciplinary support.
Is hyperthyroidism underestimated in pregnancy and misdiagnosed as hyperemesis gravidarum?
2010, Medical Hypotheses
Thyroid changes are considered to be normal events that happen as a large maternal multiorganic adjustment to pregnancy. However, hyperthyroidism occurs in pregnancy with clinical presentation similar to hyperemesis gravidarum (HG) and pregnancy itself. Moreover, 10% of women with HG will continue to have symptoms throughout the pregnancy suggesting that the underlying cause might not be elevation of human chorionic gonadotropin in the first trimester. Variable frequency of both hyperthyroidism and HG worldwide might suggest the puzzlement of inclusion criteria for both diagnoses enhanced by the alternation of thyroid hormone levels assessed in normal pregnancy. Increased number of hyperthyroidism among women population without the expected rise in gestational hyperthyroidism encouraged us for creating the hypotheses that hyperthyroidism could be underestimated in normal pregnancy and even misdiagnosed as HG. This hypothesis, if confirmed, might have beneficial clinical implications, such as better detection of hyperthyroidism in pregnancies, application of therapy when needed with the reduction of maternal or fetal consequences.
Maternal subclinical hypothyroidsm and gestational diabetes mellitus: A meta-analysis
2014, Endocrine Practice

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Thyroid disorders in pregnancy: Frequency and association with selected diseases and obstetrical complications in Tunisian women

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study design

Results

Discussion

Acknowledgments

Best Pract Res Clin Endocrinol Metab

Best Pract Res Clin Endocrinol Metab

Best Pract Res Clin Endocrinol Metab

Obstet Gynaecol

Trends Endocrinol Metab

Thyroid function during pregnancy

Clin Chem

Perinatal outcome in hypothyroid pregnancies

Obstet Gynaecol

Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism

Obstet Gynaecol

Maternal thyroid deficiency and pregnancy complications: implications for population screening

J Med Screen

Fetal loss associated with excess thyroid hormone exposure

J Am Med Assoc

Subclinical hypothyroidism and pregnancy outcomes

Obstet Gynaecol

Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child

N Engl J Med

Neurologic development of the newborn and young child in relation to maternal thyroid function

Acta Paediatr.

Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study

Clin Endocrinol (Oxford)

Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies

J Am Med Assoc

Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders

J Clin Endocrinol Metab

High frequency of anti-thyroid auto antibodies in pregnant women at increased risk of gestational diabetes mellitus

Eur J Endocrinol

Autoimmune thyroid disease in pregnancy and the postpartum period: relationship to spontaneous abortion

Thyroid

Post-partum thyroiditis—a clinical update

Eur J Endocrinol

Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development?

J Clin Endocrinol Metab

Iodine deficiency in the middle east

IDD Newsletter

Subclinical thyroid disease: clinical applications

J Am Med Assoc