Risk Index For Babies Score Research Articles

Antenatal steroids and risk of bronchopulmonary dysplasia: a lack of effect or a case of over‐adjustment?

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.

Intraventricular hemorrhage in preterm newborns: Risk factors and results from a University Hospital in Istanbul, 8 years after

In this prospective study, the authors aimed to show intraventricular hemorrhage (IVH) incidence of premature newborns in the Neonatal Intensive Care Unit of Cerrahpasa Faculty of Medicine, Istanbul, Turkey, and its risk factors, and they tried to compare these results with those they reported 8 years ago. A total of 103 premature newborns, hospitalized between August 2003 and January 2005 with a gestational age equal or less than 33 weeks, were included in this study. IVH rates and changes in the incidences of risk factors were compared with those that had been reported between January 1995 and January 1997. Mean birthweight of this population was 1400 +/- 380 g (min, 550 g; max, 2000 g) and gestational age 30.3 +/- 2.1 weeks (min, 25 weeks; max, 33 weeks). IVH was diagnosed in 13 (13%) of them. IVH rates were 37, 10 and 5% for birthweight groups 501-1000, 1001-1500 and 1501-200 g, respectively. Statistically significant risk factors were found to be birthweight, gestational age, clinical risk index for babies score >5, mechanical ventilation, sepsis and hypotension. Maternal corticosteroid administration was found to be significantly protective. IVH rates and incidences of risk factors in this study were decreased compared to those reported 8 years ago. In developing countries, where well equipped Neonatal Intensive Care Units are limited, prevention of prematurity, better prenatal care and maternal corticosteroid administration become essential points for the prevention of IVH and its neurological consequences.

Hyperglycemia Is a Risk Factor for Early Death and Morbidity in Extremely Low Birth-Weight Infants

The objectives of this study were to determine the prevalence of hyperglycemia in extremely low birth-weight infants and to determine whether hyperglycemia increases the risk of early adverse outcomes (death or intraventricular hemorrhage of grade 3 or 4) and/or affects the length of hospital stay among survivors without intraventricular hemorrhage. The charts of all extremely low birth-weight infants (n = 93) admitted to Texas Children's Hospital (Houston, TX) during 2001 were reviewed. The highest daily blood glucose concentrations, highest dopamine infusion rates, highest daily percentage of inspired oxygen, and mean blood sodium concentrations were averaged over the first week of life or before death or occurrence of grade 3 or 4 intraventricular hemorrhage. Among survivors without severe intraventricular hemorrhage, the time ratio for blood glucose concentrations of >150 mg/dL was calculated. More than 50% of the infants had persistent blood glucose concentrations of >150 mg/dL during their first week of life. Early adverse outcomes were associated with the average highest daily blood glucose concentration through interaction with the Clinical Risk Index for Babies score and with the average highest daily percentage of inspired oxygen. The length of hospital stay was associated with the time ratio for blood glucose concentrations of >150 mg/dL through interaction with birth weight and the average highest daily percentage of inspired oxygen. These data confirm the high prevalence of hyperglycemia among parenterally fed, extremely low birth-weight infants and show that high blood glucose concentrations increase the risk of early death and grade 3 or 4 intraventricular hemorrhage and the length of hospital stay among survivors without intraventricular hemorrhage, which suggests that prevention and treatment of hyperglycemia may improve the outcomes of extremely low birth-weight infants.

Alterations of exhaled nitric oxide in pre-term infants with chronic lung disease

Animal models suggest that reduced nitric oxide (NO) synthase activity results in lower values of exhaled NO (eNO) present at birth in those individuals who are going to develop chronic lung disease of infancy (CLDI). Online tidal eNO was measured in 39 unsedated pre-term infants with CLDI (mean gestational age (GA) 27.3 weeks) in comparison with 23 healthy pre-term (31.6 weeks) and 127 term infants (39.9 weeks) at 44 weeks post-conceptional age, thus after the main inflammatory response. NO output (NO output (V'(NO)) = eNO x flow) was calculated to account for tidal- flow-related changes. Sex, maternal atopic disease and environmental factors (smoking, caffeine) were controlled for. The mean eNO was not different (14.9 ppb in all groups) but V'(NO) was lower in CLDI compared with healthy term infants (0.52 versus 0.63 nL x s(-1)). Values for healthy pre-term infants were between these two groups (0.58 nL x s(-1)). Within all pre-term infants (n = 62), V'(NO) was reduced in infants with low GA, high clinical risk index for babies scores and longer duration of oxygen therapy but not associated with post-natal factors, such as ventilation or corticosteroid treatment. After accounting for flow, the lower nitric oxide output in premature infants with chronic lung disease of infancy is consistent with the hypothesis of nitric oxide metabolism being involved in chronic lung disease of infancy.

Dopamine Versus Epinephrine for Cardiovascular Support in Low Birth Weight Infants: Analysis of Systemic Effects and Neonatal Clinical Outcomes

Early postnatal adaptation to transitional circulation in low birth weight infants frequently is associated with low blood pressure and decreased blood flow to organs. Catecholamines have been used widely as treatment, despite remarkably little empirical evidence on the effects of vasopressor/inotropic support on circulation and on clinically important outcomes in sick newborn infants. To explore the effectiveness of low/moderate-dose dopamine and epinephrine in the treatment of early systemic hypotension in low birth weight infants, evaluate the frequency of adverse drug effects, and examine neonatal clinical outcomes of patients in relation to treatment. Newborns of <1501-g birth weight or <32 weeks of gestational age, with a mean blood pressure lower than gestational age in the first 24 hours of life, were assigned randomly to receive dopamine (2.5, 5, 7.5, and 10 microg/kg per minute; n = 28) or epinephrine (0.125, 0.250, 0.375, and 0.5 microg/kg per minute; n = 32) at doses that were increased stepwise every 20 minutes until optimal mean blood pressure was attained and maintained (responders). If this treatment was unsuccessful (nonresponders), sequential rescue therapy was started, consisting first of the addition of the second study drug and then hydrocortisone. These included: (1) short-term changes (first 96 hours, only responders) in heart rate, mean blood pressure, acid-base status, lactate, glycemia, urine output, and fluid-carbohydrate debit; and (2) medium-term morbidity, enteral nutrition tolerance, gastrointestinal complications, severity of lung disease, patent ductus arteriosus, cerebral ultrasound diagnoses, retinopathy of prematurity, and mortality. Patients enrolled in this trial did not differ in birth weight or gestational age (1008 +/- 286 g and 28.3 +/- 2.3 weeks in the dopamine group; 944 +/- 281 g and 27.7 +/- 2.4 weeks in the epinephrine group). Other main antenatal variables were also comparable. However, responders and nonresponders differed significantly with respect to the need for cardiorespiratory resuscitation at birth (3% vs 23%), Critical Risk Index for Babies score (3.8 +/- 3 vs 7 +/- 5), and premature rupture of membranes >24 hours (39.5% vs 13.6%), respectively. No differences were found in the rate of treatment failure (dopamine: 36%; epinephrine: 37%) or need for rescue therapy according to treatment allocation. Groups did not differ in age at initiation of therapy (dopamine: 5.3 +/- 3.9 hours; epinephrine: 5.2 +/- 3.3 hours), but withdrawal was significantly later in the dopamine group. For short-term changes, mean blood pressure showed a significant increase from baseline throughout the first 96 hours with no differences between groups. However, epinephrine produced a greater increase in heart rate than dopamine. After treatment began, epinephrine patients showed higher plasma lactate (first 36 hours) and lower bicarbonate and base excess (first 6 hours) and received more bicarbonate. Patients in the epinephrine group also had higher glycemia (first 24 hours) and needed insulin therapy more often. Groups did not differ in urine output or fluid-carbohydrate supply during the first 96 hours. For medium-term morbidity, there were no differences in neonatal clinical outcomes in responders. However, significant differences were found in the incidence of patent ductus arteriosus, bronchopulmonary dysplasia, need for high-frequency ventilation, occurrence of necrotizing enterocolitis, and death between responders and nonresponders. Low/moderate-dose epinephrine is as effective as low/moderate-dose dopamine for the treatment of hypotension in low birth weight infants, although it is associated with more transitory adverse effects.

Neurodevelopmental and Respiratory Follow-up Results at 7 Years for Children From the United Kingdom and Ireland Enrolled in a Randomized Trial of Early and Late Postnatal Corticosteroid Treatment, Systemic and Inhaled (the Open Study of Early Corticosteroid Treatment)

The goals were to compare early school-age neurodevelopmental and respiratory outcomes for children who were treated with either early (<3 days) or delayed selective (>15 days) postnatal corticosteroid therapy and to compare systemic dexamethasone treatment with inhaled budesonide treatment. One hundred twenty-seven (84%) of 152 survivors from the United Kingdom and Ireland who were recruited to the Open Study of Early Corticosteroid Treatment, a randomized trial of inhaled and systemic corticosteroid therapy to prevent chronic lung disease, were traced and assessed at a median age of 7 years. Outcome measures were level of disability, presence of cerebral palsy, cognitive ability, behavioral difficulties and competencies, growth, and respiratory symptoms. Results were adjusted for potential confounding variables (gestational age, birth weight, gender, prenatal steroid therapy, method of delivery, Apgar score at 5 minutes, and Clinical Risk Index for Babies score). There were no significant differences among the treatment groups in cognitive ability, behavioral competencies or difficulties, overall disability rates, cerebral palsy, combined outcomes of death or cerebral palsy and death or moderate/severe disability, growth, respiratory morbidity, or diastolic blood pressure. Those assigned to dexamethasone were more likely to have high systolic blood pressure and to have a diagnosis of asthma than were those assigned to budesonide. Although postnatal steroid therapy has been associated with poor long-term outcomes, this study failed to show significant differences in cognitive function between dexamethasone- and budesonide-allocated groups. There may be increased systolic blood pressure and a greater likelihood of developing asthma in childhood after postnatal dexamethasone treatment.

Morphine Administration and Short-term Pulmonary Outcomes Among Ventilated Preterm Infants

The use of opioid therapy for sedation and analgesia among ventilated infants varies among care providers. The impact of opioid therapy early in the neonatal course of respiratory distress syndrome (RDS) on pulmonary outcomes is not known. We tested the hypothesis that preterm neonates randomized to the morphine infusion group would have improved ventilatory outcomes, measured as shorter durations of ventilator or oxygen therapy, fewer air leaks, and lower incidence of bronchopulmonary dysplasia. All 898 subjects (gestational age [GA] of > or =23 to < or =32 weeks) who were enrolled in the Neurologic Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial formed the study cohort (morphine: 449 patients; placebo: 449 patients). Subjects received the masked study drug until they were weaned from the ventilator or for 14 days, whichever occurred earlier. Outcome measures included air leaks, duration of ventilation or oxygen therapy, hospitalization, bronchopulmonary dysplasia, and death. Subjects in the 2 groups had similar baseline characteristics (mean +/- SD, morphine versus placebo: GA: 27.3 +/- 2.3 vs 27.4 +/- 2.3 weeks; birth weight: 1037 +/- 340 vs 1054 +/- 354 g). Infants in the morphine group required ventilator therapy significantly longer, compared with the placebo group (median [interquartile range]: 7 days [4-20 days] vs 6 days [3-19 days]). This difference in ventilation duration was significant for infants with GA of 27 to 29 weeks (6 days [4-12 days] vs 5 days [2-9 days]) and 30 to 32 weeks (4 days [3-6 days] vs 3 days [2-5 days]). Infants who received additional analgesia with intermittent morphine doses in both groups were sicker than those who were not given open-label morphine. After adjustment for birth weight, Clinical Risk Index for Babies scores, maternal chorioamnionitis, RDS requiring surfactant, and patent ductus arteriosus in a logistic regression model, the use of additional analgesia with morphine was associated independently with increased air leaks and longer durations of high-frequency ventilation, nasal continuous positive airway pressure, and oxygen therapy. Morphine infusions do not improve short-term pulmonary outcomes among ventilated preterm neonates. Additional morphine doses were associated with worsening respiratory outcomes among preterm neonates with RDS.

Morphine, Hypotension, and Adverse Outcomes Among Preterm Neonates: Who’s to Blame? Secondary Results From the NEOPAIN Trial

Hypotension occurs commonly among preterm neonates, but its cause and consequences remain unclear. Secondary data analyses from the NEOPAIN trial identified the clinical factors associated with hypotension and examined the contributions of morphine treatment or hypotension to severe intraventricular hemorrhage (IVH) (grades 3 and 4), any IVH (grades 1-4), or death. In the NEOPAIN trial, 898 ventilated neonates between 23 and 32 weeks of gestation were enrolled, with equal numbers randomized to receive masked morphine or placebo infusions. Additional doses of open-label morphine were administered as necessary by medical staff members. IVH was diagnosed with centralized readings of early and late cranial ultrasonograms. Hypotension was assessed before study drug infusion, during the loading dose, and at 24 and 72 hours during study drug infusion. Logistic regression analyses with stepdown elimination identified the predictor factors associated with the hypotension, severe IVH, any IVH, or death outcomes at each time point. Hypotension was associated with 23 to 26 weeks of gestation, morphine infusions, severity of illness, additional morphine doses, and prior hypotension. Severe IVH was associated with shorter gestation, higher Clinical Risk Index for Babies scores, no prenatal steroids, pulmonary hemorrhage, hypotension before the loading dose, and morphine doses before intubation and at 25 to 72 hours. Neonatal deaths were associated with 23 to 26 weeks of gestation, higher Clinical Risk Index for Babies scores, pulmonary hemorrhage, patent ductus arteriosus, thrombocytopenia, and hypotension before the loading dose. Morphine infusions were not a significant factor in logistic models for severe IVH, any IVH, or death. Preemptive morphine infusions, additional morphine, and lower gestational age were associated with hypotension among preterm neonates. Severe IVH, any IVH, and death were associated with preexisting hypotension, but morphine therapy did not contribute to these outcomes. Morphine infusions, although they cause hypotension, can be used safely for most preterm neonates but should be used cautiously for 23- to 26-week neonates and those with preexisting hypotension.

Late-Onset Septicemia in a Norwegian National Cohort of Extremely Premature Infants Receiving Very Early Full Human Milk Feeding

To investigate the occurrence of and risk factors for late-onset septicemia (LOS) in a national cohort of extremely premature infants who received very early full human milk feeding. A prospective study of all infants born in Norway in 1999 and 2000 with gestational age of <28 weeks or birth weight of <1000 g was performed. Extensive clinical information, including data on feeding practices and episodes of septicemia, was collected on predefined forms. LOS was defined as growth of bacteria or fungi in blood cultures in conjunction with clinical symptoms consistent with systemic infection occurring after day 6 of life. Cox regression models, including models allowing for time-dependent covariates, were applied in the analysis of LOS. Of 464 eligible infants, 462 (99.6%) were enrolled and 405 (87.7%) survived until day 7. LOS was diagnosed for 80 (19.7%). The predominant pathogens were coagulase-negative staphylococci, followed by Candida spp. Case fatality rates associated with septicemia were 10% in general and 43% for Candida spp septicemia. Necrotizing enterocolitis or bowel perforation was diagnosed for 19 infants (4%). Enteral feeding with human milk was initiated within the third day for 98% of patients, and 92% were receiving full enteral feeding (FEF) with human milk within the third week. Both high Clinical Risk Index for Babies scores and an umbilical venous catheter in situ at 7 days of age significantly predicted LOS. However, the overall most influential risk factor for LOS was the number of days without establishment of FEF with human milk, with an adjusted relative risk of 3.7 (2.0-6.9) for LOS if FEF was not established within the second week of life. The incidence and case fatality rate of septicemia for this cohort of extremely preterm infants were lower than values in comparable studies. The main difference, compared with other studies, was the feeding practice, and the data suggest that very early FEF with human milk significantly reduces the risk of LOS among extremely premature infants.

The Danish national study in infants with extremely low gestational age and birthweight (the ETFOL study): respiratory morbidity and outcome.

To describe and analyse neonatal care, short and long-term morbidity with special reference to ventilatory support and chronic lung disease (CLD) in a population-based study. During 1994 and 1995 a prospective, nation-wide, multicentre study was conducted, comprising 477 liveborn infants with gestational age (GA) < 28 wk and/or birthweight < 1000 g. Of these, 407 infants received active treatment. The ventilatory treatment was based on the principle of permissive hypercapnia and early nasal continuous positive airway pressure (NCPAP) supplemented with surfactant and ventilator therapy in case of CPAP failure. Among actively treated infants 85% received CPAP and 23% mechanical ventilation from the first day of life. A total of 269 infants (56%) survived to discharge. Of these, 195 had a GA < 28 wk. One-hundred and five survivors with GA < 28 wk survived with NCPAP as sole respiratory support. In surviving infants, periventricular leucomalacia/intraventricular haemorrhage grade 3-4 was found in 10%, retinopathy of prematurity grade > 2 in 4%, and oxygen requirement at 36 and 40 wk of postmenstrual age (CLD) in 16 and 5%, respectively. Three infants either died of CLD (n = 1) or required oxygen therapy beyond 43 wk of postmenstrual age. Logistic regression analysis showed significant associations between oxygen requirement at 40 wk and GA, septicaemia, mechanical ventilation, symptomatic patent ductus arteriosus and Clinical Risk Index for Babies score. Only the two last-mentioned factors proved significant in infants with GA < 28 wk. No infant died after discharge and 253 (94%) were followed up at 2 y of corrected age; one or more moderate to severe impairments were found in 66 (26%) of the examined children. Ventilatory treatment in extremely premature and extremely low-birthweight infants based on early NCPAP and permissive hypercapnia may result in comparable survival rates and sensorineural outcome; however, the incidence of CLD seems lower than that reported on conventional treatment.

The Danish national study in infants with extremely low gestational age and birthweight (the ETFOL study): respiratory morbidity and outcome

Aim: To describe and analyse neonatal care, short and long‐term morbidity with special reference to ventilatory support and chronic lung disease (CLD) in a population‐based study. Methods: During 1994 and 1995 a prospective, nation‐wide, multicentre study was conducted, comprising 477 liveborn infants with gestational age (GA) &gt;28 wk and/or birthweight &gt;1000 g. Of these, 407 infants received active treatment. The ventilatory treatment was based on the principle of permissive hypercapnia and early nasal continuous positive airway pressure (NCPAP) supplemented with surfactant and ventilator therapy in case of CPAP failure. Results: Among actively treated infants 85% received CPAP and 23% mechanical ventilation from the first day of life. A total of 269 infants (56%) survived to discharge. Of these, 195 had a GA &gt;28wk. One‐hundred and five survivors with GA &gt;28 wk survived with NCPAP as sole respiratory support. In surviving infants, periventricular leucomalacia/intraventricular haemorrhage grade 3–4 was found in 10%, retinopathy of prematurity grade &gt;2 in 4%, and oxygen requirement at 36 and 40 wk of postmenstrual age (CLD) in 16 and 5%, respectively. Three infants either died of CLD (n= 1) or required oxygen therapy beyond 43 wk of postmenstrual age. Logistic regression analysis showed significant associations between oxygen requirement at 40 wk and GA, septicaemia, mechanical ventilation, symptomatic patent ductus arteriosus and Clinical Risk Index for Babies score. Only the two last‐mentioned factors proved significant in infants with GA &gt;28 wk. No infant died after discharge and 253 (94%) were followed up at 2 y of corrected age; one or more moderate to severe impairments were found in 66 (26%) of the examined children. Conclusion: Ventilatory treatment in extremely premature and extremely low‐birthweight infants based on early NCPAP and permissive hypercapnia may result in comparable survival rates and sensorineural outcome; however, the incidence of CLD seems lower than that reported on conventional treatment.

Early pituitary-adrenal responses and retinopathy of prematurity in very low birth weight infants.

This longitudinal prospective study aimed to investigate the relationship between pituitary-adrenal responses and severity of retinopathy of prematurity (ROP) in 92 preterm, very low birth weight infants < or = 30 wk gestation. The human corticotropin releasing hormone stimulation test was performed on these infants at D 7 and 14 of postnatal life. Univariate analysis revealed significant associations between severity of ROP and gestational age (r = -0.53, p < 0.0001), birth weight (r = -0.56, p < 0.0001), Apgar score at 1 min (r = -0.27, p < 0.05), Clinical Risk Index for Babies score (r = 0.48, p < 0.0001), duration of mechanical ventilation (r = 0.48, p < 0.0001), oxygen dependency (r = 0.48, p < 0.0001), and length of hospitalization (r = 0.49, p < 0.0001). The stage of ROP was also significantly associated with the basal and peak plasma ACTH (r > -0.22, p < 0.05) and peak serum cortisol (r = -0.21, p = 0.05) at d 7. Multivariate analysis using the classification and regression trees indicated that the two most influential risk factors affecting the development of advanced stages of ROP (> or = stage 3) were i) birth weight and ii) oxygen dependency at 28 d of life or at 36 wk postconceptional age. Our findings suggest that early endogenous or stimulated pituitary-adrenal responses are not independent risk factors associated with the development of severe ROP. Low birth weight and prolonged oxygen exposure are likely to be important factors that influence the degree of damage inflicted on the retina.

CRIB II: an update of the clinical risk index for babies score

The clinical risk index for babies (CRIB) score is a risk-adjustment instrument widely used in neonatal intensive care. Its appropriateness with contemporary data has been questioned. We have examined these questions, developed a new five-item CRIB II score with data from a UK-wide sample of infants admitted to neonatal intensive care in 1998-99, and shown how mortality after neonatal intensive care has fallen in the past 12 years. CRIB II provides a recalibrated and simplified scoring system that avoids the potential problems of early treatment bias. A valid and simple method of risk-adjustment for neonatal intensive care is important to ensure accurate assessment of quality of care. Such assessments should be done in tandem with national audit systems for neonatal intensive care, incorporating measures of morbidity as well as mortality.

Measuring intramucosal pH in very low birth weight infants.

Maintenance of adequate perfusion is essential for health of the intestinal mucosa. Methods available to assess intestinal perfusion provide information on mesenteric blood flow, which may differ from mucosal flow. Intramucosal pH (pH(i)) is influenced by tissue oxygenation and perfusion. Gastric pH(i) can be measured using the technique of tonometry. A prospective observational clinical study was performed to examine relationships between measured gastric pH(i) and mucosal CO(2) (mCO(2)), and acid-base balance, gastrointestinal complications (necrotizing enterocolitis and perforation), and death in infants <1500 g birth weight. A nasogastric tonometry catheter (size 5F) was inserted into the stomach of infants, and pH(i) was calculated from mCO(2) levels measured using saline tonometry. Measurements were performed at 3, 12, 24, and 48 h, then daily until arterial access was unavailable. Two hundred eleven sets of measurements were performed on 38 infants [birth weight (mean +/-SD), 863 +/- 241 g; gestation, 26.5 +/- 1.8 wk; and median Clinical Risk Index for Babies score, 8.0 (interquartile range, 5.0-10.75)]. Mean pH(i) was 7.27 (95% confidence interval, 7.26-7.28) and mean mCO(2) was 47.0 mm Hg (95% confidence interval, 45.7-48.3 mm Hg). pH(i) and mCO(2) correlated significantly with arterial pH (pH(a)), arterial PCO(2) (PaCO(2)), and arterial base excess. There were no significant relationships between pH(a) and pH gap (pH(a)-pH(i)) or CO(2) gap (mCO(2)-PaCO(2)). Recurrent low pH(i) (<7.2 on more than one occasion) and an mCO(2)/PaCO(2) ratio of > or =1.29 were significantly associated with an increase in gastrointestinal complications. There were no statistically significant associations with death. In conclusion, changes in pH gap and CO(2) gap can occur without alteration in pH(a). Abnormalities in pH(i) might predict gastrointestinal complications in infants <1500 g.

An Outbreak of Influenza A in a Neonatal Intensive Care Unit

Investigation of an outbreak of influenza A in a neonatal intensive care unit (NICU) with examination of risk factors for infection and outcomes. Retrospective cohort study of infants admitted to the unit during the outbreak period. Prospective survey of NICU staff and mothers of infants in the cohort study. Level III nursery in a university-affiliated tertiary referral center. Nineteen infants in the NICU were infected with influenza A There were six symptomatic cases and one death who had evidence of virus-associated hemophagocytic syndrome at autopsy. Amantadine prophylaxis was offered to the NICU staff, and amantadine therapy was given to five of the six symptomatic infants. Mechanical ventilation, gestational age, birth weight, Clinical Risk Index for Babies score, and twin pregnancy were associated with acquisition of influenza A on univariate analysis. Mechanical ventilation (odds ratio [OR], 6.2; P=.02) and twin pregnancy (OR, 7.0; P=.04) remained as significant risk factors for infection on multiple logistic regression analysis. Only 15% of respondents to the NICU staff survey were vaccinated against influenza. There was no association between a history of an influenza-like illness during pregnancy and acquisition of influenza A by infants of mothers who responded to the maternal survey (OR, 0.91; P=1.0). Influenza A is an important pathogen in the neonatal population and is readily transmissible in the NICU setting.

Bacterial endocarditis in neonatal intensive care.

To ascertain the incidence of bacterial endocarditis in a level III neonatal nursery. To document the clinical features, assess survival, and evaluate the role of central venous catheters in neonates with bacterial endocarditis. Index cases were identified by retrospective review of the echocardiographic records of infants admitted to the neonatal nursery from 1983 to 1995. Data obtained by review of the clinical records of these infants, and case-matched controls. From January 1983 to December 1995, 12,249 infants were admitted to the Special Care Nursery. Eight infants with endocarditis were identified, an incidence of 0.07%. Presenting symptoms and signs were often vague and nonspecific. Gestation less than 32 weeks, birthweight less than 1500 g, thrombocytopenia and neutropenia or neutrophilia were common features. Infants with endocarditis had a significantly higher Clinical Risk Index for Babies score than those without endocarditis. The tricuspid valve was involved in seven infants, six of whom had a percutaneous central venous catheter in situ before diagnosis. Mitral valve involvement occurred in two infants, neither of whom had central lines inserted. However, compared to infants without endocarditis, the placement of a central venous line was not of statistical significance. Seven of the eight infants survived following prolonged antibiotic therapy. Bacterial endocarditis is a rare but serious condition which is usually not fatal. In the premature newborn infant, presenting signs and symptoms are often nonspecific. Endocarditis should therefore be considered in the unwell very low birthweight infant.

Plasma creatinine rises dramatically in the first 48 hours of life in preterm infants.

Published data show that plasma creatinine falls steadily during the first 28 days of life and that creatinine levels in the neonatal period are higher in more premature infants. However, the best reference data commence on day 2 of life. The objective of this study was to document how plasma creatinine changes in the first 48 hours of life and to examine the reason for the apparently high levels of creatinine in preterm infants, compared with maternal levels. A prospective observational study on a regional neonatal intensive care unit. A total of 42 preterm infants, mean gestational age of 29.4 weeks (range: 23-35), mean birth weight of 1.42 kg (.55-2.77), divided into 4 gestation groups: 23 to 26 weeks (n = 9), 27 to 29 weeks (n = 13), 30 to 32 weeks (n = 12), and 33 to 35 weeks (n = 8). Measurement of plasma creatinine and urea concentration in cord blood and in serial samples taken for routine arterial blood gas analysis. Changes in creatinine concentration with time and relationship to gestational age, birth weight, and illness severity. Mean creatinine at birth was 73 micromol/L (95% confidence interval [CI]: 68-79 micromol/L). Plasma creatinine rose significantly over the first 48 hours. Mean peak creatinine in the most preterm infants (23-26 weeks) was 221 micromol/L (CI: 195-247 micromol/L). Peak plasma creatinine was inversely related to gestation (Spearman's coefficient: -.73) and birth weight (Spearman's coefficient: -.76). Significant differences in creatinine concentration were seen among different gestational groups at 24 and 48 hours of life. Peak creatinine correlated with a high Clinical Risk Index for Babies score (Spearman's coefficient:. 64). The fall in creatinine began later in more premature infants. All 38 surviving infants had normal renal function; their mean plasma creatinine at discharge was 52 micromol/L (CI: 46-58 micromol/L). Rather than falling steadily from birth, creatinine rises dramatically in the first 48 hours of life, especially in infants of <30 weeks' gestation. Even large rises in creatinine in the first 48 hours may be expected and should not be used in isolation to diagnose renal failure.

Analgesia and Sedation in Preterm Neonates Who Require Ventilatory Support

Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo. To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis. Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia. No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group. This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.