Gestational Subclinical Hypothyroidism Research Articles

Effect of different initiation timing of levothyroxine on pregnancy outcomes and development of offspring in women with gestational subclinical hypothyroidism

Objective: To explore the impact of levothyroxine (L-T4) administration at different time points on pregnancy outcomes and offspring development in patients with subclinical hypothyroidism (SCH). Methods: In this retrospective study, medical records of 107 patients with SCH treated in Huzhou Nanxun District People’s Hospital from February 2021 to March 2023 were retrospectively reviewed. Of them, 55 patients received treatment before eight gestational weeks (Early group), and 52 patients received treatment after eight gestational weeks (Mid group). Levels of thyroid function indicators, occurrence of adverse pregnancy outcomes, occurrence of adverse reactions, and development of offspring before and after the treatment were compared. Results: After the treatment, the thyroid function indicators in both groups improved compared to before treatment, and the improvement in the Early group was significantly better than that in the Mid group (P<0.05). The incidence of adverse pregnancy outcomes in the early group (5.45%) was lower than that in the mid group (19.23%) (P<0.05). There was no significant difference in the incidence of adverse reactions between the groups (P>0.05). The scores of fine motor, gross motor, language, personal-social behavior, and adaptability in offspring of patients the Early group were higher than those of the mid group (P<0.05). Conclusions: Early administration of L-T4 is safe and can effectively improve thyroid function in SCH patients, reduce adverse pregnancy outcomes, and ensure growth and development of offspring. doi: https://doi.org/10.12669/pjms.40.10.9724 How to cite this: Fei M, Shen L, Ding X, Li G, You J. Effect of different initiation timing of levothyroxine on pregnancy outcomes and development of offspring in women with gestational subclinical hypothyroidism. Pak J Med Sci. 2024;40(10):2400-2404. doi: https://doi.org/10.12669/pjms.40.10.9724 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy: Pooled Analysis of Data from Two Randomized Controlled Trials.

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

HDAC1/2/3-mediated downregulation of neurogranin is involved in cognitive impairment in offspring exposed to maternal subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.

Association between levothyroxine treatment for maternal subclinical hypothyroidism with negative TPOAb and early child neurodevelopment: A prospective real-world clinical trial.

Subclinical hypothyroidism (SCH) during pregnancy is reported to have detrimental impact on pregnancy and child development. However, its treatment indications require further investigation in different thyroid peroxidase antibody (TPOAb) status. This was a secondary analysis of a Chinese prospective cohort in a real-world setting. Pregnant women with gestational SCH were enrolled at the first antenatal visit and grouped by TPOAb positivity. Child neurodevelopment was assessed by the Gesell development diagnosis scale (GDDS) at one, three, six, 12, and 24 months of age. Subgroup analyses and sensitivity analyses were also conducted. ClinicalTrials.gov NCT01744743. From January 2012 to December 2013, a total of 171 participants were enrolled, including 116 of SCH with TPOAb negative (SCH-TPOAb [-]) and 55 of SCH with TPOAb positive (SCH-TPOAb [+]). Compared to women in the SCH-TPOAb (+) group, those in the SCH-TPOAb (-) group had lower thyroid-stimulating hormone (TSH) levels at enrollment and 12-16+6 gestational weeks, and unexpectedly higher TSH levels at 30-34+6 gestational weeks and delivery, with a correspondingly lower levothyroxine dosage throughout pregnancy (all p < 0.05). Offspring in the SCH-TPOAb (-) group displayed lower GDDS scores at one year old than did their counterparts (adjusted p < 0.05), which was possibly related to the worse thyroid function control of maternal SCH-TPOAb (-). No statistically significant difference was found in the GDDS assessments of children at one, three, six, and 24 months of age. These results were also confirmed in subgroup analyses stratified by maternal thyroid characteristics at enrollment, namely TSH levels, free levothyroxine (T4 ) levels, and anti-thyroglobulin antibody (TgAb) status, as well as in sensitivity analyses excluding participants with no levothyroxine treatment at enrollment. In the current clinical practice, infants born to mothers with SCH-TPOAb (-) displayed slightly lower neurodevelopmental scores at one year old than did those born to mothers with SCH-TPOAb (+) but this difference was not seen at two years.

Association between gestational blood lipids and TSH levels and pregnancy outcome of patients with subclinical hypothyroidism.

To investigate the association between gestational blood lipids and thyroid stimulating hormone (TSH) levels and pregnancy outcomes of patients with subclinical hypothyroidism (SCH). In this retrospective observational study, we analyzed the clinical data of 82 patients (case group) with gestational SCH treated in our hospital from January 2021 to January 2022 at gestational weeks 25-33 and grouped them according to whether SCH was well controlled by treatment (case Group-A: well controlled, n=55; case Group-B: poorly controlled, n=27), and the clinical data of 41 pregnant women (control group) undergoing physical examination during the same period. After comparing the blood lipids and TSH levels of the three groups, we compared their adverse pregnancy outcomes to assess the possible correlations between blood lipids and TSH levels and pregnancy outcomes. The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and TSH in the case Group-B were significantly higher than those in the case Group-A and the control group (P<0.05). Compared with case Group-B and the control group, the incidence of premature delivery, abortion and neonatal growth restriction was higher in case Group-A (P<0.05). Among 82 patients in the case group 42 presented adverse pregnancy outcomes. The levels of TC, TG, LDL-C and TSH in mothers and infants in the adverse outcome group were significantly higher than those in the favorable outcome group (P<0.05). Our Pearson analysis results showed that the levels of TC, TG and LDL-C were positively correlated with the TSH levels and the pregnancy outcomes, and that TSH was positively correlated with pregnancy outcomes (P<0.05). The levels of TC, TG, LDL-C and TSH in patients with poorly controlled SCH were increased during pregnancy, and were associated with the pregnancy outcomes and positively correlated with each other.

Posthemithyroidectomy Pregnancy Thyroid Function Surveillance: Frequency, Adherence, and Guideline Impact

ObjectivePosthemithyroidectomy women are at an increased risk for gestational subclinical hypothyroidism. Therefore, the American Thyroid Association (ATA) recommends increased thyroid function surveillance for this subgroup of pregnant women. The purpose of this study was to evaluate the frequency of thyroid function surveillance during pregnancy in posthemithyroidectomy women and to evaluate the adherence to the 2017 ATA guidelines and its possible impact since being published on thyroid function surveillance rates. MethodsA retrospective study of pregnant posthemithyroidectomy women operated at our institution between 1997 and 2020 was performed. The study cohort was subdivided by pregnancy dates before 2018 and 2018 onward to evaluate the impact of the 2017 ATA guidelines. Adherence to the guidelines was defined as at least 1 thyroid-stimulating hormone test in each trimester. ResultsAfter exclusions, a total of 120 pregnancies conceived by 66 women who underwent hemithyroidectomy surgeries were included in this study. Overall, serum thyroid-stimulating hormone examinations were performed during the first, second, and third pregnancy trimesters in 86.6%, 40%, and 16.6% of pregnancies, respectively (P <.005). The examination rate since 2018 was 88%, 40%, and 8% for the first, second, and third trimesters, respectively (P <.005). ConclusionAdherence to the latest ATA guidelines is low, and its publication in 2017 did not increase the thyroid function surveillance rate in posthemithyroidectomy women. Better patient education regarding the risks of gestational hypothyroidism following hemithyroidectomy and improved communications among treating surgeons, obstetricians, and endocrinologists may improve these rates.

Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring.

Background: The adverse impact of maternal negative TPOAb of gestational subclinical hypothyroidism (SCH-TPOAb-) on the development of the offspring has not yet been clearly identified. A lingering controversy exists over the treatment of SCH-TPOAb- diagnosed during pregnancy. Therefore, this study was designed to evaluate the intellectual development of children of mothers who had SCH-TPOAb-. Methods: A number of 139 children were recruited; 112 children were born to SCH TPOAb- and 27 children were born to euthyroid TPOAb- mothers. Based on the mothers' thyrotropin (TSH) levels during pregnancy and whether or not they received levothyroxine (LT4) treatment, the children were assigned to four groups: Group A (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 31) and Group B (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 26), whose mothers were treated with LT4 before eight gestational weeks, and Group C (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 27) and Group D (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 28), whose mothers received no treatment. A total number of 27 children whose mother's serum TSH was <2.5 mIU/L and were TPOAb- during their pregnancy served as the control group (Group E). The intellectual development of two-year-old children was assessed and compared using the Gesell Development Diagnosis Scale. Results: The developmental quotient (DQ) in Group D was 8.67 lower than this in Group E (p < 0.001). More specifically, gross motor quotient, fine motor quotient, adaptability quotient (ABQ), language quotient (LQ), and individual social behavior quotient (ISBQ) of DQ in Group D were significantly lower than those in Group E. No significant differences were observed in DQ among Group A, Group B, Group C, and Group E (p > 0.05). Spearman's rank correlation analysis showed that DQ, FMQ, ABQ, LQ, and ISBQ were significantly negatively correlated with the TSH level (r = -0.417, -0.253, -0.273, -0.436, and -0.272; p < 0.05). In addition, multivariate logistic regression analysis revealed that mothers' education (short education), mothers' education (medium education), and TSH level (4.0 mIU/L < TSH ≤10.0 mIU/L) were both risk factors affecting the intellectual development of the offspring (p < 0.05). Conclusion: The effects of the intellectual development of the offspring with SCH-TPOAb- are related to the level of TSH. Standardized treatment for SCH-TPOAb- pregnant women before eight gestational weeks, whose TSH level was from 4.0 to 10.0 mIU/L, may significantly improve the intellectual development levels of the approximately two-year-old offspring. Although our study was a historical cohort study, the data analyzed provide the foundation for further investigation. Further prospective intervention trials with large numbers of participants are needed to confirm our conclusions. The Clinical Trial Registration number is 2021-K-84-02.

Do Women with Gestational Subclinical Hypothyroidism Require Postpartum Monitoring?

Do Women with Gestational Subclinical Hypothyroidism Require Postpartum Monitoring?

MON-LB094 Matrix Metalloproteinases Are Linked with Preeclampsia and May Be Useful as a Biomarker in Gestational Subclinical Hypothyroidism

Gestational hypothyroidism has 5.1% prevalence and is associated with severe consequences as hypertensive complications and preeclampsia (PE). Based on the higher mortality associated with PE, the objective of this study is to identify new biomarkers useful as prognostic and therapeutically parameters. Methodology: The study was approved by the IRB Number: 665331/679727. We selected three volunteers to each group and constructed libraries of circulating RNA, for healthy pregnant women (HPW), preeclampsia (PEC) and gestational hypothyroidism (GHT). We collected blood samples for TSH and Free T4 (FT4) measurement and a PAX Gene Tube for RNA analysis. RNA extraction was performed by the PAXgene Blood RNA extraction kit (Qiagen NL, DE). NGS platform, Ion Proton System was used with Ion AmpliSeq Gene human transcriptome (Thermo Fisher Scientific Manufacturer) kit to construct the transcriptome libraries. The R software platform version 3.4.1 (R Foundation for Statistical Computing, Vienna, Austria. URL: R-project.org/) with the edgeR package 3.16.5 were used to determine the differentially expressed genes (DEG). We compared our GHT DEG with plasma transcriptome libraries from healthy pregnant women in the second and third trimesters (access number: GSE56899) available in GEO Dataset (ncbi.nlm.nih.gov/geo) using the limma package 3.26.8, p <0,05. We also used Random Forest (RF) analysis to rank the variables, Spearman Correlation, and multiclass ROC. Results: We encountered 713 DEG in the HPW with matrix metalloproteinases (MMP) upregulated, MMP8 (logFC 4.91) and MMP9 (logFC 3.44). In GEO Dataset we also found the MMP8 upregulated. We detected 195 DEG in PEC with MMP9 downregulated (logFC -2.49) and 745 DEG in GHT with MMP8 (logFC -4.06) and MMP9 (logFC -3.26) downregulated. We obtained 571 DEG in the analysis obtained by GEO Dataset and 26 genes are in common with our GHT DEG, including the MMP8. Between the 26 in common, 88.46% of genes were downregulated in GHT and 92.30% were upregulated GEO Dataset. We found a negative correlation of MMP8 with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r: -0.313; r: -0.285), MMP9 with SBP and DBP (r: -0.349; r: -0.384), MMP8 and MMP9 with weight (r: -0.223; r: -0.209) and MMP9 with TSH (r: 0.633). From our RF model, we selected the variables SBP and DBP, FT4 and weight that is possibly modified by the difference in expression of MMP8 and MMP9. We obtained an area under the curve of 0.97 for TSH, weight and those genes. Conclusion: Several metalloproteinases are involved in placental development, implantation and angiogenesis. We observed MMP8 and MMP9 downregulated in GHT. Although more studies are necessary, we found in the predictive model, TSH, weight and MMP8/MMP9 as the best combination to predict PE in GHT. Sources of Research Support: CNPq awarded to HD; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) awarded to CPC Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Influence of thyroid peroxidase antibodies on TSH levels of pregnant women and maternal–fetal complications

IntroductionDuring pregnancy, thyroid peroxidase (TPO) antibodies may increase the risk of developing subclinical hypothyroidism (SCH). Both conditions appear to be associated to maternal–fetal complications. The objectives of this study were to analyze if a relationship exists between TSH and TPO levels during pregnancy and the potential effects on gestational and perinatal complications, and to assess whether detectable, but not positive, TPO levels have an impact on development of gestational SCH. MethodsA prospective study was conducted at the Leon Health Area (CAULE), where universal screening for gestational thyroid dysfunction is performed between weeks 7–13 of pregnancy. Data on TSH and TPO levels and gestational and perinatal complications were collected for all 2016 deliveries. Positive TPO antibodies were defined as values≥35IU/ml. In a previous study, a TSH level>3.72mU/l was established as the cut-off value for gestational SCH. ResultsRecords corresponding to 1980 deliveries at CAULE, 21 abortions, and 18 deliveries outside the hospital were analyzed. Of the 1670 pregnant women screened (84.34%), 142 (8.50%) had positive TPO antibodies and their presence was associated to diagnosis of SCH (p<0.01) and to significantly higher mean TSH levels (3.51mU/l versus 2.46mU/l, p=0.03). There were no significant differences in gestational or neonatal complications. In the group with undetectable TPO antibodies (<10lU/ml), the mean TSH levels was slightly lower than in the group with TPO values ranging from 10 to 35IU/ml, but the difference was not significant (p=0.89). ConclusionPresence of positive TPO antibodies is associated to higher TSH levels and higher risk of gestational SCH, but does not increase the rate of maternal–fetal complications.

Influencia de los anticuerpos antiperoxidasa tiroidea en los valores de TSH de gestantes y en las complicaciones materno-fetales

IntroductionDuring pregnancy, thyroid peroxidase (TPO) antibodies may increase the risk of developing subclinical hypothyroidism (SCH). Both conditions appear to be associated to maternal-fetal complications. The objectives of this study were to analyze if a relationship exists between TSH and TPO levels during pregnancy and the potential effects on gestational and perinatal complications, and to assess whether detectable, but not positive, TPO levels have an impact on development of gestational SCH. MethodsA prospective study was conducted at the Leon Health Area (CAULE), where universal screening for gestational thyroid dysfunction is performed between weeks 7-13 of pregnancy. Data on TSH and TPO levels and gestational and perinatal complications were collected for all 2016 deliveries. Positive TPO antibodies were defined as values≥35IU/mL. In a previous study, a TSH level>3.72mU/L was established as the cut-off value for gestational SCH. ResultsRecords corresponding to 1,980 deliveries at CAULE, 21 abortions, and 18 deliveries outside the hospital were analyzed. Of the 1,670 pregnant women screened (84.34%), 142 (8.50%) had positive TPO antibodies and their presence was associated to diagnosis of SCH (P<0.01) and to significantly higher mean TSH levels (3.51mU/L vs. 2.46mU/L, P=0.03). There were no significant differences in gestational or neonatal complications. In the group with undetectable TPO antibodies (<10lU/mL), the mean TSH levels was slightly lower than in the group with TPO values ranging from 10-35 IU/mL, but the difference was not significant (P=0.89). ConclusionPresence of positive TPO antibodies is associated to higher TSH levels and higher risk of gestational SCH, but does not increase the rate of maternal-fetal complications.

Effects of gestational subclinical hypothyroidism and TPO-Ab on pregnancy outcomes

The prevalence of gestational subclinical hypothyroidism has been increasing with years, and it has become one of the common diseases happened to women during pregnancy in China. Gestational subclinical hypothyroidism can not only increase the incidence of adverse pregnancy outcomes, but also have a negative impact on the development of the offspring. Therefore, it is necessary to make an early detection, diagnosis and treatment.

Diagnosis and Management of Subclinical Hypothyroidism in Pregnancy: A Retrospective Review Study

Back ground: The hormones of thyroid organ play an important role for a normal pregnancy without maternal or fetal complexities. However, using different methods and thyrotropin (TSR) ranges for diagnosis subclinical hypothyroidism (SCH) in different population are challenging. The aim of this study is to clarify the world wide variation in prevalence of SCH, the accurate methods been used for diagnosing (SCH) in pregnant women, main adverse pregnancy outcomes related to (SCH) and the clinical impact of levothyroxine on gestational SCH related complications. Methods: Meta-analysis of the results of all studies that were investigated the screening methods, adverse pregnancy outcomes and the treatment of SCH during pregnancy which was published in English language during the last two decade including the popular guidelines in this regard. Results: The studies revealed a strong linear association between preterm delivery, miscarriage and TSH level with more events, if combined with positive thyroid antibodies. The difference in TSH (TSR) ranges among different ethnicity and countries should be considered for diagnosis and treatment. Conclusion: Early diagnosis and treatment of SCH during pregnancy is cost effective in reducing the preterm labour, miscarriage and its complications. Using specific TSH cut off level for each population is essential for accurate diagnosis and screening should include not only high risk cases but patients in countries with high prevalence of SCH.

Delaying Thyroxine Until Positive Beta-Human Chorionic Gonadotropin is Safe for Patients Receiving Fertility Therapy: Applying New ATA Guidelines to Subclinical Hypothyroidism.

This study sought to examine the effect of changing TSH threshold recommendations from 2.5 to 4 mIU/L before fertility therapy on the prevalence of early gestational subclinical hypothyroidism (SCH) (TSH2 >2.5 mIU/L) and to evaluate implications on progression to clinical pregnancy (defined as detection of cardiac activity on ultrasound). A retrospective chart review was performed in an academic fertility clinic on all patients with a measured pre-treatment TSH (TSH1) and positive beta-human chorionic gonadotropin following fertility treatment. The study assessed the effect of TSH2 on ongoing pregnancy, both in patients newly diagnosed with SCH and in patients previously receiving LT4, stratified by initial TSH. Of 482 women included in the study, baseline TSH (TSH1) was <2.5 mIU/L in 333 women (69%) and 2.5-4 mIU/L in 64 women (13.2%). Eighty-five women were taking LT4 at baseline (17.6%). Among women with a TSH1 between 2.5 and 4 mIU/L, the corresponding TSH in early pregnancy (TSH2) was <2.5 mIU/L in 35 women (55%). Overall, there was no difference in progression to clinical pregnancy between women with a TSH2 of 2.5-4 mIU/L compared with women with a TSH2 <2.5 mIU/L (OR 0.70; 95% CI 0.44-1.09). Similarly, when excluding women taking LT4 at baseline, there was no difference in progression to clinical pregnancy (OR 0.90; 95% CI 0.28-2.86). Rate of progression to clinical pregnancy was equivalent between women with an early pregnancy TSH (TSH2) <2.5 and women with a TSH2 of 2.5-4.0 mIU/L. Our findings support initiating LT4 in early pregnancy, as opposed to pre-pregnancy if the TSH remains above cut-off because there does not appear to be a difference in in early pregnancy outcomes if treatment is delayed.

696: Progression of gestational subclinical hypothyroidism and hypothyroxinemia to overt hypothyroidism after pregnancy

696: Progression of gestational subclinical hypothyroidism and hypothyroxinemia to overt hypothyroidism after pregnancy

Effect of gestational subclinical hypothyroidism on early neurodevelopment of offspring

To evaluate the effects of gestational subclinical hypothyroidism (SCH) on early neurodevelopment of offspring. A prospective study included 106 infants born to mothers with gestational SCH and 106 infants born to mothers who were euthyroid during pregnancy. The neurodevelopment of 12 to 24-month-old infants was assessed and compared using the Gesell developmental test (revised version). Infants born to mothers with gestational SCH and those born to euthyroid mothers had similar scores on the Gesell development test. No correlations were observed between maternal TSH concentration and Gesell developmental test scores of offspring. Infants born to mothers who had gestational SCH during the first trimester specifically and those born to euthyroid mothers had similar scores on the Gesell development test. No significant correlations were detected between maternal TSH concentration during the first trimester and offspring neurodevelopment. No detectable neurodevelopment deficit was observed in offspring up to 24 months old from mothers who had gestational SCH.

The sequelae of untreated maternal hypothyroidism

The concept that gestational subclinical hypothyroidism could have deleterious effects on the intellectual outcome of progeny was championed more than three decades ago by Evelyn Man in a series of publications. Her studies lay fallow until the Spanish group directed by Morreale de Escobar and the Dutch group headed by Vulsma provided the rationale for her results. Although the findings of the Spanish and Dutch groups elucidated the pathophysiologic basis for Man's conclusions, questions remained regarding the reliability of her biochemical measurements and possible bias in patient selection. In view of the uncertainty surrounding the validity of Man's work, we decided to try to confirm her findings. Our initial goal was to obtain an estimate of the prevalence of subclinical hypothyroidism in an unselected population living in New England. We accomplished this with two separate prospective studies involving 12 000 pregnant women residing in Maine. We found that 2.3% had TSH concentrations of >6.0 mU/l and 0.3% had TSH values of >12 mU/l at 17 weeks' gestation. We next did a retrospective study, utilizing sera that had been stored at -20 degrees C for 8 years, obtained in week 17 of gestation from 25 000 women. We identified 62 women with subclinical hypothyroidism and 124 matched controls. Fourteen of the hypothyroid mothers had been diagnosed and treated before and during pregnancy on a dosage of thyroxine that was unchanged. WISC IQs of the offspring of the 124 control and 62 hypothyroid mothers were determined at 8+/-0.5 years. The mean and s.d. of IQs of the children of the 124 control and of the 14 treated hypothyroid mothers were significantly higher than those of the children of the 48 untreated hypothyroid women. More than twice as many children of the untreated mothers had IQs of >1 s.d. below the control mean, and four times as many of the children had IQs 2 s.d. below the control mean, as did the children of the controls. A comparison of the mean hormonal values of the treated and untreated mothers at 17 weeks showed no significant difference in any of the biochemical markers. We surmise that the circulating level of thyroxine was normal in the treated mothers at a critical time before 17 weeks' gestation, but by 17 weeks it was insufficient to meet the growing demands of pregnancy. Treatment should begin as early as possible in pregnancy with the goal of maintaining free thyroxine (FT(4)) in the upper half of the normal reference range and TSH in the lower half of the normal reference range. In view of these data, we believe that all pregnant women should be screened for hypothyroidism as early in pregnancy as possible (or even before conception). To be cost-effective, screening programs should be based on those designed for congenital hypothyroidism, in which filter-paper blood specimens are forwarded to regional laboratories for thyroid function determinations.