Objective Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably ...detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). Study Design This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). Results MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. Conclusion High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.
Our objective was to evaluate whether pregnancy is prolonged by the use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the ...PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in the preterm birth rate. Rather than considering a dichotomous outcome (preterm versus term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with the PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36–0.78, p < 0.01). Newborns of screened subjects had significantly shorter NICU stays but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We conclude that screening with the PreTRM test followed by interventions for screen-positive pregnancies may prolong pregnancy and reduce NICU LOS, but these observations need to be confirmed by additional research.
Objective We sought to evaluate a recently proposed protocol whereby transabdominal ultrasound of the cervix might be used as a prescreen to select women to undergo or to forgo measurement of ...cervical length via transvaginal ultrasound (CLvag ). Study Design This was a prospective cohort study. Measurements of cervical length via transabdominal ultrasound (CLabd ) and CLvag were made in women with singleton pregnancy during routine obstetrical ultrasound examination at 180/7 to 236/7 weeks of gestation. The transabdominal screen was considered positive if CLabd was ≤36 mm with the maternal bladder full or ≤35 mm with the bladder empty, or adequate imaging of the cervix could not be obtained. Sensitivity, specificity, predictive values, and likelihood ratios of a positive screen to detect a short cervix (CLvag ≤25 mm) were calculated. Results An interim analysis identified several technical problems with CLabd measurements, so the protocol was extensively revised. Under the revised protocol, 1580 women were included. Adequate views of the cervix were obtained via transabdominal imaging in 46% of subjects with the bladder empty and 56% with the bladder full. The correlation between CLabd and CLvag was poor (r = 0.38). Of the 17 patients with a short cervix, 15 had suboptimal transabdominal exams (screen positive) and 2 had CLabd ≤35 mm with bladder empty (screen positive). Sensitivity of the screen was 100% (95% confidence interval, 80.5–100%) but specificity was only 32.2% (95% confidence interval, 29.9–34.6%) and screen positive rate was 66.3%. Several technical problems and limitations of transabdominal imaging of the cervix are shown. Conclusion Using modern, high-resolution ultrasound equipment, we were unable to adequately image the cervix via transabdominal ultrasound in half the cases. Although we confirmed that a CLabd cutoff value of 35-36 mm is appropriate for detection of short cervix, the technique for measuring CLabd is fraught with technical problems. Practitioners must validate the technique in their own practice before adopting this or similar prescreening protocols. We decided not to adopt this protocol.
Hypercoagulability frequently complicates moderate or severe COVID-19 and can result in venous thromboembolism, arterial thrombosis, or microvascular thrombosis. Disseminated intravascular ...coagulation, however, is uncommon.
We sought to describe the clinical presentation and outcome in a series of pregnant patients with mild or asymptomatic COVID-19 who had disseminated intravascular coagulation.
This was a retrospective case series. Cases were solicited via e-mails targeted to obstetrical providers in the Mednax National Medical Group and a restricted maternal–fetal medicine Facebook page. Inclusion criteria were: hospital admission during pregnancy, positive test for SARS-CoV-2 within 2 weeks of admission, and maternal disseminated intravascular coagulation defined as ≥2 of the following: platelet count ≤100,000 per mm3, fibrinogen ≤200 mg/dL, and prothrombin time ≥3 seconds above the upper normal limit. Exclusion criteria were severe COVID-19 requiring ventilation within an hour of diagnosis of coagulopathy or use of anticoagulants at the time of diagnosis. Maternal and newborn records were abstracted and summarized with descriptive statistics.
Inclusion criteria were met in 19 cases from October 2020 through December 2021. Of these, 18 had not received any COVID-19 vaccine, and 1 had unknown vaccination status. Median gestational age on hospital admission was 30 weeks (interquartile range, 29–34 weeks). The main presenting symptom or sign was decreased fetal movement (56%) or nonreassuring fetal heart rate pattern (16%). COVID-19 was asymptomatic in 79% of cases. Two of the 3 defining coagulation abnormalities were found in 89% of cases and all 3 in the remaining 11%. Aspartate aminotransferase was elevated in all cases and ≥2 times the upper normal limit in 69%. Only 2 cases (11%) had signs of preeclampsia other than thrombocytopenia or transaminase elevation. Delivery was performed on the day of admission in 74% and on the next day in the remaining 26%, most often by cesarean delivery (68%) under general anesthesia (62%) because of nonreassuring fetal heart rate pattern (63%). Postpartum hemorrhage occurred in 47% of cases. Blood product transfusions were given in 95% of cases, including cryoprecipitate (89% of cases), fresh/frozen plasma (79%), platelets (68%), and red cells (63%). Placental histopathology was abnormal in 82%, with common findings being histiocytic intervillositis, perivillous fibrin deposition, and infarcts or necrosis. Among the 18 singleton pregnancies and 1 twin pregnancy, there were 13 live newborns (65%) and 7 stillbirths (35%). Among liveborn neonates, 5-minute Apgar score was ≤5 in 54%, and among cases with umbilical cord blood gases, pH ≤7.1 was found in 78% and base deficit ≥10 mEq/L in 75%. Positive COVID-19 tests were found in 62% of liveborn infants.
Clinicians should be alert to the possibility of disseminated intravascular coagulation when a COVID-19 patient complains of decreased fetal movement in the early third trimester. If time allows, we recommend evaluation of coagulation studies and ordering of blood products for massive transfusion protocols before cesarean delivery if fetal tracing is nonreassuring.
Continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin infusion (CSII) systems, or insulin pumps, offer great promise for improved glycemic control during pregnancy. ...Combined, these two devices could potentially constitute an artificial pancreas, where real-time blood glucose readings are relayed to an insulin pump that uses a personalized algorithm to decide how much insulin is needed by the patient's body. However, the promise of these two systems have not yet been proven individually or in combination in controlled clinical trials to improve pregnancy outcomes. Such trials are urgently needed before the widespread use of these devices in pregnancy can be justified.
First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), ...and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.
A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.
Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.
We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward.
Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone.
PROSPERO, CRD42018090866.
Objective The decision of whether to retain or remove a previously placed cervical cerclage in women who subsequently rupture fetal membranes in a premature gestation is controversial and all studies ...to date are retrospective. We performed a multicenter randomized controlled trial of removal vs retention of cerclage in these patients to determine whether leaving the cerclage in place prolonged gestation and/or increased the risk of maternal or fetal infection. Study Design A prospective randomized multicenter trial of 27 hospitals was performed. Patients included were those with cerclage placement at ≤23 weeks 6 days in singleton or twin pregnancies, with subsequent spontaneous rupture of membranes between 22 weeks 0 days and 32 weeks 6 days. Patients were randomized to retention or removal of cerclage. Patients were then expectantly managed and delivered only for evidence of labor, chorioamnionitis, fetal distress, or other medical or obstetrical indications. Management after 34 weeks was at the clinician's discretion. Results The initial sample size calculation determined that a total of 142 patients should be included but after a second interim analysis, futility calculations determined that the conditional power for showing statistical significance after randomizing 142 patients for the primary outcome of prolonging pregnancy was 22.8%. Thus the study was terminated after a total of 56 subjects were randomized with complete data available for analysis, 32 to removal and 24 to retention of cerclage. There was no statistical significance in primary outcome of prolonging pregnancy by 1 week comparing the 2 groups (removal 18/32, 56.3%; retention 11/24, 45.8%) P = .59; or chorioamnionitis (removal 8/32, 25.0%; retention 10/24, 41.7%) P = .25, respectively. There was no statistical difference in composite neonatal outcomes (removal 16/33, 50%; retention 17/30, 56%), fetal/neonatal death (removal 4/33, 12%; retention 5/30, 16%); or gestational age at delivery (removal mean 200 days; retention mean 198 days). Conclusion Statistically significant differences were not seen in prolongation of latency, infection, or composite neonatal outcomes. However, there was a numerical trend in the direction of less infectious morbidity, with immediate removal of cerclage. These findings may not have met statistical significance if the original sample size of 142 was obtained, however they provide valuable data suggesting that there may be no advantage to retaining a cerclage after preterm premature rupture of membranes and a possibility of increased infection with cerclage retention.
