Expanded Prader-Willi syndrome due to chromosome 15q11.2-14 deletion: report and a review of literature.

We report on a male infant with de novo unbalanced t(5;15) translocation resulting in a 17.23 Mb deletion within 15q11.2-q14 and a 25.12 kb deletion in 5pter. The 15q11.2-q14 deletion encompassed the 15q11.2-q13 Prader-Willi syndrome (PWS) critical region and the recently described 15q13.3 microdeletion syndrome region while the 5pter deletion contained no RefSeq genes. From our literature review, patients with similar deletions in chromosome 15q exhibit expanded phenotype of severe developmental delay, protracted feeding problem, absent speech, central visual impairment, congenital malformations and epilepsy in addition to those typical of PWS. The patient reported herein had previously unreported anomalies of mega cisterna magna, horseshoe kidney and the rare neonatal interstitial lung disease known as pulmonary interstitial glycogenosis. Precise breakpoint delineation by microarray is useful in patients with atypical PWS deletions to guide investigation and prognostication.

Risk factors associated with outcomes of very low birthweight infants in four Asian countries.

AIM: The study aims to determine the risk factors associated with mortality and necrotising enterocolitis (NEC) among very low birthweight infants in 95 neonatal intensive care units in the Asian Network on Maternal and Newborn Health. METHODS: This is a cross-sectional study using an international collaborative database of 17,595 very low birthweight infants admitted within 28 days of birth between 2003 and 2006 in four Asian countries. Information on the mortality and morbidity of neonates admitted to the neonatal intensive care units was recorded. Factors associated with the death and diseases of infants were estimated using multilevel multivariate logistic regression. Random effects were included to account for the clustering of the observations. RESULTS: Overall discharge mortality was 15% and it was significantly different by countries and units. The mortality rate was found to be significantly higher in neonates with pulmonary haemorrhage (odds ratio 1.83, 95% confidence interval 1.63-2.04) and air leak syndrome (odds ratio 1.51, 95% confidence interval 1.30-1.72). The incidence of NEC was 4.3% and was strongly associated with other morbidities. Multivariate logistic regression showed that patent ductus arteriosus was the most significant risk factor associated with NEC. CONCLUSIONS: Our analysis has highlighted the great potential that multi-country, collaborative datasets have in terms of epidemiologic research when it comes to identifying issues in perinatal health that are common throughout Asia, and in relation to particular issues pertaining to specific countries and neonatal units. Establishing collaborative networks, conducting analyses of common datasets and further epidemiologic research are now essential measures to improve newborn health in Asia.

Bacillus bloodstream infections in a tertiary perinatal centre: an 8-year study.

BACKGROUND: Isolates of nonanthrax Bacillus species in clinical samples are frequently considered as contaminants. However, there were case reports describing Bacillus sepsis among infants, associated with high mortality and morbidity. METHODS: We performed a retrospective review of the clinical and epidemiological features of Bacillus bacteremia at our neonatal intensive care unit from January 2002 to December 2009. RESULTS: Bacillus bacteremia was considered to be clinically significant in 11 infants. The median gestational age was 30 weeks. All had either central catheters or peripherally inserted arterial lines in situ. The mean neutrophil and lymphocyte counts were 6.73 × 10(9)/L (0.78 to 12.56 × 10(9)/L) and 2.75 × 10(9)/L (0.82 to 6.15 × 10(9)/L), respectively. All 11 infants received intravenous vancomycin, with an average duration of 12.4 days. In general, the earlier the catheter was removed, the quicker the clearance of bacteremia was achieved. All infants survived and were discharged from the hospital. CONCLUSIONS: The growth of Bacillus species in blood cultures cannot simply be regarded as a contaminant. Hematologic parameters are frequently unremarkable at the disease onset. Increased vigilance, early diagnosis, and effective therapy in conjunction with prompt catheter removal are the keys to successful management of Bacillus bacteremia.

Review of primary hypothyroidism in very low birthweight infants in a perinatal centre in Hong Kong.

AIMS: To review the incidence and risk factors of primary hypothyroidism in very low birthweight (VLBW) infants in our centre and to assess their neurodevelopmental outcome. METHOD: Retrospective, descriptive review of VLBW infants with primary hypothyroidism from 1 January 2000 to 31 December 2008 in a perinatal centre. Case control comparisons for neurodevelopmental outcome at 18 months, nested to a prospective VLBW cohort (Vermont Oxford Database). RESULTS: Twelve cases were identified, with the incidence of primary hypothyroidism of 1 in 55 live births in our VLBW cohort during the 9-year study period. Umbilical cord blood thyroid-stimulating hormone was abnormal in less than half of the cases using the current cut-off (≤14 mIU/L). Five cases were transient in nature, four cases were permanent and the causes for the rest remained undetermined at the time of review. Elevation of thyroid-stimulating hormone was first evident at a mean of 2.4 weeks post-natally. Follow-up assessment reviewed normal development in 83% of cases (10 out of 12 cases). There was no statistically significant difference in Griffith's scores at 18 months between the case and matched controls. CONCLUSIONS: The high incidence of primary hypothyroidism in our VLBW cohort deserved stringent monitoring of thyroid function post-natally. Umbilical cord blood screening was not useful as a screening tool because of its low sensitivity. Neurodevelopmental outcome for treated primary hypothyroidism was favourable as assessed at 18 months of age.

End-of-life Characteristics and Palliative Care Provision for Patients With Motor Neuron Disease.

Motor neuron disease (MND) is a neurodegenerative disease and manifested as progressive decline in physical, respiratory, swallowing and communication function, and ultimately death. Traditional model of care was fragmented and did not match with multifacet needs of patients and carers. Furthermore, there could be lack of integrated care at end of life for patients with MND in most lower- and middle-income countries or in places with inadequate palliative care (PC) coverage. In view of this, a special workgroup for patients with MND, which includes neurologist, respiratory physician, rehabilitation specialist, and PC physician was formed in Hong Kong since year 2011. In various disease phase, each specialty team plays a leading role in coordinated care of patients with MND. From July 2011 to June 2017, a total of 52 patients with MND were referred for PC; 41 deceased patients with MND were included into data analysis. Major cause of death remains pneumonia (54.8%) and respiratory failure (40.5%). Most of the patients with MND (66.7%) died in acute ward and neurology units, with only 11.9% dying in PC units and hospices. The PC team plays a major role in advance care planning (ACP), and most patients had their ACP documented at second or third PC clinic visit (93.8%). Patients with MND often have limitations in mobility, swallowing difficulty, respiratory insufficiency requiring ventilator support, and various psychosocial needs. This highlighted the importance of early PC referral.

Supportive & palliative interventions in motor neurone disease: what we know from current literature?

Although there is no cure for motor neurone disease (MND), the advent of supportive interventions including multidisciplinary care (MDC) has improved treatment interventions and enhanced quality of life (QOL) for MND patients and their carers. Our integrative review showed evidence-based MDC, respiratory management and disease-modifying therapy that have improved the outcomes of patients diagnosed with MND. Supportive approaches to nutritional maintenance and optimization of symptomatic treatments, including management of communication and neuropsychiatric issues, improve the QOL for MND patients. Notwithstanding improvement to care and QOL, survival benefit has become evident with the advent of a MDC framework, early treatment with non-invasive ventilation (NIV). In addition, weight maintenance remains critical, as weight loss is associated with more rapid disease progression. The endof- life phase is poorly defined in MND patients and treatment remains challenging, yet effective symptom control through palliative care (PC) is achievable and essential.

Short- and long-term outcome of severe neonatal nonhemolytic hyperbilirubinemia.

We studied the effects of hyperbilirubinemia on brainstem auditory pathways and neurodevelopmental status in 99 full-term neonates with severe nonhemolytic hyperbilirubinemia (total serum bilirubin level = 301 to 500 micromol/L) born between 1995 and 2000. These were divided into three groups: group 1, moderate hyperbilirubinemia (n = 30; mean maximum total serum bilirubin = 320.7 micromol/L or 18.9 mg%); group 2, severe hyperbilirubinemia (n = 63; mean maximum total serum bilirubin = 369.0 micromol/L or 21.7 mg%); and group 3, super hyperbilirubinemia (n = 6; mean maximum total serum bilirubin = 457.2 micromol/L or 26.9 mg%). All received phototherapy, and three neonates also had exchange transfusion. Initial brainstem auditory evoked potentials were recorded in all at the mean age of 3.1 months (range 1-9 months). At initial assessment, only nine neonates (9.1%) had abnormal brainstem auditory evoked potentials. All except two returned to normal at 2 years. These two children had a hearing threshold at 50 nHL. We then compared serial brainstem auditory evoked potentials until 2 years for these nine cases with initial abnormal brainstem auditory evoked potentials, and nine cases with initial normal brainstem auditory evoked potentials were recruited for comparison. All 99 children had regular physical, neurologic, visual, and auditory assessments every 3 to 6 months until the age of 3 years. There was no significant correlation between demographic factors (gender, gestational age, or birthweight), maximum total serum bilirubin, and total serum bilirubin at discharge with an abnormal brainstem auditory evoked potential. There was no significant difference in the rate of brainstem auditory evoked potential abnormalities between the three groups: moderate (10%), severe (7.9%), and super (16.7%). All had normal neurodevelopmental status at 3 years. Only two children had transient mild motor delay and hypotonia, and both had normal brainstem auditory evoked potentials. There was no relationship between the abnormalities of the brainstem auditory evoked potentials and neurodevelopmental status. None of the three children receiving exchange transfusion had abnormal brainstem auditory evoked potentials or neurodevelopmental outcome. With the neurophysiologic and clinical outcomes in our cohort with severe nonhemolytic hyperbilirubinemia, we propose that the toxic effect of hyperbilirubinemia on auditory brainstem pathways might be transient provided that prompt treatment is initiated.

Neurodevelopmental outcome of severe neonatal hemolytic hyperbilirubinemia.

We recruited 128 neonates with hyperbilirubinemia over a 5-year period (1995-2000) to study the short- and long-term effects of hemolytic hyperbilirubinemia on the auditory brainstem pathway and neurodevelopmental status. These children were divided into two groups: (1) a hemolytic group (n = 29; ABO incompatibility [n = 19], Rh incompatibility [n = 1], glucose-6-phosphate dehydrogenase deficiency [n = 8] and both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency [n = 1]) and (2) a nonhemolytic group (n = 99). All received phototherapy. Exchange transfusions were performed for four (13.8%) in the hemolytic group and three (3%) in the nonhemolytic group. The brainstem auditory evoked potential was recorded at a mean age of 3.2 months in the hemolytic group and 3.1 months in the nonhemolytic group. Serial brainstem auditory evoked potential assessments were performed until 2 years of age (3 in the hemolytic group and 18 in the nonhemolytic group). All had regular physical, neurologic, visual, and auditory evaluation until 3 years of age. The rate of exchange transfusion was significantly higher in the hemolytic group than in the nonhemolytic group (P < .05). Brainstem auditory evoked potential abnormalities at the initial assessment occurred in three (10.4%) in the hemolytic group (all related to ABO incompatibility) and nine (9.1%) in the nonhemolytic group. At 2 years, the brainstem auditory evoked potential returned to normal except in three cases with a slightly increased hearing threshold (one [3.5%] in the hemolytic group at 60 dB nHL and two [2%] in the nonhemolytic group at 50 dB nHL]). There were no significant differences in the rate of brainstem auditory evoked potential abnormalities at the initial or subsequent assessments between both groups. All except five cases had a normal neurodevelopmental outcome at 3 years (three [two with ABO incompatibility and one with glucose-6-phosphate dehydrogenase deficiency] in the hemolytic group [10.4%] and two [2%] in the nonhemolytic group). All had mild motor delay and hypotonia, which returned to normal at 3 years. The rate of abnormal neurodevelopmental outcome was higher in the hemolytic group than in the nonhemolytic group, although with no significant difference between both groups (P = .08). All five cases in both groups with abnormal neurodevelopment had a normal brainstem auditory evoked potential at the initial assessment. There was no relationship between the abnormal initial brainstem auditory evoked potential and the final neurodevelopmental outcome. The toxic effect of hyperbilirubinemia on the auditory brainstem pathway and neurodevelopmental status in our cohort was transient. The prognosis of neonatal hemolytic hyperbilirubinemia in our Chinese cohort is excellent, possibly owing to an aggressive early-intervention approach.

Cardiac Mechanics in Children with Bronchopulmonary Dysplasia.

BACKGROUND: Disruption of pulmonary vasculogenesis occurs in bronchopulmonary dysplasia (BPD). Increased impedance to pulmonary flow secondary to abnormal vascular development may affect ventricular mechanics. OBJECTIVES: We aimed to test the hypothesis that cardiac mechanics are altered in prematurely born children with BPD. METHODS: A cohort of 47 children was studied: 22 aged 48.9 ± 6.4 months born preterm with BPD (group I), 13 aged 46.3 ± 8.1 months born preterm without BPD (group II), and 12 healthy children aged 53.4 ± 12.2 months born at term (group III). Left (LV) and right ventricular (RV) strain and strain rate were assessed by speckle-tracking echocardiography. RESULTS: The global RV systolic strain rate (p = 0.022) was significantly lower, while RV systolic strain (p = 0.05) and early diastolic strain rate (p = 0.05) and LV longitudinal systolic strain rate (p = 0.06) also tended to be lower in group I than group III. Group I also tended to have lower RV systolic strain (p = 0.09) and early diastolic strain rate (p = 0.049) and LV longitudinal systolic strain rate (p = 0.08) than group II. An increasing trend from group I to III was observed for RV lateral wall and septal systolic strain and strain rate (all p < 0.05). The LV but not RV size was significantly smaller in group I compared with group III (p < 0.05). Multiple regression identified duration of invasive ventilation (ß = -0.66, p = 0.032) as an independent determinant of RV systolic strain after adjustment for perinatal risk factors. CONCLUSION: Impairment of RV myocardial deformation occurs in children with BPD, the magnitude of which is associated negatively with the duration of invasive ventilation.

Randomized trial comparing two natural surfactants (Survanta vs. bLES) for treatment of neonatal respiratory distress syndrome.

Exogenous surfactants have been used as an effective treatment of neonatal respiratory distress syndrome (RDS). Different preparations of surfactant carry different biophysical and clinical properties. To study the response pattern and treatment outcome of two natural surfactants (bLES and Survanta) for the treatment of RDS, we conducted a randomized clinical trial at the neonatal unit of a university teaching hospital. Premature babies with birth weight between 500-1,800 g who developed RDS requiring mechanical ventilation with an oxygen requirement of more than 30% within 6 hr of life were randomized into two treatment groups. Oxygenation indices (OIs) within 12 hr of treatment were compared as primary outcomes, while neonatal complications were analyzed as secondary outcomes of the study. Sixty babies were recruited, with 29 in the bLES and 31 in the Survanta treatment group. Both groups had significant and sustained improvements in OI after surfactant replacement therapy (SRT), while the bLES group was associated with a significantly lower OI throughout the initial 12 hr after treatment compared with the Survanta group. There was no difference in secondary outcomes including mortality, ventilator days, and occurrence of chronic lung disease. We conclude that infants with RDS respond favorably to both types of surfactant replacement, and that bLES achieved a faster clinical response in terms of improvement in OI than Survanta.

Perinatal outcome in large-for-gestational-age infants. Is it influenced by gestational impaired glucose tolerance?

OBJECTIVE: To examine the relationship between the World Health Organization category of impaired glucose tolerance (IGT) (two-hour value of the 75-g oral glucose tolerance test at 8-10.9 mmol/L) and outcome in large-for-gestational age (LGA) infants to determine whether IGT affects perinatal morbidity in addition to affecting infant size. STUDY DESIGN: A retrospective study was performed on 461 LGA newborns (birth weight > 90th percentile) from singleton pregnancies delivering after 36 completed weeks in a 12-month period to determine the difference in perinatal outcome between nondiabetic pregnancies (n = 382) and pregnancies with diet-treated IGT (n = 79). RESULTS: The IGT group had significantly higher mean maternal age, prepregnancy weight and body mass index (BMI) but lower absolute and percent gestational weight gain and no difference in infant gestational age, birth weight, BMI, incidence of macrosomia (birth weight > or = 4,000 g) or obstetric complications. However, the IGT group had an increased incidence of Erb's palsy (OR 7.81, 95% CI 1.76-34.62), meconium aspiration syndrome (OR 5.29, 95% CI 1.27-22.02), phototherapy (OR 2.10, 95% CI 1.03-5.69), sepsis (OR 2.90, 95% CI 1.25-6.74) and shoulder dystocia (OR 5.64, 95% CI 1.06-29.89) after adjusting for confounding factors (maternal age and BMI, postdate pregnancy, mode of delivery and infant sex). CONCLUSION: Despite dietary treatment, maternal IGT is associated with increased perinatal morbidity independent of its effect on fetal size.

Cost-benefit analysis of hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency: for consideration of expanded newborn screening in Hong Kong.

OBJECTIVES: To evaluate the cost-benefit of implementing an expanded newborn screening programme for hyperphenylalaninemias due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency in Hong Kong. SETTING: Regional public hospitals in Hong Kong providing care for cases of inborn errors of metabolism. METHODS: Implementational and operational costs of a new expanded mass spectrometry-based newborn screening programme were estimated. Data on various medical expenditures for the mild and severe phenotypic subtypes were gathered from a case cohort diagnosed with PTPS deficiency from 2001 to 2009. Local incidence from a previously published study was used. RESULTS: Implementation and operational costs of an expanded newborn screening programme in Hong Kong were estimated at HKD 10,473,848 (USD 1,342,801) annually. Assuming a birthrate of 50,000 per year and an incidence of 1 in 29,542 live births, the medical costs and adjusted loss of workforce per year would be HKD 20,773,207 (USD 2,663,232). Overall the annual savings from implementing the programme would be HKD 9,632,750 (USD 1,234,968). CONCLUSIONS: Our estimates show that implementation of an expanded newborn screening programme in Hong Kong is cost-effective, with a significant annual saving for public expenditure.

Bordetella bronchiseptica Pneumonia in an Extremely-Low-Birth-Weight Neonate.

Bordetella bronchiseptica, a gram-negative coccobacillus, is a common veterinary pathogen. In both domestic and wild animals, this bacterium causes respiratory infections including infectious tracheobronchitis in dogs and atrophic rhinitis in swine. Human infections are rare and have been documented in immunocompromised hosts. Here, we describe an extremely-low-birth-weight infant with B. bronchiseptica pneumonia. This is the first report that describes the microorganism's responsibility in causing nosocomial infection in a preterm neonate. He recovered uneventfully after a course of meropenem. It is possible that the bacteria colonize the respiratory tracts of our health care workers or parents who may have had contact with pets and then transmitted the bacterium to our patient. Follow-up until 21 months of age showed normal growth and development. He did not suffer from any significant residual respiratory disease.

Gastric pneumatosis in a premature neonate.

Gastric pneumatosis is extremely rare during infancy. It has been reported in association with necrotizing enterocolitis or congenital abnormalities such as pyloric stenosis. Here, we report a case of gastric pneumatosis in a premature neonate on synchronized nasal intermittent positive pressure ventilation. No pneumatosis was noted in the rest of the bowel or esophagus. There could have been mild damage in the gastric mucosa, either related to the placement of the feeding tube or secondary to the use of indomethacin or both. The condition was further aggravated by noninvasive ventilation. An increase in intragastric pressure resulted in the submucosal dissection of air followed by the development of gastric pneumatosis. Conservative management strategies, including the use of a nasogastric tube for decompression and the withholding of feeding, successfully managed the gastric pneumatosis in our patient. An uneventful recovery was made after conservative management. Prompt recognition and evaluation of this condition were essential for making the diagnosis.