Faculty Bibliography

OBJECTIVE:We sought to evaluate the efficacy of maintenance tocolysis with vaginal progesterone compared to control (placebo or no treatment) in singleton gestations with arrested preterm labor (PTL) in a metaanalysis of randomized controlled trials. STUDY DESIGN/METHODS:Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of key words and text words related to "progesterone," "tocolysis," and "preterm labor" from 1966 through November 2014. We included all randomized trials of singleton gestations that had arrested PTL and then were randomized to maintenance tocolysis treatment with either vaginal progesterone or control (either placebo or no treatment). All published randomized studies on progesterone tocolysis were carefully reviewed. Exclusion criteria included maintenance tocolysis in women with preterm premature rupture of membrane, maintenance tocolysis with 17-alpha-hydroxyprogesterone caproate, and maintenance tocolysis with oral progesterone. The summary measures were reported as relative risks (RRs) with 95% confidence interval (CI). The primary outcome was preterm birth (PTB) <37 weeks. RESULTS:Five randomized trials, including 441 singleton gestations, were analyzed. Women who received vaginal progesterone maintenance tocolysis for arrested PTL had a significantly lower rate of PTB <37 weeks (42% vs 58%; RR, 0.71; 95% CI, 0.57-0.90; 3 trials, 298 women). Women who received vaginal progesterone had significantly longer latency (mean difference 13.80 days; 95% CI, 3.97-23.63; 4 trials, 368 women), later gestational age at delivery (mean difference 1.29 weeks; 95% CI, 0.43-2.15; 4 trials, 368 women), lower rate of recurrent PTL (24% vs 46%; RR, 0.51; 95% CI, 0.31-0.84; 2 trials, 122 women), and lower rate of neonatal sepsis (2% vs 7%; RR, 0.34; 95% CI, 0.12-0.98; 4 trials, 368 women). CONCLUSION/CONCLUSIONS:Maintenance tocolysis with vaginal progesterone is associated with prevention of PTB, significant prolongation of pregnancy, and lower neonatal sepsis. However, given the frequent lack of blinding and the generally poor quality of the trials, we do not currently suggest a change in clinical care of women with arrested PTL. We suggest instead well-designed placebo-controlled randomized trials to confirm the findings of our metaanalysis.

We sought to evaluate the efficacy of maintenance tocolysis with 17-alpha-hydroxyprogesterone caproate (17P) compared to control (either placebo or no treatment) in singleton gestations with arrested preterm labor (PTL), in a metaanalysis of randomized trials. Electronic databases (MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials) were searched from 1966 through July 2014. Key words included "progesterone," "tocolysis," "preterm labor," and "17-alpha-hydroxyprogesterone caproate." We performed a metaanalysis of randomized trials of singleton gestations with arrested PTL and treated with maintenance tocolysis with either 17P or control. Primary outcome was preterm birth (PTB) <37 weeks. This metaanalysis was performed following the Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) statement. The protocol was registered with PROSPERO (registration no: CRD42014013473). Five randomized trials met inclusion criteria, including 426 women. Women with a singleton gestation who received 17P maintenance tocolysis for arrested PTL had a similar rate of PTB <37 weeks (42% vs 51%; relative risk [RR], 0.78; 95% confidence intervals [CI], 0.50-1.22) and PTB <34 weeks (25% vs 34%; RR, 0.60; 95% CI, 0.28-1.12) compared to controls. Women who received 17P had significantly later gestational age at delivery (mean difference, 2.28 weeks; 95% CI, 1.46-13.51), longer latency (mean difference, 8.36 days; 95% CI, 3.20-13.51), and higher birthweight (mean difference, 224.30 g; 95% CI, 70.81-377.74) as compared to controls. Other secondary outcomes including incidences of recurrent PTL, neonatal death, admission to neonatal intensive care unit, neonatal respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal sepsis were similar in both groups. Maintenance tocolysis with 17P after arrested PTL is not associated with prevention of PTB compared to placebo or no treatment in a metaanalysis of the available randomized trials. As 17P for maintenance tocolysis is associated with a significant prolongation of pregnancy, and significantly higher birthweight, further research is suggested.

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. With research efforts, the rate of PTB decreased to 11.4% in 2013. Transvaginal ultrasound (TVU) cervical length (CL) screening predicts PTB. In asymptomatic singletons without prior spontaneous PTB (sPTB), TVU CL screening should be done. If the cervix is 20 mm or less, vaginal progesterone is indicated. In asymptomatic singletons with prior sPTB, serial CL screening is indicated. In multiple gestations, routine cervical screening is not indicated. In symptomatic women with preterm labor, TVU CL screening and fetal fibronectin testing is recommended.

Cervical cerclage is an obstetric procedure performed for prevention of prematurity. Cerclage was first introduced by Drs Shirodkar and McDonald in the mid-1950s for women with repeated second trimester losses and cervical changes in current pregnancy. Currently, cerclage placement is based on 3 common indications in singleton gestations, including history-indicated (prior multiple early preterm births or second trimester losses), ultrasound-indicated (cervical length <25 mm before 24-wk gestational age in women with prior spontaneous preterm birth) and physical examination-indicated (cervical dilation on manual or physical examination before 24 wk).

OBJECTIVE:To determine whether the acceleration/ejection time ratio of the fetal main pulmonary artery Doppler waveform (PATET) can accurately predict the results of fetal lung maturity testing in amniotic fluid. METHODS:We prospectively studied pregnant women attending our ultrasound unit for clinically indicated fetal lung maturity testing. An ultrasound examination that included measurement of the PATET was performed before the results of the amniocentesis were reported. The results of the PATET and the surfactant/albumin ratio were compared, and a receiver operating characteristic curve was used to determine the PATET cutoff with the optimal sensitivity and specificity for predicting surfactant/albumin ratio results. p < 0.05 was considered statistically significant. RESULTS:Forty-three patients were included in this study. The receiver operating characteristic curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93% (95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58-96%) for predicting immature surfactant/albumin ratio results. CONCLUSION/CONCLUSIONS:The PATET may provide a noninvasive means of determining fetal lung maturity with acceptable levels of sensitivity, specificity, and predictive values.

This study was performed to determine if cerclage height is associated with spontaneous preterm birth in patients with a history-indicated cerclage. We performed a retrospective cohort study of women with a history-indicated cerclage. Functional cervical length and the cerclage height (distance from cerclage to the external cervical os) were obtained. The cohort was grouped into thirds, based on cerclage height percentile. Our primary outcome was spontaneous preterm birth <35 weeks. There were 21 women in group 1 (cerclage height <10 mm), 53 in group 2 (cerclage height 10 to 19 mm), and 31 in group 3 (cerclage height ≥20 mm). The rates of spontaneous preterm birth <35 weeks were similar between each group: 24, 17, and 10%, respectively ( P = 0.38). Cerclage height is not associated with a reduction in spontaneous preterm birth for women with a history-indicated cerclage. The association between longer cerclage height and decrease in preterm birth was nonsignificant possibly due to the small sample size.

We estimated the optimal gestational age for placement of a history-indicated cerclage in a retrospective cohort study of pregnancies during the period between 1994 to 2007. Pregnancies were divided into two groups: group 1, cerclage <14 weeks (N = 83), and group 2, cerclage >or=14 weeks (N = 59). The primary outcome was spontaneous preterm birth (SPTB) <35 weeks. Parametric and nonparametric tests were performed where appropriate. One hundred forty-two pregnancies by 130 women were included. Demographic characteristics were similar between groups. The median gestational age at cerclage was 12 weeks (group 1) and 15 weeks (group 2). There was no difference in the primary outcome, incidence of SPTB <35 weeks (17% versus 20%; P = 0.59) between groups 1 and 2, respectively. Likewise, the secondary outcomes, mean gestational age at birth (38 versus 37 weeks; P = 0.96), incidence of low birth weight (28% versus 23%; P = 0.50), and the incidence of preterm premature rupture of membranes (17% versus 18%; P = 0.89) were similar between groups. No other gestational age cutoff was predictive of SPTB <35 weeks using a receiver operator characteristic curve (13 to 17 weeks; area = 0.52; P = 0.64). Gestational age of history-indicated cerclage placement was not associated with a significant effect on preterm birth in high-risk women. The optimal gestational age for placement of a history-indicated cerclage is probably 12 to 14 weeks, after screening for fetal anomalies and aneuploidy.

OBJECTIVE:The purpose of this study was to estimate the time interval between elective cerclage removal and spontaneous delivery. METHODS:Singleton pregnancies with McDonald cerclage were evaluated for the interval between elective cerclage removal (36-37 weeks) and spontaneous delivery. We also compared spontaneous delivery within 48 hours after cerclage removal between women with ultrasound-indicated vs history-indicated cerclage. RESULTS:We identified 141 women with elective cerclage removal. The mean interval between removal and delivery was 14 days. Only 11% of women delivered within 48 hours. Women with ultrasound-indicated cerclage were more likely to deliver within 48 hours, compared with women with history-indicated cerclage (odds ratio, 5.14; 95% confidence interval, 1.10-24.05). CONCLUSION/CONCLUSIONS:The mean interval between elective cerclage removal and spontaneous delivery is 14 days. Women with cerclage who achieved 36-37 weeks should be counseled that their chance of spontaneous delivery within 48 hours after elective cerclage removal is only 11%.