The Chest Radiographic Thoracic Area Can Serve as a Prediction Marker for Morbidity and Mortality in Infants With Congenital Diaphragmatic Hernia

Objective: Valid postnatal prediction parameters for neonates with congenital diaphragmatic hernia (CDH) are lacking, but recently, the chest radiographic thoracic area (CRTA) was proposed to predict survival with high sensitivity. Here, we evaluated whether the CRTA correlated with morbidity and mortality in neonates with CDH and was able to predict these with higher sensitivity and specificity than prenatal observed-to-expected (O/E) lung-to-head ratio (LHR).Methods: In this retrospective cohort study, all neonates with CDH admitted to our institution between 2013 and 2019 were included. The CRTA was measured using the software Horos (V. 3.3.5) and compared with O/E LHR diagnosed by fetal ultrasonography in relation to outcome parameters including survival, extracorporeal membrane oxygenation (ECMO) support, and chronic lung disease (CLD).Results: In this study 255 neonates were included with a survival to discharge of 84%, ECMO support in 46%, and 56% developing a CLD. Multiple regression analysis demonstrated that the CRTA correlates significantly with survival (p = 0.001), ECMO support (p < 0.0001), and development of CLD (p = 0.0193). The CRTA displayed a higher prognostic validity for survival [area under the curve (AUC) = 0.822], ECMO support (AUC = 0.802), and developing a CLD (AUC = 0.855) compared with the O/E LHR.Conclusions: Our data suggest that the postnatal CRTA might be a better prognostic parameter for morbidity and mortality than the prenatal O/E LHR.

Diagnostic value of systematic ultrasonography for trisomy 18 syndrome in fetuses before 16 weeks gestation

Purpose To explore the diagnostic value of systematic fetal ultrasonography for trisomy 18 (T18) syndrome before 16 weeks gestation. Methods A total of 12 fetuses with T18 were selected as research subjects and their nuchal translucency (NT) screening and fetal systematic ultrasonographic images acquired at 11–15 weeks were retrospectively analyzed. Results In the 12 fetuses’ NT screening, ten fetuses showed NT thickening, one showed nuchal cystic hygroma, four showed reversed a-wave ductus venosus flow, and three showed omphalocele. The most common anomalies on the systematic ultrasonography before 16 weeks gestation were cardiac defects (12/12, 100%), omphalocele (4/12, 33.3%), limb anomalies (5/12, 41.7%), and facial anomalies (3/12, 25.0%). Seven of the 12 fetuses had multiple structural malformations: three had two structural malformations (25.0%), three had three structural malformations (25.0%), and one had four structural malformations (8.3%). Conclusion Systematic fetal ultrasonography before 16 weeks gestation can detect most of the structural malformations of T18, effectively shortening the prenatal diagnosis time. It is therefore of great importance for reducing the birth rate of children with T18 and minimizing the physical and mental damage to mothers and their families.

Prenatal diagnosis and multidisciplinary management: a case report of congenital granular cell epulis and literature review

Congenital granular cell epulis (CGCE) is a rare benign soft tissue lesion that usually originates from the neonatal gingiva and can lead to difficulty in breathing and feeding upon birth. This current case report describes a female newborn with a gingival mass that was identified by prenatal fetal ultrasonography. At birth, the oral mass was observed to protrude from the mouth, which adversely affected feeding. The lips could not be closed. The breathing was unaffected. Through a multidisciplinary team approach involving several healthcare professionals, the mass was successfully removed under general anaesthesia during an uncomplicated surgical procedure. Postoperative histopathological examination confirmed that the mass was a CGCE of the newborn. The infant recovered well after the operation.

Association Between Ultrasonography Fetal Anomalies and Autism Spectrum Disorder

Background: Prenatal ultrasound is frequently used to monitor fetal growth and identify fetal anomalies that may suggest genetic or developmental abnormalities which may develop into congenital anomalies and diseases. Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, associated with a wide range of congenital anomalies. Nevertheless, very little has been done to investigate organ development using prenatal ultrasound as a means to identify fetuses with ASD susceptibility. Methods: A retrospective matched case-sibling-control study. ASD cases were matched to two control groups: typically developing sibling (TDS) closest in age to ASD child; and typically developing population (TDP), matched for age, sex, and ethnicity. The study comprised 659 children: 229 ASD, 201 TDS, and 229 TDP; 471 (71.5%) males. Results: Ultrasonography fetal anomalies (UFAs) were found in 29.3% of ASD cases vs. only 15.9% and 9.6% in the TDS and TDP groups (aOR=2.23, 95%CI=1.32-3.78, and OR=3.50, 95%CI=2.07- 5.91, respectively). Also, multiple co-occurring UFAs were significantly more prevalent among ASD cases. UFAs in the urinary system, heart, and head&brain were the most significantly associated with ASD diagnosis (aORUrinary =2.08, 95%CI=0.96-4.50 and ORUrinary=2.90, 95%CI=1.41-5.95; aORHeart=3.72, 95%CI=1.50-9.24 and ORHeart=8.67, 95%CI=2.62-28.63; and aORHead&Brain=1.77, 95%CI=0.68-4.64 and ORHead&Brain=6.50, 95%CI=1.47-28.80; vs. TDS and TDP, respectively). ASD fetuses were characterized by a narrower head and a relatively wider ocular-distance vs. TDP fetuses (ORBPD=0.81, 95%CI=0.70-0.94, and aOROcular-Distance=1.29, 95%CI=1.06-1.57). Finally, UFAs were associated with more severe ASD symptoms. Conclusions: Our findings shed important light on the abnormal multiorgan embryonic development of ASD and suggest fetal ultrasonography biomarkers for ASD.

Case Report: Subtotal Hemispherotomy Modulates the Epileptic Spasms in Aicardi Syndrome

The mechanism of epileptic spasms (ES) in Aicardi syndrome (AS) remains obscure. We compared intraoperative high-frequency oscillations (HFOs) and phase-amplitude coupling (PAC) before and after subtotal hemispherotomy in a 3-month-old girl with drug-resistant ES secondary to AS. Fetal ultrasonography showing corpus callosum agenesis, bilateral ventricular dilatation, and a large choroid plexus cyst confirmed AS diagnosis. Her ES started when she was 1 month old and had ten series of clustered ES per day despite phenobarbital and vitamin B6 treatment. After subtotal hemispherotomy, her ES dramatically improved. We analyzed two intraoperative electrocorticography modalities: (1), occurrence rate (OR) of HFOs; (2), PAC of HFOs and slow wave bands in the frontal, central, and parietal areas. We hypothesized that HFOs and PAC could be the biomarkers for efficacy of subtotal hemispherotomy in AS with ES. PAC in all three areas and OR of HFOs in the frontal and parietal areas significantly decreased, while OR of HFOs in the central area remained unchanged after subtotal hemispherotomy. We have demonstrated the usefulness of evaluating intraoperative HFOs and PAC to assess subtotal hemispherotomy effectiveness in AS patients with ES. Disconnecting the thalamocortical and subcortical pathways in the epileptic network plays a role in controlling ES generation.

A Bi-allelic Frameshift Mutation in NPNT Causes Bilateral Renal Agenesis in Humans

Background: Bilateral renal agenesis (BRA) is a lethal congenital anomaly caused by the failure of normal development of both kidneys early in embryonic development. Oligohydramnios upon fetal ultrasonography reveals BRA. Although exact causes are not clear, BRA is associated with mutations in many renal development genes. However, molecular diagnostics cannot pick up many clinical cases. Nephronectin (NPNT) may be a candidate protein for widening diagnosis. It is essential in kidney development and knockout of Npnt in mice frequently leads to kidney agenesis or hypoplasia. Methods: A consanguineous Han family experienced three cases of induced abortion in the second trimester of pregnancy due to suspicion of BRA. Whole-exome sequencing-(WES)-:based homozygosity mapping detected underlying genetic factors, and a knock-in mouse model confirmed the renal agenesis phenotype. Results: WES and evaluation of homozygous regions in II-3 and II-4 revealed a pathological homozygous frameshift variant in NPNT (NM_001184690:exon8:c.777dup/p.Lys260*), which leads to a premature stop in the next codon. The truncated NPNT protein exhibited decreased expression, as confirmed in vivo by the overexpression of WT and mutated NPNT. A knock-in mouse model homozygous for the detected Npnt mutation replicated the BRA phenotype. Conclusions: A biallelic loss-of-function NPNT mutation causing an autosomal recessive form of BRA in humans was confirmed by the corresponding phenotype of knock-in mice. Our results identify a novel genetic cause of BRA, revealing a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA.

A Fetus with Imperforate Anus Developing Pulmonary Hypoplasia Triggered by Transient Urethral Obstruction

Pulmonary hypoplasia is a rare entity in a fetus with imperforate anus. The fetus was diagnosed with high-type imperforate anus with rectourethral fistula based on the dilated fetal bowel and the presence of bowel calcification at 19 weeks of gestation. As gestation advanced, fetal ultrasonography demonstrated development of pulmonary hypoplasia, progressive bowel dilation, and persistent oligohydramnios from 28 weeks of gestation despite a fluid-filled bladder without hydroureter or hydronephrosis. To prevent further worsening of pulmonary hypoplasia caused by thoracic compression due to bowel dilation and oligohydramnios, a male neonate was delivered by cesarean section at 32 weeks of gestation. The neonate showed respiratory failure requiring full respiratory support. Although a catheter did not pass through the urethra into the bladder at birth, cystourethrography revealed the patency of fistula and stenosed lower urinary tract. Prenatal and postnatal findings strongly suggested that the meconium in the colon might have passed into the urethra in the penis, resulting in the physical blockage of urine outflow to the amniotic space which leads urine flow from the bladder to the colon through the fistula, which resulted in subsequent oligohydramnios and bowel dilation. To the best of our knowledge, this is the first case report of a fetus with imperforate anus developing pulmonary hypoplasia possibly due to urethral obstruction.