Evaluation of a simple intervention to reduce exchange transfusion rates among inborn and outborn neonates in Myanmar, comparing pre- and post-intervention rates.

BACKGROUND: In Myanmar, approximately half of all neonatal hospital admissions are for hyperbilirubinaemia, and tertiary facilities report high rates of Exchange Transfusion (ET). The aim of this study was to evaluate the effectiveness of the pilot program in reducing ET, separately of inborn and outborn neonates. METHODS: The study was conducted in the Neonatal Care Units of four national tertiary hospitals: two exclusively treating inborn neonates, and two solely for outborn neonates. Prior to intervention, no high intensity phototherapy was available in these units. Intervention in late November 2011 comprised, for each hospital, provision of two high intensity LED phototherapy machines, a photo radiometer, and training of personnel. Hospital-specific data were assessed as Relative Risk (RR) ratios comparing ET rates pre- and post-intervention, and individual hospital results were pooled when appropriate. RESULTS: In 2011, there were 118 ETs among inborn neonates and 140 ETs among outborn neonates. The ET rate was unchanged at Inborn Hospital A (RR = 1.07; 95 % CI: 0.80-1.43; p = 0.67), and reduced by 69 % at Inborn Hospital B (RR = 0.31; 95 % CI: 0.17-0.57; p < 0.0001). For outborn neonates, the pooled estimate indicated that ET rates reduced by 33 % post-intervention (RRMH = 0.67; 95 % CI: 0.52-0.87; p = 0.002); heterogeneity was not a problem. CONCLUSION: Together with a photoradiometer and education, intensive phototherapy can significantly reduce the ET rate. Inborn Hospital A had four times as many admissions for jaundice as Inborn Hospital B, and did not reduce ET until it received additional high intensity machines. The results highlight the importance of providing enough intensive phototherapy units to treat all neonates requiring high intensity treatment for a full course. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615001171505 , 2 November 2015.

Effect of prolonged dexamethasone on oxygen-dependency in infants with chronic lung disease.

To determine the effect of prolonged dexamethasone therapy on oxygen-dependency clinical phase of prematures with bronchopulmonary dysplasia, we examined a consecutive group of 27 infants (birth weight, < 1500 g and gestational age, < 32 weeks), who remained with a static or deteriorating oxygen-dependency after weaning from the respirator [pre-treatment FiO2, mean +/- SEM over three days (31 +/- 2)%, range (27-73)%]. Twenty five out of 27 infants were weaned from supplemental oxygen during the 42-day steroid treatment period, with a mean (+/- SEM) duration of oxygen supplementation of 16 +/- 4 days. The distribution of the ratios of successive post-treatment FiO2 values with respect to pre-treatment FiO2 shows, on average, a progressive reduction with time. The percentage of the FiO2 decrease is statistically significant at a level of 2 and 3 SD after 3 days and 7 days, respectively and the average FiO2 fall, as function of time, follows an exponential law. It follows that the time spent in oxygen for a single patient may be determined, accounting for the individual severity of pre-treatment FiO2.

Serum enzyme activities in premature infants with bronchopulmonary dysplasia.

Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (gamma-GT) and lactate dehydrogenase (LDH) activities were measured in 26 premature infants with bronchopulmonary dysplasia (BPD) (group 1), and in 24 premature controls, matched for gestational age and birth weight (group 2). Blood samples were taken serially on 3, 10, 20, 30 and 60 postpartum days. Group 1 and group 2 premature infants showed statistically higher LDH activities on the 3rd postpartum day. These differences disappeared later and LDH activities progressively decreased with time in both premature groups. Mean AST values of group 1 and group 2 premature infants were also significantly higher on the 3rd postpartum day. Subsequently, in all groups, AST showed a postpartal decrease, and a stabilization from the 10th day of life until the 2nd postnatal month. Mean ALT values were instead, comparable on the 3rd postnatal day and subsequently increased, although not significantly. Like the AST, gamma-GT of group 1 and group 2 premature infants were slightly more elevated on the 3rd postpartum day. The subsequent decrease was however transitory, and at 1 and 2 postnatal months a noticeable, significant progressive increase in mean values was found. It is concluded that serum ALT, AST, LDH and gamma-GT measurement of sick premature infants within the first 2 months of life are not significantly altered by the occurrence of BPD.

[The prevalence and characteristics of persistent pulmonary hypertension of the newborn. A multicenter study. The Study Group of the Società Italiana di Cardiologia Pediatrica (SICP)]. / Prevalenza e caratteristiche della ipertensione polmonare persistente del neonato. Studio multicentrico. Gruppo di Studio della Società Italiana di Cardiologia Pediatrica (SICP).

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a rare syndrome with a severe prognosis, in which a prompt diagnosis can be life-saving. The aim of our study was to verify its prevalence in a neonatal population, define clinical and echocardiographic criteria for the diagnosis of PPHN and discuss therapeutic choices. METHODS: The following clinical and echocardiographic criteria for the diagnosis of PPHN were defined: 1. cyanosis and hypoxemia non-responsive to O2 therapy; 2. right to left shunt at an atrial or ductal level. All neonates fulfilling these criteria referred to the neonatal units of seven pediatric or general hospitals over a two-year period were enrolled. RESULTS: From January 1995 to December 1996, thirty neonates with PPHN (8%) were observed. Birth was pre-term in 5 out of 30. Ten (33%) had experienced chronic and/or fetal asphyxia (FA). Death occurred in 7 (22%), four of whom with FA. Echocardiography showed tricuspid insufficiency in 18 (60%); mean pulmonary systolic pressure was 67 +/- 16 mmHg (range 41-95). In 23 surviving neonates, normalization of clinical and echocardiographic parameters occurred in 8 +/- 5 days. THERAPY: In most neonates, vasodilators (tolazoline, prostacyclin) and/or nitric oxide were employed. CONCLUSIONS: PPHN is confirmed to be a rare pathological condition; prognosis is severe, particularly in neonates with FA. Echocardiography is a reliable non-invasive method for a prompt diagnosis and follow-up. Subsequent studies are needed to assess therapeutic choices.

Home oxygen therapy in infants with bronchopulmonary dysplasia: a prospective study.

UNLABELLED: We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O2 therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25-36 weeks) and mean birth weight 1093 g (range 630-2750 g). Infants were regularly monitored to maintain pulse oximeter O2 saturation over 94%-95%. The source of O2 was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO2 measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7-8.6) and mean weight 2830 g (range 2150-3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O2 therapy was 97 days (range 15-320 days) and the mean age of discontinuation of O2 was 6.9 months (range 3-14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O2 therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving. CONCLUSION: Home O2 therapy permits the safe early discharge of O2-dependent BPD infants and it reduces significantly the length of time spent in hospital which represents a considerable financial saving.

Non-furosemide-related renal calcifications in premature infants with bronchopulmonary dysplasia.

Renal calcification is a known complication of long-term furosemide therapy in infants with bronchopulmonary dysplasia (BPD). In a prospective study the clinical course and long-term renal sequelae of renal calcifications of 19 consecutive premature neonates (birthweight < 1250 g) with bronchopulmonary dysplasia who did not receive furosemide were examined. Infants were divided into two different groups on the basis of ultrasound evidence of renal calcifications (RC group) or absence of renal calcifications (NRC group). Serial examinations, performed at the age of 1, 2, 3, 6, 9 and 12 months, showed that 12 infants at the mean age of 68.5 +/- 12.8 days of life had renal calcifications (63%), and 3 of them had nephrolithiasis; 8 had bilateral renal calcifications. Among the 9 survivors, 2 had chronic renal calcifications at the age of 9 months; however, all normalized at the age of 12 months. Twelve infants received hydrochlorothiazide and spironolactone (63%), 17 had prolonged courses of xanthines and dexamethasone (89.5%), while furosemide was not part of the routine pharmacological administration. Statistical analysis showed that birthweight, gestational age, Apgar score and length of parenteral nutrition were comparable in the RC and NRC group infants. Mean serum creatinine, creatinine clearance, fractional sodium excretion and urinary calcium excretion values during the 12-month study period were comparable in the RC and NRC groups. Mechanical ventilation and hospital stay length were instead associated with renal calcification occurrence. The strongest indicator of renal calcification risk for this high-risk population is the severity of the unresolved acute lung disease, where different facets of respiratory management, other than the addition of furosemide, represent sufficient stimuli and renal injury to potentiate stone formation.

Prenatal theophylline and necrotizing enterocolitis in premature newborn infants.

To determine whether prenatal theophylline therapy would increase the incidence of neonatal necrotizing enterocolitis (NEC) we studied bowel dysfunction in 59 consecutive premature infants (g.s. < 34 weeks), whose mothers were treated with theophylline as a tocolytic during the last trimester, or as surfactant synthesis inductor, for at least three days prior to premature labor (Group A). As case-control we considered the premature, matched for gestational age born immediately before, and whose was untreated with theophylline (Group B). NEC occurred in one patient from group A during the second postnatal week, and surgery was performed. First passage of meconium and start of enteral feeding were comparable in groups A and B, while gastric residuals lasting more than 4 days were found statistically increased (p < 0.03) in antenatally treated group A prematures. Furthermore, 18 out of 49 prematures postnatally treated with theophylline had gastric residuals (36%) with respect to 5 out of 69 untreated (7%) (p < 0.001). Also the premature infants treated ante and postnatally with theophylline showed a statistically significant increase of lasting gastric residuals with respect to the untreated, 13/16 vs 5/7, respectively (p < 0.03). Antenatal theophylline administered to high risk mothers, when maternal diseases do not allow the use of steroids, does not appear to later increase the risk of NEC in premature infants, and provides a chance to avoid the risks related to premature birth. Inhibitory activity on gut motility and gastric irritability are only detectable during the first postnatal days, enhanced by gut immaturity of preterm infants.

Pulmonary function until two years of life in infants with bronchopulmonary dysplasia.

To evaluate the physiologic course of pulmonary function in infants with bronchopulmonary dysplasia (BPD) weighing less than 1,250 g at birth, 24 infants with BPD underwent serial pulmonary function evaluations from birth until 2 yr of age. All infants were intubated at birth and the mean duration of mechanical ventilation was 38 +/- 4 d. Passive respiratory system compliance (Crs) and resistance (Rrs) were measured between 10 and 20 d of life during mechanical ventilation. Thereafter pulmonary mechanics and functional residual capacity (FRC) were evaluated at 3, 6, 9, 12, and 24 mo of postnatal age. Forced expiratory flow (Vmax,FRC) was measured at 2 yr of age. A severe alteration on Crs (50% of predicted) was found during the acute phase of BPD, associated with abnormal values of Rrs. A progressive improvement (ANOVA, p < 0.0001) occurred in the first year of life and, at 24 mo of age, Crs and Rrs reached the range of normalcy. FRC value was 86 +/- 7.5% of predicted at 3 mo and gradually increased to a mean value of 115 +/- 5% of predicted at 2 yr of age. In spite of the good resistance time course over the 2-yr evaluation, less favorable data of Vmax,FRC were found with individual values reduced more than 40% of predicted values in 70% of the children. In conclusion, although pulmonary mechanics of BPD survivors improves during the first years of life, reaching the range of normal values, at 2 yr of age they still present a substantial airway function impairment as revealed by the low forced expiratory flows.

Oxygen saturation in premature neonates with bronchopulmonary dysplasia in a hammock.

Premature neonates with bronchopulmonary dysplasia (BPD) frequently present borderline hypoxemia and the risk for oxygen desaturation may increase in relation to the posture. Our aim was to see if infants with BPD experience severe hypoxemia (SaO2 < 85%) in a hammock, a 'containing' posture considered advantageous to neuromotor and relational development of the preterm. Fifteen pulse oximetry recordings (Ohmeda B105 3760 Pulse Oximeter) were obtained in 15 subjects (range of gestational age and postnatal age 27-30 and 33-48 weeks, respectively; range of birth weight and body weight at entrance to the study 0.64-1.35 and 0.97-2.24 kg, respectively) before, during and after placement in a hammock; each testing period lasted 15 min, and each baby served as his or her own control. BPD preterm infants were receiving oxygen therapy by continuous flow standard nasal cannulas (FiO2 > 25%, < 40%). The analysis of the data, that have a rough gaussian distribution, indicates a worsening of SaO2 in the hammock position. In fact, mean +/- SEM, median and range of the SaO2 values in pre- and posthammock position are comparable, but are significantly different at 99.9% confidence level (CL) in prehammock vs. hammock posture and at 98% CL in posthammock vs. hammock posture. Moreover, the percent of time with SaO2 < 85% during the periods recorded increased about 10 +/- 5% in a hammock (24 +/- 4%), in comparison to pre- (14 +/- 3%) and posthammock position (15 +/- 3%). These results suggest that oxygen-dependent BPD preterm infants in the hammock posture may experience severe hypoxemia that in part limits the possible advantages of the 'containment'.

"Silent" patent ductus arteriosus and bronchopulmonary dysplasia in low birth weight infants.

We conducted a clinical study on the antecedents of bronchopulmonary dysplasia (BPD) in 290 premature RDS infants with < or = 1.75 kg birth weight (BW). They were enrolled in a prospective trial of indomethacin treatment for "silent" patent ductus arteriosus (PDA), screened by 2-D echocardiographic and pulsed Doppler evaluation on the third day of life. The trial took place at the NICU of the Pediatric Department of Padua University between January 1987 and December 1991. Out of 290 infants screened, 96 had evidence of "silent" PDA (33%) and 77 responded to indomethacin treatment (80%). Comprehensively 79 (27%) developed BPD, and from these the incidence of BPD was statistically increased in infants with "silent" PDA, 47 out of 96 (49 +/- 9%), with respect to 32 out of 194 (16 +/- 3%) preterm infants without PDA. Statistical analysis showed that in preterm infants with "silent" PDA the development of BPD was correlated at 99% C.L. to their low BWs (mean BW = 1.13 kg): in fact the mean and the mode of BW distributions were statistically lower in the presence of BPD, 1.03 kg versus 1.24 kg, and 0.88 kg versus 1.65 kg respectively. Moreover, the preterm infants with "silent" PDA unresponsive to the first course of indomethacin and/or submitted later to surgical closure, presented a statistically lower BW with respect to the early responders, 1.06 kg versus 1.18 kg, and at the same time a statistically higher incidence of BPD (63 +/- 20% versus 43 +/- 9%). From these data we conclude that, although "silent", PDA increase per se the incidence of BPD, even if benefits from an early induced closure. Furthermore, a lower BW of infants affected by "silent" PDA represents a contributing factor to the development of BPD.

"Silent" patent ductus arteriosus and bronchopulmonary dysplasia in low-birthweight twins.

During a screening protocol of early echocardiographic diagnosis (ATL MK 600) and treatment of "silent" PDA in RDS preterms with BW < or = 1.750 kg, clinical data on premature twins were collected, including diagnosis of both PDA and BPD, to investigate whether twin birth influences PDA incidence and BPD development. Out of the 290 RDS preterms evaluated, 96 (33%) showed evidence of PDA, and a total of 79 (27%) developed BPD, 47 (16%) with associated PDA and 32 (11%) without PDA. Out of 238 singletons, 74 (31%) presented "silent" PDA and a total of 75 (31%) developed BPD, 44 (18%) with associated PDA, and 31 (13%) without PDA. In 52 other twins (18% of the total number of babies studied), 22 (42% of this subgroup) presented evidence of "silent" PDA, and 4 (8% of the subgroup), developed BPD, 3 with associated PDA (6% of the subgroup), and 1 without PDA (2% of the subgroup). From these data, it is inferred that that low-birthweight twins are at high risk for PDA hemodynamic complications during RDS, and may benefit from early induced ductal closure. Instead, in RDS twins, BPD was statistically less frequent (at the 99% C.L.) probably because twinning enhances fetal lung maturity, influencing enzymatic and nonenzymatic protective systems of lung defence.

[Computerization of a clinical chart of perinatal data]. / La computerizzazione di una cartella clinica dai dati perinatali.

A computerized protocol, PADOVA-BPD, has been set-up to study prematures affected by RDS, PDA and/or BPD. This protocol consists of a Data Bank, BPDdata, where the information of traditional clinical chart has been stored and of the BPDPadova program, written for this purpose in FORTRAN 77, that allows a wide band of clinical and statistical analysis.

Does the respiratory distress syndrome in twins and singletons run different risks of persistent ductus arteriosus?

The incidence and evolution of patent ductus arteriosus (PDA) was evaluated in twins and preterm singletons with birth weight less than or equal to 1750 g admitted to our Department in 1987 for respiratory distress syndrome (RDS). Screening by echocardiography and Doppler-flow studies (AT MK 600) was performed on the third day of life. Out of 91 neonates who needed intubation and ventilation during this 12-month period (23.8% of admissions), 40 weighed less than 1750 g and of these 40, 14 were twins (35%). Hemodynamically significant PDA was documented in 13 patients; of these, only 5 were preterm singletons and 8 were twins. Two twins weighing less than 1000 g received no therapy for ductus closure; one ductus closed spontaneously, the other had an early demise. Three twins and 2 preterm singletons received indomethacin; one of the twins needed a second cycle for definitive ductus closure. Three twins and three preterm singletons underwent surgery, while one twin died on the 10th postoperative day. Screening and early therapy of PDA during RDS could be of great clinical importance. Twinning seems to play a role in the incidence and evolution of PDA and this needs to be evaluated in further studies.