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Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in high-risk populations. This systematic evidence review evaluates NIPS performance in a general-risk population.Medline (PubMed) and Embase were used to identify studies examining detection of Down syndrome (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, rare autosomal trisomies, copy number variants, and maternal conditions, as well as studies assessing the psychological impact of NIPS and the rate of subsequent diagnostic testing. Random-effects meta-analyses were used to calculate pooled estimates of NIPS performance (P.05). Heterogeneity was investigated through subgroup analyses. Risk of bias was assessed.A total of 87 studies met inclusion criteria. Diagnostic odds ratios were significant (P.0001) for T21, T18, and T13 for singleton and twin pregnancies. NIPS was accurate (≥99.78%) in detecting sex chromosome aneuploidies. Performance for rare autosomal trisomies and copy number variants was variable. Use of NIPS reduced diagnostic tests by 31% to 79%. Conclusions regarding psychosocial outcomes could not be drawn owing to lack of data. Identification of maternal conditions was rare.NIPS is a highly accurate screening method for T21, T18, and T13 in both singleton and twin pregnancies.

Purpose This project developed and evaluated the efficacy of a game decision aid among pregnant women about prenatal screening in a randomized controlled study. Study Design Participants were recruited from an obstetric clinic of an academic urban medical center and randomized (n = 73) to one of two study groups: the control group (n = 39) that used a brochure or the intervention group (n = 34) that also used a game decision aid. Result Participants who played the game had higher knowledge scores (m = 21.41, standard deviation [SD] = 1.74) than participants in the control group (m = 19.59; SD = 3.31), p = 0.004. The median time of game playing was 6:43 minutes (range: 2:17–16:44). The groups were similar in frequency of completing screening after the study, control = 6 (15%) versus intervention = 11 (32%), p = 0.087. However, the more interaction with the game resulted in more positive attitudes toward screening. Conclusion The addition of a game decision aid was effective in educating pregnant women about prenatal screening. As other genetic testing decisions continue to increase within clinical care, game-based decision tools may be a constructive method of informed decision-making.

Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multisociety task force to develop a consensus-based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at, or close to, 75% for each, and obtaining a set of 5 ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the task force expects that the criteria set forth in this document will evolve with time. The task force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency assessment process. Incorporating this training curriculum and the competency assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology.

Disclaimer: ACMG Clinical Laboratory Practice Resources are developed primarily as an educational tool for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these practice resources is voluntary and does not necessarily assure a successful medical outcome. This Clinical Laboratory Practice Resource should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with this Clinical Laboratory Practice Resource. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Noninvasive prenatal screening (NIPS) using cell-free DNA has been rapidly adopted into prenatal care. Since NIPS is a screening test, diagnostic testing is recommended to confirm all cases of screen-positive NIPS results. For cytogenetics laboratories performing confirmatory testing on prenatal diagnostic samples, a standardized testing algorithm is needed to ensure that the appropriate testing takes place. This algorithm includes diagnostic testing by either chorionic villi sampling or amniocentesis samples and encompasses chromosome analysis, fluorescence in situ hybridization, and chromosomal microarray.

The offering and acceptance of expanded carrier screening is increasing among pregnant women including women without an increased risk based on race, ethnicity or family history. The chances of a positive screening test have been reported to be as high as 24 % when multiple conditions are screened. Yet, little is known about the way these tests are offered and how patients are affected by a positive test result. To explore this area of genetic testing, interviews (n = 17) were conducted among women who received positive expanded carrier results in the context of obstetric care. A content analysis was conducted on the transcript data from the interviews. Outcomes of this research suggest that educational interventions are needed to improve maternal understanding of positive carrier screening results. Most of the participants in this study confused the results with other prenatal screening test options. In addition, the way the results were discussed varied greatly, and influenced participants’ thoughts about reproductive decisions that led to a range of emotional uncertainty. Our data suggests that genetic counseling improved participants’ understanding of positive results. More research is needed to further understand if our results are consistent within a larger, more diverse sample, and to explore how to best provide education about expanded carrier screening.

Over the last 50 years, screening for Mendelian disorders has progressed from screening of neonates for phenylketonuria (PKU) to screening of healthy individuals in the preconception or prenatal setting for more than 100 disorders. Traditional carrier screening has been based on ethnicity, and, as ethnic distinctions become less defined, the ability to screen effectively has become increasingly more limited. At the same time, advances in molecular technology have produced large screening panels without reliance on ethnicity. This article outlines the historical and traditional use of single gene carrier screening.

The sonologist detects a so-called "soft marker" during approximately 10% of routine second-trimester anatomy examinations and is often uncertain about what further management is appropriate. This article will specifically address the management of patients with sonographic markers for six common entities: choroid plexus cysts (CPCs), ventriculomegaly (VM), echogenic intracardiac focus (EIF), urinary tract dilation (UTD), fetal echogenic bowel (FEB), and femoral and humeral shortening. The use of cell-free DNA screening and its relationship to these sonographic findings will be reviewed.The era of ultrasound markers as a screen for fetal aneuploidy is coming to a close. The detection of these markers on an ultrasound examination should simply serve as a reminder to ensure that the patient was offered cell-free DNA screening or conventional analyte screening. Cell-free DNA testing is revolutionizing screening. With normal results on a cell-free DNA test, many isolated soft markers-including CPCs, EIF, mild rhizomelic limb shortening, and mild pyelectasis-are irrelevant from a genetic standpoint. However, further counseling and workup are indicated for VM, true FEB, femur or humerus length measurement that is less than 2.5-percentile value, and pyelectasis to evaluate for the nongenetic associations with these findings. Finally, cell-free DNA testing is currently a screening test; positive results require definitive diagnostic testing with amniocentesis or chorionic villus sampling.

The proposal by Chen and Wasserman (2017) contributes to a long-standing debate about the scope of prenatal screening services. With realistic prospects of fetal genome-scale sequencing from noninv...

Objective To characterize the types of genetic abnormalities and their prevalence in early pregnancy loss at different developmental stages. We hypothesized that the prevalence of genetic abnormalities in pregnancy loss would differ across developmental stages. Methods Women with a pregnancy loss at

Screening for genetic disorders began in 1963 with the initiation of newborn screening for phenylketonuria. Advances in molecular technology have made both newborn screening for newborns affected with serious disorders, and carrier screening of individuals at risk for offspring with genetic disorders, more complex and more widely available. Carrier screening today can be performed secondary to family history-based screening, ethnic-based screening, and expanded carrier screening (ECS). ECS is panel-based screening, which analyzes carrier status for hundreds of genetic disorders irrespective of patient race or ethnicity. In this article, we review the historical and current aspects of carrier screening for single gene disorders, including future research directions.

A pilot study assessed an electronic informed consent model within a randomized controlled trial (RCT). Participants who were recruited for the parent RCT project were randomly selected and randomized to either an electronic consent group ( n = 32) or a simplified paper-based consent group ( n = 30). Results from the electronic consent group reported significantly higher understanding of the purpose of the study, alternatives to participation, and who to contact if they had questions or concerns about the study. However, participants in the paper-based control group reported higher mean scores on some survey items. This research suggests that an electronic informed consent presentation may improve participant understanding for some aspects of a research study.

Beware the laboratory report: discrepancy in variant classification on reproductive carrier screening

In order to evaluate the utility of genetic counseling at the time of first trimester screening in patients with no previously identified genetic concerns, we reviewed family history data for 700 women seen for genetic counseling in Utah during 2005-2006. The mean maternal age was 35 years (Range: 16-47 years). The majority of patients seen were non-Jewish Caucasians (90.8%, 634/700). A three-generation pedigree was obtained from each woman by one of two certified genetic counselors and subsequently classified as "negative" (no birth defects/genetic disorders); "positive" (birth defect or genetic condition with a minimal/low risk of recurrence; additional evaluation/genetic testing during pregnancy not indicated); or "significant" (birth defect or genetic condition with an increased risk of recurrence; additional evaluation/genetic testing during the pregnancy indicated). About 72% (501/700) of the histories were negative, 19% (134/700) were positive, and about 9% (65/700) were significant. Among patients with significant family histories, 66% (n = 43) were women less than 35 years of age. We conclude that assessing a patient's family history at the time of first trimester serum screening is a valuable resource for pregnancy management.

Currently in the United States, pregnant women may obtain both medical fetal ultrasonography for screening and commercial fetal ultrasonography for entertainment purposes. The proliferation of commercial fetal ultrasonography suggests that medical screening alone does not satisfy patient expectations regarding fetal imaging. We investigated the prevalence of nonmedical fetal imaging and patient experiences and perceptions with both medical and nonmedical ultrasonography in our metropolitan area. We initiate a dialogue to explore the distinctions between medical and nonmedical fetal ultrasound imaging and the role of entertainment imaging in the medical setting. Concerns about safety, false reassurance, and unnecessary anxiety that might be generated by nonmedical ultrasonography should prompt us to examine the expectations of women regarding entertainment imaging, current clinical practice, and the potential for regulation of this commercial industry.

Common clinical problems of counseling patients about potential teratogenic risks in pregnancy are presented and principles of teratogenicity assessment.

Obesity compromises all forms of genetic screening. Although the risk for fetal aneuploidy is not altered by obesity, the risk for significant birth defects is increased. Therefore, the obese gravida is at an increased risk of fetal malformations with a diminished ability to be screened effectively by all screening methods: ultrasound, traditional serum analyte screening, and cell-free DNA screening. This chapter outlines both the current options and limitations of screening in the obese gravida. The offering of screening and diagnostic testing should not be altered in obese women despite the compromises placed on accurate fetal assessment.

The Perinatal Quality Foundation and the American College of Medical Genetics and Genomics, in association with the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the National Society of Genetic Counselors, have collaborated to provide education for clinicians and laboratories regarding the use of expanded genetic carrier screening in reproductive medicine. This statement does not replace current screening guidelines, which are published by individual organizations to direct the practice of their constituents. As organizations develop practice guidelines for expanded carrier screening, further direction is likely. The current statement demonstrates an approach for health care providers and laboratories who wish to or who are currently offering expanded carrier screening to their patients.

Objective First-trimester aneuploidy screening has high detection rates and low false-positive rates. Their use as well as the implementation of non-invasive prenatal testing may affect specialty training in prenatal diagnosis procedures. Study design Descriptive study of first-trimester aneuploidy screening and amniocentesis in an obstetric training program. Screening methods were tracked from their introduction in 2004 through 2011. The volume of amniocentesis procedures from 2000 to 2011 was evaluated. Results First-trimester screening tests increased from 283 to 1225 between 2005 and 2011, whereas genetic amniocenteses declined from 460 to 168 during the same period. The percent of older women who chose a first-trimester screen test rose from 12.7% to 44.2% Conclusion First-trimester screening options reduce genetic amniocenteses available for training. Fetal medicine and general obstetrics training programs need to evaluate their clinical experience and determine whether simulation training methods are needed for education. © 2013 John Wiley & Sons, Ltd.

Hypomethylated cell-free DNA from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor.To determine the changes in cell-free DNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term vs women without labor.In this prospective cohort study, eligible participants carried a nonanomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded. Maternal blood samples were collected at 28 weeks, 36 weeks, and at admission for delivery. Total cell-free DNA concentration, methylation ratio, and interleukin-6 were analyzed. The primary outcome was the difference in methylation ratio in women with labor vs without labor. Secondary outcomes included the longitudinal changes in these biomarkers corresponding to labor status.A total of 55 women were included; 20 presented in labor on admission and 35 presented without labor. Women in labor had significantly greater methylation ratio (P = .001) and interleukin-6 (P.001) on admission for delivery than women without labor. After we controlled for body mass index and maternal age, methylation ratio (adjusted relative risk, 1.38; 95% confidence interval, 1.13 to 1.68) and interleukin-6 (adjusted relative risk, 1.12, 95% confidence interval, 1.07 to 1.17) remained greater in women presenting in labor. Total cell-free DNA was not significantly different in women with labor compared with women without. Longitudinally, total cell-free DNA (P.001 in labor, P = .002 without labor) and interleukin-6 (P.001 in labor, P = .01 without labor) increased significantly across gestation in both groups. The methylation ratio increased significantly in women with labor from 36 weeks to delivery (P = .02).Spontaneous labor at term is associated with a greater cell-free DNA methylation ratio and interleukin-6 compared with nonlabored controls. As gestation advances, total cell-free DNA concentrations and interleukin-6 levels increase. A greater methylation ratio reflects a greater maternal contribution (vs placental) in women with labor, likely resulting from greater levels of neutrophils, lymphocytes, and uterine activation proteins at the time of labor. Although not significant, women in labor had a greater total cell-free DNA concentration and thus could theoretically have more hypomethylated DNA available for interaction with the inflammatory cascade. Larger studies are needed to investigate this theory.

Many state newborn screening programs retain residual newborn screening bloodspots for a variety of purposes including quality assurance, biomedical research, and forensic applications. This project was designed to determine the information that prospective parents want to know about this practice. Eleven focus groups were conducted in four states. Pregnant women and their partners and parents of young children (N = 128) were recruited from the general public. Focus group participants viewed two educational movies on newborn screening and DBS retention and use. Transcripts were analyzed with qualitative methods and the results were synthesized to identify key information items. We identified 14 categories of information from the focus groups that were synthesized into seven items prospective parents want to know about residual DBS. The items included details about storage, potential uses, risks and burdens, safeguards, anonymity, return of results, and parental choice. For those state programs that retain residual dried bloodspots, inclusion of the seven things parents want to know about residual dried bloodspots in educational materials may improve parental understanding, trust, and acceptance of the retention and use of stored bloodspots. © 2014 Wiley Periodicals, Inc.

PURPOSE OF REVIEW To highlight the evolution of prenatal diagnosis from invasive procedures to noninvasive assessments and to describe the efforts to educate both trainees and experienced physicians via simulation techniques. RECENT FINDINGS The rapid development of noninvasive serum analyte screening as well as molecular genetic and sonographic techniques to evaluate the fetus has altered our ability to both educate trainees as well as to maintain physician competence to perform invasive procedures. Simulation-based learning is being incorporated into medical training across a broad range of specialties, including obstetrics and gynecology. SUMMARY Prenatal diagnosis procedures will continue to be necessary for direct fetal assessment but on a much more limited scale. It is possible that all trainees will not be able to become competent in amniocentesis and other even less common procedures. Furthermore, experienced physicians may lose competence, given the lack of available procedures for skill retention. Innovative methods of skill acquisition and maintenance may be required in the near future. Although long-term assessments of efficacy are currently lacking, the introduction of comprehensive, simulation-based curriculia has the potential to both educate trainees and help maintain physician competence.

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid α-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included. A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained. Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7–27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47–128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1–38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4–80.9). MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients. J. Matern.-Fetal Med. 6:164–167, 1997. © 1997 Wiley-Liss, Inc.

The recent introduction of clinical tests to detect fetal aneuploidy by analysis of cell-free DNA in maternal plasma represents a tremendous advance in prenatal diagnosis and the culmination of many years of effort by researchers in the field. The development of noninvasive prenatal testing for clinical application by commercial industry has allowed much faster introduction into clinical care, yet also presents some challenges regarding education of patients and health care providers struggling to keep up with developments in this rapidly evolving area. It is important that health care providers recognize that the test is not diagnostic; rather, it represents a highly sensitive and specific screening test that should be expected to result in some false-positive and false-negative diagnoses. Although currently being integrated in some settings as a primary screening test for women at high risk of fetal aneuploidy, from a population perspective, a better option for noninvasive prenatal testing may be as a second-tier test for those patients who screen positive by conventional aneuploidy screening. How noninvasive prenatal testing will ultimately fit with the current prenatal testing algorithms remains to be determined. True cost-utility analyses will be needed to determine the actual clinical efficacy of this approach in the general prenatal population.

We describe the use of heteroduplex analysis to enhance the resolution of different rhesus-derived (Rh) isotypes. Heteroduplex analysis of different domains of the Rh D and Rh CE loci can be performed to diagnose a variety of blood group incompatibilities. One application of this technique is the ability to test for fetal-maternal blood group incompatibilities during pregnancy. Several new serotype-specific sequence variations were discovered in the mapping of the Rh locus, and used in the construction of artificial heteroduplex generators (HGs). HGs facilitate the resolution of the Rh isotypes by electrophoretic methods.

After years of decline, tuberculosis has again emerged as a serious public health issue. Following the introduction of effective chemotherapy at mid-century, cases of tuberculosis decreased until 1986. Since that time, the number of cases of tuberculosis have dramatically increased, particularly among young persons. The reemergence of tuberculosis is localized to urban areas and is linked to the increase in the incidence of human immunodeficiency virus infection and drug resistance. Since pregnant women are at risk for tubercular infection, an effective method exists to identify women who are asymptomatically infected, provide them with treatment to prevent progression of disease, and investigate their contacts. This review will discuss the issues of diagnosis and treatment of asymptomatic infection and active tuberculosis in pregnant women. Additionally, the need for universal screening of all prenatal patients and the benefit and potential perinatal toxicity of chemotherapy in both immunocompetent patients and those infected with human immunodeficiency virus will be addressed.

This review discusses current methods for pregnancy screening and the prenatal diagnosis of fetal Down syndrome. These include maternal serum screening ultrasonographic evaluations, and standard prenatal diagnostic techniques. In addition to noting the advantages and limitations of these methods, attention is directed to innovative prenatal diagnostic techniques that are not yet clinically available, such as the extraction of fetal cells from the maternal circulation and the preimplantation genetic diagnosis for fetal aneuploidies. © 1996 Wiley Liss, Inc.

First-trimester aneuploidy screening has high detection rates and low false-positive rates. Their use as well as the implementation of non-invasive prenatal testing may affect specialty training in prenatal diagnosis procedures.Descriptive study of first-trimester aneuploidy screening and amniocentesis in an obstetric training program. Screening methods were tracked from their introduction in 2004 through 2011. The volume of amniocentesis procedures from 2000 to 2011 was evaluated.First-trimester screening tests increased from 283 to 1225 between 2005 and 2011, whereas genetic amniocenteses declined from 460 to 168 during the same period. The percent of older women who chose a first-trimester screen test rose from 12.7% to 44.2%First-trimester screening options reduce genetic amniocenteses available for training. Fetal medicine and general obstetrics training programs need to evaluate their clinical experience and determine whether simulation training methods are needed for education.

Periconceptional folic acid supplementation has been shown to decrease the first occurrence of isolated neural tube defects (NTDs) by as much as 50%, and to decrease the recurrence risk for NTDs by more than 70%. The possible mechanisms of vitamin supplementation in the prevention of NTDs are discussed, as are the current recommendations for reproductive-age women. Further, the limitations of dietary and pharmacological recommendations with regard to patient compliance as well as the possibility of grain fortification are reviewed.

IMPORTANCE: Research clearly indicates that current approaches to newborn blood spot screening (NBS) education are ineffective. Incorporating NBS education into prenatal care is broadly supported by lay and professional opinion. OBJECTIVE: To determine the efficacy and effect of prenatal education about newborn screening and use of residual dried blood spots (DBS) in research on parental knowledge, attitudes, and behaviors. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial of prenatal educational interventions, with outcomes measured by survey at 2 to 4 weeks postpartum. Participants were recruited from obstetric clinics in Salt Lake City, Utah; San Francisco, California; and the Bronx, New York. Eligible women were English- or Spanish-speaking adults and did not have a high-risk pregnancy. A total of 901 women were enrolled. Participants who completed the follow-up survey included 212 women in the usual care group (70% retention), 231 in the NBS group (77% retention), and 221 women in the NBS + DBS group (75% retention). Those who completed the survey were similar across the 3 groups with respect to age, ethnicity, race, education, marital status, income, obstetric history, and language. INTERVENTIONS: Participants were randomized into 1 of 3 groups: usual care (n = 305), those viewing an NBS movie and brochure (n = 300), and those viewing both the NBS and DBS movies and brochures (n = 296). MAIN OUTCOMES AND MEASURES: Two to four weeks postpartum, women completed a 91-item survey by telephone, addressing knowledge, attitudes, and behavior with respect to opting out of NBS or DBS for their child. RESULTS: A total of 901 women (mean age, 31 years) were randomized and 664 completed the follow-up survey. The total correct responses on the knowledge instrument in regard to NBS were 69% in the usual care group, 79% in the NBS group, and 75% in the NBS + DBS group, a significant between-group difference (P < .05). Although all groups showed strong support for NBS, the percentage of women who were “very supportive” was highest in the NBS group (94%), followed by the NBS + DBS group (86%) and was lowest in the usual care group (73%) (P < .001). The interventions were not associated with decisions to decline newborn screening or withdraw residual DBS. Nine women stated that they had declined NBS (all the usual care group; P < .001). With respect to DBS, 5 participants indicated that they contacted the health department to have their child’s sample withdrawn after testing: 3 in the NBS + DBS group and 2 in the usual care group (P = .25). CONCLUSIONS AND RELEVANCE: Educational interventions can be implemented in the prenatal clinic, using multimedia tools and electronic platforms. Prenatal education is effective in increasing postnatal knowledge and support for these programs. These results are relevant to other contexts in which residual clinical specimens and data are used for research purposes. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02676245

Newborn screening is the largest genetic screening program in the United States with approximately four million newborns screened yearly. It has been available and in continuous development for more than 50 years. Each state manages, funds, and maintains its own individual program, which encompasses newborn screening as well as the diagnosis and coordination of care for affected infants and children. The ideal disorder for screening is one in which newborn intervention prevents later disabilities or death for infants who may appear normal at birth. There are 31 core conditions that are currently recommended for incorporation into state screening programs. To obtain a sample, several drops of blood are collected from the newborn's heel and applied to filter paper. Although testing for core disorders is fairly standardized, more extensive screening varies by state and the rigorous evaluation of new disorders for inclusion in state screening panels is ongoing. As genomic medicine becomes more accessible, screening newborns for chronic diseases that may affect their long-term health will need to be addressed as well as the use of the residual blood spots for research. Obstetric providers should, at some time during pregnancy, review the basic process of newborn screening with parents to prepare them for this testing in the neonatal period. This information can be reviewed as it best suits incorporation in an individual's practice; verbal discussion and the distribution of written materials with resources for further information are encouraged.

OBJECTIVE: Our purpose was to determine the detection and false-positive rates for maternal serum α-fetoprotein measurement to screen for fetal Down syndrome and other chromosomal abnormalities in women ≥35 years old. STUDY DESIGN: A total of 3896 women had serum maternal serum α-fetoprotein levels measured routinely before amniocentesis for the indication of advanced maternal age. RESULTS: Eighty-five percent (28/33) of fetal Down syndrome pregnancies had second-trimester risks of ≥1:270 on the basis of a combination of maternal serum α-fetoprotein measurement and maternal age. Risks were also ≥1:270 in 63% of the unaffected pregnancies. Sex chromosome aneuploidies, translocations, and other nonautosomal chromosome abnormalities in this study population were not associated with altered maternal serum α-fetoprotein levels; 51.9% (14/27) of these, however, were also assigned risks of ≥1:270. CONCLUSIONS: Maternal serum α-fetoprotein screening is more accurate than age alone for assigning individual Down syndrome risk in pregnant women ≥35 years old. Counseling for women in this age group should include information regarding the lower sensitivity of maternal serum α-fetoprotein screening for detecting fetal Down syndrome and other chromosomal abnormalities (especially sex chromosome aneuploidies) compared with offering amniocentesis to these women. (AM J OBSTET GYNECOL 1994; 170:80.)

We evaluated neonatal outcomes of apparently stillborn infants. The apparently stillborn neonate is born with an unexpected Apgar score of 0 at 1 minute and is subsequently successfully resuscitated. A retrospective cohort study was performed using electronic medical records for neonates >24 weeks' gestation born between 2002 and 2007. Adverse outcome was defined by the presence of seizures, encephalopathy, or death prior to hospital discharge. Differences in maternal demographics and clinical characteristics were compared between neonates with and without adverse outcomes at varying hospital settings. Ninety-three neonates were identified as apparently stillborn. Adverse outcomes occurred in 31.2% of neonates; 83.9% survived from birth to hospital discharge. Neonates with a 5-minute Apgar score

Achondrogenesis Type II (ACG2) is a lethal skeletal disorder caused by a dominant mutation in the type II collagen gene (COL2A1). Familial cases have been reported, suggesting both germline and somatic mosaicism. We report on two pregnancies from the same couple with gross, radiologic, and microscopic findings of ACG2. Molecular analysis of the second infant demonstrated heterozygosity for a c.2303G > A transition (p.Gly768Asp) in exon 33 of the COL2A1 gene. Although this mutation could not be proven by molecular studies in the first infant, identical findings in two affected pregnancies support germline mosaicism as the cause of ACG2 in this family.

The objective of this work was to study the prevalence of the Factor V Leiden mutation in an obstetrical clinic largely comprised of African-American women. A cross-sectional study was performed evaluating a total of 231 consecutive women of African-American origin. Of these patients, 21 were considered at high risk for thrombosis, but none was found to carry the mutation. One patient (0.4 per cent) of the total was heterozygous for the Factor V Leiden mutation. African-American women do not appear to be at an increased risk of being heterozygous or homozygous for the Leiden mutation. This low prevalence may be confounded by ascertainment bias in a population of pregnant women.

OBJECTIVE: Our purpose was to determine whether pregnancies affected by fetal Down syndrome resulting from Robertsonian translocations are associated with second-trimester maternal serum analyte levels different from those resulting from fetal trisomy 21. STUDY DESIGN: Pregnancies with Down syndrome caused by Robertsonian translocations were identified through the cytogenetics laboratories at the participating institutions. Those with maternal serum screening values between 15 and 20 weeks were evaluated. RESULTS: Eleven cases of fetal Down syndrome caused by Robertsonian translocations were identified. The median α-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels were 0.68, 0.67, and 2.83 multiples of the median, respectively. These analyte levels are similar to those for fetal trisomy 21. CONCLUSIONS: These data suggest that Down syndrome resulting from either Robertsonian translocations or trisomy 21 will be detected in a similar percentage of cases because the second-trimester maternal serum analyte levels are similar. (Am J Obstet Gynecol 1997;177:879-81.)

We present the prenatal evaluation and diagnosis of a disorganized chest wall hamartoma (with underlying sternal cleft in a family with a prior offspring with the VATER association. The possibility that these conditions are linked to mesodermal defects with a common pathogenic etiology is suggested. Copyright © 1996 International Society of Ultrasound in Obstetrics and Gynecology