Objective The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact ...membranes. Study Design Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). Results The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio OR, 4.9; 95% confidence interval CI, 2.2–11.2, OR, 3.1; 95% CI, 1.5–6.4, and OR, 1.8; 95% CI, 0.6–5.5, respectively). Conclusion We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.
There is currently no standard national approach to the management of category II fetal heart rate (FHR) patterns, yet such patterns occur in the majority of fetuses in labor. Under such ...circumstances, it would be difficult to demonstrate the clinical efficacy of FHR monitoring even if this technique had immense intrinsic value, since there has never been a standard hypothesis to test dealing with interpretation and management of these abnormal patterns. We present an algorithm for the management of category II FHR patterns that reflects a synthesis of available evidence and current scientific thought. Use of this algorithm represents one way for the clinician to comply with the standard of care, and may enhance our overall ability to define the benefits of intrapartum FHR monitoring.
Abstract Background Despite intensive efforts directed at initial training in fetal heart rate interpretation, continuing medical education, board certification/recertification, team training and the ...development of specific protocols for the management of abnormal fetal heart rate patterns, the goals of consistently preventing hypoxia-induced fetal metabolic acidemia and neurologic injury remain elusive. Objective To validate a recently published algorithm for the management of category II fetal heart rate tracings , examine reasons for the birth of infants with significant metabolic acidemia despite the use of electronic fetal heart rate monitoring and critically examine the limits of EFHRM in the prevention of neonatal metabolic acidemia. Study Design The potential performance of electronic fetal heart rate monitoring (EFHRM) under ideal circumstances was evaluated in an outcomes- blinded examination FHRTs of infants with metabolic acidemia at birth (base deficit > 12) and matched controls (base deficit < 8) under the following conditions: (1) Expert primary interpretation. (2) Use of a published algorithm developed and endorsed by a large group of national experts. (3) Assumption of a 30 minute period of evaluation for non-critical category II FHRTs, followed by delivery within 30 minutes. (4) Evaluation without the need to simultaneously provide patient care. (5) Comparison of results under these circumstances with those achieved in actual clinical practice. Results During the study period, 120 infants were identified with arterial cord blood BD > 12mM/L. Matched controls were not demographically different from subjects. In actual practice, operative intervention on the basis of an abnormal FHRT occurred in 36 of 120 fetuses (30.0%) with metabolic acidemia. Based on expert , algorithm- assisted reviews, 55 of 120 acidemic patients (45.8%) were judged as needing operative intervention for abnormal FHRT. This difference was significant (p=0.016). In infants born with BD > 12mM/L in which blinded, algorithm-assisted expert review indicated the need for operative delivery the decision for delivery would have been made an average of 131 minutes prior to the actual delivery. The rate of expert intervention for FHR concerns in the non-acidemic control group (22/120 =18.3%) was similar to the actual intervention rate (23/120= 19.2%, p =1.0) Expert review did not mandate earlier delivery in 65 of 120 patients with metabolic acidemia. (Table) The primary features of these 65 cases included the occurrence of sentinel events with prolonged deceleration just prior to delivery, rapid deterioration of non-emergent category II FHRTs prior to realistic time frames for recognition and intervention, and the failure of recognized FHR patterns such as variability to identify metabolic acidemia. Conclusions Expert, algorithm-assisted FHR interpretation has the potential to improve standard clinical performance by facilitating significantly earlier recognition of some tracings associated with metabolic acidemia without increasing the rate of operative intervention. However, this improvement is modest. Of infants born with metabolic acidemia, only about one-half could be potentially identified and have delivery expedited even under ideal circumstances which are probably not realistic in current U.S. practice. This represents the limits of EFHRM performance. Additional technologies will be necessary if the goal of preventing neonatal metabolic acidemia is to be realized.
Objective The objective of this study was to validate the clinical performance of massively parallel genomic sequencing of cell-free deoxyribonucleic acid contained in specimens from pregnant women ...at high risk for fetal aneuploidy to test fetuses for trisomies 21, 18, and 13; fetal sex; and the common sex chromosome aneuploidies (45, X; 47, XXX; 47, XXY; 47, XYY). Study Design This was a prospective multicenter observational study of pregnant women at high risk for fetal aneuploidy who had made the decision to pursue invasive testing for prenatal diagnosis. Massively parallel single-read multiplexed sequencing of cell-free deoxyribonucleic acid was performed in maternal blood for aneuploidy detection. Data analysis was completed using sequence reads unique to the chromosomes of interest. Results A total of 3430 patients were analyzed for demographic characteristics and medical history. There were 137 fetuses with trisomy 21, 39 with trisomy 18, and 16 with trisomy 13 for a prevalence rate of the common autosomal trisomies of 5.8%. There were no false-negative results for trisomy 21, 3 for trisomy 18, and 2 for trisomy 13; all 3 false-positive results were for trisomy 21. The positive predictive values for trisomies 18 and 13 were 100% and 97.9% for trisomy 21. A total of 8.6% of the pregnancies were 21 weeks or beyond; there were no aneuploid fetuses in this group. All 15 of the common sex chromosome aneuploidies in this population were identified, although there were 11 false-positive results for 45,X. Taken together, the positive predictive value for the sex chromosome aneuploidies was 48.4% and the negative predictive value was 100%. Conclusion Our prospective study demonstrates that noninvasive prenatal analysis of cell-free deoxyribonucleic acid from maternal plasma is an accurate advanced screening test with extremely high sensitivity and specificity for trisomy 21 (>99%) but with less sensitivity for trisomies 18 and 13. Despite high sensitivity, there was modest positive predictive value for the small number of common sex chromosome aneuploidies because of their very low prevalence rate.
Vasa previa: diagnosis and management Swank, Morgan L., MD; Garite, Thomas J., MD; Maurel, Kimberly, MSN ...
American journal of obstetrics and gynecology,
08/2016, Volume:
215, Issue:
2
Journal Article
Peer reviewed
Background Vasa previa is a rare condition that is associated with a high rate of fetal or neonatal death when not diagnosed antenatally. The majority of available studies are either small, do not ...include antepartum data, limited to single institutions, or are biased by inclusion of patients from registries and online vasa previa support groups. Objective The purpose of this study was to investigate the diagnostic and management strategies for this potentially catastrophic entity and to describe further maternal and placental risk factors that may aid in the establishment of a screening protocol for vasa previa. Study Design This was a retrospective multicenter descriptive study that included all pregnancies that were complicated by vasa previa that delivered between January 1, 2000, and December 31, 2012. Nine maternal fetal medicine practices and the hospitals in which they practice participated in data collection of diagnosis, treatment, and maternal-neonatal outcomes. Results Sixty-eight pregnancies were identified that included the diagnosis of vasa previa or “possible vasa previa” either in the ultrasound record or in the hospital record at the time of delivery. Four cases (5.8%) appeared to resolve on repeat ultrasound examination. Fifteen of the 64 cases that were suspected of having vasa previa could not be verified or were not documented at delivery. Of the remaining 49 cases, where vasa previa was documented, 47 cases (96%) were diagnosed by ultrasound scanning antenatally. Known risk factors for vasa previa were present in 41 of 47 cases (87%). Of the 49 cases, 41 were delivered by planned cesarean delivery at a mean gestational age of 34.7 weeks, and 8 cases required emergent cesarean delivery at a mean gestational age of 34.6 weeks (range, 32.4-36.0 weeks gestation). Seven of these emergent cesarean deliveries had been diagnosed previously; 1 case had not. All of the emergent cesarean deliveries were for vaginal bleeding; 1 case was also for a concerning fetal heart rate, but only 1 of the known cases had a documented ruptured fetal vessel. None of these cases were found to have cervical shortening before the onset of bleeding. One of the undiagnosed cases resulted in a ruptured fetal vessel and a baby with no heart beat at birth who survived but had periventricular leukomalacia at 1 month of age with mild white-matter atrophy. Of the remaining neonates in this group, there were no deaths and no major complications beyond mild respiratory distress syndrome in 9 cases. There were no other major neonatal complications, which included no cases of periventricular leukomalacia, neonatal sepsis, necrotizing enterocolitis, or any grade of intraventricular hemorrhage in the confirmed cases of vasa previa. Conclusion This study confirms most current recommendations that include risk-based ultrasound screening, early hospitalization at 30-34 weeks gestation, antenatal corticosteroids at 30-32 weeks gestation, and elective delivery at 33-34 weeks gestation. Thus, with these recommendations for current identification and management of vasa previa in this series of geographically diverse mostly private practice maternal fetal medicine practices, we have confirmed recent reports that show a dramatic improvement in neonatal survival and complications compared with earlier reports.
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.
Putting the “M” back in maternal–fetal medicine D'Alton, Mary E., MD; Bonanno, Clarissa A., MD; Berkowitz, Richard L., MD ...
American journal of obstetrics and gynecology,
06/2013, Volume:
208, Issue:
6
Journal Article
Peer reviewed
Although maternal death remains rare in the United States, the rate has not decreased for 3 decades. The rate of severe maternal morbidity, a more prevalent problem, is also rising. Rise in maternal ...age, in rates of obesity, and in cesarean deliveries as well as more pregnant women with chronic medical conditions all contribute to maternal mortality and morbidity in the United States. We believe it is the responsibility of maternal-fetal medicine (MFM) subspecialists to lead a national effort to decrease maternal mortality and morbidity. In doing so, we hope to reestablish the vital role of MFM subspecialists to take the lead in the performance and coordination of care in complicated obstetrical cases. This article will summarize our initial recommendations to enhance MFM education and training, to establish national standards to improve maternal care and management, and to address critical research gaps in maternal medicine.
Objective Laborist programs have expanded throughout the United States in the last decade. Meanwhile, there has been no published research examining their effect on patient outcomes. Cesarean ...delivery is a key performance metric with maternal health implications and significant financial impact. Our hypothesis is that the initiation of a full-time dedicated laborist staff decreases cesarean delivery. Study Design In a tertiary hospital staffed with private practice physicians, data were retrospectively reviewed for 3 time periods from 2006 through 2011. The first period (16 months) there were no laborists (traditional model), followed by 14 months of continuous in-hospital laborist coverage provided by community staff (community laborist), and finally a 24-month period with full-time laborists providing continuous in-hospital coverage. The primary hypothesis was that full-time laborists would decrease cesarean delivery rates. Results Data from 6206 term nulliparous patients were retrospectively reviewed. The cesarean delivery rate for no laborist care was 39.2%, for community physician laborist care was 38.7%, and for full-time laborists was 33.2%. With adjustment via logistic regression, full-time laborist presence was associated with a significant reduction in cesarean delivery when contrasted with no laborist (odds ratio, 0.73; 95% confidence interval, 0.64–0.83; P < .0001) or community laborist care (odds ratio, 0.77; 95% confidence interval, 0.67–0.87; P < .001). The community laborist model was not associated with an effect upon cesarean delivery. Conclusion A dedicated full-time laborist staff model is associated with lower rates of cesarean delivery. These findings may be used as part of a strategy to reduce cesarean delivery, lower maternal morbidity and mortality, and decrease health care costs.
Background Counseling for patients with impending premature delivery traditionally has been based primarily on the projected gestational age at delivery. There are limited data regarding how the ...indications for the preterm birth affect the neonatal outcome and whether this issue should be taken into account in decisions regarding management and patient counseling. Objective We performed a prospective study of pregnancies resulting in premature delivery at less than 32 weeks to determine the influence of both the indications for admission and their associated indications for delivery on neonatal mortality and complications of prematurity. Study Design This is a multicenter, prospective study in 10 hospitals where all data from the neonatal intensive care unit routinely was imported to a deidentified data warehouse. Maternal data were collected prospectively at or near the time of delivery. Eligible subjects included singleton deliveries in these hospitals between 23 0/7 and 31 6/7 weeks. The primary hypothesis of the study was to determine whether there was a difference in the primary outcome, which was defined as neonatal composite morbidity, between those neonates delivered after admission for premature labor vs premature rupture of membranes, because these were expected to be the 2 most frequent diagnoses leading to premature birth. The sample size was calculated based on a 10% difference in outcomes for these 2 entities. We based this hypothesis on the knowledge that premature rupture of membranes has a greater incidence of intra-amniotic infection and inflammation than premature labor and that outcomes for premature neonates are worse when delivery is associated with intra-amniotic infection. Additional outcomes were analyzed for all other indications for admission and delivery. Composite morbidity was defined as ≥1 of the following: respiratory distress syndrome (oxygen requirement, clinical diagnosis, and consistent chest radiograph), bronchopulmonary dysplasia (requirement for oxygen support at 28 days of life), severe intraventricular hemorrhage (grades 3 or 4), periventricular leukomalacia, blood culture-proven sepsis present within 72 hours of birth, necrotizing enterocolitis, or neonatal death before discharge from the hospital. A secondary composite of serious neonatal morbidity also was defined prospectively. Results The study included 1089 mother/baby pairs. Composite morbidity between those with premature labor (77.2%) and premature rupture of membranes (73.2%) was not significantly different ( P = .29). A few neonatal complications were associated with indications for admission and delivery, but on logistic regression adjusting for gestational age and other confounders, suspected intrauterine growth restriction was the only indication for admission or delivery associated with an increase in serious morbidity (odds ratio 4.5, 2.1 to 9.8, P < .003). Other factors not related to the indications for admission including cesarean delivery and low 5-minute Apgar were associated with an increase in morbidity. Conclusion Studies of many single factors related to the indications for preterm delivery have been shown to be associated with adverse neonatal outcome. In this study evaluating all of the most frequent indications, however, we found only suspected intrauterine growth restriction as an indication for admission and delivery was found to be so. Thus, it seems that in almost all situations counseling patients can be based primarily on gestational age along with other factors including estimated fetal weight, sex, race, plurality, and completion of a course of antenatal corticosteroids.
PDF