Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: a randomized, double-blind trial.

BACKGROUND: In women with a singleton pregnancy and sonographic short cervix in midgestation, vaginal administration of progesterone reduces the risk of early preterm birth and improves neonatal outcomes without any demonstrable deleterious effects on childhood neurodevelopment. In women with twin pregnancies, the rate of spontaneous early preterm birth is 10 times higher than that in singletons, and in this respect, all twins are at an increased risk of preterm birth. However, 6 trials in unselected twin pregnancies reported that vaginal administration of progesterone from midgestation had no significant effect on the incidence of early preterm birth. Such apparent lack of effectiveness of progesterone in twins may be due to inadequate dosage or treatment that is started too late in pregnancy. OBJECTIVE: The early vaginal progesterone for the prevention of spontaneous preterm birth in twins, a randomized, placebo-controlled, double-blind trial, was designed to test the hypothesis that among women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11 to 14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24+0 and 33+6 weeks. STUDY DESIGN: The trial was conducted at 22 hospitals in England, Spain, Bulgaria, Italy, Belgium, and France. Women were randomly assigned in a 1:1 ratio to receive either progesterone or placebo, and in the random-sequence generation, there was stratification according to the participating center. The primary outcome was spontaneous birth between 24+0 and 33+6 weeks' gestation. Statistical analyses were performed on an intention-to-treat basis. Logistic regression analysis was used to determine the significance of difference in the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation between the progesterone and placebo groups, adjusting for the effect of participating center, chorionicity, parity, and method of conception. Prespecified tests of treatment interaction effects with chorionicity, parity, method of conception, compliance, and cervical length at recruitment were performed. A post hoc analysis using mixed-effects Cox regression was used for further exploration of the effect of progesterone on preterm birth. RESULTS: We recruited 1194 women between May 2017 and April 2019; 21 withdrew consent and 4 were lost to follow-up, which left 582 in the progesterone group and 587 in the placebo group. Adherence was good, with reported intake of ≥80% of the required number of capsules in 81.4% of the participants. After excluding births before 24 weeks and indicated deliveries before 34 weeks, spontaneous birth between 24+0 and 33+6 weeks occurred in 10.4% (56/541) of participants in the progesterone group and in 8.2% (44/538) in the placebo group (odds ratio in the progesterone group, adjusting for the effect of participating center, chorionicity, parity, and method of conception, 1.35; 95% confidence interval, 0.88-2.05; P=.17). There was no evidence of interaction between the effects of treatment and chorionicity (P=.28), parity (P=.35), method of conception (P=.56), and adherence (P=.34); however, there was weak evidence of an interaction with cervical length (P=.08) suggestive of harm to those with a cervical length of ≥30 mm (odds ratio, 1.61; 95% confidence interval, 1.01-2.59) and potential benefit for those with a cervical length of <30 mm (odds ratio, 0.56; 95% confidence interval, 0.20-1.60). There was no evidence of difference between the 2 treatment groups for stillbirth or neonatal death, neonatal complications, neonatal therapy, and poor fetal growth. In the progesterone group, 1.4% (8/582) of women and 1.9% (22/1164) of fetuses experienced at least 1 serious adverse event; the respective numbers for the placebo group were 1.2% (7/587) and 3.2% (37/1174) (P=.80 and P=.06, respectively). In the post hoc time-to-event analysis, miscarriage or spontaneous preterm birth between randomization and 31+6 weeks' gestation was reduced in the progesterone group relative to the placebo group (hazard ratio, 0.23; 95% confidence interval, 0.08-0.69). CONCLUSION: In women with twin pregnancies, universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation. Post hoc time-to-event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth before 32 weeks' gestation in women with a cervical length of <30 mm, and it may increase the risk for those with a cervical length of ≥30 mm.

Three-dimensional ultrasonography for advanced neurosonography (neurosofe-3D): Validation of a brain volume acquisition guideline.

INTRODUCTION: This study aimed to evaluate the quality of the brain volumes acquired following an evidence-based guideline for the acquisition of brain volumes. MATERIAL AND METHODS: This was a prospective multicenter study. Five centers recruited five cases each, acquiring two volumes per case, at different gestational age ranges. From the collected volumes, 10 operators performed an advanced neurosonography of each case. The evaluable anatomic structures were counted in each volume and expressed as a percentage. The results were compared with those obtained in a previous study where no recommendations had been made for the acquisition of the volumes. RESULTS: Five hundred evaluations were included in the study. In the axial plane, 91.5% of the structures were satisfactorily evaluated, 81.8% in the coronal plane and 89.9% in the sagittal plane. These results were significantly better than those obtained in a previous study where the volumes had been acquired without any guidelines and the percentage of evaluable structures were 80% (P < .001), 67.1% (P < .001) and 55.1% (P < .001) in the axial, coronal and sagittal planes, respectively. CONCLUSIONS: The application of an evidence-based guideline for the acquisition of brain volumes improves the quality of these by increasing the number of evaluable structures in the volume.

Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia.

BACKGROUND: Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. RESULTS: A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events. CONCLUSIONS: Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).

In Vivo Measurement of Cervical Elasticity on Pregnant Women by Torsional Wave Technique: A Preliminary Study.

A torsional wave (TW) sensor prototype was employed to quantify stiffness of the cervix in pregnant women. A cross-sectional study in a total of 18 women between 16 weeks and 35 weeks + 5 days of gestation was performed. The potential of TW technique to assess cervical ripening was evaluated by the measurement of stiffness related to gestational age and cervical length. Statistically significant correlations were found between cervical stiffness and gestational age ( R 2 = 0.370 , p = 0.0074 , using 1 kHz waves and R 2 = 0.445 , p = 0.0250 , using 1.5 kHz waves). A uniform decrease in stiffness of the cervical tissue was confirmed to happen during the complete gestation. There was no significant correlation between stiffness and cervical length. A stronger association between gestational age and cervical stiffness was found compared to gestational age and cervical length correlation. As a conclusion, TW technique is a feasible approach to objectively quantify the decrease of cervical stiffness related to gestational age. Further research is required to evaluate the application of TW technique in obstetric evaluations, such as prediction of preterm delivery and labor induction failure.

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin on length of stay in the neonatal intensive care unit.

BACKGROUND: Preeclampsia is a major pregnancy complication with adverse short- and long-term implications for both the mother and baby. Screening for preeclampsia at 11-13 weeks' gestation by a combination of maternal demographic characteristics and medical history with measurements of biomarkers can identify about 75% of women who develop preterm preeclampsia with delivery at <37 weeks' gestation and 90% of those with early preeclampsia at <32 weeks, at a screen-positive rate of 10%. A recent trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) has reported that in women identified by first-trimester screening as being at high risk for preeclampsia, use of aspirin (150 mg/d from the first to the third trimester), compared to placebo, reduced the incidence of preterm preeclampsia, which was the primary outcome, by 62% (95% confidence interval, 26-80%) and the incidence of early preeclampsia by 89% (95% confidence interval, 53-97%). The surprising finding of the trial was that despite the reduction in preeclampsia the incidence of admission to the neonatal intensive care unit, which was one of the secondary outcomes, was not significantly affected (odds ratio, 0.93; 95% confidence interval, 0.62-1.40). OBJECTIVE: We sought to examine the effect of prophylactic use of aspirin during pregnancy in women at high risk of preeclampsia on length of stay in the neonatal intensive care unit. STUDY DESIGN: This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial to assess evidence of differences in the effect of aspirin on length of stay in neonatal intensive care. Bootstrapping was used for the comparison of mean length of stay between the aspirin and placebo groups. Logistic regression was used to assess treatment effects on stay in the neonatal intensive care unit. RESULTS: In the trial there were 1620 participants and 1571 neonates were liveborn. The total length of stay in neonatal intensive care was substantially longer in the placebo than aspirin group (1696 vs 531 days). This is a reflection of significantly shorter mean lengths of stay in babies admitted to the neonatal intensive care unit from the aspirin than the placebo group (11.1 vs 31.4 days), a reduction of 20.3 days (95% confidence interval, 7.0-38.6; P = .008). Neonatal intensive care of babies born at <32 weeks' gestation contributed 1856 (83.3%) of the total of 2227 days in intensive care across both treatment arms. These occurred in 9 (1.2%) of the 777 livebirths in the aspirin group and in 23 (2.9%) of 794 in the placebo group (odds ratio, 0.42; 95% confidence interval, 0.19-0.93; P = .033). Overall, in the whole population, including 0 lengths of stay for those not admitted to the neonatal intensive care unit, the mean length of stay was longer in the placebo than aspirin group (2.06 vs 0.66 days; reduction of 1.4 days; 95% confidence interval, 0.45-2.81; P = .014). This corresponds to a reduction in length of stay of 68% (95% confidence interval, 20-86%). CONCLUSION: In pregnancies at high risk of preeclampsia administration of aspirin reduces the length of stay in the neonatal intensive care unit by about 70%. This reduction could essentially be attributed to a decrease in the rate of births at <32 weeks' gestation, mainly because of prevention of early preeclampsia. The findings have implications for both short- and long-term health care costs as well as infant survival and handicap.

Cervical pessary placement for prevention of preterm birth in unselected twin pregnancies: a randomized controlled trial.

BACKGROUND: Preterm birth is the leading cause of neonatal death and handicap in survivors. Although twins are found in 1.5% of pregnancies they account for about 25% of preterm births. Randomized controlled trials in singleton pregnancies reported that the prophylactic use of progestogens, cervical cerclage and cervical pessary reduce significantly the rate of early preterm birth. In twin pregnancies, progestogens and cervical cerclage have been shown to be ineffective in reducing preterm birth. OBJECTIVE: The objective of this study was to test the hypothesis that the insertion of a cervical pessary in twin pregnancies would reduce the rate of spontaneous early preterm birth. STUDY DESIGN: This was a multicenter, randomized controlled trial in unselected twin pregnancies of cervical pessary placement from 20(+0)-24(+6) weeks' gestation until elective removal or delivery vs. expectant management. Primary outcome was spontaneous birth <34 weeks. Secondary outcomes included perinatal death and a composite of adverse neonatal outcomes (intraventricular haemorrhage, respiratory distress syndrome, retinopathy of prematurity or necrotizing enterocolitis) or need for neonatal therapy (ventilation, phototherapy, treatment for proven or suspected sepsis, or blood transfusion). Analysis was by intention to treat. This trial is registered in the ISRCTN registry, number 01096902. RESULTS: A total of 1,180 (56.0%) of the 2,107 eligible women agreed to take part in the trial; 590 received cervical pessary and 590 had expectant management. Two of the former and one of the latter were lost to follow up. There were no significant differences between the pessary and control groups in rates of spontaneous birth <34 weeks (13.6% vs. 12.9%; relative risk 1.054, 95% confidence interval [CI] 0.787-1.413; p=0.722), perinatal death (2.5% vs. 2.7%; relative risk 0.908, 95% CI 0.553-1.491; p=0.702), adverse neonatal outcome (10.0 vs. 9.2%; relative risk 1.094, 95% CI 0.851-1.407; p=0.524) or neonatal therapy (17.9% vs. 17.2%; relative risk 1.040, 95% CI 0.871-1.242; p=0.701). A post hoc subgroup analysis of 214 women with short cervix (≤25 mm) showed no benefit from the insertion of a cervical pessary. CONCLUSION: In women with twin pregnancy, routine treatment with cervical pessary does not reduce the rate of spontaneous early preterm birth.

Three dimensional ultrasonography for advanced neurosonography (Neurosofe-3d). Analysis of acquisition-related factors influencing the quality of the brain volumes.

OBJECTIVE: To evaluate the acquisition-related factors influencing the quality of the brain volumes for further study of advanced neurosonography. METHODS: This was a prospective multicentre study. Five centres were asked to include five cases each, acquiring two volumes per case, at different gestational ages. Ten operators performed an advanced neurosonography per case. The potential influence of the following factors on the number of evaluable structures was assessed: vaginal/ abdominal acquisition, position of the head, gestational age, subjective quality of the volume and the acquiring operator itself. RESULTS: Four hundred and thirty-two evaluations were included in the study. A total of 80% of the structures were evaluated satisfactorily in the axial plane, 67.1% and 55.1% in the coronal and sagittal plane, respectively. Sagittal volumes acquired transvaginally had a better quality than those acquired transabdominally. Gestational age affected the quality of axial and sagittal volumes (p < 0.001), and the best quality was obtained between 20 and 27 weeks. In axial and sagittal volumes, the head position influenced the percentage of structures visualized (p < 0.001, p < 0.001). CONCLUSIONS: Factors affecting the quality of the volume for advanced neurosonography are gestational age, fetal head position, transvaginal acquisition in sagittal volumes, the acquiring operator and the subjective quality of the volume. © 2016 John Wiley & Sons, Ltd.

Endoscopic laser dichorionization of the placenta in the treatment of severe twin-twin transfusion syndrome.

OBJECTIVES: To describe the results of a technique of laser ablation of placental vessels in the treatment of severe twin-twin transfusion syndrome (TTTS), which is characterized by separation of the fetoplacental vascular territories and dichorionization of the placenta. PATIENTS AND METHODS: Descriptive analysis of TTTS cases treated with the endoscopic laser dichorionization of the placenta (ELDP) procedure. The variables evaluated were the occurrence of reversal of the donor-recipient phenotype, persistence of TTTS or twin anemia-polycythemia sequence (TAPS); gestational age at delivery; discharge from the hospital of at least 1 or 2 live neonates, and incidence of neurological alterations among survivors. RESULTS: 67 patients were treated with the ELDP procedure. There was no persistence of TTTS, reversal of the donor-recipient phenotype or TAPS. The median gestational age at delivery was 33.0 (23.6-37.7) weeks. The rate of discharge from the hospital of at least 1 or 2 live neonates was 88.2% (67/76) and 71.1% (54/76), respectively. Among survivors, 17 (17/121 = 14.0%) children presented with neurodevelopmental alterations during clinical follow-up. CONCLUSIONS: The major contribution of this study was the demonstration that the ELDP technique appears to be associated with a low risk of persistence or recurrence of TTTS and TAPS.

Outcome of twin reversed arterial perfusion sequence following treatment with interstitial laser: a retrospective study.

OBJECTIVES: To determine the outcome of twin reversed arterial perfusion (TRAP) sequence treated with or scheduled for treatment with interstitial laser therapy. METHODS: This is a retrospective study on ten pregnancies diagnosed with TRAP sequence. Seven of the ten pregnancies were treated with interstitial laser therapy, and two pregnancies were scheduled for later treatment. One pregnancy was treated with fetoscopic laser ablation and excluded from analysis. The delivery reports of all pregnancies were collected, the neonatal health status recorded and the median time of delivery and the treatment to delivery interval calculated. RESULTS: Six of seven pump fetuses in TRAP pregnancies treated with interstitial laser therapy at a median of 16+2 (range 13+1 to 20+3) gestational weeks were born healthy at a median of 38+0 (range 34+3 to 40+6) gestational weeks. One fetus treated with interstitial laser died after the procedure at 20+3 weeks. Two pump twins scheduled for later treatment died before the gestational age of 16 weeks. The median treatment to delivery interval for the surviving fetuses was 153 days (range 128-194). CONCLUSION: Treatment of TRAP sequence by interstitial laser therapy is feasible from the 13th week of gestation and has a good outcome.

Large fetal goiter due to placental passage of maternal antithyroperoxidase antibodies.

We report a case of fetal goiter in a pregnant woman with Graves-Basedow disease. It was diagnosed in the third trimester by a routine ultrasound, and the cordocentesis verified increased levels of thyroxine (T4) and increased autoantibodies (antithyroperoxidase antibodies) that were also increased in maternal blood. Fetal goiter got smaller on the follow-up scans, and the newborn presented hypothyroidism. Current notions on the diagnosis and management of fetal goiter are briefly discussed.

Ultrasound in labor and delivery.

Ultrasound may play an important role in the management of labor and delivery. Induction of labor is a common obstetric intervention, performed in about 20% of pregnancies. Pre-induction cervical length, measured by transvaginal sonography, has been shown to have a significant association with the induction-to-delivery interval and the risk for cesarean section. In the management of labor there is extensive evidence that digital pelvic examination does not provide accurate assessment of the position and descend of the fetal head both during the first but also in the second stage of labor. Several recent studies using both two- and three-dimensional ultrasound have now described objective measures of progression of the fetal head during labor. In instrumental deliveries an important determinant of a successful and safe use of vacuum and forceps is the correct determination of the fetal head position and appropriate application of the instrument. However, ultrasound studies have shown that digital examination before instrumental delivery fails to identify the correct fetal position in a high proportion of cases. The use of ultrasound is of crucial importance in performing a safe operative delivery and can help in the prediction of whether a vaginal delivery would be successful.

Doppler assessment of patients with twin-to-twin transfusion syndrome and survival following fetoscopic laser surgery.

OBJECTIVE: To investigate fetal-survival rates following laser surgery for twin-to-twin transfusion syndrome (TTTS) and the impact of Doppler analysis. METHODS: The present retrospective single-center study included data from patients with pregnancies exhibiting TTTS treated with fetoscopic laser surgery between January 1, 2007, and December 31, 2016. Perinatal outcomes were examined and variables were compared between the donor and recipient fetuses that survived and died, respectively. RESULTS: There were 86 pregnancies exhibiting TTTS treated with fetoscopic laser surgery included in the study. The median length of pregnancy at the time of surgery was 21.1 weeks. Both twin fetuses and at least one fetus survived in 61 (71%) and 73 (85%) pregnancies, respectively. Among recipient fetuses, ductus venosus a-wave anomalies (P=0.026), shorter cervical length (P=0.044), and a greater than 25% discrepancy in the estimated weight of the twin fetuses (P=0.045) were associated with reduced survival. CONCLUSION: Among pregnancies exhibiting TTTS, laser surgery was associated with significant dual-fetus survival. Preoperative ductus venosus anomalies were associated with lower survival among recipient fetuses, and 1-week postsurgical ultrasonography data demonstrated lower survival among recipient fetuses with persistent anomalous ductus venosus compared with normalized ductus venosus.

Relation between increased fetal nuchal translucency thickness and chromosomal defects.

OBJECTIVE: To examine the prevalence and distribution of all chromosomal defects in fetuses with increased nuchal translucency thickness. METHODS: Assessment of risk for trisomy 21 was carried out by a combination of maternal age and fetal nuchal translucency thickness at 11-13 + 6 weeks. A search of the database was made to identify, first, all singleton pregnancies in which fetal karyotyping was carried out and, second, the cases where the fetal nuchal translucency was equal to or above the 95th centile for fetal crown-rump length. The prevalence and distribution of chromosomal defects were determined for each nuchal translucency category: between the 95th centile for crown-rump length and 3.4 mm, 3.5-4.4 mm, 4.5-5.4 mm, 5.5-6.4 mm, 6.5-7.4 mm, 7.5-8.4 mm, 8.5-9.4 mm, 9.5-10.4 mm, 10.5-11.4 mm, and 11.5 mm or more. RESULTS: The search identified 11,315 pregnancies. The median maternal age was 34.5 (range 15-50) years, and the median fetal crown-rump length was 64 (range 45-84) mm. The fetal karyotype was abnormal in 2,168 (19.2%) pregnancies, and the incidence of chromosomal defects increased with nuchal translucency thickness from approximately 7% for those with nuchal translucency between the 95th centile for crown-rump length and 3.4 mm to 75% for nuchal translucency of 8.5 mm or more. In the majority of fetuses with trisomy 21, the nuchal translucency thickness was less then 4.5 mm, whereas in the majority of fetuses with trisomies 13 or 18 it was 4.5-8.4 mm, and in those with Turner syndrome it was 8.5 mm or more. CONCLUSION: In fetuses with increased nuchal translucency, approximately one half of the chromosomally abnormal group is affected by defects other than trisomy 21. The distribution of nuchal translucency is different for each type of chromosomal defect. LEVEL OF EVIDENCE: II-3.

Maternal characteristics and cervical length in the prediction of spontaneous early preterm delivery in twins.

OBJECTIVE: The purpose of this study was to examine the value of combining maternal characteristics and measurement of cervical length at 22 to 24 weeks in the prediction of spontaneous early preterm delivery. STUDY DESIGN: Cervical length was measured by transvaginal sonography at 22 to 24 weeks in 1163 twin pregnancies attending for routine antenatal care. Logistic regression analysis was used to examine the effect of maternal demographic characteristics and cervical length on the risk of spontaneous early preterm delivery. RESULTS: The rate of spontaneous delivery before 32 weeks was 6.5%. The rate of early delivery was inversely related to cervical length, and for a false-positive rate of 10%, the detection rate of early delivery was 65.3%. The respective detection rate for maternal characteristics and obstetric history was 26.4%. Logistic regression analysis demonstrated that the only significant independent predictor of spontaneous early delivery was cervical length. CONCLUSION: In twins, the prediction of spontaneous early preterm delivery by measurement of cervical length at 22 to 24 weeks is not improved by maternal characteristics.

Cystic hygromas, nuchal edema, and nuchal translucency at 11-14 weeks of gestation.

OBJECTIVE: To estimate the incidence of septations in fetuses with increased nuchal translucency (NT) thickness, and to investigate the relationship between the length and thickness of the translucency and whether the length or septations provide useful information concerning the fetal karyotype in addition to that provided by the NT thickness alone. METHODS: We examined 386 fetuses with NT thickness equal to or above the 95th percentile for crown-rump length (CRL). A transverse suboccipitobregmatic section of the fetal head was taken to determine whether the sonolucency was septated, and a midsagittal longitudinal section was used to measure NT thickness, CRL, the longitudinal distance between the occiput and the lower end of the sonolucency toward the fetal sacrum (NT length) and the length between the occiput and the sacral tip (spinal length). Logistic regression analysis was used to investigate the effect on abnormal karyotype of CRL, NT thickness, and percentage of NT length to spinal length. RESULTS: Septations within the translucency were observed in all fetuses. The fetal karyotype was abnormal in 83 (21.5%) pregnancies, and multiple regression showed that the only significant independent predictor of abnormal karyotype was fetal NT thickness. CONCLUSION: Septations within the translucency can be seen in all fetuses, and therefore this feature cannot be used to distinguish between increased NT and cystic hygromas. The length of the translucency is related to its thickness and does not give useful information concerning the fetal karyotype in addition to that provided by the NT thickness alone. LEVEL OF EVIDENCE: II-2.

Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study.

OBJECTIVE: To investigate an approach for the analysis of samples obtained in screening for trisomy 21 that retains the advantages of quantitative fluorescent polymerase chain reaction (qf-PCR) over full karyotyping and maximises the detection of clinically significant abnormalities. DESIGN: Observational study. SETTING: Tertiary referral centre. SUBJECTS: 17,446 pregnancies, from which chorionic villous samples had been taken after assessment of risk for trisomy 21 by measurement of fetal nuchal translucency (NT) thickness at 11 to 13(+6) weeks of gestation. INTERVENTIONS: Analysis of chorionic villous samples by full karyotyping and by qf-PCR for chromosomes 13, 18, 21, X, and Y. MAIN OUTCOME MEASURE: Detection of clinically significant chromosomal abnormalities. RESULTS: The fetal karyotype was normal in 15,548 (89.1%) cases and abnormal in 1898 (10.9%) cases, including 1722 with a likely clinically significant adverse outcome. Karyotyping all cases would lead to the diagnosis of all clinically significant abnormalities, and a policy of relying entirely on qf-PCR would lead to the diagnosis of 97.9% of abnormalities. An alternative strategy whereby qf-PCR is the main method of analysis and full karyotyping is reserved for those cases with a minimum fetal NT thickness of 4 mm would require full karyotyping in 10.1% of the cases, would identify 99.0% of the significant abnormalities, and would cost 60% less than full karyotyping for all. CONCLUSIONS: In the diagnosis of chromosomal abnormalities after first trimester screening for trisomy 21, a policy of qf-PCR for all samples and karyotyping only if the fetal NT thickness is increased would reduce the economic costs, provide rapid delivery of results, and identify 99% of the clinically significant chromosomal abnormalities.