Neonatal Screening for Hyperthyroidism Proof of Concept.

CONTEXT: Early treatment is essential to avoid the cardiac complication of neonatal hyperthyroidism (NH). Our results have direct implications for clinical care. OBJECTIVE: NH can cause potentially fatal neonatal thyrotoxicosis. Here, we have evaluated the feasibility of neonatal hyperthyroidism screening using the thyroid-stimulating hormone value in dried blood collected routinely on filter paper on the third postnatal day of life for congenital hypothyroidism screening. METHODS: Retrospective case-control study. Cases were identified using data from our previously published study of 280 000 infants born in 10 maternity units in France in 2007-2014. Controls were identified among the 1 362 564 infants born in the Ile-de-France region during the same period. RESULTS: A screening thyroid-stimulating hormone level below 0.18 mIU/L on the third postnatal day had 71% (95% CI 44-90%) sensitivity, 99% (95% CI 99-100%) specificity, 81% (95% CI 74-86%) positive predictive value, and 98% (95% CI 97-99%) negative predictive value for detecting severe NH. By univariate regression analysis, the screening thyroid-stimulating hormone value was the strongest predictor of NH (P < .00001), with an area under the receiver-operating characteristics curve of 0.98 (95% CI 0.95-1.0). Expected frequencies were not significantly different from observed frequencies (Hosmer-Lemeshow test, P = .99). CONCLUSION: The screening thyroid-stimulating hormone test can be used to detect severe NH, the optimal cut-off being 0.18 mIU/L. The additional cost compared with screening for congenital hypothyroidism would be small. Infants with neonatal hyperthyroidism would benefit from an earlier diagnosis with treatment initiation at the presymptomatic stage in many cases, ensuring optimal outcomes.

Prediction of Neonatal Hyperthyroidism.

OBJECTIVES: To assess whether it is possible to identify the neonatal predictors of neonatal hyperthyroidism at the presymptomatic stage of the disease. STUDY DESIGN: This retrospective multicenter study in 10 maternity units was based on the medical records of all patients monitored for a pregnancy between January 1, 2007, and January 1, 2014. Among 280 000 births, 2288 medical records of women with thyroid dysfunction were selected and screened. Of these, 415 women had Graves disease and were positive for thyrotropin receptor antibody during pregnancy, and were included. RESULTS: A thyroid-stimulating hormone (TSH) level of less than 0.90 mIU/L between days 3 and 7 of life predicted neonatal hyperthyroidism with a sensitivity 78% (95% CI, 74%-82%) and a and specificity of 99% (95% CI, 98%-100%), a positive predictive value of 90% (95% CI, 87%-93%), a negative predictive value of 98% (95% CI, 97%-99%), and an area under the receiver operating characteristic curve of 0.99 (95% CI, 0.97-1.0). A thyrotropin receptor antibody (TRAb) elimination time was calculated using the equation: 7.28 + 2.88 × log() + 11.62 log(TRAb2). CONCLUSIONS: All newborns with a TSH level of less than 0.90 mIU/L should be examined by a pediatrician. Using TSH, it is possible to screen for neonatal hypothyroidism and for neonatal hyperthyroidism with a TSH cutoff of 0.90 mIU/L, and this shows the relevance of our study in terms of public health.

Study of the Factors Leading to Fetal and Neonatal Dysthyroidism in Children of Patients With Graves Disease.

CONTEXT: Neonatal hyperthyroidism was first described in 1912 and in 1964 was shown to be linked to transplacental passage of maternal antibodies. Few multicenter studies have described the perinatal factors leading to fetal and neonatal dysthyroidism. OBJECTIVE: To show how fetal dysthyroidism (FD) and neonatal dysthyroidism (ND) can be predicted from perinatal variables, in particular, the levels of anti-thyrotropin receptor antibodies (TRAbs) circulating in the mother and child. DESIGN AND PATIENTS: This was a retrospective multicenter study of data from the medical records of all patients monitored for pregnancy from 2007 to 2014. SETTING: Among 280,000 births, the medical records of 2288 women with thyroid dysfunction were selected and screened, and 417 women with Graves disease and positive for TRAbs during pregnancy were included. RESULTS: Using the maternal TRAb levels, the cutoff value of 2.5 IU/L best predicted for FD, with a sensitivity of 100% and specificity of 64%. Using the newborn TRAb levels, the cutoff value of 6.8 IU/L best predicted for ND, with a sensitivity of 100% and a specificity of 94%. In our study, 65% of women with a history of Graves disease did not receive antithyroid drugs during pregnancy but still had infants at risk of ND. CONCLUSIONS: In pregnant women with TRAb levels ≥2.5 IU/L, fetal ultrasound monitoring is essential until delivery. All newborns with TRAb levels ≥6.8 IU/L should be examined by a pediatrician with special attention for thyroid dysfunction and treated, if necessary.

Foetal thyroid dysfunction: treat the mother first!

A case is presented of foetal compensated hypothyroidism due to persisting low maternal serum FT4 at the beginning of pregnancy. Diagnosis was made by means of foetal ultrasound followed by foetal blood sampling because of atypical findings. Foetal thyroid hypertrophy resolved progressively as exogenous thyroxine was administered to the mother. This case highlights once again the importance of adequate thyroid function during pregnancy.