Comparison of the effects of betamethasone and dexamethasone on surfactant protein A mRNA expression in human lung cells.

OBJECTIVE: While prenatal administration of synthetic corticosteroids stimulates both fetal lung development and expression of pulmonary surfactant, the specific effects may depend on the corticosteroid formulation used. We compared the dose-dependent effects of various concentrations of two synthetic corticosteroids, betamethasone and dexamethasone, on steady state levels of surfactant protein A (SP-A) mRNA in human lung cells. METHODS: Cultured human NCI-H441 bronchoalveolar epithelial cells were exposed to varying concentrations of betamethasone or dexamethasone (10-7 to 10-12 M) for 48 h alone or in combination with dibutyryl cAMP (1 mM), which augments surfactant protein gene expression. RNA was harvested and SP-A mRNA levels were quantified by real-time quantitative reverse transcriptase polymerase chain reaction analysis. Results were compared using the Kruskal-Wallis test. RESULTS: A dose-dependent modification in SP-A mRNA levels was demonstrated with both dexamethasone and betamethasone. Cells treated with cAMP expressed higher levels of SP-A mRNA than untreated cells. A biphasic curve in the SP-A mRNA response to corticosteroids was elicited only in the presence of cAMP: at lower concentrations (10-10 through 10-12 M), SP-A mRNA levels were upregulated, whereas at higher concentrations (10-7 and 10-8 M), SP-A mRNA levels were reduced. Dexamethasone was more effective than betamethasone in inducing these changes. CONCLUSIONS: Our results support a biphasic effect on SP-A mRNA levels after exposure to corticosteroids in combination with cAMP. At higher corticosteroid concentrations, betamethasone is less inhibitory than dexamethasone on SP-A mRNA.

Indomethacin and antibiotics in examination-indicated cerclage: a randomized controlled trial.

OBJECTIVE: To evaluate whether perioperative indomethacin and antibiotic administration at the time of examination-indicated cerclage placement prolongs gestation. METHODS: This is a randomized controlled trial performed at a single tertiary care hospital between March 2010 and November 2012. Women older than 18 years of age with a singleton pregnancy between 16 0/7 and 23 6/7 weeks of gestation undergoing an examination-indicated cerclage were eligible. Women were randomly assigned to receive either perioperative indomethacin and antibiotics or no perioperative prophylactic medications. The primary outcome was gestational latency after cerclage placement. Fifty women were required to be randomized to show, with 80% power, a 28-day improvement in latency assuming a latency without intervention of 50±35 days. RESULTS: Fifty-three patients were enrolled with three lost to follow-up. A greater proportion of pregnancies were prolonged by at least 28 days among women who received indomethacin and perioperative antibiotics (24 [92.3%] compared with 15 [62.5%], P=.01). However, gestational age at delivery and neonatal outcomes were statistically similar between groups. CONCLUSIONS: Among women receiving an examination-indicated cerclage in the second trimester, gestation was significantly more likely to be prolonged by 28 days among women who received perioperative indomethacin and antibiotics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01114516. LEVEL OF EVIDENCE: I.

Three-dimensional fast acquisition with sonographically based volume computer-aided analysis for imaging of the fetal heart at 18 to 22 weeks' gestation.

OBJECTIVE: The purpose of this study was to determine how frequently cardiac images derived from 3-dimensional (3D) volume sets, acquired by fast acquisition and evaluated with sonographically based volume computer-aided analysis (sonoVCAD), were satisfactory for prenatal screening at 18 to 22 weeks' gestation. METHODS: A prospective study of 100 women with singleton pregnancies was undertaken. Three fast acquisition 3D volume sets were obtained from each patient. Four reviewers independently evaluated the 4-chamber and 5 extracted VCAD views. Factors contributing to unsatisfactory screening were also evaluated. RESULTS: The frequency with which adequate views for cardiac screening could be obtained varied widely; some single views, such as that of the stomach, were well seen frequently, whereas others, such as the ductal arch, were well seen significantly less frequently (P < .05). A satisfactory screening examination, defined as a visualized 4-chamber, left ventricular outflow tract, right ventricular outflow tract, and axial stomach view, was obtained for 43% to 65% of patients (dependent on reviewer). Logistic regression revealed that obesity (odds ratio, 3.0; 95% confidence interval, 1.7-5.0) and a fetus with the spine toward the maternal abdomen (odds ratio, 1.7; 95% confidence interval, 1.1-2.5) were independently associated with an unsatisfactory screening examination CONCLUSIONS: Three-dimensional fast acquisition volumes evaluated with sonoVCAD did not allow a satisfactory fetal cardiac screening examination to be obtained a high percentage of the time in a general obstetric population during the second trimester. Certain patient factors, such as body habitus and fetal position, are associated with unsatisfactory 3D imaging.

Bone metabolism in fetuses of pregnant women exposed to single and multiple courses of corticosteroids.

OBJECTIVE: To estimate the effect of single and recurrent doses of antenatal corticosteroids on fetal bone metabolism. METHODS: This was a secondary analysis of a cohort of pregnant women from a previously reported randomized, placebo-controlled, multicenter trial of women at risk for preterm delivery who received weekly courses of betamethasone (active) or placebo after an initial course of corticosteroids. Umbilical cord serum levels of carboxy-terminal carboxy-terminal propeptide of type I procollagen and cross-linked carboxy-terminal telopeptide of type I procollagen were measured to assess the rate of fetal bone formation and resorption, respectively. Analysis was stratified according to number of repeat antenatal study courses of betamethasone or placebo (one to three compared with at least four courses, not including the initial course). RESULTS: Of the 251 umbilical cord serum samples, the median serum carboxy-terminal telopeptide of type I procollagen levels, but not carboxy-terminal propeptide of type I procollagen levels, was significantly lower with repeat betamethasone exposure (55.0 compared with 57.9 micrograms/L, P=.01). In the fetuses exposed to at least four repeat study courses, there was a significant decrease in median carboxy-terminal telopeptide of type-I procollagen levels between repeat betamethasone exposure and placebo (53.4 compared with 58.6 micrograms/L, respectively, P=.04), but there was no difference between groups in the fetuses exposed to 1-3 repeat study courses (57.4 compared with 56.7 micrograms/L, respectively, P=.29). CONCLUSION: Levels of umbilical cord serum markers of bone resorption but not formation are reduced in fetuses exposed to repeat courses of antenatal betamethasone. Up to four courses of antenatal betamethasone do not seem to affect fetal bone metabolism. LEVEL OF EVIDENCE: II.

Randomized trial of preinduction cervical ripening: misoprostol vs oxytocin.

OBJECTIVE: The purpose of this study was to compare the vaginal delivery rate in women who undergo labor induction with preinduction misoprostol or oxytocin alone. STUDY DESIGN: Women with singleton pregnancies and Bishop scores <5 with labor induction at > or = 24 weeks of gestation were eligible; they were assigned randomly to oxytocin alone or preinduction cervical ripening with misoprostol. Labor characteristics, maternal complications, and neonatal outcomes were analyzed. RESULTS: One hundred sixty-three women received oxytocin, and 164 women received misoprostol. Maternal demographics, pretreatment Bishop scores, and labor analgesia were similar between groups. Vaginal delivery rates were also similar: 87% (n = 141) for oxytocin and 81% (n = 133) for misoprostol. Mean time from treatment to delivery was shorter for the oxytocin group, compared with the misoprostol group (13.1 vs 16.3 hours; P = .005). There was no difference in maternal complications or neonatal outcomes between groups. CONCLUSION: Preinduction cervical ripening with misoprostol did not improve the vaginal delivery rate and resulted in longer intervals to active labor and delivery. Preinduction cervical ripening with misoprostol may not be necessary.

Spontaneous version following preterm premature rupture of membranes.

Our objective was to determine the rate of spontaneous version following preterm premature rupture of membranes (PPROM). Medical charts over a 4-year period were reviewed. All women with PPROM and singleton gestation between 24 and 34 weeks gestation were included; 65 patients met the inclusion criteria. By ultrasound on admission, 48 were cephalic 16 were breech, and one was transverse lie. Mean amniotic fluid index on admission was 5.1 +/- 4.8 cm (standard deviation) and was not associated with fetal presentation at delivery. Spontaneous version from cephalic presentation at admission to noncephalic presentation at delivery occurred in one pregnancy (2.2%). Spontaneous version from noncephalic presentation at admission to cephalic presentation at delivery occurred in three pregnancies (17.6%; p = 0.05). Among women with noncephalic presentation at delivery (n = 15), 73.3% had a cesarean, compared with 23.4% of those with cephalic presentation at delivery (p < 0.05). Spontaneous version, particularly from cephalic to noncephalic presentation, is unlikely following PPROM.

Subcutaneous tissue reapproximation, alone or in combination with drain, in obese women undergoing cesarean delivery.

OBJECTIVE: To compare the efficacy of subcutaneous suture reapproximation alone with suture plus subcutaneous drain for the prevention of wound complications in obese women undergoing cesarean delivery. METHODS: We conducted a multicenter randomized trial of women undergoing cesarean delivery. Consenting women with 4 cm or more of subcutaneous thickness were randomized to either subcutaneous suture closure alone (n = 149) or suture plus drain (n = 131). The drain was attached to bulb suction and removed at 72 hours or earlier if output was less than 30 mL/24 h. The primary study outcome was a composite wound morbidity rate (defined by any of the following: subcutaneous tissue dehiscence, seroma, hematoma, abscess, or fascial dehiscence). RESULTS: From April 2001 to July 2004, a total of 280 women were enrolled. Ninety-five percent of women (268/280) had a follow-up wound assessment. Both groups were similar with respect to age, race, parity, weight, cesarean indication, diabetes, steroid/antibiotic use, chorioamnionitis, and subcutaneous thickness. The composite wound morbidity rate was 17.4% (25/144) in the suture group and 22.7% (28/124) in the suture plus drain group (relative risk 1.3, 95% confidence interval 0.8-2.1). Individual wound complication rates, including subcutaneous dehiscence (15.3% versus 21.8%), seroma (9.0% versus 10.6%), hematoma (2.2% versus 2.4%), abscess (0.7% versus 3.3%), fascial dehiscence (1.4% versus 1.7%), and hospital readmission for wound complications (3.5% versus 6.6%), were similar (P > .05) between women treated with suture alone and those treated with suture plus drain, respectively. CONCLUSION: The additional use of a subcutaneous drain along with a standard subcutaneous suture reapproximation technique is not effective for the prevention of wound complications in obese women undergoing cesarean delivery.

Postdates pregnancy in an indigent population: the financial burden.

OBJECTIVE: The objective of this study was to determine the comparative financial burden of twice-weekly fetal testing from 41 weeks of gestation until delivery, as compared with early dating ultrasound evaluation in an indigent population. STUDY DESIGN: All women who were seen for antepartum testing for postdating pregnancy at Lyndon Baines Johnson Hospital were enrolled. Patient age, parity, gestational age at initiation of prenatal care, the number of prenatal visits, gestational age at first ultrasound scan, and the number of biophysical profiles that were performed before delivery were recorded. The labor and delivery database was searched for all deliveries at >41 weeks of gestation. The charge for a single ultrasound scan at <20 weeks of gestation was compared with twice-weekly testing in the population as a whole with the use of three strategies (no dating ultrasound scans and biophysical profiles until delivery, routine dating ultrasound scan and routine induction at 41 weeks of gestation, and current practice at our institution). RESULTS: One hundred twenty-seven subjects with postdated pregnancy were enrolled (mean age, 25.2 years; median parity, 0 [range, 0-6]). The mean gestational age at the initiation of prenatal care was 21.2 +/- 10.5 weeks. Forty-seven women (38.0%) initiated care at <20 weeks. The mean number of biophysical profiles performed before delivery was 1.5 +/- 1.34; the mean gestational age at delivery was 42.1 +/- 0.87 weeks (spontaneous labor, 39.6%; induced labor, 40.4%). The charge for a biophysical profile is $492.90 US dollars and $551.00 US dollars for a 20-week ultrasound scan; there is no difference in the charge for induced or spontaneous labor. During the 4-month study period, 1638 patients were delivered at our hospital; 341 patients were delivered at >41 weeks of gestation. The estimated financial burden of antenatal testing of 341 patients from 41 weeks to delivery was calculated to be $252,118 US dollars, compared with $902,538 US dollars for a single ultrasound scan at 20 weeks for the entire population of 1638 patients. The estimated financial burden of current practice (10% of patients with no prenatal care, 38% of patients with examination at <20 weeks who were eligible for dating ultrasound scanning, and 37% of patients with examination for postdate testing) was $402,457 US dollars. CONCLUSION: Patients who were seen for postdate antepartum testing in an indigent population lack early initiation of prenatal care and early ultrasound scans. Because on average only 1.5 biophysical profiles are performed per patient before delivery, routine early ultrasound scanning and routine induction at 41 weeks of gestation would add considerable financial burden to the system.