Jane Cleary-Goldman

Impact of maternal age on obstetric outcome

OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes. METHODS: A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35–39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patients study site. RESULTS: A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35–39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35–39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35–39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. CONCLUSION: Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect. LEVEL OF EVIDENCE: II-2

Maternal thyroid hypofunction and pregnancy outcome.

OBJECTIVE: To estimate whether maternal thyroid hypofunction is associated with complications. METHODS: A total of 10,990 patients had first- and second-trimester serum assayed for thyroid-stimulating hormone (TSH), free thyroxine (freeT4), and antithyroglobulin and antithyroid peroxidase antibodies. Thyroid hypofunction was defined as 1) subclinical hypothyroidism: TSH levels above the 97.5th percentile and free T4 between the 2.5th and 97.5th percentiles or 2) hypothyroxinemia: TSH between the 2.5th and 97.5th percentiles and free T4 below the 2.5th percentile. Adverse outcomes were evaluated. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between the 2.5th and 97.5th percentiles). Patients with and without antibodies were compared. Multivariable logistic regression analysis adjusted for confounders was used. RESULTS: Subclinical hypothyroidism was documented in 2.2% (240 of 10,990) in the first and 2.2% (243 of 10,990) in the second trimester. Hypothyroxinemia was documented in 2.1% (232 of 10,990) in the first and 2.3% (247 of 10,990) in the second trimester. Subclinical hypothyroidism was not associated with adverse outcomes. In the first trimester, hypothyroxinemia was associated with preterm labor (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.00–2.62) and macrosomia (aOR 1.97; 95% CI 1.37–2.83). In the second trimester, it was associated with gestational diabetes (aOR 1.7; 95% CI 1.02–2.84). Fifteen percent (1,585 of 10,990) in the first and 14% (1,491 of 10,990) in the second trimester had antithyroid antibodies. When both antibodies were positive in either trimester, there was an increased risk for preterm premature rupture of membranes (P=.002 and P<.001, respectively). CONCLUSION: Maternal thyroid hypofunction is not associated with a consistent pattern of adverse outcomes. LEVEL OF EVIDENCE: II

First- and second-trimester thyroid hormone reference data in pregnant women: a FaSTER (First- and Second-Trimester Evaluation of Risk for aneuploidy) Research Consortium study

OBJECTIVE The purpose of this study was to calculate first and second trimester reference ranges and within-woman correlations for TSH, free T4, and thyroid antibodies. STUDY DESIGN TSH, free T4, and thyroid antibodies were measured in paired sera from 9562 women in the FaSTER trial of Down syndrome screening. RESULTS The median first trimester TSH (1.05 mIU/L) is lower than the second (1.23 mIU/L); and 98th centile is higher (4.15 vs 3.77 mIU/L). Within-woman paired TSH correlations are moderately strong (r(2) = 0.64). Among women with first trimester TSH values above the 98th centile, second trimester values are over the 95th centile in 68%. Median first trimester free T4 values (1.10 ng/dL) are higher than second (1.01 ng/dL). Paired free T4 measurements correlate weakly (r(2) = 0.23). Among women with first trimester free T4 values below the 2nd centile, second trimester values are below the 5th centile in 32%. Antibody measurements correlate strongly between trimesters (thyroperoxidase r(2) = 0.79, thyroglobulin r(2) = 0.83). CONCLUSION TSH and free T4 measurements require gestation-specific reference ranges.

Variability in Thyroid-Stimulating Hormone Suppression by Human Chronic Gonadotropin during Early Pregnancy

OBJECTIVE The objective of the study was to further explore relationships between human chorionic gonadotropin (hCG), TSH, and free T4 in pregnant women at 11 through 18 wk gestation. STUDY DESIGN The design of the study was to analyze hCG in comparison with TSH and free T4, in paired first- and second-trimester sera from 9562 women in the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy trial study. RESULTS hCG is strongly correlated with body mass index, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T4. As hCG deciles increase, body mass index and percent of women who smoke both decrease, whereas the percent of primigravid women increases (P < 0.0001). hCG/TSH correlations are weak in both trimesters (r2 = 0.03 and r2 = 0.02). TSH concentrations at the 25th and fifth centiles become sharply lower at higher hCG levels, whereas 50th centile and above TSH concentrations are only slightly lower. hCG/free T4 correlations are weak in both trimesters (r2 = 0.06 and r2 = 0.003). At 11-13 wk gestation, free T4 concentrations rise uniformly at all centiles, as hCG increases (test for trend, P < 0.0001), but not at 15-18 wk gestation. Multivariate analyses with TSH and free T4 as dependent variables and selected maternal covariates and hCG as independent variables do not alter these observations. CONCLUSIONS In early pregnancy, a womans centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland. hCG affects lower centile TSH values disproportionately.

Screening for down syndrome : Practice patterns and knowledge of obstetricians and gynecologists

OBJECTIVE: To assess obstetricians’ practice patterns and knowledge regarding screening for Down syndrome. METHODS: A questionnaire was mailed to 1,105 American College of Obstetricians and Gynecologists Fellows and Junior Fellows in 2004. RESULTS: Sixty percent of questionnaires were returned. Statistical analyses were limited to the 532 practicing obstetricians. Greater than 80% felt their training and experience qualified them to counsel patients about genetic issues in pregnancy. However, 45% rated their residency training regarding prenatal diagnosis as barely adequate or nonexistent. American College of Obstetricians and Gynecologists publications were rated by 86% as an important source of information on genetic counseling. Seventy-eight percent of practitioners counsel all obstetric patients about risks for fetal aneuploidy, and 67% provide counseling for heritable genetic abnormalities. Although the majority (99%) offer second-trimester Down syndrome screening, only 55% also offer first-trimester screening for Down syndrome. Almost one half (49%) use the quad screen, and 6% offer integrated first- and second-trimester screening. The majority (88%) routinely offer amniocentesis to patients who are at elevated risk for genetic abnormalities, whereas 44% also offer chorionic villus sampling. Few (2%) perform chorionic villus sampling. CONCLUSION: Most obstetricians manage patients at risk for fetal genetic abnormalities according to American College of Obstetricians and Gynecologists educational materials. This survey identified deficiencies related to Down syndrome screening, including a limited number of practitioners performing chorionic villus sampling and physicians’ own perception that training regarding genetic counseling should be improved. Educational strategies are needed to address these deficiencies before first-trimester screening programs are widely implemented. LEVEL OF EVIDENCE: III

Thyroperoxidase and thyroglobulin antibodies in early pregnancy and preterm delivery.

OBJECTIVE: To further evaluate the relationship between thyroid antibodies and preterm births. METHODS: This is a prospective study of pregnancy outcome and demographic data combined with retrospective measurement of thyroperoxidase and thyroglobulin antibodies. Sera were obtained at 11–13 and 15–18 weeks of gestation from 10,062 women with singleton viable pregnancies (a subset from the First- and Second-Trimester Risk of Aneuploidy [FaSTER] trial). RESULTS: Women with elevated levels of thyroperoxidase, thyroglobulin antibodies, or both in the first trimester have a higher rate of preterm delivery before 37 weeks of gestation than antibody-negative women (7.5% compared with 6.4%, odds ratio [OR] 1.18; 95% confidence interval [CI] 0.95–1.46). This is also the case for very preterm delivery before 32 weeks of gestation (1.2% compared with 0.7%, OR 1.70; 95% CI 0.98–2.94). Preterm premature rupture of membranes is also increased (2.0% compared with 1.2%, OR 1.67; 95% CI 1.05–2.44). These associations are less strong for second-trimester antibody measurements. CONCLUSION: The present data do not confirm strong associations between thyroid antibody elevations and preterm birth found in three of five previously published reports. Preterm premature rupture of membranes appears to contribute to the thyroid antibody-associated early deliveries, possibly as a result of inflammation. LEVEL OF EVIDENCE: II

Maintaining quality assurance for sonographic nuchal translucency measurement : lessons from the FASTER Trial

To evaluate nuchal translucency measurement quality assurance techniques in a large‐scale study.

Sequential first- and second-trimester TSH, free thyroxine, and thyroid antibody measurements in women with known hypothyroidism: a FaSTER trial study

OBJECTIVE The purpose of this study was to examine how closely hypothyroidism management in the general pregnancy population satisfies recently issued guidelines and to determine whether improvements are indicated. STUDY DESIGN This was an observational study in which women at 5 recruitment centers in the first- and second-trimester evaluation of risk for aneuploidy trial allowed the use of sequentially obtained first- and second-trimester sera for additional research. Three hundred eighty-nine women had hypothyroidism by self-report. Thyroid-related measurements were performed on all samples between July 2004 and May 2005. RESULTS Forty-three percent of the thyroid-stimulating hormone (TSH) values are at or above recently recommended guidelines in the first trimester (2.5 mU/L), as opposed to 33% of the values in the second trimester (3.0 mU/L). Twenty percent of the TSH values are at or above a less restrictive 98th percentile of normal in the first trimester, as opposed to 23% of the values in the second trimester. Mean TSH levels are higher in women with antibodies. Free thyroxine values are unremarkable. CONCLUSION Future strategies should focus on more effectively treating women with hypothyroidism who have persistently elevated TSH values.

The urological care and outcome of pregnancy after urinary tract reconstruction

To assess the obstetric and urological outcomes during and after pregnancy following urinary tract reconstruction, as pregnancies after such surgery can have a significant effect on the function of the reconstructed urinary tract, and the reconstruction can significantly affect the delivery of the fetus.

Management of single fetal demise in a multiple gestation.

Intrauterine fetal demise of 1 twin in a multiple gestation is a complex clinical situation. Chorionicity, gestational age at diagnosis, problems specific to the pregnancy, and the emotional needs of the patient can impact management. Strategies to optimize outcomes may include a multidisciplinary team approach and fetal surveillance. The following article reviews (1) adverse fetal and neonatal outcomes associated with intrauterine fetal demise of 1 twin, (2) the potential maternal impact, and (3) the strategies to possibly prevent poor outcomes. It is important to remember that even the most vigilant care may not avoid adverse sequelae in a portion of at-risk pregnancies. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to outline the factors that impact outcome in patients with multiples complicated by a single IUFD, to describe the pathophysiology of adverse outcomes associated with IUFD of one twin, and to list potential strategies for twin pregnancies at risk for IUFD.