Maternal Thyroid Function, Use of Antithyroid Drugs in Early Pregnancy, and Birth Defects

2019 ◽  
Vol 104 (12) ◽  
pp. 6040-6048 ◽  
Author(s):  
Stine Linding Andersen ◽  
Louise Knøsgaard ◽  
Jørn Olsen ◽  
Peter Vestergaard ◽  
Stig Andersen
Keyword(s):  
Thyroid Function ◽  
Birth Defects ◽  
Early Pregnancy ◽  
Antithyroid Drug ◽  
Maternal Blood ◽  
Antithyroid Drugs ◽  
Birth Cohorts ◽  
Increased Risk ◽  
Maternal Thyroid

Abstract Context Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified. Objective To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy. Participants Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC), 1997 to 2016; 8830 children from the Danish National Birth Cohort (DNBC), 1997 to 2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011 to 2015. Main Outcome Measures Birth defects diagnosed before 2 years of age. Results In the NRBC, altogether 2718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% CI, 6.7% to 6.8%) in nonexposed children and higher after exposure to methimazole/carbimazole (9.6%; 95% CI, 8.2% to 11.2%) and propylthiouracil (8.3%; 95% CI, 6.7% to 10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs 12.6%, P = 0.8) and the NDRPC (15.1 vs 15.4%, P = 0.8). Conclusions Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.

scholarly journals Exposure to Propylthiouracil in the First Trimester of Pregnancy and Birth Defects: A Study at a Single Institution

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Ai Yoshihara ◽  
Jaeduk Yoshimura Noh ◽  
Natsuko Watanabe ◽  
Miho Fukushita ◽  
Masako Matsumoto ◽  
...  
Keyword(s):  
Medical Treatment ◽  
Birth Defects ◽  
Antithyroid Drug ◽  
First Trimester ◽  
Control Group ◽  
Graves Disease ◽  
Increased Risk ◽  
Group A ◽  
First Trimester Of Pregnancy ◽  
Maternal Thyroid

Abstract Context Medical treatment of Graves disease during the first trimester has been the subject of controversy ever since treatment with an antithyroid drug during the first trimester was reported to possibly be associated with an increased risk of birth defects in newborns. Objective We investigated whether the incidence of birth defects among newborns born to mothers with Graves disease (GD) treated with propylthiouracil (PTU) during the first trimester of pregnancy was higher than in a control group that was not exposed to any medication. Methods We reviewed the cases of 1913 women with GD who gave birth between January 1, 2015, and May 31, 2019. Detailed information concerning the outcome of pregnancy and the presence of birth defects was collected at the first visit after the delivery and again 1 year after delivery. We classified the mothers and infants into 3 groups according to the treatment the mother had received for GD in the first trimester of pregnancy: a group in which the mothers had been treated with PTU alone (PTU group), a group in which the mothers had not been treated with any medication (control group), and a group in which the mothers had received some other medical treatment, such as thiamazole, potassium iodide, or 2 or more drugs (other treatment group). Results The incidence of malformed infant births was 5.5% (30/541 infants) in the PTU group and 5.7% (27/ 475 infants) in the control group. There were no specific birth defects in the PTU group, and there were no significant differences between PTU dosages or maternal thyroid function according to whether mothers had delivered a child with a birth defect. Conclusion The results of our retrospective study showed that treatment with PTU during the first trimester of pregnancy did not increase the incidence of birth defects among newborns.

scholarly journals THERAPY OF ENDOCRINE DISEASE: Antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk?

2014 ◽  
Vol 171 (1) ◽  
pp. R13-R20 ◽  
Author(s):  
Peter Laurberg ◽  
Stine Linding Andersen
Keyword(s):  
High Risk ◽  
Birth Defects ◽  
Early Pregnancy ◽  
Time Windows ◽  
Antithyroid Drug ◽  
Antithyroid Drugs ◽  
Relative Safety ◽  
Time Period ◽  
Major Period ◽  
Number Of Publications

BackgroundAntithyroid drugs (ATDs) may have teratogenic effects when used in early pregnancy.ObjectiveTo review the association between the time period of ATD exposure in early pregnancy and the development of birth defects.MethodsWe identified publications on birth defects after early pregnancy exposure to the ATDs methimazole (MMI; and its prodrug carbimazole (CMZ)) and propylthiouracil (PTU). Cases of birth defects after ATD treatment had been initiated or terminated within the first 10 weeks of pregnancy were identified and studied in detail.ResultsA total of 92 publications were read in detail. Two recent large controlled studies showed ATD-associated birth defects in 2–3% of exposed children, and MMI/CMZ-associated defects were often severe. Out of the total number of publications, 17 included cases of birth defects with early pregnancy stop/start of ATD treatment, and these cases suggested that the high risk was confined to gestational weeks 6–10, which is the major period of organogenesis. Thus, the cases reported suggest that the risk of birth defects could be minimized if pregnant women terminate ATD intake before gestational week 6.ConclusionBoth MMI and PTU use in early pregnancy may lead to birth defects in 2–3% of the exposed children. MMI-associated defects are often severe. Proposals are given on how to minimize the risk of birth defects in fertile women treated for hyperthyroidism with ATDs.

scholarly journals Management of Graves' hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy

2009 ◽  
Vol 160 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Peter Laurberg ◽  
Claire Bournaud ◽  
Jesper Karmisholt ◽  
Jacques Orgiazzi
Keyword(s):  
Drug Therapy ◽  
Thyroid Function ◽  
Antithyroid Drug ◽  
Autoimmune Disorder ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Limited Effect ◽  
Antithyroid Drug Therapy ◽  
Maternal Thyroid ◽  
In Pregnancy

Graves' disease is a common autoimmune disorder in women in fertile ages. The hyperthyroidism is causedby generation of TSH-receptor activating antibodies. In pregnancy both the antibodies and the antithyroid medication given to the mother pass the placenta and affect the foetal thyroid gland. Thyroid function should be controlled not only in the mother with Graves' hyperthyroidism but also in her foetus.The review includes two cases illustrating some of the problems in managing Graves' disease in pregnancy.Major threats to optimal foetal thyroid function are inadequate or over aggressive antithyroid drug therapy of the mother. It should be taken into account that antithyroid drugs tend to block the foetal thyroid function more effectively than the maternal thyroid function, and that levothyroxin (l-T4) given to the mother will have only a limited effect in the foetus.Surgical thyroidectomy of patients with Graves' hyperthyroidism does not lead to immediate remission of the autoimmune abnormality, and the combination thyroidectomy+withdrawal of antithyroid medication+l-T4 replacement of the mother involves a high risk of foetal hyperthyroidism.ConclusionAntithyroid drug therapy of pregnant women with Graves' hyperthyroidism should be balanced to control both maternal and foetal thyroid function. Surgical thyroidectomy of a pregnant woman with active disease may lead to isolated foetal hyperthyroidism.

Graves'-Basedow disease in pregnancy

2015 ◽  
Vol 54 (03) ◽  
pp. 106-111 ◽  
Author(s):  
S. L. Andersen ◽  
P. Laurberg
Keyword(s):  
Side Effects ◽  
Birth Defects ◽  
Thyroid Dysfunction ◽  
National Study ◽  
Antithyroid Drugs ◽  
Upper Limit ◽  
Special Concern ◽  
Maternal Thyroid ◽  
Toxic Reactions ◽  
Serum Tsh

SummaryThyroid hormones are essential development factors and maternal thyroid dysfunction may cause pregnancy complications and diseases in the fetus/child. In the present review we discuss new data on the incidence of Graves'-Basedow disease (GBD) in and around pregnancy, and how hyperthyroidism may affect the risk of spontaneous abortion and stillbirth.A special concern in pregnant women is the potential side effects from the use of antithyroid drugs (ATDs). One type of side effects is the allergic/toxic reactions to the drugs, which seem to be similar in and outside pregnancy, and another is that ATDs tend to over treat the fetus when the mother with GBD is made euthyroid. To avoid fetal hypothyroidism, the lowest possible ATD dose should be used to keep maternal thyroid function at the upper limit of normality with low serum TSH. Birth defects after the use of methimazole (MMI) (or its prodrug carbimazole) have been considered to be very rare, and no risk has previously been associated with the use of propylthiouracil (PTU). However, a recent Danish national study found that 1/30 of children exposed to MMI in early pregnancy had birth defects associated with this, and many defects were severe. PTU exposure was associated with defects in 1/40, and these defects were less severe. Proposals are given on how to reduce the risk of ATD associated birth defects.

scholarly journals Demographic Characteristics of Mothers Who Delivered Children with Birth Defetcs

2018 ◽  
pp. 222-227
Author(s):  
Yudianto B Saroyo ◽  
Christian Wijaya ◽  
Putri M T Marsubin
Keyword(s):  
Retrospective Study ◽  
Birth Weight ◽  
Antenatal Care ◽  
Birth Defects ◽  
Medical Records ◽  
Birth Defect ◽  
Demographic Characteristics ◽  
Comorbid Disease ◽  
Increased Risk

Abstract Objective: to determine the characteristics and background of mothers who delivered neonates with birth defects. Methods: A retrospective study was used by evaluating the medical records of patients with birth defects in Dr. Cipto Mangunkusumo Hospital during the period between September 2014 and June 2016. Results: A total of 67 (1.85%) out of 3,619 infants who were born in Dr. Cipto Mangunkusumo Hospital during the period between September 2014 and June 2016 had birth defects. Forty-seven (70.1%) mothers of the subjects irregularly attend antenatal care. The most frequent maternal comorbid disease in this study was asthma, which was found in 4 (5.97%) mothers of the subjects. 48 (58.7%) subjects had birth weight under 2500 g. Conclusion: In this retrospective study, the main highlight is that 70.1% of the mothers who delivered neonates with birth defects did not attend antenatal care regularly. 58.7% of the neonates with birth defects had low birth weight. This study could be used as base for further research investigating about the role of antenatal care in early detection and/or the planning of delivery for babies with birth defects. Trends in babies with birth defects suggested that fetuses diagnosed with IUGR/SGA should be given special attention, as they were at increased risk for birth defects. Keywords: birth defect, maternal description   Abstrak Tujuan: untuk mengetahui deskripsi/ciri-ciri  dan latar belakang ibu yang melahirkan janin dengan kelainan bawaan. Metode: Studi retrospektif digunakan dengan menggunakan data sekunder rekam medis pasien dengan kelainan bawaan di Rumah Sakit Umum Pusat Nasional Dr. Cipto Mangunkusumo pada periode September 2014-Juni 2016. Hasil: Sejumlah 67 (1.85%) dari 3,619 neonatus didapatkan dengan kelainan bawaan di RSUPN Cipto Mangunkusumo pada periode September 2014-Juni 2016 . Sejumlah 47 (70.1%) ibu dari subjek tidak teratur dalam melakukan kunjungan antenatal care. Penyakit komorbid ibu yang paling banyak ditemukan dalam studi ini adalah asma, yang ditemukan dalam 4 (5.97%) subjek. 48 (58.7%) subyek memiliki berat lahir di bawah 2500 g. Kesimpulan: Pada studi retrospektif ini didapatkan 70.1% ibu yang melahirkan bayi dengan kelainan bawaan tidak melakukan kunjungan antenatal care. Didapatkan bahwa 58,7% bayi yang lahir dengan kelainan bawaan memiliki berat badan lahir rendah (BBLR). Studi ini dapat dijadikan sebagai landasan dilakukannya studi yang lebih besar untuk mengevaluasi peran antenatal care terhadap deteksi dini dan/atau perencanaan persalinan bayi dengan kelainan bawaan. Tren pada bayi dengan kelainan bawaan menunjukkan bahwa janin yang pada antenatal care didapatkan IUGR/SGA patut diperhatikan lebih untuk kecurigaan kemungkinan adanya kelainan bawaan. Kata kunci:   deskripsi ibu,   kelainan bawaan,

scholarly journals Congenital Bands with Intestinal Malrotation after Propylthiouracil Exposure in Early Pregnancy

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Alexander A. Leung ◽  
Jennifer Yamamoto ◽  
Paola Luca ◽  
Paul Beaudry ◽  
Julie McKeen
Keyword(s):  
Birth Defects ◽  
Early Pregnancy ◽  
First Trimester ◽  
Careful Consideration ◽  
Intestinal Malrotation ◽  
Graves Disease ◽  
Increased Risk ◽  
Acute Small Bowel Obstruction ◽  
Trimester Exposure ◽  
Duration Of Pregnancy

Exposure to propylthiouracil in early pregnancy may be associated with an increased risk of birth defects. But the spectrum of associated congenital anomalies is not yet well defined. While preliminary reports suggest that most cases of propylthiouracil-associated birth defects are restricted to the preauricular and urinary systems, careful consideration should be given to other possible manifestations of teratogenicity. We propose that congenital bands may potentially represent a rare yet serious complication of propylthiouracil exposure in early pregnancy, possibly arising from an early mesenteric developmental anomaly. We report a case of a 17-day-old girl that presented with acute small bowel obstruction associated with intestinal malrotation arising from several anomalous congenital bands. Her mother was treated for Graves’ disease during pregnancy with first trimester exposure to propylthiouracil but remained clinically and biochemically euthyroid at conception and throughout the duration of pregnancy. This case suggests that the use of propylthiouracil in early pregnancy may be associated with congenital bands and intestinal malrotation. More reports are needed to further support this association.

scholarly journals Early Maternal Thyroid Function During Gestation Is Associated With Fetal Growth, Particularly in Male Newborns

2017 ◽  
Vol 102 (3) ◽  
pp. 1059-1066 ◽  
Author(s):  
Tanja G. M. Vrijkotte ◽  
E. Jessica Hrudey ◽  
Marcel B. Twickler
Keyword(s):  
Birth Weight ◽  
Thyroid Function ◽  
Fetal Growth ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Subclinical Hypothyroidism ◽  
Growth Patterns ◽  
Fetal Sex ◽  
Intrauterine Growth ◽  
Maternal Thyroid

Abstract Background: Intrauterine growth patterns are influenced by maternal thyroid function during gestation and by fetal sex. It is unknown, however, whether the relationships between maternal thyrotropin (TSH) and free thyroxine (fT4) levels in early pregnancy and fetal growth outcomes are modified by fetal sex. Design: Data were obtained from a community-based cohort study of pregnant women living in Amsterdam (Amsterdam Born Children and Their Development study). TSH and fT4 levels were determined during the first prenatal screening at median 13 weeks (interquartile range, 12 to 14). Women with live-born singletons and no overt thyroid dysfunction were included (N = 3988). Associations between these maternal hormones and birth weight, small for gestational age (SGA), and large for gestational age (LGA) were analyzed separately for each sex. Results: After adjustments, 1 pmol/L increase in maternal fT4 levels was associated with a reduction in birth weight of 33.7 g (P < 0.001) in male newborns and 16.1 g (P < 0.05) in female newborns. Increased maternal fT4 was not associated with increased odds for SGA, but was associated with a decreased odds for LGA in boys [per 1 pmol/L; odds ratio (OR), 0.79; 95% confidence interval (CI), 0.69 to 0.90]. Maternal subclinical hypothyroidism in early pregnancy (TSH > 2.5 mU/L, 7.3%) was associated with increased odds for LGA in male newborns (OR, 1.95; 95% CI, 1.22 to 3.11). Conclusion: Maternal fT4 in early pregnancy was observed to be inversely associated with birth weight, with a stronger relationship in males. Male infants also had increased odds for LGA in mothers with subclinical hypothyroidism. Sexual dimorphism appears to be present in the relationship between maternal thyroid metabolism and fetal intrauterine growth, with stronger associations in male infants.

scholarly journals High Body Mass Index Is an Indicator of Maternal Hypothyroidism, Hypothyroxinemia, and Thyroid-Peroxidase Antibody Positivity during Early Pregnancy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Cheng Han ◽  
Chenyan Li ◽  
Jinyuan Mao ◽  
Weiwei Wang ◽  
Xiaochen Xie ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Pregnant Women ◽  
Body Mass ◽  
Thyroid Function ◽  
Early Pregnancy ◽  
Thyroid Dysfunction ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibody ◽  
Maternal Thyroid ◽  
High Bmi

Background. Maternal thyroid dysfunction in early pregnancy may increase the risk of adverse pregnancy complications and neurocognitive deficiencies in the developing fetus. Currently, some researchers demonstrated that body mass index (BMI) is associated with thyroid function in nonpregnant population. Hence, the American Thyroid Association recommended screening thyroid function in obese pregnant women; however, the evidence for this is weak. For this purpose, our study investigated the relationship between high BMI and thyroid functions during early pregnancy in Liaoning province, an iodine-sufficient region of China.Methods. Serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) concentration, urinary iodine concentration (UIC), and BMI were determined in 6303 pregnant women.Results. BMI ≥ 25 kg/m2may act as an indicator of hypothyroxinemia and TPOAb positivity and BMI ≥ 30 kg/m2was associated with increases in the odds of hypothyroidism, hypothyroxinemia, and TPOAb positivity. The prevalence of isolated hypothyroxinemia increased among pregnant women with BMI > 24 kg/m2.Conclusions. High BMI during early pregnancy may be an indicator of maternal thyroid dysfunction; for Asian women whose BMI > 24 kg/m2and who are within 8 weeks of pregnancy, thyroid functions should be assessed especially.

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