Cantrell五联症新生儿一例并文献复习

患儿出生后即发现“胸外心”入院,母亲妊娠期有糖尿病、孕早期感冒,无贫血、妊娠高血压综合征、心脏病等疾病,无家族遗传及代谢性疾病。入院查体:胸骨下端至脐部皮肤变薄,长约6 cm,见一膨出物约2 ×2.5 cm2规律搏动,皮肤颜色较周围皮肤颜色深,脐部位置偏高,腹部平坦。B超和CT诊断结果显示,该患儿胸骨缺损、心包部分缺损、膈肌前部缺损、脐上腹壁中线缺如伴心脏膨出、心血管畸形,因此明确诊断为完全Cantrell五联症。患儿为部分心脏异位,属于常见的胸腹型心脏异位。Cantrell五联症是临床上一种罕见的先天性畸形疾病,临床手术难度大,患儿生存率低。产前超声筛查对早期发现及诊断该病具有重要意义。

Artificial womb:a paradigm shift for saving extremely premature infants

To the Editor:Approximately 15 million preterm babies,i.e.,those delivered at<37 weeks of gestational age(GA),are born globally every year,and of them,0.4%are extremely premature infants(EPIs),i.e.,those delivered at<28 weeks of GA.^([1])Iterations of neonatal care have significantly extended the viability of preterm babies.However,improved viability is accompanied by an increased risk of unreversed injuries,such as bronchopulmonary dysplasia and intraventricular hemorrhage.Therefore,a more physiological simulating in utero status is needed to protect EPIs’immature organs during the transitional period and ensure that they develop in the same manner that they would have in the womb.

High‑Resolution and Multidimensional Phenotypes Can Complement Genomics Data to Diagnose Diseases in the Neonatal Population

Advances in genomic medicine have greatly improved our understanding of human diseases.However,phenome is not well understood.High-resolution and multidimensional phenotypes have shed light on the mechanisms underlying neonatal diseases in greater details and have the potential to optimize clinical strategies.In this review,we first highlight the value of analyzing traditional phenotypes using a data science approach in the neonatal population.We then discuss recent research on high-resolution,multidimensional,and structured phenotypes in neonatal critical diseases.Finally,we briefly introduce current technologies available for the analysis of multidimensional data and the value that can be provided by integrating these data into clinical practice.In summary,a time series of multidimensional phenome can improve our understanding of disease mechanisms and diagnostic decision-making,stratify patients,and provide clinicians with optimized strategies for therapeutic intervention;however,the available technologies for collecting multidimensional data and the best platform for connecting multiple modalities should be considered.

High-risk phenotypes of genetic disease in a Neonatal Intensive Care Unit population

To the Editor: Genetic diseases contribute to 35% of deaths during the first year of life and are a significant cause of intensive care.[1] A previous study based on the China Neonatal Genomes Project investigated the genetic causes of early infant deaths and found that >25% of deceased neonates with genetic diagnoses can be cured if diagnosed in time.[2] Therefore, it is crucial to target and diagnose neonates with genetic diseases as early as possible. According to our experience, the typical phenotypes, such as special facial features or multiple congenital anomalies (MCAs), indicate a high risk of genetic disease and lead physicians to perform genetic testing in neonates as early as possible. However, in practice, infants without typical phenotypes typically undergo a long and costly diagnostic process before genetic diagnoses are confirmed. Moreover, a recent survey by the American College of Medical Genetics and Genomics (ACMG) and other national professional organizations indicated that there are insufficient numbers of qualified geneticists to fulfil genetic service needs.[3] The ACMG published the general clinical features for genetic testing indications. For example, patients with phenotypes or family history data that strongly implicate a genetic cause may undergo genetic testing.[1] However, the study indicated that many genetic conditions arise de novo or are inherited with no family history.[1] A previous study attempted to apply the non-phenotype-driven panel approach in neonates admitted to the neonate intensive care unit (NICU).[4] However, at present, the diagnostic yield is only 3.45% (1/29).[4] In addition, the economic and ethical issues associated with genomic screening remain challenging. Therefore, the available indications for genetic testing may improve the management of genetic diseases.

Precision medicine via the integration of phenotype-genotype information in neonatal genome project

The explosion of next-generation sequencing(NGS)has enabled the widespread use of genomic data in precision medicine.Currently,several neonatal genome projects have emerged to explore the advantages of NGS to diagnose or screen for rare genetic disorders.These projects have made remarkable achievements,but still the genome data could be further explored with the assistance of phenotype collection.In contrast,longitudinal birth cohorts are great examples to record and apply phenotypic information in clinical studies starting at the neonatal period,especially the trajectory analyses for health development or disease progression.It is obvious that efficient integration of genotype and phenotype benefits not only the clinical management of rare genetic disorders but also the risk assessment of complex diseases.Here,we first summarize the recent neonatal genome projects as well as some longitudinal birth cohorts.Then,we propose two simplified strategies by integrating genotypic and phenotypic information in precision medicine based on current studies.Finally,research collaborations,sociological issues,and future perspectives are discussed.How to maximize neonatal genomic information to benefit the pediatric population remains an area in need of more research and effort.

CYP2C9^(*)3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks

Hemodynamically significant patent ductus arteriosus(hsPDA)is a severe condition in newborns.Ibuprofen is an effective treatment to reduce the severe complications and the need for surgical treatment.Several single-nucleotide polymorphisms(SNPs)were related to the ibuprofen metabolism,treatment effects,and the onset of side effects.The effects of SNPs on hsPDA response after ibuprofen treatment are unknown.Therefore,in this study,we recruited hsPDA patients with standard ibuprofen treatment.Those patients had participated in China Neonatal Genomes Project(CNGP,ClinicalTrials.gov Identifier:NCT03931707)with next-generation sequencing data.We reanalyzed the sequencing data and compared the allele frequencies of known ibuprofen-related SNPs between ibuprofen Responder and Non-responder groups.In total,185 hsPDA patients were recruited with gestational age(GA)ranging from 24 to 40 weeks.No significant differences were detected in the basic information,period of ibuprofen treatment,rate of conservative treatment,complications,and side effects between ibuprofen Responder group and Non-responder group.Totally,17 hsPDA carried CYP2C9^(*)3 and one with CYP2C9^(*)2 were detected.In the GA group of more than 30 GA weeks(GA>30 wks group),we found higher allele frequency of CYP2C9^(*)3 in Responder group than in Non-responder group(16%vs.0,p=0.0391).In the GA group of less than 30 GA weeks(GA≤30 wks group),the sum allele frequency of CYP2C9^(*)3 and CYP2C9^(*)2 had no stastical difference between two groups(Responder group vs.Non-responder group,13%vs.11%,p=0.768).Therefore,we came to conclude that genetic tests of CYP2C9^(*)3 site may benefit the prediction of ibuprofen treatment outcome for hsPDA patients with gestational age of more than 30 weeks.