G. C. M. L. Christiaens

Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia

OBJECTIVE To determine first‐trimester fetal sex by isolating free fetal DNA from maternal plasma. METHODS The index case was a pregnant woman who previously delivered a girl with congenital adrenal hyperplasia. The SRY gene as a marker for the fetal Y chromosome was detected in maternal serum and plasma by quantitative polymerase chain reaction analysis. Simultaneously, we performed the same test in 25 and 19 women in the first and second trimester, respectively, and compared plasma results with fetal gender as assessed by prenatal karyotyping or as seen at ultrasound or birth. RESULTS In 44 of 45 patients at gestational ages ranging from 8 3/7 to 17 3/7 weeks, we correctly predicted fetal sex using quantitative polymerase chain reaction analysis of the SRY gene in maternal plasma. In one case, the test result was inconclusive. Overall, fetal sex was correctly predicted in 97.8% of cases (95% confidence interval 88.2%, 99.9%). CONCLUSION Amplification of free fetal DNA in maternal plasma is a valid technique for predicting fetal sex in early pregnancy. In case of pregnancies at risk for congenital adrenal hyperplasia, the technique allows restriction of dexamethasone treatment to female fetuses resulting in a substantial decrease of unnecessary treatment and invasive diagnostic tests.

Clinical applications of cell-free fetal DNA from maternal plasma

OBJECTIVE: To describe our clinical experience with detection and analysis of cell-free fetal DNA derived from maternal plasma for prenatal sexing and fetal rhesus-D typing. METHODS: Real-time quantitative polymerase chain reactions (PCRs) of rhesus-D sequences and the SRY gene were validated and offered to patients with an enhanced risk for sex-linked fetal pathology and patients with rhesus-D antibodies. RESULTS: In the validation group, 72 samples were analyzed. Sensitivity of the rhesus-D real-time quantitative PCR in maternal plasma was 100% (95% confidence interval [CI]91.8%, 100%) and specificity was 96.6% (95% CI 82.2%, 99.9%). Sensitivity of the SRY real-time quantitative PCR was 97.2% (95% CI 85.5%, 99.9%), and specificity was 100% (95% CI 88.1%, 100%). The technique was used successfully in a clinical setting in 24 women. Overall, invasive tests were avoided in 41.7% of these patients. CONCLUSION: Detection of cell-free fetal DNA from maternal plasma is a reliable technique that can substantially reduce invasive prenatal tests. LEVEL OF EVIDENCE: II-2

ADVERSE OBSTETRIC OUTCOME IN LOW-AND HIGH –RISK PREGNANCIES: PREDICTIVE VALUE OF MATERNAL SERUM SCREENING

OBJECTIVE To determine whether the relationship between adverse pregnancy outcome and elevated maternal serum alpha-fetoprotein (MSAFP) and/or maternal serum hCG levels in women whose fetuses have no chromosomal abnormalities or neural tube defects is restricted to pregnancies with a priori elevated risk for pathology or also present in low-risk pregnancies. METHODS The outcomes of pregnancy in two groups of patients with elevated MSAFP and/or maternal serum hCG values were compared with the outcomes of a reference group with normal serum values. The first study group consisted of 83 women without pre-existing risk for poor outcome as defined by the guidelines of the Dutch Society of Obstetrics and Gynecology. The second study group consisted of 62 women with a priori elevated risk according to these guidelines. RESULTS Fetal or neonatal death, pregnancy-induced hypertension, placental abruption, placenta previa, preterm delivery, delivery of infants with birth weights in the 2.3rd percentile, and complications during the third stage of labor occurred significantly more often in patients with elevated values and low a priori risk than in women with normal values and without pre-existing risk factors. There was no significant increase in adverse pregnancy outcome in women with elevated values and high a priori risk compared with women with normal values and elevated a priori risk. CONCLUSION In women at low risk, elevated MSAFP and/or maternal serum hCG values are predictive of adverse pregnancy outcome. In women with a priori elevated risk, abnormal serum values do not increase this risk.

Learning in medicine: chorionic villus sampling.

Operator experience is considered to influence the safety and success of medical procedures. We performed a retrospective survey to assess learning curves in chorionic villus sampling (CVS). Data of 2081 consecutive women, in whom CVS was carried out in a tertiary care university hospital for prenatal diagnosis, were available for analysis. Endpoints of the analysis were fetal loss, failure of the procedure and need for several needle insertions. Frequencies of each endpoint were calculated and plotted for consecutive series of 50 samplings per operator. Logistic regression analysis was used to quantify the effect of operator experience. We observed a statistically significant learning effect for the unit as a whole as assessed by fetal loss figures and the same tendency for need to do several insertions. We did not observe a (collective) learning effect for failure of the procedure. Individual operators showed a significant learning profile for some endpoints. The individual learning profile predominantly depended on previous experience in amniocentesis. Our study substantiates the presence of a learning curve for CVS. This supports the view that centralization and restriction of CVS to a limited number of experienced operators within centres, is likely to have a positive influence on safety and success of the procedure. Copyright

MATERNAL UNIPARENTAL DISOMY FOR CHROMOSOME 22 IN A CHILD WITH GENERALIZED MOSAICISM FOR TRISOMY 22

We report on a case of generalized mosaicism for trisomy 22. At chorionic villus sampling (CVS) in the 37th week of pregnancy, a 47,XX,+22 karyotype was detected in all cells. The indication for CVS was severe unexplained symmetrical intrauterine growth retardation (IUGR) and a ventricular septal defect (VSD) was noted. In cultured cells from amniotic fluid taken simultaneously, only two out of ten clones were trisomic. At term, a growth‐retarded girl with mild dysmorphic features was born. Lymphocytes showed a normal 46,XX[50] karyotype; both chromosomes 22 were maternal in origin (maternal uniparental disomy). Investigation of the placenta post‐delivery using fluorescence in situ hybridization showed a low presence of trisomy 22 cells in only one out of 14 biopsies. In cultured fibroblasts of skin tissue, a mosaic 47,XX,+22[7]/46,XX[25] was observed. Clinical follow‐up is given up to 19 months.

Termination of pregnancy on genetic grounds; coping with grieving

This study describes reactions of couples to the termination of their pregnancies because of a fetal anomaly. Forty women and 31 men were interviewed twice after the termination, 6 weeks and 6 months, respectively. Factors found to be of influence on decision-making and coping include: whether the anomaly was found by chance or through directed search; whether or not the anomaly was compatible with life; how far the pregnancy had progressed, and by which method the pregnancy was terminated. The feelings these couples faced were in some ways comparable to those perceived after a stillbirth or neonatal death, but the authors also encountered other, entirely different feelings. The latter include guilt, doubt, failure, and feelings of moral and social pressure. Recommendations for clinical practice are given at the end of the paper.ZusammenfassungDie vorliegende Studie beschreibt die Reaktionen von Paaren auf den Abbruch einer Schwangerschaft aufgrund einer fotalen Anomalie. Vierzig Frauen und 31 Manner wurd...