Publications by authors named "Mark I Evans"

86 Publications

Categorization of cerebral palsy cases: a different perspective.

Am J Obstet Gynecol 2021 Feb 7. Epub 2021 Feb 7.

Fetal Medicine Foundation of America, New York, NY.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2021.02.007DOI Listing
February 2021

Mid forceps did not cause "compromised babies" - "compromise" caused forceps: an approach toward safely lowering the cesarean delivery rate.

J Matern Fetal Neonatal Med 2021 Jan 25:1-9. Epub 2021 Jan 25.

Comprehensive Genetics, Fetal Medicine Foundation of America, New York, NY, USA.

Objective: Over 5 decades, Cesarean Delivery rates (CDR) have risen 6-fold while vaginal operative deliveries [VODs] decreased from >20% to ∼3%. Poor outcomes (HIE and cerebral palsy) haven't improved. Potentiating the virtual abandonment of forceps (F), particularly midforceps (Mid), were allegations about various poor neonatal outcomes. Here, we evaluate VOD and CDR outcomes controlling for prior fetal risk metrics (PR) ascertained an hour before birth.

Methods: Our 45-year-old database from a labor research unit of moderate/high risk laboring patients (288 NSVDs, 120 Lows, 30 Mids, and 32 CDs) had multiple fetal scalp samples for base excess (BE), pH, cord blood gases (CB), and umbilical artery bloods. ANOVA established relationships between birth methods and outcomes (Cord blood BE and pH and 1 and 5 min Apgar scores); correlations, and two-step multiple regression assessed PR for delivery method and neonatal outcomes. The main outcome measures were correlations of outcome measures with fetal scalp sample BE and pH up to an hour before delivery and fetal reserve index scores scored concurrently.

Results: NSVDs had the best immediate neonatal outcomes with significantly higher CB pH and BE as compared to forceps and CDs. However, controlling for PR revealed: (1) PR at 1 h before delivery correlated with delivery mode, i.e. the decrements in outcomes were already present before the delivery was performed; and (2) The presumed deleterious effects of interventional deliveries, per se, were significantly reduced, and (3) Fetal Reserve Index predicted neonatal outcomes better than fetal scalp sample BE, pH, or delivery mode.

Conclusion: The historical belief that MF deliveries caused poorer outcomes than NSVDs seems mostly backwards. Appreciating PR's impact on delivery routes, and when appropriate, properly performing VODs could safely reduce CDR. If our approach lowered CDR by only ∼2%, in the United States about 80,000 CDs might be avoided, saving ∼$750 Million yearly. In the post pandemic world, safely apportioning medical expenses will be even more critical than previously.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2021.1876657DOI Listing
January 2021

Earlier and improved screening for impending fetal compromise.

J Matern Fetal Neonatal Med 2020 Sep 1:1-9. Epub 2020 Sep 1.

Comprehensive Genetics, Fetal Medicine Foundation of America, New York, NY, USA.

Objective: The use of pH and base excess (FSSPHBE) from fetal scalp sampling (FSS) was abandoned when cardiotocography (CTG) was believed to be sufficiently accurate to direct patient management. We sought to understand the fetus' tolerance to stress in the 1st stage of labor and to develop a better and earlier screening test for its risk for developing acidosis. To do so, we investigated sequential changes in fetal pH and BE obtained from FSS in the 1st stage of labor as part of a research protocol from the 1970s. We then examined the utility of multiple of the median (MoM's) conversion of BE and pH values, and the capacity of Fetal Reserve Index (FRI) scores to be a proxy for such changes. We then sought to examine the predictive capacity of 1st stage FRI and its change over the course of the first stage of labor for the subsequent development of acidosis risk in the 2nd stage of labor.

Methods: Using a retrospective research database evaluation, we evaluated FSSPHBE data from 475 high-risk parturients monitored in labor and their neonates for 1 h postpartum. We categorized specimens according to cervical dilatation (CxD) at the time of FSSPHBE and developed non-parametric, multiples of the median (MOMs) assessments. FRI scores and their change over time were used as predictors of FSSPHBE. Our main outcome measures were the changes in BE and pH at different cervical dilatations (CxD) and acidosis risk in the early 2nd stage of labor.

Results: FSSPHBE worsens over the course of the 1st stage. The implications of any given BE are very different depending upon CxD. At 9 cm, -8 Mmol/L is 1.1 MOM; at 3 cm, it would be 2.0 MOM. The FRI level and its trajectory provide a 1st stage screening tool for acidosis risk in the second stage.

Conclusions: Fetal acid-base balance ("reserve") deteriorates beginning early in the 1st stage of labor, irrespective of whether the fetus reaches a critical threshold of concern for actual acidosis. The use of MoM's logic improves appreciation of such information. The FRI and its trajectory reasonably approximate the trajectory of the FSSPHBE and appears to be a suitable screening test for early deterioration and for earlier interventions to keep the fetus out of trouble rather than wait until high risk status develops.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2020.1811670DOI Listing
September 2020

Combined prenatal and postnatal prediction of early neonatal compromise risk.

J Matern Fetal Neonatal Med 2019 Oct 24:1-12. Epub 2019 Oct 24.

Fetal Medicine Foundation of America , New York , NY , USA.

Electronic fetal monitoring/cardiotocography (EFM) is nearly ubiquitous, but almost everyone acknowledges there is room for improvement. We have contextualized monitoring by breaking it down into quantifiable components and adding to that, other factors that have not been formally used: i.e. the assessment of uterine contractions, and the presence of maternal, fetal, and obstetrical risk factors. We have created an algorithm, the Fetal Reserve Index (FRI) that significantly improves the detection of at-risk cases. We hypothesized that extending our approach of monitoring to include the immediate newborn period could help us better understand the physiology and pathophysiology of the decrease in fetal reserve during labor and the transition from fetal to neonatal homeostasis, thereby further honing the prediction of outcomes. Such improved and earlier understanding could then potentiate earlier, and more targeted use of neuroprotective attempts during labor treating decreased fetal reserve and improving the fetus' transition from fetal to neonatal life minimizing risk of neurologic injury. We have analyzed a 45-year-old research database of closely monitored labors, deliveries, and an additional hour of continuous neonatal surveillance. We applied the FRI prenatally and created a new metric, the INCHON index that combines the last FRI with umbilical cord blood and 4-minute umbilical artery blood parameters to predict later neonatal acid/base balance. Using the last FRI scores, we created 3 neonatal groups. Umbilical cord and catheterized umbilical artery bloods at 4, 8, 16, 32, and 64 minutes were measured for base excess, pH, and PO. Continuous neonatal heart rate was scored for rate, variability, and reactivity. Neonates commonly do not make a smooth transition from fetal to postnatal physiology. Even in low risk babies, 85% exhibited worsening pH and base excess during the first 4 minutes; 34% of neonates reached levels considered at high risk for metabolic acidosis (≤-12 mmol/L) and neurologic injury. Neonatal heart rate commonly exhibited sustained, significant tachycardia with loss of reactivity and variability. One quarter of all cases would be considered Category III if part of the fetal tracing. Our developed metrics (FRI and INCHON) clearly discriminated and predicted low, medium, and high-risk neonatal physiology. The immediate neonatal period often imposes generally unrecognized risks for the newborn. INCHON improves identification of decreased fetal reserve and babies at risk, thereby permitting earlier intervention during labor (intrauterine resuscitation) or potentially postnatally (brain cooling) to prevent neurologic injury. We believe that perinatal management would be improved by routine, continuous neonatal monitoring - at least until heart rate reactivity is restored. FRI and INCHON can help identify problems much earlier and more accurately than currently and keep fetuses and babies in better metabolic shape.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2019.1676714DOI Listing
October 2019

The Fetal Reserve Index Significantly Outperforms ACOG Category System in Predicting Cord Blood Base Excess and pH: A Methodological Failure of the Category System.

Reprod Sci 2019 06 4;26(6):858-863. Epub 2019 Mar 4.

Fetal Medicine Foundation of America, New York, NY, USA.

Objective: Electronic fetal monitoring (EFM) has been used extensively for almost 50 years but performs poorly in predicting and preventing adverse neonatal outcome. In recent years, the current "enhanced" classification of patterns (category I-III system [CAT]) were introduced into routine practice without corroborative studies, which has resulted in even EFM experts lamenting its value. Since abnormalities of arterial cord blood parameters correlate reasonably well with risk of fetal injury, here we compare the statistical performance of EFM using the current CAT system with the Fetal Reserve Index (FRI) for predicting derangements in base excess (BE), pH, and pO in arterial cord blood.

Methods: We utilized a research database of labor data, including umbilical cord blood measurements to assess patients by both worst CAT and last FRI classifications. We compared these approaches for their ability to predict BE, pH, and pO in cord blood.

Results: The FRI showed a clear correlation with cord blood BE and pH with BE being more highly correlated than pH. The CAT was much less predictive than FRI ( < .05). The CAT II cases had FRI scores across the spectrum of severity of FRI designations and as such provide little clinical discrimination. The PO was not discriminatory, in part, because of neonatal interventions.

Conclusions: The Fetal Reserve Index (FRI) provides superior performance over CAT classification of FHR patterns in predicting the BE and pH in umbilical cord blood. Furthermore, the CAT system fails to satisfy multiple fundamental principles required for successful screening programs. Limitations of CAT are further compounded by assumptions about physiology that are not consistent with clinical observations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1933719119833796DOI Listing
June 2019

The price of abandoning diagnostic testing for cell free fetal DNA screening.

Prenat Diagn 2019 01 13;39(2):131-132. Epub 2019 Jan 13.

Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5405DOI Listing
January 2019

Refining the Prediction and Prevention of Emergency Operative Deliveries with the Fetal Reserve Index.

Fetal Diagn Ther 2019 21;46(3):159-165. Epub 2018 Nov 21.

Fetal Medicine Foundation of America, New York, New York, USA.

Electronic fetal monitoring (EFM) is a poor predictor of outcomes attributable to delivery problems. Contextualizing EFM by adding maternal, obstetrical, and fetal risk-related information to create an index called the Fetal Reserve Index (FRI) improves the predictive capacity and facilitates the timing of interventions. Here, we test critical assumptions of FRI as a clinical tool. Our conceptualization implies that the earlier one reaches the red zone (FRI ≤25) and the longer one spends in the red zone, the greater the likelihood of emergency operative deliveries (EOD).

Methods: We analyzed 1,402 patients using logistic regression predicting the probability of EOD and employed qualitative methodology techniques to refine predictive capabilities.

Results: Reaching the red zone early and staying there > 1 h increases the probability of EOD. When these risk factors are paired with intrauterine resuscitation (IR) in Stage 1, the reduction of EOD is substantial.

Conclusion: FRI is a capable predictor of EOD because it accurately identifies the level of malleable risk. FRI analysis increases the risk of using IR in Stage 1. Matching risk and resources dramatically reduces the chances of EOD. Earlier IR improves the outcomes if the calculated risk is high.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000494617DOI Listing
February 2020

Safely lowering the emergency Cesarean and operative vaginal delivery rates using the Fetal Reserve Index.

J Matern Fetal Neonatal Med 2020 May 1;33(9):1473-1479. Epub 2018 Oct 1.

Fetal Medicine Foundation of America, New York, NY, USA.

The cardiotocograph (CTG) or electronic fetal monitoring (EFM) was developed to prevent fetal asphyxia and subsequent neurological injury. From a public health perspective, it has failed these objectives while increasing emergency operative deliveries (emergency operative deliveries (EODs) - emergency cesarean delivery or operative vaginal delivery) for newborns, who in retrospect, actually did not require the assistance. EODs increase the risks of complications and stress for patients, families, and medical personnel. A safe reduction in the need for EOD will likely reduce both the overall Cesarean section rate as well as the risk of fetal neurological injury during labor to which it is related. We have developed the fetal reserve index (FRI), which is more comprehensive than CTG as a new screening method for early identification of the fetus at-risk of both neurological harm and the need to "rescue" by means of an EOD. Here, we compare prospectively the need for EOD in two groups of parturients undergoing a trial of labor at term. One group was managed conventionally, the other by the principles of the FRI. We compared the need for EOD of 800 parturients with singleton cases undergoing a trial of labor at term entering with normal CTG patterns (ACOG category 1). Patients were either treated routinely (400 - "early cases") or in a second group seen later actively managed using the principles of the FRI (400 - "late cases"). The FRI includes measurements of five components of the CTG: rate, variability, decelerations, accelerations, and abnormal uterine activity combined with the presence of medical, obstetrical, and fetal risk factors. The 8-point metric categorizes cases as "green", "yellow", and "red" with the latter being at risk. All 800 patients delivered babies, who were discharged in the usual time course with no untoward outcomes noted. The incidence of red zone scores was comparable in the two groups (≈25%), but the use of intrauterine resuscitation (IR) when reaching the red zone in the late group (47%) was more than double the incidence in the early group (20%) ( < .001). Despite (or because of) this, EODs were significantly reduced in the late group, from 17.3 to 4.0% ( < .001). Further, the late group spent less time in the red zone without increasing overall time in labor. Overall, EOD cases averaged >1 h in the red zone versus 0.5 h for non-EODs. The FRI may provide a metric to reduce EODs and by extension also reduce the risks of both cesarean delivery and adverse fetal/neonatal outcomes. The safe avoidance of EOD would seem to be an important metric to assess the quality of intrapartum management. This study represents the first attempt to apply the principles of the FRI "live" for the concurrent management of patients during labor. These promising results, if confirmed, in larger sample sizes, set the stage for our computerization of the FRI for widespread study. Benefits appear to come from identification and early, conservative management of fetal deterioration before the need to "rescue" the fetus by EOD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2018.1519799DOI Listing
May 2020

The epidemic of abnormal copy number variant cases missed because of reliance upon noninvasive prenatal screening.

Prenat Diagn 2018 09;38(10):730-734

Hackensack/Meridian University Medical Center, Hackensack, NJ, USA.

Objective: To assess the implications of increasing utilization of noninvasive prenatal screening (NIPS), which may reach 50% with the concomitant decrease in diagnostic procedures (DPs) for its impact on detection of chromosomal abnormalities.

Methods: We studied our program's statistics over 5 years for DPs and utilization of array comparative genomic hybridization (aCGH). We then modeled the implications in our program if DP had not fallen and nationally of a 50% DP and aCGH testing rate using well-vetted expectations for the diagnosis of abnormal copy number variants (CNVs).

Results: Our DP fell 40% from 2013-2017. Utilization of aCGH for DP nearly tripled. We detected 28 abnormal CNVs. If DP had not fallen, we likely would have detected 60. With 4 million US births per year, 2 million DPs would detect 30 000 abnormal CNVs and 4000 standard aneuploidies. At a 1/500 complication-pregnancy loss rate, the detection/complication ratio is 8.5/1.

Conclusions: Noninvasive prenatal screening has significantly changed the practice of prenatal screening. However, while increasing the detection of Down syndrome, the concomitant decrease in DP and lack of aCGH results in missing many more abnormalities than the increase in Down syndrome and complications of DP combined. From a public health perspective, such represents a missed opportunity for overall health care delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5275DOI Listing
September 2018

Folic Acid Supplementation to Prevent Recurrent Neural Tube Defects: 4 Milligrams Is Too Much.

Fetal Diagn Ther 2018 22;44(3):161-165. Epub 2018 Aug 22.

Comprehensive Genetics PLLC, Fetal Medicine Foundation of America, New York, New York, USA.

Some medical practices have been ingrained in custom for decades, long after "proof" that they were effective was established. It is necessary to periodically reevaluate these practices, as newer theories and research may challenge the evidence upon which they were based. An example is the decades' old practice of recommending a 4-mg (4,000-µg) supplement of folic acid to women who are at risk for recurrent neural tube defect (NTD) during pregnancy. This recommendation was based on findings from a randomized clinical trial in 1991. Since then, multiple studies have confirmed the utility of 400-800 µg of folic acid in lowering both primary and recurrent risks of NTDs, but no studies have established any further reduction in risk with doses over 1 mg. Current understanding of folic acid metabolism during pregnancy suggests that at higher doses, above ∼1 mg, there is not increased absorption. Recent evidence suggests that 4 mg folic acid supplementation may not be any more effective than lower doses for the prevention of recurrent NTDs. Thus, we recommend that it is time for clinicians to reexamine their reliance on this outdated recommendation and consider using current recommendations of 400-800 µg per day for all patients in conjunction with assessment of maternal folate status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000491786DOI Listing
January 2019

Re-engineering the interpretation of electronic fetal monitoring to identify reversible risk for cerebral palsy: a case control series.

J Matern Fetal Neonatal Med 2019 Aug 28;32(15):2561-2569. Epub 2018 Feb 28.

a Fetal Medicine Foundation of America , New York , NY , USA.

Background: Even key opinion leaders now concede that electronic fetal monitoring (EFM) cannot reliably identify fetal acidemia which many vouch as the only labor mediated pathophysiologic precursor for cerebral palsy (CP). We have developed the "Fetal Reserve Index" - an algorithm combining five dynamic components of EFM (1. Rate, 2. Variability, 3. Accelerations, 4. Decelerations, and 5. Excessive uterine activity) considered individually that are combined with the presence of: 6. maternal, 7. obstetrical, and 8. fetal risk factors.

Objective: Here, we compare this 8-point fetal reserve index (FRI) against the performance of ACOG monograph criteria and ACOG Category systems for predicting risk for both CP and the need for emergency operative delivery (EOD). We then studied how varied management for screen positives (Red zone-defined below) impacts the outcome of such cases.

Study Design: Four hundred twenty term patients were studied: all entered labor with normal EFMs and no apparent cause of harm except events of labor and delivery. Sixty subsequently developed CP, and 360 were apparently normal controls. An FRI, normal on all eight parameters scored 100%, 4 of the 8 was 50%, etc. We divided cases into Green zone >50%, Yellow 50-26%, and Red ≤25%. An FRI in the Red zone was considered a positive screen. We then compared performance metrics for the three evaluation schemes and differences between controls that reached Red against those controls whose worst scores were Green/Yellow.

Results: For detection of injury during labor, the FRI performed much better than the ACOG Category criteria (sensitivity 28%), and Category III (45%) (p < .001). All CP cases reached Red zone and were Red for a minimum of 2 hours (mean = 5.35 hours). Twenty-four% of controls reached Red, but were only Red for average of 1 hr. The incidence of low Apgar's, pH, FRI, and Lowest FRI increased progressively from Green/Yellow controls to red controls to CP cases. Irrespective, CP cases met ACOG Monograph criteria for labor injury less than 50% of the time. Only half of CP babies had umbilical artery pH values <7.00, and less than 50% showed Category III patterns. The earlier in labor the Red zone was reached, the more likely for a baby to develop CP or the mother to require an EOD regardless of fetal outcome. Successful intrauterine resuscitations (IR) diminished time spent in the Red zone and the need for EODs.

Conclusions: FRI shows better discrimination for adverse fetal outcome and EOD than traditional EFM interpretation. The Category system is a very poor, subjective screening method as the vast majority of CP babies never reach the "action point" result of Category III. While reaching the Red zone does not ordain a bad outcome, how it is managed, does. Compared to CP cases, Red controls were delivered faster, had higher FRIs, and often had prompt management including IR maneuvers, which improved the FRI and lowered the risk of EODs even for cases with normal outcomes. With further study and validation, the quantitative FRI approach may replace the current, very subjective interpretation with a quantitative "lab test" approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14767058.2018.1441283DOI Listing
August 2019

The price of abandoning diagnostic testing for cell-free fetal DNA screening.

Prenat Diagn 2018 03 21;38(4):243-245. Epub 2018 Feb 21.

Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5226DOI Listing
March 2018

The impact of third-trimester genetic counseling.

Arch Gynecol Obstet 2018 03 6;297(3):659-665. Epub 2018 Jan 6.

Department of Obstetrics and Gynecology, Fetal Medicine Foundation of America, Comprehensive Genetics PLLC, Mt. Sinai School of Medicine, New York, USA.

Objective: To evaluate the impact of genetic counseling (GC) during the third trimester by analyzing changes in pregnancy management and the correlation with postnatal findings.

Methods: This was a retrospective study. Pregnancy course and neonatal follow-up were analyzed according to the reason for referral and implementation of recommendations.

Results: The records of neonates born to 181 women were retrieved. Fifty-two women (group 1-29%) qualified for pregnancy termination under Israeli guidelines and laws, and 129 (group 2-71%) were not at the time they were referred. By another division: 104 women (group 3-57%) followed the physician's diagnostic recommendations completely after counseling including amniocentesis, fetal MRI, targeted ultrasound scans, fetal echocardiography. Seventy-seven declined amniocentesis (group 4-43%). Additional abnormalities were detected postpartum in all groups without statistically difference: 3/52 (10%) in group 1, 9/129 (7%) in group 2, 6/104 (6%) in group 3, and 6/77 (8%) in group 4).

Conclusion: GC in the third trimester of pregnancy provided the couple with a sharper more focused picture and assisted them to perceive the significance of new, significant fetal findings which attest to the value of the GC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-017-4638-8DOI Listing
March 2018

Reengineering Electronic Fetal Monitoring Interpretation: Using the Fetal Reserve Index to Anticipate the Need for Emergent Operative Delivery.

Reprod Sci 2018 Apr 14;25(4):487-497. Epub 2017 Nov 14.

1 Fetal Medicine Foundation of America, New York, NY, USA.

Objective: The near-ubiquitous use of electronic fetal monitoring has failed to lower the rates of both cerebral palsy and emergency operative deliveries (EODs). Its performance metrics have low sensitivity, specificity, and predictive values for both. There are many EODs, but the vast majority have normal outcomes. The EODs, however, cause serious disruption in the delivery suite routine with increased complications, anxiety, and concern for all.

Methods: We developed the fetal reserve index (FRI) as multicomponent algorithm including 4 FHR components (analyzed individually), uterine activity, and maternal, obstetrical, and fetal risk factors to assess risk of cerebral palsy and EOD. Scores were categorized into green, yellow, and red zones. Here, we studied 300 patients by the FRI, all of whom had normal neonatal outcomes. We attempted to distinguish the clinical course of those cases which required an EOD versus controls which did not.

Results: 51 cases with EOD had FRIs much lower than 249 non-EOD cases. The red zone was reached more frequently ( P < .001) and lasted longer (1.06 vs 0.05 hours; P < .001). Reaching the red zone had a sensitivity of 92% for EOD, with a positive predictive value of 64% and a false positive rate of 10.4%.

Conclusions: Our data suggest the FRI can significantly lower the incidence of EODs by identifying the opportunity for intrauterine resuscitation. Our approach can reduce the disruptive effects of EODs and their concomitant increased risks of complications. The FRI may provide a metric that can refine labor management to reduce CP and EODs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1933719117737849DOI Listing
April 2018

Challenges in non-invasive prenatal screening for sub-chromosomal copy number variations using cell-free DNA.

Prenat Diagn 2017 Nov 26;37(11):1067-1075. Epub 2017 Oct 26.

Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Non-invasive prenatal screening (NIPS) has revolutionized the approach to prenatal fetal aneuploidy screening. Many commercial providers now offer analyses for sub-chromosomal copy number variations (CNVs). Here, we review the use of NIPS in the context of screening for microdeletions and microduplications, issues surrounding the choice of disorders tested for, and the advantages and disadvantages associated with the inclusion of microdeletions to current NIPS. Several studies have claimed benefits; however, we suggest that microdeletions have not demonstrated a low enough false positive rate to be deemed practical or ethically acceptable, especially considering their low positive predictive values. Because a positive NIPS result should be confirmed using diagnostic techniques, and false positive rates are as high as 90% for some microdeletions, diagnostic testing seems preferable when the goal is to maximize the detection of microdeletion or microduplication syndromes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5161DOI Listing
November 2017

The "Fetal Reserve Index": Re-Engineering the Interpretation and Responses to Fetal Heart Rate Patterns.

Fetal Diagn Ther 2018 8;43(2):90-104. Epub 2017 Jun 8.

Fetal Medicine Foundation of America, New York, NY, USA.

Objective: Electronic fetal monitoring (EFM) correlates poorly with neonatal outcome. We present a new metric: the "Fetal Reserve Index" (FRI), formally incorporating EFM with maternal, obstetrical, fetal risk factors, and excessive uterine activity for assessment of risk for cerebral palsy (CP).

Methods: We performed a retrospective, case-control series of 50 term CP cases with apparent intrapartum neurological injury and 200 controls. All were deemed neurologically normal on admission. We compared the FRI against ACOG Category (I-III) system and long-term outcome parameters against ACOG monograph (NEACP) requirements for labor-induced fetal neurological injury.

Results: Abnormal FRI's identified 100% of CP cases and did so hours before injury. ACOG Category III identified only 44% and much later. Retrospective ACOG monograph criteria were found in at most 30% of intrapartum-acquired CP patients; only 27% had umbilical or neonatal pH <7.0.

Conclusions: In this initial, retrospective trial, an abnormal FRI identified all cases of labor-related neurological injury more reliably and earlier than Category III, which may allow fetal therapy by intrauterine resuscitation. The combination of traditional EFM with maternal, obstetrical, and fetal risk factors creating the FRI performed much better as a screening test than EFM alone. Our quantified screening system needs further evaluation in prospective trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000475927DOI Listing
August 2018

Fetal Treatment 2017: The Evolution of Fetal Therapy Centers - A Joint Opinion from the International Fetal Medicine and Surgical Society (IFMSS) and the North American Fetal Therapy Network (NAFTNet).

Fetal Diagn Ther 2017 23;42(4):241-248. Epub 2017 May 23.

The Fetal Treatment Center, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.

More than 3 decades ago, a small group of physicians and other practitioners active in what they called "fetal treatment" authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful reassessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with a brief discussion of the necessary minimum expertise and systems base for the provision of different types of interventions for both the mother and fetus. Our goal will be to present an opinion that encourages the advancement of thoughtful practice, ensuring that current and future patients have realistic access to centers with a range of fetal therapies with appropriate expertise, experience, and subspecialty and institutional support while remaining focused on excellence in care, collaborative scientific discovery, and maternal autonomy and safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000475929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739586PMC
July 2018

Re-Thinking Elective Single Embryo Transfer: Increased Risk of Monochorionic Twinning - A Systematic Review.

Fetal Diagn Ther 2017 29;42(2):81-91. Epub 2017 Mar 29.

Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, St. Barnabas Medical Center Livingston, Livingston, NJ, USA.

Background/objectives: Multiple pregnancies have tripled in the United States over the past 3 decades. Attributed to increasing maternal age at delivery but more so assisted reproductive technological advances, an effort has been made to decrease twinning through elective single embryo transfer. We sought to review and evaluate risks of monochorionic twinning as a predictable consequence of increasing utilization of elective single embryo transfer on perinatal outcomes. Primary outcomes included twinning rates, fetal anomalies, growth, preterm birth, and mortality. Secondary outcomes included neurological and pulmonary disability, intrauterine growth restriction, and congenital cardiac anomalies and twin-twin transfusion syndrome.

Data Sources: PubMed and Embase.

Results: A total of 106 studies identified by systematic search met the inclusion criteria. The trend for lower numbers of embryos transferred has inadvertently led to an increase in monochorionic twinning. This is associated with worse outcomes compared to dichorionic twinning and singleton gestations for all outcomes studied.

Discussion: Of great concern for monochorionic twins is the risk profile of significant morbidity and mortality. Transfer of 2 embryos should be considered to avoid higher risks inherent to the shared placental phenomena related to monochorionic twins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000464286DOI Listing
May 2018

Emerging Considerations for Noninvasive Prenatal Testing.

Clin Chem 2017 05 15;63(5):946-953. Epub 2017 Mar 15.

Department of Pathology and Laboratory Medicine, Women & Infants Hospital/Alpert Medical School at Brown University, Providence, RI.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1373/clinchem.2016.266544DOI Listing
May 2017

Current controversies in prenatal diagnosis 3: industry drives innovation in research and clinical application of genetic prenatal diagnosis and screening.

Prenat Diagn 2016 Dec 6;36(13):1172-1177. Epub 2016 Dec 6.

Department of Human Genetics, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.4967DOI Listing
December 2016

Screening and Testing in Multiples.

Clin Lab Med 2016 Jun 5;36(2):289-303. Epub 2016 Mar 5.

Comprehensive Genetics, 131 East 65th Street, New York, NY 10065, USA; University of Colorado, Aurora, CO, USA.

The choice of screening or invasive procedure in twin pregnancies is a personal choice of whether the patient wishes to take a small risk of having a baby with a serious disorder versus a small risk of having a complication because she wishes to avoid that. How to interpret such risks has profound effects on the perceived value of techniques, either leading to a decision to screening or going directly to chorionic villus sampling. There are profound issues surrounding the data and the interpretation of the data. No single short review can exhaustively examine all of the issues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cll.2016.01.002DOI Listing
June 2016

Cell-free DNA: Comparison of Technologies.

Clin Lab Med 2016 06 18;36(2):199-211. Epub 2016 Mar 18.

Department of Obstetrics and Gynecology, Mt. Sinai School of Medicine, New York, NY, USA; Comprehensive Genetics and Fetal Medicine Foundation of America, 131 East 65th Street, New York, NY 10065, USA. Electronic address:

Cell-free fetal DNA screening for Down syndrome has gained rapid acceptance over the past few years with increasing market penetration. Three main laboratory methodologies are currently used: a massive parallel shotgun sequencing (MPSS), a targeted massive parallel sequencing (t-MPS) and a single nucleotide polymorphism (SNP) based approach. Although each of these technologies has its own advantages and disadvantages, the performance of all was shown to be comparable and superior to that of traditional first-trimester screening for the detection of trisomy 21 in a routine prenatal population. Differences in performance were predominantly shown for chromosomal anomalies other than trisomy 21. Understanding the limitations and benefits of each technology is essential for proper counseling to patients. These technologies, as well as few investigational technologies described in this review, carry a great potential beyond screening for the common aneuploidies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cll.2016.01.015DOI Listing
June 2016

Noninvasive prenatal screening or advanced diagnostic testing: caveat emptor.

Am J Obstet Gynecol 2016 09 27;215(3):298-305. Epub 2016 Apr 27.

Columbia University College of Physicians and Surgeons, New York, NY.

The past few years have seen extraordinary advances in prenatal genetic practice led by 2 major technological advances; next-generation sequencing of cell-free DNA in the maternal plasma to noninvasively identify fetal chromosome abnormalities, and microarray analysis of chorionic villus sampling and amniotic fluid samples, resulting in increased cytogenetic resolution. Noninvasive prenatal screening of cell-free DNA has demonstrated sensitivity and specificity for trisomy 21 superior to all previous screening approaches with slightly lower performance for other common aneuploidies. These tests have rapidly captured an increasing market share, with substantial reductions in the number of chorionic villus sampling and amniocentesis performed suggesting that physicians and patients regard such screening approaches as an equivalent replacement for diagnostic testing. Simultaneously, many clinical programs have noted significant decreases in patient counseling. In 2012 the Eunice Kennedy Shriver National Institute of Child Health and Human Development funded a blinded comparison of karyotype with the emerging technology of array comparative genomic hybridization showing that in patients with a normal karyotype, 2.5% had a clinically relevant microdeletion or duplication identified. In pregnancies with an ultrasound-detected structural anomaly, 6% had an incremental finding, and of those with a normal scan, 1.6% had a copy number variant. For patients of any age with a normal ultrasound and karyotype, the chance of a pathogenic copy number variant is greater than 1%, similar to the age-related risk of aneuploidy in the fetus of a 38 year old. This risk is 4-fold higher than the risk of trisomy 21 in a woman younger than 30 years and 5- to 10-fold higher than the present accepted risk of a diagnostic procedure. Based on this, we contend that every patient, regardless of her age, be educated about these risks and offered the opportunity to have a diagnostic procedure with array comparative genomic hybridization performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2016.04.029DOI Listing
September 2016

Integrating Microarrays into Routine Prenatal Diagnosis: Determinants of Decision Making.

Fetal Diagn Ther 2016 9;40(2):135-40. Epub 2016 Jan 9.

Comprehensive Genetics, New York University Langone Medical Center, New York, N.Y.,USA.

Objectives: The explosion in genetic technologies, including array comparative genomic hybridization (aCGH), has increased the complexity of genetic counseling. We now offer chorionic villus sampling (CVS) and aCGH to all first-trimester patients, as this allows the prenatal diagnosis of an additional 1% of anomalies not otherwise detectable and can detect genetic copy number variants at a much higher resolution than conventional cytogenetics. Here, we explored some of the determinants of how patients are deciding to use or not use this new technology and evaluate risk-benefit analyses for that decision.

Methods: This is a retrospective case-control study of singleton and multiples pregnancies at our center. Those having aCGH testing along with CVS were defined as 'testers' and those who declined aCGH but had the CVS were 'nontesters'.

Results: Demographic data of 181 educated women who chose CVS were compared. Among those carrying singletons (n = 144), older women, defined as over 35 years of age (or 'advanced maternal age'; AMA), were more likely to choose the aCGH than younger women. Further, women who had a prior history of genetic testing and who wanted to know the gender of the fetus were more likely to choose the aCGH test. In women carrying multiples (n = 37), AMA ceases to be a predictor of choice. Having had prior genetic counseling remains a strong predictor for choosing aCGH, as does wanting to know the gender of the fetus. Neither prior abortions nor having prior children were significant for women carrying singletons or multiples.

Conclusion: Offering pregnant couples an individualized choice regarding aCGH seems an appropriate approach. There are discrete patterns associated with the choice of taking the aCGH that varied depending on whether the patient was carrying a singleton or multiples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000442197DOI Listing
February 2017

Sequential Amniotic Fluid Thyroid Hormone Changes Correlate with Goiter Shrinkage following in utero Thyroxine Therapy.

Fetal Diagn Ther 2016 28;39(3):222-7. Epub 2015 Aug 28.

Fetal Medicine Foundation of America and Comprehensive Genetics, PLLC, New York, N.Y., USA.

Several isolated reports of fetal goiter treatment have shown limited generalizability of approaches and provide no real guidance for optimal timing, dosages, and treatment strategies. Graves' disease accounts for >60% of these cases. Maternal treatments of hyperthyroidism include antithyroid medications such as methimazole and more commonly propylthiouracil (PTU). Here, our management of a patient with a fetal thyroid goiter from maternal exposure to PTU diagnosed at 23.6 weeks' gestation and the management of other cases allow us propose a general strategy for treatment. Intrauterine therapy with 200 and then 400 μg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid goiter volume. We collected amniotic fluid samples at the time of treatments and assayed thyroid hormones and associated antibodies which closely reflected the changes in thyroid goiter mass volume. Our observations suggest a weekly or biweekly therapeutic intervention schedule. Utilizing both goiter size as well as a novel approach in using amniotic fluid hormone levels to monitor therapy efficacy might improve the quality of treatments. Only with a standardized approach and collection of amniotic fluid thyroid panels do we have the opportunity to develop the database required to determine the number and timing of treatments needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000437367DOI Listing
January 2017

Genetics: update on prenatal screening and diagnosis.

Obstet Gynecol Clin North Am 2015 Jun;42(2):193-208

Comprehensive Genetics, PLLC and Fetal Medicine Foundation of America, 131 E65th Street, New York, NY 10065, USA.

There have been tremendous advances in the ability to screen for the "odds" of having a genetic disorder (both mendelian and chromosomal). With microarray analyses on fetal tissue now showing a minimum risk for any pregnancy being at least 1 in 150 and ultimately greater than 1%, it is thought that all patients, regardless of age, should be offered chorionic villus sampling/amniocentesis and microarray analysis. As sequencing techniques replace other laboratory methods, the only question will be whether these tests are performed on villi, amniotic fluid cells, or maternal blood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ogc.2015.01.011DOI Listing
June 2015

Long-term neurologic outcomes after common fetal interventions.

Am J Obstet Gynecol 2015 Apr 30;212(4):527.e1-9. Epub 2014 Oct 30.

Comprehensive Genetics and Fetal Medicine Foundation of America and Department of Obstetrics and Gynecology, Mt Sinai School of Medicine, New York, NY. Electronic address:

Objective: Fetal interventions have clearly decreased mortality, but the neurological outcomes of survivors are of critical concern. Here we consolidated available data on long-term neurological outcomes after common fetal interventions to guide counseling, management, and future research.

Study Design: Published studies assessing long-term neurological outcomes after common fetal interventions from 1990 through 2014 were collected. We included all studies with a cohort of more than 5 patients and with follow-up of 1 year or longer. We divided procedures into those performed for singletons and for multiples. Singleton procedures included amnioinfusion for preterm premature rupture of membranes, intrauterine transfusion for red cell alloimmunization-associated anemia, intrauterine transfusion for parvovirus-associated anemia, vesicoamniotic shunts, thoracoamniotic shunts, ventriculoamniotic shunts, fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia, and open fetal cases by myelomeningocele and others. Multiple procedures included those done for monochorionic twins including serial amnioreduction, selective fetoscopic laser photocoagulation, and selective termination.

Results: Of 1341 studies identified, 28 met the inclusion criteria. We combined available literature for all procedures. Studies varied in their length of follow-up and method of assessing neurological status. Neurological outcome after intervention varied by procedure but was normal in 40-93%, mildly impaired in 3-33%, and severely impaired in 1-40%. Follow-up to school age was rare with the exception of procedures for monochorionic twins.

Conclusion: Fetal treatments have been successful in achieving survival in previously hopeless cases, but success should also be determined by the outcomes of survivors. Except for monochorionic twins, there is a dearth of reported long-term outcomes. Standardized reporting of long-term neurological sequelae is imperative so that meaningful analysis and study comparisons can be made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2014.10.1092DOI Listing
April 2015

Fetal reduction: 25 years' experience.

Fetal Diagn Ther 2014 13;35(2):69-82. Epub 2014 Feb 13.

Comprehensive Genetics, Fetal Medicine Foundation of America, New York, N.Y., USA.

Fetal reduction (FR) began in the 1980s to salvage the pregnancies of couples needing fertility therapy who were finally successful but with too many fetuses. Since then, it has gone from a rarity performed in only the highest risk situations to an integral fail-safe of infertility practice. Our understanding of the problems of multiple and premature births has increased - even twins carry 4-5 times more risk than singletons. Evaluation of fetuses before FR has permitted more intelligent choices and improved resultant outcomes. We now perform chorionic villus sampling in approximately 85% of cases, obtain fluorescent in situ hybridization (FISH) results overnight, and then perform FR the next day. Decisions about which to reduce prioritize anomalies, but now can include fetal gender in the decision process, as couples are now just as likely to want girls as boys. In Mendelian cases, sophisticated molecular analyses permit diagnoses before FR, and new uses such as paternity analysis can be performed. Ethical arguments have also evolved; as with many technologies in which the start was for only 'life or death cases', FR has also moved into 'quality of life' issues. FR of twins to a singleton now compromise about 30% of our cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000357974DOI Listing
November 2014

Paternity balancing.

Fetal Diagn Ther 2013 30;34(3):135-9. Epub 2013 Aug 30.

Comprehensive Genetics, New York, N.Y., USA.

Background: Gestational carriers and egg donors have been used by 'traditional' and now increasingly, gay couples. Three gay male couples, all using egg donors and gestational carriers with semen from both partners, had triplets. All desired reductions to twins for the standard medical indications, but requested, if reasonably possible, to have twins with one fathered by each partner.

Methods: Following our usual clinical protocol, we performed chorionic villus sampling at 12 weeks on all fetuses obtaining FISH and karyotype. For paternity analysis, 14 polymorphic molecular markers on villi were compared to DNA samples from the two men to include or exclude each.

Results: Standard assessments were all normal. Paternity testing showed that one partner fathered two of the triplets, and the other one. In all cases, one of the 'twins' was reduced with good clinical outcomes ensuing.

Conclusions: Paternity balancing increases options for satisfying family planning desires of gay male couples. We believe it comparable to gender preferences in reductions, i.e. it can be considered but only completely subservient to any clinical criteria. Paternity balancing raises similar ethical issues as reduction with gender preferences, but may increase patient autonomy and mainstream acceptance of stable, gay families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000351857DOI Listing
June 2014

Detection of genetic abnormalities by using CVS and FISH prior to fetal reduction in sonographically normal appearing fetuses.

Prenat Diagn 2013 Oct 29;33(10):940-4. Epub 2013 Aug 29.

Department of Obstetrics & Gynecology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA.

Objective: To examine the ability of chorionic villus sampling (CVS) and fluorescence in situ hybridization (FISH) to detect aneuploidy before first trimester fetal reduction (FR) in sonographically normal-appearing fetuses.

Methods: A retrospective review of 470 patients referred to our unit for FR from January 2007-March 2011. Prenatal diagnosis was offered to all. FR was performed after next-day FISH results. Abnormalities were categorized by ultrasound, FISH, and/or karyotype. Sensitivity, specificity, positive predictive value, and negative predictive value of pre-FR FISH were calculated.

Results: Four hundred thirty-two of 470 patients seen were first trimester. 24/432 (5.2%) were excluded for abnormal ultrasound findings, including nuchal translucency (NT) > 3.0 mm, and 360 (88.2%) underwent CVS before FR. Ten fetuses were then excluded for euploid sex mosaicism. 10/350 (2.9%) patients with normal ultrasounds had abnormal FISH confirmed by karyotype. 9/350 (2.6%) patients with normal FISH had an abnormal karyotype necessitating follow up amniocentesis in which the clinically relevant discordancy was confirmed in one case (1/350, 0.3%). Pre-FR FISH had a 90% sensitivity, 99.4% specificity, 83.3% positive predictive value, and 99.7% negative predictive value.

Conclusions: 3.1% of patients with normal-appearing fetuses prior to first trimester FR had a fetus with an abnormal karyotype of which FISH detected 90%. CVS with FISH prior to FR adds significant information that can guide reduction decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.4213DOI Listing
October 2013