[Rapid prenatal diagnosis of chromosomal abnormalities; limitations and possibilities].
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Chromosome Aberrations↗
Biomedical subjects
C M Bilardo
Publications and source records attributed to C M Bilardo.
Nuchal translucency screening and anxiety levels in pregnancy and puerperium.
OBJECTIVES: To compare levels of anxiety and depression during pregnancy and puerperium between women who are offered nuchal translucency (NT) screening routinely and those who are not, and to compare levels between women accepting and those declining screening. METHODS: In 12 midwife practices in three different health districts an experimental NT screening program was offered to pregnant women between 1 June 1999 and 1 January 2001. As part of this implementation study, questionnaires including the Hospital Anxiety and Depression Scale (HADS) were completed: after the patient was informed but before screening (T1), at 20 weeks of gestation (T2), and 6 weeks after delivery (T3). A control group of women receiving routine prenatal care (i.e. no screening offered) also completed the HADS questionnaire at 12 and 20 weeks and after delivery. RESULTS: Five hundred and twenty-seven questionnaires were analyzed. There was a screening uptake of 87% in the intervention group (i.e. those offered screening). Women in this group differed significantly in the percentage of previous miscarriages and religious background compared with the control group. We adjusted for these differences in the analysis. There were no significant differences in HADS scores between the intervention and the control groups at T1, suggesting that women receiving information on screening were not more anxious compared with women who were not informed. Women who were offered screening (acceptors as well as decliners) had significantly lower HADS levels at 20 weeks and after delivery. There were no demographic differences between women accepting and those declining screening. CONCLUSION: Informing women and offering them NT screening for Down syndrome does not increase anxiety or depression levels in pregnancy. In fact, women undergoing or declining screening seem less anxious compared with those who are not offered screening. It is possible that informing women and offering them the chance to decide autonomously whether to participate in screening reduces anxiety levels.
Adult↗
Increased nuchal translucency and split-hand/foot malformation in a fetus with an interstitial deletion of chromosome 2q that removes the SHFM5 locus.
OBJECTIVES: To describe and discuss the clinical, cytogenetic and molecular findings in a fetus with the first prenatally detected interstitial deletion of chromosome 2q. CASE REPORT: A fetus with increased nuchal translucency on routine ultrasound examination at 13 weeks' gestation was found to have severe upper-limb abnormalities on follow-up ultrasound examination at 16 weeks. The pregnancy was terminated, and the autopsy revealed monodactyly of the right upper limb, oligodactyly of the left upper limb and bilateral split foot, as well as atrial and ventricular septal defects and mild facial dysmorphism. RESULTS: Cytogenetic studies and haplotype analysis of the fetus and both parents showed that the fetus carried a de novo deletion encompassing a region of about 30 Mb on the paternal chromosome 2q (karyotype 46,XX,del(2)(q24.2-q32.2)). CONCLUSION: This is the first instance of increased nuchal translucency associated with a chromosome 2q deletion. Moreover, the striking malformations affecting all four of the fetus' limbs support previous suggestions that a novel locus for split-hand/foot malformation (SHFM5) lies on chromosome 2q31.
Abnormalities, Multiple↗
Long-term psychological consequences of pregnancy termination for fetal abnormality: a cross-sectional study.
OBJECTIVE: We examined women's long-term psychological well-being after termination of pregnancy (TOP) for fetal anomaly in order to identify risk factors for psychological morbidity. METHODS: A cross-sectional study was performed in 254 women, 2 to 7 years after TOP for fetal anomaly before 24 weeks of gestation. We used standardised questionnaires to investigate grief, posttraumatic symptoms, and psychological and somatic complaints. RESULTS: Women generally adapted well to grief. However, a substantial number of the participants (17.3%) showed pathological scores for posttraumatic stress. Low-educated women and women who had experienced little support from their partners had the most unfavourable psychological outcome. Advanced gestational age at TOP was associated with higher levels of grief, and posttraumatic stress symptoms and long-term psychological morbidity was rare in TOP before 14 completed weeks of gestation. Higher levels of grief and doubt were found if the fetal anomaly was presumably compatible with life. CONCLUSION: Termination of pregnancy for fetal anomaly is associated with long-lasting consequences for a substantial number of women. Clinically relevant determinants are gestational age, perceived partner support, and educational level.
Abortion, Induced↗
Increased nuchal translucency thickness: a marker for chromosomal and genetic disorders in both offspring and parents.
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Adult↗
Double trisomy 48,XXX,+18 in association with increased nuchal translucency; two cases.
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Adult↗
Effect of antenatal glucocorticoid therapy on arterial and venous blood flow velocity waveforms in severely growth-restricted fetuses.
OBJECTIVE: To study the effects of antenatal glucocorticoid (betamethasone) therapy on blood flow velocity waveform patterns in the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) in severely intrauterine growth-restricted (IUGR) fetuses. METHODS: Fifty-five severely IUGR fetuses at 24-34 weeks of gestation were included in the study. The effect of antenatal glucocorticoid administration on Doppler findings in the UA, MCA and DV was studied using two statistical approaches, namely paired sample analysis and multilevel analysis. RESULTS: There were no effects of betamethasone on the pulsatility index (PI) of the vessels studied. The only changes noticed during the 14 days of observation were a gradual decrease of PI in the MCA, an increase in the UA-PI/MCA-PI ratio and an increase in the DV-PI. These changes with time may be explained by a progressive and gradual deterioration of the fetal condition. CONCLUSION: Antenatal glucocorticoids (betamethasone) do not affect fetal Doppler waveform patterns of the UA, MCA and DV in severely IUGR fetuses.
Betamethasone↗
Disappearance of enlarged nuchal translucency before 14 weeks' gestation: relationship with chromosomal abnormalities and pregnancy outcome.
OBJECTIVE: The aim of this study was to investigate the natural course of enlarged nuchal translucency (NT) and to determine if its disappearance before 14 weeks' gestation is a favorable prognostic sign in relation to fetal karyotype and pregnancy outcome. METHODS: A total of 147 women with increased NT (> 95th centile) at first measurement were included in this study. A second measurement was performed in all cases, at an interval of at least 2 days. Both measurements were taken between 10 + 3 and 14 + 0 weeks. All women underwent chorionic villus sampling or amniocentesis for subsequent karyotyping. In those women with a normal karyotype, a fetal anomaly scan was performed at 20 weeks' gestation. Pregnancy outcome was recorded in all cases. The finding of persistent or disappearing NT enlargement was analyzed in relation to fetal karyotype and pregnancy outcome. RESULTS: Of the 147 paired measurements, NT remained enlarged at the second measurement in 121 (82%) cases. An abnormal karyotype was found in 35% of these cases. In 26 (18%) fetuses the NT measurement was found to be below the 95th percentile at the second measurement and in only two of them an abnormal karyotype was found (8%). In the 103 chromosomally normal fetuses an adverse outcome (i.e. fetal loss or structural defects) was recorded in 22 fetuses with persistent enlargement (28%) and in four fetuses with disappearing enlargement (17%). CONCLUSIONS: Disappearance of an enlarged NT before 14 weeks' gestation is not a rare phenomenon and seems to be a favorable prognostic sign with respect to fetal karyotype. Overall, no significant difference in pregnancy outcome was found between chromosomally normal fetuses with persisting or disappearing NT enlargement.
Abortion, Spontaneous↗
Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction.
OBJECTIVE: To investigate whether pathological changes in the umbilical artery (UA), ductus venosus (DV) and short-term fetal heart variation are related to perinatal outcome in severe, early intrauterine growth restriction (IUGR). METHODS: This multicenter, prospective, longitudinal, observational study was carried out in the Departments of Fetal Medicine and Obstetrics in Hamburg, Amsterdam, Utrecht and London. In 70 singleton pregnancies with IUGR fetuses, delivered at 26-33 weeks of gestation because of antepartum fetal distress, short-term variation (STV) of fetal heart rate, pulsatility index of the fetal UA (UA PI) and DV pulsatility index for veins (DV PIV) were assessed at least weekly. The final measurement was performed within 24 h of delivery. Standard cut-off levels (2 SD or 3 SD, absent flow or reversed flow) were used and new cut-off levels were calculated by means of receiver-operating characteristics analysis. Adverse outcome was defined as perinatal death, cerebral hemorrhage (> or = Grade II) or bronchopulmonary dysplasia before discharge. The predictive value for adverse outcome was calculated for different cut-off levels of the monitoring parameters, adjusted for gestational age (GA), by multivariate logistic regression analysis. Data were analyzed separately for three different time blocks, namely 8-14, 2-7 and 0-1 days before delivery. RESULTS: Adverse perinatal outcome occurred in 18/70 (26%) infants. During the last 24 h before delivery DV PIV and UA PI were significantly higher and STV lower in the adverse outcome group, while 2-7 days before delivery only DV PIV was significantly higher. Adverse perinatal outcome could be predicted at 0-1 days before delivery by DV PIV at a cut-off of three multiples of the SD (odds ratio (OR) 11.3; 95% CI 2.3-57) and GA (OR 0.4; 95% CI 0.3-0.8), at 2-7 days by DV PIV at 2 SD (OR 3.0; 95% CI 0.8-12) and GA (OR 0.5; 95% CI 0.3-0.8) and at 8-14 days by DV PIV at 2 SD (OR 3.9; 95% CI 0.8-20) and GA (OR 0.5; 95% CI 0.3-0.8). Other parameters did not contribute to the multivariate model. CONCLUSIONS: DV PIV measurement is the best predictor of perinatal outcome. This measurement may be useful in timing the delivery of early IUGR fetuses and in improving perinatal outcome, even when delivery may be indicated at an earlier GA. However, as GA was also an important factor influencing outcome, with poorer outcome at earlier gestation at delivery, this hypothesis needs to be tested in a multicenter, prospective, randomized trial.
Blood Flow Velocity↗
Measurement of nasal bone length at 11-14 weeks of pregnancy and its potential role in Down syndrome risk assessment.
OBJECTIVES: To assess the feasibility of measuring nasal bone length in first-trimester pregnancy and to confirm if the absence of a fetal nasal bone is a marker for Down syndrome. METHODS: Fetal nasal bone assessment was attempted in 1089 consecutive singleton pregnancies between 11 and 14 weeks' gestation. All ultrasound examinations were performed transabdominally in three separate centers. If the nasal bone was present, nasal bone length was measured. RESULTS: Nasal bone assessment was successfully achieved in 1027 of 1089 (94.3%) ultrasound examinations. Within this group nasal bone was absent in 10 of 1000 (1.0%) unaffected cases, 10 of 15 (66.7%) Down syndrome cases and 5 of 12 (41.7%) cases with other pathological conditions. Regression analysis showed a significant increase (P < 0.0001) in nasal bone length from 2.48 mm at a crown-rump length of 45 mm to 3.12 mm at a crown-rump length of 84 mm. The nasal bone length in the five cases of Down syndrome in which the nasal bone was present was less than the median measurement of unaffected cases. Using modeling, the combination of nasal bone with maternal age, nuchal translucency, free beta-human chorionic gonadotropin (hCG) and pregnancy associated plasma protein-A (PAPP-A) achieved a detection rate of 95% with a false-positive rate of 2.9%. At a fixed 1% false-positive rate, the detection rate was 91%. CONCLUSIONS: Absence of the nasal bone can be used as a marker for Down syndrome in the first trimester of pregnancy. Inclusion of the nasal bone in the current first-trimester screening protocol along with nuchal translucency, free beta-hCG and PAPP-A can achieve high detection at a very low false-positive rate. Large datasets are needed to confirm whether the measurement of nasal bone length provides additional benefits beyond the assessment of the presence or absence of the nasal bone.
Crown-Rump Length↗
Audit of prenatal and postnatal diagnosis of isolated open spina bifida in three university hospitals in The Netherlands.
OBJECTIVE: To audit the current Dutch policy of prenatal detection of isolated open spina bifida based on offering detailed ultrasound examination only on indication. METHODS: A retrospective analysis of prenatally diagnosed isolated spina bifida cases and of newborns diagnosed with this condition was carried out in three university hospitals. The data were collected from databases and clinical records of the departments of prenatal diagnosis, obstetrics, neonatology, child neurology and neurosurgery of the three centers. RESULTS: Between January 1996 and December 1999, 88 cases of isolated open spina bifida were diagnosed prenatally by ultrasound investigation. Thirty-eight cases (43%) were diagnosed before the 24th week of gestation. Of these, 35 (92%) ended in termination of the pregnancy at the parents' request. Of the remaining 50 cases (57%) diagnosed after the 24th week of gestation, eight (16%) pregnancies were terminated beyond the legal limit for termination due to the severity of the condition. Of the 88 cases of isolated spina bifida, 25 infants (28%) were still alive at the age of 4 years. In the same audit period 112 newborn infants with isolated open spina bifida were admitted to the neonatology, child neurology, or neurosurgery ward of the three centers. Of these cases, 47 (42%) had been diagnosed prenatally and 65 (58%) were an unexpected finding at birth. In 24 infants (21%) surgical treatment was withheld because of the severity of the condition and predicted poor outcome, whereas the remaining 88 infants (79%) underwent surgical repair. CONCLUSION: The current practice in The Netherlands of offering ultrasound screening to high-risk patients only leads to the early detection of a minority of cases of spina bifida. Most cases are diagnosed either after the 24th week of gestation or they remain undiagnosed until after birth. When spina bifida is diagnosed before the 24th week of gestation the vast majority of parents opt for termination. In order to reduce the birth prevalence of spina bifida in The Netherlands the introduction of a policy of routine ultrasound screening should be considered.
Child, Preschool↗
[Ultrasound screening for Down's syndrome early in pregnancy: nuchal translucency thickness].
Screening for Down's syndrome (DS) in the Netherlands is based on maternal age. Women aged 36 years or above are offered amniocentesis or chorionic villus sampling to determine if the foetus has Down's syndrome or other chromosomal abnormalities. Disadvantages of this method are a low detection rate of affected pregnancies (no more than 15%) and iatrogenic miscarriages (0.5-1%). Pregnant women under the age of 36 are not eligible for screening, even though 70% of the children with Down's syndrome are born in this age group. Screening by measuring nuchal translucency thickness, an early ultrasound marker for Down's syndrome carried out in the first trimester of pregnancy, has a higher detection rate with a less invasive method and therefore fewer iatrogenic miscarriages. However, Dutch law prohibits the offer of screening to women with a low individual risk of DS (Population Screening Act), because of the anxiety this may provoke in these women. The Dutch Health Council's Prenatal Screening Committee has advised the minister of Public Health, Welfare and Sport that risk-assessment screening, in particular the triple test, should no longer be postponed and that research into (other) screening options should be stimulated.
Adult↗
Monitoring of fetuses with intrauterine growth restriction: a longitudinal study.
OBJECTIVE: To describe the time sequence of changes in fetal monitoring variables in intrauterine growth restriction and to correlate these findings with fetal outcome at delivery. METHODS: This was a prospective longitudinal observational multicenter study on 110 singleton pregnancies with growth-restricted fetuses after 24 weeks of gestation. Short-term variation of fetal heart rate, pulsatility indices of fetal arterial and venous Doppler waveforms and amniotic fluid index were assessed at each monitoring session. The study population was divided into two groups: Group 1 comprised pregnancies with severely premature fetuses, which were delivered < or =32 weeks and Group 2 included pregnancies delivered after 32 completed weeks. Logistic regression was used for modeling the probability for abnormality of a variable in relation to the time interval before delivery. Trends over time were analyzed for all variables by multilevel analysis. RESULTS: Ninety-three (60 in Group 1 and 33 in Group 2) fetuses had at least three data sets (median, 4; range, 3-27) and had the last measurements taken within 24 h of delivery or intrauterine death. The percentage of abnormal test results and the degree of abnormality were higher in Group 1 compared to Group 2. Amniotic fluid index and umbilical artery pulsatility index were the first variables to become abnormal, followed by the middle cerebral artery, aorta, short-term variation, ductus venosus and inferior vena cava. In Group 1, short-term variation and ductus venosus pulsatility index showed mirror images of each other in their trend over time. Perinatal mortality was significantly higher if both variables were abnormal compared to only one or neither being abnormal (13/33 (39%) vs. 4/60 (7%); P = 0.0002; Fisher's exact test). CONCLUSION: Ductus venosus pulsatility index and short-term variation of fetal heart rate are important indicators for the optimal timing of delivery before 32 weeks of gestation. Delivery should be considered if one of these parameters becomes persistently abnormal.
Case-Control Studies↗
Increased nuchal translucency and normal karyotype: coping with uncertainty.
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Adult↗
Ductus venosus studies in fetuses at high risk for chromosomal or heart abnormalities: relationship with nuchal translucency measurement and fetal outcome.
OBJECTIVE: To investigate, in a high-risk group of fetuses, the role of ductus venosus Doppler velocimetry as a prognostic factor, in addition to nuchal translucency measurement, for predicting chromosomal anomalies and, where the karyotype was normal, for predicting fetal outcome. METHODS: Nuchal translucency was measured and ductus venosus pulsatility index and late diastolic flow (a-wave) were recorded in 186 fetuses at a median gestational age of 12.6 weeks (range, 10-17). Fetal karyotype, the presence of structural anomalies, pregnancy outcome, neonatal examination at birth and postnatal follow up were the outcome values. RESULTS: Nuchal translucency measurement was increased in 112 fetuses. The outcome of pregnancy was normal in 130 fetuses. Fifty-six fetuses had an adverse outcome (46 chromosomal anomalies, three intrauterine deaths, six structural anomalies and one developmental disorder). The sensitivity of an abnormal ductus venosus pulsatility index or of absent or reversed flow during the a-wave was 65% for chromosomal anomalies and 68% for an adverse outcome. The specificity was 79%. There was a significant correlation between nuchal translucency and ductus venosus pulsatility index. In chromosomally normal fetuses with an enlarged nuchal translucency an abnormal ductus venosus flow was associated with a nearly nine-fold increase in adverse outcome (odds ratio 11.7). CONCLUSION: Ductus venosus Doppler velocimetry can be used in addition to nuchal translucency measurement as a predictor of chromosomal anomalies. However, as the ductus venosus blood flow pattern is correlated with nuchal translucency measurement it cannot be used as an independent variable to reduce the indication for fetal karyotyping. Ductus venosus Doppler velocimetry may have a role in the counseling of parents in the case of an enlarged nuchal translucency and normal karyotype by identifying those fetuses in need of an intensive follow up due to an increased risk of adverse outcome.
Adult↗
Outcome of fetuses with increased nuchal translucency.
Recent reports on nuchal translucency screening in unselected patient populations show results that are comparable with those reported by the thus far largest series on screening for Down's syndrome based on maternal age and nuchal translucency measurement. Much interest is focused on the prognostic value of increased nuchal translucency in fetuses with normal chromosomes. Increased nuchal translucency is regarded as a clear sign of declining fetal health, which can be associated with fetal demise, structural anomalies, rare genetic syndromes, and in particular congenital heart defects. A clear association is demonstrated between nuchal translucency above the 99th centile and congenital cardiac defects. Such a finding should prompt specialized echocardiography. However, on the whole the sensitivity of nuchal translucency screening is too low to consider this as the sole criterion to screen for critical heart defects.
Chromosome Aberrations↗
[Sensitive and specific screening for detection of spina bifida by echography in the second trimester; systematic review and meta-analysis].
OBJECTIVE: Evaluation of the diagnostic accuracy of ultrasound in the second trimester for the detection of spina bifida. DESIGN: Systematic review and meta-analysis. METHOD: Medline and Embase were searched to identify prospective studies in a general pregnant population. Also, in the Cochrane Library, references of identified reports and recent reviews were checked for relevant studies. Retrieved abstracts were selected independently by 2 authors using predefined criteria. Assessment of quality and generalizability of the included studies and data extraction were performed by 3 authors independently. The data were tested for heterogeneity and pooled estimates of sensitivity and specificity were calculated for all studies. RESULTS: 13 studies were included. Specificity was approximately 100% in all cases. Sensitivity varied from 40% to 100%. The summary point estimate for sensitivity was 71% with a 95% confidence interval of 59%-81%. CONCLUSION: Ultrasound in the second trimester is a specific investigation to detect spina bifida, which may detect seven out of ten defects. Used as a screening tool, it could contribute to a significant reduction in the number of children born with spina bifida.
Female↗
Intra- and interoperator repeatability of the nuchal translucency measurement.
OBJECTIVE: The aim of this study was to assess the repeatability of nuchal translucency measurement by well-trained sonographers either experienced or inexperienced with the measurement. METHODS: The nuchal translucency was measured three times by two out of nine operators in 161 pregnant women attending two teaching hospitals. Intra-operator and inter-operator variation was assessed by calculating the standard deviation (SD). Intraclass Correlation Coefficients (ICC) with a 95% lower confidence limit (95% CL) were calculated for each operator and for pairs of operators. Intra- and inter-operator kappa statistics were calculated, after dichotomising the results into a nuchal translucency smaller or larger than 3 mm. RESULTS: The SD of intra-operator difference was 0.35 mm. The intra-operator repeatability showed ICCs varying from 0.83 to 0.95 for the experienced operators and from 0.47 to 0.83 for the inexperienced. The SD of inter-operator differences was 0.56 mm, 0.46 mm and 0.44 mm, based on one, two and three measurements, respectively. The inter-operator repeatability showed a variation in ICC from 0.74 to 0.95 in pairs of experienced sonographers to 0.51 in one pair inexperienced with the measurement. The kappa value expressing the intra and inter-operator repeatability as being > 3 mm or < 3 mm was 0.88 and 0.85, respectively. CONCLUSION: This study supports the finding that the nuchal translucency measurement is reproducible, as long as it is performed by sonographers well trained in the technique of this measurement.
Down Syndrome↗