Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations.

OBJECTIVE: To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies. METHODS: We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort. RESULTS: Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies. CONCLUSION: Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations

Agenesis of olfactory bulbs: A forgotten diagnostic indicator of acampomelic campomelic dysplasia

Campomelic dysplasia (CD) and its variant acampomelic campomelic dysplasia (ACD) are caused by SOX9 haploinsufficiency. This gene encodes a transcription factor crucial for embryogenesis and primarily expressed in the olfactory bulbs. The detection of agenesis of olfactory bulbs could help establish a prenatal diagnosis of CD or ACD, although prevalence of this sign remains unknown.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Acute necrotizing biliary pancreatitis in an obese child.

Introduction Acute necrotizing pancreatitis is a rare but severe condition that occurs in less than 1% of children with pancreatitis. It can cause partial or complete destruction of the pancreatic tissue, leading to high morbidity and mortality. The main etiologies of pancreatitis in children include genetic mutations, trauma and gallstones. It has been shown that obesity worsen pancreatitis prognosis. Gallstones are uncommon in children. Risk factors include total parenteral nutrition, ceftriaxone, obesity, spherocytosis and Down’s syndrome; however 50% are idiopathic. With the rising prevalence of obesity in Western countries, the aim of this case is to highlight obesity as an uncommon but important risk factor for gallstones and severe pancreatitis. Case report A 10-year-old girl was admitted for severe abdominal pain and vomiting lasting for 3 days. She was overweight (BMI: 28,5kg/m², +2,9DS), but had otherwise, no relevant medical history. Her mother and maternal grandmother had a history of cholecystectomy. She had epigastric and right hypochondria sensitivity at clinical examination. Biochemical investigations showed increased liver enzymes (SGPT: 92UI/L), lipase (5509: UI/L) and cholestasis (GGT: 171UI/L, total bilirubin: 3,9mg/dl of whom 3,1mg/dl direct bilirubin). Abdominal ultrasound evidenced acute cholecystitis without dilatation of the biliary duct or gallstones. Ascites was present, but the pancreas couldn’t be explored. Pancreatitis was most likely due to gallstone migration. The patient was treated with pain medication, intravenous fluids and antibiotics. There was no gallstone visible in the common bile duct on endoscopic ultrasound (EUS) which precluded a sphincterotomy. The girl’s clinical condition progressively worsened during hospitalization. Abdominal CT-scan performed at day 7 revealed extensive necrotizing pancreatitis, with a compound solid and liquid collection (10x7,5cm) in the pancreas body. MRCP confirmed the CT findings and ruled out residual gallstones in the choledochus. EUS guided pseudocyst drainage was performed and 2 cyst-gastrostomy drains were left in place. As performing cholecystectomy in the context of severe acute pancreatitis was at high risk, it was decided to postpone the intervention. The patient’s condition slowly improved and she was discharged 13 days later. Three days later, the patient had to be rehospitalized for severe abdominal pain, increased lipase, transaminases and GGT. Abdominal ultrasound showed hyperechoic material in the papillary region suggestive of biliary sludge. Sphincterotomy and biliary drainage were performed by endoscopic retrograde pancreatography (ERCP). EUS confirmed residual gallstones in the bladder prompting semi-urgent cholecystectomy. In summary, this 10-year-old obese girl was hospitalized for 40 days with severe necrotizing pancreatitis requiring naso-jejunal nutrition, intensive pain management and endoscopic pseudocyst drainage. Conclusion The gastrointestinal consequences of obesity in children are not sufficiently recognized by paediatricians as they are less frequent than in adults. We here report the case of a child who presented dramatic biliopancreatic complications of obesity which will impact her long-term wellbeing

Outcome of publicly funded nationwide first-tier noninvasive prenatal screening

Purpose Noninvasive prenatal screening (NIPS) using cell-free DNA has transformed prenatal care. Belgium was the first country to implement and fully reimburse NIPS as a first-tier screening test offered to all pregnant women. A consortium consisting of all Belgian genetic centers report the outcome of two years genome-wide NIPS implementation. Methods The performance for the common trisomies and for secondary findings was evaluated based on 153,575 genome-wide NIP tests. Furthermore, the evolution of the number of invasive tests and the incidence of Down syndrome live births was registered. Results Trisomies 21, 18, and 13 were detected in respectively 0.32%, 0.07%, and 0.06% of cases, with overall positive predictive values (PPVs) of 92.4%, 84.6%, and 43.9%. Rare autosomal trisomies and fetal segmental imbalances were detected in respectively 0.23% and 0.07% of cases with PPVs of 4.1% and 47%. The number of invasive obstetric procedures decreased by 52%. The number of trisomy 21 live births dropped to 0.04%. Conclusion Expanding the scope of NIPS beyond trisomy 21 fetal screening allows the implementation of personalized genomic medicine for the obstetric population. This genome-wide NIPS approach has been embedded successfully in prenatal genetic care in Belgium and might serve as a framework for other countries offering NIPS