Laura Goetzl

Sequential pathways of testing after first-trimester screening for trisomy 21

OBJECTIVE: To evaluate the performance and use of second-trimester multiple-marker maternal serum screening for trisomy 21 by women who had previously undergone first-trimester combined screening (nuchal translucency, pregnancy-associated plasma protein A, and free β-hCG), with disclosure of risk estimates. METHODS: In a multicenter, first-trimester screening study sponsored by the National Institute of Child Health and Human Development, multiple-marker maternal serum screening with alpha-fetoprotein, unconjugated estriol, and total hCG was performed in 4,145 (7 with trisomy 21) of 7,392 (9 with trisomy 21) women who were first-trimester screen-negative and 180 (7 with trisomy 21) of 813 (52 with trisomy 21) who were first-trimester screen-positive. Second-trimester risks were calculated using multiples of the median and a standardized risk algorithm with a cutoff risk of 1:270. RESULTS: Among the first-trimester screen-negative cohort, 6 of 7 (86%) trisomy 21 cases were detected by second-trimester multiple-marker maternal serum screening with a false-positive rate of 8.9%. Among the first-trimester screen-positive cohort, all 7 trisomy 21 cases were also detected in the second trimester, albeit with a 38.7% false-positive rate. CONCLUSION: Our data demonstrate that a sequential screening program that provides patients with first-trimester results and offers the option for early invasive testing or additional serum screening in the second trimester can detect 98% of trisomy 21–affected pregnancies. However, such an approach will result in 17% of patients being considered at risk and, hence, potentially having an invasive test. LEVEL OF EVIDENCE: II-2

Pregnancy-associated Plasma Protein A, Free β-hcg, Nuchal Translucency, and Risk of Pregnancy Loss

OBJECTIVE: To estimate the likelihood of clinical early and late pregnancy loss as a function of first-trimester maternal serum analytes and fetal nuchal translucency measurements. METHODS: Study subjects were recruited for a National Institute of Child Health and Human Development–sponsored multicenter cohort study initially designed to study the detection of Down syndrome during the first trimester of pregnancy. The cohort consisted of women who had a live fetus between 10 and 14 weeks of gestation and had no significant vaginal bleeding. Women with prior fetal trisomy (T21/18) and those with structural or chromosomal abnormalities in the index pregnancy were excluded. First-trimester screening consisted of pregnancy-associated plasma protein A (PAPP-A), free β-hCG, and nuchal translucency. Pregnancy loss rates in women with various levels of PAPP-A, free β-hCG, or nuchal translucency (less than 1st, less than 5th, more than 95th, and more than 99th percentile) were compared with losses in women with normal values (5th to 95th percentile). RESULTS: The mean gestational age at screening of 7,932 women meeting study criteria was 12.1 weeks. Loss rates were only 0.36% at less than 20 weeks after normal free β-hCG, PAPP-A, and nuchal translucency. Conversely, low levels of PAPP-A and free β-hCG as well as increased nuchal translucency were individually associated with increased early loss. These associations persisted after controlling for maternal age and race using logistic regression analysis. CONCLUSION: Normal values of PAPP-A, free β-hCG, and nuchal translucency are associated with a very low risk of pregnancy loss at less than 20 weeks. LEVEL OF EVIDENCE: II-2

Maternal intrapartum temperature elevation as a risk factor for cesarean delivery and assisted vaginal delivery.

OBJECTIVES This study investigated the association of intrapartum temperature elevation with cesarean delivery and assisted vaginal delivery. METHODS Participants were 1233 nulliparous women with singleton, term pregnancies in vertex presentations who had spontaneous labors and were afebrile (temperature: 99.5 degrees F [37.5 degrees C]) at admission for delivery. Rates of cesarean and assisted vaginal deliveries according to highest intrapartum temperature were examined by epidural status. RESULTS Women with maximum intrapartum temperatures higher than 99.5 degrees F were 3 times as likely to experience cesarean (25.2% vs 7.2%) or assisted vaginal delivery (25.2% vs 8.5%). The association was present in epidural users and nonusers and persisted after birthweight, epidural use, and labor length had been controlled. In adjusted analyses, temperature elevation was associated with a doubling in the risk of cesarean delivery (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5, 3.4) and assisted vaginal delivery (OR = 2.1, 95% CI = 1.4, 3.1). CONCLUSIONS Modest temperature elevation developing during labor was associated with higher rates of cesarean and assisted vaginal deliveries. More frequent temperature elevation among women with epidural analgesia may explain in part the higher rates of cesarean and assisted vaginal deliveries observed with epidural use.

Abdominal cerclage for the treatment of recurrent cervical insufficiency: laparoscopy or laparotomy?

OBJECTIVE The purpose of this study was to compare the efficacy of traditional abdominal cerclage (AC) with laparoscopic cerclage (LC). STUDY DESIGN Eligible women had at least 1 second trimester pregnancy loss due to cervical insufficiency, and had undergone at least 1 failed transvaginal cerclage. A prospective cohort of patients undergoing LC was compared with a historical control group of patients who had AC. A successful primary outcome was defined as delivery of a viable infant with neonatal survival. RESULTS We were able to evaluate 19 pregnancies following unique abdominal cerclage placement, 12 laparoscopic and 7 at the time of laparotomy. Nine of 12 (75%) undergoing LC and 5 of 7 (71%) pregnancies undergoing AC successfully delivered a viable infant (P = .63). LC during pregnancy was successful in 4 of 5 (80%) cases as compared to 3 of 5 (60%) cases with AC during pregnancy (P = 1.0). CONCLUSION Operative laparoscopy is a safe and effective alternative to laparotomy for the placement of abdominal cerclage.

Intrapartum epidural analgesia and maternal temperature regulation.

OBJECTIVE: To examine maternal temperature changes after epidural analgesia. METHODS: A prospective cohort of nulliparas at term was monitored with hourly maternal tympanic temperatures after epidural analgesia (n=99). Temperature response after epidural analgesia was examined in the group as a whole. Subsequently, mean maternal temperature curves were compared between women who remained afebrile throughout labor (n=77) and women who developed intrapartum fever with body temperature greater than 100.4ºF (n=22). Baseline maternal characteristics were assessed. RESULTS: Women who later developed intrapartum fever had a higher mean temperature within 1 hour after epidural analgesia. In contrast, women who remained afebrile had no increase in core temperature. During the first 4 hours after epidural analgesia initiation, women who later develop intrapartum fever have an increase in mean tympanic temperature of 0.33ºF per hour. CONCLUSION: Epidural analgesia is not associated with increased temperature in the majority of women. Hyperthermia is an abnormal response confined to a minority subset, which occurs immediately after exposure. Our findings do not support a universal perturbation of maternal thermoregulation after epidural analgesia. LEVEL OF EVIDENCE: II

Oxytocin dose and the risk of uterine rupture in trial of labor after cesarean.

Objective To examine the association between uterine rupture and oxytocin use in trial of labor after cesarean. Methods A case-control study was performed. Cases were all women with uterine ruptures who received oxytocin during a trial of labor after a single cesarean delivery within a 12-year period (n = 24). Four controls undergoing trial of labor after a single cesarean delivery were matched to each case by 500 g birth weight category, year of birth, and by induction or augmentation (n = 96). The study had an 80% power to detect a 40% increase in oxytocin duration or a 65% increase in total oxytocin dose. Results No significant differences were seen in initial oxytocin dose, maximum dose, or time to maximum dose. Although women with uterine ruptures had higher exposure to oxytocin as measured by mean total oxytocin dose (544 mU higher) and oxytocin duration (54 minutes longer), these differences were not statistically significant. Women with uterine rupture who received oxytocin were more likely to have experienced an episode of uterine hyperstimulation (37.5% compared with 20.8%, P = .05). However, the positive predictive value of hyperstimulation for uterine rupture was only 2.8%. Conclusion Although no significant differences in exposure to oxytocin were detected between cases of uterine rupture and controls, the rarity of uterine rupture limited our power to detect small differences in exposure. In women receiving oxytocin, uterine rupture is associated with an increase in uterine hyperstimulation, but the clinical value of hyperstimulation for predicting uterine rupture is limited.

Abortion disclosure and the association with domestic violence

OBJECTIVE: To estimate the rate at which women disclose abortion to their partners and examine the association between domestic violence and partner disclosure. METHODS: A cross-sectional cohort study was performed on women presenting for elective termination of pregnancy to a single clinic in Houston, Texas. Subjects were offered an anonymous, self-administered questionnaire. The 15-question survey addressed disclosure of abortion to the partner, reasons for nondisclosure if applicable, and physical and sexual abuse using a modified Abuse Assessment Screen. RESULTS: Of 960 patients, 85.2% completed the survey, for a final sample size of 818. Overall, 139 (17.2%) of subjects chose not to disclose the abortions to their partners, and 14% of patients reported abuse within the past year. Physical or sexual abuse or both was twice as common among nondisclosers (23.7% compared with 12.0%, P = .001). Among nondisclosers, 63 (45.3%) said the relationship with the partner had no future, 52 (37.4%) did not feel obliged to notify their partners, 29 (20.9%) said the partner would oppose the abortion, and 11 (7.9%) said disclosure would result in physical harm. CONCLUSION: In this urban, racially and socioeconomically diverse population, 17.2% of women concealed pregnancy terminations from their partners. Although relationship instability and personal choice were cited as the most frequent reasons for nondisclosure, the rate of domestic abuse was twice as high in this group and may have adversely affected open communication. Of greatest concern, a subset of nondisclosers reported the direct fear of personal harm as the primary reason for nondisclosure. LEVEL OF EVIDENCE: III

Maternal inflammation in spontaneous term labor

OBJECTIVE The purpose of this study was to examine the association between peripheral markers of maternal inflammation and the onset of term labor. STUDY DESIGN A nested case-control study was performed with serum that had been collected at routine visits from a cohort of 607 term nulliparous women. Cases (n = 20) labored spontaneously within 48 hours of enrollment, and control subjects (n = 80) labored spontaneously ≥14 days after enrollment. Maternal serum cytokines were determined with the use of standard multiplex protocols. Median levels of interleukin-1, -4, -6, -8, and -10, interferon-γ, and tumor necrosis factor-α were compared with the use of the Mann-Whitney U test. Correlations between cytokine levels and maternal factors were performed (Spearmans rho). RESULTS Median interleukin-1 and -6 and tumor necrosis factor-α levels were significantly higher in cases vs control subjects (0.76 vs 0.31 pg/mL [P < .01]; 2.05 vs 0.95 pg/mL [P = .03]; 0.81 vs 0.51 pg/mL [P = .02], respectively). Latency until delivery was inversely correlated with interleukin-1 and tumor necrosis factor-α (-0.28 [P < .01]; -0.246 [P = .01]), but not with interleukin-6. CONCLUSION Maternal proinflammatory markers increase before spontaneous term labor.

Glyburide compared to insulin for the treatment of gestational diabetes mellitus: a cost analysis.

OBJECTIVE: To compare the costs associated with glyburide compared to insulin for the treatment of gestational diabetes unresponsive to dietary therapy.STUDY DESIGN: A cost model was designed. The model excluded costs that were identical for both treatment arms, such as the cost of monitoring glucose control. Insulin treatment costs included average wholesale drug costs, wholesale delivery costs (syringes, alcohol pads), and costs of office staff educating patients. Glyburide costs were based on average wholesale drug costs. Downstream costs of potential inpatient evaluation for hypoglycemia were included in the model.RESULTS: In our baseline model, glyburide was significantly less costly than insulin for the treatment of gestational diabetes. The average cost saving per patient based on wholesale drug costs and hospital costs was US

Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease.

165.84. Actual retail drug savings and hospital charge savings are potentially considerably greater. The strongest determinant of cost savings was medication cost. The model was less sensitive to the one-time costs of inpatient treatment and patient education.CONCLUSION: Glyburide is less costly than insulin for the treatment of gestational diabetes. Cost models can be useful to physicians deciding between two equally efficacious medications, allowing them to incorporate information about their individual practice styles with a complex balance of cost implications.