Division of Neonatology Department of Pediatrics Catholic University of the Sacred Heart Rome, Italy
enrizecca@rm.unicatt.it
Born in Rome, 12/01/1954. Graduated: 1979 Fellowship in Pediatrics: 1983 University Researcher: 1988
PROFESSIONAL POSITION University Grant Contract: 1982 - 1988 University Researcher: 1988 – present Senior Assistant: 1992 – present Chief of Neonatal Pathology Unit: 2004 - present
MEMBERSHIP OF SCIENTIFIC SOCIETY Italian Society of Pediatrics Italian Society of Neonatology Member of the Scientific Committee of the 3rd National Congress of the Italian Society of Neonatology in 1997. Member of the Regional Section of the Italian Society of Neonatology from 2002 to 2005 and at present.
TEACHING ACTIVITIES Practical tutoring with Faculty residents and fellows since 1982. Professor of Neonatology at the Graduation Course in Obstetrics Professor of Neonatal Pneumology and Neonatal Intensive Care at the Fellowship in Pediatrics Teaching Professor at the Master in Neonatal Pneumology Teaching Professor at the Master in Echodopplermetry Teaching Professor at the Master in Pediatric Nursing
RESEARCH ACTIVITIES Research fields in Neonatology include epidemiology, pneumology, metabolism and computer application.
Abstract: BACKGROUND AND PURPOSES: Bile acids have been implicated in some forms of acute lung injury, including meconium aspiration and bile acid pneumonia in neonates, or aspiration related ARDS in adults. Secretory phospholipase A2 (sPLA2) is now known as a key enzyme in the lung injury pathways and is supposed to be responsible for surfactant dysfunction. Our aim was to investigate the interaction between bile acids and sPLA2 in an extracellular environment representing an in vitro model of aspiration. METHODS: In vitro study using broncho-alveolar lavage (BAL) of 23 neonates/infants (<6 m) with healthy lungs. BAL supernatants were assayed for sPLA2 activity in basal condition and after addition of randomly assigned concentrations of bile acids (BA) or normal saline. Samples coming from neonates were then challenged with poractant-alfa up to a phospholipid concentration equal to that found in babies after the surfactant treatment for respiratory distress syndrome. sPLA2 activity was again measured, being corrected for serum/supernatant urea ratio and for confounding factors. RESULTS: High concentrations of BA (5 micromol/l) significantly increased (P = 0.012) sPLA2 activity, leading to increased surfactant catabolism. This finding was not observed with lower BA concentration and this is consistent with available literature data and may indicate an anionic activation of the enzyme by bile acids. Increased activity was significantly reverted by the addition of exogenous surfactant (P = 0.004) which was able to reduce sPLA2 activity almost to the baseline level. CONCLUSIONS: BA are likely to contribute to lung injury, causing surfactant inactivation through the increased sPLA2 activity. Other mechanisms cannot be excluded and require further studies to be clarified.
Abstract: The authors report a case of minimal prenatal trauma producing a large subdural hematoma in the fetus, which was diagnosed in utero by MR imaging. The occurrence of such a complication is extremely rare in the absence of significant maternal trauma. Prenatally diagnosed intracranial hemorrhages, particularly those that are subdural in origin, have a poor prognosis in most cases. After birth, brain compression required a complex neurosurgical intervention because simple hematoma evacuation was not possible. The clinical and neurological outcome at 6 months was excellent, as confirmed by the neuroimaging findings.
Abstract: BACKGROUND: The few existing studies evaluating the reliability of transcutaneous bilirubin monitoring during phototherapy gave controversial results. AIMS: To evaluate the accuracy of transcutaneous bilirubin measurement in a large population of newborn infants, during phototherapy. STUDY DESIGN AND METHODS: Total serum bilirubin and transcutaneous bilirubin on patched and unpatched skin areas were simultaneously measured in newborn infants undergoing phototherapy. Transcutaneous measurements were performed with a multiwavelength transcutaneous bilirubinometer (Respironics BiliCheck). The Passing-Bablok regression and the Bland-Altman plot were used to estimate the relationship between serum and transcutaneous bilirubin. RESULTS: We studied 364 newborn infants with a mean (SD) gestational age of 34.6 (3) weeks and a mean birth weight of 2371 (805) grams. Total serum bilirubin, patched transcutaneous bilirubin and unpatched transcutaneous bilirubin were similar before phototherapy. After 52 (33) hours of phototherapy, the difference between serum bilirubin and patched transcutaneous bilirubin was 0.2 (3.1) mg/dL (not significant) while the difference between serum bilirubin and unpatched transcutaneous bilirubin was 3.2 (3.0) mg/dL (p<0.001). Statistical analysis showed a good agreement between serum bilirubin and patched transcutaneous bilirubin, while unpatched transcutaneous bilirubin underestimates serum levels. The difference between patched and unpatched values was significantly lower in preterm than in term infants (2.8 mg/dL vs. 3.6 mg/dL; p<0.001). CONCLUSION: BiliCheck can be safely used for the evaluation of bilirubin levels in newborn infants under phototherapy. Its reliability on patched skin of the forehead is high enough to consistently reduce blood draws and to ascertain when to discontinue phototherapy. Because of the individual variance, any clinical decision has to be taken on the basis of the transcutaneous bilirubin trend more than on a single value.
Abstract: OBJECTIVE: The aim of this study was to investigate whether ibuprofen exposure was associated with increased hyperbilirubinemia in preterm infants. METHODS: Since 2000, ibuprofen has been administered to all infants at <30 weeks of gestation who are admitted to our unit, to prevent patent ductus arteriosus. We retrospectively compared data for 418 infants subjected to ibuprofen prophylaxis (2000-2007) and 288 infants not exposed to ibuprofen (1993-1999). RESULTS: The ibuprofen group had a significantly higher peak total serum bilirubin level (9.0 +/- 2.5 mg/dL vs 7.3 +/- 3.3 mg/dL), more need for phototherapy (398 infants [95%] vs 254 infants [87.6%]), and a longer phototherapy duration (94.3 +/- 43.6 hours vs 87.2 +/- 38.6 hours). Groups did not differ with respect to gestational age, birth weight, gender ratio, glucose-6-phosphate dehydrogenase deficiency incidence, or hypoalbuminemia (<2.5 g/dL) incidence. Hemolytic isoimmunization was diagnosed with similar incidences (no-ibuprofen group: 7 of 288 infants; ibuprofen group: 8 of 418 infants). The rates of exchange-transfusion also were similar between the groups (no-ibuprofen group: 14 infants [4.8%]; ibuprofen group: 19 infants [4.5%]). CONCLUSIONS: Ibuprofen administration was associated with higher peak total serum bilirubin levels, and the more-pronounced hyperbilirubinemia led to longer phototherapy. The potential role of competition between ibuprofen and bilirubin in the hepatic glucuronidation pathway is discussed.
Abstract: BACKGROUND: Bedside tests for C-reactive protein (CRP) have been studied in pediatric patients, but not in neonates. METHODS: This study compared the results of two rapid bedside tests for CRP (Quick-Read CRP, Orion Diagnostic, Espoo, Finland and NycoCard CRP-Single Test, Axis-Shield, Oslo, Norway) with those of our central laboratory method (CRP-Lab) in newborn infants. CRP concentrations were determined using 72 samples obtained from 43 infants with suspected sepsis occurring between 1 and 28 days of life. RESULTS: Considering positive CRP concentrations to be > or = 10 mg/L, both bedside tests had good specificity (Quick-Read 80.5%, NycoCard 83.3%) and sensitivity (Quick-Read 97.2%, NycoCard 94.4%) when compared with our CRP-Lab. The agreement of measurement with central laboratory values was high for both the bedside tests, without statistically significant differences between the methods. The Quick-Read and NycoCard methods did not show any statistically significant systematic proportional bias when compared with the central laboratory values. The accuracy of the results of both bedside tests is somewhat decreased when CRP concentrations are >100 mg/L. CONCLUSIONS: This study shows that both the Quick-Read and the NycoCard test can be used for serial determinations of CRP concentrations in newborn infants. They require small volumes of blood and provide reliable results in < 5 min.
Abstract: OBJECTIVES: To compare the accuracy of a new transcutaneous bilirubinometer, BiliMed (Medick SA, Paris, France) with BiliCheck (Respironics, Marietta, GA, USA), a widely available instrument, and with total serum bilirubin measurement. DESIGN: A prospective double-blind study comparing the two devices was carried out. 686 healthy newborns needing measurement of their bilirubin were enrolled over a 4-month period. Serum and transcutaneous bilirubin measurements were taken with both devices within 15 minutes. The order of use of the instruments was randomised. SETTING: Well-baby nursery ward in a university hospital, tertiary referral centre. RESULTS: The linear regression analysis showed a better correlation between BiliCheck and serum bilirubin (r = 0.75) than between BiliMed and serum bilirubin (r = 0.45). BiliCheck variability (+/-2 SD of the mean bias from serum bilirubin) was within -87.2 to 63.3 micromol/l, while BiliMed variability was within -97.5 to 121.4 micromol/l. The receiver operating characteristic analysis (for serum bilirubin levels >205.2 micromol/l or >239.4 micromol/l) showed significantly higher areas under the curve for BiliCheck than those for BiliMed (p<0.001). CONCLUSIONS: Despite the potential practical advantages of BiliMed, its reduced diagnostic accuracy in comparison with BiliCheck does not justify its use in clinical practice.
Abstract: OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) has been associated with prematurity and fetal mortality. Recently, ICP has also been recognised as a risk factor for neonatal respiratory distress syndrome (RDS) in term or near-term neonates. Since fetal mortality is more frequent in pregnancies with an early ICP onset, we speculated that the time of exposure (ET) to maternal bile acids at the delivery (BAdeliv) could be involved in neonatal lung damage too. Study aim was to develop a scoring system to predict the RDS occurrence. DESIGN: We conducted a retrospective analysis of 77 pregnancies complicated by ICP (years 2000-2004) looking for factors associated to the neonatal RDS. We developed a risk score as follows: RDS risk score=BAdeliv x ET/gestational age and we prospectively applied it to 30 neonates from ICP pregnancies (years 2005-2006). RESULTS: ROC analysis indicated 9 as the score with the highest sensitivity (83.3%) and specificity (87.5%). Considering a RDS incidence of about 25% in babies coming from ICP pregnancies, the post-test probability showed a risk increased to 66.7% with a score>9 and reduced to 4.8% with a score<or=9. CONCLUSION: Our score is easy to apply and is based on the three most important variables involved in the RDS genesis. Score reliability is high enough to use it in clinical practice and to verify it in wider populations.
Abstract: AIM: Hour-specific nomogram evaluation of serum or skin bilirubin is a suitable approach for managing neonatal hyperbilirubinemia and it is recommended by American Academy of Paediatrics. We aimed to provide data about skin bilirubin levels during the natural course of hyperbilirubinemia in European healthy neonates. METHODS: We enrolled 2198 healthy newborn infants (gestational age [GA]>or= 35 weeks), from 24 to 96 h of life and performed transcutaneous bilirubin (TcB) measurement, in order to draw the nomogram for 10th, 25th, 50th, 75th and 95th percentiles of skin bilirubin, both for term and near term babies. All measurements were performed with a multiwavelength transcutaneous bilirubinometer (Respironics BiliCheck), within 2 h of the designed time and data were analysed with linear and local smoother regression. RESULTS: We described the peculiar pattern of skin bilirubin increasing rate over different time periods. Bilirubin linearly increases rapidly in the first 48 h and less rapidly from 48 to 72 h, while the increment is insignificant from 72 to 96 h. Conclusion: We provide the first data on skin bilirubin trend in a large predominantly breastfed and healthy European newborn population during the natural course of nonpathologic hyperbilirubinemia. Nomogram and increment rate of skin bilirubin are useful to identify neonates requiring closer evaluation and to plan an adequate follow-up.
Abstract: OBJECTIVES: Neonatal respiratory distress syndrome is associated with intrahepatic cholestasis of pregnancy, and bile acids may play a major role in neonatal bile acid pneumonia. Our aim was to demonstrate the bile acid presence in the bronchoalveolar lavage fluid of neonates affected by respiratory distress syndrome who were born from intrahepatic cholestasis of pregnancy and to investigate bile acid mechanisms of action in acute lung injury. METHODS: In this prospective study, we enrolled 10 neonates delivered from intrahepatic cholestasis of pregnancy, affected by respiratory distress syndrome requiring mechanical ventilation (intrahepatic cholestasis of pregnancy group) and 2 control groups. The first group consisted of 20 infants with respiratory distress syndrome delivered from pregnancies without any sign of intrahepatic cholestasis of pregnancy (respiratory-distress-syndrome group), and the second group included 20 neonates with no lung disease who were ventilated for extrapulmonary reasons (no-lung-disease group). We measured bile acid and pH in the bronchoalveolar lavage fluid and serum bile acid levels in the first 24 hours of life. RESULTS: Bile acids were measurable in the bronchoalveolar lavage fluid of all of the infants in the intrahepatic cholestasis of pregnancy group but were absent in the 2 control groups. Bronchoalveolar lavage fluid pH was not different among the 3 groups. Infants in the intrahepatic-cholestasis-of-pregnancy group had significantly higher serum bile acid levels compared with those in both of the control groups. CONCLUSIONS: Bile acids are detectable in the bronchoalveolar lavage fluid of newborns from intrahepatic cholestasis of pregnancy affected by respiratory distress syndrome. Elevated serum bile acid levels in these infants allow us to hypothesize that bile acid reaches the lung after an uptake from the circulation. These findings strongly support a role for bile acid in causing bile acid pneumonia.
Abstract: Secrecy and anonymity related to heterologous assisted reproduction may hide basic newborn data to neonatologists. Secrecy and anonymity are discussed in view of their possible consequences on relational dynamics and on developmental psychology. Nevertheless, they can also involve the offspring's genetic status regarding inheritable diseases. International guidelines have been recently published on this topic. Because no guidelines are 'ideal' unfortunate and possibly dramatic consequences can occur. We aimed to embark on a debate about this matter starting with a real clinical experience. In our case a rarely fatal but widespread disease, together with the lack of knowledge about parental status led, in a fast succession of clinical events, to the unavoidable insurgence of kernicterus.
Abstract: PURPOSES: Secretory phospholipase A2 hydrolyzes phosphoglycerides and it has been shown to be involved in alveolar inflammation and surfactant degradation. It plays an important role in acute lung injury but it has never been studied in newborn infants. We were aimed to investigate the phospholipase A2 activity in neonatal lung injury and its relationship with ventilatory findings. SETTING: Third level university hospital NICU. METHODS: We measured phospholipase activity in broncho-alveolar lavage fluid of 21 neonates with hyaline membrane disease, 10 with pneumonia or sepsis and 10 controls, ventilated for extrapulmonary reasons. Fluid was obtained before surfactant administration on the first day of life and phospholipase activity was measured using an ultrasensitive enzymatic method. Before lavage, lung mechanics in pressure controlled synchronized intermittent mandatory ventilation was analyzed. RESULTS: Phospholipase A2 was higher in babies ventilated for sepsis/pneumonia compared to hyaline membrane disease and to control babies. Phospholipase correlated negatively with dynamic compliance, positively with inspired oxygen fraction, mean airway pressure and oxygenation index. These correlations still remained significant after multivariate analysis, adjusting for possible confounding factors. Phospholipase was not correlated with blood and alveolar pH, gestational age, birth weight, blood gases, Apgar score, tidal volume, surfactant need and ventilation time. CONCLUSIONS: These are the first data about phospholipase A2 in neonates. The enzyme plays a role in neonatal lung injury, especially in infection related respiratory failure. It is associated with lung stiffness, higher mean airway pressure and need for oxygen.
Abstract: Our aim was to study the usefulness of jaundice visual assessment combined with skin bilirubin determination in 517 healthy newborns. Yellowness assessment was made and babies were included in three different bilirubin classes. Skin bilirubin and total serum bilirubin were determined within 10 minutes from the visual assessment. This latter led to underestimation of serum bilirubin in 16.7-40.4% and overestimation in 4.9-35.7% of newborns. Skin bilirubin measurement after the visual assessment decreased the risk of underestimation to 0-9.2% and the risk of overestimation to 2.1-11.1%. The majority of visual assessment errors were performed in the more lighted hours of the morning (75%), while the smallest number (39%) occurred during the afternoon. Skin bilirubin measurement significantly corrected these diagnostic errors (p < 0.001, p < 0.02) without differences during the day. Clinical estimate is unreliable for evaluating the need for serum bilirubin assay. Using the addition of skin bilirubin determination is a more advisable approach.
Abstract: BACKGROUND: BiliCheck (BC), a new transcutaneous bilirubinometer is thought to be lacking in the disadvantages of old devices and could be potentially useful for diagnosing jaundice in preterm babies. Although its accuracy is well known in healthy term babies, there is a lack of knowledge about its usefulness in preterm infants. AIMS: To investigate BC usefulness in preterm babies and its suitability in a sub-intensive neonatal unit. STUDY DESIGN: In 340 preterm infants between 30 and 36 weeks of gestational age, transcutaneous and serum bilirubin measurement were performed. Hematocrit, pH, postnatal age, gestational age, and sex were also studied to clarify their influence on BC accuracy. For a subset of 100 neonates transcutaneous measurement, blood collection and serum analysis were timed and costs were considered. RESULTS: Correlation coefficient is 0.795 (p<0.001) and this is not affected by factors previously supposed to be important. Overall sensitivity was 100% and specificity were comprised between 40% and 72%. BC has a tendency to overestimate serum bilirubin, at high values. Considering the whole time for serum bilirubin measurement, transcutaneous bilirubinometry is a faster (p<0.0001), but more expensive technique with a cost of about 5 euro/measurement. Nevertheless, using BC as a screening-device we could safely avoid 58-79% of blood samples, since its positive predictive values is about 21-42%. This would allow to a cost reduction of 1555-2120 euro/year. CONCLUSIONS: BC has a good reliability in preterm infants although not as good as in healthy term babies. BC is a time-sparing tool and can improve the management of neonatal jaundice in preterm infants; however, its tendency to overestimate suggests its use only for screening purposes.
Abstract: OBJECTIVE: To assess the effectiveness of an incomplete course of antenatal corticosteroids (ACS) on neonatal morbidity and mortality of preterm infants. METHODS: Preterm infants born at 25-34 weeks' gestational age between January 1, 1998 and December 31, 2003 were included in this study. Studied infants were divided in two groups: the ACS group included those infants who had been exposed to a single 12-mg dose of betamethasone before delivery while the control group included those infants who had been delivered without any antenatal corticosteroids treatment. The most important neonatal outcomes were compared between the two groups. RESULTS: One hundred and seventy neonates (41.4%) were exposed to one 12-mg dose of betamethasone before delivery, while 241 neonates (58.6%) did not receive any antenatal corticosteroids treatment. Mean gestational age at delivery (30.4+/-2.4 weeks versus 31.2+/-2.9 weeks, p=0.004) and mean birth weight (1375+/-454 g versus 1625+/-580 g, p<0.001) were lower in the ACS group. The univariate analysis showed that delivery room intubation and respiratory distress syndrome were more frequent in the ACS group and that the length of stay was also significantly longer in this group. No differences were found concerning survival, neonatal morbidity, need for and duration of mechanical ventilation and oxygen therapy. The incidence of major outcomes in survivors was also similar. Logistic regression adjusted for gestational age showed that the exposure to a single dose of betamethasone before delivery was not associated with a significant reduction in the rate of any neonatal outcome. We also compared the outcomes in function of gestational age subclasses. In the 25-27 weeks subgroup, delivery room intubation, surfactant treatment and patent ductus arteriosus (PDA) were less frequent in ACS infants; they had also shorter ventilation and oxygen duration. In the 30-31 weeks subgroup, ACS infants had a lower incidence of mechanical ventilation and a shorter duration of oxygen therapy. Finally, no differences were found in the 28-29 weeks subgroup and in the 32-34 weeks subgroup. CONCLUSION: Effects of incomplete antenatal corticosteroids are variable: they give some benefits to infants of 25-27 weeks gestational age, fail to show any difference in outcomes in the 32-34 weeks subgroup and are doubtful between these extremes.
Abstract: AIM: To assess the correlation of echocardiographic signs of myocardial damage to serum cardiac troponin T (cTnT) concentrations in newborn infants with perinatal asphyxia. METHODS: Electocardiograms (ECG) and echocardiograms (Echo) were obtained during the first 24 h of life from 29 asphyxiated and 30 control infants and correlated with cTnT concentrations. The echocardiographic parameters included systolic ventricular performance, preload, afterload, diastolic function, stroke volume (SV), left ventricular output (LVO), hyperechogenity of the papillary muscles and insufficiency of the atrioventricular valves. RESULTS: LVO and SV were lower but CTnT were significantly higher in asphyxiated than in control infants: 0.15 (010-0.23) vs. 0.05 (0.02-0.13), p < 0.001). Asphyxiated infants with signs of myocardial damage were associated with significantly higher cTnT than those without, 0.20 (0.11-0.28) and 0.11 (0.05-0.14 ug/L), p = 0.04. CONCLUSION: Cardiac troponin may prove to be valuable in evaluating myocardial damage in birth asphyxia. However, the degree of prematurity may complicate the assessment.
Abstract: OBJECTIVE: The aim of this study was to evaluate the presence and the severity of neurological and cognitive impairment at 2 years of age in 16 infants (9 term born, 7 preterm of mean gestation 33.6 weeks) with cerebral ventriculomegaly of antenatal onset associated with intraventricular haemorrhage. METHODS: Ventricular dilatation, with or without associated lesions, was, with one exception, not identified on the antenatal routine scan at approximately 22 weeks but was obvious on the scans performed between weeks 27 and 33. In 8 of the 16 cases there were signs of parenchymal involvement or of abnormalities of the corpus callosum or cerebellum. In all patients the diagnosis of antenatal IVH was confirmed by early neonatal imaging. Outcome was measured using the Hammersmith infant neurological examination and the Griffiths developmental scales at 2 years. RESULTS AND CONCLUSIONS: At 2 years, 8 infants had normal motor outcome and 8 had cerebral palsy. The presence and severity of cerebral palsy or neurodevelopmental delay was not always related to the magnitude or symmetry of the ventricular dilatation per se. The presence of associated lesions was a negative prognostic marker. The early development of epilepsy was also associated with an abnormal outcome.
Abstract: The aim of this study is to generate normal reference values of cerebral blood flow velocities (CBFV) and Doppler indices (DI) in the anterior (ACA) and the middle (MCA) cerebral arteries during the first month of life in "healthy" preterm infants. CBFV were obtained with color Doppler technique in seventy selected preterm infants divided in four groups of gestational age (GA) (25 to 28; 29 to 30; 31 to 32; 33 to 35 wk). Our data demonstrate that CBFV increase with rising GA, birth weight (BW) and postnatal age. Additionally, we can provide the median values, tenth and ninetieth percentiles of CBFV and DI, in the ACA and MCA in each GA group as reference normal values of CBFV and DI in preterm newborn.
Abstract: OBJECTIVE: To compare the effectiveness of various phototherapy systems in lowering serum bilirubin levels in preterm infants. METHODS: This randomized clinical trial enrolled 140 preterm infants with gestational age < or =30 weeks and presenting nonhemolytic hyperbilirubinemia. When total serum bilirubin level reached 6.0 mg/dl (102.6 micromol/l), eligible infants were randomly assigned to four study groups: conventional, fiberoptic Wallaby, fiberoptic Biliblanket, and combined phototherapy. Efficacy was assessed by comparing highest serum bilirubin levels, duration of treatment, and number of infants requiring exchange transfusion. RESULTS: Our results confirm that fiberoptic phototherapy, both Wallaby and Biliblanket, had the same effectiveness of conventional phototherapy. The best results have been obtained using combined phototherapy, which allowed to reach lower serum bilirubin levels, a shorter duration of treatment and a significant reduction of exchange transfusions. CONCLUSION: Our data suggest that combined phototherapy should be the method of choice in treating hyperbilirubinemia in very preterm infants.
Abstract: OBJECTIVES: We sought to verify the association between maternal intrahepatic cholestasis of pregnancy (ICP) and neonatal respiratory distress syndrome (RDS) and to determine how bile acids levels alter the risk of developing neonatal RDS. METHODS: We extracted data from our divisional database about all of the newborns born during the years 2000-2004. We compared 77 neonates born from pregnancies complicated by ICP with 427 neonates in the same range of gestational age born from noncomplicated pregnancies. We studied maternal bile acids levels immediately before delivery in mothers with ICP and measured bile acid levels during the first 24 hours of life in their newborns. RESULTS: The incidence of RDS in newborns from cholestatic pregnancies was twice that the reference population (28.6% vs 14%). The multivariate analysis showed that the risk of RDS in these newborns was approximately 2.5 times higher than in control infants. Within the ICP group, maternal and neonatal bile acid levels of infants affected by RDS were not significantly higher than those of healthy infants. The multivariate analysis showed that a low gestational age was the most important risk factor, but the probability of respiratory distress syndrome also increased by 2 per thousand for every additional micromole of the interaction term "neonatal by maternal bile acids level." CONCLUSIONS: Maternal ICP is significantly associated with the occurrence of RDS in the newborn. We hypothesize that bile acids can produce surfactant depletion in the alveoli reverting the reaction of phospholipase A2. This hypothesis could potentially be confirmed by bronchoalveolar lavage study.
Abstract: OBJECTIVE: To investigate the effect of different delivery room strategies on survival, short term morbidity, and outcomes in extremely premature infants. METHODS: This retrospective cohort study included all preterm infants with a gestational age between 24 and 28 weeks who were born in 1992-1997 (period A; n = 161) and in 1998-2003 (period B; n = 163). In period A, elective intubation was performed. In period B, if spontaneous breathing was present, nasal continuous positive airway pressure (nCPAP) was applied. RESULTS: Survival rate and the number of never-intubated infants significantly increased in period B. No differences were found concerning short-term morbidity. Among major outcomes, the need for retinopathy of prematurity (ROP) surgery and the length of stay were significantly lower in period B. Subgroup analysis showed no significant differences from period A to period B in infants with gestational age 24-26 weeks. In the 27-28 weeks subgroup, the never-intubated infants rate increased from 2.8% to 21.3% and survival rate increased from 63% to 79%. A reduced need for ROP surgery and a shorter hospital stay were also observed. CONCLUSIONS: Changes in delivery room strategy tending to reduce mechanical ventilation in extremely premature infants are likely to benefit essentially infants of 27-28 weeks of gestation. Extension of such benefits to premature infants at the limit of viability requires further research.
Abstract: BACKGROUND: Frequent premature ventricular contractions (PVCs), couplets (CPLTs) and episodes of ventricular tachycardia are extremely rare in the neonatal population. Limited information is available with regard to clinical relevance and outcome. OBJECTIVES: To evaluate the clinical characteristics and outcomes of a group of newborns with ventricular arrhythmias without heart disease. Patients and design: Between January 2000 and January 2003, 16 newborns with ventricular arrhythmias in the absence of heart disease were studied. The newborns were divided into three groups: PVC group (n = 8), CPLT group (n = 4) and ventricular tachycardia group (n = 4). All patients underwent physical examination, electrocardiography, Holter monitoring and echocardiography at diagnosis and at follow-up (1, 3, 6 and 12 months, and yearly thereafter). RESULTS: Mean (standard deviation, SD) age of the patients was 3 (1.19) days in the PVC group, 3.25 (0.95) days in the CPLT group and 6.5 (9.1) days in the ventricular tachycardia group. Median follow-up was 36 months (range 24-48 months). PVCs disappeared during follow-up in all the neonates, in the PVC group, at a mean (SD) age of 2.1 (1.24) months; in the CPLT group, couplets disappeared at a mean (SD) age of 6.5 (1) months. All patients with ventricular tachycardia were treated; ventricular tachycardia disappeared at a mean (SD) age of 1.7 (0.9) months. Neither death nor complications occurred. CONCLUSIONS: Ventricular arrhythmias in newborns without heart disease have a good long-term prognosis. Frequent PVCs and CPLTs do not require treatment. Sustained ventricular tachycardia or high-rate ventricular tachycardia must be treated, but the prognosis is generally favourable.
Abstract: OBJECTIVE: Ventilation strategies for preterm neonates may influence the severity of pulmonary dysfunction and later development of chronic lung disease. The objective of this report is to compare the effects of high-frequency oscillatory ventilation (HFOV) versus synchronized intermittent mandatory ventilation (sIMV) from the points of views of biochemical and functional variables. DESIGN: Randomized controlled trial. SETTING: Third level NICU. PATIENTS AND PARTICIPANTS: Forty preterm neonates with a gestational age of 24-29 weeks were randomly assigned to one of the two above-mentioned ventilation strategies within 30 min from birth. MEASUREMENTS AND RESULTS: At 1, 3, 5, and 7 days, the babies were monitored by means of ventilator indices, pulmonary function, and eight pro-inflammatory or anti-inflammatory cytokines measured in bronchoalveolar lavage fluid. The neonates assigned to the HFOV procedure benefited from early and sustained improvement in pulmonary mechanics and gas exchange-significantly higher dynamic respiratory compliance values, significantly lower expiratory airway resistance and oxygenation index values-with earlier extubation as compared to the neonates assigned to sIMV treatment, and showed significantly lower transforming growth factor-beta1 concentrations in bronchoalveolar lavage fluid. CONCLUSIONS: The results of this randomized clinical trial support the hypothesis that early and exclusive use of HFOV, combined with optimum volume strategy, has a beneficial effect during the acute phase of lung injury.
Abstract: BACKGROUND: Ketorolac is a powerful nonsteroidal anti-inflammatory drug widely used for pain control in children and adults. The aim of this study was to evaluate its safety and analgesic efficacy in the neonate. METHODS: Ketorolac was used in a group of 18 spontaneously breathing neonates presenting with chronic lung disease, for the control of postsurgical pain and pain from invasive procedures. Pain scores (Neonatal Infant Pain Scale) were assessed before and after i.v. administration of 1 mg.kg(-1) of ketorolac. RESULTS: Total pain control was achieved in 94.4% of the neonates. None of the neonates had haematological, renal or hepatic changes prior to treatment, and these complications did not occur after treatment. No neonate had systemic haemorrhage or bleeding from injection and blood withdrawal sites. CONCLUSIONS: Ketorolac could represent an efficacious analgesic alternative to opioids, particularly in neonates. It would avoid the side-effects associated with opioid analgesics, especially respiratory depression.
Abstract: The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.
Abstract: OBJECTIVE: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (< 125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants. METHODS: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation < 125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h. RESULTS: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37-56) breaths/min and 240 (160-353) ml/min per kg vs. 53 (28-67) breaths/min and 309 (223-434) ml/min per kg, respectively (p = 0.0129 and p = 0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p < 0.0001). Percentage of time spent with spontaneous expiratory minute ventilation < 125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2 and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves. CONCLUSION: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.
Abstract: We describe 3 cases of neonatal respiratory distress syndrome (RDS) in near-term infants, born from mothers with severe intrahepatic cholestasis of pregnancy. Common pictures of the cases were: good indices of lung maturity in the amniotic fluid; severe RDS requiring mechanical ventilation; high serum bile acid (BA) levels in the early days of life; no meconium aspiration; negative cultures; and absence of indirect laboratory signs of infection. After the first case, we hypothesized that abnormally high BA levels could have reversed the action of phospholipase A2 in the lungs, causing a degradation of phosphatidylcholines to lysophosphatidylcholines and the consequent lack of surfactant activity, leading to the severe respiratory distress. Consequently, in cases 2 and 3, we gave intratracheal surfactant to the infants, which, although administered around the first 24 hours of life, showed to be helpful. Our experience suggests that a high level of attention in the management of newborn infants (even near-term infants) born from women with intrahepatic cholestasis of pregnancy is necessary to detect as soon as possible signs and symptoms of this "unexpected" RDS, which can assume a very severe clinical picture. In such instances, we recommend that the diagnosis of BA pneumonia be kept in mind and that exogenous surfactant be given as soon as possible, even in the presence of indices of normal lung maturity in the amniotic fluid. Finding high levels of BA and lysophosphatidylcholines in the bronchoalveolar lavage of affected infants would aid in support of the diagnosis.
Abstract: OBJECTIVE: To assess the effect of moderately early postnatal dexamethasone treatment on growth and neurodevelopmental outcome in preterm infants. METHODS: Thirty preterm infants enrolled in a randomised clinical trial to investigate the effectiveness of moderately early dexamethasone administration in the treatment of chronic lung disease were routinely followed up. Fifteen babies received a total dose of 4.75 mg/kg over 14 days from the 10th day of life, and 15 babies were untreated. Five infants in each group received open label steroids to facilitate extubation later in their clinical course. Growth and neurodevelopmental outcome are reported. RESULTS: The mean body weight, height, and head circumference as well as the number of babies with anthropometric measurements within normal range were similar in treated and untreated babies. There was no significant difference between treated and control groups with respect to incidence of cerebral palsy, major neurosensory impairment, mean intelligence quotient scores, and behavioural abnormalities. CONCLUSIONS: Postnatal dexamethasone treatment with the schedule used in this study did not impair growth and neurodevelopmental outcome in preterm infants. Data from larger trials have raised major concern that postnatal steroid treatment may increase neurodevelopmental impairment. The full extent of the risk will only be known when more trials have reported follow up data.
Abstract: OBJECTIVE: There is increasing concern in regard to the possible long-term adverse effects of postnatal dexamethasone treatment in preterm infants. The purpose of this study was to assess growth and neurodevelopmental outcome in preterm infants at high risk of chronic lung disease (CLD), treated with early (<96 hours) postnatal dexamethasone. DESIGN: Three-year follow-up data of physical growth and neurodevelopmental outcome of preterm infants enrolled in a controlled trial to study the effectiveness of early postnatal dexamethasone administration for the prevention of CLD were reviewed. The original trial included 25 treated neonates who received dexamethasone intravenously from the fourth day of life for 7 days (0.5 mg/kg/d for the first 3 days, 0.25 mg/kg/d the next 3 days, and 0.125 mg/kg/d on the seventh day), and 25 untreated neonates as controls. Forty-five surviving infants (22 untreated and 23 treated) completed the 3-year follow-up. RESULTS: At the end of follow-up, infants pertaining to both study groups had similar values for body weight, height, and head circumference, and a similar incidence of infants with anthropometrics data below the third percentile. Moreover, no differences were detected between the groups in regard to incidence of major cranial ultrasound abnormalities, cerebral palsy, major neurosensory impairment or IQ scores, and distribution. CONCLUSIONS: Early (<96 hours) postnatal dexamethasone administration at the doses employed in this study did not impair physical or neurodevelopmental outcome in preterm infants at high risk of CLD. However, the small sample size of our study was not tailored to look for long-term outcomes and our results are not in agreement with those of larger trials and systematic reviews. The real risks of postnatal dexamethasone administration could be definitely assessed only when more well-designed trials using long-term neurodevelopmental assessment as the primary outcome will be reported.
Abstract: The aim of this study was to investigate the relationship between adrenocortical function and chronic lung disease (CLD) of pre-term infants. Plasma F and ACTH were measured at 7, 14, 21 and 28 days of life in 25 pre-term infants with gestational age < or = 32 weeks and birth weight < or = 1,250 g. Fourteen infants developed CLD (CLD group) and 11 recovered without CLD (NOCLD group). Response to ACTH stimulation was tested on days 7 and 28. The results show that at the 7th day of life plasma F and ACTH levels were similar in the NOCLD and CLD group. CLD group had significantly higher plasma F and ACTH concentrations at the 14th (p=0.006 for F and p=0.020 for ACTH) and at the 21st (p=0.008 for F and p=0.024 for ACTH) day of life, while no significant differences were detected at the 28th day of life. The response to ACTH stimulation test was similar between the NOCLD and CLD group. These data demonstrate the lack of any significant association between adrenal insufficiency and CLD and discourage the use of baseline or stimulated plasma F levels to predict the development of CLD in pre-term infants.
Abstract: OBJECTIVES: To verify whether early pulmonary mechanics measurements are useful to predict subsequent bronchopulmonary dysplasia (BPD) and its severity. METHODS: Pulmonary mechanics were studied at 3, 5, 7 and 10 days of age in 52 preterm infants with birth weight < 1250 g, affected by respiratory distress syndrome and ventilated for more than 72 h. Pulmonary function was assessed using a previously standardized method based on the measurement of airflow with a Fleisch OO pneumotachograph and airway pressure with a model P7D differential pressure transducer. At 28 days pulmonary outcome was classified into three groups: no BPD, mild BPD (oxygen dependency and hazy lung on X-ray) and severe BPD (oxygen dependency and Northway stage 3/4). RESULTS: Of the 52 infants, 39 survived to 28 days: no BPD (11 infants), mild BPD (16 infants) and severe BPD (12 infants). The no-BPD group had significantly higher gestational age and birth weight, fewer males and a lower incidence of patent ductus arteriosus than both BPD groups, while no differences were detected between the BPD groups. Lung compliance was significantly higher in the mild-BPD group than in the severe-BPD group at 7 and 10 days of life (p < 0.01 and p < 0.001, respectively). The corresponding odds ratio confirmed that ventilated infants with lower lung compliance values had a significantly higher probability of developing severe BPD. Respiratory system resistance did not show any predictive value. CONCLUSIONS: Our findings indicate that low lung compliance values determined on the 7th and 10th days of life are a reliable predictive tool of the severity of later BPD.
Abstract: This study was designed to evaluate left ventricle dimensions in preterm infants during the first month of life, in order to define reference values and their correlation with gestational age, birth weight, gender and baseline. Thirty-five infants, gestational age 25-29 (mean 27.9 +/- 1.4) weeks, birth weight 750-1249 (mean 965 +/- 206) g, were measured using echocardiography on days 3, 7, 14, 21 and 28 of life. The following dimensions were measured: end-systolic and end-diastolic interventricular septum thickness, end-systolic and end-diastolic left ventricle posterior wall thickness, end-diastolic and end-systolic left ventricle diameter. A progressive and significant increase of all the left ventricle measurements was observed during the first month of life. Left ventricle dimensions at the first scan (Day 3) correlated with birth weight but not with gestational age and gender. The degree of the increase observed during the first month of life was inversely related to the baseline, suggesting that the smaller the left ventricle is at birth, the higher is its postnatal increase toward dimensions similar to those of term infants. Our study gives reference data about left ventricle dimensions of preterm infants during the first month of life and is helpful when making a diagnosis of left ventricular hypertrophy in these subjects.
Abstract: PURPOSE: To define standard values of blood flow velocities and indices in the ophthalmic and central retinal arteries in the neonatal period. METHODS: Forty-two healthy full-term neonates comprised the study population. A color Doppler with mechanical sector probe was used for measuring blood flow velocity in the ophthalmic and central retinal arteries. Systolic, end diastolic, and mean-enveloped velocities were measured, and the resistance index and pulsatility index were calculated. RESULTS: Ophthalmic artery Doppler velocities were similar on the first and third days of life, but increased significantly on the fifth and seventh days of life; resistance index significantly increased during the first week of life, whereas pulsatility index did not change significantly. Doppler velocities of the central retinal artery were similar on the first and third days; they show a delayed increase compared to the ophthalmic artery. Central retinal artery blood flow velocities increased significantly from the third to seventh postnatal day. Resistance index also increased between the first two days and on the fifth and seventh postnatal days, while pulsatility index did not change. CONCLUSION: These data constitute a starting point for studying the possible relationship between eye circulation and pathogenesis of retinopathy of prematurity.
Abstract: This study evaluates the effects of early administration of dexamethasone on left ventricle dimensions and their clinical significance in preterm infants. Fifty preterm infants with birth weight < or = 1250 g and gestational age < or = 30 weeks were randomly assigned after 72 hours of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the 7th day). Serial echocardiographic measurements of end systolic interventricular septum thickness, end diastolic interventricular septum thickness, end systolic left ventricle posterior wall thickness, end diastolic left ventricle posterior wall thickness, left ventricle end diastolic diameter, and left ventricle end systolic diameter were taken before starting dexamethasone, on days 3 and 7 of treatment, 7 days after the interruption of treatment, and at the 28th day of life. Five infants of each group were excluded by the final analysis because of the lack of a complete cardiac evaluation, leaving 20 treated and 20 control infants. Infants receiving dexamethasone had a significantly larger increase in mean septal and left posterior wall thickness during the treatment and 7 days after the dexamethasone weaning. The mean left ventricle diameter of treated infants was significantly lower than that of control infants from the 7th day of treatment to the 28th day of life. Four neonates (20%) in the dexamethasone group developed left ventricular myocardial hypertrophy without left ventricle outflow tract obstruction, showing signs of decreased cardiac output and ischemic changes on ECG. The daily fluid intake was increased to 200 ml/kg to ensure an adequate preload volume, and the complete resolution of left ventricle hypertrophy was obtained within the 2nd to 3rd week after dexamethasone weaning. Preterm infants receiving an early (< 96 hours of life) short course of dexamethasone develop a left ventricular myocardial hypertrophy that can be symptomatic and clinically significant. Preterm infants included in future studies with the goal to find the minimum dose and duration of dexamethasone treatment should be strictly monitored echocardiographically for this side effect.
Abstract: This study was aimed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus (PDA) in very preterm neonates and at detecting eventual side-effects. A total of 46 preterm neonates with gestational age under 31 weeks were randomly assigned at 2 h of life: 23 to the prophylaxis group and 23 to the control group. The prophylaxis group received intravenous treatment with ibuprofen lysine (10 mg/kg), followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group. No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group (87%) nor in 7 of the 23 control neonates (30.4%). All neonates with PDA received treatment with indomethacin. One neonate in the prophylaxis group and three in the control group underwent surgical ligation. Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance. CONCLUSION: Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment. No significant early side-effects were found due to ibuprofen.
Abstract: The effect of O2 exposure, expressed by mean daily fractional inspired oxygen concentration (FiO2), was evaluated during the first 6 d of life in the tracheobronchial aspirate fluid of 16 mechanically ventilated preterm infants in terms of both antioxidant response and oxidative damage, by measuring total antioxidant activity, uric acid concentrations and protein carbonyl content. Each day linear regression analysis was performed and a positive correlation was found between total antioxidant activity and FiO2 during the study period, especially on day 2 of life (r = 0.91, p < 0.0001), but uric acid correlated only in the first 3 d, especially on the 2nd day (r = 0.83, p < 0.0001). No correlation was found between carbonyl content and FiO2. The highest values of total antioxidant activity (416 and 790 micromol l(-1)) were found in 2 babies ventilated with highest FiO2: 1 and 0.80, respectively. Total antioxidant activity was not detectable or was very low in the babies not requiring O2 therapy. The highest value of uric acid (270 micromol l(-1)) was found in the baby ventilated with 100% oxygen. Uric acid concentrations obtained in these babies were much higher then those reported in the bronchoalveolar lavage fluid of adults. Preterm babies seem to have an antioxidant response in the tracheobronchial aspirate fluid following an oxidative stress and uric acid may be physiologically important as an antioxidant of the respiratory tract, especially during the first days of life.
Abstract: Comparing a group of infants treated with recombinant erythropoietin and iron supplementation to a group of control infants, no difference was observed concerning the transfusion need. The incidence of retinopathy of prematurity was significantly higher in the treated group. These data need to be confirmed in randomized controlled studies.
Abstract: OBJECTIVE: The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration. DESIGN: Randomised clinical trial. SETTING: Neonatal intensive care unit. PATIENTS: 50 infants at high risk of CLD were randomly assigned after 72 h of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment. RESULTS: The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration. CONCLUSIONS: Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD.
Abstract: A randomized study was designed to evaluate the effects of two different dexamethasone courses on the growth of preterm infants. The first phase included 30 preterm infants at high risk for chronic lung disease (CLD). 15 babies (moderately early dexamethasone group) were treated with dexamethasone for 14 days, from the 10th day of life, and received a total dose of 4.75 mg/kg; 15 babies were assigned to the control group. The second phase included 30 preterm infants at high risk for CLD. 15 babies (early dexamethasone group) were treated with dexamethasone for 7 days, from the 4th day of life, and received a total dose of 2.38 mg/kg; 15 babies were assigned to the control group. All the main clinical baseline characteristics were similar between the groups both in the first and in the second phase. Infants given the two dexamethasone courses showed significantly reduced weight gain during the period of treatment when compared to the respective control group, but they had a weight catch-up soon after the end of treatment. At 30 days of life the weight and length gain of each treated group were similar to those of control infants, but the moderately early dexamethasone group showed a significantly poorer head growth. No differences between the groups were observed at discharge. Dexamethasone treatment induces a slower weight gain which is time-limited to the period of treatment and is followed by a body weight catch-up. However, the poorer head growth detected at 30 days of life in the infants who received a higher dose of dexamethasone could indicate important adverse effects, possibly dose-related, on postnatal brain growth and development.
Abstract: OBJECTIVE: The purpose of this study was to develop and validate an empirical scoring system to predict the evolution of neonatal respiratory distress syndrome (RDS) into chronic lung disease (CLD) in preterm infants, by comparing it with a more complicated logistic regression model. DESIGN: Clinical study. SETTING: Neonatal intensive care unit. PATIENTS: The retrospective analysis of a 3-year experience showed that a gestational age (GA) of less than 30 weeks, a birth weight (BW) of less than 1000 g, the diagnosis of hyaline membrane disease (HMD) and pulmonary interstitial emphysema (PIE) during the first 72 h of life, the peak inspiratory pressure (PIP) and the fraction of inspired oxygen (FIO2) were the highest relative risk factors correlated with the evolution of CLD. On this basis an empirical and a statistical scoring system were defined and prospectively applied at 3 and 5 days of life to 228 neonates with BW less than 1,250 g. The results obtained with both scoring systems were then compared. RESULTS: Of the 149 infants surviving at 28 days of life, 67 (GA: 29.9 +/- 2.3 weeks; BW: 1,058 +/- 143 g) were normal and 82 (GA: 27.5 +/- 3.9 weeks: BW: 838 +/- 200 g) had CLD. Using a cut-off value of 4.0, the empirical scoring system showed a specificity of 97.0% and a sensitivity of 92.7% on the 3rd day of life; on the 5th day of life the specificity was still 95.5%, while sensitivity remained 92.7%. The areas under the ROC curves plotted with both scoring systems tested were similar. CONCLUSIONS: The proposed empirical scoring system is easy to use and is highly reliable. The application of this scoring system provides the opportunity to direct aggressive treatment for CLD toward only very high risk patients between the 3rd and 5th days of life.
Abstract: BACKGROUND: The objective of this study was to determine if the value of respiratory system compliance and lung resistance could be a good predictor of chronic lung disease (CLD) in an early stage of this disease. METHODS: The study was carried out on 48 preterms infant (BW < 1500 g) who were ventilated for respiratory distress, calculating pulmonary mechanics at 3, 5, 7 and 10 days of life with a standardized protocol of measurements. RESULTS: Infants who did not develop CLD showed higher values of respiratory system dynamic compliance (Crsdyn) than the CLD group since the 5th day of life (p < 0.001). The values of lung resistance show a statistical significant difference between groups since the 7th day of life. CONCLUSIONS: These findings indicate that, with a well standardized method of measurements, the value of Crsdyn can well be a good predictor and a sensible prognostic factors for CLD.
Abstract: OBJECTIVE: To determine whether furosemide could prevent renal side effects of indomethacin (INN, indometacin) used for the pharmacologic closure of the patent ductus arteriosus (PDA) in preterm infants. METHODS: Thirty-six preterm infants with birth weights < 1750 gm affected by hemodynamically significant PDA were randomly assigned to one of two study groups. Group 1 consisted of 18 infants treated with three doses of indomethacin (0.20 mg/kg every 12 hours); each dose was followed by a dose of furosemide (1 mg/kg). Group 2 consisted of 18 infants treated only with the same doses of indomethacin. Body weight, urine output, glomerular filtration rate (GFR), fractional excretion of sodium (FENa+) and potassium (FEK+), and osmolal and free water clearance were evaluated in both groups before, during, and after treatment. RESULTS: The body weight trend, serum sodium, chloride and potassium concentrations, plasmatic and urinary osmolality were similar during the treatment in both the groups. A significant reduction of urine output (p < 0.01) was detected in group 2 but not in group 1. A significant increase of blood urea nitrogen and serum creatinine was detected at the end of treatment in group 1 compared with group 2. During the treatment, a significantly higher GFR (p < 0.05) was found in group 2 than in group 1. FENa+ and FEK+ were significantly higher (p < 0.05 and p < 0.001, respectively) in group 1 than in group 2 during and after the treatment. The osmolol clearance and free water clearance were significantly higher during and after treatment (p < 0.01 and p < 0.001, respectively) in group 1 than in group 2. CONCLUSIONS: Our findings show that furosemide cannot prevent the indomethacin-induced renal failure, but it does not have any negative influence on its therapeutic effectiveness.
Abstract: Osteopenia is a metabolic bone disease which affects a great deal of preterm infants. X-Ray evaluation is still the main step of the diagnostic and follow-up procedures. The Authors prospectively studied 77 newborn infants with birth weight less than 2500 grams, to identify specific clinical and biochemical features of the osteopenic infants. From the 2nd to the 12th week of life clinical, biochemical and radiological signs of osteopenia were looked for, every 2 weeks: the diagnosis of osteopenia was made on the basis of X-Ray. 26 osteopenic subjects with ga less than or equal to 32 weeks and/or bw less than or equal to 1500 grams were compared with 20 controls with ga less than or equal to 32 weeks and/or bw less than or equal to 1500 grams and with 31 control infants with ga greater than 32 weeks and bw greater than 1500 grams. Wider anterior funtanels, their progressively increasing dimensions, and craniotabe (with the "ping pong ball" sign) were the most characteristic features, as well as the increasing pattern of alkaline phosphatase activity, of the osteopenic babies. The Authors suggest a specific clinical and biochemical score to make the correct diagnosis and a non invasive follow-up in the osteopenic subjects and to avoid dangerous X-Ray exposure to babies that are not osteopenic.
Abstract: The effectiveness of caffeine citrate in preventing idiopathic apnea in premature infants was evaluated. Thirty-seven preterm infants born before the 32nd week of gestation were studied. After an intravenous loading dose of 10 mg/kg of caffeine citrate, two different oral maintenance regimens were followed: 5 mg/kg in Group I and 2.5 mg/kg in Group II. A significant decrease in the number of apneic spells occurred in both treated groups as compared with a control group. In Group II, the frequency of side effects such as tachycardia and gastrointestinal intolerance was significantly lower than in Group I. Group II theophylline plasma levels were significantly lower than those of Group I. The lower Group II theophylline levels presumably explain the reduced frequency of side effects.
Abstract: This study was designed to verify the effectiveness of parenteral nutrition (NP) and continuous nasogastric feeding (AOG) in providing a good caloric intake and a good growth in the very low birth weight infants during the first 60 days of life. The study included 108 preterm babies with birth weight less than or equal to 1500 g: 26 received parenteral nutrition, 82 nasogastric feeding. Infants in NP showed a smaller postnatal weight loss and regained birth weight earlier than the AOG group. Caloric intake greater than 120 kcal/kg/die was achieved in 10.2 days of life in the NP group and in 14.1 days in the AOG group. Full enteral feeding was achieved later in the NP than in the AOG group (25.7 days vs 20.7 days). Weight gain at 60 days of life was better in the NP group (23.2 g/die vs 18.2 g/die), while there was no difference in the head circumference gain. The study shows the efficacy of NP in providing a good caloric intake in the very low birth weight infants in the first weeks of life.
Abstract: The effectiveness of a new device for phototherapy in the treatment of nonhemolytic hyperbilirubinemia (Wallaby Phototherapy System) was evaluated. 46 healthy term infants, appropriate for gestational age and with serum bilirubin > 12 mg/dl in the first 3 days of life or > 15 mg/dl after 3rd day were randomly assigned to a treatment group (24 hours of light exposure with Wallaby Phototherapy System) and to a control group (any treatment for hyperbilirubinemia). Body temperature, weight, feeding and hydration were recorded during the study period. Serum bilirubin and haematocrit were done every 12 hours in all babies. In the treated group we found a decrease of 5.1% and of 7.8% at 12 and 24 hours, while an increase of 3.37% and of 2.9% at 12 and 24 hours was found in the control group. After 24 hours the serum bilirubin level was significantly lower in the treated group than in the control group (p < 0.05). No newborn of the treated group needed conventional phototherapy versus 4 control infants (17.4%). The conclusion of our study is that the Wallaby System is useful in the treatment of neonatal nonhemolytic hyperbilirubinemia even if its effectiveness for higher bilirubin levels has still to be tested.
Abstract: During the first week of life, 400 IU per day of 25(OH)D3 were given to 126 preterm and 112 full-term, small for date newborn infants, while 1000 UI per day of Vitamin D2 were given to 18 preterm and 27 full-term, small for date newborn infants, in order to compare their effectiveness for the prevention of neonatal hypocalcemia. 67 preterm and 67 full-term newborns were included in the control group. The incidence of late hypocalcemia was reduced from 16.4% to 0 in full-term babies and from 6% to 2.4% in preterm babies by the 25(OH)D3 but not by Vit. D2 administration. The incidence of early hypocalcemia was not modified at all. The Authors suggest 25(OH)D3 administration to prevent the late hypocalcemia and, together with calcium support, to treat the early hypocalcemia in the low birth weight newborn.
Abstract: The aim of this study is to investigate if nasogastric feeding may provide an adequate caloric intake and a good growth in preterm infants. One hundred and thirty-one newborns with gestational age less than or equal to 33 weeks, admitted to the Neonatal Unit of the Catholic University of Rome over a period of three years, were included in the study. Infants were divided according to birth weight in four groups: the first includes 22 neonates weighing less than or equal to 1000 g; the second 60 newborns with birth weight of 1001-1500 g; the third includes 36 prematures weighing 1501-2000 g; the fourth group 19 neonates with birth weight greater than 2000 grams. Body weight was measured daily and head circumference weekly for all the study period (60-90 days). Mean postnatal weight loss was greater in the lowest birth weight group (13.2% of the birth weight) as compared to the other three groups (8%-9%). Birth weight was regained at 18th day of age in the newborns of the first group and in the second week of age in the other three groups. A caloric intake greater than 100 Kcal/Kg/day was achieved in the second week, ranging between the 8th day (forth group) and 14th day (first group). The achievement of full enteral feeding was inversely related to the birth weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The serum concentration of phenobarbital used as an anticonvulsant was monitored in 30 preterm babies. The therapeutic serum concentration was achieved with a loading dose of 20 mg/kg i.v., 10 min after administration. Thirty-six hours after loading, it was possible to maintain therapeutic serum levels with a daily intramuscular dose of 5 mg/kg, avoiding toxicity. A comparison of CSF and serum concentrations indicated that the drug passage to CSF is rapid and depends on a brain lesion. Serum monitoring of phenobarbital is important in preterm neonates under 30 weeks gestation and/or with severe pathological complications.
Abstract: The authors studied the effects of different kinds of phototherapy in 186 newborns with a gestational age less than 33 weeks and weighing less than 2500 g. A control group of 60 infants was compared with a group of 31 infants submitted to photoprophylaxis, a group of 54 infants treated with day light, and a group of 41 infants treated with day light + special blue light. As far as the serum bilirubin variations in the first week, the maximum levels attained and the number of exchange transfusions are concerned, phototherapy always proved effective in reducing potentially neurotoxic serum bilirubin concentrations. Among the infants subjected to treatment, those treated with the day light showed a significant smaller decrease of serum bilirubin compared to those treated with the day light + special blue light, even if levels above 15 mg/dl were found in a similar percentage. Only 3.2% of the babies treated with photoprophylaxis showed serum bilirubin values above 15 mg/dl. The authors conclude that prophylaxis seems to be preferable to other phototherapeutic schedules used in the treatment of hyperbilirubinemia in low gestational age infants.
Abstract: During the first week of life serum calcium, phosphorus, magnesium, immunoreactive thyrocalcitonin hormone, and parathyroid hormone concentrations were determined daily in 36 preterm and 29 small for gestational age, full term, healthy infants. Preterm babies with early neonatal hypocalcaemia had significantly higher concentrations of serum thyrocalcitonin hormone in the first four days of life than normocalcaemic preterm babies. Parathyroid hormone concentrations were similar in hypocalcaemic and normocalcaemic infants. In contrast, in the full term group no significant differences were detected in thyrocalcitonin hormone and parathyroid hormone patterns between hypocalcaemic and normocalcaemic subjects. This suggests two different pathogeneses for early hypocalcaemia in low birthweight infants. Hyperthyrocalcitoninaemia seems to be the main determining factor in preterm infants, while a non-hormonal pathogenesis should be considered in full term infants who are small for gestational age.
Abstract: The incidence of skeletal changes in preterm low-birth-weight infants is rising. This is probably related to today's higher survival rate of these babies. The late positivity of biochemical data and the lack of clinical prognostic signs justify the role of radiology in such pathology. Radiology, however, although useful in detecting rachitic changes, seems to be less sensitive to minimal osteoporotic modifications, for which densitometric studies should be preferred. The authors report their personal experience in 8 cases of skeletal pathology in preterm infants and suggest a radiological follow-up of the skeleton from the 5th to the 12th week of life, whenever a densitometric method is not available.
Abstract: Neonatal hyperibilirubinaemia is a real problem for its possible repercussion on the psychomotor development, mainly in low birth weight infants. The Authors studied the physiologic course of bilirubinaemia in 513 low birth weight newborns and then related it to gestational age, birth weight and intrauterine growth. Results obtained show that neonatal hyperbilirubinaemia is strictly depending on gestational age, while both the birth weight and the intrauterine growth have no significant influence on its course. Certainly the very low birth weight infants run the higher risk of Kernicterus and brain injury due to hyperbilirubinaemia; they need therefore a quicker therapeutic approach, though the treatment of physiologic hyperbilirubinaemia must always be planned on the basis of gestational age.
Abstract: Phototherapy is largely used in the management of neonatal hyperbilirubinaemia, but its safety is very far from being proved. The Authors studied the effectiveness of daylight in low-birth-weight newborns. The results obtained show that the reduction of bilirubin induced by phototherapy is related with gestational age and intra-uterine growth. The very low-birth-weight infants, at higher risk of kernicterus, as they are more responsives to phototherapy, as well they are, probably, more susceptibles to side-effects. The Authors think that phototherapy should be planned on the basis of such observations.
Abstract: We have compared three different fluorescent light sources (true light, blue light, true light + blue light) for phototherapy in 155 low birth weight newborn babies affected with non haemolytic hyperbilirubinaemia. Our data suggest that blue light is significantly more effective than true light. Surprisingly the association of true light with blue light is significantly more effective than both true light and blue light separately. The greater effectiveness associated with the better tolerance of true light + blue light respect to blue light only, makes it preferable than phototherapy regimen, even if more extensive study on its effectiveness and on short and long term side effects are need.
Abstract: Phototherapy causes a higher incidence of hypocalcemia in preterm infants by still unknown pathogenetic mechanism. The authors studied 100 preterm newborns in order to verify whether Calcifediolo (25-OH-D3) could be useful to prevent the phototherapy-induced hypocalcemia. Results obtained show that Calcifediolo is not able, anyway, to lower the increase of the phototherapy-induced hypocalcemia in preterm infants. Vit D is therefore unlikely to play any important role in the patogenesis of phototherapy-induced hypocalcemia.
Abstract: Inside a pilot screening program for Congenital Hypothyroidism, T4 and TSH have been tested in sick and healty preteam and fullterm low birth weight (LBW) newborns during the first two months of life, 36 newborns affected by respiratory distress syndrome and 15 by sepsis have been included in the study. Blood samples were collected by heel puncture on 3rd, 10th, 20th, 40th and, in some cases, up to 60th day of life, and adsorbed on filter paper. Our findings show that hypothyroxinaemia in LBW newborns is strictly related to gestational age. In fact, among preterm infants with GA less than or equal to 33 weeks, 25 subjects (69,44%) showed T4 levels less than or equal to 6 micrograms/dl and 5 infants (13,88%) had T4 concentrations less than or equal to 2 micrograms/dl. The incidence of subjects with T4 values less than or equal to 6 micrograms/dl falls to 42,18% in the group of infants with GA = 34-36 weeks and to 17,27% in the group of fullterm LBW infants. None of these newborns showed thyroxine levels less than or equal to 2 micrograms/dl. All the examined infants showed normal TSH levels. The low T4 values may appear soon after birth or later (3rd-20th day of life) and sometimes persist up to 40th or 60th day, despite of always normal TSH levels. The mean of low T4 values at each sampling time is strictly and directly related to gestational age. (ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The Authors studied the possible pathogenetic factors in hypocalcemia of 66 low birth weight healthy newborn infants, 28 preterm and 38 small for gestational age babies. To clarify the pathogenesis of neonatal hypocalcemia, the Authors determined daily in the first week of life serum calcium, phosphorus and magnesium concentrations, the serum natrium and kalium level and E.A.B. on capillary blood. Total serum proteins was determined on the 2nd and on the 7th day of age. The incidence of hypocalcemia was 25.7% for all considered babies: 32.1% for preterm infants and 21% for small for gestational age babies. The hypocalcemia of preterm babies appears early during the first three days of life and it results not correlated with the serum phosphorus and the serum magnesium concentrations. On the contrary the small for gestational age babies show a "late" hypocalcemia directly related with an elevated serum concentration of phosphorus and with a reduced serum magnesium level. Both the preterm and the small for gestational age newborn infants had asymptomatic hypocalcemia and the orally administration of high doses of calcium gluconate 10% was able to normalize rapidly the serum calcium level.
