A single-center observational study on congenital diaphragmatic hernia: Outcome, predictors of mortality and experience from a tertiary perinatal center in Singapore.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a common birth defect associated with significant mortality and morbidity. There is limited outcome data on CDH in the Southeast Asian region. Rapid accessibility to our CDH Perinatal Center, as a consequence of the small geographic size of our country and efficient land transportation system, has largely eliminated deaths of live outborn babies prior arrival at our center. We selected a study period when extracorporeal membrane oxygenation (ECMO) support was not available at our institution. The data will therefore be relevant in developing management guidelines and antenatal counselling for perinatal centers in this region managing CDH with limited resources, without ECMO facilities. METHODS: A retrospective study of antenatally or postnatally diagnosed CDH infants born between January 2002 and June 2005 was performed. We selected this study period as ECMO support was not available over this period. We studied the demographics, clinical characteristics, postnatal predictors of mortality and outcomes of CDH infants in a single tertiary institution. RESULTS: A total of 24 patients with CDH were identified. Seventy-nine percent of liveborns with CDH survived to hospital discharge. Antenatal detection rate was 83.3%. Significant postnatal predictors of mortality were preoperative pneumothorax (p = 0.035), high CRIB score (p = 0.007), low one- and five-minute Apgar score (p = 0.011, p = 0.026 respectively) and high pCO2 on initial arterial blood gas (p = 0.007). At one-year follow-up, three patients had delayed gross motor milestones which resolved subsequently. Re-admissions were required for recurrent bronchiolitis (33%) and oesophageal reflux which resolved in all cases. Two (13.3%) infants had surgical complications and needed re-admission for probable adhesive intestinal obstruction; one required adhesiolysis and the other was managed conservatively with good outcome. CONCLUSION: A single-center CDH outcome in Singapore, without ECMO use, was good. This is a cohort now with long-term survival outcome which will be valuable to the neonatology community.

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.

Body composition measurement in young children using quantitative magnetic resonance: a comparison with air displacement plethysmography.

BACKGROUND: Quantitative magnetic resonance (QMR) has been increasingly used to measure human body composition, but its use and validation in children is limited. OBJECTIVE: We compared body composition measurement by QMR and air displacement plethysmography (ADP) in preschool children from Singapore's multi-ethnic Asian population (n = 152; mean ± SD age: 5.0 ± 0.1 years). METHODS: Agreements between QMR-based and ADP-based fat mass and fat mass index (FMI) were assessed using intraclass correlation coefficient (ICC), reduced major axis regression and Bland-Altman plot analyses. Analyses were stratified for the child's sex. RESULTS: Substantial agreement was observed between QMR-based and ADP-based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression analysis suggested that QMR measurements were generally lower than ADP measurements. Bland-Altman analysis similarly revealed that QMR-based fat mass were (mean difference [95% limits of agreement]) -0.5 (-2.1 to +1.1) kg lower than ADP-based fat mass and QMR-based FMI were -0.4 (-1.8 to +0.9) kg/m2 lower than ADP-based FMI. Stratification by offspring sex revealed better agreement of QMR and ADP measurements in girls than in boys. CONCLUSIONS: QMR-based fat mass and FMI showed substantial agreement with, but was generally lower than, ADP-based measures in young Asian children.

Which anthropometric measures best reflect neonatal adiposity?

BACKGROUND: Studying the determinants and the long-term consequences of fetal adipose accretion requires accurate assessment of neonatal body composition. In large epidemiological studies, in-depth body composition measurement methods are usually not feasible for cost and logistical reasons, and there is a need to identify anthropometric measures that adequately reflect neonatal adiposity. METHODS: In a multiethnic Asian mother-offspring cohort in Singapore, anthropometric measures (weight, length, abdominal circumference, skinfold thicknesses) were measured using standardized protocols in newborn infants, and anthropometric indices (weight/length, weight/length2 (body mass index, BMI), weight/length3 (ponderal index, PI)) derived. Neonatal total adiposity was measured using air displacement plethysmography (ADP) and abdominal adiposity using magnetic resonance imaging (MRI). Correlations of the anthropometric measures with ADP- and MRI-based adiposity were assessed using Pearson's correlation coefficients (rp), including in subsamples stratified by sex and ethnicity. RESULTS: Study neonates (n=251) had a mean (s.d.) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADPFM) and anthropometric measures were moderate (rp range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (rp=0.67, 0.66, 0.62, 0.62, respectively, all P<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADPFM, indicating that skinfold measures may have more discriminative power in terms of neonatal total body adiposity. For MRI-based measures, weight and weight/length consistently showed strong positive correlations (rp⩾0.7) with abdominal adipose tissue compartments. These correlations were consistent in boys and girls, across different ethnic groups, and when conventional determinants of neonatal adiposity were adjusted for potential confounding. Abdominal circumference was not strongly associated with ADPFM or abdominal fat mass. CONCLUSIONS: Simple anthropometric measures (weight and weight/length) correlated strongly with neonatal adiposity, with some evidence for greater discriminative power for skinfold measures. These simple measures could be of value in large epidemiological studies.

Neonatal outcome of extremely preterm Asian infants ⩽28 weeks over a decade in the new millennium.

OBJECTIVE: To evaluate predischarge neonatal mortality and morbidity and associated risk factors in extremely preterm Asian infants ⩽28 weeks, over a decade, so as to facilitate formulation of perinatal guidelines and counseling. STUDY DESIGN: Cohort study of 887 liveborn extremely preterm neonates between 2000 and 2009 at KKH, the centralized perinatal center in Singapore. Outcome measures were predischarge mortality, presence of one or more major neonatal morbidities and the composite outcome of mortality or neonatal morbidity. RESULT: Overall survival to discharge was 709/887 (80%) and was significantly higher with increasing gestational age (GA) (19% at 23 weeks to 93% at 28 weeks, P<0.001). Survival remained unchanged between 78 and 86% during the decade with no significant secular trend. Overall incidence of major morbidities were bronchopulmonary dysplasia (29%), late onset sepsis (23%), severe retinopathy of prematurity (21%), Grade 3 to 4 intraventricular hemorrhage (12%) and necrotizing enterocolitis ⩾Bells' stage II/focal intestinal perforation (9%). Composite morbidity was seen in 465/835 (56%) neonatal intensive-care unit admissions, decreased with increasing GA (P<0.001; odds ratio 0.65 (95% confidence interval 0.56 to 0.75) and was independently predicted by birth weight, Clinical Risk Index for Babies-revised version II score, male gender, presence of patent ductus arteriosus and airleaks. CONCLUSION: Although there was no significant trend in neonatal survival or composite morbidity over the decade, improved survival and morbidity were seen with increasing GA.

Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program.

IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore.

Current controversies in the management of patent ductus arteriosus in preterm infants.

OBJECTIVE: Patent ductus arteriosus is very commonly seen in very low birth weight (VLBW) infants, affecting about one-third. The present review tries to identify the group of VLBW infants who need active intervention in day-to-day practice and to determine the mode of intervention, based on current published literatures. METHODS: We searched the Cochrane library, MEDLINE, EMBASE and CINAHL databases, and reference that of identified trials. RESULTS AND CONCLUSIONS: Preterm infants with a birth weight of <800g are at risk of significant morbidity and mortality from PDA; it would be reasonable to treat them when symptomatic or if requiring positive pressure ventilator support. Those weighing >800g are unlikely to need treatment unless they are ventilator-dependent or show evidence of congestive heart failure.

Neonatal hepatic abscess in preterm infants:a rare entity?

INTRODUCTION AND OBJECTIVE: Neonatal pyogenic hepatic abscess in preterm infants is a rare entity. We present 6 cases of neonatal liver abscesses diagnosed in our hospital as well as an approach that will facilitate the early diagnosis and management of neonatal pyogenic liver abscess based on our case series and review of the literature. MATERIALS AND METHODS: Retrospective review of case records of all 6 patients diagnosed with neonatal liver abscess from January 2000 to December 2002 in KK Women's and Children's Hospital, Singapore. RESULTS: All neonates were premature with gestational ages between 24 and 34 weeks. Persistence of positive blood culture despite appropriate antibiotic treatment in 67% of the cases prompted use of hepatobiliary ultrasounds to detect liver abscess. Surgical drainage of liver abscess was performed in 33% of the cases, with the remainder treated conservatively with appropriate intravenous antibiotics. Half of the infants recovered with resolution of their liver abscess on serial hepatobiliary ultrasound. The other half died of fulminant sepsis. CONCLUSIONS: Neonatal pyogenic liver abscess, though rare, is associated with good outcome if diagnosed promptly and appropriate treatment instituted. In a preterm infant with sepsis, a high index of suspicion is required if there is persistence of positive blood culture despite appropriate antibiotic treatment, and hepatobiliary ultrasound should be done to detect and monitor neonatal liver abscess.

Closed versus partially ventilated endotracheal suction in extremely preterm neonates: physiologic consequences.

This randomized cross over study aimed to compare the severity and incidences of desaturation and bradycardia between the partially ventilated endotracheal suction method (PVETS) and closed tracheal suction system (CTSS) in extremely preterm neonates. Fifteen intubated and ventilated extremely low birth weight preterm infants (mean birth weight 689g) randomly underwent both suction techniques within a 12-h period to obtain a paired reading group. The process was repeated 24-48h apart until three pairs of reading groups were collected. Changes in oxygen saturation measured with pulse oximetry and heart rate changes measured with electrocardiogram were recorded using Hewlett-Packard m240A monitor trending software. The mean of each parameter's variation from baseline was obtained using SPSS descriptive statistics and analyzed using SPSS repeated measures ANOVA. Fisher Exact Test was used to analyze the incidence of desaturation and bradycardia. The closed tracheal suction system reported a significantly smaller degree of oxygen saturation fall (P<0.005) and significantly fewer incidences of desaturation. There was also a significantly smaller degree of heart rate reduction although episodes of bradycardia were not significantly different between the two methods. Oxygen saturation and heart rate were significantly more stable during the use of CTSS compared to PVETS in the extremely low birth weight preterm population.

Immunogenicity and reactogenicity of two regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio and Haemophilus influenzae type b vaccines administered to infants primed at birth with hepatitis B vaccine.

An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course. One vaccinee in the DTPa HBV-HPV- Hib group failed to respond to the poliovirus type 1 antigen. Response to the three pertussis antigens ranged from 92-97% in the DTPa-IPV-Hib plus separate HBV group and 100% in the DTPa HBV-IPV-Hib group. The most frequently reported post-vaccination symptoms were irritability in the DTPa-IPV-Hib plus separate HBV group (49% of vaccinees) and fever, defined as axillary temperature > or =37.5 degrees C, in the DTPa HBV- IPV-Hib group (50% of vaccinees).

Severe newborn encephalopathy unrelated to intrapartum hypoxic events: 3 case reports.

INTRODUCTION: Newborn encephalopathy is an important clinical problem associated with considerable morbidity and mortality and is pertinent in the assignment of blame in obstetrics litigation. CLINICAL PICTURE: We report 3 babies with severe neonatal encephalopathy. OUTCOME: In all 3 cases, intrapartum hypoxic insult was unlikely to be a significant contributing factor towards the development of neonatal encephalopathy. The aetiology was unclear in the first 2 cases and there was antecedent antenatal cause of feto-maternal haemorrhage in the last case. CONCLUSION: Prevention of neonatal encephalopathy was not possible in these 3 cases. We recommend that umbilical cord blood gases be clearly documented in such cases to reduce unnecessary obstetrics litigation of intrapartum asphyxia as the significant contributing factor to the poor neonatal outcome. Clinicians must have a high index of suspicion of antecedent causes and perform the necessary investigations to elucidate the aetiology of the neonatal encephalopathy.

The use and abuse of steroids in perinatal medicine.

Corticosteroids are one of the most powerful drugs increasingly used in the perinatal and neonatal period. This review discusses the merits and demerits of antenatal as well as postnatal use of steroids. A single course of antenatal corticosteroids in women at risk of premature delivery is highly effective in reducing respiratory distress syndrome (RDS), intraventricular haemorrhage and neonatal mortality and also neurodevelopmental sequelae including cerebral palsy. However, there is less evidence to support the practice of multiple courses of corticosteroids, with some animal and retrospective human studies suggesting an association with neurological impairment and reduction in birth weight as well as lung weight. Postnatal systemic corticosteroids have shown benefits in reducing chronic lung disease and improving survival for infants. However, besides short-term adverse effects, the follow-up studies have raised concern that they may increase the risk of neurodevelopmental disability, particularly cerebral palsy in survivors. Systemic corticosteroids may have a role in infants who had repeated and prolonged intubations and those with pressor-resistant hypotension. Alternative strategies for prevention of chronic lung disease, such as inhaled steroids, methylprednisolone and hydrocortisone, may need further studies with larger sample sizes. Data from animal research have revealed that fetal glucocorticoid exposure may have a role in programming the individual to adult degenerative diseases. Based on the current evidence, it is recommended that women at risk of preterm delivery receive a single course of glucocorticoids. Randomised controlled trials are needed to establish the true effects of multiple courses of antenatal corticosteroids. More research is also needed to study the long-term neurodevelopmental outcome of both multiple courses of antenatal corticosteroids, as well as postnatal corticosteroid therapy.

Transient paralytic ileus following the use of cyclopentolate-phenylephrine eye drops during screening for retinopathy of prematurity.

Cyclopentolate-phenylephrine eye drops are commonly used for mydriasis during routine screening for retinopathy of prematurity in preterm infants. Although systemic absorption is minimal, it can result in side effects. We report two cases of transient paralytic ileus associated with transient oxygen desaturation and hypertension following the use of cyclopentolate-phenylephrine eye drops.

Ureaplasma urealyticum and its association with chronic lung disease in Asian neonates.

OBJECTIVE: The aim of the present prospective cohort study was to evaluate the relationship between lower respiratory tract colonization with Ureaplasma urealyticum and development of chronic lung disease (CLD) in a high-risk neonatal population. METHODS: Prospective cohort study of preterm infants with a birthweight < 1,500 g needing mechanical ventilation within 24 h of birth in a tertiary care neonatal unit. Endotracheal aspirates from these infants were cultured within 24 h for U. urealyticum and the rate of colonization was determined. The primary outcome measure was the incidence of CLD at 28 days of life. RESULTS: Of the 41 infants studied, 10 (24%) infants were colonized with U. urealyticum. The colonization rate was higher in babies < 1,000 g compared with babies weighing 1,000-1,500 g (P = 0.04). There was no significant difference between the colonized and non-colonized groups with regard to the antenatal use of steroids, maternal prolonged rupture of membranes, gestational age, birthweight, sex, respiratory distress syndrome, use of surfactant, patent ductus arteriosus and gastrooesophageal reflux. Of the 37 survivors, 20 (54%) developed CLD; eight infants (88.5%) in the colonized group developed CLD compared with 12 infants (42.8%) in the non-colonized group (P = 0.01). CONCLUSIONS: Neonates colonized with U. urealyticum were twice as likely to have CLD than non-colonized babies (relative risk 2.01; 95% confidence interval 1.27-3.37). These data suggest a significant association between colonization with U. urealyticum and CLD in infants weighing < 1,500 g.

Twin-twin transfusion syndrome: a five year review.

OBJECTIVE: To determine the incidence, complications, management, and outcome in infants with twin-twin transfusion syndrome (TTTS) over a period of five years. METHODS: TTTS was diagnosed in monochorionic twins if one was pale and the other plethoric with a haemoglobin difference > or =5 g/100 ml and/or birthweight differences > or =15%. RESULTS: Eighteen (6.2%) of the 292 twin pairs had TTTS. Eight pairs (44%) had the acute type and the rest (56%) had the chronic type of TTTS. The mean (SEM) intrapair haemoglobin difference in the acute type was 4.8 (2.1) g/100 ml which gave a discordance of 7.1 (4.6)%, whereas that in the chronic type was 6.9 (2.9) g/100 ml and 24.4 (6.1)% respectively. Infants with the acute type had a significantly higher incidence of vaginal delivery (p<0.03), hypotension (p<0.025), and respiratory distress (p<0.01) compared with those with the chronic type. There was no significant difference in the incidence of anaemia, polycythaemia, asphyxia, hypoglycaemia, and hyperbilirubinaemia. Two recipients died in utero as the result of chronic TTTS, while their survivors developed spastic cerebral palsy. There were no neonatal deaths. CONCLUSIONS: TTTS, although uncommon, may have an adverse neurodevelopmental outcome especially if one twin dies in utero. Prompt recognition and management of the haemodynamic and haematological problems of infants with the acute types of TTTS will result in optimal neurodevelopmental outcome.

Parainfluenza type 3 viral outbreak in a neonatal nursery.

An outbreak of parainfluenza virus type 3 infection that occurred in a special neonatal care unit is described. Birth weights of affected infants ranged from 1860 to 2080 g and gestational ages were between 28 and 32 weeks. Three infants presented with recurrent episodes of apnoea associated with oxygen desaturations on postnatal ages of 16 days, 26 days and 66 days respectively; upper respiratory tract infection symptoms such as coryza were absent in them. Two older infants who had oxygen dependent bronchopulmonary dysplasia presented with worsening of the respiratory status due to bronchiolitis at 5 and 6 months of age respectively. All infants required supplemental oxygen and assisted ventilatory support and there were no deaths. Parainfluenza virus type 3 was identified by direct antigen detection in 3 cases and was isolated in the other two. The outbreak was controlled by isolating the infected infants, use of gowns and strict hand washing. Nonporous surfaces contaminated with parainfluenza virus type 3 were cleansed with water and detergent. Viral respiratory infections should be considered in the differential diagnosis when growing premature infants present with recurrent apnoeic episodes and they may be severe enough to require assisted ventilatory support. The source of the outbreak was possibly a medical officer and a medical student who had an upper respiratory tract infection prior to the outbreak in the nursery. Medical and nursing staff with viral respiratory infections should avoid working in the nurseries until they are well.

Blood pressure standards for very low birthweight infants during the first day of life.

Blood pressures during the first day of life were measured prospectively in 61 very low birthweight infants using umbilical or peripheral arterial lines. Video recordings of real time waveforms were reviewed. Blood pressure correlated linearly with birthweight and gestation. Comparison with available standards showed that infants weighing under 800 g had lower acceptable mean arterial pressure (MAP). The lower limits of MAP for infants between 26 to 32 weeks of gestation were numerically similar to the gestational ages.

Term infants with hypoxic ischaemic encephalopathy: poor neurodevelopmental outcome despite standard neonatal intensive care.

Perinatal asphyxia may be severe and affect the neurological system, causing hypoxic ischaemic encephalopathy (HIE). Twenty-three term infants with HIE were studied over 3.5 years. Nine died and of the 14 survivors, eight were normal and the rest had abnormal neurological sequelae. Favourable prognostic markers were a 5 minute Apgar score > 5, first pH > 7.1, and stage I HIE. Despite standard neonatal intensive care management, the mortality and morbidity rates for these infants remained high.