Maternal Thyroid Autoimmunity Research Articles

Selenium levels and their association with thyroid autoimmunity and severe preeclampsia in pregnancy: Insights from a prospective ideal breast milk cohort study.

This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. 'Ideal Breast Milk (IBM) Cohort Study' included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 μg/L), suboptimal (70-99 μg/L), and optimal (≥ 100 μg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. The median plasma selenium was 98.8 (range: 46.7-206.4) μg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

Sex-Specific Associations between Maternal Thyroid Peroxidase Antibodies and Cognitive Development in Preschool Children: A Prospective Cohort Study.

Background: An association between maternal thyroid dysfunction throughout pregnancy and the subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. Methods: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. Results: A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06 to 4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10 to 5.05). Maternal TPOAb positivity in the third trimester (T3) was associated with below-average working memory index (WMI) (OR: 2.51; 95% CI: 1.02 to 6.20) in girls. In girls, the WMI (β = -3.17, 95% CI: -5.82 to -0.52), fluid reasoning index (FRI) (β = -4.49, 95% CI: -7.18 to -1.80), and FSIQ score (β = -2.43, 95% CI: -4.77 to -0.08) decreased, whereas in mothers, the level of log-transformed thyroid peroxidase antibody (lgTPOAb) increased during pregnancy. Conclusions: Positive maternal TPOAb levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Associations of Ambient Particulate Matter with Maternal Thyroid Autoimmunity and Thyroid Function in Early Pregnancy.

This prospective birth cohort study evaluated the association of exposure to PM2.5 (diameter ≤2.5 μm), PM1-2.5 (1-2.5 μm), and PM1 (≤1 μm) with maternal thyroid autoimmunity and function during early pregnancy. A total of 15,664 pregnant women were included at 6 to 13+6 gestation weeks in China from 2018 to 2020. Single-pollutant models using generalized linear models (GLMs) showed that each 10 μg/m3 increase in PM2.5 and PM1-2.5 was related with 6% (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01, 1.12) and 15% (OR = 1.15, 95% CI: 1.08, 1.22) increases in the risk of thyroid autoimmunity, respectively. The odds of thyroid autoimmunity significantly increased with each interquartile range increase in PM2.5 and PM1-2.5 exposure (P for trend <0.001). PM1 exposure was not significantly associated with thyroid autoimmunity. GLM with natural cubic splines demonstrated that increases in PM2.5 and PM1-2.5 exposure were associated with lower maternal FT4 levels, while a negative association between PM1 and FT4 levels was found when exposure exceeded 32.13 μg/m3. Only PM2.5 exposure was positively associated with thyrotropin (TSH) levels. Our findings suggest that high PM exposure is associated with maternal thyroid disruption during the early pregnancy.

Thyroid autoimmunity in euthyroid pregnant women is associated with slower productive language acquisition: the Odense child cohort study.

Maternal thyroid autoimmunity and thyroid function in early pregnancy may impact fetal neurodevelopment. We aimed to investigate how thyroid autoimmunity and thyroid function in early pregnancy were associated with language acquisition in offspring at 12-36 months of age. This study was embedded in the prospective Odense child cohort. Mother-child dyads were excluded in case of maternal intake of thyroid medication during pregnancy. The parents completed MacArthur-Bates Communicative Development Inventories (MB-CDI) every third month to assess their offspring's productive vocabulary. All completed reports for each child were included in the analyses. Logistic growth curve models evaluated associations between MB-CDI scores and levels of maternal thyroid peroxidase antibodies (TPOAb), free thyroxine (FT4), and thyrotropin, respectively, measured in early pregnancy (median gestational week 12). All models were stratified by offspring sex and adjusted for maternal age, education, pre-pregnancy body mass index, parity, breastfeeding, and offspring age. The study included 735 mother-child dyads. Children born to mothers with TPOAb ≥11 kIU/L, opposed to TPOAb <11 kIU/L, had a lower probability of producing words at age 18-36 months for girls (OR = 0.78, P < 0.001) and 33-36 months for boys (OR = 0.83, P < 0.001). The probability of producing words was higher in girls at 30-36 months of age with low-normal maternal FT4 vs high-normal FT4 (OR = 0.60, P < 0.001), and a similar trend was seen in boys. Results were ambiguous for thyrotropin. In women without known thyroid disease, TPOAb positivity in early pregnancy was negatively associated with productive vocabulary acquisition in girls and boys. This association was not mediated by a decreased thyroid function, as low-normal maternal FT4, unexpectedly, indicated better vocabulary acquisition. Our results support that maternal thyroid autoimmunity per se may affect fetal neurodevelopment.

Maternal preconception thyroid autoimmunity is associated with neonatal birth weight conceived by PCOS women undergoing their first in vitro fertilization/intracytoplasmic sperm injection

BackgroundThyroid autoimmunity and polycystic ovary syndrome (PCOS) are the most common endocrinopathies and have close relationships based on common etiology and pathogenesis, including genetic susceptibility, metabolic disorders, hormonal dysregulation, immune response, and inflammatory activation. The co-occurrence of both diseases is associated with adverse reproductive outcomes, but its effect on neonatal outcomes remains largely unknown. We aim to explore the effect of thyroid autoimmunity on neonatal birth weight in PCOS women undergoing IVF/ICSI.MethodsThis is a retrospective analysis of 486 PCOS women who underwent the first IVF/ICSI cycles and gave birth to 361 singletons and 125 twins during 2018 – 2020 at a reproductive center. The associations between maternal preconception serum thyroid function and autoimmunity indicators and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs) and generalized estimate equations (GEEs), respectively. Analyses were further stratified by neonatal sex, maternal age, and maternal preconception BMI to assess the possible interaction effects.ResultsMaternal preconception serum TPOAb had a significant negative association with singleton birth weight (P for trends = 0.03). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in singleton birth weight of − 119.72 g (95% CI: − 222.68 g, − 16.70 g). Maternal preconception serum TPOAb had a significant positive association with twin birth weight (P for trends = 0.01). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in twin birth weight of 138.62 g (95% CI: 33.96 g, 243.30 g). Besides, maternal preconception serum TPOAb had a specific association with increased twin birth weight for female neonates, a specific association with decreased singleton birth weight for PCOS women under 35 years, and a specific association with decreased twin birth weight for overweight PCOS women (all P for interactions < 0.05).ConclusionsMaternal preconception thyroid autoimmunity may affect the birth weights of both singleton and twin neonates. Further large cohorts and experimental studies are required to confirm these findings and explore the underlying mechanisms.

Maternal Thyroid Autoimmunity Affects the Emotional and Behavioral Development of the Offspring

Maternal Thyroid Autoimmunity Affects the Emotional and Behavioral Development of the Offspring

Maternal hypothyroidism and adverse outcomes of pregnancy.

Hypothyroidism has been associated with pregnancy complications, but uncertainty prevail regarding the severity and the role of thyroid autoimmunity. This study aimed to evaluate adverse pregnancy outcomes by exposure to maternal hypothyroidism and thyroid autoimmunity. Retrospective cohort study. 14,744 singleton pregnancies from the North Denmark Region Pregnancy Cohort (2011-2015). Maternal thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) were retrospectively measured in early pregnancy blood samples (ADVIA Centaur XPT, Siemens Healthineers). Adjusted odds ratio (aOR) with 95% confidence interval (CI) was used to estimate associations between maternal hypothyroidism (TSH cut-offs: 6.0 and 10 mIU/L), thyroid autoimmunity (TPO-Ab cut-off: 60 U/ml, Tg-Ab cut-off: 33 U/ml), and adverse pregnancy outcomes. Pregnancy outcomes were 93.2% live births, 6.5% spontaneous abortions, and 0.3% stillbirths. The frequency of spontaneous abortion was 6.5% when TSH was below 6.0 mIU/L, 6.5% when above 6.0 mIU/L (aOR 1.0 [95% CI: 0.5-2.0]), and 12.5% when above 10 mIU/L (aOR: 2.0 [95% CI: 0.8-5.2]). For outcome of preterm birth, the frequency was 5.4% when TSH was below 6.0 mIU/L, 7.8% when above 6.0 mIU/L (aOR 1.5 [95% CI: 0.7-2.9]), and 11.4% when above 10 mIU/L (aOR: 2.6 [95% CI: 0.9-7.3]). No association was found between thyroid autoantibodies and spontaneous abortion (TPO-Ab: aOR: 1.0 [0.8-1.3], Tg-Ab: 1.0 [0.8-1.2]) or preterm birth (TPO-Ab: aOR: 1.0 [0.8-1.2], Tg-Ab: 0.9 [0.7-1.2]). A high frequency of adverse pregnancy outcomes was seen among pregnancies exposed to maternal TSH above 10 mIU/L, whereas no association with thyroid autoantibodies was seen.

ODP534 Repercussions of Thyroid Autoimmunity on Neonatal Outcomes in Pregnant Hypothyroid Women

Abstract Introduction The impact of thyroid autoimmunity in pregnancy on neonatal outcomes remains unclear. Studies to date have revealed a positive correlation between thyroid antibodies and preterm births and miscarriages. However other aspects of neonatal outcomes need further exploration. Advanced maternal age is associated with the escalation of the prevalence of thyroid antibodies. Not only this, advanced maternal age in itself is a proven factor for unfavourable fetal outcomes. Most of the studies to date in this regard have an age-related bias as women of all groups were included to assess the neonatal outcomes in women with thyroid antibodies. Our study was conducted in hypothyroid women who were less than 35 years of age with thyroid antibodies to assess outcomes on the neonates unbiased of advanced maternal age. Hypothesis To evaluate the effects of maternal thyroid autoimmunity on neonatal outcomes. Methodology A retrospective chart review was conducted on 7978 women delivered in the study timeline in a secondary hospital of Qatar. 287 women were hypothyroid and out of these 198 women with age less than 35 years were included in the study. Neonatal outcomes such as preterm births, small for date babies, admission to neonatal intensive care units (NICU) and intrauterine fetal deaths (IUFD) were noted and compared with 200 euthyroid women who were selected by random sampling. Statistical Package for the Social Sciences version 27. 0 was used for statistical analysis. The Odds’ ratio was calculated and results with a value of p&amp;lt;0. 05 was considered significant. Results Thyroid autoimmunity was noted in 30.30% of hypothyroid pregnant women. All these women had thyroid peroxidase antibody and thyroglobulin antibody was observed in 4.44%. The range of TPO antibodies was 67-1350 IU/ml (mean 497 IU/ml). 10% vs 4.5% (OR- 2.22, 95%CI-0.760 to 6.495, P = 0.14) preterm births and 10% vs 3% (OR-3.33, 95%CI-1. 037-10.71, p&amp;lt;0. 05) small for dates babies were observed in women with thyroid antibodies in comparison to the control (euthyroid pregnant women). Higher incidence of NICU admissions (22% Vs 8.5%, p&amp;lt;0. 05) and IUFD rates (5% Vs 0.5%, p&amp;lt;0. 05) were noted in women with thyroid autoimmunity. Conclusion This study demonstrates the detrimental effects of thyroid autoimmunity on neonates of hypothyroid women less than 35 years of age. In this age group of hypothyroid women, testing for thyroid immunity should be considered. Antenatal fetal surveillance is advisable in the presence of thyroid antibodies.

PSAT271 The Impact of Maternal Autoimmune thyroid disease on neonatal thyroid conditions in Urban City Population

Abstract Background There is a wide spectrum of maternal autoimmune thyroid disorders (AITD) in pregnancy ranging from Graves’ hyperthyroidism (GD) to Hashimoto thyroiditis (HT), both of which share similar immunological properties. A variety of maternal thyroid autoantibodies can cross transplacentally which may potentially cause varying degrees of neonatal thyroid dysfunction. Objective To study the neonatal outcomes of thyroid function in mothers with AITD in urban setting. Methods Mothers with AITD and newborns were included for retrospective analysis over 12 months. AITD encompassed all mothers diagnosed prior/during pregnancy with either HT or GD. Results Maternal Data: A total of 147 mothers were included (HT 87%, GD 13.6%). Among mothers with HT, thyroid auto-Abs were tested in 51/127 (40%) mothers, of which 32/47(68%) were positive for TPO, 11/21(2%) positive for ATA, 2/6(33%) positive for TSI, 1/2 (50%) positive for TRAb. L-Thyroxine was administered to 90% HT mothers. Among mothers with GD, thyroid auto-Abs were tested in 17/20 (85%) mothers, of which 7/17(41%) were positive for TSI, 6/10(60%) positive for TRAb, 7/14(50%) were positive for TPO, 3/5 positive for ATA. Methimazole (MMI) was administered to 25% GD mothers. Neonatal outcome: A total of 150 neonates (115 FT, 35 PT) were born to AITD mothers. Newborn screen was abnormal in 2 infants. 7 neonates (4.6%) were tested for thyroid auto-Abs, of which 1/2 was positive for TPO, 1/2 positive for ATA, 3/3 negative for TSI, 5/5 negative for TRAb. Serum TFTs were performed in 62/150 neonates; majority 57/62(92%) were normal, 3 had mild compensated hyperthyrotropinemia (mean TSH 17.1 mIU/L, FT4 1.93 ng/dl) and were followed elsewhere. 2 neonates developed congenital hypothyroidism requiring L-Thyroxine. Infant 1: TSH 4.56mIU/L, FT4 1.1 ng/dl, TPO and ATA positive on DOL7 and had ectopic thyroid, infant born to TPO positive HT mother on Synthroid. Infant 2: TSH 149.5mIU/L, FT4 0.8 ng/dl, TSI negative on DOL7 and had hyperemic thyroid, born to TSI, TPO and TRAb positive GD mother on MMI. Overall, only 3.3% of neonates had evidence of thyroid function abnormality which may have either been transient or permanent. Conclusion Although rare, mothers with AITD might potentially impair neonatal thyroid function. This may be due to various thyroid auto-Abs or anti- thyroid medication that cross transplacentally. Maternal history of AITD should therefore raise suspicion to screen neonates and thus warrants continued vigilance. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Association of maternal thyroid dysfunction and autoimmunity with adverse birth outcomes.

This study aimed to explore the relationship between thyroid function and autoimmunity and adverse birth outcomes. Serum levels of thyroid function were detected by electrochemiluminescence assay. Urine iodine concentration was detected using the acid digestion method. We used multiple linear regression to assess the correlation between thyroid function indicators and birth weight according to trimester stratification and binary logistic regression to evaluate the correlation between thyroid dysfunction and adverse birth outcomes. Reference ranges for trimester-specific thyroid hormones were established in our 2564 pregnant women cohort with mild iodine deficiency. The higher the maternal thyroid-stimulating hormone in the first trimester (B = 0.09, P = 0.048) and total triiodothyronine (TT3) in the third trimester (B = 0.16, P < 0.001) of TPOAbnegative women, the higher the birth weight Z-score, whereas in the second trimester, free-thyroxine of mothers with TPOAb negative was lower (B = −0.10, P = 0.026) and the birth weight Z-score was higher. Pregnant women with overt and subclinical hyperthyroidism had a higher risk of preterm births than euthyroid women (11.9% vs 4.5%; odds ratio (OR): 2.84; P = 0.009). Women with higher TT3 had a higher risk of preterm (17.0% vs 4.5%; OR: 4.19; P < 0.001) and LGA (34.0% vs 11.1%; OR: 3.70; P < 0.001) births than euthyroid women. In conclusion, thyroid function during pregnancy could affect birth weight and birth outcome.

TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review.

A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.

Maternal mild thyroid dysfunction and offspring cognitive and motor development from infancy to childhood: the Rhea mother–child cohort study in Crete, Greece

BackgroundMaternal thyroid hormones’ supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid...

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth

Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. The primary authors provided individual participant data that were analyzed using mixed-effects models. The primary outcome was preterm birth (<37 weeks' gestational age). From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

The Association of Maternal Thyroid Autoimmunity During Pregnancy With Child IQ.

Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation. To study the association of maternal TPOAb positivity during pregnancy with child IQ. This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC). Child IQ at 5 to 10 years of age. In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results. TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences.

Does maternal thyroid autoimmunity predict adverse pregnancy outcomes?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The Effect of Subclinical Maternal Thyroid Dysfunction and Autoimmunity on Intrauterine Growth Restriction: A Systematic Review and Meta-Analysis.

The objective of this study was to evaluate the association between maternal subclinical thyroid dysfunction and autoimmunity with the risk for intrauterine growth restriction (IUGR).Design is a systematic review and meta-analysis.A literature search was conducted using PubMed, Embase, and Cochrane database. A combination of 2 key words was used to search for the eligible studies: one indexed thyroid dysfunction or antithyroid antibodies; and the other one indexed the adverse neonatal outcomes of pregnancy, such as IUGR, small for gestational age, fetal growth restriction, or low birth weight.Two reviewers selected the studies, and eligible studies met the following criteria: prospective cohort studies or case control studies, studies of maternal thyroid dysfunction and positive antithyroid antibodies as the exposure of interest, and studies of IUGR or small for gestational age as the outcome of interest.Data were recorded, including data from maternal thyroid disorders and IUGR, and compared with a reference group.There were 22 individual data from the 13 cohort articles. Among these, 7 were focused on subclinical hypothyroidism (SCH), 4 on subclinical hyperthyroidism, 7 on positivity for thyroid peroxidase antibody (TPOAb), and 4 on isolated hypothyroxinemia. Meta-analysis showed that there was no effect of subclinical hyperthyroidism (odds ratio (OR) = 0.98; 95% confidence interval (CI), 0.40–2.41), TPOAb positivity (OR = 1.57; 95% CI, 0.77–3.18), or isolated hypothyroxinemia (OR = 1.05, 95% CI: 0.37–2.92) on IUGR. However, SCH is associated with IUGR (OR = 1.54; 95% CI, 1.06–2.25).SCH is associated with IUGR; however, subclinical hyperthyroidism, TPOAb positivity, or isolated hypothyroxinemia do not affect the risk of IUGR.

Maternal Thyroid Function and Autoimmunity in 3 Trimesters of Pregnancy and their Offspring's Thyroid Function.

This study was performed to evaluate maternal thyroid dysfunction and autoimmunity during pregnancy and its correlation with thyroid function of offspring. In this cohort study, Serum TT4, TT3, T3U, TSH, TPOAb, and TgAb were measured. Serum samples of 120 pregnant women were collected during 3 trimesters as well as in 57 cord bloods, 69 neonates, 34, 37, and 36 infants aged 2, 4, and 6 months. Repeated measure and Pearson correlation test were used to compare thyroid hormone values and to assess the correlations, respectively. Main outcomes were correlations between thyroid hormones and antibodies in mothers and offspring. An increasing trend for TT3 (p for trend < 000.1) and TSH (p for trend 0.01) was found over the course of gestation. Among 120 mothers, 10 (8%) had subclinical hyperthyroidism and 18 mothers (15%) showed subclinical hypothyroidism. We found one hypothyroid (0.8%) and 3 hyperthyroid (2.5%) mothers during pregnancy. Correlations among maternal thyroid hormones were found but not with auto-antibodies. A positive correlation between maternal thyroid auto-antibodies in all trimesters with cord blood and neonates was found. Cord blood TSH had a good correlation with maternal TSH, but only in the first trimester (r=0.29, p<0.05). A positive correlation between neonatal TSH and maternal TT4 was found only in the third trimester (r=0.25, p<0.05). Subclinical hypothyroidism was the most common thyroid dysfunction in the pregnant women studied. The association between maternal auto-antibodies and thyroid hormones of offspring was observed mostly in the neonatal period and became weaker after one month of age.

Thyroid function and autoimmunity in Danish pregnant women after an iodine fortification program and associations with obstetric outcomes.

Aberrations in maternal thyroid function and autoimmunity during pregnancy have been associated with negative obstetric outcome. In Denmark, a national iodine fortification program was implemented in the year 2000 with the aim to alleviate the mild-moderate iodine deficiency. Following the iodine implementation, there has been an increase in thyroid autoimmunity in the background population. This study investigates the thyroid status of pregnant Danish women following the iodine fortification program, and a possible association with preterm delivery. Historical cohort study of 1278 randomly selected pregnant Danish women attending the national Down's syndrome screening program. The main outcome measures were thyroid status according to laboratory- and gestational-age-specific reference intervals, and association with risk of abnormal obstetric outcome. Antibody-positivity was defined as an antibody-level (thyroid peroxidase and/or thyroglobulin antibodies) above 60 U/ml. Establishing laboratory-specific gestational-age-dependent reference intervals, we found a prevalence of maternal thyroid dysfunction of 10%-15.8% by use of the cut-off suggested by the American Thyroid Association. Thyroid dysfunction was significantly associated with antibody-positivity (P<0.05). No associations were found between preterm delivery and thyroid dysfunction (adjusted OR 0.6, 95% CI: 0.1-2.3) or autoimmunity (adjusted OR 1.1, 95% CI: 0.4-2.7). After the implementation of the Danish iodine fortification program, the prevalence of thyroid dysfunction and autoimmunity in Danish pregnant women is high - even higher by use of pre-established reference intervals from international consensus guidelines. However, no associations were found with abnormal obstetric outcome. Large randomized controlled trials are needed to clarify the benefit of treating slight aberrations in pregnant women's thyroid function.

Maternal autoimmune thyroid disease: Relevance for the newborn

Background and objectiveAutoimmune thyroid disease is amongst the most frequent endocrine disorders during pregnancy. It is associated with an increase in perinatal morbidity, congenital defects, neurological damage, foetal and neonatal thyroid dysfunction. Maternal thyroid hormones play a key role in child neurodevelopment. We aimed to evaluate the thyroid function and the clinical course of neonates born from mothers with autoimmune thyroid disease during the first months of life in order to define the follow-up. Patients and methodWe monitored thyroid function and clinical status during the first months in 81 newborns of mothers with autoimmune thyroid disease; 16 had Graves disease and 65 autoimmune thyroiditis. ResultsA percentage of 4.93 newborns had congenital defects, and 8.64% neonates showed an increase in thyrotropin (TSH) (>9.5μUI/mL 2 times) and required thyroxin within the first month of life. A 85.7% of these showed a negative newborn screening (due to a later increase of TSH). A higher TSH value in the newborn was related to an older age of the mother, higher levels of thyroid peroxidase (TPO) antibody during pregnancy and lower birth weight. A higher free thyroxine (FT4) value in the newborn was related to fewer days of life and mothers with Graves disease. ConclusionsWe recommend the evaluation of TSH, T4 and TPO antibodies before 10 weeks in all pregnant women with follow-up if maternal thyroid autoimmunity or disorders is detected. It is also recommended to test children's serum TSH and FT4 at 48h of life in newborns of mothers with autoimmune thyroid disease and repeat them between the 2nd and 4th week in children with TSH>6μUI/mL. Careful endocrine follow-up is advised in pregnant women and children if hyperthyroidism is detected.

Neonatal thyroid function born to mothers living with long-term excessive iodine intake from drinking water.

The effects of long-term excessive maternal iodine intake on neonatal thyroid function are less known. This study aimed to assess the effects of maternal excessive iodine intake from drinking water on thyroid functions of both mothers and their neonates. This observational study was performed in high iodine (HI) areas and adequate iodine (AI) intake areas, including 384 healthy pregnant women in late gestation (mean week 39·3 ± 1·6 weeks) and their newborns. Blood and urine samples were obtained from pregnant women, while cord blood samples were obtained from neonates. Urinary iodine concentration (UIC) and thyroid function were evaluated. The median maternal UIC was 1241 and 217 μg/l in HI and AI areas, respectively (P < 0·001). The concentrations of serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) in neonates in HI areas were 7·33 mIU/l (range 5·47, 11·06 mIU/l), 2·93 ± 0·59 and 15·03 ± 1·92 pmol/l, respectively, while that were 4·71 mIU/l (range 3·96, 6·04 mIU/l), 2·31 ± 0·28 and 16·50 ± 1·35 pmol/l in AI neonates (P < 0·05). Similar changes were also observed in neonates in HI areas when excluding the effect of maternal thyroid autoimmunity. Cord blood TSH concentration (r = 0·31, P = 0·001) and FT3 concentration (r = 0·43, P = 0·001) were positively correlated with maternal UIC. Cord blood FT4 concentration was negatively correlated with maternal UIC (r = -0·25, P = 0·001). Mothers living in HI areas (β = 0·296, 95% CI: 0·163, 0·255) and with subclinical hypothyroidism (β = 0·360, 95% CI: 0·034, 0·175) contributed to elevated cord blood TSH concentration in neonates, while male neonates were more likely to present with higher TSH concentration compared with female infants (β = -0·760, 95% CI: -0·119, -0·033). Excessive iodine intake during pregnancy was associated with an increased rate of hyperthyrotropinaemia in neonates and their mothers, especially in male neonates.