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

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Bronchopulmonary dysplasia in very preterm infants: Outcome up to preschool age, in a single center of Austria.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in infancy and is associated with neonatal comorbidity and impairment in pulmonary and neurodevelopmental (ND) long-term outcome. METHODS: This was a retrospective, single-center, cohort study to compare a cohort of very preterm infants (gestational age [GA], 24+0 -28+6 weeks) with BPD (n = 44), with a cohort of GA-matched preterm infants without BPD (n = 44) with regard to neonatal morbidity, incidence of lower respiratory tract infection (LRTI), ND outcome and growth to 2 years' corrected age (CA) and preschool age. RESULTS: Bronchopulmonary dysplasia (incidence, 11.3%) was associated with a higher rate of neonatal pneumonia (26% vs 7%, P = 0.001), longer total duration of mechanical ventilation (mean days, 21 vs 13, P < 0.001), and a higher rate of pulmonary hypertension (20.5% vs 0%, P = 0.002) and of severe retinopathy of prematurity (13.6% vs 0%, P = 0.026). Incidence of LRTI was significantly higher in the BPD infants (50% vs 26%, P = 0.025). ND outcome did not differ between the two groups. Growth at neonatal intensive care unit discharge was similar. In the BPD cohort, rate of weight < 10th percentile was higher at 2 years' CA (52% vs 30%, P = 0.041) and rate of head circumference < 10th percentile was higher at preschool age (59% vs 27%, P = 0.028). CONCLUSION: Neonatal respiratory morbidity was significantly higher in the BPD cohort, but long-term ND outcome did not differ. Infants with BPD had poorer growth.

Severe case of fetal hemolytic disease caused by anti-C(w) requiring serial intrauterine transfusions complicated by pancytopenia and cholestasis.

BACKGROUND: Anti-C(w) are rarely found as a source for severe fetal and neonatal hemolytic diseases. We report a case with serial intrauterine transfusions complicated by pancytopenia and cholestasis in the neonatal period. CASE REPORT: A 37-year-old woman revealed anti-C(w) with a titer of 512 in her fourth pregnancy. The fetus developed fetal anemia and a severe hydrops requiring three intrauterine red blood cell (RBC) transfusions. After birth at 33 + 0 weeks the newborn presented only transfused RBCs and suffered from anemia, thrombocytopenia, leukopenia, and a cholestatic liver disease. Blood counts improved after transfusion of 2 RBC units and one platelet concentrate and administration of hematopoietic growth factors. The symptoms of cholestasis improved slowly after therapy with ursodeoxycholic acid, vitamins, and medium-chain triglyceride-enriched formula feeding. CONCLUSION: Anti-C(w) may lead to severe fetal anemia and consecutive complications. Surveillance of affected pregnancies with high antibody titers using sonographic evaluation of the middle cerebral artery peak systolic velocity should be warranted, especially in multiparous women.

Sirolimus for the treatment of children with various complicated vascular anomalies.

Vascular anomalies include a heterogeneous group of disorders that are categorized as vascular tumors or vascular malformations. Treatment options include resection, embolization, laser therapy, and sclerotherapy or medical treatment such as propranolol, steroids, interferon, and cytostatic chemotherapy. Mammalian target of rapamycin seems to play a key role in the signal pathway of angiogenesis and subsequently in the development of vascular anomalies. Recently, the successful use of sirolimus has been reported in children with lymphatic malformations and kaposiform hemangioendotheliomas. We report on six patients with different vascular anomalies (kaposiform hemangioendothelioma n = 2, combined lymphatico-venous malformation n = 2, pulmonary lymphangiectasia n = 1, and orbital lymphatic malformation n = 1) who were treated with peroral sirolimus. Three of the children initially presented with a Kasabach-Merrit phenomenon. Median duration of treatment was 10 months; two children are still on treatment. Three children each achieved complete and partial remission. Kasabach-Merrit phenomenon resolved within 1 month in all patients. Treatment with sirolimus was tolerated well; only mild reversible leukopenia was observed. CONCLUSION: Sirolimus proved to be effective in children with complicated lymphatic or lymphatico-venous malformations and kaposiform hemangioendotheliomas. Treatment was tolerated well with acceptable side effects. The optimum length of treatment and possible long-term side effects have to be evaluated. WHAT IS KNOWN: • Vascular anomalies including vascular tumors and vascular malformations may lead to life-threatening conditions.• Some patients are refractory to established treatment and/or are not available for local invasive procedures. WHAT IS NEW: • We reviewed the literature focusing treatment of vascular anomalies inc hildren and adolescents.• Our data support recent studies that sirolimus is an effective treatment option in patients with complicated vascular tumors andmalformations

Severe primary pulmonary lymphangiectasis in a premature infant: management and follow up to early childhood.

Primary pulmonary lymphangiectasis (PPL) is a rare congenital developmental abnormality of the lung with a generally poor prognosis. Only a limited number of patients with neonatal-onset PPL have been reported to survive. We present the case of a male preterm infant (gestational age 34 weeks 6 days) with histologically confirmed PPL, complicated by hydrops fetalis, bilateral hydrothorax (treated in utero with pleuro-amniotic shunts), and immediate respiratory distress at birth. He survived after extensive neonatal intensive care therapy and was discharged home at the age of 7 months. At last follow up he was 3 years 7 months old, still requiring assisted ventilation via tracheostomy, having recurrent episodes of wheezing and had mild global developmental delay. This case demonstrates that survival beyond the neonatal period is possible even with severe PPL but long-term morbidity may be relevant, and multidisciplinary management and close follow up are essential.

Congenital pulmonary lymphangiectasis.

Congenital pulmonary lymphangiectasis (CPL) is a rare vascular malformation causing dilated lymph vessels and disturbed drainage of lymph fluid. Based on the pathogenesis and clinical phenotype it can be classified as primary or secondary CPL. Associated genetic syndromes with or without lymphedema, familial occurrence and gene mutations have been described. In utero, it may present as non-immune hydrops with pleural effusions. At birth neonates may have respiratory failure due to chylothorax and pulmonary hypoplasia, causing very high short term mortality rates. Other cases may become symptomatic any time later in childhood or even during adult life. CPL is usually diagnosed based on the combination of clinical signs, imaging and histological findings. Open-lung biopsy is considered the gold standard for the diagnosis of CPL. Treatment is primarily supportive featuring aggressive mechanical ventilation and the management of problems associated with congenital chylothorax including chest-drainage, medium-chain triglycerides (MCT) diet, and octreotide.

Extremely premature infants born at 23-25 weeks gestation are at substantial risk for pulmonary hypertension.

OBJECTIVE: Extremely low gestational age newborns (ELGANs) represent an especially vulnerable population. Herein, we aimed to determine incidence and severity of pulmonary hypertension associated with bronchopulmonary dysplasia (BPD-PH) in extremely immature ELGANs (gestational age: 230/6-256/7 weeks). METHODS: In this prospective observational cohort study, we assessed BPD-PH by means of several echocardiography markers and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at 3 and 12 months of chronological age. In addition, we analyzed incidence and efficacy of pharmacologic treatment for BPD-PH. RESULTS: At 3 months 15/34 ELGANs had echocardiographic evidence of BPD-PH, while at 12 months of age 6/34 still had PH. PH-targeted therapy consisted of sildenafil monotherapy in 11 and dual oral combination therapy (sildenafil and macitentan) in four ELGANs at 3 and 12 months. CONCLUSION: 44% (15/34) of ELGANs developed BPD-PH. All received PH-targeted pharmacotherapy at 3 months, leading to hemodynamic improvements at 12 months in most infants.

Electrical impedance segmentography: A promising tool for respiratory monitoring?

BACKGROUND: Non-invasive, radiation free bedside monitoring methods have gained increased popularity in the respiratory field. The aim of our study was to report the experience with electrical impedance segmentography (EIS), a rather new technique, which allows continuous visual and quantitative monitoring of regional lung ventilation. METHODS: Prospective, pilot trial in spontaneously breathing, healthy, non-sedated term neonates between 24 and 72 hours post-delivery using a commercially available EIS-device. Systematic review of the literature. RESULTS: A total of 12 neonates were eligible for complete data analysis in our study. EIS was found to be a safe and easy to perform method. The median duration of the study time was 25 minutes (16-40). Individual total and regional impedance values, given in arbitrary units and it's percentage of distribution in the upper and lower right and left lung segments (UR, UL, LR, LL), were variable (median total impedance 207 arbitrary units (AU), UR% 17, LR 27%,UL 28%, LL 23%). A number of influencing factors such as body movements, sucking, jawing, and electrode issues have to be considered for correct data interpretation. The literature search revealed two small experimental studies in neonatal piglets and two human studies (one study in preschool children with bronchopulmonary dysplasia and one case report in a neonate with respiratory distress). CONCLUSIONS: EIS is an innovative technique and a potentially useful tool in studying regional lung ventilation in research and clinical care.

Unchanged heart rate-respiratory frequency ratio in preterm infants during spontaneous arousals.

AIM: To find out whether a correlation of heart rate (HR) and respiratory frequency (RF) defined as HR-RF-ratio (HRR) may be helpful to identify arousals in term and preterm infants. METHODS: Polygraphic recordings were performed in 25 term infants (gestational age 40.1 +/- 1.1 weeks) and 25 preterm infants (gestational age 31.1 +/- 1.3 weeks) during undisturbed daytime sleep. Arousals were scored as suggested by the 'International Paediatric Work Group on Arousals' and divided into cortical arousals and subcortical arousals. HRR was defined as HR over RF. Arousals were compared to a 30-sec period preceding an arousals. RESULTS: Two hundred arousals were scored (100 cortical arousals and 100 subcortical arousals). HRR increased during arousals in term infants (p < 0.001). This was true for cortical arousals (p < 0.001) and subcortical arousals (p < 0.05) of term infants. In contrast, in preterm infants HRR remained unchanged during cortical arousals and subcortical arousals. CONCLUSION: An increase of HRR during arousals is a simple parameter to identify arousals in term infants, but not in preterm infants suggesting that an unchanged HRR might be an indicator of an immature arousal response.

Is bladder voiding in sleeping preterm infants accompanied by arousals?

BACKGROUND: As it has been reported that bladder voiding in sleeping full-term infants is consistently accompanied by a cortical arousal, it was the aim of the present study to find out whether this could also hold true for preterm infants. METHODS: Polygraphic recordings were performed in 21 healthy preterm infants (10 female). The infants' gestational age at birth was 31+/-2.7 weeks and postnatal age at study entry was 26+/-8 days (mean+/-standard deviation). Bladder voiding was recorded by an adapted enuresis detector which was connected to the polygraphic computer unit. Arousals were defined as suggested by the International Paediatric Work Group on Arousals. RESULTS: Bladder voiding was recorded 50+/-7 min after sleep onset and occurred during quiet sleep (QS) only. Heart rate (HR), respiratory frequency (RF) and electroencephalographic (EEG) frequency did not change during bladder voiding. Body movements were recorded in 52% of all preterm infants. CONCLUSION: We found that bladder voiding was not accompanied by arousals, suggesting that the arousal process in preterm infants may be delayed due to immaturity.

Respiratory syncytial virus associated hospitalizations in children with congenital diaphragmatic hernia.

BACKGROUND: To evaluate the risk of RSV infection in infants and children with congenital diaphragmatic hernia (CDH) over two consecutive RSV seasons. METHODS: Retrospective, single-center cohort study from southern Austria including infants with CDH born between 1993 and 2012. Infants were retrieved by searching via ICD-10 codes Q79.0 and Q79.1 and by using a local electronic database. Children were followed over 2 years of life including at least two consecutive RSV seasons (November to April). We also defined a group of hypothetical RSV infections with the following criteria: 70% of the admissions due to a respiratory infection (diagnosis of bronchiolitis and/or LRI score ≥3) during the RSV seasons over the first 2 years of life, when no test for RSV was performed. RESULTS: Twenty-nine of 45 infants with CDH comprised the study population (6 were lost to follow-up and 10 died) of whom 9 (31%) exhibited 17 hospitalizations due to respiratory illness. Two hospitalized infants (6.9% of the study population) tested RSV positive, one during the first and the other during the second RSV season. Nine of 29 infants (31%) had documentation of palivizumab prophylaxis, none (0%) had proven RSV hospitalization compared to 1 of 20 (5%) without prophylaxis during the first RSV season (p = 0.256). Including the hypothetical cases, we calculated 0 of 9 (0%) in the palivizumab group and 4 of 20 (20%) in the group without prophylaxis (p = 0.079). CONCLUSIONS: We found a moderate rate of proven RSV hospitalizations in infants with CDH, and palivizumab prophylaxis led to a non-significant reduction of proven and hypothesized RSV hospitalizations.

Neonatal Extracorporeal Membrane Oxygenation Due to Respiratory Failure: A Single Center Experience Over 28 Years.

Background: ECMO therapy is worldwide declining in the neonatal population; hence, its therapeutic value is sometimes questioned. Objectives: To report our experience with neonatal ECMO due to respiratory failure over a 28 year time period. Methods: Retrospective single center observational study including all neonates admitted to ECMO due to respiratory failure between 1989 and 2016 at Graz, Austria. Data were collected regarding survival rate, duration of ECMO, complications, length of hospital stay, changes over time, and follow-up. Results: Sixty-seven neonates were admitted and 43 (64%) needed ECMO-median birth weight 3390 grams (range 1810-4150) and gestational age 39 weeks (32-43). Survival rate was 65% (28/43); with higher rates in meconium aspiration syndrome (MAS) 89% vs. congenital diaphragmatic hernia (CDH) 46% and septic shock 44% (p = 0.005 and p = 0.006, respectively). ECMO duration was median 5 days (1-30) and veno-arterial ECMO (52%) dominated. Need for ECMO therapy decreased over time (p < 0.001). Complications occurred in 31 (72%) neonates. Five neonates had cerebral hemorrhages (11.4%) and four had cerebral infarction (9.1%). Of 26 survivors 17 (65%) showed normal neurodevelopmental outcome at median follow-up of 73 months. Motor deficits were present in one case, cognitive deficits in 9 (35%). Median length of hospital stay was 78 days in those with deficits and 29 in those with normal neurodevelopmental outcome (p < 0.001). Conclusions: Survival rate did not change over the study time but indications for ECMO did. Cognitive impairment was the major long-term deficit following neonatal ECMO being associated with longer hospital stay.

Esophageal Perforation with Unilateral Fluidothorax Caused by Nasogastric Tube.

Preterm infants are highly susceptible to injuries following necessary and often life-saving medical interventions. Esophageal perforation is a rare, yet serious complication that can be caused by aerodigestive tract suction, endotracheal intubation, or nasogastric tube placement. We present the case of a neonate born at 23 weeks plus three days of gestation with chest radiography showing malposition of the nasogastric feeding tube and massive right-sided effusion of Iopamidol in the pleural cavity due to esophageal perforation. In addition, the article summarizes common signs and symptoms associated with esophageal perforation in infants and discusses diagnostic approaches.

Aortic coarctation associated with alveolar capillary dysplasia and misalignment of the pulmonary veins.

After surgical repair of an aortic coarctation a term infant presented with severe pulmonary hypertension and cyanosis unresponsive to treatment including extracorporeal membrane oxygenation. The atypical clinical course became apparent once the accompanying diagnosis of congenital alveolar capillary dysplasia with misalignment of the pulmonary veins had been established at autopsy. In infants with congenital heart defects and with refractory pulmonary hypertension unexplainable on anatomic findings, a lung biopsy at the time of cardiac repair should be considered to avoid further therapies that would not alter the uniformly fatal course of this rare lung disorder.

Pancytopenia due to suppressed hematopoiesis in a case of fatal hemolytic disease of the newborn associated with anti-K supported by molecular K1 typing.

The authors report on a fatal case of hemolytic disease of the newborn (HDN) due to anti-K antibodies with subsequent trilineage pancytopenia in a preterm infant of 28 weeks gestational age, with pronounced leukopenia and neutropenia. In addition, molecular typing of the Kk polymorphism was necessary to confirm HDN. This case of HDN associated with anti-K provides additional evidence that trilineage pancytopenia due to suppressed hematopoiesis is part of the disease. Therefore, antibodies against antigens of the Kell blood group system should be considered as a potential cause of unexplained inhibition of myelopoiesis.