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424: Pregnancy outcomes in women with antithyroid peroxidase antibodies
SMFM Abstracts 421
CAN CURRENT THYROID HORMONE IMMUNOASSAY TECHNIQUES BE RELIED UPON TO IDENTIFY SIGNIFICANT HYPOTHYROIDISM IN PREGNANCY? FIONNUALA M BREATHNACH1, CATHY ROONEY2, ACHIM TREUMANN2, JENNIFER DONNELLY3, SHARON COOLEY3, MICHAEL GEARY3, FERGAL D. MALONE1, 1Royal College of Surgeons in Ireland, Dublin, Ireland, 2Royal College of Surgeons in Ireland, Molecular and Cellular Therapeutics, Dublin, D1, Ireland, 3Rotunda Hospital Dublin, Obstetrics and Gynaecology, Dublin 1, Ireland OBJECTIVE: Concern has been expressed that conventional immunoassay (IA) techniques for evaluating thyroid hormone status may be inaccurate during pregnancy. Mass spectrometry circumvents these problems associated with proteinbinding and antibody positivity, factors that are known to lead to a lack of specificity in current IA techniques for quantification of thyroid hormones. We sought to determine total thyroxine (TT4) concentrations by tandem mass spectrometry in a cohort of healthy primigravid patients at 36 weeks’ gestation and to correlate results with current standard IA determination of thyroid hormone status (thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels). STUDY DESIGN: Thyroid hormone status was determined in 416 healthy primigravid patients with no known history of thyroid disease at 36 weeks’ gestation. An Applied Biosystems API 4000 triple quadrupole mass spectrometer with a high performance liquid chromatography system (LC/MS/MS) was used to determine TT4, while fT4 and TSH were measured using standard electrochemiluminescence technology. IA and LC/MS/MS results were compared using nonparametric correlation coefficients. RESULTS: The mean IA values for TSH and fT4 at 36 weeks’ gestation were 1.5mU/L (SD ⫾ 0.7) and 10.4nmol/L (SD ⫾ 1.6) respectively. Tandem mass spectrometry identified a mean TT4 of 93.2 (nmol/L) (SD ⫾ 36.8). Antithyroid antibodies were identified in 9% (38/416) of patients. Only 18% of patients with a TT4 measurement below the 10th centile had a fT4 level below the 10th centile, while just 4.5% of such patients had a corresponding TSH level above the 98th centile. CONCLUSION: Outlying TT4 values as determined by LC/MS/MS were not reflected in corresponding extremes of IA measurements of fT4 and TSH. The poor correlation between these methods of determining thyroid hormone status particularly in the majority of out-of-range values, suggest that patients at risk for significant hypothyroidism may not be detected using current IA technology.
www.AJOG.org 423
COLLAGEN AND WATER CONCENTRATION CHANGES IN THE PREGNANT RAT CERVIX BARBARA L. MCFARLIN1, HUILING JI2, EDWARD K. S. CHIEN2, WILLIAM D. O’BRIEN, JR.3, MICHAEL L. OELZE3, 1UIC, Maternal Child Nursing, UIUC, Bioacoustics Research Laboratory, Chicago/Urbana, Illinois, 2WIHRI, Maternal Fetal Medicine, Providence, Rhode Island, 3UIUC, Bioacoustics Research Laboratory, Electrical and Computer Engineering, Urbana, Illinois OBJECTIVE: To describe the changes in collagen and water concentration in the pregnant rat cervix as pregnancy progresses. STUDY DESIGN: Cervix concentrations of water, hydroxyproline, soluble collagen, insoluble collagen and tropocollagen were measured in 42 Sprague-Dawley rats (8 each @ 15, 19, 21 days gestation; 9 each @ 17 & 20 days gestation). Water and hydroxyproline were analyzed by Official Methods of Analysis of the Association of Official Analytical Chemists (methods 934.01 & 990.26). Soluble tropocollagen and uncrosslinked collagen were measured by Sircol™ Assay (Biocolor, UK). Tropocollagen was extracted using acetic acid. Uncrosslinked collagen was extracted using acetic acid and pepsin. RESULTS:
Rat cervix collagen and water changes during pregnancy 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.439
422
ANTITHYROID ANTIBODIES IN EARLY PREGNANCY: A MARKER FOR SUBCLINICAL HYPOTHYROIDISM AND POSTPARTUM THYROIDITIS FIONNUALA M BREATHNACH1, SHARON COOLEY2, JENNIFER DONNELLY2, SOHA SAID1, MICHAEL GEARY2, FERGAL D. MALONE1, 1Royal College of Surgeons in Ireland, Obstetrics and Gynaecology, Dublin, Ireland, 2Rotunda Hospital Dublin, Obstetrics and Gynaecology, Dublin 1, Ireland OBJECTIVE: Antithyroid antibodies are prevalent in the general population and have been reported to contribute to the development of hypothyroidism during pregnancy. We sought to determine their contribution to thyroid dysfunction in a low-risk primigravid population. STUDY DESIGN: A consecutive cohort of 986 healthy primigravid patients with no history of thyroid dysfunction was screened for antithyroglobulin (ATG) and anti-thyroid peroxidise (TPO) antibodies in the early second trimester (mean gestation 14 weeks; SD ⫾ 2.6) using electrochemiluminescence technology. Antibodypositive patients had repeat titers measured at 36 weeks’ gestation and at 8 weeks’ postpartum. Antithyroid antibody status was correlated with thyroid hormone status as determined by thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels. Nonparametric correlation coefficients were used for statistical analysis. RESULTS: Antithyroid antibodies were identified in 8.5% (81/956) of the study cohort. Fifty-six patients (5.9%) screened positive for ATG antibodies and 47 (4.9%) screened positive for TPO antibodies, while 22 (2.3%) screened positive for both. Thyroid hormone indices suggestive of diminished thyroid reserve were more marked in the early second trimester than at 36 weeks’ gestation, with 50% of patients positive for both TPO and ATG antibodies having elevated TSH levels (⬎ 90th centile) in the early second trimester, falling to 26% with elevated TSH by 36 weeks. Accompanying hypothyroxinaemia (fT4 ⬍10th centile) was observed in only 18% (2/11) of this group. Antithyroid antibody positivity correlated more closely with the development of hyperthyroid status in the postnatal period than with prenatal hypothyroidism. Postnatal TSH levels below the 10th centile were observed in 45% of patients positive for both antibodies, all of whom had concomitant fT4 levels above the 90th centile. CONCLUSION: The detection of antithyroid antibodies in early pregnancy serves as a prognostic indicator both for subclinical hypothyroidism during pregnancy and for postpartum thyroiditis. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.440
CONCLUSION: The concentration of collagen decreased and water increased significantly as pregnancy progressed, (p⬍.0001). From day 20 to 21 of pregnancy, the concentration of soluble collagen (acid and pepsin extractable) and hydroxyproline decreased by 30%, and insoluble (non-extractable) decreased by 25%. Water concentration increased from 79% (day 15) to 86% (days 20-21). 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.441
424
PREGNANCY OUTCOMES IN WOMEN WITH ANTITHYROID PEROXIDASE ANTIBODIES BRIAN CASEY1, CATHERINE SPONG2, DONALD MCINTIRE1, KENNETH LEVENO1, F. GARY CUNNINGHAM1, 1University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 2National Institutes of Health (NIH), Bethesda, Maryland OBJECTIVE: To estimate the rate of positive antithyroid peroxidase antibody (TPO) levels in the general obstetric population and to compare outcomes in pregnant TPO positive women to those with negative TPO assays. STUDY DESIGN: Between November 2000 and April 2003, all women who presented for prenatal care underwent thyroid screening. Excess serum was frozen and stored at ⫺80°C. Serum samples from women without clinical hypothyroidism who had been screened in the first 20 weeks of gestation and delivered a singleton infant weighing 500 g or more were analyzed for concentrations of thyroid peroxidase antibodies. Serum TPO levels were determined using a chemiluminescent assay (Immulite 2000 Analyzer, Diagnostic Products Corporation). Pregnancy outcomes in women positive for TPO (⬎ 50 IU/mL) were compared to those without TPO. RESULTS: Serum samples from 17,298 women were tested. Of these, 1,012 (6%) women were identified with TPO. Women with TPO were less likely to be black, were older, heavier and more often parous than women without TPO. Placental abruption was 3-fold higher in women with TPO antibodies (OR 3.3; 95% CI,1.6, 6.6) after adjustment for differences in maternal demographics. Seven of the 10 abruptions associated with TPO occurred in women with normal TSH and free thyroxine.
Outcome Abruption Preterm birth ⬍33 weeks ⬍37 weeks
Positive TPO n ⫽ 1,012 10 (1) 18 (1.8) 64 (6)
Negative TPO n ⫽ 16,286
p-value
48 (0.3)
⬍.001
234 (1.4) 936 (6)
.38 .45
CONCLUSION: TPO antibodies are present in 6% of the general obstetric population and are associated with a 3-fold increase in placental abruption. Supported by a grant from the NICHD (HD-04-023). 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.442
S126
American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2007
CAN CURRENT THYROID HORMONE IMMUNOASSAY TECHNIQUES BE RELIED UPON TO IDENTIFY SIGNIFICANT HYPOTHYROIDISM IN PREGNANCY? FIONNUALA M BREATHNACH1, CATHY ROONEY2, ACHIM TREUMANN2, JENNIFER DONNELLY3, SHARON COOLEY3, MICHAEL GEARY3, FERGAL D. MALONE1, 1Royal College of Surgeons in Ireland, Dublin, Ireland, 2Royal College of Surgeons in Ireland, Molecular and Cellular Therapeutics, Dublin, D1, Ireland, 3Rotunda Hospital Dublin, Obstetrics and Gynaecology, Dublin 1, Ireland OBJECTIVE: Concern has been expressed that conventional immunoassay (IA) techniques for evaluating thyroid hormone status may be inaccurate during pregnancy. Mass spectrometry circumvents these problems associated with proteinbinding and antibody positivity, factors that are known to lead to a lack of specificity in current IA techniques for quantification of thyroid hormones. We sought to determine total thyroxine (TT4) concentrations by tandem mass spectrometry in a cohort of healthy primigravid patients at 36 weeks’ gestation and to correlate results with current standard IA determination of thyroid hormone status (thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels). STUDY DESIGN: Thyroid hormone status was determined in 416 healthy primigravid patients with no known history of thyroid disease at 36 weeks’ gestation. An Applied Biosystems API 4000 triple quadrupole mass spectrometer with a high performance liquid chromatography system (LC/MS/MS) was used to determine TT4, while fT4 and TSH were measured using standard electrochemiluminescence technology. IA and LC/MS/MS results were compared using nonparametric correlation coefficients. RESULTS: The mean IA values for TSH and fT4 at 36 weeks’ gestation were 1.5mU/L (SD ⫾ 0.7) and 10.4nmol/L (SD ⫾ 1.6) respectively. Tandem mass spectrometry identified a mean TT4 of 93.2 (nmol/L) (SD ⫾ 36.8). Antithyroid antibodies were identified in 9% (38/416) of patients. Only 18% of patients with a TT4 measurement below the 10th centile had a fT4 level below the 10th centile, while just 4.5% of such patients had a corresponding TSH level above the 98th centile. CONCLUSION: Outlying TT4 values as determined by LC/MS/MS were not reflected in corresponding extremes of IA measurements of fT4 and TSH. The poor correlation between these methods of determining thyroid hormone status particularly in the majority of out-of-range values, suggest that patients at risk for significant hypothyroidism may not be detected using current IA technology.
www.AJOG.org 423
COLLAGEN AND WATER CONCENTRATION CHANGES IN THE PREGNANT RAT CERVIX BARBARA L. MCFARLIN1, HUILING JI2, EDWARD K. S. CHIEN2, WILLIAM D. O’BRIEN, JR.3, MICHAEL L. OELZE3, 1UIC, Maternal Child Nursing, UIUC, Bioacoustics Research Laboratory, Chicago/Urbana, Illinois, 2WIHRI, Maternal Fetal Medicine, Providence, Rhode Island, 3UIUC, Bioacoustics Research Laboratory, Electrical and Computer Engineering, Urbana, Illinois OBJECTIVE: To describe the changes in collagen and water concentration in the pregnant rat cervix as pregnancy progresses. STUDY DESIGN: Cervix concentrations of water, hydroxyproline, soluble collagen, insoluble collagen and tropocollagen were measured in 42 Sprague-Dawley rats (8 each @ 15, 19, 21 days gestation; 9 each @ 17 & 20 days gestation). Water and hydroxyproline were analyzed by Official Methods of Analysis of the Association of Official Analytical Chemists (methods 934.01 & 990.26). Soluble tropocollagen and uncrosslinked collagen were measured by Sircol™ Assay (Biocolor, UK). Tropocollagen was extracted using acetic acid. Uncrosslinked collagen was extracted using acetic acid and pepsin. RESULTS:
Rat cervix collagen and water changes during pregnancy 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.439
422
ANTITHYROID ANTIBODIES IN EARLY PREGNANCY: A MARKER FOR SUBCLINICAL HYPOTHYROIDISM AND POSTPARTUM THYROIDITIS FIONNUALA M BREATHNACH1, SHARON COOLEY2, JENNIFER DONNELLY2, SOHA SAID1, MICHAEL GEARY2, FERGAL D. MALONE1, 1Royal College of Surgeons in Ireland, Obstetrics and Gynaecology, Dublin, Ireland, 2Rotunda Hospital Dublin, Obstetrics and Gynaecology, Dublin 1, Ireland OBJECTIVE: Antithyroid antibodies are prevalent in the general population and have been reported to contribute to the development of hypothyroidism during pregnancy. We sought to determine their contribution to thyroid dysfunction in a low-risk primigravid population. STUDY DESIGN: A consecutive cohort of 986 healthy primigravid patients with no history of thyroid dysfunction was screened for antithyroglobulin (ATG) and anti-thyroid peroxidise (TPO) antibodies in the early second trimester (mean gestation 14 weeks; SD ⫾ 2.6) using electrochemiluminescence technology. Antibodypositive patients had repeat titers measured at 36 weeks’ gestation and at 8 weeks’ postpartum. Antithyroid antibody status was correlated with thyroid hormone status as determined by thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels. Nonparametric correlation coefficients were used for statistical analysis. RESULTS: Antithyroid antibodies were identified in 8.5% (81/956) of the study cohort. Fifty-six patients (5.9%) screened positive for ATG antibodies and 47 (4.9%) screened positive for TPO antibodies, while 22 (2.3%) screened positive for both. Thyroid hormone indices suggestive of diminished thyroid reserve were more marked in the early second trimester than at 36 weeks’ gestation, with 50% of patients positive for both TPO and ATG antibodies having elevated TSH levels (⬎ 90th centile) in the early second trimester, falling to 26% with elevated TSH by 36 weeks. Accompanying hypothyroxinaemia (fT4 ⬍10th centile) was observed in only 18% (2/11) of this group. Antithyroid antibody positivity correlated more closely with the development of hyperthyroid status in the postnatal period than with prenatal hypothyroidism. Postnatal TSH levels below the 10th centile were observed in 45% of patients positive for both antibodies, all of whom had concomitant fT4 levels above the 90th centile. CONCLUSION: The detection of antithyroid antibodies in early pregnancy serves as a prognostic indicator both for subclinical hypothyroidism during pregnancy and for postpartum thyroiditis. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.440
CONCLUSION: The concentration of collagen decreased and water increased significantly as pregnancy progressed, (p⬍.0001). From day 20 to 21 of pregnancy, the concentration of soluble collagen (acid and pepsin extractable) and hydroxyproline decreased by 30%, and insoluble (non-extractable) decreased by 25%. Water concentration increased from 79% (day 15) to 86% (days 20-21). 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.441
424
PREGNANCY OUTCOMES IN WOMEN WITH ANTITHYROID PEROXIDASE ANTIBODIES BRIAN CASEY1, CATHERINE SPONG2, DONALD MCINTIRE1, KENNETH LEVENO1, F. GARY CUNNINGHAM1, 1University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 2National Institutes of Health (NIH), Bethesda, Maryland OBJECTIVE: To estimate the rate of positive antithyroid peroxidase antibody (TPO) levels in the general obstetric population and to compare outcomes in pregnant TPO positive women to those with negative TPO assays. STUDY DESIGN: Between November 2000 and April 2003, all women who presented for prenatal care underwent thyroid screening. Excess serum was frozen and stored at ⫺80°C. Serum samples from women without clinical hypothyroidism who had been screened in the first 20 weeks of gestation and delivered a singleton infant weighing 500 g or more were analyzed for concentrations of thyroid peroxidase antibodies. Serum TPO levels were determined using a chemiluminescent assay (Immulite 2000 Analyzer, Diagnostic Products Corporation). Pregnancy outcomes in women positive for TPO (⬎ 50 IU/mL) were compared to those without TPO. RESULTS: Serum samples from 17,298 women were tested. Of these, 1,012 (6%) women were identified with TPO. Women with TPO were less likely to be black, were older, heavier and more often parous than women without TPO. Placental abruption was 3-fold higher in women with TPO antibodies (OR 3.3; 95% CI,1.6, 6.6) after adjustment for differences in maternal demographics. Seven of the 10 abruptions associated with TPO occurred in women with normal TSH and free thyroxine.
Outcome Abruption Preterm birth ⬍33 weeks ⬍37 weeks
Positive TPO n ⫽ 1,012 10 (1) 18 (1.8) 64 (6)
Negative TPO n ⫽ 16,286
p-value
48 (0.3)
⬍.001
234 (1.4) 936 (6)
.38 .45
CONCLUSION: TPO antibodies are present in 6% of the general obstetric population and are associated with a 3-fold increase in placental abruption. Supported by a grant from the NICHD (HD-04-023). 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.442
S126
American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2007