A Novel Nomogram for Predicting the Risk of Premature Delivery Based on the Thyroid Function in Pregnant Women

BackgroundMaternal thyroid dysfunction and autoantibodies were associated with preterm delivery. However, recommendations for cutoff values of thyroperoxidase antibody (TPOAb) positivity and thyroid-stimulating homone (TSH) associated with premature delivery are lacking.ObjectiveTo identify the pregnancy-specific cutoff values for TPOAb positivity and TSH associated with preterm delivery. To develop a nomogram for the risk prediction of premature delivery based on maternal thyroid function in singleton pregnant women without pre-pregnancy complications.MethodsThis study included data from the International Peace Maternity and Child Care Health Hospital (IPMCH) in Shanghai, China, between January 2013 and December 2016. Added data between September 2019 and November 2019 as the test cohort. Youden’s index calculated the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration. Univariate and multivariable logistic regression analysis were used to screen the risk factors of premature delivery. The nomogram was developed according to the regression coefficient of relevant variables. Discrimination and calibration of the model were assessed using the C-index, Hosmer-Lemeshow test, calibration curve and decision curve analysis.Results45,467 pregnant women were divided into the training and validation cohorts according to the ratio of 7: 3. The testing cohort included 727 participants. The pregnancy-specific cutoff values associated with the risk of premature delivery during the first trimester were 5.14 IU/mL for TPOAb positivity and 1.33 mU/L for TSH concentration. Multivariable logistic regression analysis showed that maternal age, history of premature delivery, elevated TSH concentration and TPOAb positivity in the early pregnancy, preeclampsia and gestational diabetes mellitus were risk factors of premature delivery. The C-index was 0.62 of the nomogram. Hosmer-Lemeshow test showed that the Chi-square value was 2.64 (P = 0.955 > 0.05). Decision curve analysis showed a positive net benefit. The calibration curves of three cohorts were shown to be in good agreement.ConclusionsWe identified the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration associated with preterm delivery in singleton pregnant women without pre-pregnancy complications. We developed a nomogram to predict the occurrence of premature delivery based on thyroid function and other risk factors as a clinical decision-making tool.

Sex-specific effect of maternal thyroid hormone trajectories on preschoolers’ behavioral development: a birth cohort study

Context Maternal thyroid hormone trajectories are better predictor of offspring’s neurodevelopment than hormone levels in single trimester of pregnancy. Programming effect of uterine hormonal environment on offspring’s health is usually sex-specific. Objective To examine the sex-specific effect of thyroid hormone trajectories on preschoolers’ behavioral development. Design Based on Ma’ anshan Birth Cohort (MABC) in China, pregnant women were recruited at their first antenatal checkup from May 2013 to September 2014. Setting Ma’ anshan Maternal and Child Health Hospital in China. Patients or Other Participants 1860 mother-child pairs were included in the analysis. Children were followed up at age of 4. Main Outcome Measures Maternal thyroid hormones (TSH, FT4) and TPOAb in the first, second and third trimesters of pregnancy were retrospectively assayed. Preschoolers’ behavioral development was assessed by Achenbach Child Behavior Checklist (CBCL/1.5~5). Results Maternal TSH and FT4 levels were respectively fitted into high, moderate and low trajectories. In boys, maternal high TSH trajectory was related to withdrawn (OR = 2.01, 95% CI: 1.16, 3.50) and externalizing problems (OR = 2.69, 95% CI: 1.22, 5.92), and moderate TSH trajectory was associated with aggressive behavior (OR = 3.76, 95% CI: 1.16, 12.23). Maternal high FT4 trajectory was associated with anxious/depressed (OR = 2.22, 95% CI: 1.08, 4.56) and total problems (OR = 1.74, 95% CI: 1.13, 2.66), and low FT4 trajectory was associated with aggressive behavior (OR = 4.17, 95% CI: 1.22, 14.24). Conclusions Maternal thyroid hormone trajectories impact preschool boys’ behavioral development.

Does foetal gender influence maternal thyroid parameters in pregnancy?

Objective It is unknown if foetal gender influences maternal thyroid function during pregnancy. We therefore investigated the prevalence of thyroid disorders and determined first-trimester TSH reference ranges according to gender. Methods A cross-sectional study involving 1663 women with an ongoing pregnancy was conducted. Twin and assisted pregnancies and l-thyroxine or antithyroid treatment before pregnancy were exclusion criteria. Serum TSH, free T4 (FT4) and thyroid peroxidase antibodies (TPOAb) were measured at median (interquartile range; IQR) 13 (11–17) weeks of gestation. Subclinical hypothyroidism (SCH) was present when serum TSH levels were >3.74 mIU/L with normal FT4 levels (10.29–18.02 pmol/L), and thyroid autoimmunity (TAI) was present when TPOAb were ≥60 kIU/L. Results Eight hundred and forty-seven women were pregnant with a female foetus (FF) and 816 with a male foetus (MF). In women without TAI and during the gestational age period between 9 and 13 weeks (with presumed high-serum hCG levels), median (IQR range) serum TSH in the FF group was lower than that in the MF group: 1.13 (0.72–1.74) vs 1.24 (0.71–1.98) mIU/L; P = 0.021. First-trimester gender-specific TSH reference range was 0.03–3.53 mIU/L in the FF group and 0.03–3.89 mIU/L in the MF group. The prevalence of SCH and TAI was comparable between the FF and MF group: 4.4% vs 5.4%; P = 0.345 and 4.9% vs 7.5%; P = 0.079, respectively. Conclusions Women pregnant with an MF have slightly but significantly higher TSH levels and a higher upper limit of the first-trimester TSH reference range, compared with pregnancies with a FF. We hypothesise that this difference may be related to higher hCG levels in women pregnant with a FF, although we were unable to measure hCG in this study. Further studies are required to investigate if this difference has any clinical relevance.

Correlation between maternal thyroid stimulating hormone and birth weight of neonate

Background: The aim of this study is to determine the pregnancy outcomes in women with thyroid disorders.Methods: This is a retrospective observational study conducted in the department of obstetrics and gynaecology of AJ institute of medical sciences and research centre from the month of March to September 2021. The first trimester thyroid stimulating hormone (TSH) level and birth weight of new born is collected from hospital records, study participants included all the pregnant mothers who were admitted and delivered in the labour ward of AJ institute of medical sciencesResults: According to our study low birth weight in neonates in euthyroid, hypothyroid, hyperthyroid participants were 21.4%, 61.5%, and 100% respectively.Conclusions: This study indicates that there is an association between maternal thyroid levels and neonatal birth weight. A higher TSH concentration during first trimester of pregnancy is associated with low birth weight. Based on these findings, it is recommended that maternal thyroid levels be monitored closely in the first trimester and initiate timely treatment in case of altered thyroid levels during pregnancy in order to have a healthy pregnancy and healthy baby with no compromise in the fetal weight.

Altricial bird early-stage embryos express the molecular "machinery" to respond to maternal thyroid hormone cues

Maternal hormones, such as thyroid hormones transferred to embryos and eggs, are key signalling pathways to mediate maternal effects. To be able to respond to maternal cues, embryos must express key molecular "machinery" of the hormone pathways, such as enzymes and receptors. While altricial birds begin thyroid hormone (TH) production only at/after hatching, experimental evidence suggests that their phenotype can be influenced by maternal THs deposited in the egg. However, it is not understood, how and when altricial birds express genes in the TH-pathway. For the first time, we measured the expression of key TH-pathway genes in altricial embryos, using two common altricial ecological model species (pied flycatcher, Ficedula hypoleuca and blue tit Cyanistes caeruleus). Deiodinase DIO1 gene expression could not be reliably confirmed in either species, but deiodinase enzyme DIO2 and DIO3 genes were expressed in both species. Given that DIO2 coverts T4 to biologically active T3, and DIO3 mostly T3 to inactive forms of thyroid hormones, our results suggest that embryos may modulate maternal signals. Thyroid hormone receptor (THRA and THRB) and monocarboxyl membrane transporter gene (SLC15A2) were also expressed, enabling TH-responses. Our results suggest that early altricial embryos may be able to respond and potentially modulate maternal signals conveyed by thyroid hormones.

Classification of maternal thyroid function in early pregnancy using repeated blood samples

Objective: The assessment of maternal thyroid function in early pregnancy is debated. It is well-established that pregnancy-specific reference ranges preferably should be used. We speculated if the use of repeated blood samples drawn in early pregnancy would influence the classification of maternal thyroid function. Design: Cohort study Methods: Pregnant women with repeated early pregnancy blood samples were identified in the North Denmark Region Pregnancy Cohort. Each sample was used for the measurement of TSH, free T4 (fT4), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers). Method- and pregnancy week-specific reference ranges were used for classification of maternal thyroid function. Results: Among 1,466 pregnancies included, 89 women had TSH above the upper reference limit in the first sample (median pregnancy week 8), and 44 (49.4%) of these similarly had high TSH in the second sample (median week 10). A total of 47 women had TSH below the lower reference limit in the first sample, and 19 (40.4 %) of these similarly had low TSH in the second sample. Regarding women classified with isolated changes in fT4 in the first sample, less than 20% were similarly classified as such in the second sample. The percentage agreement between the samples was dependent on the level of TSH in the first sample and the presence of TPO- and Tg-Ab. Conclusion: In a large cohort of pregnant women, the classification of maternal thyroid function varied considerably with the use of repeated blood samples. Results emphasize a focus on the severity of thyroid function abnormalities in pregnant women.

A Case of Neonatal Thyrotoxicosis with Cardiac Insufficiency

Neonatal thyrotoxicosis is rare and most of the cases are secondary to maternal Graves’ disease. It is usually transient, but can be associated with significant morbidity and mortality if not recognized promptly and treated adequately. Neonates born to mothers treated with antithyroid drugs or those who receive maternal thyroid blocking antibodies may exhibit normal thyroid function or even hypothyroidism at birth. Since there may not be any obvious symptoms of hyperthyroidism at birth, it may be overlooked. Therefore, such neonates should be evaluated properly and monitored regularly to prevent serious complications of hyperthyroidism. We report a case of a 21-day-old male infant who developed thyrotoxicosis with dyspnea, irritability, tachycardia, and cardiac insufficiency. He was born to a mother who was treated for Graves’ disease with antithyroid drugs during pregnancy. We have also discussed the importance of careful examination and monitoring to prevent the development of clinical hyperthyroidism.