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Cell-free DNA testing is increasingly being used to screen pregnant women for fetal aneuploidy. This technology may also identify microdeletion syndromes, including 22q11.2 deletion syndrome, the most common microdeletion syndrome, and the 22q11.2 duplication syndrome. The purpose of this paper is to provide an overview of the 22q11.2 deletion syndrome, to review the early experience with cell-free DNA screening for this deletion and to consider the potential benefits that may be associated with prenatal detection of the deletion. © 2016 John Wiley & Sons, Ltd.

Cell-free DNA (cfDNA) testing is increasingly being used to screen pregnant women for fetal aneuploidies. This technology may also identify fetal sex and can be used to screen for sex chromosome aneuploidies (SCAs). Physicians offering this screening will need to be prepared to offer comprehensive prenatal counseling about these disorders to an increasing number of patients. The purpose of this article is to consider the source of information to use for counseling, factors in parental decision-making, and the performance characteristics of cfDNA testing in screening for SCAs. Discordance between ultrasound examination and cfDNA results regarding fetal sex is also discussed.

Objectives The objective of this study was to identify maternal characteristics associated with a failed cell-free DNA (cfDNA) test due to a low fetal fraction (FF). Method Retrospective cohort study of women with singleton pregnancies who had cfDNA screening at 10-25 weeks gestation between October 2011 and January 2016. cfDNA screening was performed using methylation techniques until October 2013; thereafter, samples were run with massively parallel sequencing. Multivariable logistic regression was performed to identify maternal characteristics associated with no cell free DNA result secondary to low FF. Results Thirty-three (1.2%) of 2890 eligible women had a failed cfDNA test, including 18 (0.6%) cases with a low FF. A failed cfDNA test due to a low FF was associated with obesity (aOR 1.11, CI 1.05-1.18, p = 0.0003) and treatment with enoxaparin (aOR 37.5, 11.19 – 125.87, p

A normocephalic, severely retarded boy with a family history suggesting aqueductal stenosis was found by computerized tomography to have aqueductal stenosis. His parents' concurrent pregnancy was monitored by ultrasonography and amniocentesis; these disclosed a male fetus which developed marked hydrocephalus after the 20th week. The pregnancy was terminated and an autopsy of the fetus demonstrated several major CNS malformations in addition to a very narrowed aqueduct. This case illustrates the diffuse CNS disease present in at least some cases of X-linked aqueductal stenosis (XLAS) and the importance of considering this variable syndrome in normocephalic, non-dysmorphic mentally retarded males. Important aspects of the prenatal diagnosis of XLAS are also illustrated.

Genetic screening is used to identify individuals who have genetic variations or mutations that are associated with a particular disorder. Genetic screening may be useful to plan for periodic evaluation, implementation of preventive strategies, or initiation of therapeutic interventions. Current practice is to offer carrier screening for certain genetic diseases during the preconception encounter or more commonly as part of early prenatal care.

Cell-free DNA (cfDNA) testing is increasingly being used to screen pregnant women for fetal aneuploidies. This technology may also identify fetal sex and can be used to screen for sex chromosome aneuploidies (SCAs). Physicians offering this screening will need to be prepared to offer comprehensive prenatal counseling about these disorders to an increasing number of patients. The purpose of this article is to consider the source of information to use for counseling, factors in parental decision-making, and the performance characteristics of cfDNA testing in screening for SCAs. Discordance between ultrasound examination and cfDNA results regarding fetal sex is also discussed.

National strategies to control health care costs have resulted in earlier hospital discharge of many patient groups. Earlier discharge may reduce hospital charges and return patients to their families sooner. However, complications after discharge may go undetected and require readmittance to the hospital and more acute care visits (Britton & Britton, 1984; Jansson, 1985; Rogers et al., 1990; Schwartzberg, 1982). To maintain good patient outcomes while lowering hospital charges, a number of programs of early hospital discharge and home follow-up have been developed for groups of patients at high risk who use a high volume of services (Brooten et al., 1986; McCorkle et al., 1989). Women delivering by unplanned cesarean birth represent such a group. Almost one in four women who give birth in the United States do so by cesarean birth (Taffel, Placek, & Korsary, 1992). The hospital stay after cesarean birth has decreased from a mean of 6.1 days in 1982 to 4.0 days in 1992 (Commission on Professional & Hospital Activities, 1991; 1993). One recent report suggested a 2-day length of stay for women after delivery by cesarean birth, provided they had no complications during pregnancy and delivery and after delivery (Strong, Brown, Brown, & Curry, 1993). Many early discharge programs for high-risk groups have home follow-up services that differ in length, services, and provider (Meissier, 1993). Data are needed on the nurse's time required for home follow-up of childbearing women at high risk when care is based on patient need and provider judgment rather than the reimbursement plan. For women delivering by cesarean birth, most follow-up services have' included one or more home visits by a nurse. The number and length of visits often are dictated by reimbursement systems (Brooten, 1995). Institutions or agencies providing these services usually have a standard fee and maximum time for the visit based on the projected needs of that patient population. However, home visits of varying lengths of time may be necessary, depending on the needs of individual patients and the complexity of their care. Currently, little data are available on the following: (a) the time required by nurses to provide home care to different patient groups; (b) differences in nursing time required within those groups, depending on patient morbidity; and (c) the number and length of home visits or other contacts when dictated by patient need and provider judgment rather than patterns of reimbursement. The purpose of this study was to examine the average time nurses spent planning for early hospital discharge and providing home care to women who delivered by unplanned cesarean birth. It also examined differences in nursing care time required for patients with and without morbidity when dictated by patient need and provider judgment.

Dr Daley : Mrs J, a 35-year-old married attorney and mother of 2 preschool-aged children, is in her first trimester of pregnancy. She is considering maternal serum screening and/or amniocentesis for the detection of neural tube defects and chromosomal abnormalities. She is insured with a managed care organization through her husband's medical insurance. Mrs J is healthy and has had 3 previous pregnancies. Her first pregnancy was uncomplicated during gestation, with a 40-hour labor, ending in a cesarean delivery of a healthy boy at term. Her second pregnancy ended in a spontaneous miscarriage during the first trimester. In the first trimester of her third pregnancy, Mrs J's obstetrician, Dr O, offered her serum screening and/or amniocentesis. She and her husband declined both, feeling that the risks of neural tube defects and chromosomal abnormalities were low and that they would not be willing to terminate a pregnancy in the second trimester if

Testing cell-free DNA (cfDNA) in maternal blood samples has been shown to have very high sensitivity for the detection of fetal aneuploidy with very low false-positive results in high-risk patients who undergo invasive prenatal diagnosis. Recent observation in clinical practice of several cases of positive cfDNA tests for trisomy 18 and trisomy 13, which were not confirmed by cytogenetic testing of the pregnancy, may reflect a limitation of the positive predictive value of this quantitative testing, particularly when it is used to detect rare aneuploidies. Analysis of a larger number of false-positive cases is needed to evaluate whether these observations reflect the positive predictive value that should be expected. Infrequently, mechanisms (such as low percentage mosaicism or confined placental mosaicism) might also lead to positive cfDNA testing that is not concordant with standard prenatal cytogenetic diagnosis. The need to explore these and other possible causes of false-positive cfDNA testing is exemplified by 2 of these cases. Additional evaluation of cfDNA testing in clinical practice and a mechanism for the systematic reporting of false-positive and false-negative cases will be important before this test is offered widely to the general population of low-risk obstetric patients. In the meantime, incorporating information about the positive predictive value in pretest counseling and in clinical laboratory reports is recommended. These experiences reinforce the importance of offering invasive testing to confirm cfDNA results before parental decision-making.

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.)

The recent discovery of the cystic fibrosis gene has offered the possibility of population-based cystic fibrosis carrier screening. Although > 100 distinct mutations have been identified, five of these in aggregate represent about 85% of the alleles in Britain and the United States. Screening programs that test for these five mutations can be designed to offer several alternative ways to communicate the risk to a pregnancy and several alternative ways to manage a pregnancy. At this time we favor a strategy of screening partners in a couple in sequence, screening the second partner only if the first is positive; nevertheless, different strategies will appeal to different couples.

The aim of this study was to calculate the risk for aneuploidy in twin pregnancies between 9-14 weeks utilizing maternal age, race and dizygotic twinning rates. Using previously published risks for aneuploidy in singletons and twins at the time of amniocentesis and at term, we calculated new risk estimates for twins at 9-14 weeks gestation or at the time of chorionic villus sampling. Using these tables, the risk for trisomy 21 in at least one fetus of a twin gestation in a 32-year-old at 9-14 weeks is 1/285 for Whites and for African-Americans. This is equivalent to the risk for trisomy 21 (1/265) in a 35-year-old woman with a singleton at the same gestational age. The risks for trisomies 18 and 13 also follow similar trends. In counseling women with twin pregnancies at the time of first trimester nuchal translucency screening or chorionic villus sampling, it should be noted that the maternal age-related risk for aneuploidy for a 32-year-old is equivalent to that of a 35-year-old woman with a singleton gestation.

We describe a second family with mother to son transmission of omodysplasia, a rare skeletal dysplasia characterized by shortened humeri, shortened first metacarpals and craniofacial dysmorphism. The mother in this family had been diagnosed previously with Robinow syndrome; subsequently, her diagnosis was reclassified. Her pregnancy was closely monitored antenatally with serial ultrasound examinations. Delayed ossification of the humerus was noted prenatally. Her son had ambiguous genitalia and similar skeletal manifestations as his mother. A comparison to other known and suspected cases of dominant omodysplasia is presented. Our observations confirm the existence of a dominant variant of omodysplasia, document genital hypoplasia as an important feature of this syndrome in males and highlight the need to differentiate this entity from Robinow syndrome.

We report the mid-trimester prenatal diagnosis of Neu-Laxova syndrome (NLS) in two at risk families utilizing serial sonographic examinations. Ultrasound and pathologic findings from seven affected pregnancies, the largest case series of NLS to date, are presented. One fetus had anencephaly and incomplete rachischisis, an anomaly that has not been previously reported in association with NLS. Ultrasonographic detection of severe intrauterine growth restriction (IUGR), abnormally postured limbs, microcephaly, and edema allowed prenatal diagnosis of NLS in five of these at risk pregnancies during the mid-trimester. Growth curves derived from serial sonograms reveal abnormalities of all standard biometric measurements. The growth discrepancy was most pronounced in the measurements of the biparietal diameter, which were consistently less than two standard deviations below the mean across all gestational ages. This case series confirms that aberrant growth and anomalies may be detected sufficiently early in gestation to permit prenatal diagnosis of NLS.

Carrier screening for cystic fibrosis as part of reproductive health care, including prenatal care, is not the standard of practice at this time. However, a recent National Institutes of Health Consensus Development Conference recommended that cystic fibrosis carrier screening should be offered to adults with a family history of cystic fibrosis, partners of individuals with cystic fibrosis, couples planning a pregnancy, and couples seeking prenatal testing. A workshop convened to discuss the implementation of these recommendations concluded that several issues must be resolved before these recommendations can be implemented. This commentary reviews the discussions that occurred and the conclusions that were reached at this workshop. Some of the subjects considered by the workshop participants were: the goals and outcomes of carrier screening; the continuum from making a test available to offering that test; to whom, when, and how cystic fibrosis testing should be offered; laboratory practice and quality assurance; provider and patient education; and insurance issues. The workshop participants concluded that those populations to whom carrier screening should be offered might include individuals and couples in high-risk groups who seek preconception counseling, infertility care, or prenatal care. High-risk groups include individuals of white northern European or of Ashkenazi-Jewish descent, those whose partners have cystic fibrosis, and those with a family history of cystic fibrosis. Before screening can be offered systematically to these individuals or couples, practice guidelines, educational materials for providers and patients, informed-consent protocols, and laboratory standards for testing must be developed.

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 alpha-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.

OBJECTIVES: This paper explores several critical assumptions and methodological issues arising in cost-effectiveness analyses of genetic screening strategies in the reproductive setting. METHODS: Seven issues that arose in the development of a decision analysis of alternative strategies for cystic fibrosis carrier screening are discussed. Each of these issues required a choice in technique. RESULTS: The presentations of these analyses frequently mask underlying assumptions and methodological choices. Often there is no best choice. In the case of genetic screening in the reproductive setting, these underlying issues often touch on deeply felt human values. CONCLUSIONS: Space limitations for published papers often preclude explaining such choices in detail; yet these decisions determine the way the results should be interpreted. Those who develop these analyses need to make sure that the implications of important assumptions are understood by the clinicians who will use them. At the same time, clinicians need to enhance their understanding of what these models truly mean and how they address underlying clinical, ethical, and economic issues.

Among 179,663 prenatal diagnosis cases collected from ten institutions and two publications, 555 (0.3 per cent) were diagnosed as having chromosome mosaicism. Of these, 57 (10.3 per cent) were mosaic for an autosomal structural abnormality, 28 (5 per cent) for a sex chromosome structural abnormality, and 85 (15.3 per cent) were mosaic for a marker chromosome. Ninety-five cases of prenatally diagnosed mosaicism with a structural abnormality in an autosome and a normal cell line, and with a known phenotypic outcome, were collected for karyotype-phenotype correlations through our collaboration (40 cases), a prior survey (26 cases), and published reports (29 cases). They included 13 balanced reciprocal translocations, one unbalanced reciprocal translocation, four balanced Robertsonian translocations, four unbalanced Robertsonian translocations, four inversions, 17 deletions, three ring chromosomes, 19 i(20q), seven +i(12p), six other isochromosomes, and 17 partial trisomies resulting from a duplication or other rearrangement. All cases mosaic for a balanced structural rearrangement resulted in a normal phenotype. All cases of 46/46,i(20q) resulted in normal liveborns. Five of seven cases with 46/47,+i(12p) had an abnormal phenotype compatible with Killian-Pallister syndrome. The overall risk for an abnormal outcome for a mosaic case with an unbalanced structural abnormality, excluding 46/46,i(20q) and 46/47,+i(12p), is 40.4 per cent. In the same category, the study also suggested a correlation between the percentage of abnormal cells and an abnormal phenotype. For mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.

To evaluate quantitative hCG measurements and transvaginal ultrasound in the diagnosis of ectopic pregnancy in patients presenting to the emergency department.A discriminatory zone for detecting the presence or absence of an intrauterine pregnancy by transvaginal ultrasound was established prospectively. Women presenting to the emergency department were evaluated prospectively using a diagnostic algorithm consisting of clinical examination, quantitative serum hCG, and transvaginal ultrasound. Finally, ectopic pregnancies diagnosed over a 22-month period were evaluated prospectively.All viable intrauterine pregnancies were identified in those subjects with hCG levels of 1500 mIU/mL (First International Reference) or greater. One thousand two hundred sixty-three subjects were evaluated prospectively; 59.8% were diagnosed with intrauterine pregnancy, 26.8% with spontaneous abortion, and 7.8% with ectopic pregnancy. At presentation, 13.2% of intrauterine pregnancies were diagnosed by clinical examination, whereas 82.9% were diagnosed by transvaginal ultrasound. Only 4% of normal intrauterine pregnancies were not confirmed on initial visit. Of 205 ectopic pregnancies diagnosed, 81.5% were hemodynamically stable; of these, 49.1% were diagnosed on initial presentation. Of all ectopics, 59% never reached an hCG level of 1500 mIU/mL and 35.8% had an hCG lower than the level at presentation. This protocol diagnosed ectopic pregnancies with a sensitivity of 100% and a specificity of 99.9%.A protocol of quantitative hCG levels (available within hours of presentation to an emergency department) combined with transvaginal ultrasound is effective in diagnosing ectopic pregnancy.

To determine the safety, efficacy, and cost savings of early hospital discharge of women delivered by unplanned cesarean delivery.Using randomized assignment, 61 postpartum women were discharged from the hospital at the usual time, and 61 were discharged early and had nurse specialist home follow-up care. The latter group received comprehensive discharge planning, instruction, counseling, home visits, and daily on-call availability from the nurse specialists. Both groups were followed from delivery to 8 weeks postpartum.Women who were discharged early and received transitional home care services by clinical nurse specialists were sent home a mean of 30.3 hours earlier than the control group (P.001). They had significantly greater satisfaction with care, more of their infants had timely immunizations at the end of follow-up, and they had a 29% reduction in health care charges compared to the control group receiving routine care. Although there were no statistically significant differences in maternal and infant rehospitalizations and acute-care visits, there were more maternal rehospitalizations in the control group than in the nurse specialist-followed group (three versus zero). No statistically significant differences were found between the groups in the outcomes of maternal affect and overall functional status.Early hospital discharge of women after unplanned cesarean birth, using the model of nurse specialist transitional home care, is safe, feasible, and cost-effective.

Both a cross-sectional and a longitudinal study were performed to investigate whether or not the collection time should be taken into consideration when generating a patient's risk for fetal Down syndrome with multiple marker screening. Diurnal variations of third-trimester alpha-fetoprotein (AFP) levels and first-trimester human chorionic gonadotropin (hCG) levels have been previously reported. In addition, large episodic fluctuations of conjugated and unconjugated oestriol (uE3) as well as a diurnal variation have also been reported in the third trimester. If the levels of these analytes routinely fluctuate during the day, they could affect a patient's risk calculation for fetal Down syndrome. The longitudinal study evaluated ten non-diabetic women who underwent sequential sampling for AFP, hCG, and uE3. The cross-sectional study evaluated 1953 patients for these three markers whose time of sampling was recorded between 8·00 a.m. and 5·59 p.m. Using either study design, no significant effect was seen in the median MOM levels of the screening analytes as a function of the time of day.

Second-trimester maternal serum screening is a noninvasive means of identifying pregnant women at an increased risk for various conditions including a fetus with open spina bifida, fetal Down syndrome, trisomy 18, multiple gestation, and adverse pregnancy outcome. Combinations of several different markers are available for screening. These include alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol. In this review, we discuss the benefits and limitations of the screening tests and the suggested protocols for the care of patients.

Osteogenesis imperfecta (OI) Type II is a rare heritable disorder of bone matrix that results in catastrophic congenital skeletal dysplasia. Two cases of OI Type II had symmetric rhizomelic skeletal dysplasia apparent on ultrasound at 16 and 20 weeks' gestation. Histologic and histochemical studies performed on skeletal tissue from fetal autopsies showed the following: (1) abnormal growth plate tissue characterized by failure of formation of primary bony spongiosa; (2) persistence of calcified cartilage bars in the diaphysis; (3) metaphyseal microfractures; (4) abundant cartilaginous fracture callus; (5) absence of bony callus; (6) failure of formation of intramembranous cortical diaphyseal bone; (7) angulation of long bones in portions of the metadiaphyses bordered by fracture callus; and (8) mechanical failure of the perichondral ring of LaCroix with a normal fibrous ossification groove of Ranvier. These findings suggest that skeletal dysplasia in OI Type II results from the action of muscular forces on a skeleton weakened by a complex disorder of endochondral and intramembranous ossification. The paucity of primary metaphyseal trabeculae and subperiosteal cortical bone leads to pathologic fractures of the immature fiber bone and an imperfect attempt at fracture repair. Angulation and shortening of long bones occurs between numerous sites of focal endochondral fracture callus. Mechanical failure of the fibrous perichondral ring leads to further collapse and shortening without obvious functional impairment of the fibrous ossification groove. Perinatal lethal OI provides insight into how a molecular disorder predominantly of Type I collagen metabolism results in pathology of numerous tissues, leading to severe skeletal dysplasia without primarily affecting chondrogenesis.

Between March 1986 and April 1990, 22 consecutive fetuses (at gestational ages of 21 to 38 weeks) with a suspected diagnosis of critical (ductus-dependent) left ventricular outflow tract obstruction on fetal echocardiogram were referred to our center for delivery and surgical treatment. Diagnoses were hypoplastic left heart syndrome (n = 16), valvular aortic stenosis (n = 2), common atrioventricular canal with subaortic stenosis (n = 3), and single ventricle with subaortic stenosis (n = 1). Postnatal echocardiography revealed that fetal echocardiography was correct in predicting left ventricular outflow tract obstruction to be critical in all but one patient, for a positive predictive value of 96%. Of the 21 patients with true, critical left ventricular outflow tract obstruction, 17 patients underwent cardiac surgery as neonates (birth to 6 days of age, median 2 days); 13 (or 77%) survived and were discharged from the hospital. In addition, one patient underwent successful balloon aortic valvotomy for critical valvular aortic stenosis but later died of sepsis. Lethal chromosomal and congenital abnormalities should be sought and are contraindications for this approach. In utero transport of fetuses with suspected critical left ventricular outflow tract obstruction to a neonatal cardiac surgical center can result in improved neonatal condition and may improve overall survival.

The optimal management of immune thrombocytopenic purpura during pregnancy remains controversial because the risk of severe neonatal thrombocytopenia remains uncertain. We studied the outcome of the index pregnancy in 162 women with a presumptive diagnosis of immune thrombocytopenic purpura to determine the frequency of neonatal thrombocytopenia and to determine whether neonatal risk could be predicted antenatally by history or platelet-antibody testing.Two maternal characteristics were identified as predicting a low risk of severe neonatal thrombocytopenia: the absence of a history of immune thrombocytopenic purpura before pregnancy, and the absence of circulating platelet antibodies in the women who did have a history of the condition. Eighteen of 88 neonates (20 percent; 95 percent confidence interval, 13 to 30 percent) born to women with a history of immune thrombocytopenic purpura had severe thrombocytopenia (platelet count less than 50 x 10(9) per liter at birth), as compared with 0 of 74 (0 percent; 95 percent confidence interval, 0 to 5 percent) born to women first noted to have thrombocytopenia during pregnancy (P less than 0.0001). Among the women with a history of immune thrombocytopenic purpura, 18 of 70 neonates (26 percent; 95 percent confidence interval, 16 to 38 percent) born to those with circulating platelet antibodies had severe thrombocytopenia, as compared with 0 of 18 infants (0 percent; 95 percent confidence interval, 0 to 18.5 percent) born to those without circulating antibodies (P less than 0.02). Thus, the risk of severe neonatal thrombocytopenia in the offspring of women without a history of immune thrombocytopenic purpura before pregnancy and of women with a history of the condition in whom circulating platelet antibodies are not detected was 0 percent (95 percent confidence intervals, 0 to 5 and 0 to 18.5 percent, respectively).The absence of a history of immune thrombocytopenic purpura or the presence of negative results on circulating-antibody testing in pregnant women indicates a minimal risk of severe neonatal thrombocytopenia in their offspring.

During an 8-year period, we managed 42 women with 101 pregnancies with previously diagnosed but uncorrected uterine malformations referred to our institution for high-risk obstetric care. All patients were managed under the same standardized protocol requiring weekly visits and decreased physical activity. The population studied consisted of four groups of pregnancies with the following uterine anomalies: unicornuate (five), bicornuate (61), septate (25), and didelphys (ten). Sixty percent of the pregnancies in the unicornuate and didelphys group reached term, 39% in the bicornuate group, and 48% in the septate group. Preterm labor requiring tocolysis occurred in 21% of the pregnancies in the bicornuate group and 15% of the pregnancies in the septate group. Cerclage was placed in 5% of the pregnancies in the bicornuate group. Before our care, the fetal survival rate for pregnancies in the bicornuate and septate groups was 52 and 53%, respectively; with our management protocol, it was 58 and 65%, differences that were not statistically significant. Our experience suggests that high-risk obstetric intervention does not obviate the potential benefit of metroplasty, especially for patients with a bicornuate or septate uterus. We believe that traditional indications for metroplasty should continue to be used.

During an 8-year period, we managed 42 women with 101 pregnancies with previously diagnosed but uncorrected uterine malformations referred to our institution for high-risk obstetric care. All patients were managed under the same standardized protocol requiring weekly visits and decreased physical activity. The population studied consisted of four groups of pregnancies with the following uterine anomalies: unicornuate (five), bicornuate (61), septate (25), and didelphys (ten). Sixty percent of the pregnancies in the unicornuate and didelphys group reached term, 39% in the bicornuate group, and 48% in the septate group. Preterm labor requiring tocolysis occurred in 21% of the pregnancies in the bicornuate group and 15% of the pregnancies in the septate group. Cerclage was placed in 5% of the pregnancies in the bicornuate group. Before our care, the fetal survival rate for pregnancies in the bicornuate and septate groups was 52 and 53%, respectively; with our management protocol, it was 58 and 65%, differences that were not statistically significant. Our experience suggests that high-risk obstetric intervention does not obviate the potential benefit of metroplasty, especially for patients with a bicornuate or septate uterus. We believe that traditional indications for metroplasty should continue to be used.

Here we describe a fetus in whom a cystic hygroma was detected by ultrasound during the second trimester. Autopsy demonstrated a female fetus with manifestations of Ullrich-Turner syndrome, including gonadal dysgenesis, generalized lymphedema, and preductal aortic coarctation. Surprisingly, the karyotype was 46,XY, with no evidence of mosaicism for a 45,X cell line. Y-DNA hybridization studies demonstrated a deletion of the sex-determining segment of the short arm of the Y chromosome. This is the first report, in a fetus, of XY Ullrich-Turner syndrome due to a Y chromosome deletion.

Midtrimester (14–22 weeks of gestation) amniotic fluid hormone levels were measured as indicators of fetal sex in 99 pregnancies (66 with a male fetus and 33 with a female fetus). Statistically significant didfferences in testosterone (T), androstenedione (A), and follicle stimulating hormone (FSH) levels were observed between pregnancies with fetuses of differing sex. No significant difference was observed for estrone (E1), estradiol (E2), or progesterone (P) levels. Fetal sex was accurately predicted in 96 of 99 pregnancies using a criterion of T ≥ 100 pg/ml for males and in 94 of 99 pregnancies using a criterion of FSH ≥ 3 mIU/ml for females. In the 3 cases in which the fetus was male but the T level was < 100 pg/ml, the FSH was clearly in the male range. Likewise, in 5 cases in which the fetal sex was not correctly predicted by the FSH level, the T level confirmed the karyotype. It is proposed that measurement of amniotic fluid testosterone levels would be of value in detecting errors in prenatal cytogenetic diagnosis when there is incorrect fetal sexing. It is suggested that FSH determinations be performed when the amniotic fluid testosterone does not confirm the karyotype, and that when there is a discrepancy between the karyotype and both of these measurements, repeat amniocentesis should be considered.

A retrospective study of a trial of labor (TOL) after prior cesarean section was conducted over 18 months in a patient population that is homogeneous with regard to race, socioeconomic class, gestational age, and medical complications. Of 171 women who had undergone previous cesarean sections, 75 were offered a TOL. Thirty-five of these patients had an elective repeat cesarean section, while 40 agreed to a TOL. Thirty-two of the latter patients delivered vaginally (80%). The criteria for offering a TOL and a protocol for TOL are presented. A comparison of the maternal and neonatal morbidity associated with repeat cesarean section versus TOL do not strongly favor either method of delivery in our population. The patients who had undergone cesarean section for cephalopelvic disproportion (CPD) had the lowest acceptance and the lowest success rate of a TOL. The hospital charges and hospital stay of the two groups are presented. The financial aspects of the two methods of delivery and the impact of Diagnosis Related Groups (DRGs) on the management of these patients are discussed. Careful selection of patients for a TOL is essential to maintain the quality of medical care while responding to pressures to reduce the cesarean section rate and to reduce the costs of medical care.

The nature and origins of amniotic fluid ALP activity Were investigated early (14 to 22 weeks) and late (25 to 44 weeks) in pregnancy. The lotal enzyme activities for both stages were significantly different and considerable changes in the activities of individual enzyme components occurred. Early activity consists of intestinal (81%.}, bone/liver/kidney (15%), and placental (4%) ALP. In late fluids, the values are 5%, 69%, and 27%, respectively. The intestinai enzyme is shown to be of fetal origin, presumably arising from the direct entry of deSquamated Intestinal mucosal cells into the amniotic fluid. The bone/liver/kidney enzyme is mostly of maternal serum origin early with an increased fetal contribution toward term. Early in pregnancy, the placental ALP activity is probably derived both directly from the placenta and from the placental activity in maternal serum. The latter source contributes more toward term.

Three cases of large postpartum vulvovaginal hematomas are reported. After conservative measures including incision and drainage, ligation of bleeding sites, vaginal packing and replacement of volume and coagulation factors failed to control the bleeding in each, pelvic angiography was performed. Brisk arterial bleeding demonstrated on arteriography was controlled by Gelfoam embolization in all three cases. Intra- or postpartum hematologic evaluation revealed a previously undiagnosed coagulation disorder in each patient. The authors suggest that angiography be considered before hypogastric artery ligation whenever possible in patients with large postpartum hematomas and that all such patients be evaluated for coagulopathy.

With the introduction of silicone indwelling cerebrospinal fluid (CSF) shunts in the 1960s, the prognosis for children with hydrocephalus changed dramatically. These individuals are leading normal and productive lives today. Many women with CSF shunts are not entering the childbearing years. Previously, only 13 cases of pregnancy occurring in patients with CSF shunts have been reported. We present two cases here and review the complications and outcome of the other reported cases. Shunt malfunction appears to be common in pregnancy due to increased intraperitoneal pressure and the enlarging uterus. Rarely is surgical correction or premature delivery necessary. A successful pregnancy ending in the vaginal delivery of a term infant can be expected in the majority of these patients.

To determine the recurrence risk for patients with one prior pregnancy affected with neural tube defects (NTD), the authors have pooled data from eight testing centers. In 831 pregnancies studied because one sib was affected with an NTD, the recurrence rate was 3.0%, with 95% confidence limits of 2.0-4.3%, and 99% confidence limits of 1.8-4.8%. The recurrent lesion, whether spina bifida or anencephaly, tended to be concordant with the first to a significant degree. Only 12.2% of recurrent NTD were different from the first, with 95% confidence limits of 4.1-26.2%, and 99% confidence limits of 1.7-30.9%. Both an accurate recurrence risk and the information that a recurrent NTD lesions tends to be concordant with that in the first affected child are useful in the genetic counseling of patients in the United States and in the selection of appropriate prenatal diagnostic studies.

Ninety-seven amniotic fluid (AF) specimens, 67 with male fetuses and 30 with female fetuses, were obtained by amniocentesis at 14 to 18 weeks of gestation for analysis of free and protein-bound estrone (E 1 ), estradiol (E 2 ), androstenedione (A), testosterone (T), and progesterone (P). Ten maternal plasma (MP) samples of comparable gestational age were analyzed for the same free and protein-bound steroids. Significantly lower total E 1 , E 2 , A, and T, but not P, levels were found in AF when compared to MP. The percentage of free steroids was higher in AF than in MP, while the percentage of specific protein-bound steroids was lower in the AF than in MP. Free (unbound) steroid levels of E 1 and P were higher in AF than in MP, whereas levels of E 2 were lower in AF than in MP. The free A and T levels in MP were lower than in AF with male fetuses, yet higher than in AF with female fetuses. Possible biologic activity of steroids in this fluid may depend on the dynamic balance between the free, the specific protein-bound, and the nonspecific protein-bound steroids.

Over the past decade, the ability to diagnose neural tube defects has changed from being limited to radio-graphic detection of anencephaly during later pregnancy to highly reliable diagnosis of the majority of neural tube defects during the early second trimester. Aspects of prenatal diagnosis of neural tube defects relevant to the perinatologist are discussed.

Mosaicism for a structural chromosome abnormality in amniotic cell cultures indicative of true fetal mosaicism is a rare event. In addition to the laboratory findings the clinical interpretation for counseling in such cases is based on observation of the same abnormality in liveborns as well as previous experience with prenatal diagnosis of the same or similar abnormalities. We report here the prenatal diagnosis of 46,XX/46,XX,-21,+t( 21q21q ) which was confirmed in fetal skin cell and amnion cell cultures.

An evaluation of 227 consecutive twin gestations was undertaken to assess the role of ultrasound (US) in the diagnosis of major obstetric complications and congenital anomalies. US accurately depicted the growth and development of fetuses in 65 patients with underlying maternal disorders that produced additional risks to the pregnancy. Complications such as malpresentations (104 cases), polyhydramnios (15 cases), oligohydramnios (five cases), and uterine myomas (seven of 11 cases) were demonstrated prenatally with US. Fetal anomalies included anencephaly (two cases), hydrocephalus (two cases), conjoined twins (three cases), twin-twin transfusion syndrome (five cases), and acardiac monsters (two cases). Demise of one twin in 20 gestations and demise of both twins in 18 gestations (overall mortality of 17%) were correctly identified with US. These 38 gestations included intrauterine demise in 12, spontaneous abortion in 13, and neonatal deaths in 13. Therefore, when multiple gestations are suspected clinically, serial real-time US scans should be obtained beginning in the first trimester.

This article has detailed the common prenatal sonographic findings that have been detected in fetuses with Down syndrome, trisomy 13, trisomy 18, Turner syndrome, and triploidy. It should be noted that not all fetuses with these five chromosomal abnormalities will have sonographically detectable malformations and that some may not be easily recognizable even at birth. It is crucial that the approach to the patient with a sonographically detected fetal malformation be thorough, systematic, and expeditious. The first step is to attempt to accurately define the abnormality. Next, syndromes with which this malformation are associated should be researched and a differential diagnosis constructed. Based on this differential, accompanying findings with which this abnormality is often associated should be looked for sonographically. A detailed history including pedigree information, possible teratogen exposure, consanguinity, and ancestry is imperative. In some cases a Mendelian disorder may be identified by obtaining a thorough prenatal genetic history. In virtually all cases of prenatally detected fetal malformations, chromosome analysis is indicated. Amniocentesis is the most common means of fetal chromosome analysis, but usually takes at least 2 weeks for results. In cases where the gestation is approaching the legal limit for elective termination, rapid karyotyping by percutaneous umbilical cord sampling should be considered and referral to a center familiar with this procedure is suggested. Chromosome analysis from fetal blood takes approximately 3 days to accomplish. Alternatively, rapid karyotyping by transabdominal chorionic villus biopsy may also be accomplished and has been performed as late as 37 weeks gestation. This procedure may be especially advantageous in cases where oligohydramnios is present. If a chromosomal abnormality is identified, genetic counseling should be arranged to discuss prognosis, cause, recurrence risks and to help the parents through this difficult time. If applicable, the option of pregnancy termination should be offered. Not all parents faced with a chromosomally abnormal fetus will wish to terminate their pregnancy and others may be too late in gestation to consider this option. In these cases, discussions with other families raising similarly affected children, social workers, clergy, psychiatrists, and geneticists may be helpful to the parents. Late pregnancy prenatal cytogenetic diagnosis may be beneficial both to the parents in helping prepare them psychologically and emotionally for an adverse outcome and in guiding obstetric management.(ABSTRACT TRUNCATED AT 400 WORDS)

Sonography has been used widely in the evaluation of singleton fetal growth. Twin gestations, however, have received less careful attention. In a statistical study of 103 twin pregnancies, the growth patterns of twin biparietal diameter (BPD), fetal femur length (FFL), and abdominal circumference (AC) were compared with those of singletons. The results of the study revealed a decrease in twin BPD growth after 31 to 32 weeks of gestation relative to singletons. Twin AC growth rate decreases after 32-33 weeks of gestation relative to singletons, but the twin FFL growth pattern does not deviate from that of singletons throughout gestation. Because of the significant difference in growth patterns of BPD and AC between twins and singletons in our population, new growth charts for twin BPD and AC are proposed.

Serum iron was measured in 30 patients with pregnancy-induced hypertension and 24 normal pregnant women. The mean iron concentration was significantly higher in the group with pregnancy-induced hypertension (111 +/- 26 micrograms/ml) than in the controls (69 +/- 17 micrograms/ml) (p less than 0.0001). Readily available laboratory variables were used to determine whether the increased serum iron was the result of (1) hemolysis, (2) hepatocellular injury, or (3) intravascular volume contraction leading to hemoconcentration. It appears that a clinically silent, ongoing hemolytic reaction is responsible for the increase in serum iron seen in patients with pregnancy-induced hypertension.

Two pregnancies at risk for Wolman disease were monitored by assay and electrophoresis of acid lipase in cultured amniotic-fluid cells. Cells from patient 1 had 5% of control levels of acid lipase, using 14C-triolein as substrate; however, when artificial substrates (esters of 4-methylumbelliferone and p-nitrophenol) were used to measure acid lipase, these cells had 30% of control levels. Electrophoresis of cell extracts revealed the absence of the A form of acid lipase, consistent with the diagnosis of Wolman disease. Analysis of fetal tissues following prostaglandin termination of this pregnancy confirmed the diagnosis. Assay of fetal-skin fibroblasts with 14C-triolein, as well as with artificial substrates, showed marked deficiency of acid lipase activity. Electrophoresis of fetal-tissue extracts also demonstrated the absence of the A form of acid lipase. Amniotic-fluid cells from patient 2 showed normal levels of acid lipase with all substrates tested; the electrophoretic pattern of acid lipase was normal. The results suggest that the prenatal diagnosis of Wolman disease be made using the radioassay of acid lipase and/or electrophoresis.