The intent of this study was to document current practices in breast cancer genetic counseling and identify areas of variability for patients with a variant of uncertain significance (VUS) in the BRCA1 or BRCA2 gene. Registered members of the National Society of Genetic Counselors (NSGC) Cancer Special Interest Group (SIG) were sent an invitation via electronic mail to participate in an online questionnaire. The questionnaire was divided into three sections: clinical experience, clinical meaning, and risk perceptions and clinical recommendations for clinical situations involving a VUS. Fifty-seven of the eligible members responded. During the pre-test counseling session for a BRCA risk assessment patient, the vast majority of counselors (80.7%) mention VUS as a possible test result. Nearly half, 49.1%, report having given such a result to their patients at least one to four times. However, only 63.2% felt as though their patients understood the meaning of a VUS result. When asked to conclude the implication of a VUS and make medical management recommendations, the responses were varied. Nevertheless, a good proportion of counselors expressed the importance of testing other family members to help clarify the proband's risk and aid in medical management issues. Although the recent recommendations by the American College of Medical Genetics suggest standards for the interpretation of sequence variations, they do not provide guidelines for making clinical recommendations based on these variations. The results of this study reveal significant diversity in the personal interpretation of a VUS result, leading to various clinical recommendations, and suggest a need for clinical management recommendations as well.

The underlying cause of polyhydramnios, rather than the relative excess of amniotic fluid as defined by this study, appears to determine when preterm labor will occur.

Cornelia de Lange syndrome (CdLS) is a genetic disorder associated with delayed growth, intellectual disability, limb reduction defects and characteristic facial features. Germline mosaicism has been a described mechanism for CdLS when there are several affected offspring of apparently unaffected parents. Presently, the recurrence risk for CdLS has been estimated to be as high as 1.5%; however, this figure may be an underrepresentation. We report on the molecularly defined germline mosaicism cases from a large CdLS database, representing the first large case series on germline mosaicism in CdLS. Of the 12 families, eight have been previously described; however, four have not. No one specific gene mutation, either in the NIPBL or the SMC1A gene, was associated with an increased risk for germline mosaicism. Suspected or confirmed cases of germline mosaicism in our database range from a conservative 3.4% up to 5.4% of our total cohort. In conclusion, the potential reproductive recurrence risk due to germline mosiacism should be addressed in prenatal counseling for all families who have had a previously affected pregnancy or child with CdLS.

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Objective: To evaluate maternal and fetal factors associated with congenital malformations in patients with polyhydramnios. Study Design: The study group consisted of 275 singleton pregnancies with an amniotic fluid index (AFI) >25.0 cm. An equal number of controls were matched for maternal age, gravidity, parity and gestational age. The proportion of cases and controls with malformations was compared. Polyhydramnios cases were categorized into three groups by severity: mild (AFI 25–30 cm), moderate (AFI: 30.1–35.0 cm) and severe (AFI >35.1 cm). Among cases, logistic regression analysis was utilized to estimate the risk for fetal congenital malformations in relation to severity of polyhydramnios, estimated fetal weight, maternal diabetic status and gestational age at delivery. Results: Congenital malformations were detected in 40 of 275 cases (14.5%) with polyhydramnios and in 9 cases (3.3%) of the control group (p < 0.01). The relative risks of congenital malformations increased with the severity of polyhydramnios: 3.2 (95% CI 1.5–6.8), 5.7 (95% CI 2.4–13.3) and 13.1 (95% CI 5.8–29.5) for mild, moderate and severe polyhydramnios, respectively. Congenital malformations among polyhydramnios cases were present in 54.5% of small-for-gestational age fetuses, in contrast to 12.7% for average-for-gestational age fetuses and 10.8% for large-for-gestational age fetuses (p < 0.001). Maternal diabetic status did not significantly affect the fetal anomaly rate once polyhydramnios was detected. Premature newborns in the polyhydramnios group had a higher malformation rate (24%) than did term newborns (11.3%) (p < 0.02). In the study group, multiple logistic analysis confirmed the significance of severe polyhydramnios, small-for-gestational age status and preterm delivery as independent contributors to the malformation risk. Conclusions: Polyhydramnios (AFI >35 cm), small-for-gestational age fetus and preterm delivery are independent risk factors for congenital malformations.

Objective To use ultrasound to explore the impact of malaria in pregnancy on fetal growth and newborn outcomes among a cohort of women enrolled in an intermittent presumptive treatment in pregnancy (IPTp) with sulfadoxine/pyrimethamine (SP) program in coastal Kenya. Methods Enrolled women were tested for malaria at first prenatal care visit, and physical and ultrasound examinations were performed. In total, 477 women who had term, live births had malaria tested at delivery and their birth outcomes assessed, and were included in the study. Results Peripheral malaria was detected via polymerase chain reaction among 10.9% (n=87) at first prenatal care visit and 8.8% (n=36) at delivery. Insecticide-treated bed nets (ITNs) were used by 73.6% (n=583) and were associated with decreased malaria risk. There was a trend for impaired fetal growth and placental blood flow in malaria-infected women in the second trimester, but not later in pregnancy. Among women with low body mass index (BMI), malaria was associated with reduced birth weight (P=0.04); anthropometric measures were similar otherwise. Conclusion With IPTp-SP and ITNs, malaria in pregnancy was associated with transient differences in utero, and reduced birth weight was restricted to those with low BMI.

The purpose of this investigation was two-fold, first, to determine the incidence of amniotic sheets in our obstetric population; and, second, to elucidate the maternal and fetal complications associated with this particular finding. In this retrospective study, we searched the computerized records of the ultrasound department for the presence of amniotic sheets in singleton pregnancies from 1 March 1991 to 17 September 1993. Sonographic criteria for an amniotic sheet included the findings that (1) a reflective membrane attached to the placenta at one end or the other, with measurable thickness, was identified traversing the amniotic fluid; and (2) the fetus was not attached to the membrane, and fetal ability to move without restriction was ascertained. An amniotic sheet was identified in 79 of 17,553 examinations (0.45%) performed between 12 and 28 weeks' gestation. Two subsets of amniotic sheets were identified: perpendicular and not perpendicular. The sheets in the first subset were orientated perpendicular to the placental surface and were more likely to be associated with an abnormal presentation at delivery (p < 0.001) and a history of pelvic inflammatory disease, but not with a history of prior Cesarean section, or previous dilatation and curettage. The second subset of amniotic sheets were non-perpendicular, either oblique or parallel, in orientation to the placental surface and were associated with fewer maternal complications. Of the study group, 40.7% had a history of vaginal bleeding. The incidence of vaginal bleeding was not significantly different between those patients with perpendicular or those with non-perpendicular amniotic sheets. We conclude that perpendicular, in contrast to non-perpendicular, amniotic sheets are more commonly associated with breech presentation at term and a past history of pelvic inflammatory disease.

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