Neurodevelopmental outcomes among extremely premature infants with linear growth restriction.

OBJECTIVE: To compare neurodevelopmental outcomes in linear growth-restricted (LGR) infants born <29 weeks with and without weight gain out of proportion to linear growth. STUDY DESIGN: We compared 2-year neurodevelopmental outcomes between infants with and without LGR and between LGR infants with and without weight gain out of proportion to linear growth. The outcomes were Bayley-III cognitive, motor, and language scores, cerebral palsy, Gross Motor Function Classification System (GMFCS) level ≥ 2, and neurodevelopmental impairment. RESULT: In total, 1227 infants were analyzed. LGR infants were smaller and less mature at birth, had higher BMI, and had lower Bayley-III language scores (82.3 vs. 85.0, p < 0.05). Among infants with LGR, infants with high BMI had lower language scores compared with those with low-to-normal BMI (80.8 vs. 83.3, p < 0.05), and were more likely to have GMFCS level ≥2 and neurodevelopmental impairment. CONCLUSION: Among infants with LGR, weight gain out of proportion to linear growth was associated with poorer neurodevelopmental outcomes.

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

OBJECTIVE: To analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns. STUDY DESIGN: The original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment. RESULTS: Two hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window. CONCLUSION: Despite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives.

Neurodevelopmental outcomes in postnatal growth-restricted preterm infants with postnatal head-sparing.

OBJECTIVE: To compare neurodevelopmental outcomes in postnatal growth-restricted infants born <29 weeks with and without postnatal head-sparing (PHS). STUDY DESIGN: We analyzed developmental outcomes at 2 years of age among postnatally growth-restricted infants with and without head-sparing. The primary outcome was Bayley III cognitive composite score; secondary outcomes included Bayley III motor composite score, moderate/severe cerebral palsy, gross motor functional classification scale level⩾2, and presence or absence of neurodevelopmental impairment (NDI). RESULTS: Of 1098 infants evaluated at 18 to 22 months, 658 were postnatally growth restricted, of whom 301 had head-sparing. In the multivariate model including independent risk factors for poor growth and poor developmental outcome, infants with head-sparing had higher adjusted motor composite scores (mean difference 4.65, P<0.01), but no differences in other neurodevelopmental outcomes. CONCLUSION: PHS is associated with improved neurodevelopmental outcome in extremely preterm infants, specifically Bayley III motor scores, but whether beneficial effects of PHS persist later in life is unknown.

Inhaled nitric oxide usage in preterm infants in the NICHD Neonatal Research Network: inter-site variation and propensity evaluation.

OBJECTIVE: The use of inhaled nitric oxide (iNO) in preterm infants remains controversial. In October 2010, a National Institutes of Health consensus development conference cautioned against use of iNO in preterm infants. This study aims (1) to determine the prevalence and variability in use of iNO in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) before and after the consensus conference and (2) separately, to examine associations between iNO use and severe bronchopulmonary dysplasia (BPD) or death. STUDY DESIGN: The NICHD NRN Generic Database collects data including iNO use on very preterm infants. A total of 13 centers contributed data across the time period 2008 to 2011. Infants exposed or not to iNO were compared using logistic regression, which included factors related to risk as well as their likelihood of being exposed to iNO. RESULT: A total of 4885 infants were assessed between 2008 and 2011; 128 (2.6%) received iNO before day 7, 140 (2.9%) between day 7 and 28, and 47 (1.0%) at >28 days. Center-specific iNO use during 2008 to 2010 ranged from 21.9 to 0.4%; 12 of 13 sites reduced usage and overall NRN iNO usage decreased from 4.6 to 1.6% (P<0.001) in 2011. The use of iNO started between day 7 and day 14 was more prevalent among younger infants with more severe courses in week 1 and associated with increased risk of severe BPD or death (odds ratio 2.24; 95% confidence interval 1.23 to 4.07). CONCLUSION: The variability and total use of iNO decreased in 2011 compared with 2008 to 2010. iNO administration started at ⩾ day 7 was associated with more severe outcomes compared with infants without iNO exposure.

Outcomes of extremely preterm infants following severe intracranial hemorrhage.

OBJECTIVE: Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH. STUDY DESIGN: Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI). RESULT: Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI. CONCLUSION: Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.

Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous intestinal perforation or surgical necrotizing enterocolitis.

OBJECTIVE: To determine if extremely low birth weight infants with surgical necrotizing enterocolitis have a higher risk of death or neurodevelopmental impairment and neurodevelopmental impairment among survivors (secondary outcome) at 18-22 months corrected age compared with infants with spontaneous intestinal perforation and infants without necrotizing enterocolitis or spontaneous intestinal perforation. STUDY DESIGN: Retrospective analysis of the Neonatal Research Network very low birth weight registry, evaluating extremely low birth weight infants born between 2000 and 2005. The study infants were designated into three groups: (1) spontaneous intestinal perforation without necrotizing enterocolitis; (2) surgical necrotizing enterocolitis (Bell's stage III); and (3) neither spontaneous intestinal perforation nor necrotizing enterocolitis. Multivariate logistic regression analysis was performed to evaluate the association between the clinical group and death or neurodevelopmental impairment, controlling for multiple confounding factors including center. RESULT: Infants with surgical necrotizing enterocolitis had the highest rate of death before hospital discharge (53.5%) and death or neurodevelopmental impairment (82.3%) compared with infants in the spontaneous intestinal perforation group (39.1 and 79.3%) and no necrotizing enterocolitis/no spontaneous intestinal perforation group (22.1 and 53.3%; P<0.001). Similar results were observed for neurodevelopmental impairment among survivors. On logistic regression analysis, both spontaneous intestinal perforation and surgical necrotizing enterocolitis were associated with increased risk of death or neurodevelopmental impairment (adjusted odds ratio 2.21, 95% confidence interval (CI): 1.5, 3.2 and adjusted OR 2.11, 95% CI: 1.5, 2.9, respectively) and neurodevelopmental impairment among survivors (adjusted OR 2.17, 95% CI: 1.4, 3.2 and adjusted OR 1.70, 95% CI: 1.2, 2.4, respectively). CONCLUSION: Spontaneous intestinal perforation and surgical necrotizing enterocolitis are associated with a similar increase in the risk of death or neurodevelopmental impairment and neurodevelopmental impairment among extremely low birth weight survivors at 18-22 months corrected age.

When to transfuse preterm babies.

The physiological anaemia experienced by preterm babies is exacerbated by common care practices such as early clamping of the umbilical cord at birth and gradual exsanguination by phlebotomy for laboratory monitoring. The need for subsequent transfusion with red blood cells can be reduced by delaying cord clamping for 30-60 s in infants who do not require immediate resuscitation. The need for transfusions can be further reduced by limiting phlebotomy losses, providing good nutrition, and using standard guidelines for transfusion based on haemoglobin or haematocrit. What those guidelines should be is not clear. Analysis of two recent large clinical trials comparing restrictive and liberal transfusion guidelines leads to several conclusions. Restrictive transfusion guidelines may reduce the number of transfusions given, but there is no reduction in donor exposures if a single-donor transfusion programme is used. There is some evidence that more liberal transfusion guidelines may help to prevent brain injury, but information on the impact of transfusion practice on long-term outcome is lacking. Until further guidance emerges, transfusion thresholds lower than those used in the two trials should not be used, as there is no evidence that lower thresholds are safe.

Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants.

BACKGROUND: Most premature infants are not sufficiently mature physiologically to ingest all of their required water and nutrients orally. Therefore, premature infants rely on their caregivers to regulate their volume of water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants. OBJECTIVES: The objective of this review is to examine the effects of water intake on postnatal weight loss and on the risks of dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death in premature infants. SEARCH STRATEGY: Randomized clinical trials identified in previous versions of this review were re-examined and, in each case, retained. Additional trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to experimental protocol. Such trials were sought in a list of trials provided by the Cochrane Neonatal Review Group, with a PubMed search, and in the authors' personal files. SELECTION CRITERIA: Only randomized clinical trials of varying water intake in premature infants are included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by intravascular infusion. Included studies reported at least one of the following outcomes: postnatal weight loss, dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration were used. The studies to be included were selected by two reviewers, each of whom also assessed the methodological quality of each trial. Data were independently extracted by the reviewers, who agreed on the key details. The data were then entered into tables using RevMan 4.3.1. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk and risk difference were computed. In addition, the maximal weight loss results were recorded, and the weighted mean difference was computed. The analyses - including calculation of relative risk, risk difference, and weighted mean difference - and tests of heterogeneity were accomplished using RevMan 4.3.1 software. MAIN RESULTS: The analysis of the five studies taken together indicates that restricted water intake significantly increases postnatal weight loss and significantly reduces the risks of patent ductus arteriosus and necrotizing enterocolitis. With restricted water intake, there are trends toward increased risk of dehydration and reduced risks of bronchopulmonary dysplasia, intracranial hemorrhage, and death, but these trends are not statistically significant. AUTHORS' CONCLUSIONS: Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis without significantly increasing the risk of adverse consequences.

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants.

BACKGROUND: Treating very low birth weight (VLBW) infants with pharmacologic doses of vitamin E as an antioxidant agent has been proposed for preventing or limiting retinopathy of prematurity, intracranial hemorrhage, hemolytic anemia, and chronic lung disease. However, excessive doses of vitamin E may result in side effects. OBJECTIVES: The aim of this systematic review was to assess the effects of vitamin E supplementation on morbidity and mortality in preterm infants. SEARCH STRATEGY: We searched MEDLINE (October 2002), EMBASE (March 2002), the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library, 2003, Issue 1, and personal files for clinical trials assessing vitamin E in preterm infants. SELECTION CRITERIA: We selected trials analyzing primary outcomes (mortality or combined long-term morbidity) or secondary outcomes (other morbidity) in infants with gestational age less than 37 weeks or birth weight less than 2500 grams. The intervention was allocation to routine supplementation with vitamin E in the treatment group versus placebo, no treatment or another type, dose or route of administration of vitamin E. DATA COLLECTION AND ANALYSIS: We used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly increased hemoglobin concentration by a small amount. Vitamin E significantly reduced the risk of germinal matrix/intraventricular hemorrhage and increased the risk of sepsis; however, heterogeneity limits the strength of these latter two inferences. Vitamin E did not significantly affect other morbidity or mortality. In VLBW infants, vitamin E supplementation significantly increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Subgroup analyses showed (1) an association between intravenous, high-dose vitamin E supplementation and increased risk of sepsis and of parenchymal cerebral hemorrhage; (2) an association between vitamin E supplementation by other than the intravenous route and reduced risk of germinal matrix-intraventricular hemorrhage and of severe intraventricular hemorrhage; and (3) an association between serum tocopherol levels greater than 3.5 mg/dl and increased risk of sepsis and reduced risk for severe retinopathy among those examined. REVIEWER'S CONCLUSIONS: Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants it increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses, or aiming at serum tocopherol levels greater than 3.5 mg/dl.

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants.

BACKGROUND: Treating very low birth weight (VLBW) infants with pharmacologic doses of vitamin E as an antioxidant agent has been proposed for preventing or limiting retinopathy of prematurity, intracranial hemorrhage, hemolytic anemia, and chronic lung disease. However, excessive doses of vitamin E may result in side effects. OBJECTIVES: The aim of this systematic review was to assess the effects of vitamin E supplementation on morbidity and mortality in preterm infants. SEARCH STRATEGY: We searched MEDLINE (October 2002), EMBASE (March 2002), the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library, 2003, Issue 1, and personal files for clinical trials assessing vitamin E in preterm infants. SELECTION CRITERIA: We selected trials analyzing primary outcomes (mortality or combined long-term morbidity) or secondary outcomes (other morbidity) in infants with gestational age less than 37 weeks or birth weight less than 2500 grams. The intervention was allocation to routine supplementation with vitamin E in the treatment group versus placebo, no treatment or another type, dose or route of administration of vitamin E. DATA COLLECTION AND ANALYSIS: We used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly reduced the risk of germinal/intraventricular hemorrhage (typical relative risk [RR] 0.85, 95% confidence interval [CI] 0.73, 0.99), increased the risk of sepsis (typical RR 1.52, CI 1.13, 2.04) and increased hemoglobin concentration by a small amount, but did not significantly affect mortality and other morbidity. In VLBW infants, vitamin E supplementation increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Subgroup analyses in VLBW infants showed (1) an association between serum tocopherol levels greater than 3.5 mg/dl and increased risk of sepsis and reduced risk for severe retinopathy among those examined; and (2) an association between intravenous, high-dose administration of vitamin E and increased risk of sepsis. REVIEWER'S CONCLUSIONS: Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants it increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses, or aiming at serum tocopherol levels greater than 3.5 mg/dl.

Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants.

BACKGROUND: Most premature infants are not sufficiently mature physiologically to take all of their required water and nutrients orally, and so they cannot regulate their own water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants. OBJECTIVES: The objective of this review is to examine the effects of water intake on postnatal weight loss and on the risks of dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death in premature infants. SEARCH STRATEGY: Randomized clinical trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to experimental protocol. Such trials were sought in a previous review by one of the authors (Bell EF. Fluid therapy. In: Effective Care of the Newborn Infant, eds JC Sinclair, MB Bracken. Oxford: Oxford University Press, 1992: 59-72), in a list of trials provided by the Cochrane Neonatal Review Group, and in the authors' personal files. SELECTION CRITERIA: Only randomized clinical trials of varying water intake in premature infants are included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by parenteral means. Studies were included regardless of outcomes examined. DATA COLLECTION AND ANALYSIS: Trials were selected by two reviewers, who also assessed the methodological quality of each trial. Data were independently extracted by the reviewers, and differences were reconciled. The data were then entered into tables using RevMan 3.1 for Windows. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk was computed. In addition, the maximal weight loss results were recorded, and the weighted mean difference was computed. The analyses (including calculation of relative risk, risk difference, and weighted mean difference) and tests of heterogeneity were accomplished with MetaView 3.1 software and a fixed effects model. No subgroup analyses were conducted. MAIN RESULTS: The analysis of the four studies taken together indicates that restricted water intake significantly increases postnatal weight loss and significantly reduces the risks of patent ductus arteriosus, necrotizing enterocolitis, and death. With restricted water intake, there are trends toward increased risk of dehydration and reduced risk of bronchopulmonary dysplasia, but these trends are not statistically significant. REVIEWER'S CONCLUSIONS: Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis--and perhaps the overall risk of death--without significantly increased risk of adverse consequences.

A cost-benefit analysis of RSV prophylaxis in high-risk infants.

OBJECTIVE: To determine the cost and benefit of using RSV-IG and palivizumab as prophylactic therapy against respiratory syncytial virus (RSV)-associated illness in high-risk infants. METHODS: A nonrandomized, retrospective, cohort control study was conducted comparing the outcomes of patients who received either RSV-IG or palivizumab therapy against RSV during the 1998-1999 RSV season with patients identified from the 1994-1995 RSV season who would have been eligible to receive prophylaxis had either agent been available at that time. Medical record reviews were conducted to gather data regarding the costs associated with both the administration of the prophylactic drugs and the treatment of RSV-associated hospitalizations in both groups. Decision analysis was used to determine the average cost per patient for both groups. A cost-benefit analysis was then conducted to determine the return on investment, if any, for the use of these drugs. A sensitivity analysis was also conducted to determine the robustness of the data. RESULTS: Patients who received RSV-IG or palivizumab had a hospitalization rate of 1.6% compared with 25% for the group who did not receive prophylactic drugs. The average costs for the RSV prophylaxis group were less per patient $3,733 compared with $4,258 in the group who did not receive prophylaxis. The benefit is a 23.4% lower chance of hospitalization for each infant or, in dollar figures, $3,985 ($17,031 x 0.234). The benefit-cost ratio is 1.15:1 ($3,985:3,461). The benefits, therefore, exceed the costs associated with the prophylaxis program. The prophylaxis program saved healthcare dollars by preventing RSV-related hospital-izations. CONCLUSIONS: Results demonstrate that when used according to our institution's criteria, RSV prophylaxis is of benefit to our institution.

Hematocrit correlates well with circulating red blood cell volume in very low birth weight infants.

Although circulating red blood cell (RBC) volume is a better measure of total body oxygen delivering capacity than hematocrit (HCT), circulating RBC volume is more difficult to measure. Thus, the HCT is often used in RBC transfusion decisions. However, several previous studies of low birth weight infants have reported that the correlation between HCT and circulating RBC volume is poor. Using a robust nonradioactive method based on in vivo dilution of biotinylated RBC enumerated by flow cytometry, the present study reexamined the correlation between HCT and circulating RBC volume in very low birth weight infants. Venous and capillary HCT levels were compared with circulating RBC volume measured using the biotin method. Twenty-six stable very low birth weight infants with birth weights less than 1300 g were studied on 43 occasions between 7 and 79 d of life. Venous HCT values correlated highly with circulating RBC volume (r = 0.907; p < 0.0001). However, the mean 95% confidence limits for prediction of circulating RBC volume from venous HCT (the average error of prediction) was +/-13.4 mL/kg. The correlation between HCT and circulating RBC volume is strong in older stable very low birth weight infants. However, clinically important uncertainty exists in estimating circulating RBC volume and the associated RBC transfusion needs of an individual infant based on venous HCT. Because direct measurement of circulating RBC volume is not yet practical, the HCT (or the blood Hb concentration) remains the best available indirect indicator.

Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants.

BACKGROUND: Most premature infants are not sufficiently mature physiologically to take all of their required water and nutrients orally, and so they cannot regulate their own water intake. Thus, the caregiver must determine the amount of water to be given each day to such infants. OBJECTIVES: The objective of this review is to examine the effects of water intake on postnatal weight loss and on the risks of dehydration, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia, intracranial hemorrhage, and death in premature infants. SEARCH STRATEGY: Randomized clinical trials were sought that compared the outcomes of interest in groups of premature infants who were given different levels of water intake according to experimental protocol. Such trials were sought in a previous review by one of the authors (Bell EF. Fluid therapy. In: Effective Care of the Newborn Infant, eds JC Sinclair, MB Bracken. Oxford: Oxford University Press, 1992: 59-72, approximately approximately Bell 1992 approximately approximately ), in a list of trials provided by the Cochrane Neonatal Review Group, and in the authors' personal files. SELECTION CRITERIA: Only randomized clinical trials of varying water intake in premature infants are included. The review was limited to trials that included infants whose water intake was provided mainly or entirely by parenteral means. Studies were included regardless of outcomes examined. DATA COLLECTION AND ANALYSIS: Trials were selected by two reviewers, who also assessed the methodological quality of each trial. Data were independently extracted by the reviewers, and differences were reconciled. The data were then entered into tables using RevMan 3.1 for Windows. The adverse event rates were calculated for the restricted and liberal water intake groups for each dichotomous outcome, and the relative risk was computed. In addition, the maximal weight loss results were recorded, and the weighted mean difference was computed. The analyses (including calculation of relative risk, risk difference, and weighted mean difference) and tests of heterogeneity were accomplished with MetaView 3.1 software and a fixed effects model. No subgroup analyses were conducted. MAIN RESULTS: The analysis of the four studies taken together indicates that restricted water intake significantly increases postnatal weight loss and significantly reduces the risks of patent ductus arteriosus, necrotizing enterocolitis, and death. With restricted water intake, there are trends toward increased risk of dehydration and reduced risk of bronchopulmonary dysplasia, but these trends are not statistically significant. REVIEWER'S CONCLUSIONS: Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis--and perhaps the overall risk of death--without significantly increased risk of adverse consequences.

Adaptive responses during anemia and its correction in lambs.

There is limited information available on which to base decisions regarding red blood cell (RBC) transfusion treatment in anemic newborn infants. Using a conscious newborn lamb model of progressive anemia, we sought to identify accessible metabolic and cardiovascular measures of hypoxia that might provide guidance in the management of anemic infants. We hypothesized that severe phlebotomy-induced isovolemic anemia and its reversal after RBC transfusion result in a defined pattern of adaptive responses. Anemia was produced over 2 days by serial phlebotomy (with plasma replacement) to Hb levels of 30-40 g/l. During the ensuing 2 days, Hb was restored to pretransfusion baseline levels by repeated RBC transfusion. Area-under-the-curve methodology was utilized for defining the Hb level at which individual study variables demonstrated significant change. Significant reciprocal changes (P < 0.05) of equivalent magnitude were observed during the phlebotomy and transfusion phases for cardiac output, plasma erythropoietin (Epo) concentration, oxygen extraction ratio, oxygen delivery, venous oxygen saturation, and blood lactate concentration. No significant change was observed in resting oxygen consumption. Cardiac output and plasma Epo concentration increased at Hb levels <75 g/l, oxygen delivery and oxygen extraction ratio decreased at Hb levels <60 g/l, and venous oxygen saturation decreased and blood lactate concentration increased at Hb levels <55 g/l. We speculate that plasma Epo and blood lactate concentrations may be useful measures of clinically significant anemia in infants and may indicate when an infant might benefit from a RBC transfusion.

Use of infrared thermographic calorimetry to determine energy expenditure in preterm infants.

BACKGROUND: Measurement of infant energy expenditure in the clinical setting is difficult and is rarely done. Both indirect and direct calorimetry require long measurement periods and frequent calibration. OBJECTIVE: The objective of this study was to validate in infants a newly developed method of determining energy expenditure, infrared thermographic calorimetry (ITC), against an established method, respiratory indirect calorimetry (IC). ITC measures mean infant body surface temperature. ITC was used in conjunction with heat loss theory to calculate radiant, convective, evaporative, and conductive heat losses and thereby determine total energy expenditure. DESIGN: Ten healthy preterm infants were studied by obtaining concurrent ITC and IC measurements over a 3.5-5.5-h study period. Continuous IC measurements were compared with ITC measurements taken every 10 min during study periods. IC values were summed over 10-min intervals covering the 5 min before and 5 min after each ITC measurement, to allow comparisons between the 2 methods. RESULTS: Comparison of paired ITC and IC mean measurements for all 10 infants over the entire study period showed no significant difference between the 2 methods. However, individual paired IC and ITC values were significantly different for 7 of 10 infants. The overall mean difference between the 2 methods was 1.3%. CONCLUSIONS: ITC is an accurate, noninvasive method for measurement of heat loss and energy expenditure in healthy preterm infants, and therefore it may be a useful clinical and research tool.

Transient surfactant protein B deficiency in a term infant with severe respiratory failure.

A 38-day-old male infant with persistent pulmonary hypertension and respiratory failure since birth was found to have a complete absence of surfactant protein B (SP-B) along with an aberrant form of SP-C in his tracheal aspirate fluid, findings consistent with the diagnosis of hereditary SP-B deficiency. Surprisingly, SP-B and SP-B messenger ribonucleic acid were present in lung biopsy tissue. However, DNA sequence analysis demonstrated a point mutation in exon 5 of one of the SP-B gene alleles. The infant's mother was found to be a carrier of this mutation. The infant's other SP-B allele did not differ from the published DNA sequence for the SP-B gene. We conclude that this patient had a transient deficiency of SP-B, in contrast to that of previously described infants with irreversible respiratory failure caused by hereditary SP-B deficiency. We recommend that infants with suspected SP-B deficiency have serial analysis of tracheal fluid samples for both SP-B and SP-C before lung biopsy, along with genetic analysis for the known SP-B mutations. We speculate that the new mutation found in one of this patient's SP-B genes was in part responsible for the transient deficiency of SP-B.

Changes in body water compartments with diuretic therapy in infants with chronic lung disease.

The effects of diuretic therapy on body water compartments were studied in preterm infants with chronic lung disease. Gestational age of the infants ranged from 24 to 28 weeks, while the median postnatal age at the time of study was 40 days. Infants were randomized to receive furosemide (1.0 mg/kg/day) alone (n = 5) or combined with metolazone (0.2 mg/kg/day, n = 7) for 4 consecutive days. Treatment in both groups produced a significant decrease (P < 0.05) in extracellular water (ECW) without changes in plasma volume, total body water or body weight. The decrease in ECW with furosemide (503 +/- 28 to 446 +/- 19 ml/kg initial body weight) was of similar magnitude to that seen with combined furosemide plus metolazone (522 +/- 30 to 454 +/- 15 ml/kg initial body weight). Water and electrolyte intakes were similar in both groups and unchanged over the course of the study. These findings suggest that in infants with chronic lung disease, diuretic therapy induces intercompartmental shifts in body water, ultimately decreasing interstitial water while preserving PV. Only combined treatment with furosemide plus metolazone produced a significant increase in urine output, confirming the increased efficacy of combination therapy in inducing diuresis.

Changing patterns of red blood cell transfusion in very low birth weight infants.

OBJECTIVE: Anemia develops in increasing numbers of critically ill very low birth weight (VLBW) infants who survive the neonatal period, and they receive multiple red blood cell (RBC) transfusions. Despite their need for prolonged medical treatment, we hypothesized that VLBW infants presently receive fewer RBC transfusions as a result of the growing awareness of transfusion risks and improvement of neonatal care. METHODS: RBC transfusion practices and clinical outcomes in infants with birth weights of 1.5 kg or less were analyzed retrospectively in three selected years: 1982, before awareness of the human immunodeficiency virus; 1989, before surfactant availability; and 1993, before erythropoietin approval. RESULTS: Progressive declines in RBC transfusions, donor exposures, and transfusion volumes occurred concurrently with decreases in morbidity and mortality rates. Transfusions per infant (mean +/- SD) declined from 7.0 +/- 7.4 in 1982 to 5.0 +/- 5.8 in 1989 to 2.3 +/- 2.7 in 1993 (p < 0.001). This decline was associated with a decrease in pretransfusion hematocrit (33.6% +/- 2.8% in 1982, 34.2% +/- 3.7% in 1989, and 29.8% +/- 5.1% in 1993; p < 0.001). The distribution of RBC transfusions given by week of life among study years did not change; 70% of RBC transfusions were given within the first 4 weeks, when infants are sickest. Although the percentage of VLBW infants weighing more than 1 kg at birth and never receiving any RBC transfusions increased with time (17% in 1982, 33% in 1989, and 64% in 1993), more than 95% of infants weighing 1 kg or less in all years received transfusions. CONCLUSIONS: Overall administration of neonatal transfusions has decreased markedly, most likely because of multiple factors. Because most RBC transfusions are given to infants weighing 1 kg or less in the first weeks of life, therapeutic strategies should focus on this group of VLBW infants during this critical period. The temporal changes observed in transfusion patterns emphasize the importance of including concurrent controls in future studies evaluating transfusion interventions.