Maxillary length at 11-14 weeks of gestation in fetuses with trisomy 21.

OBJECTIVE: To determine the value of measuring maxillary length at 11-14 weeks of gestation in screening for trisomy 21. METHODS: In 970 fetuses ultrasound examination was carried out for measurement of crown-rump length (CRL), nuchal translucency and maxillary length, and to determine if the nasal bone was present or absent, immediately before chorionic villus sampling for karyotyping at 11-14 weeks of gestation. In 60 cases the maxillary length was measured twice by the same operator to calculate the intraobserver variation in measurements. RESULTS: The median gestation was 12 (range, 11-14) weeks. The maxilla was successfully examined in all cases. The mean difference between paired measurements of maxillary length was -0.012 mm and the 95% limits of agreement were -0.42 (95% CI, -0.47 to -0.37) to 0.40 (95% CI, 0.35 to 0.44) mm. The fetal karyotype was normal in 839 pregnancies and abnormal in 131, including 88 cases of trisomy 21. In the chromosomally normal group the maxillary length increased significantly with CRL from a mean of 4.8 mm at a CRL of 45 mm to 8.3 mm at a CRL of 84 mm. In the trisomy 21 fetuses the maxillary length was significantly shorter than normal by 0.7 mm and in the trisomy 21 fetuses with absent nasal bone the maxilla was shorter than in those with present nasal bone by 0.5 mm. In fetuses with other chromosomal defects there were no significant differences from normal in the maxillary length. CONCLUSION: At 11-14 weeks of gestation, maxillary length in trisomy 21 fetuses is significantly shorter than in normal fetuses.

Absence of nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation: an observational study.

BACKGROUND: Prenatal diagnosis of trisomy 21 requires an invasive test in women regarded as being at high risk after screening. At present there are four screening tests, and for a 5% false-positive rate, the sensitivities are about 30% for maternal age alone, 60-70% for maternal age and second-trimester maternal serum biochemical testing, 75% for maternal age and first-trimester fetal nuchal translucency scanning, and 85% for maternal age with fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks. In this study, we examined the possible improvement in screening for trisomy 21 by examining the fetal nasal bone with ultrasound at 11-14 weeks of gestation. METHODS: We did an ultrasound examination of the fetal profile in 701 fetuses at 11-14 weeks' gestation immediately before karyotyping for a possible chromosomal abnormality detected by maternal age and fetal nuchal translucency screening. The presence or absence of a nasal bone was noted. FINDINGS: The fetal profile was successfully examined in all cases. The nasal bone was absent in 43 of 59 (73%) trisomy 21 fetuses and in three of 603 (0.5%) chromosomally normal fetuses. The likelihood ratio for trisomy 21 was 146 (95% CI 50-434) for absent nasal bone and 0.27 (0.18-0.40) for present nasal bone. In screening for trisomy 21, by a combination of maternal age and fetal nuchal translucency, we estimated that inclusion of examination of the fetal profile for the presence or absence of nasal bone could increase the sensitivity to 85% and decrease the false-positive rate to about 1%. INTERPRETATION: In screening for trisomy 21, examination of the fetal nasal bone could result in major reduction in the need for invasive testing and a substantial increase in sensitivity.

Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11-14 weeks of gestation.

OBJECTIVE: To examine the value of uterine artery Doppler at 11-14 weeks of gestation in the identification of women at risk of developing pre-eclampsia and fetal growth restriction. METHODS: Uterine artery Doppler was carried out at 11-14 weeks in 3324 consecutive singleton pregnancies attending for routine care in three London hospitals. The right and left uterine arteries were identified using color flow mapping and velocity waveforms were obtained using pulsed Doppler. The mean pulsatility index of the two arteries was determined and the predictive value of a mean pulsatility index > the 95th centile in the prediction of pre-eclampsia and/or fetal growth restriction was calculated. RESULTS: Satisfactory flow velocity waveforms were obtained from both uterine arteries in 3195 (96.1%) of the 3324 pregnancies examined and complete outcome information was obtained for 3045 (95.3%) of these women. The 95th centile of the uterine artery mean pulsatility index was 2.35 and did not change significantly with gestational age. The pregnancy was complicated by pre-eclampsia in 63 (2.1%) cases and by fetal growth restriction in 290 (9.5%) cases. The sensitivity of a mean pulsatility index > 2.35 for pre-eclampsia (with or without fetal growth restriction) was 27.0% but for fetal growth restriction alone it was 11.7%. The respective sensitivities for these complications requiring delivery before 32 weeks of gestation were 60.0% and 27.8%, respectively. CONCLUSION: Uterine artery Doppler at 11-14 weeks of gestation identifies a high proportion of women who develop severe pre-eclampsia and/or fetal growth restriction.

Uterine artery Doppler at 11-14 weeks of gestation in chromosomally abnormal fetuses.

OBJECTIVE: To determine whether the major chromosomal abnormalities are associated with impaired placentation in the first trimester of pregnancy. METHODS: This was a prospective study of 692 singleton pregnancies undergoing fetal karyotyping at 11-14 weeks of gestation. Uterine artery Doppler was carried out and the mean pulsatility index was calculated just before chorionic villus sampling. RESULTS: The fetal karyotype was normal in 613 pregnancies and abnormal in 79, including 39 cases of trisomy 21, 11 of trisomy 18, 11 of trisomy 13, eight of Turner syndrome and 10 with other defects. There were no significant differences in the median value of uterine artery mean PI between any of the individual groups. Although in the combined group of trisomy 18, trisomy 13 and Turner syndrome fetuses, the median pulsatility index (1.60) was significantly higher than in the chromosomally normal group (median pulsatility index, 1.51; P = 0.021), in the majority of abnormal fetuses (24 of 30) mean pulsatility index was below the 95th centile of the normal group (mean pulsatility index, 2.34). There was no significant association between uterine artery mean pulsatility index and fetal nuchal translucency thickness or fetal growth deficit. CONCLUSIONS: The high intrauterine lethality and fetal growth restriction associated with the major chromosomal abnormalities are unlikely to be the consequence of impaired placentation in the first trimester of pregnancy.

First trimester biochemical screening for Down syndrome: free beta hCG versus intact hCG.

To compare free beta hCG versus intact hCG in first trimester Down syndrome screening we analysed 63 cases of Down syndrome and 400 unaffected control pregnancies between 10 and 13 weeks' gestation. The Down syndrome median multiple of the median (MoM) was significantly higher (p=0.001) for free beta hCG (1.89 MoM) than for intact hCG (1.37 MoM). Although distributions for free beta hCG (unaffected, 0.2157; DS, 0.2322) are wider than for intact hCG (unaffected, 0.1697; DS, 0.2158), overall 27% of Down syndrome cases were above the 95th percentile for free beta hCG compared to 19% for intact hCG. Combined with maternal age, free beta hCG detected 45% of Down syndrome pregnancies at a 5% false positive rate. Intact hCG combined with maternal age demonstrated a detection efficiency comparable to maternal age alone (35% versus 32%). In contrast, a recent study (Haddow et al., 1998-NEJM 338: 955-961) indicated that intact hCG yielded a higher first trimester Down syndrome detection efficiency than free beta hCG (29% versus 25% respectively). Re-analysis of distribution parameters in the Haddow et al. study, however, show that free beta hCG was actually the better marker (23% detection for intact hCG versus 29% for free beta hCG).

[Negative second-look laparatomy in ovarian cancers. Survival analysis and prognostic factors from 64 cases treated at the Gustave Roussy Institute]. / Seconde laparotomie négative dans les cancers de l'ovaire. Analyse de la survie et des facteurs pronostiques à partir de 64 cas traités a l'Institut Gustave-Roussy.

This study describes 64 cases of ovarian adenocarcinoma seen in the Gustave-Roussy Institut between 1978 and 1988 and who had a negative second-look laparotomy. The median age was 51 years (30-74). FIGO stages were: I: 7 (11%); II: 3 (5%); III: 39 (61%); IV: 3 (5%); and undetermined: 12 (19%). There were 53% of serous type, 14% of endometrioid type, 13% of undifferencied type, 8% of clear cells type, 3% of mucinous type, and 9% of mixed type tumors. There were 50% of grade 3 tumors. Initial debulking surgery was as complete as possible in 59 patients, with a residual tumor after surgery superior or equal to 2 cm in 25 patients. Post second-look surgery treatment (n = 57) consisted of chemotherapy (CT) alone in 22 patients (34%), radiotherapy (RT) alone in 31 patients (49%), and CT associated with RT in 4 patients (6%). Median follow-up is 100 months. The overall survival rates at 3 and 5 years were respectively 86 and 81%, and disease free survival rates 70 and 61%. Among the 64 patients, 26 relapsed (39%). Median time to relapse was 96 months. There is a statistical difference in the survival between patients who had no or inferior to 2 cm residual tumor and others. Residual tumor was the only factor to be significant in univariate and multivariate analysis of survival.

Surgical pathological staging of endometrial carcinoma and results of treatment.

114 women with endometrial carcinoma at clinical stage 1 to 3 were treated with surgery as first line of treatment. Patients were classified as being low or high risk on the basis of the surgical pathological patterns of the tumor. Disease limited to the uterine body, G1-G2 tumors and myometrial invasion of less than 1/3, identified low risk patients which received no adjuvant therapy. All the others were considered high risk and treated with radiation therapy. Patients were retrospectively restaged according to 1988 FIGO guidelines and survival was analyzed. Cox's proportional hazards method was employed to identify independent prognostic factors. Disease free survival (DFS) was 90% for stage 1, 83% for stage 2, and 43% for stage 3 patients. Lymphatic spread was associated to the poorer prognosis. Proportional hazards model showed that tumor grading, myometrial invasion and lymphatic spread were significantly related to the time of relapsing. Low risk patients showed better outcomes despite not having received adjuvant treatment, thus post-operative therapy is not indicated in this subset of patients. Radiation adjuvant therapy for high risk patients did not give satisfactory results. Failures were observed both locally and distantly calling for new adjuvant strategies. Surgical pathological staging of endometrial cancer is currently mandatory. Retroperitoneal lymph node sampling is indicated in patients with high risk pre- (advanced clinical disease, undifferentiated tumors) or intra-operative (deep myometrial invasion, enlarged pelvic nodes) prognostic factors. All prognostic indicators must be obtained from surgery and pathology in order to assess the risk of relapse.