Obtaining assent for research involving children in Malaysia: a position statement from the Academy of Medicine of Malaysia College of Paediatrics.

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

Inhaled nitric oxide and intravenous magnesium sulphate for the treatment of persistent pulmonary hypertension of the newborn.

INTRODUCTION: The aim of this study was to compare the response and survival rates of term infants with persistent pulmonary hypertension of the newborn (PPHN) on high frequency oscillatory ventilation (HFOV) treated with either inhaled nitric oxide (iNO) or intravenous magnesium sulphate (MgSO4). METHODS: This was a randomised controlled study. The inclusion criteria were infants with respiratory distress, oxygen index equal to or greater than 25 despite HFOV support, and echocardiographic evidence of PPHN. Infants in the MgSO4 group (n is 13) were loaded with MgSO4 200 mg/kg infused over half an hour, followed by continuous infusion at 50-150 mg/kg/hour to attain a serum magnesium level of 5.0-7.0 mmol/L. Infants in the iNO group (n is 12) were administered nitric oxide at an initial concentration of 20 ppm. Analysis was done on an intention-to-treat basis. RESULTS: There was no significant difference in the median age when the vasodilators were commenced (MgSO4 group: 14.0 hours, interquartile range [IQR]: 7.5, 27.0; iNO group: 14.8 hours, IQR: 12.5, 35.3, p is 0.8). There was no significant difference in the proportion of infants who responded primarily to either vasodilator (MgSO4: 23.3%, iNO: 33.3%, p is 1.0) . After switching over to iNO following a failed MgSO4 therapy, a significantly higher proportion (9 out of 10) of the non-respondents in the MgSO4 group recovered from PPHN and survived compared to the non-respondents in the iNO group (1 out of 8) who switched over to intravenous MgSO4 (p is less than 0.03). CONCLUSION: Infants who were administered iNO following a failed MgSO4 therapy were associated with a better outcome than those who were administered MgSO4 following a failed iNO therapy.

The usefulness of early ultrasonography, electroencephalography and clinical parameters in predicting adverse outcomes in asphyxiated term infants.

INTRODUCTION: The early identification of asphyxiated infants at high risk of adverse outcomes and the early selection of those who might benefit from neuroprotective therapies are required. A prospective observational study was conducted to determine if there were any early clinical, neuroimaging or neurophysiological parameters that might predict the outcome in term newborns with asphyxia. METHODS: 44 term newborns with acute asphyxia had a cranial ultrasonography (US), electroencephalography (EEG) and clinical examination performed between three and eight hours of life to determine the parameters that might predict outcome. US findings were classified as normal or abnormal (ventricular dilatation or compression and/or focal/diffuse echogenicities). EEG background activity was classified into two categories: normal/mildly abnormal/intermediate, or severely abnormal (low voltage activity or "suppression-burst"). An intrapartum score (based on graded abnormalities of foetal heart monitoring, umbilical arterial base deficit and five-minute Apgar score) and a hypoxic ischaemic encephalopathy (HIE) score (based on graded abnormalities of the neurological and respiratory status at 3-8 hours of life) was also obtained. RESULTS: At one year of life, eight infants had died, six had defaulted follow-up, five had major impairment, two minor impairment and 23 were normal. On univariate analysis, poor outcome (death or major impairment) was associated with abnormal cranial US, severely abnormal EEG and a high HIE score (greater than or equal to 15). The positive predictive value was 54.5, 100 and 100 percent, respectively, while the negative predictive value was 93.8, 80.6 and 80.6 percent, respectively. Combining these factors did not improve the predictive values. CONCLUSION: There was no added advantage in combining EEG or US parameters over a clinical neurological scoring system alone in predicting the outcome of asphyxiated term newborns.

Transient abnormal myelopoeisis in newborns with Down syndrome.

Transient abnormal myelopoeisis (TAM) is a haematological phenomenon commonly seen in newborns with Down syndrome. Although the majority show spontaneous resolution, this condition should not be dismissed too readily as there have been associated fatalities. Furthermore, even for those who do show spontaneous resolution, a significant percentage will develop acute megakaryoblastic leukaemia within the next few years of life. We report a series of four patients with TAM who presented with hepatosplenomegaly and leucocytosis detected on preliminary investigations.

Unbalanced chromosomal translocation: a cause of recurrent spontaneous abortion.

Recurrent spontaneous abortion, defined as three consecutive abortions, occurs in approximately 1% to 2% of couples. Although the cause is unknown in up to 50% of cases, about 5% of these couples are found to be a balanced translocation carrier. We report a case in which the mother was identified to be a translocation carrier following the birth of a baby with multiple congenital abnormalities.

Turn-around-time of radiographs in a neonatal intensive care unit.

A quality assurance study was carried out prospectively in two phases at the Neonatal Intensive Care Unit (NICU) of Hospital Universiti Kebangsaan Malaysia. The objectives of the study were to determine the turn-around-time (TAT) of radiographs requested for infants undergoing intensive care treatment in the NICU and the effects of a standard operating procedure introduced based on initial findings of first phase of the study on subsequent TAT. The TAT was defined as the time taken for the radiograph to be ready for viewing after the attending doctor had requested for it to be done on an infant. During phase one of the study, none of the requested radiographs was ready to be viewed by the doctors within the standard TAT of 45 minutes. The problems identified were ward staffs delay in sending request forms to the radiology department, radiographers' delay in shooting and processing the films, and delay by NICU porter in collecting the processed films. Based on these findings, a standard operating procedure (SOP) was drawn up jointly by the staff of NICU and Department of Radiology. During phase two of the study conducted at one month after implementation of the SOP, there was a reduction of TAT by 50%. However, only 3 (4.3%) of the radiographs achieved the standard TAT. The main problems identified during phase two were delay in sending request forms and in collecting processed radiographs by the porter system. The dismal TAT of radiographs in NICU was related primarily to human behaviour. Besides continuous staff education, replacement of the porter system with electronic system may improve the TAT.

Incidence of nasal trauma associated with nasal prong versus nasal mask during continuous positive airway pressure treatment in very low birthweight infants: a randomised control study.

OBJECTIVE: To compare the incidence of nasal trauma associated with the use of prong or mask during nasal continuous positive airway pressure (nCPAP) support in very low birthweight (<1501 g) infants. DESIGN: Randomised controlled clinical trial. SETTING: Tertiary care university hospital, Department of Paediatrics, Kuala Lumpur, Malaysia. METHODS: All very low birthweight infants admitted to the neonatal intensive care unit between July 2001 and December 2003 who received nCPAP through the Infant Flow Driver were randomised to the use of either nasal prong or mask. The nasal cavity of these infants was inspected daily during the first week and then weekly until they were weaned off nCPAP. RESULTS: Of the 89 infants recruited, 41 were randomised to the mask group and 48 to the prong group. There was no significant difference in the incidence of nasal trauma between the two groups (p = 0.5). The primary site of trauma was at the junction between the nasal septum and the philtrum in infants in the mask group and the walls of the nasal septum in the prong group. Logistic regression analysis showed that duration of nCPAP was the only significant risk factor associated with development of nasal injury, after birth weight, gestational age, and nasal device used had been controlled for (adjusted odds ratio 1.04; 95% confidence interval 1.01 to 1.07; p = 0.003). CONCLUSION: Irrespective of the type of nasal device used, nasal trauma is common during nCPAP treatment, which should therefore be terminated as soon as possible.

The effect of a user-guided request form for chest radiographs in a neonatal intensive care unit.

The objectives of this prospective, observational study were to determine the current indications of requesting chest radiograph in sick infants in a neonatal intensive care unit (NICU) and the effect of a user-guided request form for chest radiographs of sick infants. During the three-month study period, a total of 423 chest radiographs were requested on 159 sick newborn infants in the intensive area of this NICU. A majority (55.6%) of these chest radiographs were performed to verify positions tips of either central catheters (27.4%) or endotracheal tubes (28.1%). The number of chest radiographs done during the period when the user-guided request forms were utilised was significantly lower (1.24 per patient) than before (1.37 per patient) or after (1.58 per patients) the period when these forms were in use (p=0.01). The rate of radiological abnormalities detected in radiographs requested to verify position of tips of endotracheal tubes were significantly greater during the period when user-guided forms were used than when they were not (p=0.01). A significantly higher proportion of changes in management were instituted when the user-guided forms were in use than during the period when they were not used (p=0.03). We conclude that a user-guided radiographic request form helps doctors in NICU to carry out their management more effectively.

Successful clot lysis using low dose of streptokinase in 22 neonates with aortic thromboses.

OBJECTIVE: To determine whether intravenous infusion of low dose of streptokinase was effective in lysing umbilical arterial catheter (UAC)-associated aortic thrombi. METHOD: A prospective cohort study of 31 consecutive newborn infants with UAC-associated aortic thrombi which were detected by abdominal ultrasonography after removal of UAC. Twenty-two infants were treated with intravenous infusion of low dose (1000 U/h) streptokinase, while nine others were not treated due to various contra-indications. Thrombolysis occurred after a mean interval of 2.2 days (standard deviation (SD) = 1.8) in the treated infants. In the untreated infants, spontaneous thrombolysis occurred significantly later, after a mean interval of 16.9 days (SD = 14.7) (95% confidence intervals of difference between mean intervals - 26.0, - 3.4; P = 0.02). Only one treated infant developed mild bleeding directly attributed to streptokinase therapy. CONCLUSION: Low dose streptokinase infusion was effective and safe in thrombolysing UAC-associated aortic thrombi.

Methacholine challenge in preschool children: methacholine-induced wheeze versus transcutaneous oximetry.

Tracheal/chest auscultation for wheeze and transcutaneous oximetry have both been suggested as measures of outcome in bronchial provocation tests in young children. This study aimed to compare the sensitivity and safety of these two techniques as end-points for methacholine challenge in children aged <4 yrs. Seventy-two methacholine challenges were performed in 39 children aged <4 yrs with recurrent wheeze. Arterial oxygen saturation (Sa,O2) and transcutaneous oxygen pressure tcPO2 continuously, and the test was terminated when wheeze was heard or at Sa,O2 <91%. tcPO2 was not used as an end-point. Wheeze or desaturation occurred at < or =8 mg x mL(-1) methacholine in every test. One child had transient clinical cyanosis, but no other ill-effects were seen. Fifty-six tests (78%) were terminated for wheeze, seven (10%) for fall in Sa,O2 and nine (12%) showed simultaneous responses in both parameters. Twenty-eight tests (39%) contained a fall in tcPO2 >3 kPa but six of these also showed a significant rise. Fifty-three tests (75%) contained a fall in tcPO2 >15%, but 20 of these also showed a significant rise. Tracheal/chest auscultation with Sa,O2 monitoring is a sensitive and relatively safe end-point for bronchial challenges in preschool children. The erratic pattern of transcutaneous oxygen pressure response in some children casts doubt on its reliability as a proxy measure of bronchial obstruction.

The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days. One hour before each challenge they were pretreated in double-blind fashion using a metered-dose inhaler and Babyhaler spacer. Placebo was given before one challenge, and either 25, 50 or 100 microg of salmeterol before the other. Both the dose and treatment order were random. The provocative concentration of methacholine causing wheeze (PCwheeze) was measured on each occasion. Studies were terminated when wheeze occurred or arterial oxygen saturation (Sa,o2) fell below 91%. Of the 42 children enrolled, 33 completed the study. Two subjects refused the challenge test, two failed to return and five developed upper respiratory tract infections or wheeze between the two tests. The mean (range) age of the population was 27 (8-46) months. Ratios of PCwheeze between treatment and placebo challenges were calculated for each dosage group. The treatment/placebo ratios (95% confidence intervals) were 1.2 (0.6-2.4) for 25 microg, 2.5 (1.4-4.6) for 50 microg (p<0.01), and 4.0 (2.1-7.4) (p<0.001) for 100 microg doses. In recurrently wheezy children aged <4 yrs a single dose of salmeterol between 25 and 100 microg has a dose-dependent effect on methacholine-induced wheeze, and this is significantly different from placebo at 50 and 100 microg. This study suggests that the Babyhaler effectively delivers salmeterol to children <4 yrs of age and that doses between 50-100 microg are efficacious.