Richard H. Lee

Free T4 immunoassays are flawed during pregnancy.

OBJECTIVE The purpose of this study was to evaluate the diagnostic accuracies of 2 free thyroxine immunoassays during pregnancy. STUDY DESIGN Serum was collected from healthy, thyroid peroxidase antibody-negative women during each trimester and nonpregnant controls. Thyrotropin, total T4 (TT4), free T4 index (FT4I), and 2 different FT4 immunoassays were studied. RESULTS As expected, TT4 was elevated in all 3 trimesters compared to controls (P < .001). FT4I was elevated in the 1st trimester as compared with controls (P < .05) and returned to the nonpregnant range in the 2nd and 3rd trimesters. In contrast, 1st trimester FT4 immunoassay values were either comparable or lower than controls and by the 2nd and 3rd trimesters had decreased to approximately 65% of controls. CONCLUSION Neither FT4 immunoassay accurately reflects established free T4 changes during pregnancy. TT4 and the FT4I retained an appropriate inverse relationship with TSH throughout pregnancy and appear to provide a more reliable free T4 estimate.

Cholestasis of Pregnancy

Intrahepatic cholestasis (ICP) of pregnancy is a disease that is likely multifactorial in etiology and has a prevalence that varies by geography and ethnicity. The diagnosis is made when patients have a combination of pruritus and abnormal liver-function tests. It is associated with a high risk for adverse perinatal outcome, including preterm birth, meconium passage, and fetal death. As of yet, the cause for fetal death is unknown. Because fetal deaths caused by ICP appear to occur predominantly after 37 weeks, it is suggested to offer delivery at approximately 37 weeks. Ursodeoxycholic acid appears to be the most effective medication to improve maternal pruritus and liver-function tests; however, there is no medication to date that has been shown to reduce the risk for fetal death.

Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy.

Our objective was to examine whether delivery at 37 weeks of gestation alters adverse pregnancy outcomes in Latina patients with intrahepatic cholestasis of pregnancy (ICP). We conducted a retrospective chart review of Latina patients who delivered at our institution coded with ICP between 2000 and 2007. During this time period it was our practice to offer delivery to patients with ICP at 37 weeks of gestation. Subjects were classified into three groups according to total bile acid (TBA) concentration: < 20 micromol/L (mild ICP), > or = 20 micromol/L and < 40 micromol/L (moderate ICP), and > or = 40 micromol/L (severe ICP). Meconium passage was observed in no births in patients with mild IC, but was found in 18% of deliveries with moderate/severe ICP. The risk of meconium passage increased linearly, with a 19.7% increased risk for each 10 mumol/L increase in TBA concentration ( P = 0.001). There was no association with higher TBA concentration and other adverse outcomes. There was no difference in adverse outcomes between moderate and severe ICP. We concluded that in our Latina population with ICP, an association existed between meconium passage and moderate/severe ICP. Delivering at 37 weeks was associated with a low risk of adverse outcomes due to ICP among all patients, including those with higher TBA concentrations.

The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population

Objective:To establish the prevalence of intrahepatic cholestasis of pregnancy (ICP) in a primarily Latina population in the United States.Study design:Over a period of 16 months, a convenience sample of subjects admitted to labor and delivery in the third trimester was enrolled. Each subject completed a questionnaire rating their severity of pruritus on a numeric scale of 1 to 10. Serum was analyzed via radioimmunoassay for total bile acid concentration. ICP was defined as pruritus score >4 and a total serum bile acid concentration of ⩾20 μmol/l. Ethnicity was determined from hospital record demographic data.Results:All invited participants enrolled in the study. Three hundred and forty subjects were enrolled. Three hundred and sixteen subjects (93%) were identified as Latina. The serum bile acid concentration range for the entire study population was 1 to 580 μmol/l with a mean of 10.4±34.9 μmol/l. Twenty-four (7.1%) subjects had a serum bile acid concentration ⩾20 μmol/l. A pruritus score >4 was found in 19.7% (67/340). Of the 24 subjects with a bile acid concentration ⩾20 μmol/l, 19 also had a pruritus score >4. Thus, the prevalence of ICP in this population was 5.6% (19/340). In subjects with ICP, the mean serum bile acid concentration was 89.5±124.0 μmol/l. When controlling for confounders, women with ICP were associated with higher rates of chorioamnionitis (P=0.043) and their fetuses had higher rates of thick meconium (P=0.053).Conclusions:The overall prevalence of ICP in this population was 5.6%, 10 to 100 times higher than previously reported data from the United States. Larger studies of perinatal morbidity examining the diagnostic criteria of cholestasis need to be conducted.

Pre-pregnancy weight and excess weight gain are risk factors for macrosomia in women with gestational diabetes

Objective:To determine whether women with gestational diabetes mellitus (GDM) whose weight gain exceeded the 2009 Institute of Medicine (IOM) recommendations were more likely to have macrosomia.Study Design:Retrospective cohort study of the association of weight gain in women with Class A1 GDM, with term (⩾37 weeks) singleton liveborns and macrosomia (birthweight ⩾4000 g). Multivariate logistic regression models were used to adjust for covariates and test for interactions.Result:Of 1502 women studied, pre-pregnancy body mass index (BMI) categories were: normal (39.6%), overweight (28.5%) and obese (31.9%). The mean (±standard deviation ) weight gain (lbs) for these groups was: 27.6±10.9, 24.2±13.0 and 18.8±16.3 (P<0.0001), whereas the occurrence of macrosomia was 7.4, 11.4 and 19.0%, respectively. Women with an obese BMI were twice as likely to have a macrosomic infant compared with women in the normal BMI group (odds ratio, OR 2.0; 95% CI 1.4–3.0; P=0.0005). Independently, women who exceeded the IOM guidelines were three times more likely to have a macrosomic infant (OR 3.0, 95% CI 2.2–4.2, P<0.0001).Conclusion:Maternal pre-pregnancy weight and weight gain during pregnancy appear to be significant and independent risk factors for macrosomia in women with GDM.

Sudden Fetal Death in Intrahepatic Cholestasis of Pregnancy

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with an increased risk of fetal death. The mechanism of death is unknown. CASES: The first case involved a young primipara with pruritus and a bile acid concentration of 79 &mgr;mol/dL. While undergoing fetal heart rate monitoring, the fetus had a prolonged deceleration resulting in intrauterine death. The second case involved a young multipara with cholestasis who received ursodeoxycholic acid. Her bile acid concentration improved to13 &mgr;mol/dL. At 34 weeks of gestation, she had uterine contractions with prolonged decelerations resulting in delivery of her fetus with Apgar scores of 0, 0, and 5 at 1, 5, and 10 minutes, respectively. CONCLUSION: Fetal death from intrahepatic cholestasis of pregnancy can be abrupt and not reliably predicted by the characteristics of the fetal heart rate tracing.

Effect of Environmental Perchlorate on Thyroid Function in Pregnant Women from Córdoba, Argentina, and Los Angeles, California

OBJECTIVE To determine whether environmental perchlorate exposure adversely affects thyroid function in women in the first trimester of pregnancy. METHODS First-trimester pregnant women were recruited from prenatal clinics in the Los Angeles County Hospital, Los Angeles, California, and in the Hospital Universitario de Maternidad dependent Universidad Nacional de Córdoba, Córdoba, Argentina, between 2004 and 2007. Spot urine and blood specimens were obtained during the clinic visit. Urinary perchlorate, iodine, and creatinine were measured, and thyroid function tests were performed. RESULTS The study included 134 pregnant women from Los Angeles, California (mean gestational age ± SD = 9.1 ± 2.2 weeks), and 107 pregnant women from Córdoba, Argentina (mean gestational age = 10.0 ± 2.0 weeks). Median urinary iodine values were 144 μg/L in California and 130 μg/L in Argentina. Urinary perchlorate levels were detectable in all women (California: median, 7.8 μg/L [range, 0.4-284 μg/L] and Argentina: median, 13.5 μg/L [range, 1.1-676 μg/L]). Serum thyroperoxidase antibodies were detectable in 21 women from California (16%) and in 17 women from Argentina (16%). Using Spearman rank correlation analyses, there was no association between urinary perchlorate concentrations and serum thyrotropin, free thyroxine index, or total triiodothyronine values, including within the subset of women with urinary iodine values less than 100 μg/L. In multivariate analyses using the combined Argentina and California data sets and adjusting for urinary iodine concentrations, urinary creatinine, gestational age, and thyroperoxidase antibody status, urinary perchlorate was not a significant predictor of thyroid function. CONCLUSIONS Low-level perchlorate exposure is ubiquitous, but is not associated with altered thyroid function among women in the first trimester of pregnancy.

The mechanical PR interval in fetuses of women with intrahepatic cholestasis of pregnancy

OBJECTIVE The purpose of this study was to evaluate the fetal mechanical PR interval in intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN Fetal echocardiography was performed for women with ICP and control subjects. Clinical characteristics, total bile acids, and liver profile tests were compared between groups. RESULTS Fourteen women with ICP and 7 control subjects were enrolled. Total bile acids (28.3 vs 6.2 μmol/L; P < .001), aspartate aminotransferase (53 vs 23 IU/L; P = .002), alanine aminotransferase (63 vs 19 IU/L; P = .002), and the PR interval (124 vs 110 msec; P = .006) were significantly higher in fetuses with ICP than in control fetuses. On multivariable linear regression analysis, only the presence of ICP was associated significantly with an increase in the PR interval (95% confidence interval, 4-24 msec; P = .01). CONCLUSION The fetal cardiac conduction system is altered in ICP. Further investigation is needed to determine whether fetal echocardiography can help to predict which fetuses are at risk for death that is associated with ICP.

Perioperative characteristics associated with preterm birth in twin-twin transfusion syndrome treated by laser surgery

OBJECTIVE To identify perioperative risk factors for preterm delivery (PTD) in laser-treated patients with twin-twin transfusion syndrome (TTTS). STUDY DESIGN Twin-twin transfusion syndrome patients who underwent laser surgery were followed prospectively. Univariate and multivariate analyses were performed to identify gestational and surgical characteristics associated with preterm delivery. RESULTS Of 318 eligible patients, the mean (SD) gestational age of delivery was 32.8 (4.2) weeks. The number of days from laser surgery to delivery had a bimodal distribution; group I delivered within 21 days and group II delivered after 21 days of surgery. Eighteen patients (5.7%) were in group I and demonstrated the following risk factors for delivery within 21 days: incomplete laser surgery suspected (odds ratio [OR], 11.14; P = .0106), preoperative subchorionic hematoma (OR, 7.92, P = .0361), preoperative cervical length <2.0 cm (OR, 4.71; P = .0117), and recipients maximum vertical pocket ≥14 cm (OR, 3.23; P = .0335). In group II, 92 of 300 patients (30.7%) delivered <32 weeks, and 25 (8.3%) delivered <28 weeks; multivariate logistic regression analyses identified 5 risk factors for delivery <32 weeks: incomplete laser surgery suspected (OR, 10.0; P = .0506); incidental septostomy (OR, 4.4; P = .0009); triplet gestation (OR, 2.6; P = .0689); postoperative membrane detachment (OR, 2.4; P = .0393); and nonposterior placental location (OR, 1.8; P = .0282). CONCLUSION Timing of delivery after laser for twin-twin transfusion syndrome has a bimodal distribution with distinct gestational and surgical risk factors. This information may be useful in counseling patients and in directing future avenues of research.

Vaginal birth after cesarean section: risk of uterine rupture with labor induction.

We assessed the rate of uterine rupture in patients undergoing labor induction for attempted vaginal birth after cesarean (VBAC). A retrospective study was performed of data from a computerized database. Deliveries from January 1, 1998, to June 30, 2001, in the Southern California Kaiser Permanente system were reviewed and various perinatal characteristics analyzed. A total of 16,218 patients had a prior low transverse cesarean section. Of these, 6832 (42.1%) had a trial of labor. Successful VBAC occurred in 86% of patients with spontaneous onset of labor and 66% of patients with labor induction ( p < 0.001). The uterine rupture rate was not different between patients with spontaneous or induced labor (1.0% versus 1.2%, p = 0.51). Similarly, there was no significant difference between oxytocin or prostaglandin E2 induction (1.4% versus 1.0%, p = 0.59). In our study, labor induction did not appear to increase the risk of uterine rupture in women attempting VBAC.