Nancy C. Rose

Principles and practice of teratology for the obstetrician

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

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.

Maternal serum α-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.

Diagnosis and management of fetal nuchal translucency

Fetal nuchal translucency can be measured in most pregnant women in the first and early second trimester. The size of translucency varies slightly with gestational age and crown rump length and is independent of maternal age. Most authors have used a nuchal thickness of > or = 2.5 mm or > or = 3 mm to define abnormal, although some have suggested that the normal variation with gestation requires that different thresholds be used at different gestational ages. The accuracy of nuchal translucency measurement varies between examiners and between patients, likely in relation to examiner skill and image resolution. The small size of a nuchal translucency, less than 3 mm in most cases, probably approximates the threshold of normal interexaminer and intraexaminer variability. The presence of a thickened nuchal translucency is associated with chromosomal abnormality and perhaps with structural abnormality even when the karyotype is normal. Because of the reported variations in the populations studied, the methods used, and the results of screening, it is inappropriate at this time to assign a numeric risk to any individual patient with this finding. However, in both high-risk and low-risk groups, the positive predictive value appears to be high enough that patients with increased nuchal translucency should be counseled by their obstetrician and prenatal diagnostic testing should be offered. Because early genetic diagnosis by CVS has a substantially higher procedure-associated loss rate than amniocentesis in the second trimester, many patients may elect to wait for chromosomal testing. If so, disappearance of nuchal thickening should not be taken as reassurance. As a screening test to be widely applied to a general or low-risk population, the utility of fetal nuchal translucency measurement is uncertain. The reported sensitivity for identification of trisomy 21 has ranged from about 40% to 80%, and the sensitivity for identification of other aneuploidies may be lower than for Downs syndrome. From a cost-risk-benefit standpoint, universal first-trimester ultrasound screening has not been appropriately compared with standard risk assessment using maternal age and multiple-marker serum screening, with amniocentesis as the predominant diagnostic method. Also, the issues of availability and reimbursement have not been addressed. Currently, measurement of nuchal translucency is not a substitute for the standard of obstetrical care, which is to offer multiple-marker serum screening to every pregnant woman at 15 to 20 weeks. Similarly, it is inappropriate to substitute nuchal translucency measurement for genetic counseling and CVS or amniocentesis in women above 35 years of age or those with a significant positive history. Finally, the data are not clear as to whether a normal nuchal translucency decreases the likelihood of chromosomal abnormality in a high-risk population, and such women should not be discouraged from invasive testing because of a normal first-trimester ultrasound study. The data supporting the association between thickened nuchal transluency and chromosomal abnormality are compelling, but further study is needed before adopting routine nuchal translucency screening. Combining first-trimester ultrasonography with early serum screening is currently being investigated and may ultimately prove to be the most efficient means of screening for chromosomal anomaly.

Pregnancy screening and prenatal diagnosis of fetal Down syndrome

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.

Genetic Screening and the Obese Gravida.

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.

An evaluation of the Factor V Leiden mutation in a cohort of African‐American pregnant women

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.

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.

Prenatal Characteristics of Congenital Nephrosis

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 una...

Approach to Transfusion in Obstetrics: Maternal and Fetal Considerations

Publisher Summary The increasing demands of the fetus as well as biologic differences between the fetus and the mother significantly affect the management of a patient during pregnancy. The chapter discusses several obstetric considerations including physiologic adaptations to pregnancy, issues related to the assessment of obstetric hemorrhage, and the need for maternal transfusion. It also discusses the diagnosis and treatment of fetomaternal hemorrhage (FMH) and its contribution to the hemolytic disease of the fetus and the newborn, with emphasis on rhesus (Rh) isoimmunization. The physiologic changes that occur during pregnancy are designed to protect the patient from the significant amount of blood loss caused by delivery. After delivery, mothers are screened for FMH by\ the erythrocyte rosette test. The rosette test identifies Rh(D)-positive fetal cells in the maternal circulation. The maternal red blood cell (RBC) sample is first incubated with human anti-D antibody, and then indicator Rh(D)-positive cells are added. The indicator cells form agglutinates (rosettes) around the antibody-bound Rh(D)-positive fetal cells if present. If the rosette test is positive, a Kleihauer–Betke test is used to quantitate the number of fetal cells in the maternal circulation. This technique relies on differences between fetal and adult hemoglobin resistance to acid elution. Alternative methods to quantify FMH include the enzyme-linked antiglobulin test and flow cytometry. Only 1% of deliveries have a greater than 30 cc FMH—in such cases, RhIg doses are increased accordingly to protect against Rh(D) sensitization.Publisher Summary The increasing demands of the fetus as well as biologic differences between the fetus and the mother significantly affect the management of a patient during pregnancy. The chapter discusses several obstetric considerations including physiologic adaptations to pregnancy, issues related to the assessment of obstetric hemorrhage, and the need for maternal transfusion. It also discusses the diagnosis and treatment of fetomaternal hemorrhage (FMH) and its contribution to the hemolytic disease of the fetus and the newborn, with emphasis on rhesus (Rh) isoimmunization. The physiologic changes that occur during pregnancy are designed to protect the patient from the significant amount of blood loss caused by delivery. After delivery, mothers are screened for FMH by\ the erythrocyte rosette test. The rosette test identifies Rh(D)-positive fetal cells in the maternal circulation. The maternal red blood cell (RBC) sample is first incubated with human anti-D antibody, and then indicator Rh(D)-positive cells are added. The indicator cells form agglutinates (rosettes) around the antibody-bound Rh(D)-positive fetal cells if present. If the rosette test is positive, a Kleihauer–Betke test is used to quantitate the number of fetal cells in the maternal circulation. This technique relies on differences between fetal and adult hemoglobin resistance to acid elution. Alternative methods to quantify FMH include the enzyme-linked antiglobulin test and flow cytometry. Only 1% of deliveries have a greater than 30 cc FMH—in such cases, RhIg doses are increased accordingly to protect against Rh(D) sensitization.