Cerclage plus Adjuvant Vaginal Progesterone for Preterm Birth Prevention in Patients with a Short or Dilated Cervix without Prior Preterm Birth.

OBJECTIVE: The primary objective was to determine if vaginal progesterone following cerclage for cervical length <10 mm or cervical dilation in patients without a history of spontaneous preterm birth (sPTB) decreased the risk of preterm birth at <34 weeks' gestation compared with cerclage alone. Secondary objectives were to determine if vaginal progesterone following cerclage (1) decreased the risk of preterm birth at <24, <28, and <37 weeks' gestation and (2) increased the latency period from cerclage placement to delivery compared with treatment with cerclage alone. STUDY DESIGN: Multicenter retrospective cohort study from 2015 to 2020 of singleton pregnancies, without prior sPTB, who had cerclage placement <24 weeks' gestation for cervical length <10 mm or cervical dilation. Exposure defined as cerclage plus vaginal progesterone postoperatively (dual therapy) and unexposed as cerclage alone (monotherapy), based on surgeon preference. RESULTS: We included 122 patients, 78 (64%) treated with dual therapy and 44 (36%) treated with monotherapy. In the crude analysis, dual therapy was associated with a lower risk of delivery at <28 weeks' gestation (13%) compared with monotherapy (34%; crude risk ratio: 0.38 [95% confidence interval, CI: 0.19-0.75]). When adjusted for preoperative vaginal progesterone, results were attenuated (adjusted risk ratio: 0.45 [95% CI: 0.20-1.01]). In both the crude and adjusted analyses, the risk of sPTB was not statistically different at <24, <34 or <37 weeks' gestation. Dual therapy was associated with a greater pregnancy latency from cerclage to delivery (16.3 vs. 14.4 weeks; p = 0.04), and greater gestational age at delivery (37.3 vs. 35.8 weeks' gestation; p = 0.02) compared with monotherapy. CONCLUSION: While not statistically significant, the risk of sPTB was lower at all gestational ages studied in patients treated with dual therapy compared with monotherapy. Dual therapy was associated with longer pregnancy latency and greater gestational age at delivery compared with monotherapy. KEY POINTS: · Dual therapy did not decrease preterm birth risk compared with monotherapy.. · Dual therapy prolonged pregnancy compared with monotherapy.. · Dual therapy can be considered but further studies are needed..

Inflammatory Bowel Disease in the Childbearing Adult and Newborn.

Inflammatory bowel disease (IBD) often affects people in their childbearing years and has implications for pregnancy outcomes, particularly as related to increased risk of preterm delivery and effects of immunosuppressive medications on the fetus. Ideally, people with IBD should attempt conception at a time when their disease is in remission to optimize pregnancy outcomes and reduce risks of flares. Generally, pregnant individuals should continue immunosuppressive medications throughout gestation in an attempt to control the disease. Maternal risks of IBD in pregnancy include exacerbated anemia, disease flare, cesarean delivery, and treatment risks. Fetal and neonatal risks include preterm birth, low birthweight, and medication exposures. There are too few clinical trials that include pregnant or breastfeeding patients to analyze the risk/benefit profile of immunosuppressive medications for IBD treatment during pregnancy, limiting the amount of data available to guide medical treatment in this population. More studies are needed on IBD therapies, particularly as more biologics are developed and become the mainstay of treatment. Neonatal clinicians should be aware of in utero medication exposure to help guide decisions regarding newborn care.

Incidence of small-for-gestational-age infant birthweight following early intertwin fetal growth discordance in dichorionic and monochorionic twin pregnancies.

BACKGROUND: Serial growth scans are routinely recommended for twin pregnancies to identify fetal growth restriction (defined as an estimated fetal weight of <10th percentile), which can result in increased perinatal morbidity and mortality. However, the clinical significance of early intertwin growth discordance in the absence of fetal growth restriction remains unclear. OBJECTIVE: This study aimed to compare the rates of small-for-gestational-age infants among twin pregnancies with intertwin growth discordance in the absence of fetal growth restriction with that among twin pregnancies with concordant, normal growth identified by ultrasound between 24 0/7 and 31 6/7 weeks' gestation. STUDY DESIGN: This was a retrospective cohort study of twin deliveries at a single hospital from 2010 to 2019. Pregnancies without fetal growth restriction were categorized as discordant or concordant using the earliest prenatal growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation. Discordance was defined as an estimated fetal weight difference of ≥18% between twins. Pregnancies with major fetal anomalies, no growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation, or twin-twin transfusion syndrome were excluded. The cohort was stratified by chorionicity. Our primary outcome was small-for-gestational-age defined as <10th percentile per the Fenton growth curve at delivery. Secondary outcomes included gestational age at delivery, mode of delivery, neonatal intensive care unit admission, length of stay, and neonatal complications and placental pathology. RESULTS: Of the 707 twin pregnancies that met the inclusion criteria, 558 (79%) were dichorionic and 149 (21%) were monochorionic. Most pregnancies were concordant on ultrasound between 24 0/7 and 31 6/7 weeks' gestation (dichorionic, 93%; monochorionic, 87%). Regardless of chorionicity, twin pregnancies with discordance at ultrasound, were more likely to have a small-for-gestational-age infant than concordant twin pregnancies (dichorionic: 51% vs 29%; P=.002; monochorionic: 65% vs 24%; P<.001). Furthermore, women with twin pregnancies with discordance were delivered at an earlier gestational age (dichorionic: 36 weeks [interquartile range, 33-36] vs 34 weeks [interquartile range, 34-38]; P<.001; monochorionic: 34 weeks [interquartile range, 32-34] vs 36 weeks [interquartile range, 34-37]; P=.003). Pregnancies with growth discordance were more likely to be delivered by cesarean delivery (dichorionic: 90% vs 72%; P=.01; monochorionic: 65% vs 60%; P=.70), although this was only statistically significant for dichorionic twin pregnancies. Neonates of pregnancies with growth discordance had a higher incidence of respiratory distress syndrome (dichorionic: 54% vs 37%; P=.04; monochorionic: 70% vs 45%; P=.04) and neonatal intensive care unit admission (dichorionic: 71% vs 50%; P=.01; monochorionic: 90% vs 65%; P=.03). Furthermore, dichorionic infants had longer neonatal intensive care unit stays (30 [interquartile range, 18-61] vs 18 [interquartile range, 10-35] days; P=.02). CONCLUSION: Regardless of chorionicity, twin pregnancies with discordance without fetal growth restriction identified on growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation were nearly twice as likely to develop small-for-gestational-age neonates, deliver earlier in gestation, and experience greater neonatal morbidity than twin pregnancies without discordance. Patients with pregnancies complicated by isolated intertwin discordance between 24 0/7 and 31 6/7 weeks' gestation will need counseling regarding adverse perinatal outcomes.

Cardiovascular Disease in Pregnancy.

Cardiovascular disease remains a major contributor to rising maternal morbidity and mortality. Both the pregnant woman and fetus are exposed to many potential complications as a result of the physiologic changes of pregnancy. These changes can exacerbate existing cardiac disease, as well as lead to the development of de novo issues during gestation, delivery, and the postnatal period. For women with preexisting cardiac disease, including congenital malformations, valvular disease, coronary artery disease, and aortopathies, it is crucial that they receive multidisciplinary evaluation, counseling, and optimization before conception, as well as close monitoring and medication management during pregnancy. Close monitoring is also essential for patients who develop cardiovascular complications such as preeclampsia, cardiomyopathy, congestive heart failure, coronary events, and arrhythmias during pregnancy. In addition, concerning disparities in maternal morbidity and mortality exist across many dimensions, in part because of the lack of uniformity of care in different treatment settings. Establishment of multidisciplinary cardio-obstetric teams including representatives from cardiology, anesthesia, obstetrics, maternal-fetal medicine, and specialized nursing has proven instrumental to delivering evidence-based and equitable care to high-risk patients. Multidisciplinary teams should work to guide these patients through the preconception, antepartum, delivery, and postpartum phases to ensure appropriate care for weeks to years after pregnancy.

Hemorrhagic morbidity in placenta accreta spectrum with and without placenta previa.

PURPOSE: The incidence of placenta accreta spectrum (PAS; pathologic diagnosis of placenta accreta, increta or percreta) continues to rise in the USA. The purpose of this study is to compare the hemorrhagic morbidity associated with PAS with and without a placenta previa. METHODS: This was a retrospective cohort study of 105 deliveries from 1997 to 2017 with histologically confirmed PAS comparing outcomes in women with and without a coexisting placenta previa. We used the Wilcoxon rank sum test to compare continuous data and Chi-square or Fisher's exact test for categorical data. We also performed log-binomial regression to calculate risk ratios adjusted for depth of invasion (aRR) and 95% confidence intervals (CI). RESULTS: We identified 105 pregnancies with PAS. Antenatal diagnosis of PAS was higher in women with coexisting placenta previa (72.3%) than those without (6.9%, p < 0.001). Women with coexisting placenta previa had greater median estimated blood loss and more units of packed red blood cells transfused (both p ≤ 0.03). Women with placenta previa were more likely to undergo a hysterectomy (RR 2.7; 95% CI 1.8-3.8) and be admitted to the intensive care unit (aRR 3.3; 95% CI 1.1-9.6). CONCLUSIONS: Among women with PAS, those with a coexisting placenta previa experienced greater hemorrhagic morbidity compared to those without. In addition, PAS without placenta previa typically was not diagnosed prior to delivery. This study further supports the recommendation for multi-disciplinary planning and assurance of resources for pregnancies complicated by PAS. In addition, our results highlight the need for mobilization of resources for those pregnancies where PAS is not diagnosed until delivery.

Vasa previa: a multicenter retrospective cohort study.

OBJECTIVE: The objective of the study was to describe the characteristics and outcomes of patients with antenatal diagnosis of vasa previa and evaluate the predictive factors of resolution in a contemporary large, multicenter data set. STUDY DESIGN: This was a retrospective multicenter cohort study of all antenatally diagnosed cases of vasa previa, identified via ultrasound and electronic medical record, between January 2011 and July 2018 in 5 US centers. Records were abstracted to obtain variables at diagnosis, throughout pregnancy, and outcomes, including maternal and neonatal variables. Data were reported as median [range] or n (percentage). Descriptive statistics, receiver-operating characteristics, and logistic regression analysis were used as appropriate. RESULTS: One hundred thirty-six cases of vasa previa were identified in 5 centers during the study period, 19 (14%) of which resolved spontaneously at median estimated gestational age of 27 weeks [19-34]. All subjects with unresolved vasa previa underwent cesarean delivery at a median estimated gestational age of 34 weeks [27-39] with the median estimated blood loss of 800 mL [250-2000]. Rates for vaginal bleeding, preterm labor, premature rupture of membrane, and need for blood product transfusion were not different between the resolved and unresolved group (P = NS). The odds ratio for resolution in those with the estimated gestational age of less than 24 weeks at the time of diagnosis was 7.9 (95% confidence interval, 2.1-29.4) after adjustment for confounding variables. CONCLUSION: Our data suggest that outcomes in antenatally diagnosed cases of vasa previa are excellent. Furthermore, our data report a higher chance of resolution when the condition is diagnosed before 24 weeks of gestation.

Low fetal fraction of cell-free DNA predicts placental dysfunction and hypertensive disease in pregnancy.

OBJECTIVE: To examine the association of low fetal fraction of cell-free DNA (cfDNA) with placental compromise and adverse perinatal outcomes. MATERIALS AND METHODS: This was a retrospective cohort utilizing a sample of convenience including 639 women undergoing cfDNA screening at our institution from January 2013 to January 2017. Low fetal fraction was defined as less than the 25th percentile. Indicators of placental compromise were examined individually and as a composite outcome, including hypertensive disease of pregnancy, intrauterine growth restriction, abruption, and oligohydramnios. Neonatal outcomes, including preterm delivery, low Apgar scores, and small for gestational age, also were examined. We calculated risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Low fetal fraction was associated with placental compromise (RR 1.6 [CI 1.1-2.2]), hypertensive disease of pregnancy (RR 1.6 [CI 1.003-2.6]), and preeclampsia with severe features (RR 3.3 [CI 1.2-8.9]). Low fetal faction was not associated with preterm delivery, low Apgar scores, or small for gestational age. CONCLUSIONS: Low fetal fraction of cfDNA among asymptomatic women may serve as a predictor of subsequent placental dysfunction and hypertensive disease.

Racial disparities in intrapartum group B Streptococcus colonization: a higher incidence of conversion in African American women.

OBJECTIVE: To compare the incidence of group B Streptococcus (GBS) conversion from a negative antepartum to a positive intrapartum culture among women who self-identify as non-Hispanic black, Hispanic, or non-Hispanic white. STUDY DESIGN: This was a prospective cohort study of women with a negative rectovaginal GBS culture obtained within 35 days of enrollment. An intrapartum rectovaginal swab was collected and cultured for GBS. Data were compared with chi-square, Fisher's exact, or Wilcoxon rank-sum test. Modified Poisson regression was used. RESULTS: We enrolled 737 women; 75.4% were non-Hispanic white, 17.6% were non-Hispanic black, and 6.9% were Hispanic. Non-Hispanic black women were more likely to convert to GBS positive than non-Hispanic white women, 9.2% as compared to 5.3% (RR: 2.0; 95% CI: 1.02-3.8). CONCLUSION: The increased incidence of positive intrapartum GBS cultures among non-Hispanic black women suggests that non-Hispanic black race is a risk factor for GBS conversion in the late third trimester.

Placental soluble fms-like tyrosine kinase expression in small for gestational age infants and risk for adverse outcomes.

INTRODUCTION: Soluble fms-like tyrosine kinase 1 (sFLT-1) is an anti-angiogenic factor implicated in the pathogenesis of preterm preeclampsia. We evaluated sFLT-1 expression and placental pathology in pregnancies complicated by small for gestational age (SGA) infants (<10th percentile), without evidence of preeclampsia. METHODS: Clinical and histologic data were compared between groups with high or low sFLT-1 expression determined by immunohistochemistry on archived placentas. RESULTS: Nineteen of 69 placentas showed high sFLT-1 expression. The high sFLT-1 group had higher predelivery median systolic blood pressure (BP); 140 (interquartile range (IQR) 133-152) vs. 126 (118-139) mm Hg (p = 0.003), and median diastolic BP; 87 (78-94) vs. 77.5 (71-86) mm Hg (p = 0.02). Abnormal umbilical Doppler abnormalities were more prevalent; 89.5% vs. 46% (p = 0.001). These pregnancies delivered earlier; 31.9 weeks (28.3-34.7 weeks) vs. 37.1 weeks (33.7-38.7 weeks) (p < 0.001), and infants had lower birthweight; 980 grams (520-1545 grams) vs. 2087.5 grams (1455-2340 grams) (p < 0.001). Placental-weight to fetal-weight ratios, a marker of vascular insufficiency, was increased in the high sFlt-1 group: 0.18 (0.14-0.28) vs 0.15 (0.13-0.18), p = 0.03. Placentas with high sFLT-1 showed more decidual vasculopathy; 42.1% vs. 10.0% (p = 0.005), infarction; 36.8% vs. 14.0% (p = 0.048), distal villous hypoplasia; 78.9% vs. 36.0% (p = 0.001), and fetal thrombotic vasculopathy; 47.4% vs. 16.0% (p = 0.01). DISCUSSION: Placental sFLT-1 expression is upregulated in approximately 28% of non-preeclamptic pregnancies complicated by SGA infants. These pregnancies showed increased placental vascular pathology, more umbilical Doppler abnormalities, and earlier delivery with lower birthweight. A subgroup of non-preeclamptic fetal growth restriction with upregulated sFlt-1 expression may share a common pathogenic pathway with preterm preeclampsia. This subgroup is worthy of additional study.

Cost Analysis of Following Up Incomplete Low-Risk Fetal Anatomy Ultrasounds.

OBJECTIVES: To examine the clinical utility and cost of follow-up ultrasounds performed as a result of suboptimal views at the time of initial second-trimester ultrasound in a cohort of low-risk pregnant women. METHODS: We conducted a retrospective cohort study of women at low risk for fetal structural anomalies who had second-trimester ultrasounds at 16 to less than 24 weeks of gestation from 2011 to 2013. We determined the probability of women having follow-up ultrasounds as a result of suboptimal views at the time of the initial second-trimester ultrasound, and calculated the probability of detecting an anomaly on follow-up ultrasound. These probabilities were used to estimate the national cost of our current ultrasound practice, and the cost to identify one fetal anomaly on follow-up ultrasound. RESULTS: During the study period, 1,752 women met inclusion criteria. Four fetuses (0.23% [95% CI 0.06-0.58]) were found to have anomalies at the initial ultrasound. Because of suboptimal views, 205 women (11.7%) returned for a follow-up ultrasound, and one (0.49% [95% CI 0.01-2.7]) anomaly was detected. Two women (0.11%) still had suboptimal views and returned for an additional follow-up ultrasound, with no anomalies detected. When the incidence of incomplete ultrasounds was applied to a similar low-risk national cohort, the annual cost of these follow-up scans was estimated at $85,457,160. In our cohort, the cost to detect an anomaly on follow-up ultrasound was approximately $55,000. CONCLUSIONS: The clinical yield of performing follow-up ultrasounds because of suboptimal views on low-risk second-trimester ultrasounds is low. Since so few fetal abnormalities were identified on follow-up scans, this added cost and patient burden may not be warranted.

Revisiting decidual vasculopathy.

INTRODUCTION: In the setting of preeclampsia (PE), decidual vasculopathy (DV) can be seen along the free membranes. METHODS: We describe DV using stains for CD31, CD34, Cd42b, CD68, desmin, fibrin and Masson's trichrome in patients with preeclampsia and fetal growth restriction. RESULTS: We first examined the "membrane roll" sections from the placentas of six patients with preeclampsia. Affected vessels showed endothelial proliferation with detachment. Remodeling of the media was characterized by smooth muscle loss with variable degrees of fibrin deposition. CD31 and CD34 highlighted the prominent endothelium and showed striking particulate staining throughout the media. All of these findings infer a sequence of endothelial injury, fragmentation and repair with incorporation of endothelial components into the vascular wall. We evaluated the frequency of DV by clinical presentation; in cases with PE with and without small for gestational age (SGA) (N = 15), and SGA with and without Doppler flow abnormalities (N = 15). All groups except the SGA without Doppler abnormalities showed DV. Among placentas with DV, the most severely affected group was PE with SGA; the least affected was PE without SGA. DISCUSSION: The association with SGA suggests that the DV is a subacute process of vascular injury that accelerates in the setting of PE. The majority of DV cases were not initially recognized suggesting a role for endothelial markers for DV detection. We also propose that the rampant endothelial injury seems to be a prominent finding in the decidual vessels of subjects with PE complicated by SGA and a similar process in the systemic vasculature may be responsible for the circulating endothelial microparticles reported in such patients.

Cerclage in twin pregnancy with dilated cervix between 16 to 24 weeks of gestation: retrospective cohort study.

BACKGROUND: Cervical dilation in the second trimester is associated with a greater than 90% rate of spontaneous preterm birth and a poor perinatal prognosis. OBJECTIVE: To compare the perinatal outcomes of twin pregnancies with dilated cervix in women who underwent either cerclage or expectant management. STUDY DESIGN: Retrospective cohort study of asymptomatic twin pregnancies identified with cervical dilation of ≥1 cm at 16-24 weeks (1997-2014) at 7 institutions. Exclusion criteria were genetic or major fetal anomaly, multifetal reduction at >14 weeks, prior cerclage placement, monochorionic-monoamniotic placentation, active vaginal bleeding, labor, chorioamnionitis, elective termination of pregnancy, or medically indicated preterm birth. The primary outcome was incidence of spontaneous preterm birth at <34 weeks. Secondary outcomes were incidence of spontaneous preterm birth at <32 weeks, <28 weeks, and <24 weeks; perinatal mortality; and composite adverse neonatal outcome (respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis). RESULTS: A total of 76 women with twin pregnancy with dilated cervix of 1.0-4.5 cm were managed with either cerclage (n = 38) or expectant management (n = 38). Demographic characteristics were not significantly different. Analysis was adjusted for amniocentesis and vaginal progesterone use. In the cerclage group, 29 women (76%) received prophylactic indomethacin and 36 (94%) received prophylactic antibiotics, whereas the expectant management group did not. Interval from time at diagnosis of open cervix to delivery in the cerclage group was 10.46 ± 5.6 weeks vs 3.7 ± 3.2 weeks in the expectant management group, with a mean difference of 6.76 weeks (95% confidence interval [CI], 4.71-8.81). There were significant decreases in spontaneous preterm birth at <34 weeks (52.6% vs 94.7%; adjusted odds ratio [aOR], 0.06; 95% CI, 0.03-0.34), at <32 weeks (44.7% vs 89.4%; aOR, 0.08; 95% CI, 0.03-0.34); at <28 weeks (31.6% vs 89.4%; aOR, 0.05; 95% CI, 0.01-0.2); and at <24 weeks (13.1% vs 47.3%; aOR, 0.17; 95% CI, 0.05-0.54). There were also significant reductions in perinatal mortality (27.6% vs 59.2%; aOR, 0.24; 95% CI, 0.11-0.5), neonatal intensive care unit admission (75.9% vs 97.6%; aOR, 0.07; 95% CI, 0.01-0.66), and composite adverse neonatal outcome (33.9% vs 90.5%; aOR, 0.05; 95% CI, 0.01-0.21). CONCLUSION: Cerclage, indomethacin, and antibiotics in twin pregnancies with dilated cervix ≥1 cm before 24 weeks were associated with significant longer latency period from diagnosis to delivery (6.7 weeks), decreased incidence of spontaneous preterm birth at any given gestational age, and improved perinatal outcome when compared with expectant management.

Perinatal outcomes based on the institute of medicine guidelines for weight gain in twin pregnancies.

OBJECTIVE: To estimate the impact of the Institute of Medicine's (IOM) weight gain recommendations on perinatal outcomes in twin pregnancies. METHODS: In this multicenter cohort study, using the 2009 IOM guidelines, we examined pregnancy outcomes in 570 uncomplicated diamniotic twin pregnancies. Subjects were grouped according to pre-pregnancy body mass index. Perinatal outcomes were assessed based on whether maternal weekly weight gain was less than, at, or in excess of the recommended IOM guidelines. RESULTS: In women with a normal pre-pregnancy BMI, patients whose weight gain met the IOM recommendations had a significantly higher mean gestational age at delivery; less prematurity and larger birth weight infants compared to women whose weekly weight gain was less or excess than the recommended IOM guidelines. Similarly, when compared with their low weight gain counterparts, overweight women with appropriate weight gain had improved outcomes including higher mean gestational age at delivery, higher birth weight infants and less prematurity. In obese women, the amount of pregnancy weight gain did not impact perinatal outcomes. CONCLUSION: Our results confirm that weekly maternal weight gain according to the IOM guidelines results in improved outcomes in twin pregnancies. Importantly, women with a normal or overweight pre-pregnancy BMI whose weekly weight gain was less than recommended, had increased risks of prematurity and lower birth weight infants. Similarly, women with a normal pre-pregnancy BMI whose weekly weight gain was excess than recommended had increased risks of prematurity and lower birth weight infants.