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Objective: To ascertain the extent to which neonatal analgesia for invasive procedures has changed in the last 5 years since the publication of Italian guidelines. Methods: We compared survey data for the years 2004 and 2010 on analgesia policy and practices for common invasive procedures at Italian Neonatal Intensive Care Units (NICUs); 75 NICUs answered questionnaires for both years and formed the object of this analysis. Results: By 2010 analgesia practices for procedural pain had improved significantly for almost all invasive procedures ( p < 0.05), both non-pharmacological and pharmacological methods being adopted by the majority of NICUs (unlike the situation in 2004). The routine use of medication for major invasive procedures was still limited, however (35% of lumbar punctures, 40% of tracheal intubations, 46% during mechanical ventilation). Postoperative pain treatment was still inadequate, and 41% of facilities caring for patients after surgery did not treat pain routinely. Pain monitoring had definitely improved since 2004 ( p < 0.05), but not enough: only 21% and 17% of NICUs routinely assess pain during mechanical ventilation and after surgery, respectively. Conclusion: There have been improvements in neonatal analgesia practices in Italy since national guidelines were published, but pain is still undertreated and underscored, especially during major invasive procedures. It is mandatory to address the gap between the recommendations in the guidelines and clinical practice must be addressed through with effective quality improvement initiatives. [ABSTRACT FROM AUTHOR]

There is currently no worldwide agreement on the real need to administer conjunctival antibiotics to neonates at birth to prevent neonatal conjunctivitis (usually defined as ophthalmia neonatorum) by Chlamydia trachomatis and Neisseria gonorrhoeae . Therefore, there is wide variability in antibiotic administration, conditioned mainly by the social and health context. In Italy, a law enacted in 1940 required doctors and midwives to administer ophthalmic prophylaxis with 2% silver nitrate to all newborns at birth. This law was repealed in 1975 and since then there has been no clear guidance on the use of ophthalmia neonatorum prophylaxis at birth. Since neonatal conjunctivitis caused by C. trachomatis and N. gonorrhoeae is not reported, we carried out a nationwide survey of 1,041,384 neonates across all Italian birth centers to evaluate the incidence of ophthalmia neonatorum and the current practice of prophylaxis. After analyzing the results, we formulated an intersociety position statement on the prevention of ophthalmia neonatorum to update and standardize this prevention strategy in Italy.

Background: Ophthalmia neonatorum is an acute conjunctivitis that occurs in newborns within the first month of life. The most serious infections are due to Chlamydia trachomatis and Neisseria gonorrhoeae, that may cause permanent damages. The use of ophthalmic prophylaxis varies widely around the world, according to the different health and socio-economic contexts. To date in Italy there is no a clear legislation regarding ophthalmia neonatorum prophylaxis at birth., Methods: We invited all birth centers in Italy to carry out a retrospective survey relating the last three years. We collected data regarding demographics of neonates, drugs used for ophthalmic prophylaxis and results of the screening of pregnant women for Chlamydia trachomatis and Neisseria gonorrhoeae vaginal infections., Results: Among 419 birth centers, 302 (72,1%) responded to the survey. Overall 1041384 neonates, 82,3% of those born in the three years considered, received ophthalmic prophylaxis. Only 4,585 (0,4%) of them received one of the drugs recommended by the WHO. The Centers that participated to the survey reported 12 episodes of Chlamydial conjunctivitis and no Gonococcal infection in the three years. Only 38% of the Centers performed vaginal swabs to pregnant women: 2,6% screened only for Neisseria, 9,6% only for Chlamydia and 25,8% for both germs., Conclusions: The data obtained from the survey showed a low incidence of neonatal conjunctivitis due to either Neisseria gonorrhoeae or Chlamydia trachomatis in Italy. Due to the lack of legislation regulating the prophylaxis of ophthalmia neonatorum in newborns, the Italian Society of Neonatology, the Italian Society of Obstetrics and Gynecology and the Italian Society of Perinatal Medicine have recently issued new recommendations on this topic., (© 2023. Società Italiana di Pediatria.)

Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl's pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion-1 mcg/kg/h-during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH.

Background : To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design : We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli , diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results : LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions : Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003-2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Ophthalmia neonatorum (ON) refers to any conjunctivitis occurring in the first 28 days of life. In the past Neisseria gonorrhoeae was the most common cause of ON. It decreased with the introduction of prophylaxis at birth with the instillation of silver nitrate 2% (the Credè's method of prophylaxis). Today, the term ON is used to define any other bacterial infection, in particular due to Chlamydia Trachomatis. Currently, the WHO reccomends topical ocular prophylaxis for prevention of gonococcal and chlamydial conjunctivitis for all neonates. On the contrary, several European countries no longer require universal prophylaxis, opting for screening and treatment of pregnant women at high risk of infection. And what about Italy? Have a look on Italian history of prophylaxis, starting by the first decree issued in 1940, signed by Benito Mussolini. In the following decades the law has undergone many changes. At the moment, legislation is unclear, therefore careful consideration is required in order to draft the correct appoach., (© 2021. The Author(s).)

Background: Exposure to hypothermia is somehow unavoidable when a baby comes to life. This is the reason why any possible effort should be made by every caregiver involved during birth, from labour to transfer into the maternity ward, to reduce it. Hypothermia has widely shown to be related to several neonatal problems, and the risks are more relevant when the babies are born prematurely., Method: An observational study was conducted in April 2016 to assess the current practises to avoid hypothermia at birth in 20 Italian neonatal units. Each unit introduced local improvements in clinical practice and the same observational study was repeated 1 year later., Results: A total of 4722 babies were analysed. An overall increase in adherence to local and international recommendations emerged from our study. Significant differences between 2016 and 2017 were found in regard to neonatal temperature at nursery entry (36.3 °C vs 36.5 °C, respectively, p < 0.0001), delayed cord clamping practice > 60″ (48.1% vs 68.1%, respectively, p < 0.0001) and skin-to-skin practice > 60' (56.3% vs 60.9, respectively, p = 0.03). Statistical correlations with the risk of hypothermia were found for delivery room (OR 0.88 (CI 95%0.83-0.94), p < 0.0001) and maternal temperature (OR 0.57 (CI 95% 0.48-0.67), p < 0.0001)., Conclusion: Periodical assessment of the delivery room practice has shown to be effective in improving adherence to the international recommendations. Relationship between neonatal hypothermia and several other variables including the delivery room and mother temperature underlines how neonatal thermoregulation starts immediately after birth. Hence, a multi-disciplinary approach is needed to provide the optimal environment for a safe birth.

Aim: The aim of this study was to carry out a literature review and develop clinical guidelines for pain prevention and control during screening and laser photocoagulation for retinopathy of prematurity (ROP) in neonatal intensive care units (NICUs)., Methods: The Italian Society of Neonatology assessed papers published between 1986 and June 2017 and used the Grading of Recommendations, Assessment, Development and Evaluation approach, to develop new guidelines on pain and ROP., Results: The Society's pain experts assessed the full texts of 47 papers, including randomised or quasi-randomised controlled trials and case-control studies on nonpharmacological and pharmacological measures used in NICUs during the screening and laser photocoagulation of neonates for ROP. The literature suggested methods for reducing the stress and pain associated with ROP screening procedures. The panel concluded that the literature showed that it was feasible to provide laser photocoagulation for ROP in spontaneously breathing patients with adequate analgesia., Conclusion: This literature review on managing pain in infants with ROP in NICUs led to the development of national guidelines, which will help physicians and nurses to reduce the stress and pain experienced by premature newborn infants during unavoidable screening and treatment for ROP., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: This review informed pain control guidelines for clinicians performing mechanical ventilation, nasal continuous positive airway pressure and endotracheal intubation on term and preterm newborn infants., Methods: We reviewed literature published between 1986 and June 2017 on analgesia and sedation during assisted ventilation and before endotracheal intubation in newborn infants admitted to neonatal intensive care units. The subsequent guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation approach., Results: Our review produced five strong standard of care recommendations. One, reduce neonatal stress and use nonpharmacological analgesia during invasive ventilation. Two, favour intermittent boluses of opioids, administered after pain scores and before invasive procedures, during short expected periods of mechanical ventilation, mainly in preterm infants affected by respiratory distress syndrome. Three, do not use morphine infusion in preterm infants under 27 gestational weeks. Four, always use algometric scores to titrate analgesic drugs doses. Five, use premedication before endotracheal intubation for a more rapid, less painful, less traumatic and safer manoeuvre. We also developed 30 conditional recommendations on therapeutic options., Conclusion: Our review produced 35 recommendations on standard care and therapeutic options relating to the analgesia and sedation of newborn infants during ventilation and before endotracheal intubation., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The aim of this literature review was to develop clinical guidelines for the prevention and control of needle-related pain in newborn infants. The guidelines were developed by the Italian Society of Neonatology, using the Grading of Recommendations, Assessment, Development and Evaluation approach, based on the assessment of 232 papers published between 1986 and 2015. The quality of the evidence was high or moderate for some behavioural and nonpharmacological interventions., Conclusion: There was sufficient evidence to strongly support the use of nonpharmacological interventions for common needle-related procedures in newborn infants. Combined interventions seemed to be more effective in relieving procedural pain., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.

Objective: To evaluate the analgesic superiority and the safety equivalence of continuous fentanyl infusions versus fentanyl boluses in preterm infants on mechanical ventilation., Study Design: In this multicenter, double-blind, randomized controlled trial, mechanically ventilated newborns (≤ 32(+6) weeks gestational age) were randomized to fentanyl (continuous infusion of fentanyl plus open-label boluses of fentanyl) or placebo (continuous infusion of placebo plus open-label boluses of fentanyl). The primary endpoint was analgesic efficacy, as evaluated by the Echelle Douleur Inconfort Nouveau-Né (EDIN) and Premature Infant Pain Profile scales. Safety variables were evaluated as well., Results: Sixty-four infants were allocated to the fentanyl group, and 67 were allocated to the placebo group. The need for open-label boluses of fentanyl was similar in the 2 groups (P = .949). EDIN scores were comparable in the 2 groups; 65 of 961 (6.8%) EDIN scores were >6 in the fentanyl group and 91 of 857 (10.6%) in the placebo group (P = .003). The median Premature Infant Pain Profile score was clinically and statistically higher in the placebo group compared with the fentanyl group on days 1, 2, and 3 of treatment (P < .05). Mechanical ventilation at age 1 week was required in 27 of 64 infants in the fentanyl group (42.2%), compared with 17 of 67 infants in the placebo group (25.4%) (P = .042). The first cycle of mechanical ventilation was longer and the first meconium passage occurred later in the fentanyl group (P = .019 and .027, respectively)., Conclusion: In very preterm infants on mechanical ventilation, continuous fentanyl infusion plus open-label boluses of fentanyl does not reduce prolonged pain, but does reduce acute pain and increase side effects compared with open-label boluses of fentanyl alone., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: National and international guidelines have been published on pain control and prevention in the newborn, but data on compliance with these guidelines are lacking., Aim: To document current hospital practices for analgesia at neonatal intensive care units (NICUs) 5 years after national guidelines were published in Italy., Methods: A computer-based questionnaire was sent to all registered Italian level II and level III NICUs to investigate their routine pain control practices., Main Outcome Measures: The analgesia and sedation currently used for invasive procedures as compared with best practices., Results: The questionnaire was returned by 103 of the 118 NICUs (87.3%), most of which (85.4%) knew of the national guidelines on procedural pain control and prevention, and used some analgesic measures during invasive procedures. One or more nonpharmacological interventions were only used routinely by 64.1% of the NICUs for heel pricks and venipuncture, 56.0% for percutaneous insertion of central catheters, 69.7% for nasal CPAP, and 62.4% for eye tests to screen for retinopathy of prematurity. Pain medication was routinely administered at 34.3% NICUs for tracheal intubation, 46.6% for mechanical ventilation (MV), 12.9% for tracheal aspiration, 71.4% for chest tube insertion, 33.0% for lumbar puncture, and 64.0% for postoperative pain. Pain was routinely monitored at only 22.7% of the units during MV, 12.1% for nCPAP, and 21.8% postoperatively., Conclusion: This survey showed that most Italian NICUs provide some form of analgesia and sedation for invasive procedures in accordance with national guidelines, but their routine adherence to best practices for pain control and monitoring is still suboptimal., (© 2013 Blackwell Publishing Ltd.)

Objective: To ascertain the extent to which neonatal analgesia for invasive procedures has changed in the last 5 years since the publication of Italian guidelines., Methods: We compared survey data for the years 2004 and 2010 on analgesia policy and practices for common invasive procedures at Italian Neonatal Intensive Care Units (NICUs); 75 NICUs answered questionnaires for both years and formed the object of this analysis., Results: By 2010, analgesia practices for procedural pain had improved significantly for almost all invasive procedures (p < 0.05), with both non-pharmacological and pharmacological methods being adopted by the majority of NICUs (unlike the situation in 2004). The routine use of medication for major invasive procedures was still limited, however (35% of lumbar punctures, 40% of tracheal intubations, 46% during mechanical ventilation). Postoperative pain treatment was still inadequate, and 41% of facilities caring for patients after surgery did not treat pain routinely. Pain monitoring had definitely improved since 2004 (p < 0.05), but not enough: only 21 and 17% of NICUs routinely assess pain during mechanical ventilation and after surgery, respectively., Conclusion: There have been improvements in neonatal analgesia practices in Italy since national guidelines were published, but pain is still undertreated and underscored, especially during major invasive procedures. It is mandatory to address the gap between the recommendations in the guidelines and clinical practice must be addressed through with effective quality improvement initiatives.

Infants receiving respiratory assistance may feel pain due to underlying disease or ventilation itself. Pain control during neonatal respiratory care reduces morbidity. This article summarizes the main scientific evidence about the use of drugs during ventilatory assistance, and provides some practical suggestions on pain management in neonates with respiratory support.

Unlabelled: Despite accumulating evidence that procedural pain experienced by newborn infants may have acute and even long-term detrimental effects on their subsequent behaviour and neurological outcome, pain control and prevention remain controversial issues. Our aim was to develop guidelines based on evidence and clinical practice for preventing and controlling neonatal procedural pain in the light of the evidence-based recommendations contained in the SIGN classification. A panel of expert neonatologists used systematic review, data synthesis and open discussion to reach a consensus on the level of evidence supported by the literature or customs in clinical practice and to describe a global analgesic management, considering pharmacological, non-pharmacological, behavioural and environmental measures for each invasive procedure. There is strong evidence to support some analgesic measures, e.g. sucrose or breast milk for minor invasive procedures, and combinations of drugs for tracheal intubation. Many other pain control measures used during chest tube placement and removal, screening and treatment for ROP, or for postoperative pain, are still based not on evidence, but on good practice or expert opinions., Conclusion: These guidelines should help improving the health care professional's awareness of the need to adequately manage procedural pain in neonates, based on the strongest evidence currently available.

Although antenatal steroids reduce risk factors for bronchopulmonary dysplasia (BPD) in preterm infants, their effect on BPD is conflicting. We hypothesised that the lack of protective effect found in some studies could derive from over-adjustment during analysis, caused by controlling for factors intermediate in the causal pathway between treatment and outcome. We prospectively studied a cohort of infants 23-32 weeks gestation <1500 g, admitted to 10 tertiary-level neonatal units in Lombardy (Italy) in 1999-2002; 1118 neonates out of 1314 survived to 36 weeks; 15.9% developed BPD (oxygen requirement at 36 weeks); 82% were treated with steroids. In univariable analysis, steroids were not significantly protective against BPD; some intermediate factors (mechanical ventilation, greater severity of illness as measured by Clinical Risk Index for Babies score, patent ductus arteriosus) were significantly positively associated with (i.e. were risk factors for) BPD (OR = 11.0, 1.55, 4.42, respectively, all P < 0.001), and negatively associated with (i.e. prevented by) steroids (OR = 0.58, 0.92, and 0.58, respectively, all P < 0.01). In multiple logistic regression models using propensity scores, without the above-mentioned intermediate risk factors, steroid-treated infants had a lower risk of BPD (OR 0.59 [95% CI 0.36, 0.97], P = 0.036); male sex (OR = 2.08), late-onset sepsis (OR = 4.26), and birthweight (OR = 0.63 for 100 g increase) were also associated with BPD, all P < 0.001. When intermediate risk factors for BPD were also added to the model, the effect of steroids disappeared; ventilation (OR = 3.03), increased illness severity (OR = 1.11), and patent ductus arteriosus (OR = 1.90) were significant risk factors. This study suggests that including variables that are potential mediators in the causal chain can obscure the ability to detect a protective effect of treatment. We observed such a phenomenon in our analyses of the relationship between antenatal steroids and BPD, suggesting that steroid effect is partly mediated through a reduction in the classical risk factors.

Objective: Despite accumulating evidence that procedural pain experienced by preterm infants may have acute detrimental and even long-term effects on an infant's subsequent behavior and neurological outcome, neonates admitted to Neonatal Intensive Care Units still frequently experience acute and prolonged uncontrolled pain. Many invasive and surgical procedures are routinely performed at the bedside in the NICU without adequate pain management., Aim: To develop evidence-based guidelines and recommendations for pain control and prevention in Italian i.e. heel lancing, venipuncture and percutaneous venous line positioning, tracheal intubation, mechanical ventilation, lumbar puncture, chest tube positioning, for certain surgical procedures performed at the NICU, e.g. central venous cutdown, surgical PDA ligation, and cryotherapy, laser therapy for ROP, and for postoperative pain management., Conclusion: Adequate pain prevention and management should be an essential part of standard health care at the NICU, and recognizing and assessing sources of pain should be routine in the day-to-day practice of physicians and nurses taking care of the newborn. We hope these guidelines will contribute towards increasing the NICU caregiver's awareness and understanding of the importance of adequate pain control and prevention.

Background: This study assessed current medical practice in preventative analgesia and sedation for invasive procedures in neonatal intensive care units (NICU) in Italy., Methods: A questionnaire was sent to level II and III Italian NICUs to investigate pain management, pharmacological treatment and the use of pain scores during invasive procedures. Main outcome measures were the extent to which analgesia and sedation are currently used for invasive procedures in Italian neonatal units., Results: The rate of response to the questionnaire was 88%. Written guidelines were available on acute pain control in 25% of the NICUs, and on prolonged pain control in 50%. Routine use of preventative pharmacological and nonpharmacological measures for painful procedures ranged from 13% for elective tracheal intubation to 68% for chest tube insertion. Thirty-six percent of NICUs routinely use sedation with opioids for mechanical ventilation; 14% prevent distress and pain for tracheal suctioning, 44% for heel lancing, 50% for venepuncture and percutaneous venous catheter insertion; 58% use analgesia before lumbar puncture. Validated pain assessment scores were used by 19% of NICUs., Conclusions: The need for adequate analgesia is still underestimated. Further information on the safety of analgesics in neonatology is imperative, as is an adequate education of physicians and nurses on the use of pain control guidelines as part of the standard of care in the NICU.

We hypothesized that the inter-breath variability of the breathing pattern in newborn rats varied with temperature and oxygenation. Breathing pattern was recorded in 4-day-old rats by airflow plethysmography, during normoxia in warm (control) and cold conditions, or during hypoxia (inspired O2 = 10%) in warm or cold conditions, each lasting 15 min. The warm phase (36 degrees C) either preceded or followed the cold (24 degrees C). Time-domain analysis was applied to 500 continuous breaths recorded toward the end of each phase. All parameters describing the breathing pattern (instantaneous ventilation, tidal volume, and inspiratory and expiratory time) had lower variability when the condition differed from control i.e. in cold or hypoxia, with no correlation with the absolute level of ventilation. The difference in variability between warm-normoxia and the other conditions was reduced when cold preceded the warm phase. Gaseous metabolism was increased in cold because of thermogenesis. When the cold preceded the warm phase the increased thermogenesis partly persisted into the warm phase, raising the metabolic level. We conclude that the variability of the breathing pattern in newborn rats 1) does not depend on the absolute level of ventilation, and 2) is reduced by the increased chemical stimuli occurring during cold-hypermetabolism or hypoxia. In normoxia in warm condition metabolic and chemical stimuli are low, and the variability is the highest. The results are in agreement with the clinical observations of a higher incidence of apneic episodes in infants during warm conditions.

In a previous study in conscious normoxic newborn rats, we found that the strength of the Hering-Breuer reflex (HB reflex) was greater (188%) at high (36 degrees C) than at low (24 degrees C) ambient temperature (T(a); D. Merazzi and J. P. Mortola. Pediatr. Res. 45: 370-376, 1999). We now asked what the effect would be of changes in T(a) during hypoxia. Rat pups at 3-4 days of age were studied in a double-chamber airflow plethysmograph. The HB reflex was induced by negative body surface pressures of 5 or 10 cmH(2)O and quantified from the inhibition of breathing during maintained lung inflation. Rats were first studied at T(a) = 32 degrees C in normoxia, followed by hypoxia (10% O(2) breathing). During hypoxia, oxygen consumption (VO(2)) averaged 47%, and HB reflex 115%, of the corresponding normoxic values, confirming that in the newborn, differently from the adult, hypoxia does not decrease the strength of the HB reflex. As hypoxia was maintained, lowering T(a) to 24 degrees C or increasing it to 36 degrees C, on average, had no significant effects on VO(2) and the HB reflex. However, with 5-cmH(2)O inflations, the HB reflex during the combined hypoxia and hyperthermia was significantly stronger than in normoxia. We conclude that in conscious newborn rats during normoxia the T(a) sensitivity of the HB reflex is largely mediated by the effects of T(a) on thermogenesis and VO(2); in hypoxia, because thermogenesis is depressed and VO(2) varies little with T(a), the HB reflex is T(a) independent. The observation that the reflex response to lung inflations during hypoxic hyperthermia can be greater than in normoxia may be of importance in the pathophysiology of apneas during the neonatal period.

We questioned to what extent changes in temperature could affect the newborn's ventilatory inhibition provoked by lung inflation, or Hering-Breüer (HB) inflation reflex. Conscious newborn rats (3-4 d old) were studied in a double chamber airflow plethysmograph at ambient temperatures of 32 degrees C (slightly below their thermoneutrality), 24 degrees C (cold), and 36 degrees C (warm). At these ambient temperatures, the corresponding body temperatures averaged 35.4, 31.0, and 37 degrees C. The HB reflex was triggered by negative body surface pressures of 5 or 10 cm H2O, and quantified as the duration of the expiratory time during the maintained inflation, either in absolute values or in relation to the control expiratory time. In cold the HB reflex decreased to 80%, and in warm it increased to 150%, of the values measured at 32 degrees C. Oxygen consumption, measured by an open flow system, averaged 59, 47, and 29 mL x kg(-1) x min(-1) at, respectively, 24, 32, and 36 degrees C. In cold, the ventilatory response to hypoxia (10% O2) was almost absent, that to hypercapnia (5% CO2) was greater, and that to hypoxia and hypercapnia combined was less than in warm. We conclude that in newborn rats the strength of the vagal inhibition on breathing, evaluated in the form of the HB reflex, is sensitive to temperature, becoming stronger as temperature increases. One contributing factor is the temperature-induced change in metabolic rate, whereas the role of temperature-induced changes in ventilatory chemosensitivity is variable. The strong temperature-dependency of the neonatal HB reflex implies that in newborns exposed to a warm environment breathing is more susceptible to inhibitory inputs.

Brown adipose tissue (BAT) non-shivering thermogenesis is stimulated by cold temperature and depressed by hypoxia. We investigated the extent to which changes in metabolic rate during cold and hypoxia, singly or combined, were accompanied by changes in BAT perfusion. One-month-old rabbits were instrumented for measurements of regional blood flow by the coloured microsphere technique. One group of rabbits was tested in warm (24 degrees C, n=17), and the other in cold (13 degrees C, n=9) conditions, first in normoxia (inspired oxygen concentration FIO2 about 21%, arterial oxygen saturation SaO2 approximately 88%) followed by hypoxia (FIO2 approximately 10%, SaO2 approximately 54%). In warm conditions, oxygen consumption (VO2, measured by an open-flow method) averaged 22 ml.kg-1.min-1 (STPD), and BAT blood flow 98 ml.100g-1.min-1. In hypoxia, VO2 dropped on average to 87%, whereas BAT flow dropped to 43% of the normoxic values. In the cold during normoxia, VO2 averaged 31 ml.kg-1.min-1 (STPD), and BAT blood flow was 155 ml.100g-1.min-1. In cold and hypoxia VO2 dropped to 19 ml.kg-1.min-1 (STPD) (i.e. 60% of the normoxic value), whereas BAT blood flow was not altered significantly (148 ml.100g-1.min-1). Hence, BAT blood flow decreased in hypoxia in absence of cold stimuli, whereas it remained high when hypoxia occurred during cold, despite the major drop in VO2. We conclude that cold is more important than hypoxia in determining BAT perfusion, and that changes in BAT blood flow are not a mechanism for the hypoxic control of V.O2.

Granulomatous angiitis are characterized by histologic feature of intravascular and extravascular formation of granulomas in association with necrotizing vasculitis of medium and small arteries. They are rare in childhood. The Churg-Strauss syndrome is associated with marked eosinophilia and asthma. Wegener's granulomatosis is characterized by the clinical triad of upper and lower respiratory tract diseases and renal involvement.

120 children, 71 male and 49 female, aged between 2 years and 15 years (mean 6.15 +/- 3.52 years) with recurrent respiratory infections, were treated with Immucytal, an immunomodulator of bacterial origin, based on membrane proteoglycan fractions plus bacterial ribosomes. The children, selected on the basis of the previous year's clinical score, were treated according to a random design with either Immucytal or placebo, using the same dosage of one puff per nostril plus one puff in the oropharyngeal cavity three times a day, as follows: 1st month: two weeks' treatment, one week wash out, one week's treatment. 2nd, 3rd, 4th months: two weeks' treatment, two week's wash out. Monthly throughout the treatment period the frequency and severity of airway infections episodes were assessed using the same score as for admission. Blood chemistry test, immunological assays (circulating Ig, lymphocyte subpopulations, Merieux Multitest in vivo blastization test) and respiratory tests (spirometry using a pneumotachigraph) were done before and after the treatment. 118/120 children completed treatment; the two dropouts were in the placebo group, one for compliance and the other because of headaches. Respiratory symptoms improved significantly in the actively treated children already from the first month, but not in the placebo group. This improvement consisted of reduction of the respiratory infectious episodes in both the upper and lower airways. No changes were noted in respiratory function parameters. From the immunological viewpoint, there were significant rises in serum IgA and IgM and enhanced skin response tot he Multitest; there was no change in the percentages of different circulating lymphocyte subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Kawasaki's syndrome is an acute multisystem vasculitis typical for childhood characterized by fever, conjunctivitis, stomatitis, swelling of cervical lymph-nodes, exanthema and desquamation of extremities. The etiology is so far unknown, the latest hypothesis formulated are reported. Cardiac involvement and particularly coronary aneurysmal dilatation is the most severe and characteristic SK complication.

Polyarteritis is an uncommon childhood disease. The different forms of polyarteritis are described. Polyarteritis nodosa is a rare multisystemic disease characterized by high fever, calf pain and subcutaneous nodules. Infantile polyarteritis nodosa shows a peculiar predilection for the coronary arteries and has the worst prognosis. Polyarteritis cutaneous is the localized and mild form of polyarteritis. Hypersensitivity angiitis is described as a leukocytoclastic vasculitis identified by palpable purpura.

A great number of vasculitis in childhood is associated with Rheumatic disease. Vascular lesions involve small vessels of various organs. These are described in systemic lupus erythematosus, juvenile rheumatoid arthritis, dermatomyositis, scleroderma, mixed connective tissue disease, Behçet syndrome, Sjögren syndrome.