Biomedical subjects
Mark I Evans
Publications and source records attributed to Mark I Evans.
Procedural risks versus theology: chorionic villus sampling for Orthodox Jews at less than 8 weeks' gestation.
OBJECTIVE: According to Orthodox Jewish law, abortion is only permitted before 40 days post conception. This evaluation was performed to determine the feasibility and safety of performing chorionic villus sampling (CVS) at 7 to 8 weeks' gestation so that genetic results would be useful for these patients. STUDY DESIGN: We evaluated a sequential series of 82 Orthodox Jewish patients who chose CVS at <63 days' gestation. Outcome measures included procedure success rates, laboratory success rates, pregnancy outcomes, and complications. RESULTS: CVS was successful in all cases. Ninety-one percent were performed transcervically, with 30% requiring 2 or more insertions. Abnormal results were found in 16 (20%). Of 61 cases with normal genetic and ultrasound results, spontaneous losses at less than 28 weeks occurred in 3 (5%). These rates are higher than the 2.3% loss rate and the 1.2% multiple insertion rate seen at our center when sampling is performed at the usual gestational ages of 10 to 12 weeks. One baby had a severe limb reduction defect (1.6%). CONCLUSION: In very experienced hands, CVS can be safely and reliably performed at very early gestational ages. The ability to obtain an early diagnosis may be associated with increased but acceptable complication rates, including a 1% to 2% risk of limb reduction defects. There are patients for whom the usual paradigms do not suffice, and obtaining an early disgnosis provides them the opportunity to trade increased risks for reproductive choice. The ethical issues are complex, but such decisions can be supported by extensive and detailed informed consent.
Correction for insulin-dependent diabetes in maternal serum alpha-fetoprotein testing has outlived its usefulness.
OBJECTIVE: Historically, alpha-fetoprotein (AFP) levels in insulin-dependent diabetes (IDDM) have shown an approximately 20% decrement, and a correction factor is used to standardize multiples of the median (MOMs). With new laboratory methods and improved precision, we sought to re-evaluate the correctness of this approach. STUDY DESIGN: Consecutive biochemical screens were conducted among 60,287 nondiabetic patients and 307 patients with IDDM. Analyses were conducted in one laboratory, and comparisons were made with use of standard formula weight adjustments including a 20% correction factor for IDDM. Patients were then stratified according to maternal weight. RESULTS: Nondiabetic patients averaged 1.00 MOM, IDDM patients 0.91 MOM with no adjustments, 0.96 MOM adjusting for weight only, and 1.20 MOM adjusting for weight and diabetes status. To explain the "overcorrection," analysis by maternal weight showed significant overrepresentation of IDDM patients at 175 pounds or above. In fact, the mean weight in pounds for nondiabetic subjects was 151 +/- 35 and for those with IDDM 174 +/- 52 (P <.001). With use of an upper limit weight cutoff of 200 pounds, results are within 4% of normal. CONCLUSIONS: With current methodologies, the 20% correction factor for IDDM erroneously overcorrects. Two hundred pounds is sufficient, the weight correction for diabetic status should be abandoned.
Maternal weight correction for alpha-fetoprotein: mathematical truncations revisited.
The objective of this study was to determine if maternal weight correction as implemented 20 years ago for alpha-fetoprotein (AFP) testing is still appropriate, and what should be the weight cutoff for correction. AFP measurements from 44,951 biochemical screening cases from a single laboratory were divided by maternal weight, and separated into high >/=2.5 multiples of the median (MOM), and low <0.4 MOM. Without weight correction, AFP values are still skewed to lower levels of higher maternal weight (1.1% >/= 2.5 MOM). Using a truncated range to 200 lbs. (for women greater than 200), produces more uniform results than using an upper cutoff of 250 for truncation (2.7% vs 5.0% >/= 2.5 MOM). The same relationship is seen for "lows." Without correction, higher weight lowers AFP, correction to 250 lbs. overcompensates, and 200 lbs. gives the most even distribution, and, therefore, optimizes the distribution of highs.
Principles of screening.
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Interphase FISH for prenatal diagnosis of common aneuploidies.
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The choices women make about prenatal diagnosis.
Despite the rapid advancement and increasing utilization of prenatal diagnostic technologies, there has been a paucity of investigation into the psychological, socioeconomic, and demographic features associated with the choices women make about both the uptake of services, and the actions taken after fetal abnormalities are discovered. From 1986 through 1991 we have completed four studies initiating a proposed comprehensive evaluation of these factors. The first two studies concentrated on patient features influencing uptake of prenatal diagnostic procedures in both a priori 'high risk' pregnancies (advanced maternal age) as well as in previously 'low risk' pregnancies which had become 'high risk' by virtue of abnormal maternal alpha-fetoprotein (MSAFP) screening. The second two studies evaluated features influencing abortion decisions after the discovery of either chromosomal anomalies, or non-aneuploid ultrasonographically detected structural abnormalities. Data suggested that (1) older and more highly educated women tended to choose CVS over amniocentesis; (2) perceptions of genetic risk within couples was most influenced by attributes of their partners; (3) anxiety and perception of risk was higher in young women having abnormal screening MSAFP, than in the advanced maternal age group although this difference appeared to be commensurate with actual risks; (4) for fetal aneuploidy, the specific karyotype and, to a lesser extent, coexistent structural anomalies are the major determinants of decisions to abort; (5) for euploid fetal structural abnormalities the prognostic severity and potential for beneficial medical intervention (either antenatally or postnatally) as counselled by the physician were the principal determinants influencing abortion decisions. Further study is needed and important questions still to be addressed are discussed.
Prenatal diagnosis: choices women make about pursuing testing and acting on abnormal results.
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Spontaneous abortions in couples declining multifetal pregnancy reduction.
Multifetal pregnancy reduction (MFPR) has clearly improved the outcomes of multifetal gestations. Several recent reports have also suggested improved outcomes in nonreduced cases, but there have been methodologic concerns about the denominators, i.e. have all cases been included and is there a 'hidden mortality' of unknown lost cases. Here we assessed the outcome of patients telephoning to discuss MFPR, but who chose not to have the procedure. Over a 3-year period, 446 patients had MFPR by one operator. Nineteen patients chose not to have the procedure. There were 11 preterm births, 1 term delivery, and 5 spontaneous losses (7 of 17) prior to 24 weeks, a loss rate of 35%. Two patients delivering triplets had a loss of 1 fetus/neonate. These data suggest that the loss rates of nonreduced pregnancies may be higher than generally thought, making the improvements with MFPR even bigger than generally realized.
The Wayne State experience.
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Multifetal pregnancies: evolution of methods of initiation and impact of REI certification for patients seeking reduction.
OBJECTIVE: Multifetal pregnancy as a result of ovulation induction (OI) and assisted reproductive technologies (ART) correlate with Board certification in reproductive endocrinology and infertility (REI). DESIGN: Retrospective chart analysis of 304 patients referred to Wayne State University (WSU) and Thomas Jefferson University (TJU) for multifetal pregnancy reduction (MFPR) from March 1986 to January 1995 compared to 275 patients referred from January 1 to December 31, 2000 at MCP Hahnemann University. MATERIAL AND METHODS: Chart review for fetal number, pregnancy generation (OI or ART) and physician REI Board certification from the American Board of Specialties Obstetrics and Gynecology. Information was available on 296 of 304 patients studied in the 1986-1995 WSU cohort and 275 patients studied from the MCP Hahnemann 2000 cohort. RESULTS: Analysis of 296 multifetal pregnancies at WSU and TJU for REI Board status showed non-REI Board-certified (NREI) physicians generated 174 pregnancies with quadruplets or more compared to 122 quadruplets or more by REI Board-certified physicians. Board certification did not impact quadruplet or more rates for OI or ART (p < 0.368). Of 275 patients with triplets or more at MCP Hahnemann, 156 (56.7%) were from ARTs versus 41.2% from 1986-1995 (chi(2) = 13.1, p < 0.001). Quintuplets or more decreased from 18.5 to 9.7% (chi(2) = 8.3, p = 0.004), and for REIs from 22.1 to 9.6% (chi(2) = 4.7, p < 0.01), while 14.4% of cases coming from non-REIs had quintuplets versus 9.6% from REIs (p = NS). CONCLUSIONS: Cases of MFPR from ARTs have risen, while percentage of cases with quintuplets have fallen in half. We found no difference in quintuplets between REIs and non-REIs overall, but REI quintuplets fell significantly, and NREI has not.
Demographic factors for utilization of invasive genetic testing after multifetal pregnancy reduction.
OBJECTIVE: Pregnant infertility patients are commonly old enough to be offered prenatal diagnosis. However, they may be reluctant to undergo an additional invasive procedure. We, therefore, sought to determine what demographic factors, including race and ethnic group, influenced patients' decisions to undergo genetic testing in addition to multifetal pregnancy reduction (MFPR). METHODS: We retrospectively reviewed MFPR patients from July 1997 to June 1999 at our institution. Invasive genetic testing was routinely discussed. Maternal age, race, ethnicity, religion, egg source for in vitro fertilization (IVF) patients, and the remaining fetuses following MFPR were analyzed for invasive genetic testing determinants and were compared to our experiences with genetic referents to us for singleton pregnancies. 132 consecutive patients, of whom 49 were >/=35 years, including 15 having IVF with donor eggs, were included. RESULTS: Maternal age was the single most significant determinant of testing. In donor egg cases, donor age was significant. Ethnic background, previous children, and the remaining number of fetuses after MFPR were also significant determinants. CONCLUSION: MFPR patients share similar demographics to the advanced maternal age population. Despite the very stressful situations, our data suggest that maternal age, and therefore genetic risk, is the most important determinant of choosing whether or not to have testing. However, patients' decisions are, to varying degrees, modified by religious and ethnic considerations.
Natural history of twin gestation complicated by in utero fetal demise: associations of chorionicity, prematurity, and maternal morbidity.
OBJECTIVES: To evaluate the pathophysiology by which the in utero death of 1 twin might increase morbidity to its co-twin survivor and its mother. To assess previously reported risks for maternal disseminated intravascular coagulopathy, peripartal hemorrhage, retained placenta and infection, as well as the fetal risk of prematurity. MATERIAL AND METHODS: A retrospective analysis of the natural history of twin pregnancies from three institutions was performed. A total of 1,989 cases of twin pregnancy were identified, Wayne State University included 1,266 cases from 1984 to 1993; Madigan Army Medical Center 136 cases, 1995-2000, and Rockford Regional Perinatal Center, 587 cases, 1990-2000. The findings were classified by the presence or absence of fetal death in utero (IUFD) as follows: both IUFD (0/0); 1 IUFD (0/+), and both live born (+/+). A case-control study was performed on the subgroup of patients for whom complete records as to chorionicity, etc., were available. RESULTS: Of the 1,989 cases reviewed there were 49 both IUFD (0/0), 61 complicated by 1 IUFD (0/+), and 1,879 with both live born (+/+). The overall fetal death rate for this twin cohort was 55/1,000. IUFD of 1 or both twins was related to an increased risk of previable delivery 55% in 0/0, and 28% in 0/+ versus 4% for +/+ with p<0.001. IUFD also was associated with early preterm delivery (mean gestational age at delivery of 23 (0/0) and 30 (0/+) versus 35 (+/+) weeks). Chorionicity as well as maternal risks were examined in the case-control study (24 (0/0), 43 (0/+), 134 (+/+)) with the following results: monochorionic placentation was more likely in pregnancies complicated by IUFD (54% (0/0), 51% (0/+) versus 14% (+/+); p<0.001). Retained placenta, requiring dilation and curettage, occurred more frequently when both twins died in utero, but may be related to the earlier gestational age at delivery. DISCUSSION: Independent of retained placenta, there is no difference in the maternal risks for hemorrhage, abruption, coagulopathy or infection between groups. Immaturity at delivery and monochorionicity are more common in pregnancies complicated by fetal demise. Neonatal morbidity and developmental outcome will be the focus of a longitudinal study comparing cotwin survivors to twins matched for chorionicity and gestational age at delivery.
Framing the decision: determinants of how women considering multifetal pregnancy reduction as a pregnancy-management strategy frame their moral dilemma.
OBJECTIVE: How people make decisions regarding medical technologies and procedures are affected by how they 'frame' those decisions. Medical frames are characterized by a reliance on statistics regarding outcomes and risk to mother and surviving embryos, emphasize the influence of medical authorities, and are driven by a desire to minimize medical risks. Moral frames, on the other hand, are driven more by a desire to minimize the disruption to antiabortion and antireduction moral precepts, and weight heavily the advice of religious leaders. These frames contest with one another. Our objective is to examine the biographical determinants of frame dominance in this contest as it applies to multigestation pregnancies where selective reduction is being considered as a pregnancy-management strategy. METHODS: For a sample of 55 multigestation women considering multifetal reduction as a pregnancy-management strategy, we develop a distinction between medical and moral frames. Semistructured interviews generated qualitative data that were independently coded by two researchers. These variables were then analyzed using dummy variable regression analysis. RESULTS: Conceptualizing these frames as anchoring opposite ends of a continuum, we show that 40% of the variance in frame dominance can be accounted for by three factors: how involved patients are in religious institutions that have antiabortion norms, whether they have medico-scientific careers, and how pro-reduction their advice has been from fertility specialists and obstetricians prior to coming to the clinic. CONCLUSIONS: The implication of these results for practice include recognizing the wide variation in patient's perceptions of their situations and how these perceptual frames alter how women confront risk-benefit statistics and being flexible in one's approach to counseling patients. This approach can further serve as a model for similar reproductive-health dilemmas.
2nd-trimester maternal serum human chorionic gonadotropin and alpha-fetoprotein levels in male and female fetuses with Down syndrome.
BACKGROUND/OBJECTIVE: Several studies have shown that the 2nd-trimester maternal serum alpha-fetoprotein (AFP) level is significantly lower and that the maternal serum human chorionic gonadotropin (hCG) level is significantly higher in the presence of a female fetus. This may potentially affect Down syndrome (DS) screening such that a higher false-positive rate may occur in women carrying a female fetus, whereas a lower detection rate may result in those carrying males. The purpose of this study was to evaluate the gender impact on marker levels in DS pregnancies and its effect on DS screening. METHODS: The study included 62 DS pregnancies with a single fetus of known gender (31 male and 31 female). Only pregnancies with chromosomal analysis showing trisomy 21 were included. The maternal serum levels of hCG, AFP, and unconjugated estriol were measured at 16-20 weeks of pregnancy. These levels were expressed as gestational-age-corrected multiples of the median. RESULTS: No statistically significant differences were noted in maternal serum levels of hCG or AFP in DS pregnancies between women carrying a female and those carrying a male DS fetus. No statistically significant differences in 'screen-negative' rates were noted among male and female fetuses. CONCLUSIONS: In normal pregnancies, the maternal serum hCG level is higher, and the AFP level is lower in the presence of a female fetus. However, this gender-related difference is not apparent in DS pregnancies. Therefore, the gender-related differences in serum marker levels would not result in a lower detection rate of DS in male fetuses.