Antenatal screening for thyroid dysfunction: pre-term birth, low birth-weight, and growth restriction.

OBJECTIVE: To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment. METHODS: This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile). RESULTS: Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21-2.36, p < .002) and low birth-weight (RR 1.72, 95% CI 1.13-2.62, p < .02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78-4.14, p = .16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93-1.65, p = .14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight. CONCLUSIONS: Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery.

The prevalence of maternal hypothyroidism in first trimester screening from 11 to 14 weeks of gestation.

AIM: The aim of this study was to determine the prevalence of maternal hypothyroidism in the first trimester from 11 to 14 weeks of gestation according to the American Thyroid Association (ATA) guidelines from 2017 and to compare the rates for singleton and twin pregnancies. METHODS: A total of 4965 consecutive Caucasian singleton pregnancies and 109 Caucasian twin pregnancies were included in the investigation. Patients with a history of thyroid gland disorder were excluded. Subclinical maternal hypothyroidism was defined as a thyroid stimulating hormone (TSH) concentration above the 97.5th percentile and free thyroxine (fT4) within the range of a reference population of women at 11-14 weeks of gestation. Overt maternal hypothyroidism was defined as a TSH concentration above the 97.5th percentile and an fT4 below the 2.5th percentile of the reference population.TSH, fT4, and anti thyroid peroxidase antibody (TPOAb) were measured by immunochemiluminescent assays on an 16200 Abbott Architect analyzer. RESULTS: The prevalence of hypothyroidism for twin pregnancies was no higher than that for singleton pregnancies; 6.42% (7/109) vs. 5.32% (264/4965), respectively; P=0.61. All twin pregnancies were subclinical. Singleton hypothyroid pregnancies included 4.91% (244 cases) of subclinical and 0.41% (20 cases) of overt hypothyroidism. The prevalence of TPOAb positive hypothyroid women for twin pregnancies and singleton pregnancies was 71% (5/7) vs. 52% (137/264 cases), respectively but the differences were not statistically significant; P=0.31. CONCLUSION: Each first trimester screening center should establish its TSH and fT4 reference ranges. Our center had higher upper reference limits of TSH than that of the universally fixed limit of 2.5 mU/L, which led to a lower measured prevalence of maternal hypothyroidism. A large number of hypothyroid women were TPOAb positive.

Maternal thyroid-stimulating hormone reference ranges for first trimester screening from 11 to 14 weeks of gestation.

BACKGROUND: To establish maternal thyroid-stimulating hormone (TSH) reference ranges for first trimester screening from 11 + 0 to 13 + 6 weeks of gestation. METHODS: A total of 10 592 singleton and 201 twin consecutive Caucasian pregnant women who underwent simultaneously prenatal first trimester Down's syndrome screening and thyroid function screening from January 2010 to November 2017 were included in the study. Women with positive antithyroid peroxidase antibody (TPOAb) and positive personal history of thyroid disease were previously excluded. TSH was measured by immunochemiluminescent assay on ci 16200 Abbott Architect analyzer. Nonparametric percentile method (also known as CLSI C28.A3) was used for the determination of reference ranges. RESULTS: We established reference ranges of TSH for the period of gestation from 11 + 0 to 13 + 6 weeks of pregnancy as 0.16-3.43 mU/L for singleton Caucasian pregnancies and 0.02-2.95 mU/L for twin Caucasian pregnancies. The median (IQR) of TSH for singleton pregnancies was higher than that for twin pregnancies (1.25 mU/L (0.83-1.81) vs 0.84 (0.37-1.47), respectively; P < .0001). CONCLUSIONS: Each first trimester screening center should be aware of which type of immunoassay their laboratory uses. TSH reference ranges in women during the first trimester of pregnancy are lower than those for general population. Twin pregnancies have lower TSH than singleton pregnancies.

Incorporating thyroid markers in Down syndrome screening protocols.

OBJECTIVE: The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. METHODS: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. RESULTS: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. CONCLUSIONS: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd.