William A. Grobman

Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum

Pregnancy has a profound impact on the thyroid gland and thyroid function. The gland increases 10% in size during pregnancy in iodine-replete countries and by 20%– 40% in areas of iodine deficiency. Production of thyroxine (T4) and triiodothyronine (T3) increases by 50%, along with a 50% increase in the daily iodine requirement. These physiological changes may result in hypothyroidism in the later stages of pregnancy in iodine-deficient women who were euthyroid in the first trimester. The range of thyrotropin (TSH), under the impact of placental human chorionic gonadotropin (hCG), is decreased throughout pregnancy with the lower normal TSH level in the first trimester being poorly defined and an upper limit of 2.5 mIU/L. Ten percent to 20% of all pregnant women in the first trimester of pregnancy are thyroid peroxidase (TPO) or thyroglobulin (Tg) antibody positive and euthyroid. Sixteen percent of the women who are euthyroid and positive for TPO or Tg antibody in the first trimester will develop a TSH that exceeds 4.0 mIU/L by the third trimester, and 33%–50% of women who are positive for TPO or Tg antibody in the first trimester will develop postpartum thyroiditis. In essence, pregnancy is a stress test for the thyroid, resulting in hypothyroidism in women with limited thyroidal reserve or iodine deficiency, and postpartum thyroiditis in women with underlying Hashimoto’s disease who were euthyroid prior to conception. Knowledge regarding the interaction between the thyroid and pregnancy/the postpartum period is advancing at a rapid pace. Only recently has a TSH of 2.5 mIU/L been accepted as the upper limit of normal for TSH in the first trimester. This has important implications in regards to interpretation of the literature as well as a critical impact for the clinical diagnosis of hypothyroidism. Although it is well accepted that overt hypothyroidism and overt hyperthyroidism have a deleterious impact on pregnancy, studies are now focusing on the potential impact of subclinical hypothyroidism and subclinical hyperthyroidism on maternal and

Sleep Disturbances in Pregnancy

OBJECTIVE: To estimate the prevalence and patterns of sleep disturbances during pregnancy among healthy nulliparous women. METHODS: This was a prospective, cohort study of healthy nulliparous women, recruited between 6 and 20 weeks of gestation, who completed a baseline sleep survey at enrollment with follow-up in the third trimester. The survey was composed of the following validated sleep questionnaires: Berlin Questionnaire for Sleep Disordered Breathing, Epworth Sleepiness Scale, National Institutes of Health/International Restless Legs Syndrome Question Set, Women’s Health Initiative Insomnia Rating Scale, and the Pittsburgh Sleep Quality Index. Differences in sleep characteristics between the baseline and third trimester were compared using the paired t test or McNemar test for continuous or categorical data, respectively. RESULTS: One hundred eighty-nine women completed both baseline and follow-up sleep surveys. The mean gestational age was 13.8 (±3.8) and 30.0 (±2.2) weeks at the first and second surveys, respectively. Compared with the baseline assessment, mean sleep duration was significantly shorter (7.4 [±1.2] hours compared with 7.0 [±1.3] hours, P<.001), and the proportion of patients who reported frequent snoring (at least three nights per week) was significantly greater (11% compared with 16.4%, P=.03) in the third trimester. The percentage of patients who met diagnostic criteria for restless leg syndrome increased from 17.5% at recruitment to 31.2% in the third trimester (P=.001). Overall poor sleep quality, as defined by a Pittsburgh Sleep Quality Index score greater than 5, became significantly more common as pregnancy progressed (39.0% compared with 53.5%, P=.001). CONCLUSION: Sleep disturbances are prevalent among healthy nulliparous women and increase significantly during pregnancy. LEVEL OF EVIDENCE: II

Development of a nomogram for prediction of vaginal birth after cesarean delivery.

OBJECTIVE: To develop a model based on factors available at the first prenatal visit that predicts chance of successful vaginal birth after cesarean delivery (VBAC) for individual patients who undergo a trial of labor. METHODS: All women with one prior low transverse cesarean who underwent a trial of labor at term with a vertex singleton gestation were identified from a concurrently collected database of deliveries at 19 academic centers during a 4-year period. Using factors identifiable at the first prenatal visit, we analyzed different classification techniques in an effort to develop a meaningful prediction model for VBAC success. After development and cross-validation, this model was represented by a graphic nomogram. RESULTS: Seven-thousand six hundred sixty women were available for analysis. The prediction model is based on a multivariable logistic regression, including the variables of maternal age, body mass index, ethnicity, prior vaginal delivery, the occurrence of a VBAC, and a potentially recurrent indication for the cesarean delivery. After analyzing the model with cross-validation techniques, it was found to be both accurate and discriminating. CONCLUSION: A predictive nomogram, which incorporates six variables easily ascertainable at the first prenatal visit, has been developed that allows the determination of a patient-specific chance for successful VBAC for those women who undertake trial of labor. LEVEL OF EVIDENCE: II

Chronic stress and low birth weight neonates in a low-income population of women

OBJECTIVE: To estimate whether there is an association between chronic psychosocial stress and low birth weight neonates in low-income women. METHODS: Between 1999 and 2004, a random sample of women receiving welfare in nine Illinois counties was selected. The women were then interviewed annually. Women who delivered during this period were identified. Self-reported stress that occurred in temporal proximity to the delivery was assessed by 1) external stressors, 2) enhancers of stress, 3) buffers against stress, and 4) perceived stress and was compared between women who delivered low birth weight neonates and women who delivered normal birth weight neonates. RESULTS: Of the 1,363 women in the study, 294 women (21.6%) became pregnant and delivered during the study period. Of the 294 deliveries, 39 (13.3%) were low birth weight. The only demographic factor associated with a low birth weight delivery was increasing maternal age. However, multiple psychosocial factors, including food insecurity (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4–7.2), a child with chronic illness in the home (OR 3.4, 95% CI 1.5–7.9), increased crowding in the home (OR 2.7, 95% CI 1.3–5.6), unemployment (OR 3.1, 95% CI 1.2–7.9), and poor coping skills (OR 3.8, 95% CI 1.7–8.7), were significantly associated with low birth weight delivery (P < .01 for all comparisons). These significant associations persisted after adjusting for maternal age in multivariable analysis. CONCLUSION: This study provides evidence that chronic psychosocial stress may be associated with low birth weight neonates in a low-income population of women. LEVEL OF EVIDENCE: II

Effectiveness of timing strategies for delivery of individuals with placenta previa and accreta.

OBJECTIVE: To compare strategies for the timing of delivery in individuals with placenta previa and ultrasonographic evidence of placenta accreta, and to determine the optimal gestational age at which to deliver individuals. METHODS: A decision tree was designed comparing nine strategies for delivery timing in an individual with placenta previa and ultrasonographic evidence of placenta accreta. The strategies ranged from a scheduled delivery at 34, 35, 36, 37, 38, or 39 weeks of gestation to a scheduled delivery at 36, 37, or 38 weeks of gestation only after amniocentesis confirmation of fetal lung maturity. Outcomes factored into the model included maternal intensive care unit admission, perinatal mortality, infant mortality, respiratory distress syndrome, mental retardation, and cerebral palsy. RESULTS: A scheduled delivery at 34 weeks of gestation was the preferred strategy and resulted in the highest quality-adjusted life years under the base case assumptions. Strategies awaiting confirmation of fetal lung maturity failed to result in better outcome than strategies that delivered at the corresponding gestational age without amniocentesis. After sensitivity analyses, delivery at 37 weeks of gestation without amniocentesis was the preferred strategy in limited situations, and delivery at 39 weeks of gestation was the preferred strategy only in unlikely situations. CONCLUSION: This decision analysis suggests the preferred strategy for timing of delivery in individuals with ultrasonographic evidence of placenta previa and placenta accreta under a variety of circumstances is delivery at 34 weeks of gestation. At any given gestational age, incorporating amniocentesis for verification of fetal lung maturity does not assist in the management of such individuals. LEVEL OF EVIDENCE: III

Self-reported short sleep duration and frequent snoring in pregnancy: impact on glucose metabolism.

OBJECTIVE We sought to evaluate the impact of short sleep duration (SSD) and frequent snoring (FS) on glucose metabolism during pregnancy. STUDY DESIGN We conducted a prospective cohort study of healthy nulliparas who participated in a sleep survey study. SSD was defined as <7 hours of sleep per night and FS, as snoring >or=3 nights per week. Outcomes included 1-hour oral glucose tolerance results and the presence of gestational diabetes mellitus (GDM). Univariate and multivariate analyses were performed. RESULTS A total of 189 women participated; 48% reported an SSD and 18.5% reported FS. SSD and FS were associated with higher oral glucose tolerance values: SSD (116 +/- 31 vs 105 +/- 23; P = .008) and FS (118 +/- 34 vs 108 +/- 25; P = .04). Both SSD (10.2% vs 1.1%; P = .008) and FS (14.3% vs 3.3%; P = .009) were associated with a higher incidence of GDM. Even after controlling for potential confounders, SSD and FS remained associated with GDM. CONCLUSION SSD and FS are associated with glucose intolerance in pregnancy.

Pregnancy outcomes for women with placenta previa in relation to the number of prior cesarean deliveries

OBJECTIVE: To estimate the association between the number of prior cesarean deliveries and pregnancy outcomes among women with placenta previa. METHODS: Women with a placenta previa and a singleton gestation were identified in a concurrently collected database of cesarean deliveries performed at 19 academic centers during a 4-year period. Maternal and perinatal outcomes were analyzed after stratifying by the number of cesarean deliveries before the index pregnancy. RESULTS: Of the 868 women in the analysis, 488 had no prior cesarean delivery, 252 had one prior cesarean delivery, 76 had two prior cesarean deliveries, and 52 had at least three prior cesarean deliveries. Multiple measures of maternal morbidity (eg, coagulopathy, hysterectomy, pulmonary edema) increased in frequency as the number of prior cesarean deliveries rose. Even one prior cesarean delivery was sufficient to increase the risk of an adverse maternal outcome (a composite of transfusion, hysterectomy, operative injury, coagulopathy, venous thromboembolism, pulmonary edema, or death) from 15% to 23%, which corresponded, in multivariable analysis, to an adjusted odds ratio of 1.9 (95% confidence interval 1.2–2.9). Conversely, gestational age at delivery and adverse perinatal outcome (a composite measure of respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage grade 3 or 4, seizures, or death) were unrelated to the number of prior cesarean deliveries. CONCLUSION: Among women with a placenta previa, an increasing number of prior cesarean deliveries is associated with increasing maternal, but not perinatal, morbidity. LEVEL OF EVIDENCE: II

17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm

OBJECTIVE We sought to evaluate whether 17 alpha-hydroxyprogesterone caproate (17-OHP) reduces preterm birth (PTB) in nulliparous women with a midtrimester cervical length (CL) <30 mm. STUDY DESIGN In this multicenter randomized controlled trial, nulliparous women with a singleton gestation between 16 and 22 3/7 weeks with an endovaginal CL <30 mm (<10th percentile in this population) were randomized to weekly intramuscular 17-OHP (250 mg) or placebo through 36 weeks. The primary outcome was PTB <37 weeks. RESULTS The frequency of PTB did not differ between the 17-OHP (n = 327) and placebo (n = 330) groups (25.1% vs 24.2%; relative risk, 1.03; 95% confidence interval, 0.79-1.35). There also was no difference in the composite adverse neonatal outcome (7.0% vs 9.1%; relative risk, 0.77; 95% confidence interval, 0.46-1.30). CONCLUSION Weekly 17-OHP does not reduce the frequency of PTB in nulliparous women with a midtrimester CL <30 mm.

The cost-effectiveness of universal screening in pregnancy for subclinical hypothyroidism

OBJECTIVE The purpose of this study was to determine whether routine screening for subclinical hypothyroidism during pregnancy would be cost-effective. STUDY DESIGN We developed a decision analysis model to compare the cost-effectiveness of 2 screening strategies during pregnancy for subclinical hypothyroidism: (1) no routine screening of serum thyroid-stimulating hormone (TSH) levels (standard) and (2) routine screening of TSH levels. In the latter, women with subclinical hypothyroidism received thyroid hormone replacement. We assumed that thyroid hormone replacement could reduce the incidence of an offspring IQ < 85 for pregnancies with subclinical hypothyroidism. The main outcome measure was marginal cost per quality-adjusted life year (QALY) gained. RESULTS Our model predicts that universal screening is the dominant strategy. For every 100,000 pregnant women who were screened,

Racial/ethnic standards for fetal growth: The NICHD Fetal Growth Studies

8,356,383 are saved, and 589.3 QALYs are gained. When subclinical hypothyroidism prevalence is reduced to 0.25%, screening remains cost-effective at