[Chorioamnionitis and inflammatory disease in the premature newborn infant]. / Corioamnionite e malattie infiammatorie del neonato pretermine.

Preterm births occurs in 6-12% of all pregnancies, accounts for 75% of neonatal death and causes significant neonatal morbidity. A large number of preterm birth is associated with infection (30%), because of the release of many cytokines. In fact acute chorioamnionitis represents the inflammatory response to extracellular microorganisms that gain access to the gestational sac. Clinical signs of infection compare in the 12% of cases, while the prevalence of positive amniotic fluid cultures is approximately 50% in patients with preterm PROM. Despite the recent studies about the dosage of inflammatory biomarkers in the amniotic fluid or in fetal and maternal blood, placenta histology remains the gold standard for the diagnosis of chorioamnionitis. Histological chorioamnionitis describes the progression of the inflammatory process. Organisms first colonise the chorioamnionic surface. Then, the neutrophils migrates to the chorion (chorionitis) and to the amnion (chorioamnionitis) and, in the last stage, amnionic epithelial cells undergo necrosis (necrotising chorioamnionitis). It represents the mother inflammatory response and it differs from the fetal inflammatory response (funisitis). Funisitis first appears in vessels of the chorionic plate (chorionic vasculitis) or in the umbilical vein (umbilical phlebitis), then in the umbilical artery (umbilical arteritis), and in the Wharton's jelly (umbilical perivasculitis). The fetal inflammatory response has been associated with inflammatory diseases of preterm infants, increasing the risk of neonatal sepsis and meningitis, bronchopulmonary dysplasia and cerebral palsy. We present our experience on the relationship between histological chorioamnionitis, preterm birth and inflammatory diseases of VLBW infants.

Reliability of hearing screening in high-risk neonates: comparative study of otoacoustic emission, automated and conventional auditory brainstem response.

OBJECTIVE: To compare the diagnostic reliability of automated transient evoked otoacoustic emissions (a-TEOAE), automated auditory brainstem response (a-ABR) and conventional brainstem auditory evoked potential (BAEP/ABR) for identification of hearing loss in high-risk neonates. METHODS: Two hundred and six neonatal intensive care unit (NICU) admitted neonates were tested pre-discharge. Follow-up included a-TEOAE in all children, repetition of a-ABR or BAEP if failed in NICU. Sensitivity and specificity were compared and correlated with auditory risk factors. RESULTS: BAEP had the highest sensitivity (100%) and specificity (90.8%), a-ABR the lowest (88.9% and 70.6%). A statistically significant difference in risk factors for temporary hearing loss was observed between normal and false positive a-TEOAE and BAEP, but not a-ABR outcome. Differences in specificity between a-ABR and a-TEOAE explain the pattern of "absent a-ABR/present a-TEOAE" in 13.8% of ears. CONCLUSIONS: The BAEP appears the more reliable test for hearing screening of high-risk neonates because of highest sensitivity and specificity and should be used to confirm the diagnosis of "auditory neuropathy" in high-risk neonates. The reliability of a-ABR devices in critically ill neonates needs further investigation. SIGNIFICANCE: This is, to our knowledge, the first attempt to compare the diagnostic reliability of a-TEOAE, a-ABR and BAEP in high-risk neonates.

Tetralogy of Fallot with absent pulmonary valve: a case complicated by bilateral relapsing pneumothorax.

We report a case of a neonate with tetralogy of Fallot with aneurysmal dilatation of the pulmonary artery, complicated by bilateral relapsing pneumothorax. The relapsing air leak made it necessary to place up to five chest drains and to switch from conventional ventilation to high frequency ventilation. In the course of 30 days, all drains were removed. Once other anatomical and functional malformations of the respiratory system had been appropriately excluded and reasonable haemodynamic stability had been achieved, the patient underwent successful radical corrective heart surgery in hypothermia and cardioplegia. We emphasize the advantage of resolving respiratory failure preoperatively to guarantee the success of corrective heart surgery and treatment of other surgically severe cases.

Home oxygen therapy in infants with bronchopulmonary dysplasia: assessment of parental anxiety.

BACKGROUND: It is conceivable that a complicated recovery course in a high-risk premature infant managed at home generates apprehension and anxiety in parents. AIMS: We attempted to define the evolution of anxiety levels in a population of parents of low-birth-weight premature infants with bronchopulmonary dysplasia enrolled in a prospective home O(2) therapy program. STUDY DESIGN: In the immediate pre-discharge [mean postnatal age 95 (45-158) days], a questionnaire (State-Trait Anxiety Inventory form Y) was given to all parents of the premature infants [mean birth weight 1106 (0.610-1.770) kg; mean gestational age 27.1 (24-31) weeks] present for the discharge. Subsequently, the parents were assessed twice, initially after a week from the discharge of their infants and then at the end of the oxygen therapy phase [mean postnatal age 185 (60-361) days]. They included 10 mothers and 10 fathers, aged 33.5+/-0.5 and 37+/-0.2 years, respectively. RESULTS: Our results indicate that these parents present an increased state anxiety level upon hospital discharge of their oxygen-dependent premature infants, which decreases as the improvement of respiratory status and the cessation of oxygen-dependency become evident [mean+/-S.D. related to age (T) maternal values 47.1+/-7.0, 41.8+/-5.6, 39.1+/-4.7, respectively; mean+/-S.D. related to age (T) paternal values 42.2+/-8.5, 41.1+/-8.1, 40.5+/-8.2, respectively]. When assessed separately by parental gender, in the maternal group, state anxiety decreased significantly (ANOVA, p<0.05). CONCLUSIONS: These data indicate that although neonatologists generally define the discharge of prematures with chronic lung disease based upon the acquired stabilization of vital parameters, in the oxygen-dependent group, they should also pay special attention to the emotional support of the parents who we have identified as being at increased risk for pre-discharge anxiety.

Neonatal leukemoid reaction and early development of bronchopulmonary dysplasia in a very low-birth-weight infant.

The factors controlling the recruitment of inflammatory cells and the activation of the cytokine cascade in low-birth-weight premature infants have been implicated in the sequence of multiorgan inflammatory diseases, including the chronic lung disease of prematurity, bronchopulmonary dysplasia. This article describes a 982-gram, 25 (+2 days) weeks' gestation male infant, who had a leukemoid reaction throughout the first week of life, followed by early development of bronchopulmonary dysplasia.

Dexamethasone does not affect vasopressin release in bronchopulmonary dysplasia.

Elevated levels of vasopressin (AVP) have been found in premature infants with bronchopulmonary dysplasia (BPD), and may be related to abnormalities of water handling, and to non-pulmonary signs of edema. Dexamethasone treatment improves pulmonary function in infants with BPD, and is frequently associated with a significant increase in diuresis and a decrease in weight gain. To determine whether this diuresis is primarily the result of AVP inhibition (potentially induced by steroid treatment), we measured endogenous AVP levels in nine premature babies with BPD [birth weight 802 +/- 141 (SD) g; gestation 26 +/- 2 weeks, age 26 +/- 17 days], before initiation, and 3 and 7 days after the start of dexamethasone therapy (0.5 mg/kg/day). All study infants required mechanical ventilation, and none was receiving diuretics or cardiac inotropes during the study. Results indicated that premature infants with BPD have functionally unmodified AVP levels after 3 and 7 days of dexamethasone therapy (pre-dexamethasone 5.9 +/- 2.1 ng/l vs post-dexamethasone 7.0 +/- 3.0 and 8.0 +/- 1.9 ng/l at 3 and 7 days, respectively). Pulmonary function improved with oxygenation indexes decreasing (pre-dexamethasone 14 +/- 7 vs post-dexamethasone 9 +/- 7 and 7 +/- 4 at 3 and 7 days, respectively). A concurrent reduction in weight gain occurred (pre-dexamethasone 12 +/- 10 g/kg/day vs post-dexamethasone 7 +/- 3 g/kg/day and 3 +/- 1.5 g/kg/day on days 3 and 7, respectively). These data suggest that the improvement in lung function with dexamethasone treatment for BPD in premature infants does not correlate with a diuresis that results from vasopressin inhibition, and potentially induced by dexamethasone.

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.

Lysosomal enzymes in preterm infants with bronchopulmonary dysplasia: a potential diagnostic marker.

Some lysosomal glycohydrolases (N-acetyl-beta-D-glucosaminidase and their major isoenzymes, beta-D-glucuronidase, alpha-D-galactosidase, beta-D-galactosidase and alpha-D-glucosidase) were investigated in the plasma of 36 preterm infants with respiratory distress, 11 of whom developed bronchopulmonary dysplasia (BPD), in order to evaluate the role of the lysosomal apparatus in the disease. Enzyme activity was assayed fluorimetrically; the major N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes were separated using a routine chromatofocusing procedure; the diagnostic efficiency was evaluated by Bayes theorem. The mean levels of almost all glycohydrolases considered were significantly higher in BPD than in non-BPD infants. Among NAG major isoenzymes, an increase was found only in form A. No variation was evident in the plasma levels of glycohydrolases during dexamethasone therapy. Data from a retrospective analysis performed in all preterms considered, show that alpha-D-galactosidase and beta-D-galactosidase differentiate a posteriori BPD and non-BPD subjects. These enzymes, after a priori verification of their diagnostic potential in preterm infants at risk of BPD development, could acquire an important predictive value.

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.