Screening for Down syndrome based on maternal age or fetal nuchal translucency: a randomized controlled trial in 39,572 pregnancies.

OBJECTIVES: Nuchal translucency (NT) screening increases antenatal detection of Down syndrome (DS) compared to maternal age-based screening. We wanted to determine if a change in policy for prenatal diagnosis would result in fewer babies born with DS. METHODS: A total of 39,572 pregnant women were randomized to a scan at 12-14 gestational weeks including NT screening for DS (12-week group) or to a scan at 15-20 weeks with screening for DS based on maternal age (18-week group). Fetal karyotyping was offered if risk according to NT was > or = 1:250 in the 12-week group and if maternal age was > or = 35 years in the 18-week group. Both policies included the offer of karyotyping in cases of fetal anomaly detected at any scan during pregnancy or when there was a history of fetal chromosomal anomaly. The number of babies born with DS and the number of invasive tests for fetal karyotyping were compared. RESULTS: Ten babies with DS were born alive with the 12-week policy vs. 16 with the 18-week policy (P = 0.25). More fetuses with DS were spontaneously lost or terminated in the 12-week group (45/19,796) than in the 18-week group (27/19 776; P = 0.04). All women except one with an antenatal diagnosis of DS at < 22 weeks terminated the pregnancy. For each case of DS detected at < 22 weeks in a living fetus there were 16 invasive tests in the 12-week group vs. 89 in the 18-week group. NT screening detected 71% of cases of DS for a 3.5% test-positive rate whereas maternal age had the potential of detecting 58% for a test-positive rate of 18%. CONCLUSIONS: The number of newborns with DS differed less than expected between pregnancies that had been screened at 12-14 weeks' gestation by NT compared with those screened at 15-20 weeks by maternal age. One explanation could be that NT screening--because it is performed early in pregnancy--results in the detection and termination of many pregnancies with a fetus with DS that would have resulted in miscarriage without intervention, and also by many cases of DS being detected because of a fetal anomaly seen on an 18-week scan. The major advantage of the 12-week scan policy is that many fewer invasive tests for fetal karyotyping are needed per antenatally detected case of DS.

Intraocular pressure-reducing effect of PhXA41 in patients with increased eye pressure. A one-month study.

PURPOSE: To establish the dose-response relationship for the effect on intraocular pressure (IOP) and side effects during long-term treatment of patients with ocular hypertension with the prostaglandin F2 alpha (PGF2 alpha) analog PhXA41. METHODS: A three-center, randomized, double-masked study where IOP, conjunctival hyperemia, and ocular irritation were followed during a 1-month twice-daily treatment with placebo or 35, 60, or 115 micrograms/ml PhXA41 in 60 patients with ocular hypertension, primary open-angle glaucoma, or capsular glaucoma. RESULTS: The three concentrations of PhXA41 reduced the average IOP between 31% and 38% during the second day of treatment, with only a weak dose-response relationship. The initial effect declined somewhat during the first 2 weeks of treatment but then remained at the same level for the rest of the study, with a pressure reduction of approximately 20% for all three concentrations. On the second day of treatment, mild conjunctival hyperemia could be observed in most treated patients. Nineteen of 45 PhXA41-treated patients, compared with 2 of 15 placebo-treated patients, reported to have mild to moderate ocular irritation. These side effects became less pronounced during the study, and at the end there was little difference in the degree of conjunctival hyperemia between placebo- and drug-treated eyes, and no drug-related ocular irritation was reported with the two lowest concentrations of PhXA41. CONCLUSIONS: It is confirmed that the PGF2 alpha analog PhXA41 is a major improvement with respect to the effect-side effect relationship and that it may become a valuable new agent for the treatment of glaucoma.

Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension.

In a randomized, double-masked, parallel study, one drop of 0.003% (1 microgram; n = 9) or 0.01% (3 micrograms; n = 10) PhXA34, a new phenyl-substituted prostaglandin F2 alpha analogue (13,14-dihydro-15[R,S]-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), or its vehicle (n = 10) was applied topically twice daily for 6 days to one eye in each of 29 patients with ocular hypertension. Compared with either baseline, contralateral, or vehicle control values, PhXA34 caused a significant (P < .001) dose-dependent reduction of intraocular pressure. The reduction lasted at least 12 hours after each drop and 24 to 48 hours after the last drop, with a significant (P < .0001) mean +/- SEM reduction of as much as 10 +/- 1 mm Hg (40%). Conjunctival hyperemia was not produced by 0.003% PhXA34, but was noted in some eyes treated with 0.01% PhXA34, and after repeated tonometry with either concentration. The prostaglandin analogue did not produce clinically obvious miosis, anterior chamber flare or cellular response, or any subjective adverse effects. PhXA34 is a potent, effective, and well-tolerated ocular hypotensive agent based on our results in this small, short-term study. Its potential as a new drug for glaucoma therapy warrants further investigation in long-term, larger studies.