Trends in preterm birth: an academic center's campaign to reduce the incidence.

OBJECTIVE: To evaluate if the implementation of five protocols aimed at reducing the preterm birth rate were associated with a decrease in incidence of PTBs at an academic center. METHODS: This is an observational study of women with singleton gestations delivered at TJUH between 2004 and 2014. Primary outcome was the annual incidence of PTB <37 weeks at TJUH. Secondary outcome was the rate of change for PTBs at TJUH compared against that of the nation. Linear regression, Pearson correlation coefficients, and t-tests were used to analyze preterm birth rates over time. RESULTS: TJUH incidence of PTB < 37 weeks significantly decreased from 10.8% (n = 206) in 2004 to 9.1% (n = 169) in 2014 (p = .001). Linear regression showed a dramatically greater rate of decline at TJUH (0.32% per year, p = .001) compared to that of the USA (0.14% per year, p < .0001). Early PTBs (28-33 6/7 week) at TJUH had the steepest rate of decline at 0.13% per year (p = .001). Late PTBs (34-36 6/7 week) at TJUH were the only group to not have a significant rate of decline (p = .114). CONCLUSION: The incidence of PTBs at TJUH decreased more than the USA national average in the study period, which may be due to early adoption of guidelines for prevention of PTB. CONDENSATION: The incidence of PTBs at TJUH decreased more than the USA national average in the study period, which may be due to early adoption of guidelines for prevention of PTB.

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study.

Background: The coronavirus disease 2019 pandemic has had an impact on healthcare systems around the world with 3 million people contracting the disease and 208,000 cases resulting in death as of this writing. Information regarding coronavirus infection in pregnancy is still limited. Objective: This study aimed to describe the clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnant women with positive laboratory testing for severe acute respiratory syndrome coronavirus 2. Study Design: This is a cohort study of pregnant women with severe or critical coronavirus disease 2019 hospitalized at 12 US institutions between March 5, 2020, and April 20, 2020. Severe disease was defined according to published criteria as patient-reported dyspnea, respiratory rate >30 per minute, blood oxygen saturation ≤93% on room air, ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen <300 mm Hg, or lung infiltrates >50% within 24-48 hours on chest imaging. Critical disease was defined as respiratory failure, septic shock, or multiple organ dysfunction or failure. Women were excluded from the study if they had presumed coronavirus disease 2019, but laboratory testing was negative. The primary outcome was median duration from hospital admission to discharge. Secondary outcomes included need for supplemental oxygen, intubation, cardiomyopathy, cardiac arrest, death, and timing of delivery. The clinical courses are described by the median disease day on which these outcomes occurred after the onset of symptoms. Treatment and neonatal outcomes are also reported. Results: Of 64 hospitalized pregnant women with coronavirus disease 2019, 44 (69%) had severe disease, and 20 (31%) had critical disease. The following preexisting comorbidities were observed: 25% had a pulmonary condition, 17% had cardiac disease, and the mean body mass index was 34 kg/m2. Gestational age was at a mean of 29±6 weeks at symptom onset and a mean of 30±6 weeks at hospital admission, with a median disease day 7 since first symptoms. Most women (81%) were treated with hydroxychloroquine; 7% of women with severe disease and 65% of women with critical disease received remdesivir. All women with critical disease received either prophylactic or therapeutic anticoagulation during their admission. The median duration of hospital stay was 6 days (6 days [severe group] and 10.5 days [critical group]; P=.01). Intubation was usually performed around day 9 on patients who required it, and peak respiratory support for women with severe disease was performed on day 8. In women with critical disease, prone positioning was required in 20% of cases, the rate of acute respiratory distress syndrome was 70%, and reintubation was necessary in 20%. There was 1 case of maternal cardiac arrest, but there were no cases of cardiomyopathy or maternal death. Thirty-two of 64 (50%) women with coronavirus disease 2019 in this cohort delivered during their hospitalization (34% [severe group] and 85% [critical group]). Furthermore, 15 of 17 (88%) pregnant women with critical coronavirus disease 2019 delivered preterm during their disease course, with 16 of 17 (94%) pregnant women giving birth through cesarean delivery; overall, 15 of 20 (75%) women with critical disease delivered preterm. There were no stillbirths or neonatal deaths or cases of vertical transmission. Conclusion: In pregnant women with severe or critical coronavirus disease 2019, admission into the hospital typically occurred about 7 days after symptom onset, and the duration of hospitalization was 6 days (6 [severe group] vs 12 [critical group]). Women with critical disease had a high rate of acute respiratory distress syndrome, and there was 1 case of cardiac arrest, but there were no cases of cardiomyopathy or maternal mortality. Hospitalization of pregnant women with severe or critical coronavirus disease 2019 resulted in delivery during the clinical course of the disease in 50% of this cohort, usually in the third trimester. There were no perinatal deaths in this cohort.

Azithromycin vs erythromycin for the management of preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes complicates 2-3% of pregnancies. Many institutions have advocated for the use of azithromycin instead of erythromycin. This is secondary to national shortages of erythromycin, ease of administration, better side effect profile, and decreased cost of azithromycin as compared with erythromycin. OBJECTIVE: The objective of the study was to evaluate whether there are differences in the latency from preterm premature rupture of membranes to delivery in patients treated with different dosing regimens of azithromycin vs erythromycin. STUDY DESIGN: This is a multicenter, retrospective cohort of women with singleton pregnancies with confirmed rupture of membranes between 230 and 336 weeks from January 2010 to June 2015. Patients were excluded if there was a contraindication to expectant management of preterm premature rupture of membranes. Patients received 1 of 4 antibiotic regimens: (1) azithromycin 1000 mg per os once (azithromycin 1 day group); (2) azithromycin 500 mg per os once, followed by azithromycin 250 mg per os daily for 4 days (azithromycin 5 day group); (3) azithromycin 500 mg intravenously for 2 days, followed by azithromycin 500 mg per os daily for 5 days (azithromycin 7 day group); or (4) erythromycin intravenously for 2 days followed by erythromycin per os for 5 days (erythromycin group). The choice of macrolide was based on institutional policy and/or availability of antibiotics at the time of admission. In addition, all patients received ampicillin intravenously for 2 days followed by amoxicillin per os for 5 days. Primary outcome was latency from diagnosis of rupture of membranes to delivery. Secondary outcomes included clinical and histopathological chorioamnionitis and neonatal outcomes. RESULTS: Four hundred fifty-three patients who met inclusion criteria were identified. Seventy-eight patients received azithromycin for 1 day, 191 patients received azithromycin for 5 days, 52 patients received azithromycin for 7 days, and 132 patients received erythromycin. Women who received the 5 day regimen were younger and less likely to be non-African American, have hypertension, have sexually transmitted infection, or experienced substance abuse. There was no statistical difference in median latency time of azithromycin 1 day (4.9 days, 95% confidence interval, 3.3-6.4), azithromycin 5 days (5.0, 95% confidence interval, 3.9-6.1), or azithromycin 7 days (4.9 days, 95% confidence interval, 2.8-7.0) when compared with erythromycin (5.1 days, 95% confidence interval, 3.9-6.4) after adjusting for demographic variables (P = .99). Clinical chorioamnionitis was not different between groups in the adjusted model. Respiratory distress syndrome was increased in the azithromycin 5 day group vs azithromycin 1 day vs erythromycin (44% vs. 29% and 29%, P = .005, respectively). CONCLUSION: There was no difference in latency to delivery, incidence of chorioamnionitis, or neonatal outcomes when comparing different dosing regimens of the azithromycin with erythromycin, with the exception of respiratory distress syndrome being more common in the 5 day azithromycin group. Azithromycin could be considered as an alternative to erythromycin in the expectant management of preterm premature rupture of membranes if erythromycin is unavailable or contraindicated. There appears to be no additional benefit to an extended course of azithromycin beyond the single-day dosing, but final recommendations on dosing strategies should rely on clinical trials.

A retrospective cohort study of fetal assessment following preterm premature rupture of membranes.

OBJECTIVE: To evaluate maternal and neonatal outcomes following management of preterm premature rupture of membranes (PPROM) by two fetal assessment strategies. METHODS: In a retrospective cohort study performed at two hospitals in Philadelphia, Pennsylvania between July 2010 and June 2015, data were reviewed from 180 singleton pregnancies with PPROM at 230 -336  weeks of gestation that underwent expectant management. Outcomes were compared between continuous electronic fetal heart monitoring (EFM) with daily biophysical profile (BPP) ("continuous monitoring") and non-stress test (NST) three times per day ("periodic monitoring") using Mann-Whitney U and Fisher exact tests. RESULTS: Overall, 119 (66.1%) pregnancies were assessed by continuous monitoring and 61 (33.9%) by periodic monitoring. There was no difference in frequency of intrauterine death between the continuous monitoring (1, 0.8%) and periodic monitoring (3, 4.9%) groups (OR, 0.16; 95% CI, 0.02-1.61). The continuous monitoring group was more likely to have an interventional (OR, 2.17; 95% CI, 1.06-4.44) or cesarean (OR 3.30, 95% CI 1.70-6.38) delivery. CONCLUSION: Continuous EFM with daily BPP was associated with higher rates of intervention and cesarean delivery compared with periodic NST, but there was no difference in intrauterine or perinatal mortality.

Decrease in the incidence of threatened preterm labor after implementation of transvaginal ultrasound cervical length universal screening.

BACKGROUND: It is unknown if universal second-trimester transvaginal ultrasound (TVU) cervical length (CL) screening in asymptomatic women with singleton gestations and no prior spontaneous preterm birth (SPTB) affects the incidence of symptoms of preterm labor (PTL) later in pregnancy. OBJECTIVE: To evaluate the incidence of threatened PTL before and after the implementation of universal second trimester TVU CL screening. STUDY DESIGN: This was a retrospective cohort study of all consecutive singleton gestations without prior SPTB presenting to obstetric triage for threatened PTL between 23 0/7 and 33 6/7 week in 2011 (1 January-31 December), and in 2014 (1 January-31 December) at Thomas Jefferson University Hospital (TJU) (Philadelphia, PA). These 2 years were chosen as a new protocol for universal TVU CL screening was started on 1 January 2012. This protocol involved one measurement of TVU CL in all singleton gestations without a prior SPTB at 18 0/7 - 23 6/7 week, the time of the "anatomy" scan. Women with prior SPTB were excluded from this study. The primary outcome included the incidence of threatened PTL, defined as the number of women with singleton gestations without prior SPTB who presented with threatened PTL to our labor and delivery (L&D) triage unit annually, divided by the total number of annual deliveries of women with singleton gestation without prior SPTB. Secondary outcomes were the incidence of PTL, defined as the number of women with singleton gestations without prior SPTB admitted for PTL annually divided by the total number of annual deliveries of women with singleton gestation and without prior SPTB; and length of stay in the hospital. We aimed to compare primary and secondary outcome in the "2011" versus the "2014" group. RESULTS: In 2011, there were a total of 1745 deliveries at TJU, of which 1550 (88.8%) were singletons without prior SPTB. In 2014, there were a total of 1924 deliveries at TJU, 1751 (91.0%) were singletons without prior SPTB who were offered universal TVU CL screening. One hundred and seventy-two women with singletons without prior SPTB presented in L&D triage unit in 2011; and 118 women with singletons without prior SPTB presented in L&D triage unit in 2014. There were significant decreases in the incidence of threatened PTL from 11.1% (172/1550) in 2011 to 6.7% (118/1751) in 2014 (p < .001), as well as in the rate of admission for PTL from 2.3% (35/1550) to 1.4% (24/1751), respectively (p = .04). Length of stay was not significantly different between the two groups. CONCLUSION: The introduction of a universal TVU CL screening program in women with singleton gestations without a history of SPTB is associated with a reduction in the frequency of threatened PTL and admission for PTL. Key Message The introduction of a second trimester universal transvaginal ultrasound (TVU) cervical length (CL) screening program in women without a history of spontaneous preterm birth (SPTB) is associated with a reduction in the incidence of threatened preterm labor (PTL) and admission for PTL.

Progesterone as a tocolytic agent for preterm labor: a systematic review.

PURPOSE OF REVIEW: Tocolytic agents have been used for over 60 years in the fight against preterm labor, which ultimately can lead to preterm birth. Currently, clinicians can choose from a variety of drug classes to achieve the primary goal of delaying delivery by 48 h, thereby allowing time for administration of corticosteroids for fetal lung maturity, and if appropriate, starting magnesium sulfate for fetal neuroprotection. However, there are currently no known therapies to maintain the tocolytic effect beyond those initial 48 h. RECENT FINDINGS: Progesterone, which has been used in the prevention of preterm birth for over 10 years, has long been known to have the effect of uterine quiescence. It was first studied as a tocolytic agent in the 1960s. In the last several years, more studies have been done that suggest a potential use for maintenance tocolysis after the successful arrest of preterm labor. Although the studies are conflicting, the meta-analyses on progesterone show some promise in different outcomes of delayed delivery, reduced incidence of preterm birth, and reduced neonatal morbidity. SUMMARY: Progesterone is currently the most promising agent for maintenance tocolysis. Although further trials are certainly needed, this is an exciting advancement in the realm of tocolysis.

Tocolysis for Acute Preterm Labor: Where Have We Been, Where Are We Now, and Where are We Going?

Tocolytics have been used for over 60 years for women with preterm labor, which ultimately can lead to preterm birth (PTB). Diagnosing preterm labor is challenging, but use of objective tests such as transvaginal ultrasound of cervical length assists in the identification of women at the highest risk for PTB. Once preterm labor has been diagnosed, clinicians can choose from a variety of drug classes (cyclooxygenase inhibitors, calcium channel blockers, and betamimetics) to achieve the primary goal of delaying delivery by 48 hours, thereby allowing time for administration of corticosteroids for fetal lung maturity, and if appropriate, starting magnesium sulfate for fetal neuroprotection. Cyclooxygenase inhibitors are the only class of tocolytics proven to decrease PTB < 37 weeks. Knowledge of the safety and effectiveness of these medications is paramount. Several additional agents (e.g., oxytocin receptor antagonists) have significant promise, but further studies are required before these medications can be approved for tocolysis in the United States. As we look into the future of tocolysis, we anticipate that deeper understanding of the complex physiology of preterm labor will allow us to uniquely target different etiologies that lead to the final path resulting in spontaneous preterm delivery.

Failed induction of labor.

Induction of labor will affect almost a quarter of all pregnancies, but historically there has been no generally accepted definition of failed induction of labor. Only recently have studies analyzed the lengths of latent labor that are associated with successful labor induction ending in a vaginal delivery, and recommendations for uniformity in the diagnosis of failed induction have largely resulted from this data. This review assesses the most recent and inclusive definition for failed induction, risk factors associated with failure, complications, and special populations that may be at risk for a failed induction.

Detection of fetal structural anomalies in a basic first-trimester screening program for aneuploidy.

OBJECTIVES: The purpose of this study was to determine whether first-trimester aneuploidy screening sonography initially performed by credentialed sonographers was useful for detecting fetal anomalies between 11 and 14 weeks' gestation. METHODS: We conducted a retrospective cohort study of consecutive patients referred to a private ultrasound facility between January 1, 2008, and June 30, 2012, for measurement of the nuchal translucency (NT) and crown-rump length as part of a screening protocol for aneuploidy. Patients were included if there was at least 1 live fetus with a crown-rump length between 34 and 84 mm. No specific anatomic imaging protocol was followed. The presence of anomalies was based on the sonographic report and review of the medical record. The absence of anomalies was based on the report from the anatomic survey. Anomalies were categorized as lethal, major, and minor. The anomaly category and gestational age at diagnosis (≤14 versus >14 weeks) were compared. RESULTS: An NT scan was performed on 9692 fetuses. Anatomic surveys were done on 9077 (93.7%) of these fetuses at a mean of 18 weeks' gestation. Anomalies were detected in 180 fetuses (1.8%): 50 (0.5%) at the NT scan and 130 (1.3%) at the anatomic scan. Overall, 46 of 111 fetuses (41.4%) with major or lethal anomalies were detected at the NT scan. Two suspected abnormalities at the NT scan were not present at the anatomic scan. CONCLUSIONS: First-trimester aneuploidy screening sonography initially performed by credentialed sonographers can identify a substantial proportion of major and lethal anomalies.

What is the importance of second-trimester "soft markers" for trisomy 21 after an 11- to 14-week aneuploidy screening scan?

OBJECTIVES: The purpose of this study was to evaluate the importance of second-trimester "soft markers" for trisomy 21 after an 11- to 14-week aneuploidy screening scan. METHODS: We conducted a retrospective cohort study of consecutive patients referred for measurement of the nuchal translucency (NT) as part of a screening protocol for aneuploidy. Patients who returned for an anatomic survey between 16 and 20 weeks' gestation were evaluated. The sonographic markers and anomalies associated with the detection of trisomy 21 in the second trimester were analyzed. RESULTS: There were 42 fetuses (0.4%) with trisomy 21 identified in the study cohort of 9692 patients. Trisomy 21 was suspected at the NT scan in 28 fetuses (67%) and at the second-trimester anatomic survey in 14 (33%). In fetuses first suspected of having trisomy 21 in the second trimester, 9 of 14 had normal anatomic survey results, and 5 of 14 had congenital malformations. All 14 fetuses had soft markers for aneuploidy. A thickened nuchal fold was identified in 5 of 9 fetuses with trisomy 21 and normal anatomic survey results, all of whom had an NT of less than 3.0 mm at the initial screening scan. CONCLUSIONS: Second-trimester soft markers, especially a thickened nuchal fold, remain important observations in the detection of trisomy 21 by sonography among fetuses who have had first-trimester sonographic screening for aneuploidy.