The role of molecular microsatellite identity testing to detect sampling errors in prenatal diagnosis.

OBJECTIVE: The objective was to determine the risk of sampling error in amniocentesis and chorionic villus sampling (CVS) in singleton and multiple pregnancies. Data from this and other published studies were used to discuss current practice guidelines for molecular identity testing. METHOD: Clinical and laboratory records of all patients undergoing molecular-based identity testing in our clinical laboratory from July 2002 until March 2008 were reviewed. DNA microsatellite testing was performed to determine zygosity in multiple pregnancies and maternal cell contamination (MCC) in both singleton and multiple pregnancies. RESULTS: MCC was detected in 6/148 (4%) CVS and 1/87 (1%) amniotic fluids from singleton pregnancies. In two of the CVS, only maternal cells were found. In 2/24 (8%) twin pregnancies, the same fetus was tested twice. In a total of 285 pregnancies (235 singleton, 24 twin, 26 with >or= 3 fetuses), without molecular identity testing, four women would have received erroneous results. CONCLUSION: Current guidelines recommend molecular identity testing for MCC in conjunction with molecular diagnostic testing, but not for cytogenetic testing. No published guidelines were found for zygosity testing in multiple pregnancies. We suggest that identity testing be considered for all prenatal testing of multiple pregnancies, especially if CVS is performed.

Anesthesia for cesarean section in a patient with Holt-Oram syndrome.

Holt-Oram syndrome is a rare genetic disorder affecting the heart and upper limbs (atriodigital dysplasia). The manifestations of the limb defects may vary in severity from subtle carpal bone defects and triphalangeal thumb to digit aplasia and upper extremity phocomelia. Cardiac abnormalities include atrial and/or ventricular septal defects, anomalies in pulmonary venous return and various dysrhythmias. We present the anesthetic management of a parturient with this syndrome who underwent elective cesarean section and tubal ligation, conducted under combined spinal-epidural anesthesia with a low dose of intrathecal bupivacaine. Our goal was to avoid an excessively high sympathetic block or excessive sympathetic stimulation accompanied by potential deleterious effects on cardiac rhythm. Cardiac monitoring was continued in the postoperative period for 6 h because of the possibility of dysrhythmia.

RhD status of a fetus at risk for haemolytic disease with a discrepant maternal DNA-based RhD genotype.

The cloning of the RHD gene has made it possible to determine the RhD status of fetuses at risk for haemolytic disease due to RhD iso-immunization using amniotic fluid or chorionic villi-derived DNA and the polymerase chain reaction. However, some Rh haplotypes are associated with false-positive or negative DNA-based results with the potential for an adverse outcome. We determined the RhD status of a fetus using amniotic fluid-derived DNA for an anti-D iso-immunized woman. Initially, we obtained the ethnic background and the complete RhD and RhCcEe phenotypes of both parents. The mother was RhD negative (Cde/cde) but her DNA was positive for exon 10 of the RHD gene. The fetus was positive for both exons 4 5 and exon 10. Southern analysis confirmed that the maternal DNA contained a portion of the RHD gene with a restriction pattern that was similar to RhD-positive individuals. This report illustrates that, in addition to fetal DNA genotyping, the same PCR assays, complete with RhD and RhCcEe phenotypes, and ethnic background of the parents should be obtained to alert the molecular diagnostic laboratory to the presence of rare Rh haplotypes that are associated with DNA genotyping errors.

Failure of magnesium sulfate infusion to inhibit uterine activity in pregnant sheep.

OBJECTIVES: Our purpose was to determine the effect of magnesium sulfate infusion on nonlabor uterine contractures and corticotropin-induced preterm uterine contractions in pregnant sheep. STUDY DESIGN: Fetal and maternal vascular catheters and uterine electromyographic electrodes were surgically placed in 15 pregnant sheep between 118 and 125 days' gestation. After 3 to 5 days of recovery, magnesium sulfate was infused into 7 ewes with a 0.11 gm/kg bolus over 20 minutes, followed by 0.08 gm/kg/hr. In 8 animals labor was induced with use of an intrafetal corticotropin infusion, after which 4 ewes received magnesium sulfate and 4 received saline solution. Continuous recordings of uterine electromyographic activity, amniotic pressure, fetal heart rate, blood pressure, and tracheal pressure were made. Maternal and fetal magnesium, calcium, albumin concentrations, and blood gases were determined before and during the infusion. RESULTS: Maternal magnesium concentrations increased from an average of 0.94 +/- 0.03 mmol/L to 2.73 +/- 0.1 mmol/L at the end of the bolus, remaining elevated (2.44 +/- 0.17 mmol/L) for 8 hours. Fetal magnesium concentrations (0.89 +/- 0.03 mmol/L before the bolus) did not change with the maternal infusion. In ewes not in labor, uterine contractures occurred 3.7 +/- 0.7 times per 2 hours before and did not change significantly with the infusion of magnesium sulfate. During corticotropin-induced preterm labor uterine contractions were present 13 +/- 3.2 times per hour before infusions and were unchanged by infusion of magnesium sulfate to the ewes. CONCLUSIONS: Magnesium sulfate infusion in pregnant sheep has no effect on either nonlabor uterine contractures or on corticotropin-induced preterm uterine contractions.

Seroprevalence of toxoplasma antibody in a Toronto population.

OBJECTIVE: To determine the prevalence of infection with toxoplasmosis by country of birth and age in a sample of convenience. DESIGN: Banked sera and the computerized data base of demographic and other factors from an earlier epidemiological study were retrieved. SETTING: Thirty-eight infant-toddler day care centres in Toronto. POPULATION: Day care providers from whom informed consent was obtained and banked sera were available. MAIN RESULTS: Of the 124 providers whose serum was tested, 16 (12.9%) were seropositive. Of those providers born in Canada, 8.2% were seropositive, while of those born outside of Canada, 19.6% were positive (P=0.067, OR 2.68, 95% CI 0.91, 7.94). While there was no significant association of seropositivity with age, the association of seropositivity with country of birth was different in the providers under 30 years of age. Among those born in Canada, 4.6% were seropositive, while among those born outside of Canada 23.1% were seropositive. CONCLUSIONS: The data supplement the limited existing data on toxoplasmosis infection in Canada. Among Canadians, those born outside of Canada were more likely to be seropositive than those born in Canada, suggesting that there may be a differential risk of congenital infection for infants whose parents were born outside of Canada.

Oxytocin augmentation of labor and perinatal outcome in nulliparas.

Recent pharmacologic observations in vivo suggest the use of a lower starting dose (0.5-0.1 mU/minute) of oxytocin and a longer interval between dose augmentations (30-60 minutes) than previously advocated. In this study, a high-dose oxytocin protocol was used to augment nonprogressive labor in normal nulliparous women. The rate of oxytocin infusion started at 6 mU/minute and was increased by 6 mU/minute every 15 minutes to a maximum dose of 40 mU/minute. Charts were reviewed of 1080 nulliparous women for whom the principles of active management of labor were followed and delivery occurred between March 1, 1986 and December 31, 1988. Four hundred fifty-six who required oxytocin augmentation in labor were compared with 624 who did not receive oxytocin. There were no statistically significant differences in birth asphyxia or perinatal morbidity.

Active management of labor and operative delivery in nulliparous women.

There has been a fourfold increase in cesarean births in Canada in the last 20 years. The two main indications are dystocia and repeat cesarean section. Of all primary cesarean sections, about half are due to dystocia. This is largely confined to nulliparous women. Work from Ireland suggests that a policy of active management of labor may reduce dystocia. This involves a uniform policy of amniotomy once a diagnosis of labor is established, followed by oxytocin augmentation if labor is nonprogressive (less than 1 cm/hr). From October 1, 1985, to December 31, 1986, this policy was carried out on 552 consecutive normal nulliparous women in spontaneous labor at greater than or equal to 37 weeks' gestation with a single fetus in vertex presentation with no fetal distress. These results were compared with a control group of 533 similar nulliparous women delivered between January 1, 1984 and March 31, 1985. The cesarean section rate dropped to 4.3% from 13% (p less than 0.005) and the forceps delivery rate dropped to 19.4% from 29% (p less than 0.005). The duration of labor greater than 12 hours dropped to 7% from 20% (p less than 0.005). There was no increase in fetal morbidity or mortality.

Traumatic constipation.

In 4 patients, trauma to the lumbosacral area produced abnormalities similar to those seen after resection of the nervi erigentes. Mechanisms of the resulting constipation and fecal incontinence for liquid stools included a prolonged transit time through the entire colon, a low rectal pressure, spasticity of the anal canal, and abnormal anal reflexes. Previous trauma to the lower spine must be considered in the differential diagnosis of chronic constipation.