Maternal Thyroid-stimulating Hormone Research Articles

Maternal Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. Retrospective cohort study. Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51-0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

A confusing situation in the clinic: isolated maternal hypothyroxinemia

Isolated maternal hypothyroxinemia (IMH) is a common problem in the clinic. There is a normal maternal thyroid stimulating hormone (TSH) level with a low maternal free thyroxine (FT4) level. The aim of this review is to explain IMD in the light of current literature and to contribute to clinicians in the management of IMH. Iodine deficiency is the most important factor in etiology. The effects of IMH on the pregnant woman and the fetus are not clear. However, it is a serious concern among serious clinicians, especially considering the importance of the effect of thyroid hormones on fetal brain development. As for the treatment of IMH, the number of studies conducted is not sufficient and there is no consensus and evidence on levothyroxine treatment. However, there is a consensus on iodine supplementation and it is recommended to take 250 mg of iodine daily. As a result, IMH is a problem that should be taken seriously during pregnancy and care should be taken regarding its diagnosis and treatment. Additionally, more research is needed on the effects and treatment of IMH on pregnant and fetal health

Iodine supply and thyroid function in women with gestational diabetes mellitus: a cohort study.

Maternal urinary iodine concentration (UIC) and blood neonatal thyroid stimulating hormone (TSH) concentration reflect iodine status in pregnancy. As dietary measures in gestational diabetes mellitus (GDM) could affect iodine intake, our study aimed to investigate iodine supply in women with GDM compared to healthy pregnant women and to evaluate its relationship to thyroid function. UIC and serum TSH, free thyroxine (FT4) and autoantibodies against thyroid peroxidase (TPOAb) were analysed in 195 women with GDM and 88 healthy pregnant women in the 2nd trimester. Subsequently, neonatal TSH concentrations measured 72 hours after delivery in a subgroup of 154 newborns (115 of mothers with GDM and 39 controls) from the national register were analysed. Optimal iodine intake was found only in nine women with GDM (4.6%) and 33 healthy pregnant women (37.5%) (P<0.001). Most pregnant women with GDM (88.7%) as compared to one half of controls (50%) had iodine deficiency (P<0.001). Also, hypothyroxinaemia was more prevalent in GDM compared to controls (12.3% vs 3.4%, P = 0.032). Consistently, neonatal TSH >5.0 mIU/L indicating iodine deficiency was found in 6 (5.2%) newborns of women with GDM as compared to none in controls. In the multiple logistic and linear regression models in women with GDM, hypothyroxinaemia was associated with preterm births, and a negative association of serum FT4 and HbA1c was found. Iodine deficiency in pregnancy was more prevalent among women with GDM compared to healthy pregnant controls. Hypothyroxinaemia was associated with preterm births in women with GDM.

Overt hypothyroidism in pregnancy and language development in offspring: is there an association?

PurposeOvert hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications.MethodsGroup 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10 mU/L, > 10 µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5–2.5 mU/L, 0.5–2.5 µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale.ResultsPregnancy outcome showed an average gestational age at delivery of 38.2 weeks for hypothyroid women, compared to 40 weeks for controls, and average birth weight of 2855.6 g versus 3285 g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores.ConclusionFetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

Massive fetal goiter treated by intra-amniotic injection of levothyroxine: a case report

Abstract Objectives Fetal dyshormonogenetic goiter is a rare condition associated with perinatal complications and sequelae in infants. Although prenatal management remains controversial, further evidence is required for optimal management. Case presentation A 30-year-old pregnant woman with no history of thyroid disease was referred to our hospital with polyhydramnios. Fetal ultrasonography revealed fetal goiter. Cordocentesis revealed increased thyroid-stimulating hormone (TSH) and low levels of free thyroxine 4 (fT4), which was the basis of diagnosis of fetal hypothyroidism. Intra-amniotic injections of levothyroxine were administered, resulting in a reduction in the goiter size, amount of amniotic fluid, and level of maternal TSH. The mother was euthyroid during pregnancy. The infant was delivered vaginally at full term with a normal thyroid size and no respiratory disorders except hypothyroidism. At 2 years of age, her neurodevelopment is normal. Conclusions Intra-amniotic injections of levothyroxine for fetal hypothyroidism with massive goiter and polyhydramnios may improve perinatal outcomes.

Fluoride exposure and thyroid hormone levels in pregnancy: The MIREC cohort

BackgroundFluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce. ObjectivesWe examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects. MethodsWe measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder. ResultsA 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: −0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05–0.32 mg/L), those with levels in the third quartile (0.49–0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13–0.52 mg/L) and third (0.52–0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04–0.13 mg/L). Adjustment for maternal iodine status did not change the results. DiscussionFluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.

Fetal sexual dimorphism of maternal thyroid function parameters during pregnancy, a single center retrospective real-world study.

Thyroid function during pregnancy fluctuates with gestational weeks, seasons and other factors. However, it is currently unknown whether there is a fetal sex-specific thyroid function in pregnant women. The purpose of this study was to investigate the fetal sex differences of maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in pregnant women. This single-center retrospective real-world study was performed by reviewing the medical records of pregnant women who received regular antenatal health care and delivered liveborn infants in Shanghai First Maternity and Infant Hospital (Pudong branch), from Aug. 18, 2013 to Jul. 18, 2020. Quantile regression was used to evaluate the relationship between various variables and TSH and FT4 concentrations. The quantile regression also evaluated the sex impact of different gestational weeks on the median of TSH and FT4. A total of 69,243 pregnant women with a mean age of 30.36 years were included. 36197 (52.28%) deliveries were boys. In the three different trimesters, the median levels (interquartile range) of TSH were 1.18 (0.66, 1.82) mIU/L and 1.39 (0.85, 2.05) mIU/L, 1.70 (1.19, 2.40) mIU/L; and the median levels (interquartile range) of FT4 were 16.63 (15.16, 18.31) pmol/L, 14.09 (12.30, 16.20) pmol/L and 13.40 (11.52, 14.71) pmol/L, respectively. The maternal TSH upper limit of reference ranges was decreased more in mothers with female fetuses during gestational weeks 7 to 12, while their FT4 upper limit of the reference ranges was increased more than those with male fetuses. After model adjustment, the median TSH level was 0.11 mIU/L lower (P <0.001), and FT4 level was 0.14 pmol/L higher (P <0.001) for mothers with female fetuses than those with male fetuses during gestational weeks 9 to 12. We identified sexual dimorphism in maternal thyroid function parameters, especially during 9-12 weeks of pregnancy. Based on previous research, we speculated that it may be related to the higher HCG levels of mothers who were pregnant with girls during this period. However, longitudinal studies are needed to determine if fetal sex differences impact the maternal thyroid function across pregnancy.

Relationship between infant hypothyroidism and maternal thyroid disease

Background: Due to the very high complications of neonatal hypothyroidism in the country, neonatal screening program is performed for timely diagnosis and treatment of neonates. The aim of this study to investigate the relationship between infant hypothyroidism and maternal thyroid disease. Methods: This cross-sectional study was done on 195 neonates with a diagnosis of hypothyroidism. Necessary data were collected by a checklist and then analyzed by statistical methods in statistical package for the social sciences (SPSS) version 21 by statistical methods. Results: Of all mothers, 21.0% had a history of thyroid disease. There was no statistically significant relationship between maternal age and infant thyroid stimulating hormone (TSH). There was no significant relationship between the history of maternal hypothyroidism and maternal hypothyroidism (during experiments) with the amount of TSH in the newborn. There was a direct and significant relationship between maternal TSH level and maternal free T4. But there was no statistically significant relationship between infant TSH level and maternal TSH level and free T4. There was no significant difference in neonatal TSH levels with maternal anti-TPO status. There was no significant relationship between the history of maternal diabetes and the history of maternal hypertension with neonatal TSH. There was no significant difference in neonatal TSH levels by maternal thyroid status. Conclusions: In the present study, no significant relationship was found between the incidence of neonatal hypothyroidism and the presence of thyroid disease in mothers. The existence of different genetic and environmental factors and the significant impact of each of these factors can justify this result.

P-133 A study of the relationship between in vitro embryo development and maternal hypothyroidism

Abstract Study question Are there an association between the maternal thyroid condition and in vitro fertilization (IVF) outcomes? Summary answer Maternal hypothyroidism was found to be related to oocyte maturation and blastocyst development. What is known already Previous studies have shown that thyroid-stimulating hormone (TSH) levels affect ovarian stimulation in assisted reproductive technology (ART). In addition, changes in serum TSH levels have been linked to a sub-optimal environment for the implantation and development of the embryo. Thyroid-related receptors are present in granulosa cells, ovaries, and the endometrium. In addition, those receptors play a role in ovulation and folliculogenesis. This study aims to determine the association between maternal hypothyroidism and adverse implications for IVF outcomes in IVF/ICSI treated women. Study design, size, duration This retrospective study performed 333 cycles of 208 patients with TSH levels ranging from 0.043-16.627 µIU/mL, treated at the RMC National IVF Center between 2019 and 2022. The study population consisted of 1171 oocytes, which were divided into two groups based on their maternal basal TSH levels: normal TSH ≤ 2.5 µIU/mL (control group, n = 865, euthyroid) and higher TSH &amp;gt; 2.5 µIU/mL (case group, n = 306, hypothyroid). Participants/materials, setting, methods Maternal basal serum TSH levels were measured using Fluorescence Enzyme Immunoassay on the third day of the menstrual cycle. IVF outcome expressed oocyte maturation, fertilization, cleavage, and blastocyst formation rate. Oocytes were divided into mature (metaphase II) and immature (metaphase I and prophase I) groups. Blastocysts are graded by the Kato Ladies Clinic classification system and divided into high potential (A and B grades) and low potential (C, D, and E grades) groups. Main results and the role of chance In our study, there was no statistically significant difference in age and partner’s semen criteria between the two groups (p &amp;gt; 0.05). As regards oocyte maturation, MII oocytes retrieved significantly higher in the control group (82.2% vs. 75.8%). Logistic regression analysis found that TSH levels &amp;gt; 2.5 µIU/mL were related to statistically significantly increased risks of oocyte maturation stages like MI or GV (Age affect adjusted model: B = 0.456, p = 0.005; OR = 1.578, 95% CI = 1.146-2.175). The fertilization, cleavage, and blast formation rates have no differences between the groups. However, 91% (n = 324/356) of higher potential blastocysts in the control group were significantly higher than the case group (79.7%, n = 106/133). While, by the logistic regression analysis found that higher TSH levels ( &amp;gt; 2.5 µIU/mL) were related to statistically significantly increased risks of lower potential for implantation grades (B = 0.947, p = 0.001; OR = 2.579, 95%CI = 1.477-4.502). Limitations, reasons for caution The study relied on TSH as the primary indicator of thyroid function and excluded participants with abnormal prolactin levels. Other markers, such as FT4 and TSHR, should also be considered for a thorough evaluation of thyroid function. Wider implications of the findings Thyroid dysfunction can negatively impact IVF success, and screening and managing thyroid function in women undergoing IVF are essential. More research is needed to understand the mechanisms and develop strategies to improve oocyte and blastocyst quality. Trial registration number not applicable

What Should be the Thyroid Stimulating Hormone Cut-off Level in the First-Trimester Screening? A prospective Cohort Study and Mini Review of The Guidelines

Aim: Thyroid Stimulating Hormone (TSH) and Human Chorionic Gonadotropin (hCG) are glycoproteins that the alpha subunit common. As a consequence of this, hCG has intrinsic thyrotropic activity. Because of high levels of hCG, maternal serum thyrotropin level is seen to decrease in 80% of pregnancies. Novel investigation and several commission opinions recommend that the TSH cut-off value should be 2.5 mU/L in the first-trimester thyroid function screening.. We aimed to evaluate the contributions of the maternal serum TSH cut-off value of 2.5 mU/L to the development of maternal and fetal complications. Materials and Methods: We constructed the study with pregnancies in their first 12 weeks and planned to do only observation prospectively. We excluded pregnant women with systemic disease and any history of thyroid surgery or thyroid pathology. According to the TSH level, a case group(TSH level &amp;gt;2.5 mU/L) and a control group (TSH level&amp;lt;2.5 mU/L) were created through the pregnants with normal Thyroxine (T4) levels. The cohort group were divided into four subgroups according to whether they were anti-thyroid peroxidase (anti-TPO) positive or not. We observed the fetomaternal outcomes like pregnancy loss, hyperemesis gravidarum, hypertensive disorders, gestational diabetes, prelabour rupture of membranes, placental abruption, with routine prenatal visits until delivery; also delivery style, birth weight, shoulder dystocia, newborn intensive care needs, and postpartum hemorrhage were recorded. Results: The incidence of miscarriage in the subgroup with TSH &amp;gt;2.5 mU/L and anti-TPO (+) was significantly higher than in those with TSH &amp;lt;2.5 mU/L and anti-TPO (+) (p&amp;lt;0.05). All groups had no significant difference in other maternal or fetal/neonatal complications. Conclusion: If only the population-based nomograms are created, we may advise maternal serum TSH level as &amp;lt;2.5 mU/L for first-trimester screening. Single or multiple pregnancy status, gestational age, and the presence of thyroid peroxidase antibodies should also be taken into account when creating these nomograms.

The Relationship Between Iodine Excess and Thyroid Function During Pregnancy and Infantile Neurodevelopment at 18–24 Months

BackgroundThyroid disease is a prevalent condition during pregnancy, and excessive iodine intake can lead to changes in thyroid function. However, research on the relationship between maternal iodine excess, thyroid hormones during pregnancy, and infantile neurodevelopment is limited. ObjectivesThis study aimed to explore the relationship between maternal iodine excess and thyroid hormones during pregnancy and infantile neurodevelopment. The objective was to provide evidence to support and enhance the prevention of neurodevelopmental retardation in infants. MethodsFrom 2016 to 2018, a prospective study was conducted from pregnancy to 18–24 mo postpartum. Maternal urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), total serum iodine (TSI), and nonprotein-bound serum iodine during pregnancy were determined. The Gesell Development Scale was used to assess neurodevelopment of infants aged 18–24 mo. The iodine status of pregnant females was divided into following 4 groups on the basis of the distribution of maternal UIC: <100 μg/L (moderate deficiency), 100–149 μg/L (mild deficiency), 150–249 μg/L (sufficiency), and >250 μg/L (above requirement). ResultsOur study included 469 mother-infant pairs. Compared with the maternal UIC of 150–249 μg/L during pregnancy, risk of adaptive developmental delay was increased in infants with maternal UIC ≥250 μg/L (OR: 2.38; 95% CI: 1.06, 5.35). Pregnant females with TSI >90th quantiles were more likely to have offspring with language developmental delay than those with lower TSI in 10th–90th quantiles (OR: 3.06; 95% CI: 1.09, 8.58). Risk of fine motor developmental delay was increased in infants with maternal TSH ≥2.5 mIU/L during pregnancy (OR: 4.32; 95% CI: 1.43, 13.0). ConclusionsMaternal iodine nutritional status above requirement (UIC ≥250 μg/L or TSI >90th quantiles) during pregnancy negatively affects infantile neurodevelopment. Maternal TSH ≥2.5 mIU/L during pregnancy was an independent risk factor for infantile neurodevelopment. This trial was registered at clinicaltrials.gov as NCT03710148.

Prevalence, causes, and impact of non-visualized pregnancy losses in a recurrent pregnancy loss population.

Does the occurrence of non-visualized pregnancy loss (NVPL) affect future reproductive outcomes in patients with recurrent pregnancy loss (RPL)? The number of previous NVPLs is a significant predictor of subsequent live birth in patients with RPL. The number of preceding miscarriages is a strong indicator for future reproductive outcomes. However, NVPL particularly has been sparsely addressed in previous literature. We performed a retrospective cohort study of 1981 patients attending a specialized recurrent pregnancy loss clinic (RPL) from January 2012 to March 2021. A total of 1859 patients met the inclusion criteria of the study and were included in the analysis. Patients with a history of RPL, defined as ≥2 pregnancy losses before 20 weeks gestation, who attended a specialized RPL clinic in a tertiary care center were included. Patients' evaluation included parental karyotyping, antiphospholipid antibodies screening, uterine cavity assessment with hysterosalpingography (HSG) or hysteroscopy, maternal thyroid stimulating hormone (TSH) testing, and serum hemoglobin A1C testing. Other investigations were performed only when indicated such as testing for inherited thrombophilias, serum prolactin, oral glucose tolerance test, and endometrial biopsy. Patients were divided into three groups; patients who experienced NVPLs only (pure NVPLs group), patients with only visualized pregnancy losses (pure VPLs group), and patients with history of both NVPLs and VPLs (mixed group). Statistical analysis was performed using Wilcoxon rank-sum tests for continuous variables and Fisher's exact tests for categorical variables. Significance was detected when P values <0.05. A logistic regression model was used to determine the impact of NVPLs and VPLs numbers on any live birth subsequent to the initial RPL clinic visit. The prevalence of patients with pure NVPLs, pure VPLs, and mixed losses was 14.7% (274/1859), 31.8% (591/1859), and 53.5% (994/1859), respectively. The prevalence of acquired and congenital uterine anomalies diagnosed by HSG or hysteroscopy was significantly different between pure NVPLs, pure VPLs, and mixed groups (16.8% versus 23.7% versus. 20.7%, respectively P = 0.05). There were no significant differences in the results of other RPL investigations or baseline demographics between the three groups. A logistic regression model controlling for maternal age at the initial RPL clinic visit and the follow-up duration showed that the numbers of NVPLs (odds ratio (OR): 0.77, CI: 0.68-0.88) and VPLs (OR: 0.75, CI: 0.64-0.86) are strong predictors for subsequent live births after the initial RPL clinic visit (P < 0.001). The odds of having a live birth decreased by 23% and 25% with each additional NVPL and VPL, respectively. This study may be limited by its retrospective design. Some of our data, including home pregnancy tests and obstetric history, are based on patient self-reporting, which could have overstated the true prevalence of NVPLs. Another limitation is the lack of available live birth data for all patients at the time of the analysis. To our knowledge, this is the first study to examine and analyze the reproductive outcomes of patients with pure NVPLs in a substantial cohort of patients with RPL. NVPLs seem to affect future live births the same way as clinical miscarriages, which supports their inclusion in RPL definitions. This study was supported in part by Canadian Institute Heath Grant (CIHR): Reference Number/W11-179912 and Women's Health Research Institute (WHRI), Vancouver, BC, Canada. M.A.B: Research grants from Canadian Institute for Health Research (CIHR) and Ferring Pharmaceutical. M.A.B. is on the advisory board for AbbVie and Baxter. N/A.

Incidence of and Risk Factors for Neonatal Hypothyroidism Among Women with Graves' Disease Treated with Antithyroid Drugs Until Delivery.

Background: The incidence of neonatal hypothyroidism among newborns born to mothers with Graves' disease (GD) who continued antithyroid drug (ATD) treatment until delivery has never been reported. Objective: Our primary objective was to investigate the incidence of neonatal hypothyroidism among newborns born to mothers with GD who were treated with ATD until delivery. Our secondary objective was to identify the cutoff ATD daily doses for neonatal hypothyroidism risk, based on maternal thyrotropin (TSH) receptor antibody (TRAb) levels. Methods: We conducted a retrospective cohort study. We included 305 pregnant women with GD who were treated with an ATD until delivery (63 treated with methimazole [MMI] and 242 treated with propylthiouracil [PTU]). Umbilical cord TSH, free thyroxine (fT4), and TRAb levels were measured at delivery, and we investigated the respective relationships between neonatal hypothyroidism at delivery and maternal fT4 levels, TRAb levels, and daily ATD doses during pregnancy. Neonatal hypothyroidism was diagnosed when the umbilical cord fT4 level was below the lower limit of the reference range. Results: The incidence of neonatal hypothyroidism at delivery was 19.0% ([confidence interval, CI, 11.2-30.4]; 12/63) in the MMI group and 12.8% ([CI, 9.2-17.6]; 31/242) in the PTU group. Neonatal goiter was observed in one neonate in the PTU group, and two infants in the PTU group required levothyroxine treatment. The daily ATD dose in the third trimester was the strongest predictor of neonatal hypothyroidism at delivery; the cutoff MMI dose was 10 mg/day, and the cutoff PTU dose was 150 mg/day. When the maternal TRAb level in the third trimester was above three times the upper limit of the normal range, the cutoff MMI dose was 20 mg/day, and the cutoff PTU dose was 150 mg/day. Conclusions: Maternal fT4 and TRAb levels were higher in the neonatal hypothyroid group, which suggested prolonged GD activity. Careful follow-up is necessary when maternal GD remains active and the ATD dose to control maternal thyrotoxicosis cannot be reduced.

Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain.

Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its formation was preceded by loss of radial glia cell polarity. As radial glia mediate cell migration and originate in a progenitor cell niche called the ventricular zone (VZ), we hypothesized that TH action may control cell signaling in this region. Here we addressed this hypothesis by employing laser capture microdissection and RNA-Seq to evaluate the VZ during a known period of TH sensitivity. Pregnant rats were exposed to a low dose of propylthiouracil (PTU, 0.0003%) through the drinking water during pregnancy and lactation. Dam and pup THs were quantified postnatally and RNA-Seq of the VZ performed in neonates. The PTU exposure resulted in a modest increase in maternal thyroid stimulating hormone and reduced thyroxine (T4). Exposed neonates exhibited hypothyroidism and T4 and triiodothyronine (T3) were also reduced in the telencephalon. RNA-Seq identified 358 differentially expressed genes in microdissected VZ cells of hypothyroid neonates as compared to controls (q-values ≤0.05). Pathway analyses showed processes like maintenance of the extracellular matrix and cytoskeleton, cell adhesion, and cell migration were significantly affected by hypothyroidism. Immunofluorescence also demonstrated that collagen IV, F-actin, radial glia, and adhesion proteins were reduced in the VZ. Immunohistochemistry of integrin αvβ3 and isoforms of both thyroid receptors (TRα/TRβ) showed highly overlapping expression patterns, including enrichment in the VZ. Taken together, our results show that TH action targets multiple components of cell junctions in the VZ, and this may be mediated by both genomic and nongenomic mechanisms. Surprisingly, this work also suggests that the blood-brain and blood-cerebrospinal fluid barriers may also be affected in hypothyroid newborns.

Prevalence and Complications of Subclinical and Overt Hypothyroidism in Pregnancy at North Indian Tertiary Care Center.

Thyroid disorders are one of the commonest endocrine problems among pregnant women. It is often argued that it is not only overt, but subclinical thyroid dysfunction also has similar adverse effects on maternal and fetal outcomes. There is a huge deficiency of data from the Indian population to assess the prevalence of thyroid dysfunction in pregnancy. This study aimed to determine the prevalence of thyroid disorders in pregnancy and their impact on obstetrical outcomes in the Indian population. The study also had the objective of finding a correlation between maternal and fetal thyroid-stimulating hormone (TSH) levels in hypothyroid pregnancies. Around 1055 pregnant women in the first and second trimesters were enrolled in the study. A detailed history was noted and general examinations were done. Apart from routine obstetrical investigations, TSH level estimation was done. If the TSH level was deranged, then free T4 (fT4) and free T3 (fT3) levels were also estimated. Furthermore, 50 hypothyroid and euthyroid pregnant women from the same cohort were followed till delivery. Their obstetrical and perinatal outcomes were noted. The prevalence of thyroid dysfunction was 36.5% in this study, which was quite high in the population. Moreover, hypothyroid groups were prone to have pregnancy-induced hypertension (P = 0.03), intrauterine growth restriction (P = 0.05), and preterm delivery (P = 0.04) as compared to control. Cesarean section rate for fetal distress was significantly higher among pregnant hypothyroid women (P = 0.05). Neonatal respiratory distress and low appearance, pulse, grimace, activity, and respiration (APGAR) () scores were significantly more in the hyperthyroidism group (P = 0.04 and P = 0.02, respectively). Maternal TSH was significantly correlated with hemoglobin levels, HbA1c, and systolic blood pressure. Significant adverse effects on maternal and fetal outcomes were seen emphasizing the importance of routine antenatal thyroid screening.

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.

Cholestasis and Pulmonary Hypertension in Neonatal Thyrotoxicosis: A Case Report

AbstractNeonatal thyrotoxicosis is mostly caused by the transplacental passage of maternal thyroid stimulating hormone (TSH) receptor antibodies (TRAb) to the fetus. Although rare and transient, this condition may be associated with significant morbidity and mortality if not diagnosed and treated in an appropriate and timely manner. Anti-thyroid drugs are the main therapy. Here, we report a preterm newborn that presented with two uncommon presentations of neonatal thyrotoxicosis, cholestasis and pulmonary hypertension that significantly improved following the administration of anti-thyroid medications.

Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone- analyses based on the Huizhou mother-infant cohort.

ObjectivesThis study aimed to explore the relationship of maternal thyroid function and thyroid resistance parameters with neonatal thyroid-stimulating hormone (TSH).MethodsThis work was a longitudinal study. Singleton pregnant women without a history of thyroid disorders were recruited in their first prenatal visit from October 2018 to June 2020. Maternal thyroid markers including TSH, free triiodothyronine (FT3), free thyroxine (FT4), and neonatal TSH were tested in the clinical laboratory of the hospital by electrochemiluminescence immunoassay. Thyroid resistance indices including Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI) were estimated in accordance with maternal FT4 and TSH levels. Multivariable linear and logistic regression was applied to explore the associations of maternal thyroid indices with infantile TSH level.ResultsA total of 3,210 mothers and 2,991 newborns with valid TSH data were included for analysis. Multivariable linear regression indicated that maternal thyroid variables were significantly and positively associated with neonatal TSH levels with standardized coefficients of 0.085 for TSH, 0.102 for FT3, 0.100 for FT4, 0.076 for TSHI, 0.087 for TFQI, and 0.089 for TT4RI (all P < 0.001). Compared with the lowest quartile, the highest quartile of TSHI [odds ratio (OR) = 1.590, 95% CI: 0.928–2.724; Ptrend = 0.025], TFQI (OR = 1.746, 95% CI: 1.005–3.034; Ptrend = 0.016), and TT4RI (OR = 1.730, 95% CI: 1.021–2.934; Ptrend = 0.030) were significantly associated with an increased risk of elevated neonatal TSH (>5 mIU/L) in a dose–response manner.ConclusionThe longitudinal data demonstrated that maternal thyroid resistance indices and thyroid hormones in the first half of gestation were positively associated with neonatal TSH levels. The findings offered an additionally practical recommendation to improve the current screening algorithms for congenital hypothyroidism.

A prospective observational study on maternal thyroid-stimulating hormone and its impact on maternal and perinatal outcome

Background: Numerous hormonal changes and metabolic demands occur during pregnancy, resulting in complex changes in maternal thyroid function. Thyroid disorder is the second most common endocrine disorder found in pregnancy next to the diabetes group. It affects 1–2% of women of reproductive age. Overt hypothyroidism complicates 0.3–0.5% of pregnancies. The incidence of subclinical hypothyroidism in pregnant women is about 2–3%. Hyperthyroidism is present in 0.1–0.4%. Aims and Objectives: The aim of the study was to assess the maternal thyroid function test during pregnancy and its effect on maternal and fetal outcomes. Materials and Methods: A prospective observational study was conducted in the Department of Obstetrics and Gynaecology at Dhanalakshmi Srinivasan Medical College and Hospital, Tamil Nadu over a period of 1 year February 2019 to January 2020. The study is to screen pregnant women for thyroid disorders based on their serum thyroid stimulating hormone (TSH) at the first antenatal visit and its impact on maternal and perinatal outcomes. Results: In our study, overall thyroid abnormality incidence was found to be 5.5%. It is statistically significant (P&lt;0.001). Subclinical hypothyroid was found as a major thyroid disorder in the study population (significant P&lt;0.002). In the study overt hyperthyroidism: 0.5%, subclinical hypothyroidism: 3.5%, primary hypothyroidism 1.5% was found. More than 54% of the study population had no high-risk factors and were found to have a thyroid disorder. In our study, maternal complications in women with thyroid disorders were analyzed. One woman with overt hypothyroidism, one with subclinical hypothyroidism developed mild preeclampsia. One hypothyroid woman had preterm labor at 32 weeks of gestational age. Maternal complications were less inadequately treated patients resulting in a normal incidence of these complications. In our study birth weight of the babies, &lt;2.5 kg was 18.2%, 2.5–3 kg was 63.6%, and &gt;3 kg was 18.2%. Perinatal outcomes were in terms of preterm, intrauterine growth restriction, low birthweight, and fetal distress. Conclusion: All pregnant women irrespective of their low risks or high risks for a thyroid disorder should be screened for serum TSH at the first booking visit to prevent the maternal and perinatal complications of thyroid disorders and close monitoring and effective treatment could be provided to them.

Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes

Previous literature on prenatal phenol exposure and thyroid hormone (TH) alteration is conflicting, and the possible mechanisms of action involved remain unclear. We aimed to examine the association between prenatal phenol exposure and levels of maternal and neonatal THs, as well as the possible role of iodothyronine deiodinase (DIO) gene polymorphisms in this relation.We studied 387 Spanish mother–neonate pairs with measurements of maternal phenols, total triiodothyronine (TT3) and free thyroxine (FT4), maternal and neonatal thyroid-stimulating hormone (TSH), and maternal genotypes for single nucleotide polymorphisms in the DIO1(rs2235544) and DIO2(rs12885300) genes. We implemented multivariate linear and weighted quantile sum (WQS) regressions to examine the association between phenols and THs (including sex-stratified models for neonatal TSH) and investigated effect modification of genotypes in the maternal phenol-TH associations.In single exposure models, we found negative associations between maternal triclosan (TCS) and neonatal TSH (% change [95%CI]: −2.95 [-5.70, -0.11], per twofold phenol increase) – stronger for girls – and less clearly for maternal ethylparaben (EPB) and TSH (−2.27 [-4.55, 0.07]). In phenol mixture models, we found no association with THs. In the genetic interaction models, we found some evidence of effect modification of DIO gene polymorphisms with stronger negative associations between methylparaben (MPB), propylparaben (PPB), butylparaben (BPB) and TT3 as well as bisphenol A (BPA) and FT4 for DIO1(rs2235544)-CC. Stronger inverse associations for genotypes DIO2(rs12885300)-CC and DIO2(rs12885300)-CT and positive ones for DIO2(rs12885300)-TT were also reported for BPA and FT4.In conclusion, we found some evidence of an association between phenols and TSH during pregnancy and at birth in single exposure models, the latter being stronger for girls. Since no association was observed between maternal levels of phenols and TT3 or FT4, the possible role of the genetic background in these associations warrants further investigation.