Screening for trisomy 13 by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation

In 42 cases of trisomy 13 at 10-14 weeks of gestation, compared with 947 controls, the median multiple of the median (MoM) of maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy associated plasma protein A (PAPP-A) was significantly decreased (0.506 MoM and 0.248 MoM respectively), whilst fetal nuchal translucency was increased (2.872 MoM). In 38% and 71% of cases of trisomy 13 maternal serum free beta-hCG and PAPP-A was below the 5th centile of the appropriate normal range for gestation and in 62% of cases the nuchal translucency was above the 95th centile. When combined together in a multivariate algorithm with maternal age, 90% of cases of trisomy 13 could be detected at a 0.5% false positive rate or 84% at a 0.1% false positive rate. We conclude that specific trisomy 13 risks should be part of developing risk algorithms combining maternal serum biochemistry and nuchal translucency for use in first trimester screening alongside those for trisomy 21 and trisomy 18.     

Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes

OBJECTIVE: The purpose of this study was to determine the association between first-trimester trisomy 21 screening markers (free human chorionic gonadotropin-beta [hCG], pregnancy-associated plasma protein A [PAPP-A], and nuchal translucency) and adverse pregnancy outcome. STUDY DESIGN: This was a cohort study of 8012 patients enrolled in a National Institute of Child Health and Human Development-sponsored study of first-trimester trisomy 21 and 18 screening. Trisomy 21 and 18 risk results and individual marker levels in unaffected pregnancies and pregnancies with adverse outcomes were evaluated. RESULTS: PAPP-A <1st percentile (OR 5.4, 95% CI 2.8-10.3) and PAPP-A <5th percentile (OR 2.7, 95% CI 1.9-3.9) and free beta-hCG <1st percentile (OR 2.7, 95% CI 1.3-5.9) were associated with increased risk of intrauterine growth restriction (IUGR) with positive predictive values of 24.1%, 14.1%, and 14.3%, respectively. PAPP-A <5th percentile (OR 2.3 95% CI 1.1-4.7) and nuchal translucency >99th percentile (OR 3.5, 95% CI 1.1-11.3) were associated with increased risk of preterm delivery before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16 of the 29 other chromosomal abnormalities (55%). Low free beta-hCG, low PAPP-A, and increased nuchal translucency were all associated with an increased rate of fetal abnormality. CONCLUSION: Extreme values of first-trimester free beta-hCG, PAPP-A, and nuchal translucency are all associated with adverse outcomes. The especially high predictive value for IUGR of PAPP-A levels below the 1st percentile suggests that patients within this group may benefit from increased surveillance for this condition.     

Second-trimester levels of pregnancy-associated plasma protein-A and free beta-hCG in pregnancies with trisomy 13

OBJECTIVE: To examine the levels of free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in second-trimester maternal serum from pregnancies affected by trisomy 13 and compare these with the known reduced levels of these markers in first-trimester cases in an attempt to better understand the pathophysiology of changes in marker levels in chromosomally abnormal pregnancies between the first and second trimester. METHODS: Using the Kryptor immunoassay system, we measured free beta-hCG and PAPP-A in 32 singleton pregnancies affected by trisomy 13 between 14 and 20 weeks of gestation. Using medians established in a previous study, these results were compared against 450 normal singleton pregnancies over the same gestational range. The data were combined with data from 82 cases of trisomy 13 previously examined in the first trimester (11-13 weeks) and an analysis of analyte trend was performed. RESULTS: The median free beta-hCG in multiples of the appropriate gestational median (MoM) in the second-trimester samples was not significantly different from the controls (1.15 (95% CI 0.827-1.651) vs 1.00). The median PAPP-A MoM in the second-trimester samples was significantly lower (p<0.001) than in controls (0.25 (95% CI 0.164-0.373) vs 1.00). Seventy-eight percent of cases were below the 5th centile of normal for PAPP-A. The combined cases in the first trimester had a median free beta-hCG MoM of 0.58 (95% CI 0.454-0.668) and a median PAPP-A MoM of 0.26 (95% CI 0.218-0.320). For PAPP-A, there was no significant change in median across the gestational period of 11 to 20 weeks, whilst for free beta-hCG, there was a significant increase with gestation (r=0.458, p<0.001). CONCLUSIONS: Although PAPP-A levels are reduced in trisomy 13 pregnancies in the second trimester, this isolated lower marker value is unlikely to be of value in screening for trisomy 13 in the second trimester. The aetiology of reduced levels of PAPP-A in cases with trisomy 13 may be similar to that in cases with trisomy 18, but different from that in cases with trisomy 21 since the temporal pattern in trisomies 13 and 18 are different from that in trisomy 21.     

Risk of mosaicism and uniparental disomy associated with the prenatal diagnosis of a non-homologous Robertsonian translocation carrier

OBJECTIVE: To estimate the fetal risk of uniparental disomy (UPD) associated with the presence of a Robertsonian translocation (RT) in a parent or in the fetus, to determine whether it is clinically indicated to test these pregnancies for UPD. METHODS: Retrospective analysis of our Centre's experience in testing prenatal specimens for UPD in cases of known familial RTs or fortuitous RT finding. In addition, all reports dealing with prenatal UPD testing in similar populations obtained from PUBMED and the 1995-2001 American Society of Human Genetics Meeting's abstracts were assessed. RESULTS: No case of UPD 14 or 15 was found among the 51 tests performed at our Centre. Meta-analysis identified one case of UPD13 out of 687 UPD studies, conducted in 400 prenatal diagnoses. The 95% confidence interval of the risk of UPD in the population studied (1 in 738) is 0.02-0.76%. In one report, trisomy mosaicism for one of the chromosomes involved in the translocation was found in 3 cases out of 169 (95% confidence interval: 0.1-3 %). CONCLUSIONS: Fetuses carrying a Robertsonian translocation have a risk of UPD of 0.02-0.76% (95% CI). In this population, trisomy mosaicism is more frequent than UPD. This finding justifies the study of additional colonies in all cases of prenatally diagnosed RT.     

Second trimester prenatal screening for Down's syndrome using alpha-fetoprotein and free beta hCG: a seven year review

OBJECTIVE: To determine the value and impact over a seven year period of a second trimester screening programme for trisomy 21 and trisomy 18, using the two maternal serum markers alpha-fetoprotein and free beta human chorionic gonadotrophin. DESIGN: Retrospective review. SETTING: A biochemical screening laboratory serving three health districts with three antenatal clinics in both teaching and nonteaching hospitals. POPULATION: 67,904 pregnancies in women of all ages screened between 14 and 22 weeks of gestation between 1 April 1991 and 31 March 1998. METHODS: All women booked into three major antenatal clinics were offered biochemical screening. Women at increased risk of trisomy 21 or trisomy 18 (> or =1 in 250 at term) were offered an invasive diagnostic procedure. Follow up of the outcome of all pregnancies was performed. MAIN OUTCOME MEASURES: Detection rate for trisomy 21 and trisomy 18, false positive rates, uptake of screening, uptake of amniocentesis in women identified at increased risk, prevalence of trisomy 21 at birth, detection and false positive rates by maternal age, fetal loss rate after amniocentesis, report turn around time, and identification of other anomalies. RESULTS: Overall, 87% (67,904/78,501) of women underwent screening. The rate of detection of trisomy 21 was 75% (80/107; 95% CI 66 to 83) with a 5.1% false positive rate (3466/67,904; CI 4.9 to 5.3%). In women under 30 years of age the detection rate was 60% (18/30; CI 41 to 77) with a 2.6% false positive rate (956/36,371; CI 2.5 to 2.8). The rate of detection of trisomy 18 was 57% (8/14; CI 29 to 82) with a 0.7% false positive rate (475/67,904; CI 0.64 to 0.76). Uptake of amniocentesis was 83% (2912/3508). Women were 3.3 times more likely to refuse amniocentesis if the risk was close to the cutoff (1 in 250) than if the risk was > or =1 in 50. Fetal loss within 28 days of amniocentesis was 0.9% (25/2912). Prenatal screening identified 84 other anomalies in addition to 41 cases of impending fetal death. CONCLUSION: Second trimester prenatal screening for trisomy 21 and trisomy 18 using a simple two marker approach incorporating free beta hCG can achieve high detection rates over a long period of time. Health authorities who still have not introduced trisomy 21 screening should be encouraged by what can be achieved and should consider making such screening available to all women. Established second trimester detection rates of 75% for a 5% false positive rate will be the benchmark by which first trimester screening using nuchal translucency, PAPP-A and free beta hCG will be judged.     

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.     

A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness,maternal serum free beta-hCG and PAPP-A

This study examines 45 cases of trisomy 13 and 59 cases of trisomy 18 and reports an algorithm to identify pregnancies with a fetus affected by trisomy 13 or 18 by a combination of maternal age fetal nuchal translucency (NT) thickness, and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of gestation. In this mixed trisomy group the median MoM NT was increased at 2.819, whilst the median MoMs for free beta-hCG and PAPP-A were reduced at 0.375 and 0.201 respectively. We predict that with the use of the combined trisomy 13 and 18 algorithm and a risk cut-off of 1 in 150 will for a 0.3% false positive rate allow 95% of these chromosomal defects to be identified at 11-14 weeks. Such algorithms will enhance existing first trimester screening algorithms for trisomy 21.     

Prospective first-trimester screening for trisomy 21 in 30,564 pregnancies

OBJECTIVE: This study was undertaken to evaluate the performance of a 1-stop clinic for first-trimester assessment of risk (OSCAR) for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness, and maternal serum-free ss- human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein-A (PAPP-A). STUDY DESIGN: OSCAR was carried out in 30,564 pregnancies at 11 to 13 + 6 weeks. Patient-specific risks for trisomy 21 and detection and false-positive rates were calculated. RESULTS: The median maternal age was 34 (range 15-49) years. Chromosomal abnormalities were identified in 330 pregnancies, including 196 cases of trisomy 21. The estimated risk for trisomy 21 was 1 in 300 or greater in 7.5% of the normal pregnancies, in 93.4% of those with trisomy 21 and in 88.8% of those with other chromosomal defects. CONCLUSION: The most effective method of screening for chromosomal defects is by first-trimester fetal NT and maternal serum biochemistry.     

Ultrasonographic occiput position in early labour in the prediction of caesarean section

OBJECTIVE: To investigate the value of ultrasonographically determined occiput position in the early stages of the active phase of labour, in addition to traditional maternal, fetal and labour-related characteristics, in the prediction of the likelihood of caesarean section. DESIGN: Prospective observational study. SETTING: District general hospital in the UK. POPULATION: Six hundred and one singleton pregnancies with cephalic presentation in active labour at term with cervical dilatation of 3-5 cm. METHODS: Transabdominal sonography to determine fetal occiput position was carried out by an appropriately trained sonographer immediately before or after the routine clinical examination by the attending midwife or obstetrician. MAIN OUTCOME MEASURE: Caesarean section. RESULTS: Delivery was vaginal in 514 (86%) cases and by caesarean section in 87 (14%). The fetal occiput position was posterior in 209 (35%) cases and in this group the incidence of caesarean section was 19% (40 cases), compared with 11% (47 of 392) in the non-occiput posterior group. Multiple regression analysis revealed that significant independent contribution in the prediction of caesarean section was provided by maternal age (OR 1.1, 95% CI 1.0-1.2), Afro-Caribbean origin (OR 2.4, 95% CI 1.2-4.6), height (OR 0.93, 95% CI 0.89-0.97), parity (OR 0.2, 95% CI 0.1-0.4), type of labour (OR 2.2, 95% CI 1.3-3.8), gestation (OR 1.4, 95% CI 1.1-1.7), fetal head descent (OR 0.6, 95% CI 0.4-0.9), occiput posterior position (OR 2.2, 95% CI 1.3-3.7) and male gender (OR 2.0, 95% CI 1.2-3.5). CONCLUSIONS: The risk of caesarean section can be estimated during the early stage of active labour by the sonographically determined occiput position, in addition to traditional maternal, fetal and labour-related characteristics.     

Examination of a first-trimester Down syndrome screening concept on a mix of 11,107 high- and low-risk patients at a private center for prenatal medicine in Germany

Objective

To assess the performance of a combined first-trimester screening concept for trisomies 21, 18 and 13 applied to a low- and high-risk patient sample in a specialized private center for prenatal medicine.

Study design

The quality of different first-trimester screening algorithms (risk calculation based on maternal age and nuchal translucency alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both) was evaluated in a study population of low- and high-risk cases for fetal aneuploidies. All measurements were performed between the 11th + 0 and 13th + 6 weeks of gestation during the study period from November 2000 to December 2006, in accordance with the guidelines of the Fetal Medicine Foundation (FMF), London.

Results

Of 11,107 women included in the study, we had a complete follow-up on 10,668. The difference between the detection rate was insignificant for both the low-risk and the high-risk groups. In the overall study population, 52 of 59 cases of trisomy 21 were detected when a pre-defined cut-off of 1:300 was applied (detection rate (DR) 88.1%; 95% confidence interval (CI): 79.8–96.4 and false-positive rate (FPR) 4.9%; 95% CI: 4.5–5.3). For trisomies 13 and 18 with a pre-defined cut-off of 1:150, 26 of 32 cases were detected (DR 81.3%; 95% CI: 67.8–94.8 and FPR 0.7%; 95% CI: 0.5–0.9). The highest sensitivity was between 11 + 0 and 11 + 6 weeks of gestation with all cases of trisomy 21 detected with a FPR 5.1%; 95% CI: 3.7–6.5.

Conclusion

In our study population of different risk categories, the detection rate using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels was superior to the application of either parameter alone.     

Interaction between risk factors for fetal growth retardation associated with abnormal umbilical artery Doppler studies

BACKGROUND: The role of antenatal risk factors associated with the occurrence of fetal growth restriction complicated by abnormal umbilical artery Doppler studies has not yet been studied extensively. We evaluated the role and the interactions of antenatal antecedents of fetal growth restriction complicated by abnormal umbilical artery end-diastolic velocities. METHODS: We compared antenatal variables in 183 pregnancies complicated by fetal growth retardation and abnormal umbilical artery Doppler studies and 549 appropriately grown fetuses with normal end-diastolic velocity waveform in the umbilical artery. Logistic regression was used to evaluate the association between antenatal variables and fetal growth retardation and to test for interaction. RESULTS: In logistic models, increasing maternal age [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01-1.11], nulliparity (OR 2.2, 95% CI 1.37-3.5), smoking during pregnancy (OR 2.56, 95% CI 1.56-4.22), preeclampsia (OR 27.5, 95% CI 15.1-49.9), first-trimester hemorrhage (OR 2.25, 95% CI 1.32-3.82) and low (< 0.2 kg/week) weight gain in pregnancy (OR 3.48, 95% CI 1.71-3.05) were significantly associated with an increased risk of fetal growth restriction complicated by abnormal Doppler studies. These risk factors were also significantly correlated with the occurrence of absent/reversed end-diastolic blood flow in the umbilical artery. Maternal smoking during pregnancy interacted negatively with preeclampsia but positively with a low weight gain in pregnancy. CONCLUSIONS: The results of this study have shown that antenatal risk factors for intrauterine growth retardation (IUGR) complicated by abnormal Doppler studies are similar to those associated with the birth of a small-for-gestational-age infant. Preeclampsia, maternal smoking and low weight gain in pregnancy play a significant causal role in the origin of fetal growth restriction associated with abnormal uteroplacental blood flow.     

First-trimester ductus venosus, nasal bones, and Down syndrome in a high-risk population

OBJECTIVE: Assessing the role of fetal ductus venosus and nasal bones evaluation in first-trimester screening for Down syndrome. METHODS: This was a prospective cohort study in a tertiary referral fetal medicine unit involving 628 consecutive fetuses undergoing chorionic villus sampling. The indication for chorionic villus sampling was an increased risk (more than 1:300) for trisomy 21 based on maternal age and nuchal translucency screening in 313 cases (54.7%), increased maternal age in 195 (34.1%), and other in 64 (11.2%). Immediately before chorionic villus sampling, an ultrasound examination was performed. The pattern of blood flow in the ductus venosus and the presence or absence of the nasal bones was noted. RESULTS: A satisfactory examination of both ductus venosus and nasal bones was possible in 572 fetuses. Of these, 497 (86.9%) had a normal karyotype, and 47 (8.2%) were affected with Down syndrome. The likelihood ratio for trisomy 21 was 7.05 (95% confidence interval 4.27-11.64) in the case of abnormal ductus venosus flow and 6.42 (95% confidence interval 3.86-10.67) in the case of absent nasal bones. CONCLUSION: In addition to increased fetal nuchal translucency, Down syndrome is significantly associated with first-trimester abnormal flow velocity patterns in the ductus venosus and hypoplasia of the nasal bones.     

Prenatal diagnosis of congenital heart disease in the Naples area during the years 1994-1999 -- the experience of a joint fetal-pediatric cardiology unit

OBJECTIVES: To analyse the spectrum and frequencies of observed malformations; to evaluate associated extracardiac and chromosomal anomalies and outcomes in each diagnostic category; to demonstrate the need for a multidisciplinary approach to the diagnosis of CHD in the fetus. METHODS: From January 1994 to December 1999, 450 cases of CHD were detected among 4052 pregnancies at risk of fetal CHD seen at our combined unit. Confirmation of the diagnosis was not available in 50 cases, leaving 400 cases for analysis. From our computerized database, the following variables were retrieved and analysed: indication, gestational age at diagnosis, associated extracardiac anomalies, karyotype, natural history, pregnancy and feto-neonatal outcome. RESULTS: CHDs most commonly detected were VSD (75 cases), AVSD (40 cases) and HLH (37 cases). The aneuploidy rate was 29.3% in the 355 cases submitted for karyotyping (25.9% in the whole series), with a prevalence of trisomy 21 and 18 (48 and 30 cases, respectively). The aneuploidy rate was highest for AVSD (80%), coarctation (49%), tetralogy of Fallot and VSD (45%). Associated extracardiac anomalies were present in 29.5% of the cases (118/400). As for pregnancy outcome, there were 150 (37.5%) terminations of pregnancy, 16 (4%) intrauterine fetal deaths and 85 (21.3%) neonatal deaths. The remaining 149 neonates are alive (37.3% survival rate). The termination rate for pregnancies in which CHD was detected at a gestational age <25 weeks was 65.2%. Evolutive changes determined progressive prognostic deterioration in 21 cases (5%), consisting of semilunar valve obstructions and development of ventricular hypoplasia. CONCLUSIONS: The high association rate with extracardiac and chromosomal anomalies (29.3% and 25.9%) and the possible progressive prognostic deterioration require a multidisciplinary team for correct management and follow-up. Survival of fetuses with certain CHD is severely reduced, in comparison with postnatal figures, for the common association with aneuploidies.     

The second-trimester fetus with isolated choroid plexus cysts: a meta-analysis of risk of trisomies 18 and 21

Objective: To assess the risk of trisomy 18 and trisomy 21 associated with isolated choroid plexus cysts diagnosed by ultrasound in the second trimester.Methods of Study Selection: We reviewed the unabridged PREMEDLINE and MEDLINE databases for articles written in the English language regarding second-trimester fetal isolated choroid plexus cysts and trisomies 18 and 21, published in the period 1987–1997. Selection criteria included only second-trimester, prospective studies in which the rate of fetal isolated choroid plexus cysts could be calculated, the number of fetuses with trisomy 18 and 21 was reported clearly, and pregnant women of all ages were included, rather than only those at high risk for aneuploidy due to advanced maternal age.Tabulation and Results: Thirteen prospective studies, comprising 246,545 second-trimester scans, were selected. Among 1346 fetuses with isolated choroid plexus cysts, seven had trisomy 18, and five had trisomy 21. For each study, a 2 × 2 table was constructed and the likelihood ratio of a positive test was computed. The likelihood ratios for trisomies 18 and 21 were found to be homogeneous (P = .08 for trisomy 18, and P = .16 for trisomy 21). The summary likelihood ratio and 95% confidence interval (CI) for each chromosomal abnormality were calculated using the Mantel-Haenszel fixed effects model of meta-analysis. The summary likelihood ratio for trisomy 18 was 13.8 (CI 7.72, 25.14, P < .001) and for trisomy 21 was 1.87 (CI 0.78, 4.46, P = .16).Conclusion: The likelihood of trisomy 18 was 13.8 times greater than the a priori risk in fetuses with isolated choroid plexus cysts diagnosed in the second trimester. However, the likelihood of trisomy 21 was not significantly greater than the a priori risk with isolated choroid plexus cysts. The data supported offering pregnant women karyotyping to rule out trisomy 18 when maternal age at delivery is 36 years or older, or when the risk for trisomy 18 detected by serum multiple-marker screen is more than one in 3000.     

Use of peripartum ST analysis of fetal electrocardiogram without blood sampling: a large prospective cohort study

Objective

Fetal peripartum surveillance with ST analysis of fetal electrocardiogram (STAN) alone or in combination with fetal blood sampling (FBS) is a worldwide debate. STAN monitoring without FBS support was implemented in 2000 in the authors’ department when it took part in a European multicentre project. The aim of this study was to evaluate neonatal outcomes associated with peripartum STAN monitoring without FBS support in a large prospective cohort of patients at high risk of peripartum fetal asphyxia.

Study design

This prospective cohort study included all consecutive high-risk women monitored with STAN technology over a 77-month period, excluding fetuses with congenital anomalies. Outcome variables were fetal metabolic acidosis, umbilical pH ≤ 7.05 and normal extracellular base deficit, transfer to a neonatal intensive care unit, neonatal encephalopathy and neonatal death related to peripartum asphyxia. Cases with metabolic acidosis were reviewed by a referent midwife and referent obstetricians to check whether or not labour management was consistent with the STAN guidelines.

Results

In total, 3112 women were included in the study. The caesarean section rate for suspected fetal distress was 9.5% [95% confidence interval (CI) 8.5-10.5]. Acid-base status was available for 3067 (98.5%) neonates. There were 14 cases of fetal metabolic acidosis (0.45%; 95% CI 0.2-0.7), 62 cases with umbilical pH ≤ 7.05 and normal extracellular base deficit (2%; 95% CI 1.5-2.5), 27 neonates with 5-min Apgar scores ≤ 7 (0.87%; 95% CI 0.54-1.20) and 16 neonates were transferred to the neonatal intensive care unit (0.51%; 95% CI 0.26-0.76) due to peripartum asphyxia. No cases of neonatal encephalopathy, or fetal or neonatal death occurred. Out of the 14 cases of fetal metabolic acidosis, 11 were not managed in accordance with the STAN guidelines. Specificity was 80.5% and the negative predictive value was 99.9%. Sensitivity was highly affected by medical staff interpretation, varying from 9.1% in the authors’ experience to 90.9% with appropriate labour management according to the STAN guidelines.

Conclusions

STAN monitoring without FBS support was associated with a low rate of fetal metabolic acidosis. Most cases of fetal metabolic acidosis were not managed in accordance with the STAN guidelines. This study not only supports STAN usage without FBS support, but also warns of possible guideline violations and subsequent adverse neonatal outcomes.     

First-trimester ultrasonographic screening for trisomy 21 using fetal nuchal translucency and nasal bone

OBJECTIVE: To report our experience with first-trimester screening for trisomy 21 by using the combination of nuchal translucency thickness and nasal bone assessment. METHODS: Pregnant women from a predominantly Latin American population consisting of patients at both low risk and high risk for chromosomal defects underwent first-trimester ultrasonographic screening. Nuchal translucency thickness and nasal bone were assessed by two accredited fetal medicine specialists. Cases of trisomy 21 were identified from the cytogenetics laboratory logbook. RESULTS: Over a 3-year period, 1,287 consecutive singleton pregnancies were screened. The median maternal age was 33 years (range 14-47 years), with 456 (35.4%) women aged 35 years or older at the time of the scan. Overall, 110 fetuses (8.5%) had nuchal translucency thickness greater than the 95th percentile for gestational age and 25 (1.9%) had absent nasal bone. Trisomy 21 was diagnosed in 31 cases. Among them, the nuchal translucency thickness was increased in 28 and the nasal bone was absent in 13 (detection rates of 90.3% and 41.9%, respectively; P<.01). All but one (92.3%) of the trisomy 21 fetuses with absent nasal bone had increased nuchal translucency. Only two of the normal fetuses had an absent nasal bone in the first trimester. CONCLUSION: In our population, increased nuchal translucency thickness is the most important ultrasonographic marker of trisomy 21. In contrast, the nasal bone seems to have a less prominent role in identifying the fetus at risk for trisomy 21 due to its lower detection rate. However, an absent nasal bone should be considered as a highly predictive marker of trisomy 21.     

Cesarean delivery or vaginal birth: a survey of patient and clinician thresholds

OBJECTIVE: To estimate what level of additional fetal risk women and their caregivers in late pregnancy considered acceptable to avoid a cesarean and achieve a vaginal birth. METHODS: Six hundred women in late pregnancy and 294 obstetric consultants, registrars, midwives, and medical students were recruited to the study. With the assistance of a visual probability aid representing 10,000 births, they were asked to consider what level of fetal risk of death or serious disability they would consider acceptable to avoid cesarean and achieve vaginal birth. RESULTS: The median level of fetal risk deemed acceptable to achieve a vaginal birth for pregnant women was 10 per 10,000 births (95% confidence interval [CI] 10-13 per 10,000), although the range of responses was wide (1-5,000 per 10,000). Among staff, the median level of acceptable fetal risk was 13 per 10,000 births (95% CI 10-20 per 10,000). Women participating in lower intervention models of care, such as the birth center or team midwifery, were more tolerant of fetal risk (odds ratios [ORs] 2.1, 95% CI 1.6-2.9 and 1.5, 95% CI 1.0-2.3, for accepting a fetal risk of 20 per 10,000 or greater), whereas women with a complicated pregnancy were less tolerant of fetal risk (OR 0.7, 95% CI 0.5-0.9). CONCLUSION: Pregnant women and their caregivers have a low tolerance for fetal risk associated with vaginal birth. This study demonstrates the difficulty of minimizing obstetric intervention rates in the face of high expectations for fetal outcome. Obstetric and demographic factors were found to significantly impact the "acceptable fetal risk" threshold, which highlights the importance of individualized counseling regarding mode of birth. LEVEL OF EVIDENCE: III.     

A case-control study of unexplained antepartum stillbirths.

OBJECTIVE: To ascertain factors that will identify women who are at increased risk of unexplained antepartum stillbirth. DESIGN: Matched case-control study. The cases and controls were initially analysed as a whole group and again after dichotomizing into those of low birthweight (< 2500 g) and those of normal birthweight (> or = 2500 g). SETTING: Western Australia 1980-1983. SUBJECTS: Unexplained antepartum stillbirths of > or = 1000 g birthweight (cases) and liveborn infants individually matched for year of birth, plurality, sex and birthweight of infant and race of mother (controls). RESULTS: The case pregnancies had more polyhydramnios (OR 10.83, 95% CI 2.41-48.69) and cord problems (OR 6.57 95% CI 1.36-31.75) than the controls but, paradoxically, other obstetric and medical complications were less common in the cases. The association with polyhydramnios persisted when the analysis was confined to those with low birthweight. With normal birthweight fetal distress was more frequent in the cases (OR 3.65 95% CI 1.36-9.80) but there were few other differences. CONCLUSIONS: The clinical and diagnostic systems currently in use are unable to identify many fetuses at risk of death. Decreases in the rate of unexplained antepartum stillbirths await the discovery of new preventable causes, or of innovations in clinical or laboratory aspects of obstetric care.     

Prospective audit of a one-centre combined nuchal translucency and triple test programme for the detection of trisomy 21

OBJECTIVES: To determine detection and false-positive rates for trisomy 21 using two-stage combined nuchal translucency (NT) and triple testing, whilst disclosing abnormal nuchal measurements at the scan. METHODS: A prospective audit in a UK women's hospital, of 3188 women with singleton pregnancies, requesting screening for trisomy 21. Median age was 37 years (range 19-46). Women were offered NT screening at 11 to 14 weeks. Those with NT > or =3 mm were offered chorionic villus sampling. Those declining CVS, and those with NT <3 mm, were offered early triple tests. Women with a term combined risk of trisomy 21 > or = 1:250, based on age, NT, and triple test results were offered amniocentesis. RESULTS: Using a 3-mm NT 'cut-off' identified 16/25 cases of trisomy 21 (64%; 95% CI 38.8, 78.9). Of 2725 women who had a combined nuchal plus triple test assessment, 79 (2.6%) had a > or = 1:250 term risk of trisomy 21. Forty (1.3%) had amniocentesis identifying 6/9 remaining cases (67%:95% CI:27.9, 92.5). Overall, the detection rate was 88% (95% CI:68.8, 97.5) for a 4.8% FPR. For the screened population, to achieve an 88% detection rate using the triple test alone, the predicted FPR would be 20%. Conversely, for an FPR of 4.8% using the triple test alone, the detection rate would be only 60%. CONCLUSION: In a high-risk group, the combination of NT with triple test offers detection of trisomy 21 at least equivalent to either test, while allowing disclosure of an abnormal NT at the scan and reducing the FPR. Importantly, the FPR is less than 5%, considerably lower than expected for triple test alone for this population.     

The epidemiologic incidence of congenital gastroschisis in Western Australia

OBJECTIVE: The purpose of this study was to review the population incidence of congenital gastroschisis in Western Australia over the past 2 decades. STUDY DESIGN: A population-based incidence study of congenital gastroschisis from 1980 to 2001. Maternal and perinatal outcome data were collected to ascertain incidence, treatment, and outcome trends. RESULTS: One hundred twenty-two cases of gastroschisis were identified. The median maternal age was 23 years (range, 16-35 years). Women aged <20 years were at a 7.82 increased risk (95% CI, 4.34-14.08); women aged 20 to 24 years were at a 3.24 increased risk (95% CI, 1.88-5.61) for fetal gastroschisis compared with women aged >or=25 years. An incidence analysis over time indicated a significant increase of gastroschisis cases from 1 of 10,000 births during the period 1980-1990 to the current rate of 2.4 of 10,000 births (P<.001). The perinatal mortality rate was 12.7% (95% CI, 8.7-16.7) with a 9.8% stillbirth rate (95% CI, 6.3-13.3). CONCLUSION: There has been a sustained increase in the birth incidence of gastroschisis over the past decade, particularly in teenage women. A significant fetal death rate in the third trimester is observed.