Thyroid stimulating hormone and free thyroxine in pregnancy: expressing concentrations as multiples of the median (MoMs)

Background: Thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations vary during pregnancy and conventional units can vary between laboratories. Reference ranges are widely quoted but are arbitrary and do not allow for inter-laboratory differences or gestational age. We therefore explored using multiple of the median (MoM) values to overcome these limitations. Methods: TSH and FT4 concentrations from 16,346 UK and 5500 Italian women less than 16 weeks of gestation collected as part of the CATS study were converted into MoMs. Effects of maternal age, gestational age, maternal weight, smoking, parity and season of blood sampling were analysed and values adjusted for influencing factors. Distributions of adjusted MoMs were determined. Results: TSH and FT4 (MoMs) significantly reduced the difference between UK and Italian samples (FT4 > TSH) compared with conventional units. TSH and FT4 MoMs were statistically significantly influenced by weight, smoking and parity; season also influenced TSH and age influenced FT4. The first and 99th centile MoMs were TSH 0.2 and 4.01, and FT4 0.75 and 1.39. Conclusion: Use of TSH and FT4 MoMs in early pregnancy allows for systematic differences between laboratories and other factors. Their use indicates high or low levels in a quantitative manner independent of reference ranges

Antenatal thyroid screening and childhood cognitive function

Background. Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function. Methods. We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T4). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T4 levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 μg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments. Results. Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], −1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, −2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results. Conclusions. Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age

Antenatal Thyroid Screening and Childhood Cognitive Function

Background. Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function. Methods. We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T4). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T4 levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 μg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments. Results. Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], −1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, −2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results. Conclusions. Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age