Is there benefit to continue magnesium sulphate postpartum in women receiving magnesium sulphate before delivery? A randomised controlled study.

OBJECTIVE: To determine if the use of magnesium sulphate postdelivery reduces the risk of eclampsia in women with severe pre-eclampsia exposed to at least 8 hours of magnesium sulphate before delivery. DESIGN: Randomised multicentre controlled trial. SETTING: Latin America. POPULATION: Women with severe pre-eclampsia that had received a 4-g loading dose followed by 1 g per hour for 8 hours as maintenance dose before delivery. METHODS: In all, 1113 women were randomised; 555 women were randomised to continue the infusion of magnesium sulphate for 24 hours postpartum and 558 were randomised to stopping the magnesium sulphate infusion immediately after delivery. OUTCOME MEASURES: Primary outcome was the incidence of eclampsia in the first 24 hours postdelivery. Secondary outcomes included maternal death, maternal complications, time to start ambulation and time to start lactation. RESULTS: The maternal characteristics at randomisation between the groups were not different. There were no differences in the rate of eclampsia; 1/555 (0.18%) versus 2/558 (0.35%) [relative risk (RR 0.7, 95% CI 0.1-3.3; P = 0.50] or maternal complications between the groups (RR 1.0, 95% CI 0.8-1.2; P = 0.76). Time to start ambulation was significantly shorter in the no magnesium sulphate group (18.1 ± 10.6 versus 11.8 ± 10.8 hours; P = 0.0001) and time to start lactation was equally shorter in the no magnesium sulphate group (24.1 ± 17.1 versus 17.1 ± 16.8 hours; P = 0.0001). CONCLUSIONS: Women with severe pre-eclampsia treated with a minimum of 8 hours of magnesium sulphate before delivery do not benefit from continuing the magnesium sulphate for 24 hours postpartum. TWEETABLE ABSTRACT: No benefit of continuing magnesium sulphate postpartum in severe pre-eclampsia exposed to this drug for a minimum of 8 hours before delivery.

Prevention of preterm birth with pessary in singletons (PoPPS): randomized controlled trial.

OBJECTIVE: To determine if pessary use prevents preterm birth (PTB) in women with singleton pregnancy, with short cervical length (CL) measured on transvaginal sonography (TVS) and without prior spontaneous PTB (sPTB). METHODS: This was an open-label multicenter randomized trial of asymptomatic women presenting at 18 + 0 to 23 + 6 weeks' gestation with a singleton pregnancy, CL ≤ 25 mm on TVS and no prior sPTB. sPTB included those with spontaneous onset of labor and those with rupture of membranes prior to labor. Subjects were randomized to receive either a Bioteque cup pessary or no pessary. Pessaries were inserted by trained maternal-fetal medicine staff. Vaginal progesterone was recommended to women with CL ≤ 20 mm. The primary outcome was PTB < 37 weeks. A sample size of 121 women in each group (n = 242) was needed to detect a reduction in the primary outcome from 30% in the no-pessary group to 15% in the pessary group. The trial was stopped early before complete enrollment. RESULTS: Between 17 March 2014 and 29 July 2016, 17 383 women underwent CL measurement on TVS. Of these, 422 (2.4%) had CL ≤ 25 mm and 391 (92.7%) met the full eligibility criteria, of which 122 (31.2%) agreed to randomization. Sixty-one (50%) women were randomized to the pessary group and 61 (50%) to the no-pessary group. Baseline characteristics were similar between the groups. There were no significant differences between the pessary and no-pessary groups in the rate of PTB < 37 weeks (43% vs 40%; relative risk 1.09; 95% CI, 0.71-1.68) or in secondary outcomes, such as rate of PTB < 34 weeks, rate of PTB < 28 weeks, gestational age at delivery, birth weight and rate of composite adverse neonatal outcome. CONCLUSIONS: Cervical pessary use was not associated with prevention of PTB in women with a singleton pregnancy, short CL on TVS and no prior sPTB in this small, underpowered randomized controlled trial. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prevention of preterm birth with pessary in twins (PoPPT): a randomized controlled trial.

OBJECTIVE: To evaluate whether cervical pessary placement prevents preterm birth (PTB) in twin gestations with a short mid-trimester cervical length (CL) on transvaginal sonography (TVS). METHODS: This was a multicenter randomized controlled trial of asymptomatic women with a twin gestation and a TVS-CL of ≤ 30 mm at 18 + 0 to 27 + 6 weeks' gestation. TVS-CL was measured at the time of the fetal anatomy scan at 18 + 0 to 23 + 6 weeks and at subsequent scheduled ultrasound scans prior to 28 weeks. Women with a TVS-CL of ≤ 30 mm at 18 + 0 to 27 + 6 weeks were randomized to receive either the Bioteque™ cup cervical pessary or no pessary. Randomization was stratified by gestational age, study site and chorionicity. Women with a monoamniotic twin gestation, twin-twin transfusion syndrome, early selective intrauterine growth restriction or placenta previa were excluded. Cervical pessaries were inserted by maternal-fetal medicine staff centrally trained in proper placement. No other treatment for women with a short cervix was recommended. Primary outcome was PTB < 34 weeks. The trial was stopped early before complete enrollment. RESULTS: A total of 421 women with a twin gestation were screened for TVS-CL, and 85 (20%) had a TVS-CL of ≤ 30 mm. Of these, 80 (94%) met the eligibility criteria and 46 (58%) of the eligible women agreed to randomization. Twenty-three (50%) women were randomized to pessary placement and 23 (50%) to no pessary. Demographic characteristics, including median gestational age (21.0 vs 21.2 weeks; P = 0.69) and TVS-CL (16.7 vs 22.9 mm; P = 0.45) at randomization, were similar between the pessary and no-pessary groups, except for level of education (more than high school education: 48% vs 78%, respectively; P = 0.03) and proportion of spontaneous conceptions (83% vs 43%, respectively; P = 0.01). There were no significant differences between the pessary and no-pessary groups in rate of primary outcome, PTB < 34 weeks (39% vs 35%; relative risk, 1.13 (95% CI, 0.53-2.40)), as well as other outcomes, including PTB < 37 weeks and < 28 weeks, gestational age at delivery, birth weight and composite adverse neonatal outcome. CONCLUSION: Treatment with cervical pessary was not associated with the prevention of PTB in women with a twin gestation and a mid-trimester TVS-CL of ≤ 30 mm in this small underpowered randomized controlled trial. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Anatomy and physiology of the uterine cervix.

The human uterine cervix undergoes extensive changes during pregnancy. Collagen is reorganized and consolidated early in gestation with proliferation and hyperplasia of the cellular component. As term approaches, multiple factors work together in complex interactions that cause collagen dispersion and the cervix to ripen (clinically become softer). Increases in decorin levels, hyaluronic acid, and physiologic cell death are in part responsible for this remodeling process. As the collagen bundles disperse and lose strength, cytokines, hyaluronic acid, collagenases, and elastase possibly work together to allow effacement. Then, the mechanical forces of uterine contractions extend the elastin and allow dilatation. During dilation, levels of cytokines and hyaluronic acid begin to decrease, which may serve to decrease collagenolytic activity and allow the cervix to begin the process of repairing itself. Despite this advance knowledge of cervical ripening, the signals responsible for the initiation of these changes remain to be elucidated. If we can understand the exact mechanisms that affect these changes, then we may be better able to address such complex issues as cervical incompetence, preterm delivery, postterm delivery, and proper "ripening" of the cervix to avoid surgical delivery for arrest disorders of the active phase.

Urinary cyclic GMP, endothelin, and prostaglandin E2 in normal pregnancy and preeclampsia.

Cyclic GMP, endothelin and prostaglandin E2 (PGE2) all have systemic vasoactive properties (with cyclic GMP acting as a second messenger of nitric oxide). Intrarenally they act as natriuretics and urinary levels reflect intrarenal production. Cyclic GMP and PGE2 also act as important inhibitors of platelet activation and thrombosis. The purpose of this study was to determine if urinary levels of cyclic GMP, endothelin, and PGE2 differ in preeclamptic as compared to normal pregnancies. Parameters were compared in 13 normotensive, nonpreeclamptic pregnancies, and 32 preeclamptic pregnancies. Preeclamptic women had significantly lower levels of urinary cyclic GMP (0.67 +/- 0.12 vs. 2.1 +/- 0.5 nmol/g creatinine), endothelin (0.88 +/- 0.09 vs. 3.75 +/- 1.4 ng/g creatinine), and PGE2 (26 +/- 4 vs. 9 ng/g creatinine) as compared to normals (p < 0.05). Intrarenal production of cyclic GMP, endothelin, and PGE2 are all disturbed in preeclampsia and may have implications in the sodium retention, hypertension, and intrarenal thrombosis and vasospasm of preeclamptic pregnancy.

Placenta accreta: evaluation with color Doppler US, power Doppler US, and MR imaging.

PURPOSE: To determine the value of transabdominal ultrasound (US), transvaginal US, color Doppler US, power Doppler US, and magnetic resonance (MR) imaging in the diagnosis of placenta accreta. MATERIALS AND METHODS: Nineteen patients in the third trimester of pregnancy who were at risk for placenta accreta underwent color Doppler and power Doppler US; 18 patients also underwent MR imaging. Images were interpreted prospectively for signs of accreta by two reviewers. The reviewers' confidence in their diagnosis was graded on a five-point scale. RESULTS: Outcomes at delivery were as follows: normal placenta (n = 11), hysterectomy owing to uncontrollable bleeding (n = 1), and placenta accreta (n = 7). Five cases of lower-uterine-segment placenta accreta were diagnosed with a high level of confidence with vaginal and power Doppler US. In one patient with a posterior placenta who had previously undergone myomectomy, MR imaging enabled the diagnosis of placenta accreta, which was not well depicted at US. CONCLUSION: In patients with a history of uterine scars, vaginal US with power Doppler US performed well in the evaluation of lower-uterine-segment placenta accreta. MR imaging depicts posterior placenta accreta.

Cost-effectiveness of fetal lung maturity testing in preterm labor.

OBJECTIVE: To determine the marginal cost-effectiveness of two strategies for preventing respiratory distress syndrome (RDS) resulting from preterm birth: 1) tocolysis with beta-mimetic agonists and treatment with corticosteroids (TREATALL), and 2) amniocentesis and testing for fetal lung maturity, with treatment based on test results (TESTALL), compared with no treatment. METHODS: We used a Markov decision analytic model to estimate the outcomes of each strategy, from a hospital-based perspective. Probability variables were obtained from the literature, whereas cost variables came from the Beth Israel-Deaconess Medical Center. Sensitivity analysis was performed on all variables. RESULTS: The most cost-effective strategy varied with the probability of RDS. TREATALL was the most cost-effective strategy above a probability of 17% (before 34 weeks' gestation), TESTALL was most cost-effective from 17% to 2% (34-36 weeks), and it was most cost-effective to use no treatment at probabilities less than 2% (after 36 weeks). TREATALL and TESTALL were both cost-saving compared with no treatment at probabilities of RDS above 2%. TREATALL was more highly favored as the costs of RDS and preterm birth increased, whereas TESTALL was more favored as the specificity of the test and the cost of maternal hospitalization increased. CONCLUSION: Although testing for fetal lung maturity is useful in many clinical situations, the cost-effectiveness of such testing in the setting of idiopathic preterm labor from a tertiary medical center perspective depends primarily on the probability and costs of RDS and the costs of non-RDS-related morbidity. At our institution, such testing is cost-effective between 34 and 36 weeks' gestation.

Performance of the dipalmitoyl phosphatidylcholine test in predicting respiratory distress syndrome in contaminated samples of amniotic fluid.

OBJECTIVE: To evaluate the reliability of the dipalmitoyl phosphatidylcholine test in predicting respiratory distress syndrome (RDS) in the presence of common contaminants of amniotic fluid. METHODS: Forty specimens of amniotic fluid collected within 72 hours of delivery were divided in five 25 microL aliquots and diluted with either phosphate-buffered saline (control), meconium, blood, vaginal fluid, or semen. The concentration of dipalmitoyl phosphatidylcholine in all five groups of samples, as measured by the dipalmitoyl phosphatidylcholine test, was compared by paired t test, Dunnett test, and analysis of variance, and correlated with the neonatal respiratory status of the newborns. RESULTS: No significant differences in the concentration of dipalmitoyl phosphatidylcholine were found between control and the corresponding contaminated samples (P = .33). Of the 200 samples evaluated, 80 had dipalmitoyl phosphatidylcholine concentrations below 12 micrograms/mL and 120 had at least 12 micrograms/mL. Using a cutoff dipalmitoyl phosphatidylcholine concentration of 12 micrograms/mL, the presence of RDS was predicted accurately in all 15 control and in 61 of 65 contaminated samples. The absence of RDS, as predicted by a dipalmitoyl phosphatidylcholine value at least 12 micrograms/mL, was predicted accurately in 24 of 25 control samples and 96 of 100 contaminated samples. The overall accuracy of the dipalmitoyl phosphatidylcholine test in predicting RDS in contaminated samples was 98%. CONCLUSION: The dipalmitoyl phosphatidylcholine test is a reliable predictor of RDS in contaminated samples.

Maternal postural challenge as a functional test for cervical incompetence.

We studied the effect of an upright maternal position on the cervix. Of 41 high risk patients (17 to 33 weeks' gestational age), 14 of 16 who had a greater than 33% decrease in cervical length in the upright position compared to supine position delivered their infants prematurely, compared to 1 of 25 patients who had a decrease of less than 33% (P < 0.0005). No change in the cervical length was noted in 24 low-risk patients, all of whom were delivered at term. When the finding of a cervical length of less than 2 cm was combined with a postural change, the sensitivity for prediction of preterm delivery was 100%. We conclude that for patients at high risk for incompetent cervix, maternal posture-related cervical shortening can assist in predicting those who will undergo premature delivery.

Analysis of dipalmitoyl phosphatidylcholine in amniotic fluid by high-performance liquid chromatography.

A novel method for the determination of dipalmitoyl phosphatidylcholine (DPPC) in amniotic fluid by high-performance liquid chromatography (HPLC) is described. Aliquots of 50 microliters of amniotic fluid were hydrolyzed with phospholipase C from Bacillus cereus and the resulting dipalmitoylglycerol analyzed by HPLC. Run-to-run and day-to-day precision for DPPC analysis were 4.2 and 6.1%, respectively, and analysis time was 10 min. Recoveries for DPPC ranged between 92 and 98%. In summarizing, this method provides a high precision and fast turnaround time means for the analysis of DPPC in amniotic fluid.

Racial differences in the predictive value of the TDx fetal lung maturity assay.

OBJECTIVE: Black newborns have lower rates of neonatal respiratory distress syndrome compared with nonblack newborns. This has been attributed to accelerated lung maturation. Previous studies have demonstrated a difference in the predictive value of the lecithin/sphingomyelin ratio, a test for lung maturity, between races. Our study examines the predictive value of the newer TDx Fetal Lung Maturity Surfactant-to-Albumin assay. STUDY DESIGN: We reviewed the records of 393 nonblack and 87 black infants delivered within 72 hours of the TDx FLM S/A assay testing. We compared the rates of neonatal respiratory distress syndrome by race, stratified by results. RESULTS: In our study population black newborns had less than one half the rate of respiratory distress syndrome compared with nonblack newborns (4.6% vs 10.4%). To adjust for possible differences in the timing of lung maturation, the results were stratified by the TDx FLM S/A assay result. Black race had a protective effect (Mantel-Haenszel weighted odds ratio 0.30, 95% confidence interval 0.06 to 0.93, p < 0.05). This significant racial difference remained when both TDx FLM S/A assay result and gestational age were controlled in a multiple logistic regression analysis. CONCLUSIONS: There are differences in the predictive value of the TDx FLM S/A assay among races. Black fetuses are less likely to have respiratory distress syndrome. The difference in rates of respiratory distress syndrome between races must be due to either a qualitative difference in the surfactant or to an anatomic difference in fetal lungs. Consideration should be given to a lower cutoff value for a mature test result in black women.

Prediction of respiratory distress syndrome by the novel dipalmitoyl phosphatidylcholine test.

OBJECTIVE: To determine the accuracy of a new test that measures the concentration in amniotic fluid (AF) of dipalmitoyl phosphatidylcholine (DPPC) in predicting respiratory distress syndrome (RDS). METHODS: The neonatal respiratory status of 176 newborns delivered within 72 hours of sampling was correlated with the concentration of DPPC, fluorescence polarization (TDx-FLM), lecithin-sphingomyelin ratio (L/S), and phosphatidyl-glycerol (Amniostat-FLM) in AF. RESULTS: Thirty infants developed RDS (17%), all correctly predicted with DPPC values less than 12 micrograms/mL (sensitivity 100%). Only six of the 146 cases with no RDS had DPPC values less than 12 micrograms/mL (specificity 96%). The overall accuracy of the DPPC test was 98% compared with 70% for TDx-FLM, 71% for the L/S, and 67% for Amniostat-FLM. Receiver operating characteristic analysis area was 0.98 +/- 0.01, indicating that the DPPC test is superior to both the TDx-FLM and L/S tests. CONCLUSION: The DPPC test is an accurate predictor of RDS and fetal lung maturity.

Obstetric outcome after failed termination of pregnancy--a report of two cases.

Unsuccessful therapeutic abortion resulting in continued viability of the fetus is rare. No case of a live birth after unsuccessful vacuum curettage has been published. We report two cases with persistent pregnancies after failed termination, with outcomes complicated by premature rupture of membranes and preterm delivery.

Ultrasound evaluation of cervical shortening after loop excision of the transformation zone (LETZ).

OBJECTIVES: To assess cervical shortening after loop excision of the transformation zone (LETZ), and confirm the validity of ultrasound measurement of cervical length. METHODS: Subjects (n = 29) were patients at the colposcopy clinic of Beth Israel Hospital who underwent vaginal ultrasound measurement of cervical length before and after LETZ. The pathologic specimen was measured by ruler. Mean cervical length (+/- S.D.), mean percentage (+/- S.D.) of cervical length removed, and correlation (r) between ultrasound and pathology specimen measurement were determined. RESULTS: Mean (+/- S.D.) cervical length measurements prior to LETZ were 3.2 +/- 0.9 cm and after LETZ were 2.6 +/- 0.9 cm, with a difference of 0.7 +/- 0.4 cm. The pathologic specimen (mean +/- S.D.) was 0.6 +/- 0.3 cm. The correlation between ultrasound and pathology measurement was r = 0.9 (p = 0.0001). Mean (+/- S.D.) cervical length was shortened by 22 +/- 12%. CONCLUSIONS: There is excellent correlation between ultrasound and ruler measurement of the cervix. There is significant cervical length shortening after LETZ, but further study is needed to see whether this persists or leads to pregnancy complications.

Deep venous thrombosis treated with an inferior vena cava filter in a pregnant woman after recent neurosurgery. A case report.

A pregnant woman developed iliofemoral thrombosis several weeks after neurosurgery; anticoagulation was contraindicated. The thrombosis was treated successfully with an inferior vena cava filter.

Analysis of dipalmitoyl phosphatidylcholine in amniotic fluid by enzymatic hydrolysis and high-performance thin-layer chromatography reflectance spectrodensitometry.

A novel test for the determination of dipalmitoyl phosphatidylcholine (DPPC) in amniotic fluid (AF) as free dipalmitoylglycerol (DPG), is described. Aliquots of amniotic fluid were hydrolyzed with Bacilus cereus phospholipase C, and the resulting diglycerides analyzed by AgNO3-modified high-performance thin-layer chromatography (HPTLC)-reflectance spectrodensitometry. This HPTLC system provided resolution of DPG and palmitoylpalmitoleoylglycerol (POG) from other 1,2-diglycerides and cholesterol. The turn-around analysis time for triplicate aliquots of amniotic fluid was 40 min. Recoveries ranged between 90 and 98%. In summary, this method provides a quantitative, specific, highly reproducible, and fast turn-around means of analysis of DPPC in amniotic fluid.

Poor perinatal outcome associated with retained cerclage in patients with premature rupture of membranes.

OBJECTIVE: To evaluate the role of immediate cerclage removal versus retention in patients experiencing premature rupture of the membranes remote from term (PROM). METHODS: Thirty patients with prophylactic cerclage experiencing PROM at 24-32 weeks were managed expectantly after either immediate removal in 20 (67%) or retention of the cerclage in ten (33%). Thirty-three patients without cerclage and with PROM at the same gestational age were used as controls. RESULTS: More patients with retained cerclage (nine of ten, 90%) had delivery delayed for at least 48 hours after PROM compared to patients with immediate cerclage removal (ten of 20, 50%) (P < .05). Perinatal mortality was significantly higher for those with retained cerclage (seven of ten, 70%) than with immediate removal (two of 20, 10%) or in the control group (six of 33, 18%) (P < .001). Sepsis was responsible for most of the poor outcomes in the retained-cerclage group (71%). CONCLUSIONS: Although retaining the cerclage prolonged the latency period between PROM and delivery, that benefit was more than offset by a greatly increased perinatal mortality rate. Our study supports immediate cerclage removal regardless of gestational age in cases of PROM.