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Biomedical subjects

Mark I Evans

Publications and source records attributed to Mark I Evans.

At least 19 recordsLinked to original sources

Information-sharing among couples considering multifetal pregnancy reduction.

OBJECTIVE: To determine the information-sharing strategies of couples considering fetal reduction, and the impact of these strategies on the chances of encountering hostility in their social networks. DESIGN: Cross-sectional design of semistructured qualitative interviews, coded with respect to sharing strategies and level of personally directed hostility encountered. SETTING: Multiple Pregnancy Management Program, Comprehensive Genetics, New York, New York. PATIENT(S) AND INTERVENTION(S): Fifty women and their partners who were making a first visit to our maternal-fetal management facility, in order to consider the possibility of multifetal reduction as a pregnancy-management strategy. MAIN OUTCOME MEASURE(S): Development of information-sharing strategies, and the chances of encountering personally directed hostility regarding multifetal reduction associated with more and less selective strategies. RESULT(S): Four information-sharing strategies emerged from the analysis. Two of these strategies were relatively open (extended network, and both parents). Two other strategies were relatively selective (qualified family and friends, and defended relationship). The selective strategies were significantly less likely to encounter to encounter personally directed hostility (odds ratio, 3.88; 95% confidence intervals, 0.87-17.30). CONCLUSION(S): Selective sharing of information for couples considering multifetal prgnancy reduction is a potentially useful strategy for moderating potentially stressful relationships in their social networks. Clinics should find a way of integrating the discussion of selective sharing into their clinic's cultural repertoire of patient-support services.

Communication↗

Automated microscopy of amniotic fluid cells: detection of FISH signals using the FastFISH imaging system.

OBJECTIVE: FISH (fluorescence in situ hybridization) analysis is a valuable adjunct to cytogenetics that provides a rapid screen for common abnormalities. However, FISH is expensive, labor-intensive, and requires a high skill level and subjective signal interpretation. A fully automated system for FISH analysis could improve laboratory efficiency and potentially reduce errors and costs. METHODS: In this study we blindly compared automated FISH signal acquisition and display against standard FISH analysis. A total of 62 amniocentesis samples were prepared using the AneuVysion multicolor DNA probe kit and probed for chromosomes 13, 18, 21, X, and Y. Two sets of slides were produced from each sample. Fifty cells were scored in each slide. One set was evaluated using standard manual microscopy and the other using the automated image acquisition and display capabilities of the Ikoniscope fastFISH amnio Test System. This system uses epifluorescence optics, along with optimized slide management to process slides automatically. RESULTS: A 100% concordance was observed between the results obtained using manual microscopy and the automated system. There was also 100% concordance between the FISH results and those obtained by conventional karyotyping. CONCLUSION: Our data suggest that the automated system is capable of providing accurate and rapid identification and display of cells and FISH signals.

Adolescent↗

Matching risk and resources in high-risk pregnancies.

OBJECTIVE: To evaluate the joint impact of pregnancy risk and the timing of referral of high-risk pregnancies from obstetricians to maternal fetal medicine (MFM) sub-specialists on gestational age (GA) at delivery. METHODS: For the period 1992-2002, 2567 consecutive deliveries from pregnancies of at least 23 weeks gestational age (GA) from a community-level sub-specialty perinatal center were studied. A multiple regression model was developed specifying the impact of various risk factors and referral timing. RESULTS: Prior pregnancy risk was inversely related to GA at birth. Referral timing, operationalized as a continuous variable, did not have a significant additive impact on GA at birth, but several dummy-variable interaction effects combining risk factors and referral before 20 weeks as a dichotomy were significant. CONCLUSION: There are identifiable risks that occur either before the pregnancy or early into it that should lead to early referral to a sub-specialist because of their impact on GA at birth. Early referral is an important tactic in a larger preterm prevention strategy, but it needs to be embedded in a broader maternal-fetal health initiative in which both generalists and sub-specialists play important roles.

Adult↗

Update on selective reduction.

Over the past 25 years fetal reduction has been utilized to reduce the risks of higher-order multiple pregnancies that have resulted from overly successful infertility therapies. The demographics of multiple pregnancy patients have evolved over the past decade, with increasing proportions coming from IVF as opposed to ovulation induction, being older and a higher proportion with donor eggs. Genetic diagnosis prior to reduction is becoming more common and is very safe in experienced hands. For all starting numbers, including twins, reduction to a lower number of fetuses reduces fetal losses, prematurity, and infant mortality and morbidity.

Female↗

Invasive prenatal diagnostic procedures 2005.

Amniocentesis and Chorionic Villus Sampling have been the two most common prenatal diagnostic procedures for decades. There are wide variations in utilization, operator skills, quoted procedure risks, actual observed risks, and patient choices that come from highly variable counseling as to those risks. The compilation of published data suggests procedure risks of amniocentesis to be about 1/200 and in very skilled hands to be slightly lower. The risks of CVS in very experienced hands may also be about 1/200. Most studies comparing CVS to amniocentesis in skilled hands have found equivalency of risks. No well controlled studies support claims of amniocentesis risk at 1/1000 or lower. There is no increased risks of limb reduction defects following CVS at 10 weeks or greater, but there is an increase in Talipes from "Early Amniocentesis." In the first trimester CVS is the safer procedure.

Abortion, Spontaneous↗

Fetal reduction.

Fetal Reduction has been employed over the past two decades as a mechanism to reduce the morbidity and mortality of multiple pregnancies. Utilization of the procedure has increased dramatically as IVF has become commonplace but the average starting number has decreased with the transfer of fewer embryos. Success rates from fetal reduction have improved as a function of increasing experience, better ultrasound, and lower starting numbers. Genetic diagnosis prior to reduction can improve the overall outcomes. Reduction of triplets or more clearly improves outcomes, and reduction of twins to a singleton is now a reasonable consideration.

Female↗

Principles of screening.

Screening and diagnostic testing are sequentially-oriented procedures for progressively analyzing risk. Screening is broadly based and aimed at identifying those at high risk of a disease or condition. Diagnostic testing is designed to more definitively answer the question of whether or not a person has a disease or condition. Understanding the differences among four key measures of evaluation for tests (sensitivity, specificity, positive predictive value and negative predictive value) are necessary for proper utilization of screening tests.

Acquired Immunodeficiency Syndrome↗

Re-evaluating the role of the MFM specialist: lead, follow, or get out of the way.

OBJECTIVE: To assess the effect of sub-specialty prenatal care provided to high-risk obstetrical patients in a community perinatal center as a function of whether consultation and referral to a Maternal-Fetal Medicine (MFM) sub-specialist was at the discretion of the generalist, required by the insurance carrier, or by patient choice. METHODS: Demographics, management, and perinatal outcomes for high-risk patients managed exclusively by MFM were compared with those managed by generalists who were later referred to MFM after problems arose. RESULTS: Despite similar demographics, high-risk patients managed exclusively by a single MFM had less prematurity, lower cesarean section rates, fewer low 5-minute Apgar scores (1.3% vs. 5.5%, p < 0.001), and lower perinatal mortality rates (8.0/1000 vs. 47.6/1000, p < 0.001) than those referred at a later date. CONCLUSIONS: In this setting, earlier MFM care resulted in better outcomes. These data suggest that the 'gatekeeper' model of generalist to MFM might be better the other way around.

Adult↗

Automated detection of rare fetal cells in maternal blood: eliminating the false-positive XY signals in XX pregnancies.

OBJECTIVE: The purpose of this study was to develop a new method to help differentiate XX from XY signals in maternal blood from women carrying XY fetuses. STUDY DESIGN: We have developed a system to scan automatically for cells that bear X and Y fluorescence in situ hybridization signals. These XY target cells are identified by scans at low (x20) magnification, and all identified targets are revisited and verified at high (x100) magnification. The viewer software component of the system displays x20 images of all cells and intracellular fluorescence in situ hybridization signals that are present in each of the 4000 optical fields per slide, along with x100 images of automatically detected target cells. RESULTS: We initially examined 36,000 fields from 18 slides in 12 pregnancies (6 male and 6 female) using our system that is based on fluorescence in situ hybridization with a single probe for the X-chromosome and a single probe for the Y-chromosome and found XY nuclei in all samples, regardless of fetal gender. In the second phase of the study, a refinement of the approach that incorporated 2 independent probes for the Y-chromosome resulted in a false-positive rate for detection of XY nuclei in XX cases <0.00005%. CONCLUSION: Our data suggest that this system may allow for excellent "signal to noise" separation, which is required absolutely for fetal cell methods to differentiate aneuploid from normal pregnancies. Quantitation of fetal cells in the maternal circulation and standardization of processes that have been developed for their enrichment are crucial to moving fetal cell assessment from esoteric basic science to applied new technology.

Aneuploidy↗

Do reduced multiples do better?

Dramatic successes in infertility care have allowed millions of previously fertile women to have their own children. However, an epidemic of multiple pregnancies has resulted, with catastrophic increases in morbidity and mortality, and in the economic costs to society. Multifetal pregnancy reduction (MFPR) has been used to decrease fetal number in the late first trimester and has dramatically improved outcomes. Recent data suggest that pregnancies starting with three or four, and in some cases five fetuses, which are reduced to twins, do as well as starting with twins. Patients with triplets do better reduced to twins. Reduction to a singleton is becoming more common, particularly for women over 40. Combining MFPR with chorionic villus sampling in patients over 30 years of age has enabled couples to maximize the health of the resultant children.

Abortion, Spontaneous↗

Impact of folic acid fortification in the United States: markedly diminished high maternal serum alpha-fetoprotein values.

OBJECTIVE: Folic acid fortification of breads and grains was implemented in the United States in 1998 in an attempt to reduce the incidence of neural tube defects. Outcome data from birth registries have shown a 20% drop-less than originally predicted. In this study, we ascertain if the impact of folic acid fortification is better seen at the time of midtrimester prenatal diagnosis by looking at incidence of high maternal serum alpha-fetoprotein (MSAFP) values. METHODS: Data regarding MSAFP levels in 61,119 patients undergoing maternal serum screening at a large commercial laboratory were categorized by multiples of the median (MoM). The data were compared between 2 groups: before mandatory supplementation in the United States in 1997 and after mandatory supplementation in 2000. High MSAFP values were further categorized as high (2.75-4.00 MoM) or very high (more than 4.00 MoM). Data were analyzed by chi(2) analysis. RESULTS: Comparative data showed a 32% decrease of patients with MoM greater than 2.75 + (2.5% -1.7%). Further categorizations revealed similar decreases. CONCLUSION: The introduction of folic acid fortification has produced a profound decrease in the number of high MSAFP values, reflective of a decreased incidence of neural tube defects. Our results help to validate the decision to fortify food with folic acid, which represents a highly successful public health policy for primary prevention of birth defects. LEVEL OF EVIDENCE: II-2

Cohort Studies↗

Fetal reduction from twins to a singleton: a reasonable consideration?

OBJECTIVE: In the past, our group took the position that we would not provide multifetal pregnancy reduction to a singleton regardless of starting number except for serious maternal medical indications or as a selective termination for diagnosed fetal anomalies. With evidence of increased safety and more women (many aged 40 years or more) asking for counseling about reduction to a singleton, we reviewed our prior reasoning. METHODS: We compared outcomes of 52 first-trimester twin-to-singleton for multifetal pregnancy reduction cases performed by a single operator to twin and singleton data from recent national register studies. RESULTS: Twin-to-singleton reductions represent less than 3% of all cases. Forty of 52 patients were aged 35 years or more, 19 were aged more than 40 years, and 2 were aged more than 50 years (age range 32-54 years). Since 1999, 23 of 28 had chorionic villus sampling before multifetal pregnancy reduction. Fifty-one of 52 reached viability with mean gestational age at delivery of 37.2 weeks. One of 52 patients miscarried (1.9%). Compared with multiple sources of data for twins, the loss rate is lower in twins reduced to a singleton. CONCLUSION: Until recently, multifetal pregnancy reductions to a singleton were rare. Physicians were concerned about the unknown risks of multifetal pregnancy reduction in this situation. They also had moral doubts about the justification to go "below twins." However, physicians know that spontaneous twin pregnancy losses average 8-10%. Also, with experience, multifetal pregnancy reduction has become very safe in our hands. Our data suggest that the likelihood of taking home a baby is higher after reduction than remaining with twins. We propose that twin-to-singleton reductions might be considered with appropriate constraints and safeguards.

Abortion, Spontaneous↗

Intact fetal cells in maternal plasma: are they really there?

Rare fetal cells can be recovered from maternal blood, which suggests that non-invasive prenatal diagnosis is possible. However, recovery and analysis of fetal cells from blood is complex, and sensitivity is low because of the rarity of these cells in the maternal circulation. An alternative strategy, which suggested that intact fetal cells can be found in maternal plasma by use of simple enrichment methods, has been reported. We aimed to replicate this technique. However, five independent laboratories were unable to identify any intact male cells from the plasma of 38 women known to be carrying male fetuses. Although apoptotic intact fetal cells could contribute to the detection of fetal DNA in maternal plasma, we believe that recovery of these cells is difficult and not clinically practical.

Aneuploidy↗

Selective reduction.

Multifetal pregnancy reduction continues to be controversial. Attitudes about MFPR have not, in our experience, followed a simple "pro-choice/pro-life" dichotomy. As far back as the mid to late 1980s, opinions about the subject were varied. Even then, when much less was known about the subject, opinions did not always parallel the usual pro-choice/theological boundaries. We believe that the real debate over the next 5 to 10 years will not be whether or not MFPR should be performed with triplets or more. The fact is that MFPR does improve those outcomes. A serious debate will emerge over whether or not it is appropriate to offer MFPR routinely for twins, even natural ones, for whom the outcome is commonly considered "good enough." Our data suggest that reduction of twins to a singleton improves the outcome of the remaining fetus. No consensus on appropriateness of routine 2-1 reductions is ever likely to emerge. The ethical issues surrounding MFPR will always be controversial. Over the years, much has been written on the subject. Opinions will always vary from outraged condemnation to complete acceptance. No short paragraph could do justice to the subject other than to state that most proponents do not believe this is a frivolous procedure but do believe in the principle of proportionality ie, therapy to achieve the most good for the least harm). Over the past 15 years, MFPR has become a well-established and integral part of infertility therapy and attempts to deal with the sequelae of aggressive infertility management. In the mid 1980s, the risks and benefits of the procedure could only be guessed. We now have clear and precise data on the risks and benefits of the procedure and an understanding that the risks increase substantially with the starting and finishing number of fetuses in multifetal pregnancies. The collaborative loss rate numbers (ie, 4.5% for triplets, 8% for quadruplets. 11% for quintuplets, and 15% for sextuplets or more) seem reasonable to present to patients for the procedure performed by an experienced operator. Our experiences and anecdotal experiences from other groups suggest that less experienced operators have worse outcomes. Pregnancy loss is not the only poor outcome. The other main issue with which to be concerned is very early premature delivery, where there is an increasing rate of poor outcomes correlated with the starting number. The finishing numbers are also critical, with twins having the best outcomes for cases starting with three or more. Triplets and singletons do not do as well. We hope that MFPR will become obsolete as better control of ovulation agents and assisted reproductive technologies make multifetal pregnancies uncommon.

Female↗

Standardization of methods reduces variability: explanation for historical discrepancies in biochemical screening.

Over the past decade, many studies have argued the relative merits of different chromosome abnormality biochemical screening protocols in different labs. Results and interpretations have varied markedly (e.g., double vs. triple screening). In this study we sought to compare coefficients of variation (CV) among 12 laboratories in one system, using identical and different methodologies for the three parameters. Ten identical specimens were processed as part of the 1999 College of American Pathologists (CAP) (FP-A, FP-B) proficiency tests. Results were compared among 12 laboratories using the Abbott ELISA for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and two methods for estriol [Diagnostic Services Laboratory (DSL) and an "in house" assay]. The range on the 10 specimens of means for AFP varied from 12.56 to 117.87; hCG 14.05-68.08; and estriol 0.61-2.73. CV for AFP specimens averaged 10%, hCG 8%, and estriol 35% (F = 22.4). However, when only DSL was used for estriol, the CV was reduced to 8.7%. Standardization of AFP and hCG across 12 labs has reduced CV to <10%, which is similar to accepted between run results. Wide variation of uE3 among different methods may explain the widely divergent results in the literature. With national standardization of all parameters, the widely divergent results seen in the literature should narrow, and regional medians will no longer be necessary.

Biomarkers↗

Screening.

Historically, obstetrician/gynaecologists have utilized screening procedures as a major component of their routine clinical practice. The Papanicolaou (Pap) smear technique for cervical cancer is more than 50 years old and has saved countless lives by identifying who among the supposedly low-risk group of patients is in fact at high risk of cervical cancer. The introduction of alpha-fetoprotein screening for neural tube defects in the 1970s, low alpha-fetoprotein level for Down syndrome in the 80s, multiple markers in the 90s and now, after the millennium combined ultrasound and biochemistry for a more precise risk identification, has radically changed our approach towards optimizing the sensitivity, specificity and positive and negative predictive values of screening. As these techniques improve, old mainstays of attributable risks such as advanced maternal age will probably fade into oblivion as stand-alone criteria. The specifics of screening techniques will vary by disorder, but the general principles are important and can be applied to all new technologies as they come on line. In fact, the real 'take-home message' is that one must use these principles when looking at new technologies to understand their role in emerging practice.

Adult↗

Fetal therapy.

Over the past 40 years, a small but increasing number of fetal genetic and congenital anomalies has become amenable to in utero treatment. Successful fetal therapies have included open procedures for congenital diaphragmatic hernia, cystadenomatoid malformation of the lung and saccrococygeal teratoma, shunts for uropathies and thoracic fluids, pharmacological therapies for congenital adrenal hyperplasia and neural tube defect prevention, and the stem cell treatment of severe combined immunodeficiency disorder.

Adrenal Hyperplasia, Congenital↗