Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy.

Cerebro-oculo-facio-skeletal (COFS) syndrome is a recessively inherited rapidly progressive neurologic disorder leading to brain atrophy, with calcifications, cataracts, microcornea, optic atrophy, progressive joint contractures, and growth failure. Cockayne syndrome (CS) is a recessively inherited neurodegenerative disorder characterized by low to normal birth weight, growth failure, brain dysmyelination with calcium deposits, cutaneous photosensitivity, pigmentary retinopathy and/or cataracts, and sensorineural hearing loss. Cultured CS cells are hypersensitive to UV radiation, because of impaired nucleotide-excision repair (NER) of UV-induced damage in actively transcribed DNA, whereas global genome NER is unaffected. The abnormalities in CS are caused by mutated CSA or CSB genes. Another class of patients with CS symptoms have mutations in the XPB, XPD, or XPG genes, which result in UV hypersensitivity as well as defective global NER; such patients may concurrently have clinical features of another NER syndrome, xeroderma pigmentosum (XP). Clinically observed similarities between COFS syndrome and CS have been followed by discoveries of cases of COFS syndrome that are associated with mutations in the XPG and CSB genes. Here we report the first involvement of the XPD gene in a new case of UV-sensitive COFS syndrome, with heterozygous substitutions-a R616W null mutation (previously seen in patients in XP complementation group D) and a unique D681N mutation-demonstrating that a third gene can be involved in COFS syndrome. We propose that COFS syndrome be included within the already known spectrum of NER disorders: XP, CS, and trichothiodystrophy. We predict that future patients with COFS syndrome will be found to have mutations in the CSA or XPB genes, and we document successful use of DNA repair for prenatal diagnosis in triplet and singleton pregnancies at risk for COFS syndrome. This result strongly underlines the need for screening of patients with COFS syndrome, for either UV sensitivity or DNA-repair abnormalities.

Role of renin-angiotensin system in blood pressure regulation in pregnancy.

We gave captopril (25 mg) to nine pregnant and eight non-pregnant women. From baseline to 60 min post-captopril, mean arterial pressure decreased significantly more in pregnant than in non-pregnant women (mean 15.0 [SE 2.5] vs 5.2 [1.2] mm Hg; difference 9.8 [95% CI 3.9-15.9] mm Hg, p = 0.0036), whereas plasma renin activity increased significantly more in the pregnant group (18.0 [5.5] vs 4.5 [1.9] ng mL-1 h-1; difference 13.5 [0.71-26.5], p = 0.043). These findings support the hypothesis that stimulation of the renin-angiotensin system in pregnancy maintains blood pressure.

Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia.

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.

The effect of vibroacoustic stimulation on the nonstress test at gestational ages of thirty-two weeks or less.

The effect of vibroacoustic stimulation on the nonstress test at gestational ages of less than or equal to 32 weeks was studied in 15 patients who underwent a total of 316 nonstress tests starting at 20 to 25 weeks' gestation. There were 168 nonreactive nonstress tests that were followed by 3 seconds of vibroacoustic stimulation. The incidence of reactive nonstress tests after vibroacoustic stimulation was significantly increased after 26 weeks' gestation. This may have clinical applicability and may be related to functional maturation of the fetal auditory system.

Expectant management of abruptio placentae before 35 weeks gestation.

Forty-three patients with abruptio placentae before 35 weeks of pregnancy were managed expectantly with observation or with tocolytic therapy when contractions were present. Mean time to delivery was 12.4 days. Twenty-three patients were delivered within 1 week of admission. In the remaining 20 patients, the mean time to delivery was 26.8 days. There were no intrauterine deaths. In properly selected patients with preterm gestation and low-grade abruptio it is reasonable to defer delivery. These patients must be followed closely with antepartum fetal heart rate monitoring, serial hematologic and coagulation profiles, and serial sonograms when indicated.

Donation of blood by the pregnant patient for autologous transfusion.

A study was conducted to determine the safety and utility of autologous blood donation in third trimester pregnancy. Thirty-seven obstetric patients, 32 with an obstetric risk factor, donated an average of 485 ml of blood. Twenty-one of the 37 patients were expected to undergo cesarean section. Nonstress testing was performed before and after phlebotomy. Continuous fetal heart rate monitoring was maintained throughout the donation, which lasted an average of 9 minutes. All nonstress test results were normal before and after the phlebotomy except in one case. All fetal heart rates remained stable during phlebotomy and premature labor was not precipitated. All fetal outcomes were normal. One patient delivered on the day of phlebotomy, 6 hours after the procedure. Only one of the autologous units was used, in a patient who had a pelvic infection and moderate anemia. The incidence of primary cesarean section was 35%. Phlebotomy of the mother appears to be safe for the fetus at term. Further investigation is needed to determine the safety of removal of more than 1 unit of blood and blood donation at earlier gestational ages.

Fetal heart rate response to vibratory acoustic stimulation predicts fetal pH in labor.

Vibratory acoustic stimulation was performed during labor in 188 instances 60 seconds before fetal scalp puncture was done to determine fetal scalp blood pH. The fetal heart rate response was recorded for both vibratory acoustic stimulation and fetal scalp puncture. No instance of fetal acidosis occurred in the presence of an acceleration to either vibratory acoustic stimulation or fetal scalp puncture. Vibratory acoustic stimulation was more likely to elicit an acceleration than fetal scalp puncture in the nonacidotic fetus. Vibratory acoustic stimulation is less invasive and may be used in some instances in which fetal scalp blood puncture for pH determination is technically impossible.

Second-trimester fetal monitoring and preterm delivery in pregnancies with systemic lupus erythematosus and/or circulating anticoagulant.

Antepartum fetal monitoring was initiated at 19 to 26 weeks' gestation in 15 pregnancies: six (five with systemic lupus erythematosus, one with circulating anticoagulant) with a complicated antepartum course (group 1); three, all systemic lupus erythematosus, with a normal antepartum course (group 2); and six normal control pregnancies (group 3). Group 1 all exhibited nonperiodic fetal heart rate decelerations, without the classical appearance of early, late, or variable decelerations, and four of the six had fetal bradycardia. In three group 1 cases, there was no active intervention because of early gestational age, and fetal death occurred at 23, 27, and 27 weeks, respectively. The other three patients in group 1 received betamethasone and were delivered by cesarean section at 28 to 30 weeks. There were no cases of respiratory distress syndrome or neonatal death. Five of the six infants in group 1 were small for gestational age. The nonperiodic fetal heart rate decelerations were absent in both groups 2 and 3 who all had normal fetal outcomes at term. The abnormal finding of women with nonperiodic fetal heart rate decelerations at 20 to 28 weeks may detect the fetus at risk for intrauterine death in pregnancies complicated by systemic lupus erythematosus or circulating anticoagulant. Continued surveillance, steroid induction of lung maturity, and delivery should be considered in these cases.

Relationship of baseline fetal heart rate to gestational age and fetal sex.

A study of 37 patients who underwent 365 antepartum fetal heart rate tests showed a significant difference in heart rate between 19 to 24 weeks' and 36 to 40 weeks' gestation. Baseline heart rate remained within the normal range, suggesting that an abnormal heart rate at any gestational age should prompt further fetal assessment. Baseline fetal heart rate was not significantly different between male and female fetuses.

Effect of chorionic villus sampling on serum alpha fetoprotein levels.

Chorionic villus sampling (CVS) is a recent advance in prenatal diagnosis in the first trimester. maternal serum alpha fetoprotein (AFP) screening for neural tube defects is done from 14-17 weeks gestation. Previous studies have shown an elevation of AFP levels following amniocentesis. The aim of this study was to determine the effect of CVS on AFP levels immediately following this procedure. CVS was performed under sonographic guidance on 22 patients between 6 and 12 weeks gestation undergoing elective termination of pregnancy. A Portex catheter was used for obtaining villi. Maternal serum AFP levels were ascertained before and after CVS by radioimmunoassay. In the group of patients 8 weeks or less, no change in AFP levels was seen; in patients greater than 8 weeks gestation, a significant rise in post-biopsy AFP level was noted in 7 of 14 patients. Further studies are planned to clarify the effect of CVS on AFP levels in patients with ongoing pregnancies. Clarification of this issue is important to the role of CVS in prenatal screening.