Prospective study of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the prevalence, risk factors, and optimal timing of echocardiogram for pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD). DESIGN: In this prospective study, infants with gestational age (GA) <30 weeks admitted to a tertiary NICU between July 2015 and June 2017 who required positive pressure ventilation or oxygen therapy at ≥28 days of life were evaluated with serial echocardiograms at study enrollment (4-6 weeks of age), 32 weeks (only for ≤25 weeks), 36, and 40 weeks post-menstrual age (PMA) for PH. RESULTS: Of 126 infants (mean birth weight 858 ± 221 g; mean GA 26.1 ± 1.6 wks), 48 (38%) developed PH at any time during their hospital stay. The first study echocardiogram was performed at a median age of 31 weeks PMA. The prevalence of PH was 36/126 (28.5%) at enrollment, at 6/30 (20%) at 32 weeks, 24/111 (21.6%) at 36 weeks, and 10/59 (17%) at 40 weeks. No new cases of PH were identified at 40 weeks. At 36 weeks, none of the infants with mild BPD had PH, whereas 20% of moderate and 32% of severe BPD infants had PH. After controlling for confounding variables severe BPD (OR 3.31, 95%CI 1.12, 9.74), and ventilator associated pneumonia (VAP) (OR 17.9, 95%CI 3.9, 82.11) remained independent risk factors for BPD-associated PH. CONCLUSION: Echocardiographic screening for PH can be safely restricted to infants with moderate or severe BPD at 36 weeks PMA. We identified VAP as an independent risk factor for PH.

Prevalence and Characteristics of Intracranial Hemorrhages in Neonates with Hypoxic Ischemic Encephalopathy.

INTRODUCTION: The risk factors of intracranial hemorrhages (ICH) in the context of neonatal hypoxic ischemic encephalopathy (HIE) and related interventions are unclear. OBJECTIVE: This article examines the prevalence and risk factors associated with ICH in neonates with HIE. STUDY DESIGN: This is a retrospective cohort study of neonates with HIE in Southern Alberta. ICH (subdural [SDH], subarachnoid [SAH], intraventricular [IVH], intraparenchymal [IPH]) were diagnosed by magnetic resonance imaging (MRI). Perinatal and neonatal characteristics were examined. Relation of hemorrhages with hypoxic changes on MRI and HIE stages were assessed. RESULTS: Number of HIE patients, n = 157; brain MRI was done in 138 infants; median gestation, 40 weeks; and cooled = 103 (66%). Prevalence of SDH, IPH, IVH, and SAH were 47, 22, 11, and 10 (34.1%, 15.9%, 7.8%, 7.2%), respectively. There was no significant increase in hemorrhage with mode of delivery, seizures, hypo/hypercarbia, severe thrombocytopenia, or deranged coagulation. All hemorrhages increased with higher HIE stage, regardless of the HIE severity in MRI. Adjusting for HIE staging, cooling, and gestation, IPH was observed more in infants who received inotropes (odds ratio [OR], 3.32; 95% confidence interval [CI], 1.20, 9.20). CONCLUSION: SDH followed by IPH were the most common ICH. Thrombocytopenia and deranged coagulation did not increase risk of hemorrhages in HIE. Our study was not powered to determine the impact of inotrope use on the risk of IPH.

Cover Image, Volume 173A, Number 10, October 2017.

The cover image, by Rani A. Bashir et al., is based on the Original Article Lin-Gettig syndrome: Craniosynostosis expands the spectrum of the KAT6B related disorders, DOI: 10.1002/ajmg.a.38355.

Lin-Gettig syndrome: Craniosynostosis expands the spectrum of the KAT6B related disorders.

We report two patients with sagittal craniosynostosis, hypoplastic male genitalia, agenesis of the corpus callosum, thyroid abnormalities, and dysmorphic features which include short palpebral fissures and retrognathia. The clinical presentation of both patients was initially thought to be suggestive of Lin-Gettig syndrome (LGS), a multiple malformation syndrome associated with craniosynostosis that was initially reported in two brothers in 1990, with a third patient reported in 2003. Our first patient was subsequently found through exome sequencing to have a de novo mutation in KAT6B, c.4572dupT, p.(Thr1525Tyrfs*16). The second patient was ascertained as possible LGS, but KAT6B mutation testing was pursued clinically after the identification of the KAT6B mutation in Patient 1, and identified a de novo mutation, c.4205_4206delCT, p.(Ser1402Cysfs*5). The phenotypic spectrum of KAT6B mutations has been expanding since identification of KAT6B mutations in genitopatellar syndrome (GPS) and Say Barber Biesecker Young Simpson (SBBYS) syndrome patients. We show that craniosynostosis, which has not been previously reported in association with KAT6B mutations, may be part of the genitopatellar/Say Barber Biesecker Young Simpson spectrum. These two patients also further demonstrate the overlapping phenotypes of genitopatellar and SBBYS syndromes recently observed by others. Furthermore, we propose that it is possible that one or more of the previous cases of LGS may have also been due to mutation in KAT6B, and that LGS may actually be a variant within the KAT6B spectrum and not a distinct clinical entity.

Percutaneously Inserted Central Catheter-Related Pleural Effusion in a Level III Neonatal Intensive Care Unit: A 5-Year Review (2008-2012).

BACKGROUND: Although peripherally inserted central catheters (PICCs) provide vascular access in newborns who require parenteral nutrition and medications, they can be associated with complications that lead to significant morbidity and mortality. OBJECTIVES: To describe the characteristics of pleural effusion (PLE) associated with PICC use in a large level III neonatal intensive care unit. DESIGN/METHODS: A retrospective review of PICC-related PLE in newborns was conducted over a 5-year period, from 2008-2012. RESULTS: A total of 926 PICCs were inserted, accounting for 17,606 catheter days. PICC-related PLE was identified in 7 infants, with an incidence of 0.4 per 1000 catheter days. Infants who developed PLE had a median gestational age of 28 weeks (range, 24-38 weeks) and birth weight of 735 g (range, 500-2975 g). PICCs were inserted at a median age of 4 days (range, 3-11 days). The median time from catheter insertion to the development of PLE was 16 days (range, 7-75 days). In all cases, the catheter tips were centrally located at the time of insertion but migrated to the subclavian veins or tributaries at the time of the events. CONCLUSION: PICC-related PLE can be associated with the migration of PICC tips to noncentral locations, despite optimal positioning of the tip at the time of insertion. Attention should be paid to migration of catheter tips on subsequent x-ray films. For PICCs inserted via upper limb or scalp, serial follow-up x-rays, beginning 1 week after insertion, may be helpful to detect migration of catheter tips and identify patients at risk.

Parenteral Fish-Oil Lipid Emulsions in the Prevention of Severe Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

Objective Omega-3 fatty acids are vital for brain and retinal maturation. It is not clear if early use of ω-3 fatty acids in the form of fish-oil lipid emulsions (FLEs) prevents retinopathy of prematurity (ROP) in preterm infants. The aim of this meta-analysis is to evaluate whether early administration of parenteral FLEs reduces ROP requiring laser therapy or severe ROP ≥stage 3 in preterm infants. Methods A literature search was performed to identify studies comparing parenteral FLEs with soybean-based lipid emulsions (SLEs) in preventing ROP. The main outcome was incidence of severe ROP or ROP requiring laser therapy. Results Studies met the inclusion criteria (four RCTs and two observational studies). The pooled relative risk of ROP requiring laser therapy or severe ROP ≥ stage 3 in FLEs group was 0.47 [95% CI: 0.24-0.90] and 0.40 [95% CI: 0.22-0.76] in RCTs and observational studies, respectively. FLEs also reduced cholestasis; however, other secondary outcomes of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), and mortality were similar. Conclusion The use of FLEs may reduce the incidence of severe ROP or need for laser therapy in preterm infants. A large multicenter RCT is required to confirm this.

Chorioamnionitis at birth does not increase the risk of neurodevelopmental disability in premature infants with bronchopulmonary dysplasia.

AIM: To compare preterm infants with no bronchopulmonary dysplasia (BPD), BPD with chorioamnionitis (BPDC) and BPD with no chorioamnionitis (BPDNC) for the association with neurodevelopmental disability (NDD) at three years corrected age. METHODS: Demographic and outcome data of infants with birthweight (BW) ≤1250 g born during two epochs (1995-2000 and 2002-2007 with an interim washout period of one year) were compared on the basis of whether they had BPD, chorioamnionitis or both. Any NDD was considered present if there was either mild-severe cerebral palsy (CP), cognitive delay, visual or hearing impairment. Logistic regression modelling was performed. RESULTS: Infants (n = 1009) were included into three groups - no BPD (n = 442), BPDNC (n = 437) and BPDC (n = 130). The adjusted odds ratio (aOR) of any NDD at three years in infants with BPDC versus BPDNC was 1.37; 95% CI 0.85-2.20, and for CP the aOR was 1.66; 95% CI 0.76-3.62. Infants in the BPDC group were of lower BW, gestational age and had longer length of hospital stay, duration of mechanical ventilation, more blood transfusions and sepsis compared to BPDNC and no BPD groups (all p < 0.001). CONCLUSION: Chorioamnionitis was not associated with any increase in the odds of NDD in infants with BPD at three years corrected age.

Association between Peripherally Inserted Central Venous Catheter Insertion Site and Complication Rates in Preterm Infants.

Objective To examine whether there is an association between peripherally inserted central venous catheter (PICC) insertion site and complication rates among preterm infants. Design We performed a retrospective analysis of the first PICCs placed in preterm infants in a tertiary neonatal intensive care unit between January 2006 and December 2010. The PICC-related complications resulting in catheter removal were compared based on site of insertion. Results Of the 827 PICCs, 593 (72%) were inserted in upper extremity. Lower extremity PICC group infants had higher illness severity (SNAP-II) score and more likely to be inserted later as compared with the upper extremity group. There was no significant difference in the total PICC-related complications between upper and lower extremity PICCs (31.3 vs. 26%; p > 0.05). Logistic regression analysis after adjusting for gestational age, day of line insertion, and SNAP-II score revealed that upper extremity PICCs were associated with increased risk of line infiltration (adjusted odds ratio [aOR], 2.41; 95% confidence interval [CI], 1.36-4.29) but not the total PICC complication (aOR, 1.29; 95% CI, 0.91-1.83). Conclusion There is no difference in total PICC-related complication between upper and lower extremity PICCs; however, the PICC-related mechanical complications vary depending on the site of insertion in preterm infants.

Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients.

BACKGROUND: Sengers syndrome is an autosomal recessive condition characterized by congenital cataract, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. Mutations in the acylglycerol kinase (AGK) gene have been recently described as the cause of Sengers syndrome in nine families. METHODS: We investigated the clinical and molecular features of Sengers syndrome in seven new families; five families with the severe and two with the milder form. RESULTS: Sequence analysis of AGK revealed compound heterozygous or homozygous predicted loss-of-function mutations in all affected individuals. A total of eight different disease alleles were identified, of which six were novel, homozygous c.523_524delAT (p.Ile175Tyrfs*2), c.424-1G > A (splice site), c.409C > T (p.Arg137*) and c.877 + 3G > T (splice site), and compound heterozygous c.871C > T (p.Gln291*) and c.1035dup (p.Ile346Tyrfs*39). All patients displayed perinatal or early-onset cardiomyopathy and cataract, clinical features pathognomonic for Sengers syndrome. Other common findings included blood lactic acidosis and tachydyspnoea while nystagmus, eosinophilia and cervical meningocele were documented in only either one or two cases. Deficiency of the adenine nucleotide translocator was found in heart and skeletal muscle biopsies from two patients associated with respiratory chain complex I deficiency. In contrast to previous findings, mitochondrial DNA content was normal in both tissues. CONCLUSION: We compare our findings to those in 21 previously reported AGK mutation-positive Sengers patients, confirming that Sengers syndrome is a clinically recognisable disorder of mitochondrial energy metabolism.

Outcome of scorpion sting envenomation after a protocol guided therapy.

OBJECTIVE: Scorpion sting (SS) envenomation is a life threatening emergency in children, though not so severe in adults. Attempt to develop protocol using prazosin and dobutamine and few other drugs to treat SS. METHODS: Children aged 0-13 years with a history of scorpion sting were studied. Clinical features, complications, drug therapy and outcome of the cases for the period 1992-97(N = 186) was collected by the authors and also from the medical records department (RETROSPECTIVE GROUP). Cases treated during 1997-2000 (N = 198) as per the protocol were recorded as PROSPECTIVE GROUP. All the cases were observed for at least for 24 hours. Cases coming within 4 hours of a sting were given a dose of Prazosin (30 mic.gm/Kg/dose) and were observed. Those who came after 4 hours & were asymptomatic received only symptomatic treatment. Cases with signs of envenomation received Prazosin every 6 hourly till recovery. Cases having acute pulmonary edema (APE) were treated with dobutamine and sodium nitroprusside drip. Complicated cases were monitored in PICU as per the protocol. RESULT: Complications associated with excessive parasympathetic and sympathetic stimulation were observed. Myocarditis was observed due to the toxin and excessive catecholamine, which complicated in left ventricular failure (LVF) and APE. Nearly half of the children with acute myocarditis developed APE. Death was mainly due to myocarditis and APE, with or without encephalopathy. Mortality was high in children who received steroid and antihistaminics outside and who came late (> 4 hours). CONCLUSION: Complication rate remained almost same in both the groups. There was a significant reduction in overall mortality (P = < 0.0155) and in deaths associated with APE (P = < 0.0001) after the protocol guided therapy. There was also a reduction in mortality in encephalopathy group though not statistically significant. This treatment protocol and aggressive management of APE reduced the mortality due to SS significantly.