Split notochord syndrome — prenatal ultrasonographic diagnosis

Split notochord syndrome is a rare condition that is characterized by a persistent connection of the gut and dorsal skin of the back, an enteric cyst and vertebral anomalies. We present two cases in which prenatal ultrasound showed polyhydramnios. In one case it was associated with vertebral abnormalities and a right-sided mediastinal cyst found to be the stomach. Postnatal evaluation confirmed the diagnosis of split notochord syndrome. The association of sonographic findings of hydramnios, thoracic cysts and vertebral anomalies suggests prenatal diagnosis of split notochord syndrome. Copyright © 2001 John Wiley & Sons, Ltd.     

高残留农药福美双对斑马鱼胚胎脊索的特异性影响

福美双在我国是一种广泛使用的二硫代甲氨基甲酸盐类农药,它的高残留性已经引起世界各国的重视. 以斑马鱼胚胎作为试验动物模型,从分子水平探讨了福美双对胚胎脊索弯曲的毒性作用机制.结果表明,福美双造成斑马鱼胚胎脊索弯曲与重叠等形态学变化,脊索弯曲程度与福美双的染毒浓度呈正相关. 通过Ⅱ型胶原蛋白抗体染色表明,福美双引起软骨发育的变化与Ⅱ型胶原蛋白表达的降低密切相关. 试验进一步表明,斑马鱼胚胎适合作为农药毒性评价的模型.      

Unexpected phenotypes of malformations induced in Xenopus tropicalis embryos by combined exposure to triphenyltin and 9-cis-retinoic acid

Xenopus tropicalis embryos were exposed for 48 hr to the mixtures of 5 g Sn/L triphenyltin(TPT), which is a well-known endocrine disruptor, and 0.25–5 g/L 9-cis retinoic acid(9c-RA), which is the natural ligand of retinoid X receptor. The phenotypes induced by combined exposure were more variable than those resulting from single exposure to either TPT or 9c-RA. The prominent phenotypes included underdeveloped head structures, abnormal eyes, narrow fins, enlarged proctodaeum, etc. Especially, combined exposure induced unexpected notochord malformations, which ranged from small swellings of the surface of the tails to the extension and extrusion of notochord out of the posterior tails. Compared with the 5 g Sn/L TPT-treated group, the index of fin deficiency was not affected, and the index of axis deficiency was significantly increased with increasing RA concentrations in the mixtures. Our results suggest that combined exposure to TPT and 9c-RA induced not only more variable phenotypes of malformations than exposure to single compound but also some new and unexpected phenotypes.     

浮选剂黄药对蛙类胚胎的致畸毒性

报道了黑斑蛙(Rana nigromaculata)受精卵短期暴露于黄药溶液后对胚胎发育所引起的影响.浓度高于0.1ppm的黄药溶液能显著引起蛙胚的畸形发育,使孵出的蝌蚪呈现单一的畸形症状——脊索蜿蜒弯曲,为黄药污染的水体之水质监测提供了一个生物学指标.     

Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20–21-week fetuses

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified. Copyright © 2002 John Wiley & Sons, Ltd.     

Expanding multiple marker screening for Down's syndrome to include Edward'S syndrome

Information on maternal age and maternal serum alpha-fetoprotein, unconjugated oestriol (uE₃), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi-marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10–12 (67–80 per cent) cases with a false-positive rate of 0.3–0.6 per cent depending on the risk cut-off. A further case would have been detected as a result of screening for Down's syndrome alone. Similar results were obtained when the Edward's syndrome risk was based on uE₃ and hCG only. These data suggest that extending Down's syndrome screening to include Edward's syndrome risk will yield a high detection rate with only a small increase in the false-positive rate.     

Development of a simulator for training of fetoscopic myelomeningocele surgery

Objective

To develop a realistic simulation model for laparotomy-assisted fetoscopic spina bifida aperta (SBa) surgery, to be used for training purposes and preoperative planning.

Methods

The predefined general requirement was a realistic model of an exteriorized uterus, allowing all neurosurgical steps of the intervention. The uterus was modelled using ultrasound and MRI images of a 25 weeks’ gravid uterus, consisting of flexible polyurethane foam coated with pigmented silicone. The fetal model, contained an opening on the dorsal side for a customizable spinal insert with all the aspects of a SBa, including a cele, placode, and myofascial and skin layer. The model was assessed in a series of validation experiments.

Results

Production costs are low, uterus and fetus are reusable. Placental localization and the level and size of the spinal defect are adjustable, enabling case-specific adaptations. All aspects of the simulator were scored close to realistic or higher for both appearance and functional capacities.

Conclusions

This innovative model provides an excellent training opportunity for centers that are starting a fetoscopic SBa repair program. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning is promising.     

Maternal serum free beta hCG screening: Results of studies including 480 cases of down syndrome

The median maternal serum free beta human chorionic gonadotropin (hCG) multiple of the median (MOM) of 480 Down syndrome cases in the second trimester was 2·64, significantly greater than the reported median MOM of intact hCG (p<0·0001). In 234 of these cases from retrospective and prospective studies, the effectiveness of maternal serum free beta hCG was evaluated in combination with alpha-fetoprotein (AFP) and maternal age in second-trimester Down syndrome screening. Down syndrome detection in the gestational age range of 14–16 weeks was 82 per cent. In all gestational weeks (14–22), a 77·7 per cent Down syndrome detection rate was achieved. In prospective screening of 44 272 patients under the age of 35 years, 69 per cent of Down syndrome cases were detected (73 per cent in gestational weeks 14–16). The false-positive rate for the prospective study was 3·8 per cent. The use of free beta hCG combined with maternal serum AFP and maternal age-related risk for Down syndrome in a screening population (i.e., women under 35 years) yields an improved detection efficiency over other protocols.     

Second-trimester maternal serum immunoreactive inhibin as a marker for fetal Down's syndrome

We measured immunoreactive inhibin in the maternal serum of 80 pregnancies with a chromosomally normal fetus and ten Down's syndrome pregnancies in the second trimester. The inhibin level in all Down's syndrome pregnancies was above the normal median; the multiple of the normal median (MoM) was 1.9. We found a statistically significant difference between the levels of inhibin in unaffected and affected pregnancies (Kolmogorov–Smirnov test: p <0.002). Using an arbitrarily chosen cut-off of 2.4 MoM, 40 per cent of Down's syndrome and 5 per cent of the normal pregnancies were found. We conclude that immunoreactive inhibin may be useful as a marker for fetal Down's syndrome.     

Urinary multiple marker screening for down's syndrome

We have examined the possibility of using multiple markers in maternal urine rather than serum in order to screen for Down's syndrome. Urine samples were available from 36 cases (24 Down's syndrome, five Edwards' syndrome, three Turner's syndrome, one Klinefelter's syndrome, one triploidy, one triple-X, one twin discordant for Down's syndrome) and 294 controls, including three twins. Three markers were tested: the β-core fragment of human chorionic gonadotrophin (hCG), total oestrogen (tE) and the free a subunit of hCG. Levels were corrected for creatinine excretion and expressed as multiples of the gestation-specific median (MOM) level from the singleton controls. The median value for the singleton Down's syndrome cases was 6.02, 0.74, and 1.08 MOM for β-core-hCG, tE, and a-hCG, respectively. The increases in β-core-hCG and the reduction in tE levels were highly significant (P<0.0001 and 0.005, respectively; Wilcoxon rank sum test) but the increase in free a-hCG was not (P=0.40). On the basis of a mathematical model, the expected detection rate for a 5 per cent false-positive rate was 79.6 per cent for β-core-hCG alone, which increased to 82.3 per cent when combined with tE. Aneuploidies other than Down's syndrome were characterized by low levels of tE and either low or high β-core-hCG.     

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was −0.21 which was statistically significant (p=0.02, 95% confidence interval −0.38 to −0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester. Copyright © 2001 John Wiley & Sons, Ltd.     

Accuracy of Down syndrome risks produced in a first-trimester screening programme incorporating fetal nuchal translucency thickness and maternal serum biochemistry

Over the past three years approximately 12 000 women have been screened in the first trimester through our OSCAR programme, which utilizes fetal NT and maternal serum free β-hCG and PAPP-A. During this time 30 cases of Down syndrome were identified either prenatally or postnatally. Using an established procedure the accuracy of predicted risk for Down syndrome was assessed in a population of 30 cases of Down syndrome and 11 758 unaffected pregnancies. The correlation between predicted risk and prevalence of Down syndrome was very high (r=0.9995). It is concluded that risks produced by the Fetal Medicine Foundation combined risk algorithm agree very closely with Down syndrome prevalence and can be used with confidence when counselling women of their risk. Copyright © 2002 John Wiley & Sons, Ltd.     

Urinary β-core human chorionic gonadotrophin: A new approach to Down's syndrome screening

Human chorionic gonadotrophin (hCG) is the most discriminatory maternal serum marker of Down's syndrome. We have carried out a study to establish whether urinary β-core-hCG, a major metabolic product of hCG, might be an even better marker. Urine samples were available from seven singleton pregnancies with Down's syndrome, and one each of Edwards' syndrome, triploidy, and twins discordant for Down's syndrome. β-Core-hCG levels were corrected for creatinine and expressed as multiples of the normal gestation-specific median (MOM) level derived from 67 singleton controls. There was a highly statistically significant elevation in level among the singleton Down's syndrome cases (P<0·0005; Wilcoxon rank sum test). All had levels exceeding 2 MOM with a median of 6·11 MOM (95 per cent confidence interval 3·7–10·0). The levels were extremely low in Edwards' syndrome (0·08 MOM) and triploidy (0·02 MOM), but the twin pregnancy discordant for Down's syndrome did not have a raised β-core-hCG level (0·64 MOM). The findings are sufficiently encouraging to investigate the possibility of urinalysis as a routine modality in the prenatal screening for Down's syndrome and other common serious aneuploidies.     

Late-onset growth restriction in Galloway–Mowat syndrome: a case report

Galloway–Mowat syndrome (GMS) is a rare autosomal recessive disorder and is characterized by marked intrauterine growth retardation, central nervous system anomalies, and early onset nephrotic syndrome. Of the reported cases in the literature, all were diagnosed postnatally. We describe a case of GMS in which only late-onset intrauterine growth restriction was detected by prenatal ultrasound. In her fourth pregnancy, the mother had delivered a male baby with clinical features of GMS who died at seven months of age due to early onset of nephrotic syndrome. In her fifth pregnancy, serial ultrasound examinations were normal during the first and second trimester of pregnancy. Growth restriction and microcephaly were not detectable until 28 to 32 weeks' gestation. At 40 weeks' gestation, a female baby was born with dysmorphic features of GMS. Nephrotic syndrome developed after birth and renal biopsy revealed minimal change nephrotic syndrome. The prenatal course of this case suggests GMS may not be diagnosed in early pregnancy and the only abnormality detected before birth was intrauterine growth restriction. Copyright © 2005 John Wiley & Sons, Ltd.     

Agreement between predicted risk and prevalence of Down syndrome in first trimester nuchal translucency screening

The agreement between predicted risks of Down syndrome and observed prevalence was investigated in a population of 11 847 singleton pregnancies screened by first trimester nuchal translucency at a single institution. Twenty-seven cases of Down syndrome were observed; 20 were detected prenatally by nuchal translucency and maternal age screening, three by other means and four postnatally. The screened women were grouped according to their predicted risk of having an affected pregnancy, and this was compared with the observed prevalence. A significant correlation between predicted and observed prevalences was noted, thus demonstrating that risk estimates for Down syndrome based on first trimester nuchal translucency screening are accurate. Copyright © 2002 John Wiley & Sons, Ltd.     

First-trimester maternal serum alpha-fetoprotein as a marker for fetal chromosomal disorders

We evaluated first-trimester maternal serum alpha-fetoprotein (MS-AFP) as a marker for fetal chromosomal disorders. The multicentre study was performed under the auspices of the Dutch Working Party on Prenatal Diagnosis. MS-AFP was measured in 2404 normal pregnancies and 72 chromosomally abnormal pregnancies. The median multiple of the normal median (MOM) in 32 Down's syndrome pregnancies was 0·83 with a 95 per cent confidence interval ranging from 0·60 to 1·04. The difference between the distributions of first-trimester MS-AFP in normal and Down's syndrome pregnancies was statistically significant (t-test: t = 2·34, P<0·05). Thirty-one per cent of the Down's syndrome pregnancies were found below the tenth percentile. We found no difference between normal pregnancies and pregnancies with other chromosomal disorders (eight cases with trisomy 18, MOM = 1·26; seven cases with sex chromosome abnormalities, MOM = 1·07; 22 cases with a chromosomal mosaic pattern in chorionic villi, MOM = 1·08). We conclude that first-trimester MS-AFP can discriminate between normal and Down's syndrome pregnancies, but is not an effective marker. First-trimester MS-AFP has no value as a marker for other fetal chromosomal disorders.     

Macrocephaly–cutis marmorata telangiectatica congenita syndrome—prenatal signs in ultrasonography

A new case of macrocephaly–cutis marmorata telangiectatica congenita (M-CMTC) syndrome is described. The patient presented typical congenital findings in utero, although the syndrome was diagnosed postnatally. The M-CMTC syndrome should be considered when there is a marked fetal overgrowth and progressive macrocephaly with no indications of maternal hyperglycemia or fetal hyperinsulinism. Our patient also had unilateral pleural effusion, curved femur and frontal bossing. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal treatment of fetal hydrops associated with the hypertelorism-dysphagia syndrome (opitz-g syndrome)

Non-immunological fetal hydrops diagnosed prenatally presents a difficult diagnostic and therapeutic problem. In the case presented, fetal hydrops was recognized at 19 weeks gestation and no specific cause was found prenatally in spite of extensive investigations. The fetal hydrops was treated in utero by thoracocentesis and an intravenous infusion of albumin carried out at fetoscopy. After birth the infant was recognized to have the hypertelorismdysphagia syndrome (or Opitz-G syndrome, McK no. 30710). This autosomal dominant syndrome consists of hypertelorism, laryngeal abnormalities, swallowing difficulties, hyprospadias and an imperforate anus. Fetal hydrops has been reported on one previous occasion in this syndrome. The intrauterine treatment given in this case may have been successful in reducing the neonatal complications of the Opitz-G syndrome.     

Prenatal ultrasound diagnosis of the Holt-Oram syndrome

The Holt-Oram syndrome is an autosomal dominant disorder consisting of a congenital heart defect in combination with characteristic upper limb abnormalities. This report presents the ultrasonographic follow-up of two fetuses at risk for the Holt-Oram syndrome. In the first fetus, the existence of Holt-Oram syndrome was suspected at 22 weeks of gestation; a ventricular septal defect, an atrial septal defect, and a minor skeletal defect were found. In the second fetus, no structural abnormalities were discovered until the 30th week, when a small atrial septal defect was detected. In both pregnancies, it was possible to exclude early in gestation the more severe forms of the Holt-Oram syndrome.     

Second-trimester cancer antigen 125 and Down's syndrome

This study explores if assay of cancer antigen 125 (CA 125) in maternal serum might aid the detection of Down's syndrome in the second trimester of pregnancy. CA 125 levels were determined retrospectively in stored maternal serum samples from ten Down's syndrome pregnancies and 78 controls matched for gestational and maternal age. In addition, second-trimester amniotic fluid samples from nine Down's syndrome and 109 unaffected pregnancies were analysed for CA 125. Maternal serum CA 125 values for Down's syndrome pregnancies were lower, with the median being 0.72 multiples of the unaffected population median. The medians for affected and unaffected pregnancies did not differ significantly and there was a considerable overlap in the range of values of cases and controls. The distribution of amniotic fluid CA 125 levels for Down's syndrome pregnancies resembled that for controls. From our present results, we could not find an association between Down's syndrome and second-trimester maternal serum or amniotic fluid CA 125 levels.