Prenatal Differentiation Research Articles

Association between fetal echogenic and/or dilated bowel and adverse perinatal outcomes.

Echogenic and/or dilated bowel is uncommonly encountered on prenatal ultrasound and may represent either a panel of differential diagnoses or a transient normal variant with excellent outcome. Prenatal differentiation between the two entities remains uncertain. Here, we aimed to review prenatal cases associated with echogenic and/or dilated bowel and analyze their prospective perinatal outcomes. This was a retrospective cohort study, carried out at a single center. All relevant data was retrieved from the hospital electronic records. Bowel echogenicity is defined as grade 0-3, in relation to the surrounding liver or bone echogenicity. Bowel dilatation is defined as the largest diameter >7 mm with the length >15 mm. Out of 59 cases with prenatal echogenic and or dilated bowel, 32 cases were analyzed, and 10/32 (31%) neonates among all categories showed intestine related pathologies that required postnatal care. Two out of 19 (11%) cases with echogenic bowel and one out of three (34%) cases with bowel dilatation revealed structural abnormality that required postnatal surgery. All cases were in stable conditions upon discharge from the hospital. There were no cases of perinatal death associated with bowel abnormalities. Echogenic bowel in isolation carries a low risk for structural bowel anomalies that require surgery. Dilated bowel represents an increased risk for intestinal obstruction. Combination of two ultrasonographic features, echogenicity and dilatation of the intestine should be considered as a suspicious sign of a genetic syndrome which may alter bowel function but may not require surgery.

Interneuron function and cognitive behavior are preserved upon postnatal removal of Lhx6

LIM homeobox domain transcription factor 6 (Lhx6) is crucial for the prenatal specification and differentiation of hippocampal GABAergic interneuron precursors. Interestingly, Lhx6 remains to be expressed in parvalbumin-positive hippocampal interneurons (PVIs) long after specification and differentiation have been completed, the functional implications of which remain elusive. We addressed the role of adult-expressed Lhx6 in the hippocampus by knocking down Lhx6 in adult mice (> 8 weeks old) using viral or transgenic expression of Cre-recombinase in Lhx6loxP/loxP mice. Late removal of Lhx6 did not affect the number of PVIs and had no impact on the morphological and physiological properties of PVIs. Furthermore, mice lacking Lhx6 in PVIs displayed normal cognitive behavior. Loss of Lhx6 only partially reduced the expression of Sox6 and Arx, downstream transcription factors that depend on Lhx6 during embryonic development of PVIs. Our data thus suggest that while Lhx6 is vitally important to drive interneuron transcriptional networks during early development, it becomes uncoupled from downstream effectors during postnatal life.

How to Better Distinguish between Type II and III Selective Fetal Growth Restriction in Monochorionic Twin Pregnancies?

Objectives: The objective of this study is to determine additional variables, next to umbilical artery (UA) Doppler, to help differentiate between Type II and III selective fetal growth restriction (sFGR). Methods: Retrospective analysis categorizing monochorionic diamniotic twin pregnancies with sFGR and abnormal UA Doppler as either Type II or III sFGR based on the diameter of the artery-to-artery (AA) anastomosis of ≤2 or >2 mm, respectively on placental examination after birth. This exploratory study compared maternal characteristics, pregnancy outcome, placental characteristics, and ultrasound features between the two groups. Results: We included 40 sFGR placentas, 13 were classified as Type II and 27 as Type III. Maternal age was higher in Type II. Small Type II twins had lower birth weights (BWs) for gestational age and BW discordance was higher in Type II. Type III placentas were more unevenly divided, but Type III pairs differed less in BW than expected relative to their placental discordance. Type III placentas more commonly had a vein-to-vein anastomosis and larger artery-to-vein anastomoses than Type II placentas, and proximate cord insertions were only observed in Type III. On the ultrasound scan at first diagnosis, small Type II twins were more growth-restricted. An AA anastomosis was detected in half of the Type III cases and in none of the Type II group. Signs of high-output cardiac strain were observed only in large Type III twins. In contrast, placental dichotomy was detected in nearly half of the Type II cases and only one Type III case. Conclusions: The presence of an AA anastomosis, signs of cardiac strain in the large twin, and proximate cord insertions suggested Type III sFGR, whereas placental dichotomy and a severe growth restriction were typically present in Type II. Prospective studies need to validate if these markers help prenatal differentiation between Type II and III sFGR.

Анатомічні варіанти вродженої діафрагмальної кили, їх клінічне значення та можливості пренатальної диференціації

Purpose — to present verified typical anatomical variants of isolated congenital diaphragmatic hernia and clinical outcomes in newborns depending on the type of pathology, to compare with data of prenatal examination, and to assess feasibility of prenatal differentiation of congenital diaphragmatic hernia. Materials and methods. The data of operation protocols and autopsy results of newborn patients with isolated congenital diaphragmatic hernia for the period 2007–2020 were analyzed, and then compared with prenatal exam data and clinical outcomes. Data from different anatomical variants of congenital diaphragmatic hernia were analyzed using descriptive statistics methods. Results. Anatomical data were evaluated in 67 cases with the following typical variants: left-sided non-communicating defect (20.9%), left-sided communicating with herniation of intestine (19.4%), intestine and stomach (26,9%), intestine, stomach and liver (19.4%, 13/67), right- sided communicating with intestine and liver herniation (10.4%), right- sided non-communicating (1.5%), bilateral communicating defects (1.5%). Mortality at the stage of stabilization in these variants was 0%, 0%, 11.1%, 30.8%, 71.4%, 0% and 100%, postoperative mortality, respectively, 7.1%, 0%, 12.5%, 44.4%, 0%, 0% (excluding bilateral hernia), total mortality 7.1%, 0%, 22.2%, 61.5%, 71.4%, 0%, 100%. Comparison of lung indices in patients with left-sided hernias showed their similarity in groups with non-communicating defects and communicating with herniation of intestine. Significant differences were found in the groups with herniation of the intestine and stomach, and intestines, stomach and liver. The mean liver-to-lung ratio in right-sided communicating defects was 3.7±1.9, in left-sided communicating defects 1.7±0.8 and in non-communicating 0.44±0.25, the difference between all groups was highly significant. Patterns of stomach position in different variants of pathology were determined. Conclusions. Analysis of postnatally verified cases of diaphragmatic hernia showed marked anatomical variability. The highest mortality and the lowest rate of surgical correction registered was in communicating right-sided defects, and in communicating left-sided with simultaneous herniation of the intestine, stomach and liver. The best outcomes were found in non-communicating defects, or in communicating with herniation of intestine. Prenatal evaluation of stomach position may be the basis to differentiation between clinico-anatomical variants of the pathology. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the Institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: congenital diaphragmatic hernia, congenital malformations, prenatal diagnosis.

VP09.07: Correlation between prenatal echogenic and/or dilated bowel and neonatal outcomes

Echogenic and/or dilated bowel is often encountered on prenatal ultrasound and may represent a feature of gastrointestinal pathology, chromosomal abnormality or sign of prenatal infection. Prenatal differentiation between transient, physiological versus pathological manifestation is often difficult and remain uncertain. As a consequence, patients' counselling and timely involvement of pediatric surgeons is challenging. We aimed to review prenatal cases with echogenic or/and dilated bowel and analyse their neonatal outcomes. This is a retrospective observational study. All ultrasound scans demonstrating fetal echogenic and/or dilated bowel were retrieved from the viewpoint and grouped into three categories: 1. echogenic; 2. dilated and 3. combined cases. Bowel echogenicity has been defined as grade 1 to 3, in relation to the surrounding liver or bone echogenicity. Bowel dilatation is defined as the largest diameter measuring >7mm during second and third trimester. Out of 26,353 screened prenatal ultrasound scans: 30, 3 and 8 cases were identified with bowel echogenicity (grade 2 or 3), dilatation and their combination respectively. 9/41 (21%) neonates had confirmed gastrointestinal related pathologies; 5 with echogenic and 2 from each, dilated and combined bowel abnormalities group. 3/30 (10%) cases with echogenic and 1/8 (13%) case with dilated bowel required postnatal intestinal surgery. None among neonates with combined echogenic and dilated bowel exhibited structural intestinal abnormality that needed surgical correction. Prenatal diagnosis of isolated echogenic and/or dilated bowel carries overall favourable neonatal outcomes. However, still minority of cases with fetal echogenic or dilated bowel may elucidate of possible gastrointestinal abnormalities that require thorough parents' counselling, prenatal work up and multidisciplinary team involvement. Further research is needed to more precisely define prenatal ultrasound features of severe gastrointestinal abnormalities that require neonatal interventions.

Prenatal exposure to excess chromium attenuates transcription factors regulating expression of androgen and follicle stimulating hormone receptors in Sertoli cells of prepuberal rats

We have reported that gestational exposure to hexavalent chromium (CrVI) represses androgen receptor (Ar) and follicle stimulating hormone receptor (Fshr) in Sertoli cells (SCs) of adult rats, while the mechanism underlying remains obscure. We tested the hypothesis “transient gestational exposure to CrVI during the critical embryonic windows of testicular differentiation and growth may have adverse impact on transcription factors controlling the expression of Ar and Fshr in SCs of the F1 progeny”. CrVI (K2Cr2O7) was given through drinking water (50 ppm, 100 ppm and 200 ppm), to pregnant rats from gestational day 9–14 (testicular differentiation) and 15 to 21 (prenatal differentiation and proliferation of SC); male progenies were sacrificed on postnatal day 30 (Completion of postnatal SC maturation). A significant increase in free radicals and decrease in enzymatic and non-enzymatic antioxidants were observed in SCs of experimental rats. Real time PCR and western blot data showed decreased expression of Ar, Fshr, Inhibin B, Transferrin, Androgen binding protein, Claudin 11 and Occludin in SCs of experimental rats; concentrations of lactate, pyruvate and retinoic acid also decreased. Serum FSH, luteinizing hormone and estradiol increased, whereas testosterone and prolactin decreased in experimental rats. Western blot detection revealed decreased levels of transcription factors regulating Fshr viz., USF-1, USF-2, SF-1, c-fos, c-jun and GATA 1, and those of Ar viz., Sp-1, ARA54, SRC-1 and CBP in experimental rats, whereas the levels of cyclinD1 and p53, repressors of Ar increased. ChIP assay detected decreased USF-1 and USF-2 binding to Fshr promoter, and binding of Sp-1 to Ar promoter. We conclude that gestational exposure to CrVI affects SC structure and function in F1 progeny by inducing oxidative stress and diminishing the expression of Ar and Fshr through attenuation of their specific transcriptional regulators and their interaction with the respective promoter.

UHL’S ANOMALY: AN UNCOMMON CAUSE OF FETAL CARDIOMEGALY

Uhl’s anomaly is a rare congenital heart defect associated with RV and TV dysplasia. Prenatal differentiation from Ebstein anomaly is difficult. A 29 year old woman underwent fetal echocardiography at 22 weeks gestation due to fetal cardiomegaly. Imaging revealed an abnormal cardiac axis (80°),

Postnatal Effects of Sex Hormones on Click-Evoked Otoacoustic Emissions: A Study of Adolescents with Gender Dysphoria

Click-evoked otoacoustic emissions (CEOAEs) are echo-like sounds, generated by the inner ear in response to click-stimuli. A sex difference in emission strength is observed in neonates and adults, with weaker CEOAE amplitudes in males. These differences are assumed to originate from testosterone influences during prenatal male sexual differentiation and to remain stable throughout life. However, recent studies suggested activational, postnatal effects of sex hormones on CEOAEs. Adolescents diagnosed with gender dysphoria (GD) may receive gonadotropin-releasing hormone analogs (GnRHa) in order to suppress endogenous sex hormones and, therefore, pubertal maturation, followed by cross-sex hormone (CSH) treatment. Using a cross-sectional design, we examined whether hormonal interventions in adolescents diagnosed with GD (62 trans boys, assigned female at birth, self-identifying as male; 43 trans girls, assigned male at birth, self-identifying as female), affected their CEOAEs compared to age- and sex-matched controls (44 boys, 37 girls). Sex-typical differences in CEOAE amplitude were observed among cisgender controls and treatment-naïve trans boys but not in other groups with GD. Treatment-naïve trans girls tended to have more female-typical CEOAEs, suggesting hypomasculinized early sexual differentiation, in support of a prominent hypothesis on the etiology of GD. In line with the predicted suppressive effects of androgens, trans boys receiving CSH treatment, i.e., testosterone plus GnRHa, showed significantly weaker right-ear CEOAEs compared with control girls. A similar trend was seen in trans boys treated with GnRHa only. Unexpectedly, trans girls showed CEOAE masculinization with addition of estradiol. Our findings show that CEOAEs may not be used as an unequivocal measure of prenatal androgen exposure as they can be modulated postnatally by sex hormones, in the form of hormonal treatment.

Gene expression profiling reveals differential patterns between microcystic congenital cystic adenomatoid malformation and congenital lobar emphysema

IntroductionCongenital cystic adenomatoid malformation (CCAM), especially type-III, shares similar sonographic features with congenital lobar emphysema (CLE) in routine ultrasound scan. Thus, prenatal differentiation of CLE from a microcystic CCAM is challenging and difficult in practice. Discovery of molecular biomarkers has important clinical significance. MethodsWe profiled gene expression in lung tissue from four CCAM type-III and five CLE subjects by microarray. A bioinformatic tool was used for signal pathways enrichment analysis. Further, quantitative reverse transcriptase PCR (qRT-PCR) was used to verify the results. ResultsA total of 426 genes were identified to be significantly differentially expressed (fold-change >2.0, q value <0.05) between microcystic CCAM and CLE. Of these differentially expressed genes (DEGs), 392 were upregulated and 34 were downregulated in microcystic CCAM compared with CLE. Unsupervised clustering of the “expressed” genes could clearly delineate the CCAM and CLE samples. We also confirmed that eight randomly chose genes were differentially expressed at the mRNA level between CCAM and CLE. ConclusionsCCAM type-III and CLE have differential gene expression patterns. Our pilot study may gain a deeper understanding of the organogenetic origins and pathogenesis of these conditions. The suggestive candidates may serve as potential biomarkers for definitive diagnosis of congenital cystic lung lesions and eventually to treat them appropriately.

Prenatal diagnosis of megacystis microcolon intestinal hypoperistalsis syndrome by biochemical analysis of fetal urine.

The objective of the study is to determine a model of fetal urine biochemical markers to differentiate megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) from other megacystis. This is a retrospective study of biochemical analysis of fetal urine in patients who presented prenatally with megacystis. We studied β2-microglobulin, sodium, calcium, and phosphorus. Twenty-six patients subsequently diagnosed with MMIHS were compared with 2 control groups: one of end-stage renal failure (64 fetuses) and the second of "good" postnatal renal function (control group, 64 fetuses). Mean fetal urine β2-microglobulin was significantly higher (P<.001) in end-stage renal failure (15.7mg/L) than in MMIHS (2.2mg/L) and the control group (3.2mg/L). Fetal urine profiles differed significantly (P<.001) between MMIHS and the control group: median sodium 46.5 and 51mmol/L, median calcium 1.12 and 0.73mmol/L, and median phosphorus 0.03 and 0.15mmol/L respectively. Fetal urinary ionic index [ratio: calcium/(phosphorus×sodium)] gave an area under the ROC curve of 0.86, at 54% sensitivity and 97% specificity, with correct classification in 84% of cases. We defined a nomogram to obtain a probability for MMIHS. Fetal urinalysis can be helpful in prenatal differentiation of MMIHS from posterior urethral valves with good postnatal renal function.

Light and Electron Microscopic Studies on Prenatal Differentiation of Exocrine Pancreas in Buffalo.

The study was conducted on pancreas of 24 buffalo fetuses collected from abattoir and Veterinary clinics, GADVASU, Ludhiana. The buffalo fetuses were divided into three groups after measuring their CVRL, namely, group I (CVRL between 0 and 20 cm), group II (CVRL above 20 cm and up to 40 cm), and group III (CVRL above 40 cm) and their approximate age was calculated. The tissues were processed for light and ultrastructural studies. In group I, at 1.2 cm CVRL (34 days), the pancreas comprised tubules and solid nest of undifferentiated epithelial cells. At 7.5 cm CVRL (63 days) acinar cells with zymogen granules were observed. These acinar cells varied in shape from columnar to pyramidal. At 12.8 cm CVRL (86 days), parenchyma began to organize into lobes and lobules. The centroacinar cells were observed at 12.8 cm CVRL (86 days). In group II, at 28.3 cm CVRL (137 days), there was extensive branching of tubules that resulted in highly branched ductal tree connecting exocrine secretary units to the duct system. The interlobular and intralobular ducts were well observed at this age yet the intercalated ducts were not completely developed. In group III, exocrine pancreas showed a massive growth at 48 cm CVRL (182 days) with distinct pancreatic lobes and lobules. At 54 cm CVRL (195 days), well developed pancreatic architecture was seen with the presence of extensive development of exocrine part organized in lobes and lobules with interlobular and intralobular ducts whereas the intercalated ducts were observed in 80 cm CVRL (254 days).

Epigenetic and transcriptional determinants of the human breast.

While significant effort has been dedicated to the characterization of epigenetic changes associated with prenatal differentiation, relatively little is known about the epigenetic changes that accompany post-natal differentiation where fully functional differentiated cell types with limited lifespans arise. Here we sought to address this gap by generating epigenomic and transcriptional profiles from primary human breast cell types isolated from disease-free human subjects. From these data we define a comprehensive human breast transcriptional network, including a set of myoepithelial- and luminal epithelial-specific intronic retention events. Intersection of epigenetic states with RNA expression from distinct breast epithelium lineages demonstrates that mCpG provides a stable record of exonic and intronic usage, whereas H3K36me3 is dynamic. We find a striking asymmetry in epigenomic reprogramming between luminal and myoepithelial cell types, with the genomes of luminal cells harbouring more than twice the number of hypomethylated enhancer elements compared with myoepithelial cells.

MR-based morphometry of the posterior fossa in fetuses with neural tube defects of the spine.

ObjectivesIn cases of “spina bifida,” a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs.MethodsThe TDPF and the CSA of 238 fetuses (20–37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18–37 GW, mean: 24.3 GW) were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences.ResultsNormal fetuses showed a significant increase in the TDPF (r = .956; p<.001) and CSA (r = .714; p<.001) with gestational age. In ONTDs the CSA was significantly smaller (p<.001) than in normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller than in controls (p = .160). In both ONTDs and in CNTDs the TDPF was significantly different from controls (p<.001).ConclusionsThe skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect.

Prenatal differential diagnosis of complete hydatidiform mole with a twin live fetus and placental mesenchymal dysplasia by magnetic resonance imaging.

To assess the use of magnetic resonance imaging (MRI) for prenatal differentiation between complete hydatidiform mole with a twin live fetus (CHMTF) and placental mesenchymal dysplasia (PMD). Three CHMTF cases and three PMD cases, from two institutions over a 6-year period, were retrospectively included in this study. Clinical findings including age, pregnancy history, serum hCG level, ultrasonography findings, complications of the mother, outcome of the fetus, and results of chromosomal study of fetus, amniotic fluid and lesion, if possible, were noted. MRI findings were evaluated by two radiologists with respect to the location of the disease (intra- or extra-fetal sac), the presence of multicystic component, and presence of intra- or extra-lesional hemorrhage. In all six cases, the diseases were recognized as multicystic lesions by ultrasonography and MRI. In two of three CHMTF cases, patients continued with the pregnancy, which resulted in spontaneous abortion. In one case of CHMTF, the patient underwent artificial abortion, after which the mole progressed into an invasive mole with lung metastases. All three PMD patients had live births, and two of the three babies had fetal growth restriction. By MRI, CHMTF was located within an extra-fetal sac accompanied by intra- and/or extra-lesional hemorrhage, while PMD was located within the placenta in the fetal sac without hemorrhage. MRI could provide important information about the prenatal differential diagnosis of CHMTF and PMD, based on the pathophysiology and characteristics of the diseases.

Endocrine disrupter effects on the gonads and pubertY

Evidence accumulating the past decades indicates that human populations are exposed to environmental chemicals interfering with endocrine systems. There is growing concern of the potential adverse impact of exposure to such endocrine disrupting chemicals (EDCs) on human health, based on observations in wildlife, animal model systems and reports of yet unexplained increased incidences of hormone related disorders in humans. Exposure in fetal and neonatal age may be associated with developmental and reproductive disturbances due to interference with the programming of normal hormone signaling and metabolic pathways. Boys are conceived to be more vulnerable than girls due to their more complicated and androgen driven prenatal sex differentiation. Male prenatal sex differentiation is crucially dependent on the functioning of fetal Leydig cells. Exposure of these cells to EDCs at critical time windows of development may result in undermasculinization and disorder (s) of sex development (DSD), such as hypospadias, cryptorchidism and ambiguous genitalia. Furthermore, a novel trend of earlier start of puberty has been found during the past few decades, at least in some regions and mostly affecting girls. Among plausible causes behind this phenomenon it has been suggested that exposure to EDCs affecting the programming or triggering of the pubertal clock could result in premature activation of gonadotropin secretion. Another hypothesis is that gonadotropin independent effects of EDCs are associated with an earlier start of puberty. Proof of principle of such potential roles of EDCs has been obtained from a multitude of studies in experimental animals and gained some support by case studies, exposure data and epidemiological investigations in humans. This presentation will review recent data and ongoing studies on the mechanism(s) of action of EDCs, including effects of mixtures, on the hypothalamuspituitary-gonadal axis in experimental animals and humans. The impact of genetic susceptibility on the degree of disrupting activity caused by certain EDCs will be discussed on the basis of ongoing animal studies.

P19.17: Rare case of multiple schisis associated defects in both twins in dichorionic pregnancy

and a large neural tube defect suggestive of a large thoracic myelomeningocele. A subsequent MRI suggested a meningocele containing no neural elements. At US, we confirmed a large thoracic meningocele with spinal cord tethering to the overlying skin. Fetal MRI confirmed the findings and a limited dorsal myeloschisis was suspected. Elective caesarean section was performed at 38 weeks. Postnatal examination confirmed a large dorsal midline fluid filled mass at the level of T7-T12 covered by a thin layer of normal skin. The structure transilluminated easily without evidence of neural tissue within. No neurological deficits were found on neonatal examination. Post partum MRI confirmed the diagnosis of limited dorsal myeloschisis. The infant underwent surgery on day 2 to remove the exophytic lesion and to release the tethered neural tissue. His post operative course was uncomplicated and he was discharged home well 10 days later. Despite the markedly abnormal prenatal appearance of LDM, with a large meningocele and a tethered fibroneural stalk, it is associated with a good prognosis. Prenatal differentiation between meningomyelocele and LDM is therefore essential for appropriate couselling. The role of fetal MRI is invaluable to aid in the diagnosis. Children born with such a lesion usually have no neurological deficit and a normal neurological outcome can be expected. However, neurological deterioration can occur in the absence of timely corrective surgery to release the tethered spinal cord and remove the exophytic skin lesion.

Fetale Lageanomalien und Heterotaxien

Disorders of laterality and heterotaxy syndromes are rare diseases with an incidence of 1-1.5/10,000 live births. They are associated with numerous viscerocardiac anomalies and malformations. In particular, heterotaxy syndromes are associated with complex cardiac and extracardiac malformations that have an important impact on the prenatal and postnatal course. A prenatal differentiation between the 2 main variants of heterotaxy--left and right isomerism--is possible by assessment of cardiac rhythm, anomalies of caval veins and descending aorta and concomittant cardiac and extracardiac anomalies. An exact diagnosis is mandatory for adequate counselling of the parents and planning of postnatal care. Left isomerism has a high intrauterine mortality, caused by early atrioventricular block with subsequent cardiac failure and hydrops. In contrast, right isomerism has a high postnatal mortality due to the more complex type of cardiac defects and splenic disorders. The type of associated cardiac and extracardiac anomalies determines the postnatal morbidity and mortality. Polysplenia and asplenia may be associated with immunological disorders, that cannot be ruled out in the prenatal period, and further complicate the postnatal course.

Cx36 Is a Target of Beta2/NeuroD1, Which Associates with Prenatal Differentiation of Insulin-producing β Cells

The insulin-producing β cells of pancreatic islets are coupled by connexin36 (Cx36) channels. To investigate what controls the expression of this connexin, we have investigated its pattern during mouse pancreas development, and the influence of three transcription factors that are critical for β-cell development and differentiation. We show that (1) the Cx36 gene (Gjd2) is activated early in pancreas development and is markedly induced at the time of the surge of the transcription factors that determine β-cell differentiation; (2) the cognate protein is detected about a week later and is selectively expressed by β cells throughout the prenatal development of mouse pancreas; (3) a 2-kbp fragment of the Gjd2 promoter, which contains three E boxes for the binding of the bHLH factor Beta2/NeuroD1, ensures the expression of Cx36 by β cells; and (4) Beta2/NeuroD1 binds to these E boxes and, in the presence of the E47 ubiquitous cofactor, transactivates the Gjd2 promoter. The data identify Cx36 as a novel early marker of β cells and as a target of Beta2/NeuroD1, which is essential for β-cell development and differentiation.

P12.18: Prenatal differentiation of fetal akinesia deformation sequence by DNA-analysis of Acetylcholine receptor subunits

P12.18: Prenatal differentiation of fetal akinesia deformation sequence by DNA-analysis of Acetylcholine receptor subunits

Prenatal diagnosis and postnatal outcome of fetal spinal defects without Arnold–Chiari II malformation

To determine the prenatal evolution/natural history and postnatal outcome of fetuses diagnosed with a neural tube defect (NTD) lacking the Arnold-Chiari-II malformation (ACM II). This retrospective study reviewed 16 fetuses evaluated with ultrasound (US) and MRI at a single referral center from 1/2000 to 8/2007. Follow-up studies and available postnatal outcomes were reviewed. Postpartum diagnosis was terminal myelocystoceles 7/16 (44%); myelomeningoceles (MMCs) 3/16 (19%); lipomyelomeningoceles 2/16(13%); and thoracic myelocystocele 1/16 (6%). Three patients (19%) were lost to follow-up or termination of pregnancy. Two prenatally diagnosed 'closed' NTD were postnatally found to be MMCs. Three of the myelocystoceles had additional omphalocele, bladder extrophy, imperforate anus and spinal defect (OEIS complex). For the total cohort, impaired lower extremity function was seen in 38%, impaired bladder function in 64%, and ventriculoperitoneal shunting in 8%. Four fetuses with a myelocystocele developed hindbrain herniation in the third trimester of pregnancy. The preterm delivery rate was 38%. Five of eight (63%) neonates with postnatally diagnosed myelocystoceles had mothers with a body mass index over 30. Prenatal differentiation between closed and open NTD is not always possible. Postnatal outcome of isolated myelocystocele and MMC seems to be more favorable than for an NTD with ACM II (shunt requirement). Incontinence is the major childhood morbidity. Maternal obesity may be a risk factor for closed NTDs.