Victor Samuel Rajadurai

Establishing enteral feeding in preterm infants with feeding intolerance: A randomized controlled study of low-dose erythromycin

Objective A prospective, double-blind, randomized, controlled trial was conducted to evaluate the effect of low-dose erythromycin on the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance. Methods Two groups of preterm infants (birth weight ≤ 1500 g) with feeding intolerance were randomized to either low-dose erythromycin (5 mg/kg every 8 hours) or 5% dextrose placebo, both of which were discontinued 1 week after full enteral feedings were tolerated. The primary outcome variable was the time taken to attain full enteral feedings of at least 130 mL/kg/d. Results The gestational age at birth was similar in the two groups (erythromycin, 27.1 ± 1.9 weeks; placebo, 27.5 ± 2.9 weeks). The mean birth weight of the erythromycin group was lower (806.3 ± 215.6 g) than the placebo group (981.4 ± 285.4 g; P = 0.18), and included more infants who were small for gestational age (4/13 = 31% versus 1/11 = 9%; P = 0.224). There was no difference between the two groups with regard to the volume of feedings they were receiving at the time of enrollment. Reduction in symptoms of gastroesophageal reflux was similar in the two groups. 3 of 13 in the erythromycin group and 4 of 11 in the placebo group improved during the study (P = 0.565). The mean time to attain full enteral feedings after enrollment was 24.9 + 2.9 days in the erythromycin group and 30.8 ± 4.1 days in the placebo group, a difference that did not reach statistical significance (P = 0.17). Conclusions Low-dose erythromycin did not reduce the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance. Gastroesophageal reflux decreased as a consequence of maturation of the gastrointestinal tract and not because of erythromycin. These preliminary results justify verification in larger multicenter trials.

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

Abstract:  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.

Associations of gestational glycemia and prepregnancy adiposity with offspring growth and adiposity in an Asian population

BACKGROUND Maternal obesity and hyperglycemia increase risk of obesity and diabetes in offspring later in life. OBJECTIVE We examined the relation between gestational glycemia and prepregnancy body mass index (ppBMI) with offspring growth in an Asian mother-offspring cohort. DESIGN Pregnant mothers undertook a 75-g 2-h oral-glucose-tolerance test at 26-28 wk of gestation. In 937 singleton offspring, ≤9 serial measurements of weight and length were obtained from birth until 36 mo of age. RESULTS Gestational fasting plasma glucose (FPG) was positively associated with birth weight (B: 0.17; 95% CI: 0.10, 0.24; P < 0.001) and birth BMI (B: 0.15; 95% CI: 0.06, 0.40; P = 0.001) but not at ≥3 mo of age. In contrast, maternal ppBMI was positively associated with birth variables and conditional growth in weight and BMI in the first 36 mo of life. However, gestational FPG and prepregnancy obesity status interacted significantly for the association with offspring growth and overweight status in the first 36 mo of life (P-interaction < 0.01). In nonobese mothers, each unit increase in gestational FPG was associated with increased offspring weight (B: 0.08; 95% CI: 0.008, 0.16; P = 0.03) and BMI (B: 0.08; 95% CI: 0.003, 0.15; P = 0.04) as well as increased risk of overweight in the first 36 mo of life (OR: 1.36; 95% CI: 1.10, 1.68). However, in obese mothers, each unit increase in gestational FPG was associated with decreased offspring weight (B: -0.01; 95% CI: -0.02, -0.003) and BMI (B: -0.008; 95% CI: -0.01, -0.002) velocity (P < 0.01 for both) and decreased risk of overweight (OR: 0.59; 95% CI: 0.41, 0.86) in the first 36 mo of life. CONCLUSIONS Prepregnancy adiposity was associated with offspring growth in early childhood. Although pooled analyses showed no demonstrable difference by 3 mo of age, there were contrasting and opposite associations of gestational glycemia with weight and BMI in the first 36 mo of life in offspring of nonobese and obese mothers separately. This study was registered at clinicaltrials.gov as NCT01174875.

Abdominal adipose tissue compartments vary with ethnicity in Asian neonates: Growing Up in Singapore Toward Healthy Outcomes birth cohort study

BACKGROUND A susceptibility to metabolic diseases is associated with abdominal adipose tissue distribution and varies between ethnic groups. The distribution of abdominal adipose tissue at birth may give insights into whether ethnicity-associated variations in metabolic risk originate partly in utero. OBJECTIVE We assessed the influence of ethnicity on abdominal adipose tissue compartments in Asian neonates in the Growing Up in Singapore Toward Healthy Outcomes mother-offspring cohort. DESIGN MRI was performed at ≤2 wk after birth in 333 neonates born at ≥34 wk of gestation and with birth weights ≥2000 g. Abdominal superficial subcutaneous tissue (sSAT), deep subcutaneous tissue (dSAT), and internal adipose tissue (IAT) compartment volumes (absolute and as a percentage of the total abdominal volume) were quantified. RESULTS In multivariate analyses that were controlled for sex, age, and parity, the absolute and percentage of dSAT and the percentage of sSAT (but not absolute sSAT) were greater, whereas absolute IAT (but not the percentage of IAT) was lower, in Indian neonates than in Chinese neonates. Compared with Chinese neonates, Malay neonates had greater percentages of sSAT and dSAT but similar percentages of IAT. Marginal structural model analyses largely confirmed the results on the basis of volume percentages with controlled direct effects of ethnicity on abdominal adipose tissue; dSAT was significantly greater (1.45 mL; 95% CI: 0.49, 2.41 mL, P = 0.003) in non-Chinese (Indian or Malay) neonates than in Chinese neonates. However, ethnic differences in sSAT and IAT were NS [3.06 mL (95% CI:-0.27, 6.39 mL; P = 0.0712) for sSAT and -1.30 mL (95% CI: -2.64, 0.04 mL; P = 0.057) for IAT in non-Chinese compared with Chinese neonates, respectively]. CONCLUSIONS Indian and Malay neonates have a greater dSAT volume than do Chinese neonates. This finding supports the notion that in utero influences may contribute to higher cardiometabolic risk observed in Indian and Malay persons in our population. If such differences persist in the longitudinal tracking of adipose tissue growth, these differences may contribute to the ethnic disparities in risks of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT01174875.

Alveolar capillary dysplasia: absence of CD117 immunoreactivity of putative hemangioblast precursor cells.

Alveolar capillary dysplasia is a rare cause of irreversible persistent pulmonary hypertension in newborns resulting from failure of formation of peripheral capillary loops with consequent reduction in the blood-gas barrier. The basic defect in morphogenesis is unknown, although it is postulated that there is a structural abnormality of the hemangioblast precursors of the primitive lung mesenchyme in the septal regions of the developing lung leading to abnormal vasculogenesis. Two cases of alveolar capillary dysplasia evaluated immunohistochemically showed uniform CD117 negativity in the septal interstitial cells forming the pulmonary capillaries. A series of 12 control cases showed positive immunoreactivity for CD117 in a subset of septal interstitial cells forming the putative hemangioblast precursor cells. This novel finding is a useful adjunctive diagnostic tool and may support the hypothesis that absence of putative CD117-positive hemangioblast precursor cells is a key structural defect. This defect results in abnormal vasculogenesis and consequent failure of formation of an adequate blood-gas barrier.

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

ObjectivePatent 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.MethodsWe searched the Cochrane library, MEDLINE, EMBASE and CINAHL databases, and reference that of identified trials.Results and ConclusionsPreterm 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.

Paternally inherited ABCC8 mutation causing diffuse congenital hyperinsulinism

Summary Background: Congenital hyperinsulinism (CHI) is a rare genetic disorder characterised by inappropriate insulin secretion in the face of severe hypoglycaemia. There are two histological subtypes of CHI namely diffuse and focal. Diffuse CHI is most common due to recessive mutations in ABCC8/KCNJ11 (which encode the SUR/KIR6.2 components of the pancreatic β-cell KATP channel) whereas focal CHI is due to a paternally inherited ABCC8/KCNJ11 mutation and somatic loss of heterozygosity for the 11p allele inside the focal lesion. Fluorine-18-l-dihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA-PET/CT) is used in the pre-operative localisation of focal lesions prior to surgery. Diffuse CHI if medically unresponsive will require a near total pancreatectomy whereas focal CHI will only require a limited lesionectomy, thus curing the patient from the hypoglycaemia. Aims: To report the first case of genetically confirmed CHI in Singapore from a heterozygous paternally inherited ABCC8 mutation. Methods/Results: A term male infant presented with severe hyperinsulinaemic hypoglycaemia (HH) after birth and failed medical treatment with diazoxide and octreotide. Genetic testing (paternally inherited mutation in ABCC8/p.D1472N) suggested focal disease, but due to the unavailability of 18F-DOPA-PET/CT to confirm focal disease, a partial pancreatectomy was performed. Interestingly, histology of the resected pancreatic tissue showed changes typical of diffuse disease. Conclusion: Heterozygous paternally inherited ABCC8/KCNJ11 mutations can lead to diffuse or focal CHI. Learning points HH is a cause of severe hypoglycaemia in the newborn period. Paternal mutations in ABCC8/KCNJ11 can lead to diffuse or focal disease. 18F-DOPA-PET/CT scan is the current imaging of choice for localising focal lesions. Gallium-68 tetra-aza-cyclododecane-N N′N″N-‴-tetra-acetate octreotate PET scan is not a useful imaging tool for localising focal lesions. The molecular mechanism by which a heterozygous ABCC8 mutation leads to diffuse disease is currently unclear. Focal lesions are curable by lesionectomy and so genetic studies in patients with HH must be followed by imaging using 18F-DOPA-PET/CT scan.

Medications That Increase Osmolality and Compromise the Safety of Enteral Feeding in Preterm Infants

Background: Medications added to preterm milk feeds have the potential to raise osmolality, causing feed intolerance and necrotizing enterocolitis. Objective: The aim of this study was to evaluate changes in the osmolality of milk feeds and water with 14 medications and the diluent amounts required to keep the osmolality below the safety threshold of ≤450 mOsm/kg. Changes in the osmolality of milk with medications while on continuous infusion over 2 and 4 h were determined. Methods: This study was designed to measure the osmolality of 14 commonly used medications in preterm infants both neat and when supplemented with expressed breast milk (EBM), EBM with fortifier (EBMF), preterm formula (PTF), and water. Dose-effect curves were plotted, and the volume of each diluent was calculated to keep the osmolality ≤450 mOsm/kg. Time-effect curves were plotted at 2 and 4 h for each medication for both EBM and EBMF. Results: Neat osmolality of all except 5 medications were above 2,000 mOsm/kg. The osmolality rose with decreasing proportions of diluents used, depicting an indirect curvilinear relationship between the increasing dilution and osmolality for all except 2 medications. As a diluent, EBM was required in lower dilutions than EBMF. Dilutions needed for additives with PTF were very similar to those of EBM. The change in osmolality over time with additives was statistically significant for EBMF. Conclusions: EBM and PTF were found to be safer diluents than EBMF for enteral additives. The practice of keeping milk feeds with medications for continuous feeding is safe for a period of 4 h in EBM.

Meconium Peritonitis: Correlation of Antenatal Diagnosis and Postnatal Outcome - An Institutional Experience over 10 Years.

Objective: To identify the fetal and neonatal imaging characteristics of meconium peritonitis (MP) and their clinical outcome. We also studied the role of prenatal ultrasound (US) in antenatal diagnosis and its use in predicting the need for surgical intervention postnatally. Material and Methods: We conducted a retrospective analysis of a cohort of 18 infants with MP from April 2004 to March 2014. Results: Prenatal US detected MP-related abnormalities in 15/18 (83.3%) fetuses. The median gestational age at initial diagnosis of MP was 24 weeks (range 19-31). Fetal ascites (93.3%) was the most common prenatal US finding. Of the 18 infants, 12 (66.7%) required surgical intervention. The overall survival rate was 94.4%. All infants with a prenatal US scan showing meconium pseudocyst or bowel dilatation required surgical intervention postnatally. Discussion: A combination of ascites, intraperitoneal calcification, and echogenic bowel on fetal US raises a high suspicion of MP. Surgical intervention is indicated in the presence of meconium pseudocyst on fetal or postnatal US scan. Antenatal US has high specificity (100%) but low sensitivity (22.2%) in detecting meconium pseudocyst. A favorable outcome can be expected with early antenatal diagnosis and timely surgical intervention in a tertiary hospital.