Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.

OBJECTIVES: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. METHODS: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. RESULTS: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. CONCLUSIONS: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

Cell-free DNA Screening for Aneuploidy.

Cell-free DNA (cfDNA) screening has high detection for the common fetal autosomal aneuploidies, but is not diagnostic. The positive predictive value should be utilized in counseling after a positive cell-free DNA screen, and diagnostic testing should be offered for confirmation. cfDNA screening does not report a result in ~3% of cases; nonreportable results indicate an increased risk for aneuploidy and some adverse perinatal outcomes. False-positive cfDNA screening occurs due to confined placental mosaicism, maternal copy number variants, mosaicism, and cancer. Pretest education and counseling should be provided with emphasis on the potential benefits, risks, and limitations before cfDNA screening.

Noninvasive prenatal screening and maternal malignancy: role of imaging.

Noninvasive prenatal screening (NIPS) tests for fetal chromosomal anomalies through maternal blood sampling. It is becoming widely available and standard of care for pregnant women in many countries. It is performed in the first trimester of pregnancy, usually between 9 and 12 weeks. Fragments of fetal cell-free deoxyribonucleic acid (DNA) floating in maternal plasma are detected and analyzed by this test to assess for chromosomal aberrations. Similarly, maternal tumor-derived cell-free DNA (ctDNA) released from the tumor cells also circulates in the plasma. Hence, the presence of genomic anomalies originating from maternal tumor-derived DNA may be detected on the NIPS-based fetal risk assessment in pregnant patients. Presence of multiple aneuploidies or autosomal monosomies are the most commonly reported NIPS abnormalities detected with occult maternal malignancies. When such results are received, the search for an occult maternal malignancy begins, in which imaging plays a crucial role. The most commonly detected malignancies via NIPS are leukemia, lymphoma, breast and colon cancers. Ultrasound is a reasonable radiation-free modality for imaging during pregnancy, specially when there are localizing symptoms or findings, such as palpable lumps. While there are no consensus guidelines on the imaging evaluation for these patients, when there are no localizing symptoms or clinically palpable findings, whole body MRI is recommended as the radiation-free modality of choice to search for an occult malignancy. Based on clinical symptoms, practice patterns, and available resources, breast ultrasound, chest radiographs, and targeted ultrasound evaluations can also be performed initially or as a follow-up for MRI findings. CT is reserved for exceptional circumstances due to its higher radiation dose. This article intends to increase awareness of this rare but stressful clinical scenario and guide imaging evaluation for occult malignancy detected via NIPS during pregnancy.

Protocol for the Phase 2 EDELIFE Trial Investigating the Efficacy and Safety of Intra-Amniotic ER004 Administration to Male Subjects with X-Linked Hypohidrotic Ectodermal Dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (EDA). Most affected males are hemizygous for EDA null mutations that lead to the absence or inactivity of the signalling protein ectodysplasin A1 (EDA1) and, thus, to the full-blown phenotype with inability to perspire and few if any teeth. There are currently no long-term treatment options for XLHED. ER004 represents a first-in-class protein replacement molecule designed for specific, high-affinity binding to the endogenous EDA1 receptor (EDAR). Its proposed mechanism of action is the replacement of missing EDA1 in yet unborn patients with XLHED. Once bound to EDAR, ER004 activates the EDA/NFκB signalling pathway, which triggers the transcription of genes involved in the normal development of multiple tissues. Following preclinical studies, named-patient use cases demonstrated significant potential of ER004 in affected males treated in utero during the late second and third trimesters of pregnancy. In order to confirm these results, we started the EDELIFE trial, a prospective, open-label, genotype-match controlled, multicentre clinical study to investigate the efficacy and safety of intra-amniotic ER004 administration as a prenatal treatment for male subjects with XLHED. This article summarises the rationale, the study protocol, ethical issues of the trial, and potential pitfalls.

Incidental Detection of Maternal Malignancy by Fetal Cell-Free DNA Screening.

Cell-free DNA is an advancing technology with increasing applications in screening, diagnosis, and treatment for several disease processes. The shared physiologic, genetic, and epigenetic characteristics of placental physiology and tumor development have become apparent to both clinicians and researchers. Maternal malignancy has been reported as a cause of false-positive prenatal cell-free DNA screening results. The detection of multiple aneuploidies or a single autosomal monosomy increases the chance for an underlying maternal malignancy when the result is discordant with fetal diagnostic testing. There is currently no consensus guideline on counseling and evaluation of patients with concern for malignancy from cell-free DNA testing. Furthermore, laboratories differ significantly in reporting policies, terminology, and in reporting strategies and methods used for unexpected or incidental findings. The ordering practitioner is therefore tasked to understand the policies of their laboratory of choice to provide adequate pretest and posttest genetic counseling. In pretest counseling, the potential for incidental or unexpected findings or nonreportable results should be explained. With an abnormal, unanticipated, or nonreportable result, posttest counseling should include a description of possible fetal or maternal diagnoses, including malignancy. Health care professionals should explain options for further evaluation and management, including a recommendation for fetal diagnostic testing. The medical workup recommended by various authors to evaluate cancer risk is based on consensus, experience, and expert opinion. These strategies should incorporate the patient's desire for information, cost, and family and personal medical history. Ongoing research and multi-disciplinary collaboration in this area is critical to identify best practices in management of complex results from this increasingly common screening test.

Care Levels for Fetal Therapy Centers.

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels for fetal therapy centers are proposed to match the anticipated care complexity, with appropriate resources to achieve an optimal outcome at an institutional and regional level. A level I fetal therapy center should be capable of offering fetal interventions that may be associated with obstetric risks of preterm birth or membrane rupture but that would be very unlikely to require maternal medical subspecialty or intensive care, with neonatal risks not exceeding those of moderate prematurity. A level II center should have the incremental capacity to provide maternal intensive care and to manage extreme neonatal prematurity. A level III therapy center should offer the full range of fetal interventions (including open fetal surgery) and be able manage any of the associated maternal complications and comorbidities, as well as have access to neonatal and pediatric surgical intervention including indicated surgery for neonates with congenital anomalies.

Disparities in the acceptance of chromosomal microarray at the time of prenatal genetic diagnosis.

OBJECTIVE: Chromosomal microarray (CMA) increases the diagnostic yield of prenatal genetic diagnostic testing but is not universally performed. Our objective was to identify provider and patient characteristics associated with the acceptance of CMA at the time of prenatal genetic diagnostic testing. METHODS: Retrospective cohort study of patients undergoing prenatal genetic diagnostic testing (chorionic villus sampling or amniocentesis) at a single institution between 2014 and 2020. Primary outcome was the acceptance of CMA based on the genetic counselor ,GC who saw the patient. Secondary analyses assessed patient characteristics associated with the acceptance of CMA. RESULTS: 2372 participants were included. Fifty-eight percent of participants accepted CMA. Acceptance of CMA varied significantly by GC, ranging from 31% to 90%. Patients with public insurance and those who identified as Black or Hispanic/Latina were less likely to have CMA performed (aOR 0.24, 95% CI 0.20-0.30, and 0.68, 95% CI 0.50-0.92). Even among those with a structural anomaly present, public insurance was associated with significantly lower odds of CMA being performed (aOR 0.39, 95% CI 0.25-0.61). CONCLUSIONS: Acceptance of CMA at the time of prenatal genetic diagnostic testing varied based on the GC performing the counseling. Public insurance was associated with lower frequency of accepting CMA.

Society for Maternal-Fetal Medicine Consult Series #59: The use of analgesia and anesthesia for maternal-fetal procedures.

Pain is a complex phenomenon that involves more than a simple physical response to external stimuli. In maternal-fetal surgical procedures, fetal analgesia is used primarily to blunt fetal autonomic responses and minimize fetal movement. The purpose of this Consult is to review the literature on what is known about the potential for fetal awareness of pain and to discuss the indications for and the risk-benefit calculus involved in the use of fetal anesthesia and analgesia. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that fetal paralytic agents be considered in the setting of intrauterine transfusion, if needed, for the purpose of decreasing fetal movement (GRADE 2C); (2) although the fetus is unable to experience pain at the gestational age when procedures are typically performed, we suggest that opioid analgesia should be administered to the fetus during invasive fetal surgical procedures to attenuate acute autonomic responses that may be deleterious, avoid long-term consequences of nociception and physiological stress on the fetus, and decrease fetal movement to enable the safe execution of procedures (GRADE 2C); and (3) due to maternal risk and a lack of evidence supporting benefit to the fetus, we recommend against the administration of fetal analgesia at the time of pregnancy termination (GRADE 1C).

Prenatal presentation of multiple anomalies associated with haploinsufficiency for ARID1A.

The ARID1A gene is an infrequent cause of Coffin-Siris syndrome (CSS) and has been associated with severe to profound developmental delays and hypotonia in addition to characteristic craniofacial and digital findings. We present three fetuses and a male neonate with ventriculomegaly/hydrocephalus, absence of the corpus callosum (ACC), cerebellar hypoplasia, retinal dysplasia, lung lobulation defects, renal dysplasia, imperforate or anteriorly placed anus, thymus hypoplasia and a single umbilical artery. Facial anomalies included downslanting palpebral fissures, wide-spaced eyes, low-set and posteriorly rotated ears, a small jaw, widely spaced nipples and hypoplastic nails. All fetuses had heterozygous variants predicting premature protein truncation in ARID1A (c.4886dup:p.Val1630Cysfs*18; c.4860dup:p.Pro1621Thrfs*27; and c.175G>T:p.Glu59*) and the baby's microarray demonstrated mosaicism for a deletion at chromosome 1p36.11 (arr[GRCh37] 1p36.11(26,797,508_27,052,080)×1∼2), that contained the first exon of ARID1A. Although malformations, in particular ACC, have been described with CSS caused by pathogenic variants in ARID1A, prenatal presentations associated with this gene are rare. Retinal dysplasia, lung lobulation defects and absent thymus were novel findings in association with ARID1A variants. Studies in cancer have demonstrated that pathogenic ARID1A variants hamper nuclear import of the protein and/or affect interaction with the subunits of SWI/SNF complex, resulting in dysregulation of the PI3K/AKT pathway and perturbed PTEN and PIKC3A signaling. As haploinsufficiency for PTEN and PIKC3A can be associated with ventriculomegaly/hydrocephalus, aberrant expression of these genes is a putative mechanism for the brain malformations demonstrated in patients with ARID1A variants.

Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis.

BACKGROUND: Next-generation sequencing is increasingly used in prenatal diagnosis. Targeted gene panels and exome sequencing are both available, but the comparative diagnostic yields of these approaches are not known. OBJECTIVE: We compared the diagnostic yield of exome sequencing with the simulated application of commercial targeted gene panels in a large cohort of fetuses with nonimmune hydrops fetalis. STUDY DESIGN: This was a secondary analysis of a cohort study of exome sequencing for nonimmune hydrops fetalis, in which recruitment, exome sequencing, and phenotype-driven variant analysis were completed in 127 pregnancies with features of nonimmune hydrops fetalis. An Internet search was performed to identify commercial laboratories that offer targeted gene panels for the prenatal evaluation of nonimmune hydrops fetalis or for specific disorders associated with nonimmune hydrops fetalis using the terms "non-immune hydrops fetalis," "fetal non-immune hydrops," "hydrops," "cystic hygroma," "lysosomal storage disease," "metabolic disorder," "inborn error of metabolism," "RASopathy," and "Noonan." Our primary outcome was the proportion of all genetic variants identified through exome sequencing that would have been identified if a targeted gene panel had instead been used. The secondary outcomes were the proportion of genetic variants that would have been identified by type of targeted gene panel (general nonimmune hydrops fetalis, RASopathy, or metabolic) and the percent of variants of uncertain significance that would have been identified on the panels, assuming 100% analytical sensitivity and specificity of panels for variants in the included genes. RESULTS: Exome sequencing identified a pathogenic or likely pathogenic variant in 37 of 127 cases (29%) in a total of 29 genes. A variant of uncertain significance, strongly suspected to be associated with the phenotype, was identified in another 12 cases (9%). We identified 7 laboratories that offer 10 relevant targeted gene panels; 6 are described as RASopathy panels, 3 as nonimmune hydrops fetalis panels, and 1 as a metabolic panel. The median number of genes included on each of these panels is 22, ranging from 11 to 148. Had a nonimmune hydrops fetalis targeted gene panel been used instead of exome sequencing, 13 to 15 of the 29 genes (45%-52%) identified in our nonimmune hydrops fetalis cohort would have been sequenced, and 19 to 24 of the pathogenic variants (51%-62%) would have been detected. The yield was predicted to be the lowest with the metabolic panel (11%) and the highest with the largest nonimmune hydrops fetalis panel (62%). The largest nonimmune hydrops fetalis targeted gene panel would have had a diagnostic yield of 18% compared with 29% with exome sequencing. The exome sequencing platform used provided 30× or more coverage for all of the exons on the commercial targeted gene panels, supporting our assumption of 100% analytical sensitivity for exome sequencing. CONCLUSION: The broader coverage of exome sequencing for genetically heterogeneous disorders, such as nonimmune hydrops fetalis, made it a superior alternative to targeted gene panel testing.

Exome sequencing of fetuses with congenital diaphragmatic hernia supports a causal role for NR2F2, PTPN11, and WT1 variants.

BACKGROUND: To identify genes associated with congenital diaphragmatic hernia (CDH) to help understand the etiology and inform prognosis. METHODS: We performed exome sequencing on fetuses with CDH and their parents to identify rare genetic variants likely to mediate risk. We reviewed prenatal characteristics and neonatal outcomes. RESULTS: Data were generated for 22 parent-offspring trios. Six Likely Damaging (LD) variants were identified in five families (23 %). Three LD variants were in genes that contain variants in other CDH cohorts (NR2F2, PTPN11, WT1), while three were in genes that do not (CTR9, HDAC6, TP53). Integrating these data bolsters the evidence of association of NR2F2, PTPN11, and WT1 with CDH in humans. Of the five fetuses with a genetic diagnosis, one was terminated, two underwent perinatal demise, while two survived until repair. CONCLUSIONS: Exome sequencing expands the diagnostic yield of genetic testing in CDH. Correlating CDH patients' exomes with clinical outcomes may enable personalized counseling and therapies.

Society for Maternal-Fetal Medicine Consult Series #59: The use of analgesia and anesthesia for maternal-fetal procedures.

Pain is a complex phenomenon that involves more than a simple physical response to external stimuli. In maternal-fetal surgical procedures, fetal analgesia is used primarily to blunt fetal autonomic responses and minimize fetal movement. The purpose of this Consult is to review the literature on what is known about the potential for fetal awareness of pain and to discuss the indications for and the risk-benefit calculus involved in the use of fetal anesthesia and analgesia. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that fetal paralytic agents be considered in the setting of intrauterine transfusion, if needed, for the purpose of decreasing fetal movement (GRADE 2C); (2) although the fetus is unable to experience pain at the gestational age when procedures are typically performed, we suggest that opioid analgesia should be administered to the fetus during invasive fetal surgical procedures to attenuate acute autonomic responses that may be deleterious, avoid long-term consequences of nociception and physiological stress on the fetus, and decrease fetal movement to enable the safe execution of procedures (GRADE 2C); and (3) due to maternal risk and a lack of evidence supporting benefit to the fetus, we recommend against the administration of fetal analgesia at the time of pregnancy termination (GRADE 1C).

Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?

OBJECTIVE: The positive predictive values of cell free DNA (cfDNA) and rates of confined placental mosaicism (CPM), imprinting and other factors vary by chromosome. METHODS: We sought to review the literature for each of these features for each chromosome and provide recommendations on chorionic villus sampling (CVS) versus amniocentesis after an abnormal cfDNA result. RESULTS: For chromosomes with high rates of CPM (trisomy 13, monosomy X and rare autosomal trisomies [RATs]), an amniocentesis should be considered if the first trimester ultrasound is normal. For monosomy X on cfDNA with an unaffected fetus, maternal karyotyping should be considered after normal fetal diagnostic testing. In cfDNA cases with a trisomy involving a chromosome with imprinted genes (6, 7, 11, 14, 15 and 20), CVS should be considered, followed by amniocentesis if abnormal. If the fetus is unaffected, methylation studies should be considered given the risk of uniparental disomy. A third trimester growth ultrasound should be considered for patients with a positive cfDNA screen for a RAT and an unaffected fetus, especially in the case of trisomy 16. For patients with multiple aneuploidy results on cfDNA, a work-up for maternal malignancy should be considered. CONCLUSIONS: Clinicians should consider rates of CPM, imprinting, ultrasound findings and maternal factors when considering whether to recommend amniocentesis or CVS after an abnormal cfDNA result.

Expanded Carrier Screening and the Complexity of Implementation.

Advances in genetic technology have allowed for the development of multiplex panels that can test for hundreds of genetic disorders at the same time; these large panels are referred to as expanded carrier screening. This process can screen couples for far more conditions than the gene-by-gene approach used with traditional carrier screening; however, although expanded carrier screening has been promoted as an efficient means of detecting many more disorders, the complexities of genetic sequencing raise substantial challenges and concerns. In our practice, we have seen a number of complex cases in which only attention to detail on the part of thorough genetic counselors allowed identification of misclassified variants that could have resulted in significant patient harm. We raise issues that require urgent attention by professional societies, including: whether to endorse testing that uses sequencing compared with genotyping; required components of pretest and posttest counseling; reclassification of variants; whether obstetric health care professionals have a responsibility to assure that patients understand the iterative process of variant interpretation and how it relates to carrier screening results; and the question of rescreening in subsequent pregnancies. Implementation of expanded carrier screening needs to be considered thoughtfully in light of the complexity of genetic sequencing and limited knowledge of genetics of most front-line obstetric health care professionals.

Gross morphologic appearance of chorionic villi and the risk of chromosomal abnormalities.

Chromosomal abnormalities are associated with changes in complex aspects of chorionic villi histomorphology. This study used a simple scoring system to evaluate the association between atypical gross morphology and abnormal chromosomal testing on chorionic villus sampling (CVS). This retrospective cohort study included singleton pregnancies that underwent CVS at a single institution from 2006-2017. The degree of budding, branching, and vascularity (BBV) was scored from 0 to 3 for each CVS specimen, and individual scores were summed to calculate a composite BBV score. Scores were categorized into typical or atypical based on the cohort's distribution. The primary predictor was atypical BBV score, and the primary outcome was chromosomal abnormality. Fisher's exact test compared proportions, and logistic regression generated odds ratios. Among 1171 CVS specimens, 28% had chromosomal abnormalities. The chromosomally abnormal group had a higher rate of atypical BBV score than the normal group (7.3% vs 3.7%, P=0.009), a finding that remained statistically significant after controlling for maternal age, gestational age, and mode of CVS (aOR 2.2, 95% CI 1.24-3.82). Atypical chorionic villus morphology is associated with chromosomal abnormalities. This scoring system is simple, rapid, and easy to perform at the time of routine diagnosis.

Assessing the multidisciplinary team approaches to placenta accreta spectrum across five institutions within the University of California fetal Consortium (UCfC).

PURPOSE: To describe the multidisciplinary approaches to placenta accreta spectrum (PAS) across five tertiary care centers that comprise the University of California fetal Consortium (UCfC) and to identify potential best practices. MATERIALS AND METHODS: Retrospective review of all cases of pathologically confirmed invasive placenta delivered from 2009 to 2014 at UCfC. Differences in intraoperative management and outcomes based on prenatal suspicion were compared. Interventions assessed included ureteral stent use, intravascular balloon use, anesthetic type, gynecologic oncology (Gyn Onc) involvement, and cell saver use. Intervention variation by institution was also assessed. Analyses were adjusted for final pathologic diagnosis. Chi-square, Fisher's exact, Student's t-test, and Mann-Whitney's U-test were used as appropriate. Binary logistic regression and multivariable linear regression were used to adjust for confounders. RESULTS: One hundred and fifty-one cases of pathologically confirmed invasive placenta were identified, of which 82% (123) were suspected prenatally. There was no correlation between the degree of invasion on prenatal imaging and use of each intervention. Ureteral stents were placed in 33% (41) of cases and did not reduce GU injury. Intravascular balloons were placed in 29% (36) of cases and were associated with shorter OR time (161 versus 236 min, p < .01) and lower estimated blood loss (EBL) (1800 versus 2500 ml, p < .01). General endotracheal anesthesia (GETA) was used in 70% (86). EBL did not differ between GETA and regional anesthesia. Gyn Onc was involved in 58% (71) of cases and EBL adjusted for final pathology was reduced with their involvement (2200 versus 2250 ml, p = .02) while OR time and intraoperative complications did not differ. Cell saver was used in 20% (24) and was associated with longer OR time (296 versus 200 min, p < .01). Use of cell saver was not associated with a difference in EBL or number of units of packed red cells transfused. All analyses were adjusted for pathologic severity of invasion. CONCLUSIONS: Intravascular interventions such as uterine artery balloons and the inclusion of Gynecologic Oncologists as part of a multidisciplinary approach to treating PAS reduce EBL. Additionally, the placement of intravascular balloons may reduce OR time. No significant differences were seen in outcomes when comparing the use of ureteral stents, general anesthesia, or institutions. A team of experienced operators with a standard approach may be more significant than specific practices.