Publications by authors named "Ahmet A Baschat"

98 Publications

Postnatal care setting and survival after fetoscopic tracheal occlusion for severe congenital diaphragmatic hernia: A systematic review and meta-analysis.

J Pediatr Surg 2022 May 19. Epub 2022 May 19.

Department of Gynecology and Obstetrics, Johns Hopkins Center for Fetal Therapy, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Baltimore 21287, MD, United States. Electronic address:

Background: Fetoscopic endoluminal tracheal occlusion (FETO) was recently shown to improve postnatal survival in a multicenter, randomized controlled trial of infants with severe congenital diaphragmatic hernia (CDH). However, the external validity of this study remains unclear given a lack of standardization in postnatal management approaches. The purpose of this study was to evaluate the impact of an integrated prenatal and postnatal care setting on survival outcomes in severe CDH after FETO.

Study Design: A systematic review, meta-analysis, and individual participant analysis of FETO outcomes in severe CDH were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary outcome was survival to discharge. Subgroup analyses of patients managed in integrated versus nonintegrated settings were performed to identify predictors of outcome.

Results: The review generated five studies (n = 192) for the meta-analysis of FETO versus expectant prenatal management. These data revealed a significant survival benefit after FETO that was restricted to an integrated setting (OR 2.97, 95% Confidence Interval 1.69-4.26). There were nine studies (n = 150) for the individual participant analysis, which showed that FETO managed in an integrated setting had significantly increased survival rates when compared to FETO treated in a nonintegrated setting (70.7% vs. 45.7%, p = 0.003). Multi-level logistic regression identified increased availability of extracorporeal membrane oxygenation (ECMO) as the strongest determinant of postnatal survival (OR=18.8, p = 0.049).

Conclusion: This systematic review shows that institutional integration of prenatal and postnatal care is associated with the highest overall survival in children with severe CDH. These data highlight the importance of a standardized, multidisciplinary approach, including access to ECMO, as a critical postnatal component in optimizing FETO outcomes in CDH.
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http://dx.doi.org/10.1016/j.jpedsurg.2022.05.011DOI Listing
May 2022

Care Levels for Fetal Therapy Centers.

Obstet Gynecol 2022 06 2;139(6):1027-1042. Epub 2022 May 2.

Department of Gynecology & Obstetrics, Johns Hopkins Center for Fetal Therapy, Johns Hopkins University, Baltimore, Maryland; the Department of Obstetrics, Gynecology & Reproductive Sciences and the Division of Pediatric General and Thoracic Surgery, Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas; the Department of Anesthesiology, Children's Hospital Colorado/Colorado Fetal Care Center, University of Colorado School of Medicine, Aurora, Colorado; the Department of Pediatrics & Bioethics, Albany Medical College, Albany, New York; the Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Division of Pediatric, General, Thoracic and Fetal Surgery, Department of Surgery, UC Davis Medical Center, Sacramento, California; the Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, and the Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, Texas; the Department of Obstetrics & Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; the Department of Surgery, Warren Alpert Medical School of Brown University, and Hasbro Children's Hospital, Providence; Rhode Island; the Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, UNC School of Medicine, Chapel Hill, North Carolina; the Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; the Division of Pediatric Cardiology, Department of Clinical Pediatrics, and the Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, San Francisco, California; the Department of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan; the Division of Neonatology, Department of Paediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; the Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; the Department of Surgery, Centre for Surgical Research, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; the Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, Missouri; Yale University School of Nursing, Orange, Connecticut; and the Ontario Fetal Centre, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1097/AOG.0000000000004793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202072PMC
June 2022

Pathophysiology, diagnosis, and management of twin anemia polycythemia sequence in monochorionic multiple gestations.

Best Pract Res Clin Obstet Gynaecol 2022 Mar 30. Epub 2022 Mar 30.

Johns Hopkins Center for Fetal Therapy, Department of Gynecology & Obstetrics, USA.

Twin anemia polycythemia sequence (TAPS) is a consequence of unequal sharing of red blood cells between monochorionic twins resulting in anemia in the donor and polycythemia in the recipient twin. Prenatally TAPS can occur spontaneously or complicate incomplete laser surgery for twin transfusion syndrome. While there may be clinical overlap with twin transfusion syndrome or selective fetal growth restriction, diagnosis relies on Doppler measurement of middle cerebral artery peak systolic velocities. Significantly discordant velocities are diagnostic, while severity staging is based on signs of cardiovascular compromise. Conservative management, fetoscopic laser coagulation, selective twin reduction, fetal blood and exchange transfusion, and delivery may be selected guided by the gestational age of diagnosis, the severity of the condition, the likelihood of success, and the patients' priorities. Prenatal curative treatment that minimizes the risk for prematurity and residual morbidity at birth is most likely to offer the greatest short-term and long-term benefits.
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http://dx.doi.org/10.1016/j.bpobgyn.2022.03.012DOI Listing
March 2022

The role of the fetal biophysical profile in the management of fetal growth restriction.

Am J Obstet Gynecol 2022 04;226(4):475-486

Fetal Maternal Medicine Consultant, Envision Health, Nashville, TN.

Growth-restricted fetuses are at risk of hypoxemia, acidemia, and stillbirth because of progressive placental dysfunction. Current fetal well-being, neonatal risks following delivery, and the anticipated rate of fetal deterioration are the major management considerations in fetal growth restriction. Surveillance has to quantify the fetal risks accurately to determine the delivery threshold and identify the testing frequency most likely to capture future deterioration and prevent stillbirth. From the second trimester onward, the biophysical profile score correlates over 90% with the current fetal pH, and a normal score predicts a pH >7.25 with a 100% positive predictive value; an abnormal score on the other hand predicts current fetal acidemia with similar certainty. Between 30% and 70% of growth-restricted fetuses with a nonreactive heart rate require biophysical profile scoring to verify fetal well-being, and an abnormal score in 8% to 27% identifies the need for delivery, which is not suspected by Doppler findings. Future fetal well-being is not predicted by the biophysical profile score, which emphasizes the importance of umbilical artery Doppler and amniotic fluid volume to determine surveillance frequency. Studies with integrated surveillance strategies that combine frequent heart rate monitoring with biophysical profile scoring and Doppler report better outcomes and stillbirth rates of between 0% and 4%, compared with those between 8% and 11% with empirically determined surveillance frequency. The variations in clinical behavior and management challenges across gestational age are better addressed when biophysical profile scoring is integrated into the surveillance of fetal growth restriction. This review aims to provide guidance on biophysical profile scoring in the in- and outpatient management of fetal growth restriction.
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http://dx.doi.org/10.1016/j.ajog.2022.01.020DOI Listing
April 2022

Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.

Am J Obstet Gynecol 2022 03 10;226(3):366-378. Epub 2022 Jan 10.

Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.
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http://dx.doi.org/10.1016/j.ajog.2021.11.1357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125563PMC
March 2022

Implementation Process and Evolution of a Laparotomy-Assisted 2-Port Fetoscopic Spina Bifida Closure Program.

Fetal Diagn Ther 2021 8;48(8):603-610. Epub 2021 Sep 8.

The Johns Hopkins Center for Fetal Therapy, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland, USA.

Introduction: Prenatal closure of open spina bifida via open fetal surgery improves neurologic outcomes for infants in selected pregnancies. Fetoscopic techniques that are minimally invasive to the uterus aim to provide equivalent fetal benefits while minimizing maternal morbidities, but the optimal technique is undetermined. We describe the development, evolution, and feasibility of the laparotomy-assisted 2-port fetoscopic technique for prenatal closure of fetal spina bifida in a newly established program.

Methods: We conducted a retrospective cohort study of women consented for laparotomy-assisted fetoscopic closure of isolated fetal spina bifida. Inclusion and exclusion criteria followed the Management of Myelomeningocele Study (MOMS). Team preparation involved observation at the originating center, protocol development, ancillary staff training, and surgical rehearsal using patient-matched models through simulation prior to program implementation. The primary outcome was the ability to complete the repair fetoscopically. Secondary maternal and fetal outcomes to assess performance of the technique were collected prospectively.

Results: Of 57 women screened, 19 (33%) consented for laparotomy-assisted 2-port fetoscopy between February 2017 and December 2019. Fetoscopic closure was completed in 84% (16/19) cases. Over time, the technique was modified from a single- to a multilayer closure. In utero hindbrain herniation improved in 86% (12/14) of undelivered patients at 6 weeks postoperatively. Spontaneous rupture of membranes occurred in 31% (5/16) of fetoscopic cases. For completed cases, median gestational age at birth was 37 (range 27-39.6) weeks and 50% (8/16) of women delivered at term. Vaginal birth was achieved in 56% (9/16) of patients. One newborn had a cerebrospinal fluid leak that required postnatal surgical repair.

Conclusion: Implementation of a laparotomy-assisted 2-port fetoscopic spina bifida closure program through rigorous preparation and multispecialty team training may accelerate the learning curve and demonstrates favorable obstetric and perinatal outcomes.
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http://dx.doi.org/10.1159/000518507DOI Listing
November 2021

Doppler Ultrasound of the Fetal Descending Aorta: An Objective Tool to Assess Placental Blood Flow Resistance in Pregnancies With Discordant Umbilical Arteries.

J Ultrasound Med 2022 Apr 6;41(4):899-905. Epub 2021 Jul 6.

Centre for Fetal Therapy, Johns Hopkins Medicine, Baltimore, Maryland, USA.

Objectives: To determine the relationship between blood flow in the fetal descending aorta and discordant umbilical arteries (UAs).

Methods: Pulsed wave Doppler of both UAs and the descending aorta was performed at 4-weekly intervals between 14 and 40 weeks of gestation in 209 pregnant women. In datasets with discordant UAs, a linear mixed effects model was used to determine the categorical relationship between the UA pulsatility index (PI) (high, low and average) and the descending aorta PI.

Results: Of the 209 cases, 81 had a discordance of greater than 25% in UA PI during one of their visits. There were no differences in birth outcomes between the groups with concordant and discordant UA PIs. In the cases with discordant UA PIs, the descending aorta PI was most strongly associated with both the average UA PI (P = .008), and with the UA with the lower PI (P = .008).

Conclusions: The relationship between blood flow in the descending aorta and UAs is consistent with the law for combining resistances in parallel. Measurements of the descending aorta PI, particularly in a scenario with discordant UAs, may inform the stability of the feto-placental circulation where discordant UA PIs are found.
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http://dx.doi.org/10.1002/jum.15773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733057PMC
April 2022

Wave reflections in the umbilical artery measured by Doppler ultrasound as a novel predictor of placental pathology.

EBioMedicine 2021 May 5;67:103326. Epub 2021 May 5.

Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada; Translational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.

Background: The umbilical artery (UA) Doppler pulsatility index is used clinically to detect elevated feto-placental vascular resistance. However, this metric is confounded by variation in fetal cardiac function and is only moderately predictive of placental pathology. Our group developed a novel ultrasound methodology that measures wave reflections in the UA, thereby isolating a component of the Doppler signal that is specific to the placenta. The present study examined whether wave reflections in the UA are predictive of placental vascular pathology.

Methods: Standard clinical Doppler ultrasound of the UAs was performed in 241 pregnant women. Of these, 40 women met narrowly defined preset criteria for the control group, 36 had maternal vascular malperfusion (MVM) and 16 had fetal vascular malperfusion (FVM). Using a computational procedure, the Doppler waveforms were decomposed into a pair of forward and backward propagating waves.

Findings: Compared to controls, wave reflections were significantly elevated in women with either MVM (p<0.0001) or FVM pathology (p = 0.02). In contrast, the umbilical and uterine artery pulsatility indices were only elevated in the MVM group (p<0.0001) and there were no differences between women with FVM and the controls.

Interpretation: The measurement of wave reflections in the UA, combined with standard clinical ultrasound parameters, has the potential to improve the diagnostic performance of UA Doppler to detect placental vascular pathology. Identifying women with FVM pathology is particularly challenging prenatally and future investigations will determine if women at risk of this specific placental disease could benefit from this novel diagnostic technique.
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http://dx.doi.org/10.1016/j.ebiom.2021.103326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176120PMC
May 2021

Fetoscopic myelomeningocoele closure: Is the scientific evidence enough to challenge the gold standard for prenatal surgery?

Prenat Diagn 2021 Jul 5;41(8):949-956. Epub 2021 Apr 5.

Department of Obstetrics and Gynecology, Division of Obstetrics and Fetal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.

Since the completion of the Management of Myelomeningocoele Study, maternal-fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high-grade evidence.
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http://dx.doi.org/10.1002/pd.5940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360048PMC
July 2021

Sex differences in fetal Doppler parameters during gestation.

Biol Sex Differ 2021 03 10;12(1):26. Epub 2021 Mar 10.

Department of Chemistry, Memorial University of Newfoundland, 283 Prince Philip Drive, St. John's, NL, A1B 3X7, Canada.

Background: Fetal sex is known to affect pregnancy outcomes. In current clinical practice, monitoring of fetal well-being is based on Doppler ultrasound measurements of major placental and fetal vessels. The objective of this study was to investigate the effect of fetal sex on Doppler parameters throughout gestation in healthy pregnancy.

Methods: A prospective study was conducted in 240 pregnant women with ultrasound examinations at a 4-weekly interval between 12 and 38 weeks of gestation. Pulsed Doppler spectra were collected for the umbilical arteries (UAs), middle cerebral artery (MCA), descending abdominal aorta (DAo), and ductus venosus (DV). Linear mixed effects models were used to determine if the pulsatility indices (PIs) of these vessels depended on gestational age and fetal sex.

Results: While there were no differences in the MCA PI and DV PIV over gestation between female and male fetuses, the trajectory of the UA and DAo PIs differed by fetal sex (p = 0.02 and p = 0.01, respectively).

Conclusions: Doppler ultrasound parameters were found to be dependent on fetal sex for some vessels and not for others in healthy pregnancies. Further investigations are needed to understand the physiological mechanisms for these sex differences and the relevance for disease processes in pregnancy.
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http://dx.doi.org/10.1186/s13293-021-00370-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944891PMC
March 2021

Sex differences in uterine artery Doppler during gestation in pregnancies complicated by placental dysfunction.

Biol Sex Differ 2021 02 2;12(1):19. Epub 2021 Feb 2.

Department of Chemistry, Memorial University of Newfoundland, 283 Prince Philip Drive, St John's, Newfoundland and Labrador, A1B 3X7, Canada.

Background: There is growing evidence of sex differences in placental vascular development. The objective of this study was to investigate the effect of fetal sex on uterine artery pulsatility index (PI) throughout gestation in a cohort of normal and complicated pregnancies.

Methods: A prospective longitudinal study was conducted in 240 pregnant women. Pulsed wave Doppler ultrasound of the proximal uterine arteries was performed at a 4-weekly interval between 14 and 40 weeks of gestation. The patients were classified retrospectively as normal or complicated (one or more of maternal preeclampsia, preterm birth, or small for gestational age). To assess if the change in uterine artery PI during gestation differed between normal and complicated pregnancies and between fetal sexes, the uterine artery PI was modeled using a linear function of gestational age and the rate of change was estimated from the slope.

Results: While the uterine artery PI did not differ over gestation between females and males for normal pregnancies, the trajectory of this index differed by fetal sex for pregnancies complicated by either preeclampsia, preterm birth, or fetal growth restriction (p < 0.0001). The male fetuses in the complicated pregnancy group had an elevated slope compared to the other groups (p < 0.0001), suggesting a more progressive deterioration in uteroplacental perfusion over gestation.

Conclusions: The uterine artery PI is widely used to assess uteroplacental function in clinical settings. The observation that this metric changes more rapidly in complicated pregnancies where the fetus was male highlights the importance of sex when interpreting hemodynamic markers of placental maturation.
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http://dx.doi.org/10.1186/s13293-021-00362-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852081PMC
February 2021

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

Health Technol Assess 2020 12;24(72):1-252

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management.

Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers.

Design: This was an individual participant data meta-analysis of cohort studies.

Setting: Source data from secondary and tertiary care.

Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey.

Primary Outcomes: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia.

Analysis: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for -statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using and τ. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals.

Results: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary -statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia.

Limitations: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data.

Conclusion: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings.

Future Work: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate.

Study Registration: This study is registered as PROSPERO CRD42015029349.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780127PMC
December 2020

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BMC Med 2020 11 2;18(1):302. Epub 2020 Nov 2.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting.

Methods: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis.

Results: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%.

Conclusions: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice.

Trial Registration: PROSPERO ID: CRD42015029349 .
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http://dx.doi.org/10.1186/s12916-020-01766-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604970PMC
November 2020

ACC-AHA Diagnostic Criteria for Hypertension in Pregnancy Identifies Patients at Intermediate Risk of Adverse Outcomes.

Am J Perinatol 2021 08 23;38(S 01):e249-e255. Epub 2020 May 23.

Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Objective: The aim of the study is to compare maternal and neonatal outcomes among patients who are normotensive, hypertensive by Stage I American College of Cardiology-American Heart Association (ACC-AHA) criteria, and hypertensive by American College of Obstetricians and Gynecologists (ACOG) criteria.

Study Design: Secondary analysis of a prospective first trimester cohort study between 2007 and 2010 at three institutions in Baltimore, MD, was conducted. Blood pressure at 11 to 14 weeks' gestation was classified as (1) normotensive (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] <80 mm Hg); (2) hypertensive by Stage I ACC-AHA criteria (SBP 130-139 mm Hg or DBP 80-89 mm Hg); or (3) hypertensive by ACOG criteria (SBP ≥140 mm Hg or DBP ≥90 mm Hg). Primary outcomes included preeclampsia, small for gestational age (SGA) neonate, and preterm birth.

Results: Among 3,422 women enrolled, 2,976 with delivery data from singleton pregnancies of nonanomalous fetuses were included. In total, 20.2% met hypertension criteria (Stage I ACC-AHA  = 254, 8.5%; ACOG  = 347, 11.7%). The Stage I ACC-AHA group's risk for developing preeclampsia was threefold higher than the normotensive group (adjusted relative risk [aRR] 3.70, 95% confidence interval [CI] 2.40-5.70). The Stage I ACC-AHA group had lower preeclampsia risk than the ACOG group but the difference was not significant (aRR 0.87, 95% CI 0.55-1.37). The Stage I ACC-AHA group was more likely than the normotensive group to deliver preterm (aRR 1.44, 95% CI 1.02-2.01) and deliver an SGA neonate (aRR 1.51, 95% CI 1.07-2.12). The Stage I ACC-AHA group was less likely to deliver preterm compared with the ACOG group (aRR 0.65, 95% CI 0.45-0.93), but differences in SGA were not significant (aRR 1.31, 95% CI 0.84-2.03).

Conclusion: Pregnant patients with Stage I ACC-AHA hypertension in the first trimester had higher rates of preeclampsia, preterm birth, and SGA neonates compared with normotensive women. Adverse maternal and neonatal outcomes were numerically lower in the Stage I ACC-AHA group compared with the ACOG group, but these comparisons only reached statistical significance for preterm birth. Optimal pregnancy management for first trimester Stage I ACC-AHA hypertension requires active study.

Key Points: · Women with first trimester American College of Cardiology-American Heart Association (ACC-AHA) Stage I hypertension were more likely to develop preeclampsia, deliver preterm, and deliver a small-for-gestational age neonate than normotensive women.. · Women with first trimester American College of Obstetricians and Gynecologists (ACOG) hypertension (consistent with stage II ACC-AHA hypertension) had the highest numeric rate of adverse outcomes; however, compared with Stage I ACC-AHA hypertension, there was only statistically significant difference for preterm delivery.. · The risk profile for pregnant women with Stage I ACC-AHA hypertension and women with hypertension by conventional ACOG criteria may be more similar than previously understood..
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http://dx.doi.org/10.1055/s-0040-1709465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923636PMC
August 2021

Maternal azithromycin therapy for Ureaplasma parvum intraamniotic infection improves fetal hemodynamics in a nonhuman primate model.

Am J Obstet Gynecol 2020 10 25;223(4):578.e1-578.e11. Epub 2020 Apr 25.

Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases.

Objective: This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes.

Study Design: Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (10 colony-forming units/mL, n=15), and intraamniotic infection plus azithromycin treatment (12.5 mg/kg twice a day intravenously, n=8) groups. At approximately 135 days' gestation (term=165 days), pulsed and color Doppler ultrasonography was used to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebroplacental ratio, and left and right ventricular cardiac outputs) and cardiac function (ratio of peak early vs late transmitral flow velocity [marker of ventricular function], Tei index [myocardial performance index]). These indices were stratified by amniotic fluid proinflammatory mediator levels and cardiac histology.

Results: Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P<.05). Azithromycin treatment restored values to control levels. Amniotic fluid prostaglandin F2 alpha levels were significantly higher in animals with abnormal umbilical artery pulsatility index (>1.1) than in those with normal blood flow (P<.05; Spearman ρ=0.6, P<.05). In the intraamniotic inoculation with Ureaplasma parvum group, left ventricular cardiac output was significantly decreased (P<.001), and more animals had abnormal right-to-left ventricular cardiac output ratios (defined as >1.6, P<.05). Amniotic fluid interleukin-6 concentrations were elevated in cases of abnormal right-to-left ventricular cardiac output ratios compared with those in normal cases (P<.05).

Conclusion: Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.
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http://dx.doi.org/10.1016/j.ajog.2020.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591241PMC
October 2020

A comparison of first trimester blood pressures obtained at the time of first trimester pre-eclampsia screening and those obtained during prenatal care visits.

Eur J Obstet Gynecol Reprod Biol 2020 May 7;248:77-80. Epub 2020 Mar 7.

Center for Fetal Therapy, Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA.

Objective: To determine if enrollment blood pressures in a study on first trimester preeclampsia prediction significantly differed from those obtained during routine prenatal care visits in the first trimester.

Study Design: Women carrying a singleton gestation were prospectively enrolled in a first trimester study on preeclampsia prediction, and had systolic and diastolic blood pressure (SBP, DBP) measured at the time of enrollment. Blood pressure was also measured with the same technique by clinic nurses during the routine prenatal visits throughout the first trimester of pregnancy (9-14 weeks). The enrollment-BP (E-BP) and average first trimester-BP (aFT-BP) were compared using a paired samples t-test or Wilcoxon test, as appropriate. Smokers and patients on antihypertensive medications were excluded from the analysis. test.

Results: 644 women had prenatal care in the primary study center and met study criteria. The mean gestational age at study enrollment was 12.5 weeks. No significant difference was found between E-SBP and aFT-SBP (p = 0.10). Enrollment DBP and mean arterial pressure (MAP) were significantly lower than the aFT- DBP and -MAP (median DPB 67 vs 70 mm Hg and median MAP 83.7 vs 85 mmHg, respectively, p < 0.001). However, the difference was not clinically relevant (3 mmHg for DBP, and 1.3 mmHg for MAP).

Conclusions: Blood pressures obtained in a setting of preeclampsia screening are not higher than those obtained during regular prenatal care in the first trimester. This suggests that the setting in which pre-eclampsia screening is performed is unlikely to be a confounder for blood pressure measurements and the risk assessment.
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http://dx.doi.org/10.1016/j.ejogrb.2020.03.018DOI Listing
May 2020

Single-Center Outcome of Fetoscopic Tracheal Balloon Occlusion for Severe Congenital Diaphragmatic Hernia.

Obstet Gynecol 2020 03;135(3):511-521

Center for Fetal Therapy, Department of Gynecology & Obstetrics, the Department of Anesthesiology and Critical Care Medicine, the Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, the Division of Neonatology and the Pediatric Intensive Care Unit, Department of Pediatrics, and the Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School Medicine, Baltimore, Maryland.

Objective: To assess feasibility and maternal and infant outcome after fetoscopic tracheal balloon occlusion in patients with severe congenital diaphragmatic hernia.

Methods: We conducted a prospective cohort study of fetuses with congenital diaphragmatic hernia and observed/expected lung/head ratio less than 30%. Eligible women had planned fetoscopic tracheal balloon occlusion at 26 0/7-29 6/7 weeks of gestation and balloon removal 4-6 weeks later. Standardized prenatal and postnatal care was at a single institution. Fetoscopic tracheal balloon occlusion details, lung growth, obstetric complications, birth outcome, and infant outcome details until discharge were evaluated.

Results: Of 57 women screened, 14 (25%) were enrolled between 2015 and 2019. The congenital diaphragmatic hernia was left in 12 (86%); the pre-fetoscopic tracheal balloon occlusion observed/expected lung/head ratio was 23.2% (range 15.8-29.0%). At a median gestational age of 28 5/7 weeks (range 27 3/7-29 6/7), fetoscopic tracheal balloon occlusion was successful in all cases, and balloons remained in situ. Removal was elective in 10 (71%) patients, by ultrasound-guided needle puncture in eight (57%), and occurred at a median of 33 4/7 weeks of gestation (range 32 1/7-34 4/7; median occlusion 34 days, range 17-44). The post-fetoscopic tracheal balloon occlusion observed/expected lung/head ratio increased to a median of 62.8% (44.0-108) and fell to a median of 46.6% (range 30-92) after balloon removal (all Mann Whitney U, P<.003). For prevention of preterm birth, all patients received vaginal progesterone; 11 (79%) required additional tocolytics, three (21%) had vaginal pessary placement for cervical shortening, and five (36%) had amnioreduction for polyhydramnios. Median gestational age at birth was 39 2/7 weeks (range 33 6/7-39 4/7), with term birth in eight (57%) patients. Twelve (86%) neonates required high-frequency ventilation, and seven (50%) required extracorporeal membrane oxygenation for a median of 7 days (range 3-19). All neonates needed patch repair. Neonatal survival was 93% (n=13, 95% CI 49-100%), and survival to hospital discharge was 86% (n=12, 95% CI 44-100%).

Conclusion: Fetoscopic tracheal balloon occlusion for severe congenital diaphragmatic hernia was feasible in our single-center setting, with few obstetric complications and favorable infant outcome.

Clinical Trial Registration: ClinicalTrials.gov, NCT02710968.
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http://dx.doi.org/10.1097/AOG.0000000000003692DOI Listing
March 2020

Acceleration and plateau: two patterns and outcomes of isolated severe fetal cerebral ventricular dilation.

J Matern Fetal Neonatal Med 2021 Sep 16;34(18):3014-3020. Epub 2019 Oct 16.

Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Objectives: We sought to characterize patterns of dilation in isolated severe fetal ventriculomegaly (ISVM) and investigate their value in predicting obstetrical and postnatal outcomes.

Methods: This is a retrospective cohort study. ISVM was defined as a sonographic cerebral ventricle atrial with width ≥15 mm in the absence of additional cerebral or other anatomic anomalies. The aim of this study was to characterize two ISVM groups using a receiver operator curve to evaluate the rate of ventricular progression versus need for ventriculoperitoneal (VP) shunt postnatally. Outcomes were compared between the groups using Pearson's chi-squared test, Student -test, and descriptive statistics.

Results: Based on the ROC analysis, ventricular growth of ≥3 mm/week versus <3 mm/week distinguished fetuses likely to require a postnatal VP shunt. Fetuses were characterized as accelerators if ventricle growth was ≥3 mm/week at any point and plateaus if <3 mm/week. Accelerators showed a greater average rate of ventricle progression than plateaus (4.1 vs. 1.0 mm/week, respectively,  = .031) and were more likely to be delivered at earlier gestational ages (34.7 vs. 37.1 weeks respectively,  = .02). Ninety percent of accelerators demonstrated a need for shunt placement compared with 18.8% of plateaus ( < .001). Significantly more plateaus (87.5%) underwent a trial of labor while accelerators were more likely to have planned cesareans (70%,  = .009).

Conclusions: This study characterizes ISVM into two distinct populations based upon the rate of ventricle expansion, differentiated by the need for postnatal shunting. Once a ventricular growth pattern is determined, these distinctions should prove useful in prenatal management and delivery planning.
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http://dx.doi.org/10.1080/14767058.2019.1677590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324013PMC
September 2021

Prenatal diagnosis of Desbuquois dysplasia Type 1: Utilization of high-density SNP array to map homozygosity and identify the gene.

Am J Med Genet A 2019 12 6;179(12):2490-2493. Epub 2019 Oct 6.

Greenberg Center for Skeletal Dysplasias, McKusick-Nathans Institute of the Department of Genetic Medicine, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland.

Desbuquois dysplasia (DBQD1 [MIM 251450]) is an autosomal recessive chondrodysplasia with micromelia, severe joint laxity and dislocations, and a characteristic radiographic "monkey wrench" appearance at the proximal femur. Type 1 Desbuquois dysplasia is caused by mutations in CANT1 and is distinct from Type 2, caused by mutations in XYLT1, in that the former has unique hand anomalies including accessory phalangeal ossification centers, advanced carpal bone maturation, and/or axial phalangeal deviation. Severe prenatal presentations have been rarely reported. We report a Pakistani female in a consanguineous relationship with a diagnosis of Type 1 Desbuquois dysplasia in three consecutive pregnancies. Multiple similar severe fetal limb anomalies were detected by ultrasound in Pregnancy 1 and 2. Regions of homozygosity within the single nucleotide polymorphism (SNP)-microarray from both terminated fetuses were compared, revealing CANT1 as a likely disease-causing candidate gene. Insufficient fetal DNA precluded confirmatory testing, therefore parents were tested; both had a previously reported heterozygous CANT1 mutation (c.643G>T; Glu215Term). The patient presented with a third pregnancy revealing similarly abnormal limb position and probable polysyndactyly by ultrasound. Targeted testing of CANT1 revealed homozygous c.643G>T CANT1 mutations and this pregnancy was terminated. In clinical situations in which ample DNA is not available or more expensive testing (e.g., whole exome sequencing) with a longer turnaround time is not feasible, utilization of SNP-microarray in consanguineous families at risk for rare autosomal recessive disorders may dramatically narrow the list of candidate genes.
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http://dx.doi.org/10.1002/ajmg.a.61372DOI Listing
December 2019

Amnioinfusions to Treat Early Onset Anhydramnios Caused by Renal Anomalies: Background and Rationale for the Renal Anhydramnios Fetal Therapy Trial.

Fetal Diagn Ther 2019 21;45(6):365-372. Epub 2019 Mar 21.

Pediatric Surgery, Johns Hopkins University, Baltimore, Maryland, USA,

Anhydramnios caused by early anuria is thought to be universally fatal due to pulmonary hypoplasia. Bilateral renal agenesis and early fetal renal failure leading to anhydramnios constitute early pregnancy renal anhydramnios (EPRA). There have been successful reports of amnioinfusions to promote lung growth in the setting of EPRA. Some of these successfully treated EPRA fetuses have survived the neonatal period, undergone successful dialysis, and subsequently received a kidney transplant. Conversely, there are no reports of untreated EPRA survivors. This early success of amnioinfusions to treat EPRA justifies a rigorous prospective trial. The objective of this study is to provide a review of what is known about fetal therapy for EPRA and describe the Renal Anhydramnios Fetal Therapy trial. We review the epidemiology, pathophysiology, and genetics of EPRA. Furthermore, we have performed systematic review of case reports of treated EPRA. We describe the ethical framework, logistical challenges, and rationale for the current single center (NCT03101891) and planned multicenter trial.
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http://dx.doi.org/10.1159/000497472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577736PMC
January 2020

Study protocol: developing, disseminating, and implementing a core outcome set for selective fetal growth restriction in monochorionic twin pregnancies.

Trials 2019 Jan 9;20(1):35. Epub 2019 Jan 9.

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: Selective fetal growth restriction in monochorionic twin pregnancies is associated with an increased risk of perinatal mortality and morbidity and represents a clinical dilemma. Interventions include expectant management with early preterm delivery if there are signs of fetal compromise, selective termination of the compromised twin, fetoscopic laser coagulation of the communicating placental vessels or termination of the whole pregnancy. Previous studies evaluating interventions have reported many different outcomes and outcome measures. Such variation makes comparing, contrasting, and combining results challenging, limiting ongoing research on this uncommon condition to inform clinical practice. We aim to produce, disseminate, and implement a core outcome set for selective fetal growth restriction research in monochorionic twin pregnancies.

Methods: An international steering group, including professionals, researchers, and lay experts, has been established to oversee the development of this core outcome set. The methods have been guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. Potential core outcomes will be developed by undertaking a systematic review of studies evaluating interventions for selective fetal growth restriction in monochorionic twin pregnancies. Potential core outcomes will be entered into a three-round Delphi survey and key stakeholders including clinical professionals, researchers, and lay experts will be invited to participate. Repeated reflection and rescoring of individual outcomes should encourage group and individual stakeholder convergence towards consensus outcomes which will be entered into a modified Nominal Group Technique to finalize the core outcome set. Once core outcomes have been agreed, we will establish standardized definitions and recommend high-quality measurement instruments for each outcome.

Discussion: The development, dissemination, and implementation of a core outcome set for selective fetal growth restriction should ensure that future research protocols select, collect, and report outcomes and outcome measures in a standardized manner. Data synthesis will be possible on a broad level and rigorous implementation should advance the quality of research studies and their effective use in order to guide clinical practice, improve patient care, maternal, short-term perinatal outcomes, and long-term neurodevelopmental outcomes.

Trial Registration: Core Outcome Measures in Effectiveness Trials (COMET) registration number: 998. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42018092697 . 18th April 2018.
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http://dx.doi.org/10.1186/s13063-018-3153-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327411PMC
January 2019

Fetoscopic spina bifida repair.

Minerva Ginecol 2019 Apr 27;71(2):163-170. Epub 2018 Nov 27.

Department of Gynecology and Obstetrics, The Johns Hopkins Center for Fetal Therapy, Johns Hopkins University, Baltimore, MD, USA.

Introduction: Spina bifida is the most common non-lethal congenital birth defect of the central nervous system that causes chronic disability due to the combined effects of local nerve damage and the sequelae of non-communicating hydrocephalus. This abnormality can be identified early in gestation and the damage can be progressive over the course of pregnancy. Advances in fetal treatment have made minimally invasive prenatal surgery a realistic consideration for spina bifida in order to improve the outcome for children affected this condition.

Evidence Acquisition: Prenatal surgery for spina bifida via open fetal surgery with hysterotomy decreases the rate of ventriculoperitoneal shunt placement and improves motor function compared to standard postnatal surgery. Maternal risks of open fetal surgery are primarily related to complications of the hysterotomy including thinning or rupture that begins in the index pregnancy but persists for every future pregnancy. Minimizing maternal risks is the largest impetus to explore and optimize a minimally invasive fetoscopic alternative. Techniques vary from using a complete percutaneous approach to open fetoscopy, which requires laparotomy but is minimally invasive to the uterus. This allows vaginal delivery at term and no scar complications are reported thus far. Fetal short-term neurosurgical outcomes compare favorably with improvement in hindbrain herniation >70% and decreased need for treatment for hydrocephalus between 40-45% after prenatal surgery performed either fetoscopically or through open fetal surgery.

Evidence Synthesis: Maternal obstetric outcomes are superior for fetoscopic spina bifida repair compared to open fetal surgery and avoids the ongoing risk in future pregnancy. Neonatal and infant benefits appear equivalent. The open fetoscopic approach minimizes the risk of ruptured membranes and subsequent preterm delivery as opposed to a completely percutaneous procedure. International collaboration is ongoing to share experience and assess long term treatment effects.

Conclusions: Continued refinement of a minimally invasive strategy for prenatal treatment of spina bifida is necessary to maximize benefits to the child and further minimize maternal risks and preterm birth.
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http://dx.doi.org/10.23736/S0026-4784.18.04355-1DOI Listing
April 2019

Massive Fetomaternal Hemorrhage Remote from Term: Favorable Outcome after Fetal Resuscitation and Conservative Management.

Fetal Diagn Ther 2019 10;45(5):361-364. Epub 2018 Sep 10.

Center for Fetal Therapy, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,

Fetomaternal hemorrhage (FMH) is a rare condition that requires early diagnosis and appropriate treatment due to its potentially severe consequences. We report a case of massive FMH presenting as decreased fetal movement, fetal hydrops, and intracranial hemorrhage at 24 weeks. Treatment considerations were made and amniocentesis, fetal blood sampling, and fetal blood transfusion via cordocentesis were performed. Recurrent FMH required subsequent fetal transfusion 2 days later. Surveillance was continued twice weekly until the patient delivered a viable infant at 38 weeks after spontaneous labor. Recurrent FMH was unpredictable due to its unclear etiology and absence of precipitating events, however close surveillance proved effective.
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http://dx.doi.org/10.1159/000492750DOI Listing
December 2019

Preoperative Ultrasound Prediction of Essential Landmarks for Successful Fetoscopic Laser Treatment of Twin-Twin Transfusion Syndrome.

Fetal Diagn Ther 2019 6;45(5):295-301. Epub 2018 Jun 6.

Center for Fetal Therapy, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Introduction: The insertion site of the fetoscope for laser occlusion (FLOC) treatment of twin-twin transfusion syndrome (TTTS) determines the likelihood of treatment success. We assessed a standardized preoperative ultrasound approach for its ability to identify critical landmarks for successful FLOC.

Methods: Three surgeons independently performed preoperative ultrasound and deduced the likely orientation of the intertwin membrane (ITM) and vascular equator (VE) based on the sites of the cord insertion, the lie of the donor, and the size discordance between twins. At FLOC, these landmarks were visually verified and compared to preoperative assessments.

Results: Fifty consecutive FLOC surgeries had 127 preoperative assessments. Basic ITM and VE orientation were accurately predicted in 115 (90.6%), 109 (85.8%), and 105 (82.7%) assessments. Predictions were anatomically correct in 96 (75.6%), 70 (55.1%), and 58 (45.7%) assessments with no differences in accuracy between operators of different training level. The ITM/VE relationship was most poorly predicted in stage-3 TTTS (χ2, p = 0.016).

Conclusion: In TTTS, preoperative ultrasound identification of placental cord insertion sites, lie of the donor twin, and size discordance enables preoperative prediction of key landmarks for successful FLOC.
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http://dx.doi.org/10.1159/000489119DOI Listing
December 2019

Editorial: Prenatal Beginnings for Better Health.

Front Pharmacol 2018 4;9:457. Epub 2018 May 4.

Integrated Research Center for Fetal Medicine, Maternal Fetal Medicine, Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.

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http://dx.doi.org/10.3389/fphar.2018.00457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945864PMC
May 2018

Planning management and delivery of the growth-restricted fetus.

Authors:
Ahmet A Baschat

Best Pract Res Clin Obstet Gynaecol 2018 May 1;49:53-65. Epub 2018 Mar 1.

Johns Hopkins Center for Fetal Therapy Department of Gynecology & Obstetrics Johns Hopkins University Baltimore, MD, 21287, USA. Electronic address:

A uniform approach to management of fetal growth restriction (FGR) improves outcome, prevents stillbirth, and allows appropriately timed delivery. An estimated fetal weight below the tenth percentile with coexisting abnormal umbilical artery (UA), middle cerebral artery (MCA), or cerebroplacental ratio Doppler index best identifies the small fetus requiring surveillance. Placental perfusion defects are more common earlier in gestation; accordingly, early-onset (≤32 weeks of gestation) and late-onset (>32 weeks) FGR differ in clinical phenotype. In early-onset FGR, progression of UA Doppler abnormality determines clinical acceleration, while abnormal ductus venosus (DV) Doppler precedes deterioration of biophysical variables and stillbirth. Accordingly, late DV Doppler changes, abnormal biophysical variables, or an abnormal cCTG require delivery. In late-onset FGR, MCA Doppler abnormalities precede deterioration and stillbirth. However, from 34 to 38 weeks, randomized evidence on optimal delivery timing is lacking. From 38 weeks onward, the balance of neonatal versus fetal risks favors delivery.
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http://dx.doi.org/10.1016/j.bpobgyn.2018.02.009DOI Listing
May 2018

Persistent Extreme Hyperextension of the Fetal Neck: Clinical and Neuroimaging Findings.

J Neuroimaging 2018 05 5;28(3):278-282. Epub 2018 Feb 5.

Section of Pediatric Neuroradiology, Division of Pediatric Radiology and Pediatric Neuroradiology, Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD.

Background And Purpose: Persistent hyperextension of the fetal craniocervical junction or neck is one of several fetal positions commonly observed on prenatal imaging. Underlying fetal structural etiologies such as fetal neck masses and iniencephaly can be detected as causes of hyperextension. Caesarean delivery is considered in cases of vaginal delivery or obstructed labor for fear of cervical spinal cord injury. In this case series, we describe the prenatal magnetic resonance imaging (MRI) findings and their potential role in obstetric management and discuss postnatal outcomes in fetuses demonstrating prenatal imaging findings of persistent extreme hyperextension of the neck.

Methods: A retrospective cohort of fetuses with extreme fetal neck hyperextension on prenatal ultrasound and subsequent MRI is described.

Results: Persistent extreme neck hyperextension was demonstrated in four pregnancies. One patient showed resolution of head positioning prior to labor. In the other 3 patients, neck hyperextension persisted until labor. In these three pregnancies, caesarean section with early intubation was performed due to concern for airway compromise and cervical cord injury. An underlying structural neck abnormality with airway compromise was noted only in 1 patient (large venolymphatic malformation). No airway compromise, cervical spine, or spinal cord anomaly was identified in the remaining 3 patients. Noncervical fetal anomalies were detected only in 1 patient (arthogryposis multiplex and clubfoot deformities). In patients with no structural neck abnormality, early extubation was performed shortly following labor.

Conclusions: Detailed, high-resolution fetal MRI may serve as a valuable secondary imaging modality for clinical decision making regarding management of pregnancy, in utero therapy, mode of delivery, and postnatal care.
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http://dx.doi.org/10.1111/jon.12499DOI Listing
May 2018

Ethical Considerations Concerning Amnioinfusions for Treating Fetal Bilateral Renal Agenesis.

Obstet Gynecol 2018 01;131(1):130-134

Berman Institute of Bioethics, the Department of Gynecology and Obstetrics, the Center for Fetal Therapy, the Department of Surgery, Pediatric Palliative Care, the Division of Pediatric Nephrology, the Division of Neonatology, and the Human Research Protection Program, Johns Hopkins School of Medicine and University, Baltimore, Maryland; U.S. House of Representatives, Southwest Washington 3rd District, Washington, DC; the Department of Pediatric Nephrology, Transplantation and Rheumatology, Children's Hospital of Richmond, the Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia; the Department of Obstetrics, Gynecology and Reproductive Services, University of California, San Francisco, San Francisco, California; the Department of Pediatrics-Nephrology, Max Rady College of Medicine, Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada; Francis King Carey School of Law, University of Maryland, Baltimore, Maryland; the Division of Nephrology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California; the University of Washington School of Law and Institute for Public Health Genetics, Seattle, Washington; the Division of Neonatal-Perinatal Medicine and Program for Biomedical Ethics, Yale University School of Medicine, New Haven, Connecticut; Cincinnati Fetal Center, TriHealth Good Samaritan Hospital, Cincinnati, Ohio; the Department of Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia, Pennsylvania; and the Division of Nephrology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.

Congenital bilateral renal agenesis has been considered a uniformly fatal condition. However, the report of using serial amnioinfusions followed by the live birth in 2012 and ongoing survival of a child with bilateral renal agenesis has generated hope, but also considerable controversy over an array of complex clinical and ethical concerns. To assess the ethical concerns associated with using serial amnioinfusions for bilateral renal agenesis, we assembled a multidisciplinary group to map the ethical issues relevant to this novel intervention. The key ethical issues identified were related to 1) potential risks and benefits, 2) clinical care compared with innovation compared with research, 3) counseling of expectant parents, 4) consent, 5) outcome measures, 6) access and justice, 7) conflicts of interest, 8) effects on clinicians, 9) effects on institutions, and 10) long-term societal implications. These ethical issues should be addressed in conjunction with systematic efforts to examine whether this intervention is safe and effective. Future work should capture the experiences of expectant parents, women who undergo serial amnioinfusions, those born with bilateral renal agenesis and their families as well as clinicians confronted with making difficult choices related to it.
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http://dx.doi.org/10.1097/AOG.0000000000002416DOI Listing
January 2018

Fetoscopic tracheal occlusion for treatment of non-isolated congenital diaphragmatic hernia.

Prenat Diagn 2017 Oct 10;37(10):1046-1049. Epub 2017 Sep 10.

Center for Fetal Therapy, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Fetoscopic endotracheal occlusion (FETO) is a prenatal treatment that may increase survival in severe congenital diaphragmatic hernia (CDH). In the USA, FETO is offered for isolated severe left-sided CDH in the context of an FDA-approved feasibility study. FETO in non-isolated cases of severe CDH is only performed with a compassionate use exemption from US regulatory bodies. Anomalies frequently associated with CDH include congenital cystic lesions of the lung and cardiac defects. We describe two cases of non-isolated severe left-sided CDH that underwent prenatal FETO, survived after birth and underwent postnatal surgical repair. The potential benefit of FETO in this setting is discussed. © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.5139DOI Listing
October 2017
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