Prior Spontaneous Preterm Birth Research Articles

Vaginal matrix metalloproteinase-9 (MMP-9) as a potential early predictor of preterm birth.

To evaluate the differences in vaginal matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs) in pregnant patients with a history of prior preterm birth compared with controls. A prospective cohort pilot study recruited patients during prenatal care with history of prior spontaneous preterm birth (high-risk group) or no history of preterm birth(low-risk/controls). Inclusion criteria were singleton gestation at 11-16weeks and between 18 and 55 years of age. Exclusion criteria were diabetes mellitus, hypertension, diseases affecting the immune response or acute vaginitis. A vaginal wash was performed at time of enrollment, and patients were followed through delivery. Samples were analyzed using semi-quantitative analysis of MMPS and TIMPS. The study was approved by the IRB and a p-value <0.05 was considered significant. A total of 48 pregnant patients were recruited: 16 with a history of preterm birth (high-risk group) and 32 with no history of preterm birth (low-risk group/controls). Groupswere similar in age, race, BMI, and delivery mode. The high-risk group had more multiparous women (100 vs. 68.8 %; p=0.02), a greater preterm birth rate (31.2 vs. 6.3 %; p=0.02), and a lower birth weight (2,885±898 g vs. 3,480±473 g; p=0.02). Levels of vaginal MMP-9 were greater in high-risk patients than low-risk patients (74.9 %±27.0 vs. 49.4 %±31.1; p=0.01). When dividing the cohort into patients that had a spontaneous preterm birth (7/48, 14.6 %) vs. those with a term delivery (41/48, 85.4 %), the vaginal MMP-9 remained elevated in the cohort that experienced a preterm birth (85.46 %+19.79 vs. 53.20 %+31.47; p=0.01). There were no differences in the other MMPS and in TIMPs between highand low-risk groups. There was an increase in vaginal MMP-9 during early pregnancy in those at high risk for preterm birth and in those who delivered preterm, regardless of prior pregnancy outcome. Vaginal MMP-9 may have potential as a marker of increased risk of preterm birth.

Assessing the multifaceted cervix: examining cervical gland area at cervical length screening to predict spontaneous preterm birth

BACKGROUNDBiologically active cervical glands provide a mucous barrier while influencing the composition and biomechanical strength of the cervical extracellular matrix. Cervical remodeling during ripening may be reflected as loss of the sonographic cervical gland area. As sonographic cervical length remains suboptimal for universal screening, adjunctive evaluation of other facets of the mid-trimester cervix may impart additional screening benefit. OBJECTIVETo sonographically assess the cervical gland area at universal cervical length screening for preterm birth. STUDY DESIGNWe performed a retrospective cohort study of singletons with transvaginal cervical length screening universally performed during anatomic survey between 18 0/7 and 23 6/7 weeks and subsequent live delivery at a single institution in 2018. Uterine anomalies, cerclage, suboptimal imaging, or medically indicated preterm birth were excluded. Ultrasound images were assessed for cervical length and cervical gland area (with quantitative measurements when present). The primary outcome was spontaneous preterm birth <37 weeks. Absent and present gland groups were compared using χ2, Fisher's exact, T-test, and multivariate logistic regression (adjusting for parity and progesterone use, as well as the gestational age, cervical length, and gland absence at screening ultrasound). Gland measurements were evaluated using the Mann-Whitney-U Test and Spearman's correlation. RESULTSAmong the cohort of 772 patients, absent and present CGA groups were overall similar. Patients were on average 33 years old, ∼20 weeks gestation at screening ultrasound, and overall, 2.5% had history of prior spontaneous preterm birth. The absent gland group was more likely to have been taking progesterone (17% vs 4%, P=.04). Overall rate of preterm birth was 2.6%. However, the 2.3% of patients with absent cervical gland area were significantly more likely to deliver <37 weeks (aOR 23.9, 95% CI 6.4–89, P<.001). Multivariate logistic regression demonstrated better performance of a cervical length screening model for preterm birth prediction with the addition of qualitative gland evaluation (P<.001). Qualitative gland assessment was reproducible (PABAK 0.89), but quantitative gland measurements did not correlate with preterm birth. CONCLUSIONQualitative gland absence at mid-gestation cervical length screening was associated with subsequent spontaneous preterm birth, whereas quantitative gland measurements were not. Multifaceted ultrasound screening may be needed to adequately evaluate the multiple biologic functions of the cervix.

Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks’ gestation: open label, multicentre, randomised, controlled trial

ObjectiveTo compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm...

Randomized trial of screening for preterm birth in low-risk women - the preterm birth screening study

Preterm birth is a major cause of perinatal morbidity and mortality. It is unclear whether the introduction of a universal transvaginal ultrasound cervical length screening program in women at low risk for preterm delivery is associated with a reduction in the frequency of preterm birth. To test the hypothesis that the introduction of a midtrimester universal transvaginal ultrasound cervical length screening program in asymptomatic singleton pregnancies without prior preterm delivery would reduce the rate of preterm birth at <37 weeks of gestation. This study was a multicenter nonblinded randomized trial of screening of asymptomatic singleton pregnancies without prior spontaneous preterm birth, who were randomized to either cervical length screening program (ie, intervention group) or no screening (ie, control group). Participants were randomized at the time of their routine anatomy scan between 18 0/7 and 23 6/7 weeks of gestation. Women randomized in the screening group received cervical length measurement. Those who were found to have cervical length ≤25 mm were offered 200 mg vaginal progesterone daily along with cervical pessary. The primary outcome was preterm birth at <37 weeks. The risk of primary outcome was quantified by the relative risk with 95% confidence interval, and was based on the intention-to-screen principle. A total of 1334 asymptomatic women with singleton pregnancies and without prior preterm birth, were included in the trial. Out of the 675 women randomized in the transvaginal ultrasound cervical length screening group, 13 (1.9%) were found to have transvaginal ultrasound cervical length ≤25 mm during the screening. Preterm birth at <37 weeks of gestation occurred in 48 women in the transvaginal ultrasound cervical length screening group (7.5%), and 54 women in the control group (8.7%) (relative risk, 0.86; 95% confidence interval, 0.59-1.25). Women randomized in the transvaginal ultrasound cervical length screening group had no significant differences in the incidence of preterm birth at less than 34, 32, 30, 28, and 24 weeks of gestation. The introduction of a universal transvaginal ultrasound cervical length screening program at 18 0/6 to 23 6/7 weeks of gestation in singleton pregnancies without prior spontaneous preterm birth, with treatment for those with cervical length ≤25 mm, did not result in significant lower incidence of preterm delivery than the incidence without the screening program.

368 Utility of extended cervical length surveillance among asymptomatic patients with prior spontaneous preterm birth

368 Utility of extended cervical length surveillance among asymptomatic patients with prior spontaneous preterm birth

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix

A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. The primary outcome was delivery or fetal death prior to 37 weeks. A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. ClinicalTrials.gov Identifier: NCT02901626.

How to screen the cervix and reduce the risk of spontaneous preterm birth in asymptomatic women without a prior preterm birth.

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality globally. PTB rates have increased in South Korea despite reduction in birth rates. A history of PTB is a strong predictor of subsequent PTB and screening of cervical length between 16 0/7 weeks and 24 0/7 weeks of gestation is recommended in women with a singleton pregnancy and a prior spontaneous PTB. However, the prediction and prevention of spontaneous PTBs in women without a prior PTB remain a matter of debate. The scope of this review article comprises cervical screening and prevention strategies for PTB in asymptomatic women without a prior PTB, based on recent evidence and guidelines.

Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

Effect of prior spontaneous preterm birth on delivery timing in subsequent twin pregnancy

People pregnant with twins who had a prior, singleton preterm birth are known to be at risk for preterm birth; however, prior data did not distinguish between spontaneous and iatrogenic births in the prior singleton pregnancy. We aimed to investigate the recurrence risk for preterm birth in a subsequent twin pregnancy in those who had prior spontaneous preterm birth (PSPTB) compared to those without PSPTB in a modern obstetric cohort. This is a secondary analysis of data from a retrospective cohort aimed to evaluate cell-free DNA screening performance in patients with twin pregnancies from 12/2011- 2/2020. We included twin pregnancies >20 weeks gestation and excluded those with nulliparity, unknown pregnancy outcome in twin pregnancy and unknown prior pregnancy history. Presence or absence of PSPTB was confirmed by medical record review. Baseline characteristics, gestational age of twin pregnancy and preterm birth in twin pregnancy were compared between those with history of PSPTB versus those without PSPTB. Multivariable logistic regression was used to assess adjusted odds ratio and adjust for confounders. Of the 958 twin pregnancies, 877 had no PSPTB and 81 had PSPTB. Those with twin pregnancies and prior PSPTB had a higher incidence of preterm birth (PTB) overall (77.8% vs 55.2%, OR 2.84 95%CI 1.66-4.87) and lower gestational age at delivery (34.7 vs 36.6 weeks, p< 0.001) than those with twin pregnancies without PSPTB. However, the rate of spontaneous PTB was not significantly different (46.8% vs 41.7%, OR 1.28 95% CI 0.75-2.17). For patients with PSPTB the adjusted odds ratio for PTB was 3.14 (95% CI 1.72,5.72) after controlling for Black race, body mass index, tobacco use, assisted reproductive technology, chronic hypertension and pregestational diabetes. Pregnant persons who have PSPTB are at increased risk for preterm birth in a subsequent twin pregnancy, and this information may be useful for risk counseling.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Incidentally Found Midtrimester Shortened Cervical Length: Practice Patterns among American Maternal-Fetal Medicine Specialists.

The management of incidentally found short cervical length (CL) without prior spontaneous preterm birth (PTB) can vary. While most agree on starting vaginal progesterone, management after CL shortens <10 mm varies. The purpose of this study was to elucidate current practice patterns amongst maternal-fetal medicine (MFM) specialists. We conducted an online survey of MFM attending physicians and fellows in the United States from May 2019 to April 2020. The primary outcome was management of varying CL based on gestational age. Variations in management were assessed descriptively. There were 236 respondents out of 400 eligible surveyed, with a response rate of 59.2%. Universal CL screening was reported by 93.6% (49.6% abdominal and 44.1% transvaginal). Management of short CL varied based on CL measurement, rather than gestational age at presentation. At CL <10 mm, management included cerclage (17.4-18.7%), vaginal progesterone (41.3-41.7%), or cerclage plus vaginal progesterone (43.4%). Between CL of 10 to 20 mm, the majority (77.4-91.9%) would start vaginal progesterone. At CL 21 to 25 mm, management varied between expectant management (45.5-48.5%) or vaginal progesterone (51.1-52.8%). Suture material used was ethylene terephthalate (47.4%) or polypropelene (31.2). Preoperative antibiotic use was reported by 22.3%, while 45.5% used them only if the amniotic membranes were exposed, and 32.2% reported no antibiotic use. Postoperative tocolytic use varied with 19.3% reporting no use, 32.6% using it always, 8.2% only after significant cervical manipulation, 22.7% after the patient is experiencing symptoms, and 17.6% using it only if the cervix is dilated on exam. After cerclage placement, 44.5% continued CL surveillance. Substantial differences of opinion exist among MFM physicians regarding management of incidentally found short CL in patients without history of PTB. The differences in responses obtained highlight the need for evidence-based guidelines for managing this clinical scenario. · There is lack of consensus on the management of incidentally found shortened CL.. · The purpose of this study was to elucidate current trends in CL screening and management.. · Substantial differences of opinion exist regarding management of incidentally found short CL..

Regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP).

To describe regional differences in utilization of 17α-hydroxyprogesterone caproate (17-OHP). Retrospective cohort study of a large, US commercial managed care plan claims database with pharmacy coverage from 2008 to 2018. Singleton pregnancies with at least one prior spontaneous preterm birth (sPTB) were included. Regional and state-based differences in 17-OHP use were compared. Data were analyzed using t-tests and Fisher's exact tests. Of the 4,514 individuals with an indication for 17-OHP, 580 (12.8%) were prescribed 17-OHP. Regional and state-based differences in 17-OHP utilization were identified; Northeast 15.7%, Midwest 13.7%, South 12.0%, and West 10.4% (p=0.003). While significant regional differences in 17-OHP utilization were demonstrated, 17-OHP utilization remained low despite this cohort having insurance through a US commercial managed care plan. Suboptimal utilization demonstrates a disconnect between research and uptake in clinical practice. This underscores a need for implementation science in obstetrics to translate updated recommendations more effectively and efficiently into clinical practice.

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length

Introduction: The majority of pregnant women with a short cervix will deliver at term and, thus, may unnecessarily receive advanced monitoring and treatment. It is still necessary to define more accurately which sub-population of women with a short cervix is at elevated risk for early delivery. Objective: To determine if vaginal microbiome composition influenced the rate of spontaneous preterm birth in women with a short cervical length. Methods: In an exploratory, observational prospective study, vaginal secretions were obtained from 591 women at 21–24 week gestation. Vaginal microbiome composition was determined by analyzing the V1–V3 region of the bacterial 16S ribosomal RNA gene. Results: Lactobacillus crispatus was numerically dominant in the vagina in 41.7% of subjects, followed by L. iners in 32% and Gardnerella vaginalis in 12%. In women whose cervix was ≤25mm, the sensitivity to predict an spontaneous preterm birth was 11.8%. However, when L. crispatus was not the dominant vaginal bacterium, this sensitivity increased to 81.8%. Similarly, in women with a cervical length ≤30mm, the sensitivity to predict an spontaneous preterm birth increased from 21.7 to 78.3% when L. crispatus was not the dominant vaginal bacterium.In women with a prior spontaneous preterm birth and a cervix ≤25 or ≤30mm, L. crispatus dominance was also associated with a reduced rate of spontaneous preterm birth in the current pregnancy (p&lt;0.001). Conclusion: In pregnant women with a cervix ≤25mm or ≤30mm, the risk for an spontaneous preterm birth is increased if L. crispatus is not dominant in the vagina.

Latency duration beyond viability in women undergoing ultrasound-indicated cerclage

In women with short cervical length (CL< 25 mm) and prior spontaneous preterm birth (SPTB), cerclage reduces preterm & previable birth. Of women who undergo an ultrasound-indicated (USI) cerclage, approximately 5-10% will deliver prior to viability, i.e. 23 wks gestation. However, it is unknown if CL and GA at cerclage placement affect pregnancy duration beyond viability. The aim of this study is to compare pregnancy latency beyond viability by CL and GA at the time of cerclage. Secondary analysis of a multicenter cerclage trial of women with prior SPTB & mid-trimester CL< 25mm. Women who were randomized to and underwent USI cerclage and attained 23 wks gestation comprised the study sample. The primary outcome is latency (wks) beyond 23 wks gestation in those with CL < 15mm vs CL 15-24 mm at cerclage placement, and similarly in those ≤ 18 wks vs > 18 wks at cerclage. Secondary outcomes are births < 32 wks, < 37 wks and perinatal death. Of 138 eligible women, 132(95.6%) reached viability: 34 with CL < 15mm & 98 with CL 15-24 mm at cerclage. Maternal age, BMI, race, marital status, cigarette use, drug use, number of prior preterm births, GA at first scan, GA at randomization were similar between the CL groups. Women with CL < 15mm at cerclage differed in GA of earliest prior delivery (p=0.03), and in years of education (p=0.04), Table 1. Latency beyond 23 wks gestation was similar in both CL groups (< 15 mm: 12.4±5.0 wks vs 15-25 mm: 12.9±4.2 wks), p=0.60, Table 2. 30 women underwent cerclage ≤ 18 wks and 102 > 18 wks gestation. Latency was similar in the GA groups (≤ 18 wks: 12.0±4.4 wks vs > 18 wks: 12.0±4.4 wks), p=0.30, Table 2. Results were consistent after controlling for education and GA of earliest prior birth. The CL & GA groups also had similar rates of birth < 32 wks gestation, < 37 wks gestation and perinatal death. In women with prior SPTB who undergo USI cerclage for short CL and reach viability, neither CL nor GA at cerclage affect pregnancy latency or rates of PTB and perinatal death.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Vaginal versus Intramuscular Progesterone for Prevention of Recurrent Preterm Birth (VIP): a randomized controlled trial

To determine whether vaginal progesterone is superior to intramuscular 17-hydroxyprogesterone caproate (17OHPC) in prevention of recurrent preterm birth (PTB) in singletons with prior spontaneous preterm birth (sPTB).

Understanding barriers to utilization of 17-hydroxyprogesterone caproate and other interventions to prevent preterm birth in Fresno County, California

Objective Preterm birth is one of the leading causes of neonatal morbidity and mortality. A history of prior spontaneous preterm birth is a known risk factor for recurrent preterm birth. While 17-alpha-hydroxyprogesterone caproate (17P) has been found in some studies to reduce recurrent preterm birth by 34%, many women who could have benefited from its use did not receive this intervention. We sought to investigate the rate of and reasons for underutilization of 17P in Fresno County, California, where the preterm birth rate trend from 2017 and recent 2020 data showed a significantly higher rate at 10.1% and 9.8% respectively, when compared to the state average of 8.6% and 8.8% respectively. Methods We conducted a retrospective chart review of patients who delivered at Community Regional Medical Center in Fresno from January to December 2016, and surveys of providers and patients, to help identify barriers to 17P utilization. Results After controlling for age, body mass index, interpregnancy interval, and race/ethnicity, we determined that women who had private insurance were 3 times more likely to have received 17P compared to women with public insurance (adjusted odds ratio 2.97, 95% CI: 1.6–6.51, p&lt;.001). We also found that only 23.3% of patients eligible for 17P actually received this intervention. The surveys identified difficulty with completing the insurance approval process and receiving the treatment within the clinically recommended timeline as primary barriers to 17P utilization. Conclusion This study confirmed that 17P intervention for prevention of recurrent preterm birth was underutilized and disproportionately affected patients with inadequate prenatal care and those who had public insurance.

Cervical cerclage after prior uterine and cervical surgery

Objective To evaluate cerclage placement after uterine and cervical surgery. Patients and methods We compared patients with a prior uterine surgery (with or without cervical surgery) with women having a cerclage for the “classical” indications. Under the classical indications fall history of one or more second-trimester pregnancy losses related to painless cervical dilation, prior cerclage due to painless cervical dilation in the second trimester, painless cervical dilation in the second trimester, ultrasonographic finding with a history of prior preterm birth, prior spontaneous preterm birth at less than 34 weeks of gestation and short cervical length (less than 25 mm) before 24 weeks of gestation. Results Forty-seven (44.8%) patients had uterine surgery whereas 58 (55.2%) had the “classical” indications for cerclage. The risk of birth at <37 weeks and birth weight <2500 g was similar, but lower for cerclage after previous uterine/cervical surgery for births >37 weeks (OR 0.3, 95% CI 0.1, 0.8) and hence, for birth weights >2500 g (OR 0.4, 95% CI 0.2–0.9). Both groups had similar incidence of preterm rupture of membranes, chorioamnionitis, need for induction of labor, cesarean births as well as low Apgar scores and admission rates to the NICU. Conclusions The major goals of reducing births at <37 weeks and low birth weight of <2500 g are achievable with a cerclage in patients with a prior uterine/cervical surgery as it is in patients with a “classical” indication for cerclage placement.

10 A randomized trial of 17-hydroxyprogesterone caproate to prevent preterm birth among women living with HIV

Women with HIV face an increased risk of preterm birth (PTB), the leading worldwide cause of child death. 17 alpha-hydroxyprogesterone caproate (17P) has been shown in some trials to reduce early delivery among women with a prior spontaneous PTB. We conducted a randomized, double-masked, placebo-controlled trial of 17P among HIV-infected women attending public-sector antenatal care in Lusaka, Zambia. We excluded women with prior spontaneous PTB or multiple gestation. Participants were randomly allocated to receive weekly intramuscular injections of 250mg 17P or placebo, starting between 16 and 24 gestational weeks and continuing until 36 6/7 weeks, delivery, or stillbirth, whichever occurred first. The trial’s primary outcome was delivery < 37 weeks or stillbirth at any gestational age. We compared the risk of pre-specified outcomes between randomization groups using an intent-to-treat approach. 800 women were randomized between Feb 2018 and Jan 2020. Baseline characteristics were similar between treatment groups. Adherence to study drug was high in both groups (98%) and delivery outcomes were ascertained for all 800 participants. The primary outcome occurred in 36 (9.02%) participants assigned to 17P and 36 (8.98%) assigned to placebo (risk difference = 0.05; 95% CI: -3.92, 4.01). In a pre-specified analysis excluding provider-initiated PTB phenotypes, 25 (6.36%) women randomized to 17P delivered spontaneously before 37 weeks compared to 26 (6.63%) of those receiving placebo (risk difference = -0.27; 95% CI: -3.72, 3.18). The timing of antiretroviral therapy initiation relative to conception did not affect the risk of the primary outcome nor did it modify the effect of the intervention. Related adverse events were low and occurred at similar rates between the study groups. In this trial with complete ascertainment of outcomes and very high adherence to study drug, weekly antenatal 17P injections did not reduce the composite risk of preterm delivery or stillbirth among women with HIV in Zambia.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

127 Gestational latency associated with erythromycin vs azithromycin in patients admitted with PPROM

Administration of antibiotics after preterm premature rupture of membranes (PPROM) has been shown to increase gestational latency. While the original studies included ampicillin and erythromycin, shortages of erythromycin have led to use of azithromycin in its stead. We sought to evaluate whether the use of azithromycin compared to erythromycin, is associated with changes in perinatal outcomes including gestational latency. This retrospective cohort study included women with singleton gestations admitted to a quaternary center from 9/2014 to 3/2020 with a diagnosis of PPROM between 23w0d and 33w5d. In 2017, the hospital’s policy universally changed from a 7-day course of erythromycin to one dose of oral azithromycin 1000mg. The primary outcome was gestational latency. Secondary outcomes included gestational age (GA) at delivery; chorioamnionitis; birthweight; 5-minute Apgar <7; respiratory distress syndrome; necrotizing enterocolitis; intraventricular hemorrhage; neonatal length of stay; and neonatal death. An a priori power analysis determined that a sample of 120 patients per group would identify a 2-day difference in gestational latency (with a power of 80% and an alpha of 0.05). Bivariable and multivariable analyses were performed. 280 patients met inclusion criteria. Patients receiving erythromycin had a higher frequency of prior spontaneous preterm birth (PTB) and presented at a later GA with PPROM (Table 1). No other differences were observed in patient characteristics. There were no differences in gestational latency between patients who received azithromycin compared to erythromycin in bivariable [10 (4-15) vs 8.5 (3-14) days, p=0.16) or multivariable analyses [adjusted β = 0.13 days (95% CI: -0.08-0.34 days) (Table 2). There were no statistically significant differences in secondary outcomes. There was no difference in gestational latency or incidence of adverse perinatal outcomes when comparing azithromycin to erythromycin. A single dose of azithromycin appears to be a reasonable substitute to erythromycin for gestational latency in the setting of PPROM.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

964 Prior spontaneous preterm birth: subsequent pregnancy outcomes among women with PPROM vs spontaneous preterm labor

Women with a history of spontaneous preterm birth (sPTB) are at an increased risk for recurrent preterm birth. Preterm premature rupture of membranes (PPROM) and spontaneous preterm labor (sPTL) have potentially varying mechanisms and etiopathogenesis. The objective of our study was to evaluate the differential impact of history of PPROM vs sPTL on subsequent pregnancy management and perinatal outcomes. Retrospective review of women delivering at a single hospital from July 2018- November 2019 to identify women with a history of sPTB of singleton gestations. The cohort was divided into two groups based on a history of sPTL vs PPROM. Demographic data, pregnancy management, and perinatal outcomes were abstracted through a review of electronic medical records and compared across the 2 groups using student’s t test and chi squared/Fischer’s exact test for continuous and categorical data respectively. Out of 2,803 women, 168 women had a history of sPTB: 125 (74%) with a history of sPTL and 43 (23%) with a history of PPROM. Demographic characteristics were similar across groups. We found no significant differences in the pregnancy interventions (Table 1) and perinatal outcomes (Table 2) among study groups. Subgroup analyses were performed evaluating the impact of vaginal vs IM progesterone. While there were no significant differences noted in women with a history of PPROM, differences were noted among women with a history of sPTL. Women who received IM progesterone had longer cervical lengths (mean ± SD) [36.3mm ± 4.4; N=21 vs 20.5 ± 12.2; N=18 p<0.001] and delivered at a later gestational age (mean ± SD) (37.2 ± 1.6 weeks; N=28 vs 34.7 ± 5.6 weeks; N = 23) as compared to women receiving vaginal progesterone. In our cohort, similar outcomes were noted in subsequent pregnancies among women with history of PPROM and sPTL. However, subgroup analyses in women with a history of sPTL suggest a potential benefit of IM progesterone. Further research in a larger cohort is warranted to delineate the differential impact of the history of sPTB in the context of PPROM vs sPTL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Mid-Trimester Cervical Length Screening: Effect of Poorly Developed Lower Uterine Segment on Pregnancy Outcome.

To identify whether a poorly developed lower uterine segment (PDLUS) observed during cervical length (CL) screening affects the duration of gestation in women with no prior spontaneous preterm birth (sPTB). A retrospective cohort study of women with a singleton gestation and no prior sPTB, who underwent transvaginal CL screening at our institution. We excluded women with progesterone exposure, major anomalies, and women delivering elsewhere. Women with PDLUS were compared to those with a measured (normal) CL ≥25 mm. birth gestational age (GA). sPTB <35 and 37 weeks, hospital evaluation for preterm labor without delivery, delivery indication, and mode. A Cox proportional-hazards survival model considered time from CL scan to delivery. We powered the study to detect a one-half week difference in birth GA. We included 270 women with PDLUS and 985 women with normal CL. Mean birth GA was 38.9 ± 2.0 weeks with PDLUS versus 38.7 ± 2.4 weeks with normal CL (p=.10). Women with PDLUS were less likely to experience sPTB <37 weeks (1.1% vs 3.6%; p=0.04). There was no difference in sPTB <35 weeks (0.8% vs 1.7%; p=.25). Hospital evaluation for preterm labor (17% vs 19%; p=.54), delivery indication, and mode were not different. The hazard ratio for earlier birth in women with PDLUS was 0.67 (95% CI 0.46, 0.98; p=.04). We observed no difference in mean GA at birth; however, PDLUS was protective against sPTB <37 weeks and was associated with a lower hazard ratio for earlier birth.