Schizencephaly prevalence, prenatal diagnosis and clues to etiology: a register-based study.

OBJECTIVES: To establish the prevalence and antenatal diagnosis of schizencephaly in the UK. METHODS: Data on schizencephaly were extracted from six regional congenital anomaly registers. RESULTS: Thirty-eight cases of schizencephaly were identified in 2 567 165 livebirths and stillbirths, giving a total prevalence of 1.48/100 000 births (95% CI, 1.01-1.95). Eighteen (47% (95% CI, 31-63%)) of the 38 cases were identified antenatally. No affected fetus had an abnormal karyotype identified. A high proportion of cases of schizencephaly occurred in younger mothers: 63% were aged 24 years or less, significantly higher (P < 0.0001) than the corresponding proportion (26%) of mothers in England and Wales. The majority of cases were not identified until after 22 weeks of pregnancy. Additional anomalies associated with vascular disruption sequences were found in eight cases which had septo-optic dysplasia or absent septum pellucidum, one of which also had gastroschisis. CONCLUSIONS: Schizencephaly occurs more frequently in the fetuses of younger mothers. It is often associated with septo-optic dysplasia, suggesting that the two conditions may share a common origin, arising as a result of destructive processes that cause changes in the brain which only become apparent on ultrasound in the second half of pregnancy.

Unusual prenatal presentation of Beckwith-Wiedemann syndrome.

When Beckwith-Wiedemann syndrome (BWS) is detected prenatally, it is usually on the basis of macroglossia, exomphalos or enlarged kidneys. We describe a case that presented as gross hepatomegaly and a suspected enlarged pancreas at 20 weeks' gestation, with none of the usual features.

Fetal renal anomalies and genetic syndromes.

Renal abnormalities are some of the commonest and most easily detectable anomalies on ultrasound. Many are an isolated finding but the prognosis may be altered considerably by the detection of other anomalies which could indicate a genetic disorder or syndrome. It is often easier to detect presupposed anomalies and the purpose of this article is to introduce and discuss those syndromes that may present with a renal abnormality on ultrasound. Common renal findings are presented with the range of additional anomalies that should be sought and suggested diagnostic tests. It should be remembered that although for many genetic conditions specific mutation analysis is now available, this usually requires pre-pregnancy investigations. Furthermore, in some cases the definitive diagnosis may not be suspected until post mortem. By this time it may be too late to establish a cell line to confirm the suspicion using laboratory methods. It is therefore important to take tissue samples antenatally where possible, or at delivery, as postnatal samples may have a high culture failure rate.

Six year survey of screening for Down's syndrome by maternal age and mid-trimester ultrasound scans.

OBJECTIVE: To assess the effectiveness of antenatal screening for Down's syndrome by maternal age and routine mid-pregnancy ultrasound scanning. DESIGN: Retrospective six year survey. SETTING: Maternity units of a district general hospital. SUBJECTS: Pregnant women booked for delivery in hospital between 1 January 1993 and 31 December 1998. MAIN OUTCOME MEASURES: All cases of Down's syndrome occurring in district identified from regional congenital anomaly register and cytogenetic laboratory records. Women's case notes were examined to identify indication for karyotyping, gestation at diagnosis, and outcome of pregnancy. RESULTS: 31 259 deliveries occurred during study period, and 57 cases of Down's syndrome were identified, four in failed pregnancies and 53 in ongoing pregnancies or in neonates. The analysis was confined to ongoing pregnancies or liveborn children. Invasive antenatal tests were performed in 6.6% (2053/31 259), and 68% (95% confidence interval 56% to 80%) of cases of Down's syndrome were detected antenatally, giving a positive predictive value of 1.8%. There were 17 undetected cases, and in seven of these the women had declined an offer of invasive testing. In women aged less than 35 years the detection rate was 53% (30% to 76%). Most of the cases detected in younger women followed identification of ultrasound anomalies. CONCLUSIONS: The overall detection rate was considerably higher than assumed in demonstration projects for serum screening. As a result, the benefits of serum screening are much less than supposed. Before any new methods to identify Down's syndrome are introduced, such as nuchal translucency or first trimester serum screening, the techniques should be tested in properly controlled trials.

Low midpregnancy placental volume in rural Indian women: A cause for low birth weight?

OBJECTIVE: We sought to study midpregnancy placental volume in rural Indian women, its maternal determinants, and its relationship to neonatal size. STUDY DESIGN: We performed a prospective community-based study of maternal nutrition and fetal growth in 6 villages near the city of Pune. Measurements included midpregnancy placental volume determined by means of ultrasonography at 15 to 18 weeks' gestation, maternal anthropometric measurements before and during pregnancy, and maternal blood pressure and biochemical parameters during pregnancy. Neonatal size and placental weight were measured at birth. RESULTS: The mothers were short and underweight (mean height, 1.52 m; weight, 42 kg; body mass index, 18 kg/m(2)) and produced small babies (mean birth weight, 2648 g). Midpregnancy placental volume (median, 144 mL) was related to the mother's prepregnancy weight (r = 0.15; P <.001) but not to weight gain during pregnancy, blood pressure, or circulating hemoglobin, ferritin, red blood cell folate, or glucose concentrations. Midpregnancy placental volume was related to placental weight at birth (r = 0.29; P <.001) and birth weight (r = 0.25; P <.001) independent of maternal size. CONCLUSION: In Indian mothers midpregnancy placental volume is significantly associated with prepregnant maternal weight and is an independent predictor of birth weight. Our findings may provide clues to the high prevalence of low-birth-weight infants in India.

Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth.

Vascular endothelial growth factor (VEGF) has important effects on endothelial cells increasing cell proliferation, permeability and nitric oxide production; concentrations of VEGF in the maternal serum increase during the first 10 weeks of pregnancy. In this study, the relationship of maternal serum VEGF with maternal health during pregnancy and with fetal and placental size at mid-pregnancy and at term was investigated. Serum was obtained from 539 Caucasian women with singleton pregnancies between 8 and 20 weeks of pregnancy (mean 14 weeks). Total serum VEGF concentrations were measured by direct competitive radioimmunoassay. Fetal size and placental volume were measured by ultrasound between 16 and 20 weeks gestation. Birthweight, placental weight and anthropometric measurements of the baby were obtained after delivery. Serum VEGF concentrations were found to be higher in women with a lower weight before pregnancy (P = 0.01) and in those carrying a female fetus (P = 0.002). VEGF concentrations were positively correlated with placental volume (r = 0.17, P = 0.0001) but not with fetal size between 16 and 20 weeks gestation. Serum VEGF concentrations were positively correlated with both birthweight (r = 0.10, P = 0.02) and placental weight at delivery (r = 0.13, P = 0.003). The data presented support the view that VEGF may be one of the factors involved in mediating the maternal cardiovascular adaptation to pregnancy.

Bladder visualisation as a prognostic sign in oligohydramnios-polyhydramnios sequence in twin pregnancies treated using therapeutic amniocentesis.

Oligohydramnios-polyhydramnios sequence in twin pregnancies may be managed by aggressive amniocentesis and is described in nine consecutive cases. In four of the nine pregnancies both twins survived, one pair died in the neonatal period, and the other four pairs all suffered intrauterine death. The median number of amnioreductions performed was five (range 2-7). In this series the reaccumulation of urine in the bladder of the 'stuck twin' was a predictive prognostic marker of survival in both twins, with a sensitivity and specificity of 100%.

Structural chromosome anomalies in congenital diaphragmatic hernia.

In order to determine the outcome and associated chromosomal and structural anomalies in fetuses diagnosed in utero as having a congenital diaphragmatic hernia, we reviewed 48 consecutive cases referred to our regional Fetal Diagnostic Unit between 1988 and 1995. All babies were delivered in units with appropriate neonatal resuscitation facilities. Thirteen babies [34 per cent of those tested, confidence interval (CI) 19-49 per cent] had karyotypic abnormalities. Three had trisomies but the other nine had more complex karyotypic abnormalities including translocations, deletions, and marker chromosomes. Twenty-one fetuses (44 per cent, CI 30-58 per cent) had additional ultrasound abnormalities which affected the heart in ten cases (21 per cent). Overall, 13 babies survived (27 per cent, CI 14-40 per cent). In babies with normal chromosomes and no additional structural abnormalities the survival rate was 50 per cent (CI 25-75 per cent). Poor outcome was not predicted by early gestation at diagnosis, the hernial contents, or the presence of polyhydramnios. We conclude that parents should be counselled about prognosis with information derived from series of prenatally diagnosed diaphragmatic hernias. The investigations offered should include a detailed ultrasound examination, particularly of the heart, and karyotyping by fetal blood sampling.

The influence of maternal haemoglobin and ferritin on mid-pregnancy placental volume.

OBJECTIVE: To investigate whether low maternal haemoglobin and ferritin levels are associated with increased placental volume by mid-pregnancy. DESIGN: Prospective study of women attending hospital for shared antenatal care. SETTING: A teaching hospital in the south of England. SUBJECTS: Five hundred and sixty-eight women booking for delivery in the hospital. MAIN OUTCOME MEASURES: Placental volume measured by ultrasound at 18 weeks gestation. RESULTS: At 14 weeks gestation 9% of women had haemoglobin levels < or = 11 g/dl and 26% had ferritin levels < 13 micrograms/l. Placental volume at 18 weeks was inversely related to the maternal haemoglobin and ferritin levels. The influence of haemoglobin and ferritin concentrations was independent of maternal social class, parity, smoking, and weight. Larger placentae were found in taller women, those who had previously been pregnant, and in those who were smoking more than 15 cigarettes daily at the time of their last menstrual period. CONCLUSION: These data suggest that placental development is influenced from early in pregnancy by the intrauterine environment provided by the mother. In conjunction with other studies they support the proposal that, as a result of these changes, programming of adult blood pressure may be initiated in early pregnancy.

Is large loop excision of the transformation zone (LLETZ) more accurate than colposcopically directed punch biopsy in the diagnosis of cervical intraepithelial neoplasia?

In 100 women with suspected cervical intraepithelial neoplasia (CIN) attending the colposcopy clinic the histological diagnoses made from excision biopsies taken by large loop excision of the transformation zone (LLETZ) were compared with those from colposcopically directed punch biopsies taken concurrently. One unsuspected microinvasive tumour was found and the diagnosis made by LLETZ was significantly worse than that made by punch biopsy in 24 cases (24%: 95% CI 15.6 to 32.4%). LLETZ improves the accuracy of diagnosis of CIN.