Congenital Chylothorax of the Newborn: A Systematic Analysis of Published Cases between 1990 and 2018

<b><i>Background:</i></b> Congenital chylothorax (CCT) of the newborn is a rare entity but the most common cause of pleural effusion in this age-group. We aimed to find the optimal treatment strategy. <b><i>Material and Methods:</i></b> A PubMed search was performed according to the PRISMA criteria. All cases were analyzed according to prenatal, perinatal, and postnatal treatment modalities and follow-ups. <b><i>Results:</i></b> We identified 753 cases from 157 studies published between 1990 and 2018. The all-cause mortality rate was 28%. Prematurity was present in 71%, male gender dominated 57%, mean gestational age was 34 weeks, and birth weight was 2,654 g. Seventy-nine percent of newborns had bilateral CCT, the most common associated congenital anomalies with CCT were pulmonary lymphangiectasia and pulmonary hypoplasia, and the most common chromosomal aberrations were Down, Noonan, and Turner syndromes, respectively. Mechanical ventilation was reported in 381 cases for mean 17 (range 1–120) days; pleural punctuations and drainages were performed in 32% and 64%, respectively. Forty-four percent received total parenteral nutrition (TPN) for mean 21 days, 46% medium-chain triglyceride (MCT) diet for mean 37 days, 20% octreotide, and 3% somatostatin; chemical pleurodesis was performed in 116 cases, and surgery was reported in 48 cases with a success rate of 69%. In 462 cases (68%), complete restitution was reported; in 34 of 44 cases (77%), intrauterine intervention was carried out. <b><i>Conclusion:</i></b> Respiratory support, pleural drainages, TPN, and MCT diet as octreotide remain to be the cornerstones of CCT management. Pleurodesis with OK-432 done prenatally and povidone-iodine postnatally might be discussed for use in life-threatening CCT.

Correction of Vertebral Bone Development in Ectodysplasin A1-Deficient Mice by Prenatal Treatment With a Replacement Protein

X-linked hypohidrotic ectodermal dysplasia with the cardinal symptoms hypodontia, hypotrichosis and hypohidrosis is caused by a genetic deficiency of ectodysplasin A1 (EDA1). Prenatal EDA1 replacement can rescue the development of skin appendages and teeth. Tabby mice, a natural animal model of EDA1 deficiency, additionally feature a striking kink of the tail, the cause of which has remained unclear. We studied the origin of this phenomenon and its response to prenatal therapy. Alterations in the distal spine could be noticed soon after birth, and kinks were present in all Tabby mice by the age of 4 months. Although their vertebral bones frequently had a disorganized epiphyseal zone possibly predisposing to fractures, cortical bone density was only reduced in vertebrae of older Tabby mice and even increased in their tibiae. Different availability of osteoclasts in the spine, which may affect bone density, was ruled out by osteoclast staining. The absence of hair follicles, a well-known niche of epidermal stem cells, and much lower bromodeoxyuridine uptake in the tail skin of 9-day-old Tabby mice rather suggest the kink being due to a skin proliferation defect that prevents the skin from growing as fast as the skeleton, so that caudal vertebrae may be squeezed and bent by a lack of skin. Early postnatal treatment with EDA1 leading to delayed hair follicle formation attenuated the kink, but did not prevent it. Tabby mice born after prenatal administration of EDA1, however, showed normal tail skin proliferation, no signs of kinking and, interestingly, a normalized vertebral bone density. Thus, our data prove the causal relationship between EDA1 deficiency and kinky tails and indicate that hair follicles are required for murine tail skin to grow fast enough. Disturbed bone development appears to be partially pre-determined in utero and can be counteracted by timely EDA1 replacement, pointing to a role of EDA1 also in osteogenesis.

Investigating Optimal Autologous Cellular Platforms for Prenatal or Perinatal Factor VIII Delivery to Treat Hemophilia A

Patients with the severe form of hemophilia A (HA) present with a severe phenotype, and can suffer from life-threatening, spontaneous hemorrhaging. While prophylactic FVIII infusions have revolutionized the clinical management of HA, this treatment is short-lived, expensive, and it is not available to many A patients worldwide. In the present study, we evaluated a panel of readily available cell types for their suitability as cellular vehicles to deliver long-lasting FVIII replacement following transduction with a retroviral vector encoding a B domain-deleted human F8 transgene. Given the immune hurdles that currently plague factor replacement therapy, we focused our investigation on cell types that we deemed to be most relevant to either prenatal or very early postnatal treatment and that could, ideally, be autologously derived. Our findings identify several promising candidates for use as cell-based FVIII delivery vehicles and lay the groundwork for future mechanistic studies to delineate bottlenecks to efficient production and secretion of FVIII following genetic-modification.

Congenital cytomegalovirus infection in twin pregnancy

Cytomegalovirus (CMV) infection is one of the preeminent congenital viral infections, and despite its potential morbidity, uncertainty about its physiopathology, prevention and treatment remains until now. We report a case of a dichorionic and diamniotic twin pregnancy in which only one of the fetus had signs of being affected. The first twin had prenatal diagnosis of intrauterine growth restriction and hyperechogenic bowel, attributable to CMV infection, while there was no evidence of infection of the second one. Prenatal treatment was done with maternal administration of valacyclovir and postnatal treatment of the infected newborn with oral valganciclovir with normal neurodevelopment assessment at 12 months corrected age. In this case, maternal CMV infection was not equally transmitted to both fetuses, suggesting that there may be intrinsic fetal and placental factors influencing both transmission and the clinical features of the infection.

The Effect of Prenatal and Postnatal Treatment with Intravenous Immunoglobulin on Severity of Neonatal Hemochromatosis: The Tale of Two Brothers (Case Report)

Background Neonatal hemochromatosis (NH) is a rare condition that was the main reason for liver transplantation in infants. With the realization that NH results from the fetal complement-mediated liver injury, intravenous immunoglobulins (IVIG) were successfully introduced for the treatment. Case Presentation We present two cases of NH from the same family to illustrate the role of antenatal treatment with IVIG in alleviation and possible prevention of this serious morbidity. Conclusion A prenatal treatment and early postnatal administration of IVIG are effective ways to manage NH that help to reduce the severity of the symptoms, prevent liver failure, and avoid the need for liver transplantation.

Fetal ultrasound diagnosis allows effective early postnatal treatment of hematometrocolpos

Fetal hematometrocolpos is a rare finding with an incidence of 1 in 16,000 female births. Timely diagnosis enables clinicians to formulate an appropriate management plan for the newborn. We present a case of fetal hematometrocolpos managed exclusively by prenatal and postnatal ultrasound scans allowing for effective immediate postnatal surgical treatment.

Assisted Reproductive Technology and Retinopathy of Prematurity

Although ART has changed the lives of many people, it has increased the burden on neonatologist and ophthalmologists with all types of complications related to prematurity in multiple births. In the last 20 to 25 years, there has been vast improvements in ART and neonatal intensive care, which has resulted in increased survival of most of the immature infants. There are specialized centers, which provide high‐risk obstetric care, intensive neonatal care, use of steroids in the prenatal care, improved postnatal treatment with surfactant and nitric oxide and better respirators and advanced equipment for the care of extremely immature infants. All these have contributed to improved survival. Therefore, current changes in neonatal care warrant careful ongoing evaluation during the coming years regarding ROP.