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Biomedical subjects

R J Snijders

Publications and source records attributed to R J Snijders.

At least 19 recordsLinked to original sources
PubMed2000

Femur length and trisomy 21: impact of gestational age on screening efficiency.

OBJECTIVE: This study assesses two methods used to define relatively short femur in screening for trisomy 21 and examines changes in performance of screening with gestational age. DESIGN: Retrospective analysis of data on menstrual age, femur length (FL) and biparietal diameter (BPD) in 49 trisomy 21 pregnancies and 6069 normal controls. Reference ranges were derived for BPD/FL versus menstrual age and for FL versus BPD. Two methods of defining short femur (BPD/FL and observed-to-expected FL ratio) were examined for false-positive rates and detection rates for trisomy 21 at different gestational ages. RESULTS: In the control group the BPD/FL ratio and its standard deviation decreased with menstrual age. Trisomy 21 was associated with a significantly higher BPD/FL ratio (P < 0.001) and the deviation increased significantly with menstrual age (P < 0.05). Eleven percent of 28 fetuses examined at 15-17 weeks had a BPD/FL above the 95th centile compared with 24% of 21 fetuses examined at 18-20 weeks (P = 0.40). The median observed-to-expected FL ratio in the control group was 1.0 throughout the gestational age range but the standard deviation decreased significantly with menstrual age (P < 0.01). Trisomy 21 was associated with a significantly reduced observed-to-expected FL ratio (P < 0.001) and the deviation increased significantly with menstrual age (P < 0.05). A fixed cut-off of 0.91 for observed-to-expected FL ratio provided a false-positive rate of 12% at 15-17 weeks compared with 6% at 18-20 weeks of gestation (P < 0.001) with detection rates of 29 and 38%, respectively (P = 0.73). CONCLUSION: Irrespective of the definition used to define the condition, relatively short femur is a poor marker for trisomy 21 particularly when the assessment takes place before 18 weeks of gestation.

Adult↗
PubMed2000

Fetal echogenic bowel: parameters to be considered in differential diagnosis.

OBJECTIVES: To evaluate the extent that associated findings aid in the differential diagnosis and/or prognosis of fetal echogenic bowel. METHODS: Medical history, obstetric records and outcome details were examined for 131 consecutive pregnancies with fetal hyperechogenic bowel. RESULTS: In 62 (47%) cases, there were no visible anomalies other than hyperechogenic bowel and no evidence of growth restriction. This group included four (7%) pregnancies with Down syndrome, 15 (24%) with infection or a recent episode of influenza and eight (13%) with blood staining of amniotic fluid. In the remaining 69 (53%) cases, hyperechogenic bowel was accompanied by hydrops or nuchal edema (n = 16, 12.2%), growth restriction (n = 9, 6.9%), other markers for chromosome anomalies (n = 33, 25.2%) or multiple structural anomalies (n = 11, 8.4%). In this group, the prevalence of Down syndrome was 12%, infection or influenza was reported in 14 (20%) cases and there was blood staining of amniotic fluid in seven (10%). Cystic fibrosis screening was performed in 65 (50%) pregnancies; the results were negative in all cases and clinical assessment did not indicate cystic fibrosis in any of the 91 infants who were born alive. Maternal serum screening was performed in 41 (31%) pregnancies. High alpha-fetoprotein levels were associated with multiple abnormalities or severe growth restriction. CONCLUSIONS: In many pregnancies with fetal hyperechogenic bowel, there are multiple factors that may explain these findings. Thus identification of one potential underlying cause should not preclude further testing. Once chromosome defects, cystic fibrosis, structural abnormalities, infection and growth restriction have been excluded, parents can be counseled that the prognosis is good, irrespective of the presence or absence of blood stained amniotic fluid.

Adolescent↗
PubMed1999

Increased nuchal translucency in trisomy 13 fetuses at 10-14 weeks of gestation.

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10-14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10-14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT.

Chromosomes, Human, Pair 13↗
PubMed1999

Maternal age- and gestation-specific risk for trisomy 21.

OBJECTIVE: To provide estimates of maternal age- and gestational age-related risks for trisomy 21. METHODS: The prevalence of trisomy 21 was examined in 57,614 women who had fetal karyotyping at 9-16 weeks of gestation for the sole indication of maternal age of 35 years or more. On the basis of the maternal age distribution and the reported maternal age-related risk for trisomy 21 at birth, the expected number of trisomy 21 cases was calculated for each gestational age subgroup (9-10 weeks, 11-14 weeks and 15-16 weeks). The ratio of the observed to expected number of cases of trisomy 21 was then calculated and regression analysis was applied to derive a smoothened curve. The formula for maternal age- and gestational age-related risk was then applied to a population of 96,127 pregnancies that were examined at 10-14 weeks to calculate the expected number of trisomy 21 pregnancies, and this number was compared to the observed number of 326. RESULTS: In the 57,614 pregnancies there were 538 cases of trisomy 21. The relative prevalences of trisomy 21, compared to a prevalence of 1.0 at 40 weeks, was 10 exp(0.2718 x log(10)(gestation)2 - 1.023 x log10(gestation) + 0.9425). On the basis of the estimated maternal age- and gestational age-related risks, the expected number of trisomy 21 cases at 10-14 weeks of gestation in the 96,127 pregnancies was 329 (95% confidence interval 291-361), which was not significantly different from the observed number of 326 cases (chi2 = 0.02). CONCLUSION: The risk for trisomy 21 increases with maternal age and decreases with gestation. The prevalence of trisomy 21 at 12 and 16 weeks of gestation is higher than the prevalence at 40 weeks by 30% and 21%, respectively.

Adult↗
PubMed1998

UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group.

BACKGROUND: Prenatal diagnosis of trisomy 21 currently relies on assessment of risk followed by invasive testing in the 5% of pregnancies at the highest estimated risk. Selection of the high-risk group by a combination of maternal age and second-trimester maternal serum biochemistry gives a detection rate of about 60%. We investigated assessment of risk by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10-14 weeks of gestation. METHODS: The risk of trisomy 21 was estimated for 96127 women of median age 31 years (range 14-49) with singleton pregnancies. Ultrasonography was done by 306 appropriately trained sonographers in 22 centres. Risk of trisomy 21 was calculated from the maternal age and gestational-age-related prevalence, multiplied by a likelihood ratio depending on the deviation from normal in nuchal-translucency thickness for crown-rump length. The distribution of risks was investigated and the sensitivity of a cut-off risk of 1 in 300 was calculated. Phenotype was assessed by fetal karyotyping or clinical examination of liveborn infants. FINDINGS: The estimated trisomy-21 risk, from maternal age and fetal nuchal-translucency thickness, was 1 in 300 or higher in 7907 (8.3%) of 95476 normal pregnancies, 268 (82-2%) of 326 with trisomy 21, and 253 (77.9%) of 325 with other chromosomal defects. The 5% of the study population with the highest estimated risk included 77% of trisomy-21 cases. INTERPRETATION: Selection of the high-risk group for invasive testing by this method allows the detection of about 80% of affected pregnancies. However, even this method of risk assessment requires about 30 invasive tests for identification of one affected fetus.

Adolescent↗
PubMed1998

Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation.

Increased fetal nuchal translucency thickness at 10-14 weeks of gestation is a common phenotypic expression of fetal chromosomal defects, structural abnormalities and genetic syndromes. This study reports on the prevalence of structural abnormalities and genetic syndromes in 4116 chromosomally normal pregnancies with increased fetal nuchal translucency thickness and reviews the relevant literature. In fetuses with increased nuchal translucency thickness, the prevalence of major cardiac defects, diaphragmatic hernia, exomphalos, body stalk anomaly and fetal akinesia deformation sequence is substantially higher than expected in the general population. In addition, there may be an association between increased nuchal translucency thickness and a wide range of rare skeletal dysplasias and genetic syndromes that are usually found in less than one in 10,000 pregnancies; however, the number of affected cases, both in the present and in previous series of fetuses with increased nuchal translucency thickness, is too small for definite conclusions to be drawn. The rates of miscarriage and perinatal death increase, whereas the rate of survival and the prevalence of live births with no obvious abnormalities decrease with increasing nuchal translucency thickness.

Adult↗
PubMed1998

Detection of sex chromosome abnormalities by nuchal translucency screening at 10-14 weeks.

At 10-14 weeks of gestation more than 80 per cent of fetuses affected by trisomy 21 can be detected by a screening programme based on a combination of maternal age and fetal nuchal translucency thickness (NT). The screen positive group in such a programme also identifies fetuses with sex chromosome abnormalities. In this ongoing multicentre screening study, involving 61,972 singleton pregnancies, 53 cases of sex chromosome abnormalities were identified. The fetal NT was above the 95th centile in 87.9 per cent of the 33 cases with 45,XO, and in 40 per cent of the 20 cases with 47,XXX, 47,XYY or 47,XXX. However, it was estimated that at 12 weeks of gestation our population would contain 42 cases with 45,XO and 104 cases with 47,XXY, 47,XYY or 47,XXX. Since the rate of intra-uterine lethality, between 12 and 40 weeks of gestation, is about 65 per cent for 45,XO and four per cent for 47,XXY, 47,XYY or 47,XXX, the respective number of livebirths with these chromosomal abnormalities would have been 15 and 100, respectively, without prenatal diagnosis. Assuming that all intra-uterine deaths are from those with increased NT, screening for trisomy 21 by maternal age and fetal NT would have identified only 20 per cent of potential livebirths in the 45,XO group and nine per cent of those with 47,XXY, 47,XYY or 47,XXX.

Down Syndrome↗
PubMed1997

First-trimester urine free beta hCG, beta core, and total oestriol in pregnancies affected by Down's syndrome: implications for first-trimester screening with nuchal translucency and serum free beta hCG.

We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Down's syndrome) in an attempt to see if any of the analytes have a value in Down's syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Down's syndrome with average multiple of the median levels of 1.81 and 2.91, respectively. Urine total oestriol was reduced (0.83) whilst maternal serum free beta hCG was increased (1.72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Down's group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false-positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first-trimester screening. Optimal first-trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy-associated plasma protein A.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1997

Diagnosis of the Meckel-Gruber syndrome at eleven to fourteen weeks' gestation.

OBJECTIVE: Our purpose was to examine the feasibility of diagnosing the Meckel-Gruber syndrome at 11 to 14 weeks' gestation, both in high-risk pregnancies and during routine ultrasonographic screening for fetal chromosomal abnormalities. STUDY DESIGN: The high-risk population consisted of 9 pregnancies in 7 women with previous pregnancies affected by the Meckel-Gruber syndrome. At 11 to 14 weeks' gestation, systematic ultrasonographic examinations of the fetal skull, brain, kidneys, bladder, hands, and feet were undertaken in each case. The low-risk population consisted of 21,477 self-referred pregnancies undergoing first-trimester ultrasonographic screening for chromosomal defects at 11 to 14 weeks' gestation. RESULTS: The triad of fetal occipital encephalocele, bilateral polycystic kidneys, and postaxial polydactyly was detected by transabdominal ultrasonography and confirmed by transvaginal scanning in 4 of the 9 pregnancies in the high-risk group. The parents were counseled of the likely recurrence of the Meckel-Gruber syndrome, and all elected to terminate the pregnancy by transcervical evacuation at 12 to 13 weeks. In the low-risk population the only case of Meckel-Gruber syndrome was identified at 13 weeks; in the remaining screened pregnancies there were no other cases of termination of pregnancy or neonatal death with the diagnosis of Meckel-Gruber syndrome. CONCLUSION: This report demonstrates that the Meckel-Gruber syndrome can be confidently detected at the 11- to 14-week scan in both high- and low-risk populations.

Cerebellum↗
PubMed1997

Early prenatal diagnosis of triploidy.

OBJECTIVE: Our purpose was to investigate the role of ultrasonography and maternal serum human chorionic gonadotropin in the early prenatal diagnosis of triploid pregnancies. STUDY DESIGN: A retrospective study on 61,314 consecutive singleton pregnancies examined by ultrasonography at 10 to 14 weeks' gestation was performed to identify the prenatal features of those complicated by triploidy. When available, the serum human chorionic gonadotropin level was measured and ascertained retrospectively. Cases lost to follow-up or for which no karyotype was available were excluded from the final analysis. RESULTS: Overall there were 18 cases of triploidy identified in a population of 58,862 singleton pregnancies, giving a prevalence of 1 in 3270. Fetal defects were observed in 8 (44.4%) of these cases; these included holoprosencephaly (n = 4), exomphalos (n = 3), and posterior fossa cyst (n = 1). In 6 (33.3%) cases the placenta showed molar changes. The fetal crown-rump length was below the 5th percentile in 10 of the 16 (62.5%) cases for which the menstrual age was also available. Fetal nuchal translucency thickness was above the 95th percentile in 12 (66.7%) cases, and the fetal heart rate was below the 5th percentile in 4 of the 13 (30.8%) cases evaluated. The maternal human chorionic gonadotropin level was high in 11 of the 13 (84.6%) cases tested, with similar distribution of the high values in molar and nonmolar triploidies. CONCLUSION: The combination of ultrasonographic examination of the fetoplacental features and measurement of the maternal serum level of human chorionic gonadotropin enables the diagnosis of most cases of triploidy at 10 to 14 weeks' gestation.

Chorionic Gonadotropin↗
PubMed1997

Fetal nuchal translucency thickness at 10-14 weeks' gestation and congenital diaphragmatic hernia.

OBJECTIVE: To examine the possible association between increased fetal nuchal translucency thickness at 10-14 weeks and congenital diaphragmatic hernia. METHODS: This was a multicenter ultrasound screening study for chromosomal defects in singleton pregnancies by a combination of maternal age and fetal nuchal translucency at 10-14 weeks' gestation. The prevalence of diaphragmatic hernia diagnosed prenatally or postnatally was calculated in the chromosomally normal group and in those pregnancies resulting in live births with no dysmorphic features suggestive of a chromosomal abnormality. We calculated the sensitivity of nuchal translucency above the 95th centile of the normal range in the detection of diaphragmatic hernia and the possible prognostic value of increased nuchal translucency in the prediction of outcome. RESULTS: There were 78,639 pregnancies presumed to be normal chromosomally, including 19 with diaphragmatic hernia. In four cases, the parents opted for termination of the pregnancy. The other 15 pregnancies resulted in live births; nine infants survived after successful surgical repair of the hernia, but six neonates died because of pulmonary hypoplasia. At the 10- to 14-week scan, the fetal nuchal translucency was above the 95th centile for crown-rump length in seven (37%) cases of diaphragmatic hernia. The translucency was increased in five of the six cases that resulted in neonatal death, compared with two of the nine survivors (Z = 2.32, P < .05). CONCLUSION: The prevalence of diaphragmatic hernia in chromosomally normal fetuses is about one in 4000, and nearly 40% of affected fetuses have increased nuchal translucency at 10-14 weeks' gestation. Increased nuchal translucency may be a marker of intrathoracic compression-related pulmonary hypoplasia.

Adolescent↗
PubMed1997

Ultrasound screening for anencephaly at 10-14 weeks of gestation.

In an ongoing study involving seven hospitals in London and surrounding areas, 55,237 fetuses were examined by ultrasound at 10-14 weeks of gestation. There were 47 fetuses (1 in 1175) with anencephaly which presented with acrania with varying degrees of cerebral degeneration. The first audit of results was performed in April 1995. During the first phase of the study 34,830 fetuses were examined and in eight of the 31 with anencephaly the diagnosis was not made at the 10-14-week scan. Following the audit, 20,407 fetuses were examined and in all 16 with anencephaly the diagnosis was made at the 10-14-week scan (p = 0.03). These findings demonstrate that anencephaly can be reliably diagnosed at the routine 10-14-week ultrasound scan, provided a specific search is made for the sonographic features for this condition.

Anencephaly↗
PubMed1997

Prenatal diagnosis of trisomy 18 at the 10-14-week ultrasound scan.

A beneficial consequence of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness (NT) at 10-14 weeks is the early diagnosis of trisomy 18. In a multicenter study of 91,091 singleton pregnancies there were 106 fetuses with trisomy 18 and 83% were identified by NT screening. Trisomy 18 was also associated with early onset intrauterine growth retardation, decreased fetal heart rate and the presence of exomphalos.

Adolescent↗
PubMed1997

Presence of the 'lemon' sign in fetuses with spina bifida at the 10-14-week scan.

In three cases of lumbosacral spina bifida diagnosed at 12, 13 and 14 weeks of gestation there was an associated lemon sign, or scalloping of the frontal bones, and in one case the fetal nuchal translucency was increased. In a multicenter ultrasound screening study at 10-14 weeks there were 61,972 singleton pregnancies including 29 cases of spina bifida, none of which was diagnosed at the routine first-trimester scan, but 28 of the 29 cases were detected by ultrasonography at 16-22 weeks; in one case the diagnosis was missed at the 20-week scan and the defect was identified at 32 weeks during a scan for localization of the placenta. The fetal nuchal translucency was above the 95th centile in only one of the cases (3.4%). It is possible that the majority of fetuses with spina bifida have a lemon sign in the first trimester, but the sensitivity of the 10-14-week scan in the diagnosis of spina bifida and the prevalence of the lemon sign at this gestation will only be established by further studies incorporating early systematic examination of the head and spine.

Female↗
PubMed1997

Body stalk anomaly at 10-14 weeks of gestation.

In a multicenter project of screening for chromosomal defects by fetal nuchal translucency thickness and maternal age at 10-14 weeks, 14 of 106,727 fetuses examined had body stalk anomaly. The ultrasonographic features were a major abdominal wall defect, severe kyphoscoliosis and a short umbilical cord. In all cases, the upper part of the fetal body was in the amniotic cavity, whereas the lower part was in the celomic cavity. The nuchal translucency thickness was above the 95th centile in ten (71.4%) of the cases, but the fetal karyotype was normal in all 12 fetuses evaluated. The findings suggest that early amnion rupture before obliteration of the celomic cavity is a possible cause of the syndrome.

Abdominal Muscles↗
PubMed1997

Preterm delivery and growth restriction in multifetal pregnancies reduced to twins.

Gestation at delivery, birthweight and pregnancy outcome of surviving fetuses from 127 multifetal pregnancies undergoing embryo reduction to twins were compared to 354 chromosomally normal non-reduced dichorionic twin pregnancies. First-trimester embryo reduction was carried out by intracardiac injection of KCl. In 16 (12.6%) of the 127 multifetal pregnancies reduced to twins, there was miscarriage of both fetuses before 24 weeks of gestation. The median interval between reduction and fetal loss was 5 weeks (range 1-12). In livebirths, the median gestation at delivery was 36 weeks (range 24-41) and the median difference in birthweight from the appropriate mean was -0.94 SD (range -3.89-1.73 SD). Both fetal loss before 24 weeks and the interval between embryo reduction and delivery were significantly associated with the gestation at reduction (r = 0.40, P < 0.001 and r = -0.57, P < 0.001 respectively). In the pregnancies reduced to twins compared to the non-reduced twins, the percentage of miscarriages was higher (12.6 compared to 2.5%; chi 2 = 19.2, P < 0.001), the median gestation at delivery was lower (36 compared to 37 weeks; t = -1.74, P < 0.05), and the median birthweight deficit was greater (-0.94 compared to -0.65 SD: t = -4.1, P < 0.001).

Abortion, Spontaneous↗