Transvaginal cervical length scans to prevent prematurity in twins: a randomized controlled trial.

BACKGROUND: Twin pregnancies are associated with an increased risk of perinatal morbidity and mortality primarily due to spontaneous preterm deliveries. The mean gestational age for delivery is 35.3 weeks and twins account for 23% of preterm births <32 weeks. A number of strategies have been proposed to prevent preterm deliveries: tocolytics, bed rest, hospitalization, home uterine activity monitoring, cerclage, and most recently, progesterone. Unfortunately, none have proven effective. Recent metaanalyses and reviews suggest that transvaginal cervical length (TVCL) ultrasound in the second trimester is a powerful predictor of preterm birth among asymptomatic women. Indeed, TVCL has the highest positive and negative predictive values for determining the risk of spontaneous preterm delivery in twin pregnancies. It follows that TVCL assessment may allow identification of a subset of twin pregnancies that re better candidates for interventions intended to prevent prematurity. OBJECTIVE: We sought to determine whether use of TVCL prolongs gestation in twin pregnancies. STUDY DESIGN: This is a multicenter, randomized, controlled trial of 125 dichorionic or monochorionic/diamniotic twin pregnancies without prior preterm birth <28 weeks. The study group (n = 63) had TVCL and digital exams monthly from 16-28 weeks and were managed with a standard algorithm for activity restriction and cerclage. The control group (n = 62) had monthly digital cervical examinations but no routine TVCL ultrasound examinations. The primary outcome was gestational age at delivery. Secondary outcomes included percentage of deliveries <35 weeks, and maternal and neonatal outcomes. RESULTS: The mean gestational age at delivery was 35.7 weeks (95% confidence interval [CI], 35.2-36.2) among those managed with TVCL and 35.5 weeks (95% CI, 34.7-36.4) among the control patients. The Kaplan-Meier estimates of deliveries <38 weeks were not significantly different between groups. This was true whether we compared curves with a log-rank test (P = .67), Breslow test (P = .67), or Tarone-Ware test (P = .64). The percentage of deliveries <35 0/7 weeks did not differ: 27.4% for subjects managed with routine TVCL and 28.6% for control subjects (relative risk, 0.96; 95% CI, 0.60-1.54). Our study had an 80% power to detect a 12-day difference in the gestational age at delivery with 95% confidence. CONCLUSION: The overall mean length of gestation and the percentage of women delivering <35 weeks did not differ between twin gestations managed with TVCL and digital exams monthly from 16-28 weeks with a standard algorithm for activity restriction and cerclage and controls who had monthly digital cervical examinations but no routine TVCL. Routine second-trimester transvaginal ultrasound assessment of cervical length is not associated with improved outcomes when incorporated into the standard management of otherwise low-risk twin pregnancies.

The use of prostaglandin E1 in peripartum patients with asthma.

OBJECTIVE: Prostaglandin E1 (PGE1) is commonly used in obstetric practice for labor induction and cervical ripening and in treating postpartum hemorrhage; however, its use in pregnant asthmatic patients has not been studied to date. The package insert states there is an unknown causal side effect for dyspnea and bronchospasm. Other pharmacological publications have stated that bronchoconstriction may occur with the use of PGE1. The study objective was to examine peripartum pregnant asthmatic patients who received prostaglandin E1. STUDY DESIGN: Every patient who was administered PGE1 from January 2010 through December 2013 was prospectively recorded. The charts were retrospectively reviewed. Peripartum patients with asthma were identified and further analyzed for any evidence of an asthma exacerbation following administration of the drug. RESULTS: A total of 234 of 2629 patients (8.9%) who received PGE1 were identified as having asthma. None of the patients had any evidence of an asthma exacerbation (0 of 234; 95% confidence interval, 0-0.017). Of the 234 patients, 104 (44%) had active asthma and were receiving daily medication, and the remaining 130 patients had a medical history of asthma for which they used an inhaler on an as-needed basis. A total of 98 patients (42%) received greater than 400 µg of total dose. A post hoc statistical assessment was performed, and the study was sufficiently powered to detect any clinically meaningful increase in asthma exacerbation with PGE1 usage, if such a risk existed. CONCLUSION: Based on the 95% confidence interval of these data, the maximum risk for an asthma exacerbation following the use of prostaglandin E1 is less than 2%. Although all medications administered to asthmatic patients in the peripartum period should be carefully selected, this information supports the use of prostaglandin E1 in obstetric patients with asthma, if clinically indicated.

Chronic opiate use in pregnancy and newborn head circumference.

OBJECTIVE: The aim of the study is to evaluate whether chronic opiate use in pregnancy affects newborn head circumference (HC). STUDY DESIGN: All newborns from January 1, 2010, to June 30, 2012, admitted to the neonatal intensive care unit for treatment of neonatal abstinence syndrome were prospectively collected. The demographic, obstetrical, neonatal, and perinatal ultrasound data were retrospectively obtained. A gestational age-matched control was used for comparison purposes. RESULTS: Of 332 neonates admitted for the treatment of neonatal abstinence syndrome, 98 (29.5%) had a HC ≤ 10th percentile for gestational age that was significantly increased when compared with controls (p < 0.001). Of these 98, 25 had a HC ≤ 3rd percentile. Of the case population, 141 had an ultrasound in the perinatal unit within 10 days of birth. A HC < 5th percentile was found in 38.3% of cases of which 74% were ≤ 10th percentile postdelivery. The ultrasound femur and humerus length measurements were also < 5th percentile in 36.2 and 28.9%, respectively. CONCLUSION: Chronic opiate use in pregnancy appears to increase the risk for a HC ≤ 10th percentile and ≤ 3rd percentile when compared with controls. From ultrasound findings, femur and humerus lengths also appear to be shortened suggesting a possible effect on bone growth.

Blood Contaminated Amniotic Fluid and the Lamellar Body Count Fetal Lung Maturity Test.

OBJECTIVE: To determine if maternal blood contamination falsely elevates the lamellar body count fetal lung maturity test. STUDY DESIGN: Fifty mothers undergoing amniocentesis for fetal lung maturity consented to participation in the study. For each participant a blood-contaminated sample using the patient's own blood was run in tandem with the noncontaminated sample used for clinical practice. RESULTS: Of the 50 study patient samples the lamellar body count decreased by ≥ 3,000/µL in 33 (66%) and remained unchanged in 16 (32%). In only 1 case did the value increase--the actual result of 37,000/µL increased to 44,000/µL, both of which exceeded the mature level in our institution. CONCLUSION: Maternal blood contamination of amniotic fluid does not falsely increase the lamellar body count in 98% of cases. The result was falsely lowered in 2 out of 3 cases. Therefore, a mature lamellar body count test result in a blood-contaminated sample is reliable

Transplacental passage of vancomycin from mother to neonate.

OBJECTIVE: The objective of the study was to analyze a large number of patients receiving vancomycin chemoprophylaxis and evaluate the maternal and neonatal cord blood levels at the time of delivery. STUDY DESIGN: Every mother who entered labor with a positive group B streptococcal culture and a high-risk penicillin allergy with resistance to clindamycin or unknown sensitivity was consented to participate in the study. In the initial phase of the study, patients received the standard intravenous dose of 1 g every 12 hours. Based on the results, this was changed to a dosing of 15 mg/kg every 12 hours in the second phase and then further modified to 20 mg/kg every 8 hours in the third phase. Maternal and cord blood vancomycin levels were obtained at delivery and evaluated. RESULTS: A total of 55 patients consented to participate in the study, with 31 in phase I, 12 in phase II, and 12 in phase III. For the standard-dosing phase I group, only 32% of maternal and 9% of cord blood samples were therapeutic at delivery. For phase II, 50% of maternal and 33% of cord blood values were therapeutic; however, in phase III, 83% of mothers and neonates had therapeutic levels at the time of delivery. CONCLUSION: With standard dosing, only 9% of neonates have therapeutic vancomycin levels at delivery. By using a regimen of 20 mg/kg intravenous every 8 hours (maximum individual dose 2 g), the newborn therapeutic level increases above 80%. The pharmacological pattern shows that transplacental passage occurs with fetal levels equaling maternal levels, but transplacental transport is somewhat slow in both directions.

Association between cesarean delivery rate and body mass index.

OBJECTIVE: The purpose of this study was to evaluate the association between cesarean delivery rate and body mass index (BMI) for the patient population served by the University of Tennessee Medical Center in Knoxville, TN. STUDY DESIGN: A retrospective, cohort study was conducted using the perinatal birthlog fromJanuary 1, 2009 through December 31, 2009. The database totaled 2,399 women. Women who delivered > or = 23 weeks gestational age were included. Those missing data imperative to our study (height, weight, mode of delivery) were excluded. Thus, our study included 2,235 women. Cesarean delivery rate was calculated for each of the five BMI categories. Univariate analysis using Chi square, Mann-Whitney U test and independent t-test were used to describe associations between body mass index, mode of delivery and other independent variables. Additional analyses were made on the subset of nulliparous women. RESULTS: Using prepregnancy BMI, 6.7 percent of our population was underweight, 44.3 percent normal weight, 22.6 percent overweight, 20.6 percent obese, and 5.8 percent morbidly obese. The overall cesarean delivery rate was 36.2 percent. Twenty-six percent of underweight and 31.4 percent of normal weight women required cesarean delivery, while 39.1 percent of overweight, 40.8 percent of obese and 56.6 percent of morbidly obese women required cesarean delivery. In addition to cesarean delivery, hypertensive disorders (OR 3.29; 95% CI 2.51-4.31) and diabetes (OR 5.27; 95% CI 3.73-7.44) complicated significantly more pregnancies of obese women than normal weight women. CONCLUSION: There was an increased rate of cesarean delivery as BMI increased. Increased BMI is also associated with other pregnancy complications, including hypertensive disorders and diabetes.

Incidence of maternal tachycardia during the second stage of labor: a prospective observational cohort study.

OBJECTIVE: To our knowledge, this is the largest prospective study reporting on maternal heart rate (MHR) levels in laboring women (30 patients), and maternal tachycardia that is a potential risk factor in fetal monitoring confusion. Our objective was to analyze a large population of contiguous laboring patients and to assess the MHR levels attained during the second stage. METHODS: We performed a prospective study that analyzed MHR levels of second-stage laboring patients evaluating numerous predisposing maternal conditions. Univariate and stepwise multivariate logistic regression analysis were performed. RESULTS: A total of 1105 contiguous patients were analyzed and 33.9% had a sustained MHR ≥100; 18.8% had an MHR ≥110; and 9.1% had an MHR ≥120. Multivariate analysis of all potential predisposing maternal conditions did not reveal any specific variable as uniformly significant for predicting maternal tachycardia across all levels of analysis. CONCLUSIONS: The incidence of maternal tachycardia in the second stage of labor is common. We recommend that if the MHR is ≥100 during labor, the simultaneous maternal and fetal heart rate (FHR) monitoring will be used to minimize the potential for fetal monitoring confusion and risking poor fetal outcome if the fetus is in distress.

Postprandial walking reduces glucose levels in women with gestational diabetes mellitus.

The purpose of this study was to investigate blood glucose changes, as measured by a continuous glucose monitoring system, that occur in women with gestational diabetes mellitus (GDM) following an acute bout of moderate-intensity walking after consuming a high-carbohydrate/low-fat meal. This study found that moderate-intensity walking induced greater postprandial glucose control compared with sedentary activity and it appears that moderate-intensity activity may be used to reduce postprandial glucose levels in women with GDM.

17-Hydroxyprogesterone caproate reverses induced vasoconstriction of the fetoplacental arteries by the thromboxane mimetic U46619.

OBJECTIVE: This study was undertaken to determine whether 17-hydroxyprogesterone caproate (17P) has a vasoactive effect on fetoplacental vasculature. STUDY DESIGN: Two cotyledons were obtained from each of 5 placentas. Baseline perfusion was established with Hanks-based solution. One cotyledon from each pair was then infused with perfusate to which U46619 a thromboxane sympathomimetic had been added. After 30 minutes, a dose of 17P was then administered to each cotyledon. Finally, a vasoconstricting dose of angiotensin II was administered to each cotyledon. Perfusion pressures were recorded throughout. Statistical analysis of pressure change for a single cotyledon was performed by using a paired t test. Statistical analysis of mean perfusion pressure difference between U46619 exposed and nonexposed cotyledons was analyzed by using a students t test. RESULTS: 17P did not significantly alter the perfusion pressure of the control cotyledon. (30.6 +/- 8.3 mm Hg vs 30.1 +/- 7.8 mm Hg P = .48). 17P administration significantly lowered the perfusion pressure of the U46619 preconstricted vessels in comparison with preadministration. (60.1 +/- 13 mm Hg vs 27.3 +/- 7.1 mm Hg P = .03). Both groups of cotyledons responded with vasoconstriction to angiotension II with no difference in response between groups (38.3 +/- 12 mm Hg vs 45.8 +/- 8.2 mm Hg P = .63). CONCLUSION: 17P reverses induced vasoconstriction by U46619 in fetoplacental arteries.

Progesterone reduces lipopolysaccharide induced interleukin-6 secretion in fetoplacental chorionic arteries, fractionated cord blood, and maternal mononuclear cells.

OBJECTIVE: The purpose of this study was to characterize effect of progesterone (P4) on interleukin-6 (IL-6) production by fetoplacental artery explants, fetal granulocytes, and fetal and maternal mononuclear cells. STUDY DESIGN: Arteries and cord blood were obtained from 5 term pregnancies undergoing repeat cesarean section. Maternal blood was obtained from another 6 women at 16 to 20 weeks' gestation. Tissues were fractionated by dissection or Histopaque gradient. Specimens were incubated in physiologic media then exposed to lipopolysaccharide (LPS) or P4 alone, or pretreated with P4 and then exposed to LPS. Samples were evaluated for IL-6 by enzyme-linked immunosorbent assay (ELISA). RESULTS: Arteries and fetal and maternal mononuclear cells exposed to LPS increased IL-6 secretion by 9-, 27-, and 29-fold, respectively. P4 pretreatment blocked LPS induction of IL-6. Fetal granulocytes did not increase IL-6 production in response to LPS exposure. CONCLUSION: LPS induces IL-6 in arteries and fetal and maternal mononuclear cells. P4 pretreatment significantly blocks this effect in these cell populations, suggesting possible targets for anti-inflammatory actions of P4 in prevention of preterm birth.

Comparison of elective induction of labor with favorable Bishop scores versus expectant management: a randomized clinical trial.

OBJECTIVE: To determine if elective induction (IND) increases the risk of cesarean delivery compared to expectant management (EM). METHODS: A randomized clinical trial involving women 39 weeks' gestation, according to strict dating criteria, with a Bishop score of 5 or more in nulliparous patients and 4 or more in multiparous patients. The control group was expectantly managed and delivered for obstetric indications, but not later than 42 weeks' gestation. The study had 80% power to detect a three-fold increase in cesarean delivery. RESULTS: One-hundred-and-sixteen patients (45 nulliparous) were randomized to IND and 110 (58 nulliparous) to EM. Demographic characteristics were no different between the groups. The cesarean delivery rate in the IND group was 6.9% (8/116) compared to 7.3% (8/110) in the EM group (p = NS). Rates of cesarean delivery for nulliparous patients randomized to IND compared to EM were also not significantly different: 13.3% (6/45) versus 10.3% (6/58) respectively (p = NS). Neonates delivered of IND patients weighed less than those of the EM group (3459 +/- 347 versus 3604 +/- 438, p = 0.006). CONCLUSION: In women with favorable Bishop scores, elective induction of labor resulted in no increase in cesarean delivery compared to expectant management.

Accuracy of the lamellar body count in amniotic fluid contaminated by meconium.

OBJECTIVE: To determine whether meconium-contaminated amniotic fluid falsely elevates the lamellar body count in fetal lung maturity testing. METHODS: Thirty mothers undergoing amniocentesis for fetal lung maturity testing were prospectively consented. A 2 mL portion of the patient's sample was mixed with a 10% meconium solution and the meconium-stained sample was then run in tandem with the patient's sample used in clinical management. Pure meconium samples without amniotic fluid were also run through the cell counter for analysis. RESULTS: Following meconium contamination, the lamellar body count value increased in 67% of the cases, decreased in 23% and remained the same in 10%. There were 13 test results that had "immature" values in the uncontaminated patient management sample group and nine of these (69%) became elevated to a "mature" level (a false elevation) following the addition of meconium. All of the 10 pure liquid meconium samples devoid of amniotic fluid processed by the cell counter identified and quantified some particle the size of platelets. CONCLUSIONS: The lamellar body count test result is not reliable in meconium-stained amniotic fluid specimens. There is some unknown particle found in meconium that is the size of platelets/lamellar bodies that can falsely elevate the test result. Currently, the only reliable fetal lung maturity test in meconium-stained amniotic fluid is the presence of phosphatidylglycerol.

The distribution and predictive value of Bishop scores in nulliparas between 37 and 42 weeks gestation.

OBJECTIVE: The natural distribution and predictive accuracy of Bishop scores was evaluated to predict cesarean delivery (CD) in nulliparas between 37 and 42 weeks gestation. STUDY DESIGN: Subjects underwent serial digital cervical examinations. The Bishop score was evaluated as a binary and continuous factor to predict CD at each gestational week beginning at 37 weeks. Bishop scores were categorized as ≤5 or >5, and CD rates were compared across Bishop score categories using chi-square or Fisher exact tests at each gestational week beginning at 37 weeks. RESULTS: In all, 171 patients were prospectively followed. The overall CD rate was 27.5%. The prevalence of unfavorable Bishop scores, categorized as ≤5, decreased with increasing gestation age until 41 weeks. CD rates for the cohort with unfavorable Bishop scores was higher than those with favorable scores at each week. The likelihood ratio for CD was 1.35-2.00, depending on gestational age. The Bishop score that best predicted subsequent vaginal delivery following expectant management was >3 at 37 weeks and >5 at 39 weeks. CONCLUSION: A Bishop score ≤5 between 37 and 39 weeks gestation predicts a higher CD rate compared to patients with a Bishop score >5 implying an intrinsically higher CD risk despite expectant management.

Vagal nerve stimulator use during pregnancy for treatment of refractory seizure disorder.

BACKGROUND: In patients with medically refractory seizures, vagal nerve stimulation is becoming an increasingly common adjunctive therapy. Although its safety and efficacy have been proven in the general population, little is known about its use during pregnancy. CASE: A 19-year-old primigravid woman presented during the first trimester for routine prenatal care. She had a past medical history significant for generalized tonic-clonic seizure disorder since childhood. Multiple medical regimens had failed, and a vagal nerve stimulator was implanted approximately 2 months before conception. The patient continued to take phenytoin, with improved seizure control. She had a term spontaneous delivery complicated by mild preeclampsia. CONCLUSION: Adjunctive treatment of medically refractory seizures with a vagal nerve stimulator is a viable option during pregnancy.

Postpartum hemorrhage after vaginal birth: an analysis of risk factors.

OBJECTIVE: To determine, in a single tertiary obstetric hospital, the incidence of and risk factors for postpartum hemorrhage (PPH) after a vaginal birth. METHODS: PPH was defined as measured blood loss greater than 1,000 mL and/or need for a transfusion. RESULTS: Over a 4-year period, 13,868 of 19,476 women delivered vaginally, with a PPH rate of 5.15%. Identified risk factors for PPH were Asian race, maternal blood disorders, prior PPH, history of retained placenta, multiple pregnancy, antepartum hemorrhage, genital tract lacerations, macrosomia (>4 kg), and induction of labor, as well as chorioamnionitis, intrapartum hemorrhage, still birth, compound fetal presentation, epidural anesthesia, prolonged first/second stage of labor, and forceps delivery after a failed vacuum. CONCLUSIONS: Identification of risk factors for PPH after a vaginal delivery may afford prophylactic treatment of such women with reduction of morbidity.

Progesterone modulation of inflammatory cytokine production in a fetoplacental artery explant model.

OBJECTIVE: The purpose of this study was to determine if progesterone has an effect on fetoplacental artery production of inflammatory cytokines. STUDY DESIGN: Chorionic plate arteries were dissected from 5 placentas obtained from normal pregnancies after delivery at term. Arteries were incubated in Dulbecco's modified Eagle's medium (DMEM) alone, DMEM and lipopolysaccharide (LPS), DMEM with progesterone (P4), and DMEM with P4 and LPS. Samples of the tissue culture media were collected and evaluated for interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) by immunoassay. RESULTS: There was a significant decrease in the production of IL-6 in P4-exposed fetoplacental arteries after LPS stimulation (P < .001). IL-10 and TNF-alpha levels were similar in control and treatment groups after LPS exposure. CONCLUSION: Pretreating fetoplacental arteries with P4 significantly decreased the production of IL-6 after LPS stimulation without altering the production of TNF-alpha or IL-10.

The effects of a cyclo-oxygenase II inhibitor on placental artery production of thromboxane and prostacyclin.

OBJECTIVE: The study was undertaken to determine the effects of a cyclo-oxygenase II inhibitor on fetoplacental artery production of prostacyclin and thromboxane A(2). STUDY DESIGN: Eight placentas were obtained from normal parturients at delivery and four chorionic plate arteries were dissected from each placenta. Arteries were incubated in media alone, media plus angiotensin II (1x10(-10) mol), media plus rofecoxib (300 ng/mL), or media plus angiotensin II and rofecoxib. Serial samples were assayed for metabolites of thromboxane B(2) and prostacyclin by enzyme-linked immunosorbent assay. Results were compared by analysis of variance, and P<.05 was considered significant. RESULTS: At 24 hours, 6-keto-prostaglandin F(1alpha) levels in the rofecoxib group (1.74+/-1.39 ng/mg tissue, P<.01) and the rofecoxib plus angiotensin II group (2.15+/-1.85 ng/mg tissue, P<.01) were significantly lower than levels in the control group (4.25+/-2.03 ng/mg tissue). Thromboxane B(2) levels were lower in the angiotensin II group (0.65+/-0.33 ng/mg tissue) than the control group (1.22+/-0.70 ng/mg tissue, P<.05). CONCLUSION: Cyclo-oxygenase II inhibition decreases the production of prostacyclin in fetoplacental arteries and alters the normal ratio of thromboxane A(2) to prostacyclin.

Fetoplacental vascular tone is modified by magnesium sulfate in the preeclamptic ex vivo human placental cotyledon.

OBJECTIVE: The purpose of this study was to evaluate fetoplacental vascular tone and response to a vasoconstrictor in placentas of preeclamptic and normotensive pregnancies with and without the presence of magnesium sulfate. STUDY DESIGN: Two cotyledons from each placenta were selected from preeclamptic (n=8) and normotensive (n=7) pregnancies. In one cotyledon from each pair, the maternal circuit was perfused with magnesium sulfate. The fetal arteries were injected sequentially with angiotensin II (10(-10)mol and 10(-11.5) mol). Perfusion pressures and response to angiotensin II were compared, with regard to preeclampsia and exposure to magnesium sulfate. RESULTS: Perfusion pressure was higher in preeclamptic placentas, compared with normotensive placentas (30.4 mm Hg vs 24.4 mm Hg, P=.02). There was a decrease in perfusion pressure with exposure to magnesium sulfate in preeclamptic placentas (22.5 mm Hg, P<.01), but not in normotensive placentas. Fetoplacental vascular response to angiotensin II was not affected by preeclampsia or magnesium sulfate. CONCLUSION: In placentas from preeclamptic pregnancies there is increased fetoplacental perfusion pressure, which decreases with exposure to sulfate.