Early ultrasound diagnosis of Neu-Laxova 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.

Duplication of chromosome region 4q28.3-qter in monozygotic twins with discordant phenotypes.

We describe monozygotic twins with partially discordant phenotypes who were found to have a duplication of chromosome region 4q28.3-qter. The duplicated region of chromosome 4 resulted from an unbalanced segregation of a balanced maternal (4;22)(q28.3;p13) translocation. Duplication of the long arm of chromosome 4 has been described in >60 patients; however, it usually results from the unbalanced segregation of a parental balanced translocation and has an associated monosomy. Twenty cases of dup 4q without an associated monosomy have been reported, and this is the only case of dup 4q28. 3-qter. All cases of dup 4q are reviewed, and phenotypic aspects are analyzed. Issues of monozygotic twinning and other birth defects also are addressed.

Screening for cystic fibrosis carrier state.

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.

Carrier screening for cystic fibrosis: costs and clinical outcomes.

OBJECTIVES: To evaluate the costs and clinical effects of 16 alternative strategies for cystic fibrosis (CF) carrier screening in the reproductive setting; and to test the sensitivity of the results to assumptions about cost and detection rate, stakeholder perspective, DNA test specificity, chance of nonpaternity, and couples' reproductive plans. METHOD: Cost-effectiveness analysis. RESULTS: A sequential screening strategy had the lowest cost per CF birth avoided. In this strategy, the first partner was screened with a standard test that identifies 85% of carriers. The second partner was screened with an expanded test if the first partner's screen was positive. This strategy identified 75% of anticipated CF births at a cost of $367,000 each. This figure does not include the lifetime medical costs of caring for a patient with CF, and it assumes that couples who identify a pregnancy at risk will choose to have prenatal diagnosis and termination of affected pregnancies. The cost per CF birth identified is approximately half this figure when couples plan two children. CONCLUSIONS: The cost-effectiveness of CF carrier screening depends greatly on couples' reproductive plans. CF carrier screening is most cost-effective when it is performed sequentially, when the information is used for more than one pregnancy, and when the intention of the couple is to identify and terminate affected pregnancies. These conclusions are important for policy considerations regarding population-based screening for CF, and may also have important implications for screening for less common diseases.

Does cesarean section decrease the incidence of major birth trauma?

OBJECTIVE: To determine whether the increase in frequency of cesarean section is associated with a decreased incidence of major birth trauma. STUDY DESIGN: A retrospective cohort study was performed evaluating all neonatal cases of major birth trauma from January 1989 to December 1994. Major birth trauma was defined as peripheral plexus or nerve injuries, fractures, or lacerations. The data were grouped into two mutually exclusive periods (January 1989 to December 1990 vs January 1991 to December 1994) in which a significant difference in the cesarean section rate was known. RESULTS: Of 17,957 deliveries during the period, 141 cases of birth trauma occurred. One hundred thirty-seven of the 141 medical records were available for review, and 116 were classified as having had major birth trauma and were included in the study. The overall incidence of major birth trauma was 6.5/1000 deliveries. During the two-year period (January 1989 to December 1990), 18.3% of deliveries were by cesarean section and the major birth trauma rate was 8.4/1000 deliveries. During the following 4 years, the cesarean section rate was 22.3% and the major birth trauma rate was 5.3/1000 deliveries. Significant differences in the birth trauma chi(2) = 6.12, p = 0.013) and cesarean section (chi(2) = 40.80, p < 0.001) rates were observed. Controlling for the mode of delivery lessened the association between time period and birth trauma incidence (chi(2)MH = 3.28, p = 0.07). A significant decrease in the occurrence of major birth trauma in neonates delivered by cesarean section in the later period was discovered (relative risk = 0.46, 95% confidence interval 0.22 to 0.97). This decrease appeared to be mediated by a decrease in total lacerations between the periods (chi(2) = 11.76, p < 0.001), because the rates of other types of major birth trauma did not differ in neonates delivered by cesarean section or the vaginal route. CONCLUSIONS: With a 4% increase in rate of cesarean section at our institution, a significant decrease in the occurrence of major birth trauma was observed. This finding cannot be explained by a decreased risk of neonatal trauma in patients delivering vaginally, but rather by a decreased risk of neonatal trauma at cesarean section during the latter period.

Disseminated congenital neuroblastoma involving the placenta.

Neuroblastoma, a tumor of primitive neuroectodermal cells, is one of the most common solid malignancies of neonates. Placental metastases have been described in rare cases of congenital neuroblastoma, usually in association with hydrops fetalis, placentomegaly, and widespread disease in the neonate. We report a case in which the unexpected diagnosis of neuroblastoma was made based on the postnatal finding of tumor emboli confined to fetal vessels of the placenta. Radiation and chemotherapy were given based on this diagnosis, obviating the need for an invasive diagnostic procedure.

Prenatal characteristics of congenital nephrosis: results of a survey.

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.

Early discharge and home care after unplanned cesarean birth: nursing care time.

OBJECTIVE: This study examined the mean nursing time spent providing discharge planning and home care to women who delivered by unplanned cesarean birth and examined differences in nursing time required by women with and without morbidity. DESIGN: A secondary analysis of nursing time from a randomized trial of transitional care (discharge planning and home follow-up) provided to women after cesarean delivery. SETTING: An urban tertiary-care hospital. PATIENTS: The sample (N = 61) of black and white women who had unplanned cesarean births and their full-term newborn was selected randomly. Forty-four percent of the women had experienced pregnancy complications. INTERVENTIONS: Advanced practice nurses provided discharge planning and 8-week home follow-up consisting of home visits, telephone outreach, and daily telephone availability. OUTCOME MEASURE: Nursing time required was dictated by patient need and provider judgment rather than by reimbursement plan. RESULTS: More than half of the women required more than two home visits; mean home visit time was 1 hour. For women who experienced morbidity mean discharge planning time was 20 minutes more and mean home visit time 40 minutes more. CONCLUSIONS: Current health care services that provide one or two 1-hour home visits to childbearing women at high risk may not be meeting the education and resource needs of this group.

Genetic screening for reproductive planning: methodological and conceptual issues in policy analysis.

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.

Incidence and significance of chromosome mosaicism involving an autosomal structural abnormality diagnosed prenatally through amniocentesis: a collaborative study.

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.

Periconceptional folic acid supplementation as a social intervention.

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.

Prompt diagnosis of ectopic pregnancy in an emergency department setting.

OBJECTIVE: To evaluate quantitative hCG measurements and transvaginal ultrasound in the diagnosis of ectopic pregnancy in patients presenting to the emergency department. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

A randomized trial of early hospital discharge and home follow-up of women having cesarean birth.

OBJECTIVE: To determine the safety, efficacy, and cost savings of early hospital discharge of women delivered by unplanned cesarean delivery. METHODS: 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. RESULTS: 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. CONCLUSION: Early hospital discharge of women after unplanned cesarean birth, using the model of nurse specialist transitional home care, is safe, feasible, and cost-effective.

Second-trimester diurnal variation of maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated oestriol: is it present and does it affect the prediction of a patient's risk for fetal Down syndrome?

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.

Maternal serum alpha-fetoprotein screening for chromosomal abnormalities: a prospective study in women aged 35 and older.

OBJECTIVE: Our purpose was to determine the detection and false-positive rates for maternal serum alpha-fetoprotein measurement to screen for fetal Down syndrome and other chromosomal abnormalities in women > or = 35 years old. STUDY DESIGN: A total of 3896 women had serum maternal serum alpha-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 > or = 1:270 on the basis of a combination of maternal serum alpha-fetoprotein measurement and maternal age. Risks were also > or = 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 alpha-fetoprotein levels; 51.9% (14/27) of these, however, were also assigned risks of > or = 1:270. CONCLUSIONS: Maternal serum alpha-fetoprotein screening is more accurate than age alone for assigning individual Down syndrome risk in pregnant women > or = 35 years old. Counseling for women in this age group should include information regarding the lower sensitivity of maternal serum alpha-fetoprotein screening for detecting fetal Down syndrome and other chromosomal abnormalities (especially sex chromosome aneuploidies) compared with offering amniocentesis to these women.