Effects of isolated maternal hypothyroxinemia on adverse pregnancy outcomes

Nazarpour, Sima; Tehrani, Fahimeh Ramezani; Rahmati, Maryam; Amiri, Mina; Azizi, Fereidoun

doi:10.1007/s00404-021-06226-0

Cited by 11 publications

(5 citation statements)

References 56 publications

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“…However, the reported effects of isolated hypothyroxinemia on fetal birthweight are controversial. Su et al reported an increased risk of SGA in isolated hypothyroxinemia [ 17 ], and Nazarpour et al reported an increased risk of low birth weight in isolated hypothyroxinemia [ 18 ]. However, some reports have shown the association between macrosomia or LGA and isolated hypothyroxinemia [ 5 , 19-21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Iodine deficiency is a well-known risk factor for isolated hypothyroxinemia [ 22 , 23 ]. There is only 1 previous report evaluating maternal urinary iodine concentrations; Nazarpour et al reported that isolated hypothyroxinemia with adequate iodine intake showed a higher risk of low birth weight than euthyroid women [ 18 ]. Obesity has also been revealed as a common risk factor for isolated hypothyroxinemia.…”

Section: Discussionmentioning

confidence: 99%

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Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan

Sankoda

Arata

Sato

et al. 2023

Journal of the Endocrine Society

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Context Isolated hypothyroxinemia (low maternal free thyroxine [FT4] in the absence of thyroid stimulating hormone [TSH] elevation) and subclinical hypothyroidism (high TSH in the absence of FT4 elevation) during early pregnancy are common. However, there is limited data regarding pregnancy outcomes, particularly their association with birthweight. Objective We assessed the association between isolated hypothyroxinemia and subclinical hypothyroidism during the first trimester and birthweight. Methods Analyses were conducted using a database of pregnant women (n = 1,105; median age, 35 years) who delivered at the National Center for Child Health and Development, a tertiary hospital in Tokyo. The primary outcomes included the rates of small for gestational age (SGA), large for gestational age (LGA), and low birth weight. Results Of the 1,105 pregnant women, 981 were classified into the euthyroidism group, 25 into the isolated hypothyroxinemia group, and 26 into the subclinical hypothyroidism group during the first trimester. The prevalence of SGA was significantly higher in isolated hypothyroxinemia and subclinical hypothyroidism groups compared to the euthyroidism group (28.0% and 19.2%, respectively, vs. 5.7%; p < .01). The odds ratio with 95% confidence interval for SGA was 12.51 (4.41-35.53) for isolated hypothyroxinemia and 4.44 (1.57-12.56) for subclinical hypothyroidism in a multivariable adjustment model. Isolated hypothyroxinemia and subclinical hypothyroidism were not significantly associated with LGA and low birth weight. Conclusion Pregnant women with isolated hypothyroxinemia and subclinical hypothyroidism in the first trimester have an increased likelihood of SGA. Screening and careful perinatal checkups for isolated hypothyroxinemia and subclinical hypothyroidism may help identify pregnant women at high risk for SGA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan

Sankoda

Arata

Sato

et al. 2023

Journal of the Endocrine Society

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“…Kiran et al (24) found that women with hypothyroidism diagnosed before conception had significantly higher risk of neonatal low birthweight. Also a prospective cohort study not only concluded the odds ratio of neonatal low birthweight in women with maternal hypothyroidism (IMH) was 2.53-folder higher than the healthy women, but also demonstrated the women with IMH had 5.43 times higher risk of preterm premature rupture of the membranes (PPROM) (25). Other studies showed concrete evidence on the association of subclinical hypothyroidism with the adverse outcomes in both short and long term, such as higher risk of pregnancy loss (26), offspring's behavioral alterations (27).…”

Section: Discussionmentioning

confidence: 99%

Quantifying the Impacts of Pre- and Post-Conception TSH Levels on Birth Outcomes: An Examination of Different Machine Learning Models

et al. 2021

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BackgroundWhile previous studies identified risk factors for diverse pregnancy outcomes, traditional statistical methods had limited ability to quantify their impacts on birth outcomes precisely. We aimed to use a novel approach that applied different machine learning models to not only predict birth outcomes but systematically quantify the impacts of pre- and post-conception serum thyroid-stimulating hormone (TSH) levels and other predictive characteristics on birth outcomes.MethodsWe used data from women who gave birth in Shanghai First Maternal and Infant Hospital from 2014 to 2015. We included 14,110 women with the measurement of preconception TSH in the first analysis and 3,428 out of 14,110 women with both pre- and post-conception TSH measurement in the second analysis. Synthetic Minority Over-sampling Technique (SMOTE) was applied to adjust the imbalance of outcomes. We randomly split (7:3) the data into a training set and a test set in both analyses. We compared Area Under Curve (AUC) for dichotomous outcomes and macro F1 score for categorical outcomes among four machine learning models, including logistic model, random forest model, XGBoost model, and multilayer neural network models to assess model performance. The model with the highest AUC or macro F1 score was used to quantify the importance of predictive features for adverse birth outcomes with the loss function algorithm.ResultsThe XGBoost model provided prominent advantages in terms of improved performance and prediction of polytomous variables. Predictive models with abnormal preconception TSH or not-well-controlled TSH, a novel indicator with pre- and post-conception TSH levels combined, provided the similar robust prediction for birth outcomes. The highest AUC of 98.7% happened in XGBoost model for predicting low Apgar score with not-well-controlled TSH adjusted. By loss function algorithm, we found that not-well-controlled TSH ranked 4th, 6th, and 7th among 14 features, respectively, in predicting birthweight, induction, and preterm birth, and 3rd among 19 features in predicting low Apgar score.ConclusionsOur four machine learning models offered valid predictions of birth outcomes in women during pre- and post-conception. The predictive features panel suggested the combined TSH indicator (not-well-controlled TSH) could be a potentially competitive biomarker to predict adverse birth outcomes.

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“…Several studies have investigated the effects of IMH, and the results show conflicting evidence regarding adverse obstetric and neurodevelopmental outcomes. Recent studies have revealed that IMH in pregnancy is associated with unfavorable pregnancy outcomes, such as preterm delivery [ 8 , 15 ], preterm premature rupture of the membranes [ 16 ], spontaneous abortion [ 17 , 18 ], and gestational hypertension [ 19 , 20 ], etc. Also, a couple of studies have suggested a similar point of view [ 19 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Obstetric and offspring outcomes in isolated maternal hypothyroxinaemia: a systematic review and meta-analysis

Zhuo

Wang

Yang

et al. 2022

J Endocrinol Invest

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Objective To examine the association between isolated maternal hypothyroxinaemia (IMH) and adverse obstetric outcomes and offspring outcomes and also investigate the effects of levothyroxine therapy on IMH for the above outcomes. Methods We systematically searched PubMed, EMBASE, and Cochrane Library, and the reference lists of key reviews were hand searched on June 9, 2021. Two authors independently screened titles/abstracts. Full articles were further assessed if the information suggested that the study met the inclusion/exclusion criteria, and two researchers performed data extraction and risk-of-bias assessment using standardized tables. Summary relative risks or the mean difference between maternal effects and offspring outcomes were calculated by a random-effects model. Results We identified 38 eligible articles (35 cohort studies and two randomized controlled trials [RCT]). Meta-analysis showed that maternal IMH was associated with increased gestational diabetes mellitus, preterm premature rupture of membranes, preterm birth, fetal distress, and macrosomia outcomes in IMH compared to euthyroid women, and the relative risks were 1.42 (1.03–1.96), 1.50 (1.05–2.14), 1.33 (1.15–1.55), 1.75 (1.16–2.65) and 1.62 (1.35–1.94), respectively. IMH was not associated with placenta previa, gestational hypertension, pre-eclampsia, intrauterine growth restriction, and offspring outcomes like birth weight, low birth weight infants, fetal macrosomia, neonatal intensive care, neonatal death, or fetal head circumference. In addition, we did not find an association between IMH and adverse offspring cognitive defects. Due to insufficient data for meta-analysis, it failed to pool the evidence of levothyroxine’s therapeutic effect on IMH and their offspring. Conclusions and relevance IMH in pregnancy may relate to a few maternal and offspring outcomes. Moreover, there is currently no sufficient evidence that levothyroxine treatment during pregnancy reduces adverse maternal outcomes and disability in offspring. Further investigation to explore the beneficial effects of levothyroxine therapy is warranted.

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Effects of isolated maternal hypothyroxinemia on adverse pregnancy outcomes

Cited by 11 publications

References 56 publications

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan

Association of Isolated Hypothyroxinemia and Subclinical Hypothyroidism With Birthweight: A Cohort Study in Japan

Quantifying the Impacts of Pre- and Post-Conception TSH Levels on Birth Outcomes: An Examination of Different Machine Learning Models

Obstetric and offspring outcomes in isolated maternal hypothyroxinaemia: a systematic review and meta-analysis

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