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ABSTRACT: Background: Thyroid disease during pregnancy may be associated with increased risk of various pregnancy complications. It is known that serum thyroid stimulating hormone (TSH) is suppressed by human chorionic gonadotrophin (hCG) in early pregnancy, and that higher hCG levels in twin pregnancies may cause a more pronounced physiologic suppression, this is important to avoid unnecessary concern and facilitate the diagnosis of overt thyroid disease in twin pregnancy. The aim of this study is to establish normal ranges of maternal serum TSH, and free thyroxine (FT4) at 11-13 weeks' gestation in twin pregnancy. Methods: This was a case series of 177 dichorionic and 58 monochorionic twin pregnancies with normal outcome and 19 monochorionic pregnancies complicated by severe twin-to-twin transfusion syndrome (TTTS). Maternal serum concentrations of TSH, FT4, anti-thyroperoxidase and anti-thyroglobulin antibodies were measured at 11-13 weeks' gestation. The measured TSH and FT4 were converted to multiple of median (MoM) of normal singleton pregnancy and MoM values in the different groups were compared. Results: In the antithyroid antibody negative twin pregnancies with normal outcome, compared to singletons, serum TSH MoM was lower (median 0.62, IQR 0.16-1.18 vs. 1.01, IQR 0.61-1.51; P<0.0001), FT4 MoM was not significantly different (median 0.98, IQR 0.91-1.08 vs. 0.99, IQR 0.91-1.09; P=0.975) and free ß-hCG MoM was higher (median 1.91, IQR 1.33-2.59 vs. 0.98, IQR 0.66-1.50; P<0.0001). In the antibody-positive group (n=37), compared to the negative group (n=198), the median TSH was higher but FT4 and free ß-hCG were not significantly different. In the TTTS group, compared to normal twin pregnancies, TSH, FT4 and free ß-hCG were not significantly different. Conclusion: In twins, compared to singleton pregnancies, TSH is lower but FT4 is not significantly different. These normal ranges of thyroid hormones in twins can form the basis for the study of early thyroid function in pathological pregnancies and the investigation of the consequences of overt and subclinical hypothyroidism on twin pregnancy outcome.
Thyroid: official journal of the American Thyroid Association 05/2013; · 2.60 Impact Factor
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ABSTRACT: We sought to assess performance of noninvasive prenatal testing for fetal trisomy in a routinely screened first-trimester pregnancy population.
This was a cohort study of 2049 pregnant women undergoing routine screening for aneuploidies at 11-13 weeks' gestation. Plasma cell-free DNA analysis using chromosome-selective sequencing was used. Laboratory testing on a single plasma sample of 2 mL was carried out blindly and results were provided as risk score (%) for trisomies 21 and 18.
Trisomy risk scores were given for 95.1% (1949 of 2049) of cases including all 8 with trisomy 21 and 2 of the 3 with trisomy 18. The trisomy risk score was >99% in the 8 cases of trisomy 21 and 2 of trisomy 18 and <1% in 99.9% (1937 of 1939) of euploid cases.
Noninvasive prenatal testing using chromosome-selective sequencing in a routinely screened population identified trisomies 21 and 18 with a false-positive rate of 0.1%.
American journal of obstetrics and gynecology 11/2012; 207(5):374.e1-6. · 3.28 Impact Factor
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ABSTRACT: Objective: To assess the performance of chromosome-selective sequencing of maternal plasma cell-free DNA (cfDNA) in non-invasive prenatal testing (NIPT) for trisomy 13. Study design: Two phase case-control study on a single plasma sample per case. The first phase was used to optimize the trisomy 13 algorithm which was then applied to a second dataset to determine risk score for trisomy 13 by laboratory personnel who were blinded to fetal karyotype Results: In the first phase, trisomy 13 risk scores were given for 11 cases of trisomy 13 and 145 euploid cases at 11-13 weeks' gestation. The test identified 7 (63.6%) cases of trisomy 13 with no false positives. The trisomy 13 algorithm was subsequently modified and the trisomy 13 risk score was >99% in all 11 cases of trisomy 13 and <0.01% in all 145 euploid cases. In the second phase, the new algorithm was used to generate trisomy 13 risk scores for 10 cases of trisomy 13 and 1,939 euploid cases. The trisomy 13 risk scores were >99% in 8 (80%, 95% CI 49.0%-94.3%) cases of trisomy 13. In the 1,939 euploid cases the risk score for trisomy 13 was <0.01% in 1,937 (99.9%), 0.79% in 1, and >99% in 1. Therefore, at the predefined risk cut-off of 1% for classifying a sample as high versus low-risk, the false positive rate (FPR) was 0.05% (95% CI 0.0%-0.3%). Conclusions: Chromosome-selective sequencing of cfDNA can detect the majority of cases of trisomy 13 at FPR of less than 0.1%. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound in Obstetrics and Gynecology 09/2012; · 3.01 Impact Factor
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ABSTRACT: It was the aim of this study to examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free DNA (cfDNA) at 11-13 weeks' gestation.
In a nested case-control study, cfDNA was extracted from maternal plasma obtained before chorionic villous sampling from 300 euploid, 50 trisomy 21 and 50 trisomy 18 pregnancies at 11-13 weeks' gestation. Chromosome-selective sequencing of maternal cfDNA non-polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of DNA which is of fetal origin. Multivariate regression analysis was used to determine which of the factors amongst maternal weight, racial origin, smoking status, plasma storage time, serum pregnancy-associated plasma protein (PAPP)-A and free β-subunit of human chorionic gonadotropin (β-hCG), fetal crown-rump length, nuchal translucency thickness, gender and karyotype were significant predictors of the fetal fraction.
Significant independent prediction of fetal fraction was provided by maternal weight, serum PAPP-A and serum free β-hCG multiples of the median, but not by other maternal characteristics, fetal karyotype, crown-rump length or nuchal translucency thickness. Fetal fraction increased with serum metabolite levels and decreased with maternal weight.
The fetal fraction in maternal plasma cfDNA increases with serum PAPP-A and free β-hCG and decreases with maternal weight.
Fetal Diagnosis and Therapy 05/2012; 31(4):237-43. · 1.05 Impact Factor
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ABSTRACT: The purpose of this study was to assess the prenatal detection rate of trisomy 21 and 18 and the false-positive rate by chromosome-selective sequencing of maternal plasma cell-free DNA.
Nested case-control study of cell-free DNA was examined in plasma that was obtained at 11-13 weeks before chorionic villous sampling from 300 euploid pregnancies, 50 pregnancies with trisomy 21, and 50 pregnancies with trisomy 18. Laboratory personnel were blinded to fetal karyotype.
Risk scores for trisomy 21 and 18 were given for 397 of the 400 samples that were analyzed. In all 50 cases of trisomy 21, the risk score for trisomy 21 was ≥ 99%, and the risk score for trisomy 18 was ≤ 0.01%. In all 50 cases of trisomy 18, the risk score for trisomy 21 was ≤ 0.01%, and the risk score for trisomy 18 was ≥ 99% in 47 cases, 98.8% in 1 case, 88.5% in 1 case, and 0.11% in 1 case. In 3 of the 300 euploid pregnancies (1%), no risk score was provided, because there was failed amplification and sequencing. In the remaining 297 cases, the risk score for trisomy 21 was ≤ 0.01%, and the risk score for trisomy 18 was ≤ 0.01% in 295 cases, 0.04% in 1 case, and 0.23% in 1 case. Therefore, the sensitivity for detecting trisomy 21 was 100% (50/50 cases); the sensitivity for trisomy 18 was 98% (49/50 cases), and the specificity was 100% (297/297 cases).
In this study, chromosome-selective sequencing of cell-free DNA separated all cases of trisomy 21 and 98% of trisomy 18 from euploid pregnancies.
American journal of obstetrics and gynecology 04/2012; 206(4):322.e1-5. · 3.28 Impact Factor
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ABSTRACT: Studies have shown that altered thyroid function in early pregnancy may affect normal placental development and hence fetal growth. Our hypothesis is that maternal thyroid function in the first trimester is altered in pregnancies that subsequently deliver small for gestational age (SGA) neonates.
Maternal serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured at 11(+0) to 13(+6) weeks' gestation in 212 singleton pregnancies with no history of thyroid disease that subsequently delivered SGA neonates and the values were compared with the results of 3598 normal pregnancies delivering neonates with birth weight above the 5th percentile for gestation.
There were no significant differences between the normal and SGA groups in median multiple of the median (MoM) TSH (1.07 vs. 1.061 MoM), FT4 (0.992 vs. 1.010 MoM), and FT3 (0.991 vs. 0.990 MoM).
In women with no history of thyroid disease delivering SGA neonates, thyroid function during the first trimester of pregnancy is not significantly different from women delivering non-SGA neonates.
Thyroid: official journal of the American Thyroid Association 08/2011; 21(10):1127-31. · 2.60 Impact Factor
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ABSTRACT: To estimate the possible association between spontaneous early preterm delivery and maternal thyroid dysfunction in early pregnancy.
Maternal serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine, antithyroperoxidase, and antithyroglobulin antibodies at 11-13 weeks of gestation were compared in 102 singleton pregnancies, resulting in spontaneous delivery before 34 weeks and 4,318 normal pregnancies delivering after this gestation.
In the preterm delivery group, compared with the normal outcome group, there was no significant difference in antithyroid antibody positivity (16.7% compared with 16.8%). In the antithyroid antibody-negative pregnancies in the preterm delivery group, compared with the normal outcome group, the median free thyroxine multiple of the median was reduced (0.94 compared with 0.99 multiple of the median, P<.001), but the median TSH multiple of the median was not significantly different (0.99 compared with 1.01 multiple of the median, P=.331).
In pregnancies resulting in spontaneous early preterm delivery, there is no evidence of increased prevalence of antithyroid antibody positivity or maternal thyroid dysfunction at 11-13 weeks.
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Obstetrics and Gynecology 02/2011; 117(2 Pt 1):293-8. · 4.73 Impact Factor
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ABSTRACT: To examine the association between maternal serum levels of thyroid stimulating hormone (TSH) and free β-human chorionic gonadotrophin (free β-hCG) in trisomy 21, trisomy 18 and euploid pregnancies at 11-13 weeks and investigate the potential value of TSH in first-trimester screening for aneuploidies.
Maternal serum TSH and free β-hCG levels at 11-13 weeks in 25 trisomy 21 and 25 trisomy 18 pregnancies were compared with levels in 3592 unaffected pregnancies. Only women with no history of thyroid disease and negative for antithyroid antibodies were included.
Serum TSH in the trisomy 21 pregnancies was lower [0.76 multiples of the normal median (MoM), interquartile range (IQR) 0.46-1.09 MoM] and in trisomy 18 it was higher (1.25 MoM, IQR 0.88-1.98 MoM) than in unaffected pregnancies (1.01 MoM, IQR 0.61-1.51 MoM). There were significant associations between TSH and free β-hCG in the unaffected pregnancies (r = - 0.214, p < 0.0001), but not in those with trisomy 21 (r = - 0.157, p = 0.452) or trisomy 18 (r = - 0.176, p = 0.401).
hCG, rather than TSH, may be the primary thyrotropic factor in early pregnancy. Measurement of TSH does not improve the performance of screening for trisomies 21 and 18 provided by nuchal translucency, free β-hCG and pregnancy-associated plasma protein-A.
Prenatal Diagnosis 01/2011; 31(1):33-7. · 2.11 Impact Factor
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ABSTRACT: To determine if maternal thyroid function in the first trimester is altered in pregnancies that subsequently develop preeclampsia (PE).
Mean arterial pressure (MAP), uterine artery pulsatility index (PI) maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) at 11 to 13 weeks of gestation were measured in 102 singleton pregnancies that subsequently developed PE, and the values were compared to the results of 4318 normal pregnancies.
In both the PE groups that required delivery before 34 weeks (early-PE) and the late-PE group, compared with the unaffected group, the median MAP multiple of the normal median (MoM) and uterine artery PI MoM were significantly increased. In late-PE but not in early-PE, compared with the unaffected group, the median TSH MoM was significantly increased and the median FT4 MoM was decreased. Logistic regression analysis demonstrated that TSH MoM provided a significant contribution in the prediction of late-PE.
Impaired thyroid function may predispose to the development of late-PE, and measurement of maternal serum TSH can improve the prediction of late-PE provided by a combination of factors in the maternal history and the measurements of MAP and uterine artery PI.
Prenatal Diagnosis 11/2010; 30(11):1032-8. · 2.11 Impact Factor
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ABSTRACT: Studies have shown that overt hypothyroidism is associated with a substantial risk of miscarriage. There is controversy as to whether subclinical hypothyroidism has the same effect and whether such effect is mediated by the presence of antithyroid antibodies. Our hypothesis is that maternal thyroid function in the first trimester is altered in pregnancies ending in miscarriage or fetal death.
Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine, anti-thyroperoxidase antibody, and anti-thyroglobulin antibody at 11-13 weeks of gestation were measured in 202 singleton pregnancies that subsequently resulted in miscarriage or fetal death, and the values were compared with the results of 4318 normal pregnancies.
In the fetal loss group, compared to the unaffected group, there was an increase in median TSH multiple of the normal median (1.133 vs. 1.007 MoM), decrease in median FT4 MoM (0.958 vs. 0.992 MoM), and increase in the incidence of TSH above the 97.5th centile (5.9% vs. 2.5%) and FT4 below the 2.5th centile (5.0% vs. 2.5%). Logistic regression analysis demonstrated that in the prediction of fetal loss there were significant contributions from FT4 MoM, maternal black ethnic origin, history of chronic hypertension, and use of ovulation drugs. The prevalence of antithyroid antibody positivity was not significantly different in the fetal loss group compared to that of normal pregnancies (15.3% vs. 16.8%).
Impaired thyroid function may predispose to miscarriage and fetal death.
Thyroid: official journal of the American Thyroid Association 09/2010; 20(9):989-93. · 2.60 Impact Factor
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ABSTRACT: To establish normal ranges of maternal serum thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) at 11-13 weeks of gestation.
Maternal serum concentrations of FT3, FT4, TSH, anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were measured at 11-13 weeks. Normal ranges were constructed from the data of singleton pregnancies with no anti-thyroid antibodies resulting in live births after 34 weeks of phenotypically normal neonates with birth weight above the 5th percentile. Adjustments were made for maternal characteristics found by multiple regression analysis to affect the levels of TSH, FT3 and FT4.
3,592 of the 4,318 pregnancies examined were antibody negative, and in this group serum TSH increased whereas FT3 and FT4 decreased with gestation, and all three were lower in black than in white women. Serum FT3 and FT4 decreased but TSH did not change significantly with maternal age; TSH and FT3 increased whereas FT4 decreased with body mass index; TSH decreased whereas FT3 and FT4 increased with serum free beta-hCG. In the antibody-positive group, compared to the negative group, median TSH was higher and median FT3 and FT4 were lower.
The study established normal ranges for maternal thyroid function at 11-13 weeks.
Fetal Diagnosis and Therapy 01/2010; 27(3):156-63. · 1.05 Impact Factor
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ABSTRACT: The aim of this study in pregnant women with hypothyroidism treated by levothyroxine is to examine the interrelations between thyroid-stimulating hormone (TSH), free thyroxine (FT(4)) and free tri-iodothyronine (FT(3)), and examine whether in such patients the treatment is adequate.
This was a retrospective cross-sectional study. Maternal serum concentrations of FT(3), FT(4) and TSH were measured at 11-13 weeks in 164 singleton pregnancies from women with hypothyroidism before pregnancy receiving treatment with thyroxine. The values were compared to the results in 4,318 normal singleton pregnancies.
In the hypothyroid group, compared to the normal group, there was an increase in median TSH (1.990 vs. 1.007 MoM) and FT(4) (1.052 vs. 0.992 MoM) and decrease in FT(3) (0.901 vs. 0.991 MoM). Serum FT(4) was at or above the 2.5th centile in 158 (96.3%) cases but TSH was above the 97.5th centile in 48 (29.3%) and FT(3) was below the 2.5th centile in 49 (29.9%) cases. In both the hypothyroid and unaffected groups there were significant associations between TSH and FT(4), TSH and FT(3) and between FT(3) and FT(4).
In a high proportion of pregnant women with hypothyroidism treated with levothyroxine there is evidence of persistent hypothyroidism because the treatment is inadequate in correcting the levels of FT(3).
Fetal Diagnosis and Therapy 01/2010; 28(1):22-7. · 1.05 Impact Factor
