Publications by authors named "Ariel A Salas"

32 Publications

Body composition of extremely preterm infants fed protein-enriched, fortified milk: a randomized trial.

Pediatr Res 2021 Jun 28. Epub 2021 Jun 28.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Critically ill extremely preterm infants fed human milk are often underrepresented in neonatal nutrition trials aimed to determine the effects of enteral protein supplementation on body composition outcomes.

Methods: Masked randomized trial in which 56 extremely preterm infants 25-28 weeks of gestation were randomized to receive either fortified milk enriched with a fixed amount of extensively hydrolyzed protein (high protein group) or fortified milk without additional protein (standard protein group).

Results: Baseline characteristics were similar between groups. In a longitudinal analysis, the mean percent body fat (%BF) at 30-32 weeks of postmenstrual age (PMA), 36 weeks PMA, and 3 months of corrected age (CA) did not differ between groups (17 ± 3 vs. 15 ± 4; p = 0.09). The high protein group had higher weight (-0.1 ± 1.2 vs. -0.8 ± 1.3; p = 0.03) and length (-0.8 ± 1.3 vs. -1.5 ± 1.3; p = 0.02) z scores from birth to 3 months CA. The high protein group also had higher fat-free mass (FFM) z scores at 36 weeks PMA (-0.9 ± 1.1 vs. -1.5 ± 1.1; p = 0.04).

Conclusions: Increased enteral intake of protein increased FFM accretion, weight, and length in extremely preterm infants receiving protein-enriched, fortified human milk.

Impact: Extremely preterm infants are at high risk of developing postnatal growth failure, particularly when they have low fat-free mass gains. Protein supplementation increases fat-free mass accretion in infants, but several neonatal nutrition trials aimed to determine the effects of enteral protein supplementation on body composition outcomes have systematically excluded critically ill extremely preterm infants fed human milk exclusively. In extremely preterm infants fed fortified human milk, higher enteral protein intake increases fat-free mass accretion and promotes growth without causing excessive body fat accretion.
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http://dx.doi.org/10.1038/s41390-021-01628-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237544PMC
June 2021

Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.

J Pediatr 2021 Jun 19. Epub 2021 Jun 19.

National Institute of Child Health and Human Development, Bethesda, MD; Department of Global and Community Health, George Mason University, Fairfax, VA.

Objective: To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants.

Study Design: EPT infants (24-27 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed.

Results: Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score <85 at 18-22 months corrected age (P = .002).

Conclusions: EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation.
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http://dx.doi.org/10.1016/j.jpeds.2021.06.026DOI Listing
June 2021

Percent Body Fat Content Measured by Plethysmography in Infants Randomized to High- or Usual-Volume Feeding after Very Preterm Birth.

J Pediatr 2021 03 25;230:251-254.e3. Epub 2020 Nov 25.

Department of Pediatrics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.

We measured percent body fat by air-displacement plethysmography in 86 infants born at <32 weeks of gestation randomized to receive either high-volume (180-200 mL/kg/day) or usual volume feeding (140-160 mL/kg/day). High-volume feeding increased percent body fat by ≤2% at 36 weeks of postmenstrual age (within a predefined range of equivalence). TRIAL REGISTRATION: ClincialTrials.gov: NCT02377050.
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http://dx.doi.org/10.1016/j.jpeds.2020.11.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914146PMC
March 2021

Postnatal growth of preterm infants 24 to 26 weeks of gestation and cognitive outcomes at 2 years of age.

Pediatr Res 2021 May 17;89(7):1804-1809. Epub 2020 Sep 17.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Weight z scores at 36 weeks of postmenstrual age (PMA) define postnatal growth failure (PGF) and malnutrition. This study aimed to determine weight z scores at 36 weeks PMA that are associated with adverse cognitive outcomes at 2 years of age.

Methods: In this retrospective cohort study, 350 infants 24-26 weeks of gestation born between 2006 and 2014 and followed at 2 years were included. Weight z scores at birth and at 36 weeks PMA were calculated using the INTERGROWTH-21st growth curves. The primary outcome was cognitive delay at 2 years of age (Bayley-III cognitive score < 85).

Results: Neither the traditional definition of PGF (z score below -1.3) nor the recently proposed definition of malnutrition (z score decline of 1.2 or greater) was associated with cognitive delay. Both a weight z score below -1.0 at 36 weeks PMA (RR: 1.65; 95% CI: 1.10-2.49; p < 0.05) and a decline below -1.0 in weight z score from birth to 36 weeks PMA (RR: 1.40; 95% CI: 1.00-1.94; p < 0.05) were associated with a higher risk of cognitive delay.

Conclusion: With optimal cutoffs, INTERGROWTH-21st weight z scores can predict the risk of cognitive delay.

Impact: New growth curves generated with longitudinal data could overcome some limitations of traditional growth curves generated with cross-sectional data. When these new growth curves are used to assess the growth of preterm infants, alternative definitions for postnatal growth alterations may be needed. This study examines the association between postnatal growth alterations defined by the INTEGROWTH-21 growth curves and adverse cognitive outcomes at 2 years of age. With alternative definitions of postnatal growth failure and malnutrition, the INTERGROWTH-21st growth curves can help establish the association between postnatal growth of extremely preterm infants and adverse neurodevelopmental outcomes in early childhood.
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http://dx.doi.org/10.1038/s41390-020-01158-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965787PMC
May 2021

Early career investigator highlight biocommentary.

Authors:
Ariel A Salas

Pediatr Res 2020 11 11;88(5):688. Epub 2020 Sep 11.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

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http://dx.doi.org/10.1038/s41390-020-01129-3DOI Listing
November 2020

Serial assessment of fat and fat-free mass accretion in very preterm infants: a randomized trial.

Pediatr Res 2020 11 7;88(5):733-738. Epub 2020 Jul 7.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35249, USA.

Background: Clinicians could modify dietary interventions during early infancy by monitoring fat and fat-free mass accretion in very preterm infants.

Methods: Preterm infants were randomly assigned to either having reports on infant body composition available to the clinicians caring for them (intervention group) or not having reports available (control group). All infants underwent serial assessments of body composition by air-displacement plethysmography before 32 weeks of postmenstrual age (PMA) and at 36 weeks PMA. The primary outcome was percent body fat (%BF) at 3 months of corrected age (CA).

Results: Fifty infants were randomized (median gestational age: 30 weeks; mean ± SD birth weight: 1387 ± 283 g). The mean %BF increased from 7 ± 4 before 32 weeks PMA to 20 ± 5 at 3 months CA. The differences in mean %BF between the intervention group and the control group were not statistically significant at 36 weeks PMA (14.5 vs. 13.6) or 3 months CA (20.8 vs. 19.4). Feeding practices and anthropometric measurements during hospitalization did not differ between groups.

Conclusions: Serial assessments of body composition in both intervention and control groups showed consistent increments in %BF. However, providing this information to clinicians did not influence nutritional practices or growth.

Impact: Serial assessments of body composition in preterm infants at 32 and 36 weeks postmenstrual age show consistent increments in % body fat up to 3 months of corrected age. However, providing this information to the clinician did not influence nutritional practices or growth.
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http://dx.doi.org/10.1038/s41390-020-1052-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581604PMC
November 2020

Higher- or Usual-Volume Feedings in Infants Born Very Preterm: A Randomized Clinical Trial.

J Pediatr 2020 09 25;224:66-71.e1. Epub 2020 May 25.

Department of Pediatrics, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL.

Objective: To determine whether higher-volume feedings improve postnatal growth among infants born very preterm.

Study Design: Randomized clinical trial with 1:1 parallel allocation conducted from January 2015 to June 2018 in a single academic medical center in the US. In total, 224 infants with a birth weight 1001-2500 g born at <32 weeks of gestation were randomized to higher-volume (180-200 mL/kg/d) or usual-volume (140-160 mL/kg/d) feedings after establishing full enteral feedings (≥120 mL/kg/d). The primary outcome was growth velocity (g/kg/d) from randomization to study completion at 36 weeks of postmenstrual age or hospital discharge if earlier.

Results: Growth velocity increased among infants in the higher-volume group compared with the usual-volume group (mean [SD], 20.5 [4.5] vs 17.9 [4.5] g/kg/d; P < .001). At study completion, all measurements were higher among infants in the higher-volume group compared with the usual-volume group: weight (2365 [324] g, z score -0.60 [0.73] vs 2200 [308] g, z score -0.94 [0.71]; P < .001); head circumference (31.9 [1.3] cm, z score -0.30 [0.91] vs 31.4 [1.3] cm, z score -0.53 [0.84]; P = .01); length (44.9 [2.1] cm, z score -0.68 [0.88] vs 44.4 [2.0], z score -0.83 [0.84]; P = .04); and mid-arm circumference (8.8 [0.8] cm vs 8.4 [0.8] cm; P = .002). Bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or other adverse outcomes did not differ between groups.

Conclusions: In infants born very preterm weighing 1001-2500 g at birth, higher-volume feedings increased growth velocity, weight, head circumference, length, and mid-arm circumference compared with usual-volume feedings without adverse effects.

Trial Registration: ClinicalTrials.gov; NCT02377050.
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http://dx.doi.org/10.1016/j.jpeds.2020.05.033DOI Listing
September 2020

Quantitative assessment of nutritive sucking patterns in preterm infants.

Early Hum Dev 2020 07 25;146:105044. Epub 2020 Apr 25.

Department of Electrical and Computer Engineering, University of Alabama, Tuscaloosa, AL 35487, USA.

Objective: To assess patterns of nutritive sucking in very preterm infants ≤32 weeks of gestation.

Study Design: Very preterm infants who attained independent oral feeding were prospectively assessed with an instrumented feeding bottle that measures nutritive sucking. The primary outcome measure was nutritive sucking performance at independent oral feeding.

Result: We assessed nutritive sucking patterns in 33 very preterm infants. We recorded 63 feeding sessions. The median number of sucks was 784 (IQR: 550-1053), the median sucking rate was 36/min (IQR: 27-55), and the median number of sucking bursts during the first 5 min of oral feeding was 14 (IQR: 12-16). Maximum sucking strength correlated with the number of sucks (r = 0.62; p < 0.01). No safety concerns were identified during the study.

Conclusion: The quantitative analysis of nutritive sucking patterns with a newly developed instrumented bottle in stable, very preterm infants is safe and feasible. More research is needed to develop and refine the instrument further.
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http://dx.doi.org/10.1016/j.earlhumdev.2020.105044DOI Listing
July 2020

Oxygen saturation histogram monitoring to reduce death or retinopathy of prematurity: a quality improvement initiative.

J Perinatol 2020 01 10;40(1):163-169. Epub 2019 Sep 10.

University of Alabama at Birmingham, Birmingham, AL, USA.

Objectives: Maintaining preterm infants within a goal oxygen saturation range challenges care providers. Through periodic assessment of saturation trends on infants' bedside histogram reports, our initiative aimed to (1) increase time spent at goal saturations and (2) reduce death or severe retinopathy of prematurity.

Study Design: The initiative integrated histogram monitoring into provider, respiratory, and nursing care. Achieved oxygen saturations, chart audits, and bedside histogram monitoring flowsheets provided process measures with the outcome measure of death or severe retinopathy of prematurity.

Results: In infants <29 weeks' gestation (n = 518), the rate of death or severe retinopathy of prematurity prior to hospital discharge decreased from 32.1% to 18.0%. Time at goal saturations (90-95%) increased from 48.7% to 57.6%.

Conclusion: In infants born at <29 weeks' gestation, periodic, multidisciplinary oxygen saturation histogram monitoring improved time at goal saturations and was associated with a reduction in death or severe retinopathy of prematurity.
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http://dx.doi.org/10.1038/s41372-019-0486-7DOI Listing
January 2020

Does tight glycaemic control with insulin therapy in the early neonatal period improve long-term outcomes?

Acta Paediatr 2018 11 19;107(11):2032-2033. Epub 2018 Sep 19.

Division of Neonatology, Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA.

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http://dx.doi.org/10.1111/apa.14518DOI Listing
November 2018

Early progressive feeding in extremely preterm infants: a randomized trial.

Am J Clin Nutr 2018 03;107(3):365-370

Department of Pediatrics, School of Medicine; and Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.

Background: Due to insufficient evidence, extremely preterm infants (≤28 wk of gestation) rarely receive early progressive feeding (small increments of feeding volumes between 1 and 4 d after birth). We hypothesized that early progressive feeding increases the number of full enteral feeding days in the first month after birth.

Objective: The aim of this study was to determine the feasibility and efficacy of early progressive feeding in extremely preterm infants.

Design: In this single-center randomized trial, extremely preterm infants born between September 2016 and June 2017 were randomly assigned to receive either early progressive feeding without trophic feeding (early feeding group) or delayed progressive feeding after a 4-d course of trophic feeding (delayed feeding group). Treatment allocation occurred before or on feeding day 1. The primary outcome was the number of full enteral feeding days in the first month after birth. Secondary outcomes were death, necrotizing enterocolitis (NEC), culture-proven sepsis, growth percentiles at 36 wk postmenstrual age, use of parenteral nutrition, and need for central venous access.

Results: Sixty infants were included (median gestational age: 26 wk; mean ± SD birth weight: 832 ± 253 g). The primary outcome differed between groups (median difference favoring the early feeding group: +2 d; 95% CI: 0, 3 d; P = 0.02). Early progressive feeding reduced the use of parenteral nutrition (4 compared with 8 d; P ≤ 0.01) and the need for central venous access (9 compared with 13 d; P ≤ 0.01). The outcome of culture-proven sepsis (10% compared with 27%; P = 0.18), restricted growth (weight, length, and head circumference <10th percentile) at 36 wk postmenstrual age (25% compared with 50%; P = 0.07), and the composite outcome of NEC or death (27% compared with 20%; P = 0.74) did not differ between groups.

Conclusion: Early progressive feeding increases the number of full enteral feeding days in extremely preterm infants. This trial was registered at www.clinicaltrials.gov as NCT02915549.
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http://dx.doi.org/10.1093/ajcn/nqy012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692650PMC
March 2018

Reply to the Commentary "Vitamin D Intake in Preterm Infants: Too Little, Too Much, or Just the Right Amount?"

Authors:
Ariel A Salas

Neonatology 2018 24;113(3):265. Epub 2018 Jan 24.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

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http://dx.doi.org/10.1159/000486126DOI Listing
June 2019

Dose-Response Effects of Early Vitamin D Supplementation on Neurodevelopmental and Respiratory Outcomes of Extremely Preterm Infants at 2 Years of Age: A Randomized Trial.

Neonatology 2018 24;113(3):256-262. Epub 2018 Jan 24.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Many extremely preterm infants have low vitamin D concentrations at birth, but early childhood outcomes after vitamin D supplementation have not been reported.

Objective: To determine a dose-response relationship between increasing doses of enteral vitamin D in the first 28 days after birth and cognitive scores at 2 years of age.

Methods: In this phase II double-blind dose-response randomized trial, infants with gestational ages between 23 and 27 weeks were randomly assigned to receive placebo or a vitamin D dose of 200 or 800 IU/day from day 1 of enteral feeding to postnatal day 28. The primary outcome of this follow-up study was Bayley III cognitive score at 22-26 months of age.

Results: Seventy of 80 survivors had a follow-up evaluation at 2 years of age (88%). There were no significant differences in cognitive scores between supplementation groups (p = 0.47). Cognitive scores did not differ between the higher vitamin D dose group and the placebo group (median difference favoring the 800 IU group: +5 points; 95% CI: -5 to 15; p = 0.23). The linear trend between increasing doses of vitamin D and reduction of neurodevelopmental impairment (placebo group: 54%; 200 IU group: 43%; 800 IU group: 30%; p = 0.08) or language impairment (placebo group: 64%; 200 IU group: 57%; 800 IU group: 45%; p = 0.15) was not statistically significant. Respiratory outcomes at 2 years of age (need for supplemental oxygen or asthma medications) did not differ between groups.

Conclusion: In extremely preterm infants, early vitamin D supplementation did not significantly improve cognitive scores. Though underpowered for clinically meaningful differences in early childhood outcomes, this trial may help determine dosing for further investigation of vitamin D supplementation.
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http://dx.doi.org/10.1159/000484399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860938PMC
September 2019

Transfusion-associated necrotizing enterocolitis in preterm infants: an updated meta-analysis of observational data.

J Perinat Med 2018 Aug;46(6):677-685

University of Alabama at Birmingham, Department of Pediatrics, Birmingham, AL, USA.

Background: The number of observational studies that report an association between packed red blood cell (PRBC) transfusions and necrotizing enterocolitis (NEC) has increased. The primary objective of this study was to evaluate the association between PRBC transfusions and NEC in observational studies.

Methods: Medline, Embase and Cochrane Library databases as well as the Pediatrics Academic Societies abstract archives were systematically searched to identify observational studies that investigated the association between PRBC transfusions and NEC. Key search terms included premature infant, blood transfusion and necrotizing enterocolitis. The generic inverse variance method with a random-effects model was used to meta-analyze selected studies. Odds ratios (ORs) and confidence intervals (CIs) were calculated.

Results: A meta-analysis of 17 observational studies that reported the association between PRBC transfusions and NEC was performed. The meta-analysis revealed no evidence of an association between PRBC transfusions and a higher risk of NEC (OR: 0.96; 95% CI: 0.53-1.71; P=0.88). The effect estimates that suggested an association between PRBC transfusion and NEC in matched case-control studies (OR: 1.20; 95% CI: 0.58-2.47; P=0.63) differed from those reported in cohort studies (OR: 0.51; 95% CI: 0.34-0.75; P=<0.01).

Conclusions: This updated meta-analysis of predominantly low-to-moderate quality observational studies suggests that there is no significant association between PRBC transfusions and NEC. A higher quality of evidence on this topic is needed.
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http://dx.doi.org/10.1515/jpm-2017-0162DOI Listing
August 2018

Short versus Extended Duration of Trophic Feeding to Reduce Time to Achieve Full Enteral Feeding in Extremely Preterm Infants: An Observational Study.

Neonatology 2017 14;112(3):211-216. Epub 2017 Jul 14.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Trophic feeding compared to no enteral feeding prevents atrophy of the gastrointestinal tract. However, the practice of extending the duration of trophic feeding often delays initiation of full enteral feeding in extremely preterm infants. We hypothesized that a short duration of trophic feeding (3 days or less) is associated with early initiation of full enteral feeding.

Methods: A total of 192 extremely preterm infants (23-28 weeks' gestation) born between 2013 and 2015 were included. Infants were divided into 2 groups according to the duration of trophic feeding (short vs. extended). The primary outcome was time to achieve full enteral feeding and the safety outcome was necrotizing enterocolitis (NEC) and/or death.

Results: A short duration of trophic feeding was associated with a reduction in time to achieve full enteral feeding after adjustment for birth weight, gestational age, race, sex, type of enteral nutrition, and day of initiation of trophic feeding (mean difference favoring a short duration of trophic feeding: -4.1 days; 95% CI: -2.3 to -5.8; p < 0.001). A short duration of trophic feeding was not associated with a higher risk of NEC and/or death after achieving full enteral feeding (AOR: 0.91; 95% CI: 0.30-2.77; p = 0.87).

Conclusions: A short duration of trophic feeding is associated with early initiation of full enteral feeding. A short duration of trophic feeding is not associated with a higher risk of NEC, but our study was underpowered for this safety outcome. Randomized trials are needed to test this study hypothesis.
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http://dx.doi.org/10.1159/000472247DOI Listing
June 2018

A Comparison of 3 Vitamin D Dosing Regimens in Extremely Preterm Infants: A Randomized Controlled Trial.

J Pediatr 2016 07 11;174:132-138.e1. Epub 2016 Apr 11.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL. Electronic address:

Objective: To determine the optimal dose of vitamin D supplementation to achieve biochemical vitamin D sufficiency in extremely low gestational age newborns in a masked randomized controlled trial.

Study Design: 100 infants 23 0/7-27 6/7 weeks gestation were randomized to vitamin D intakes of placebo (n = 36), 200 IU (n = 34), and 800 IU/d (n = 30) (approximating 200, 400, or 1000 IU/d, respectively, when vitamin D routinely included in parenteral or enteral nutrition is included). The primary outcomes were serum 25-hydroxy vitamin D concentrations on postnatal day 28 and the number of days alive and off respiratory support in the first 28 days.

Results: At birth, 67% of infants had 25-hydroxy vitamin D <20 ng/mL suggesting biochemical vitamin D deficiency. Vitamin D concentrations on day 28 were (median [25th-75th percentiles], ng/mL): placebo: 22 (13-47), 200 IU: 39 (26-57), 800 IU: 84.5 (52-99); P < .001. There were no differences in days alive and off respiratory support (median [25th-75th percentiles], days): placebo: 1 (0-11), 200 IU: 0 (0-8), and 800 IU: 0.5 (0-22); P = .63, or other respiratory outcomes among groups.

Conclusions: At birth, most extremely preterm infants have biochemical vitamin D deficiency. This biochemical deficiency is reduced on day 28 by supplementation with 200 IU/d and prevented by 800 IU/d. Larger trials are required to determine if resolution of biochemical vitamin D deficiency improves clinical outcomes.

Trial Registration: ClinicalTrials.gov: NCT01600430.
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http://dx.doi.org/10.1016/j.jpeds.2016.03.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925243PMC
July 2016

Gestational age and birthweight for risk assessment of neurodevelopmental impairment or death in extremely preterm infants.

Arch Dis Child Fetal Neonatal Ed 2016 Nov 19;101(6):F494-F501. Epub 2016 Feb 19.

GDB and FU Subcommittee, NICHD Neonatal Research Network, Bethesda, Maryland, USA.

Background: The risk of poor outcomes in preterm infants is primarily determined by birthweight (BW) and gestational age (GA). It is not known whether BW is a better outcome predictor than GA.

Objective: To test whether BW is better than GA (measured in days, rather than completed weeks) for prediction of neurodevelopmental impairment (NDI) and death.

Design/methods: Extremely preterm infants born at the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centres between 1998 and 2009 were studied. For the unadjusted analysis, the associations of GA (in days based on best obstetrical estimate) and BW (in grams) with NDI or death were compared using area under the curve (AUC). Adjusted analyses were performed using birth year, sex, race, antenatal steroids, singleton birth, pre-eclampsia, Apgar score at 5 min and small for GA as covariates.

Results: 10 652 preterm infants (89%) had outcome data at 18-22 months' corrected age. The mean BW was 678 g (SD: 155) and the mean GA was 173 days (SD: 10) or 24 weeks (SD: 1). The AUC for NDI or death was 80% with BW and 79% with GA (p=0.82). Unadjusted and adjusted analyses did not differ. NDI or death rates decreased with increasing GA through 26 weeks (estimated risk reduction with each additional day of gestation: 2.2%).

Conclusion: Both BW in grams and GA in days are good predictors of NDI and death in a preterm population selected on the basis of reliable GA.

Trial Registration Number: NCT00009633.
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http://dx.doi.org/10.1136/archdischild-2015-309670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991950PMC
November 2016

Seasonal Variation in Solar Ultra Violet Radiation and Early Mortality in Extremely Preterm Infants.

Am J Perinatol 2015 Nov 3;32(13):1273-6. Epub 2015 Jun 3.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Vitamin D production during pregnancy promotes fetal lung development, a major determinant of infant survival after preterm birth. Because vitamin D synthesis in humans is regulated by solar ultraviolet B (UVB) radiation, we hypothesized that seasonal variation in solar UVB doses during fetal development would be associated with variation in neonatal mortality rates.

Methods: This cohort study included infants born alive with gestational age (GA) between 23 and 28 weeks gestation admitted to a neonatal unit between 1996 and 2010. Three infant cohort groups were defined according to increasing intensities of solar UVB doses at 17 and 22 weeks gestation. The primary outcome was death during the first 28 days after birth.

Results: Outcome data of 2,319 infants were analyzed. Mean birth weight was 830 ± 230 g and median gestational age was 26 weeks. Mortality rates were significantly different across groups (p = 0.04). High-intensity solar UVB doses were associated with lower mortality when compared with normal intensity solar UVB doses (hazard ratio: 0.70; 95% confidence interval: 0.54-0.91; p = 0.01).

Conclusion: High-intensity solar UVB doses during fetal development seem to be associated with risk reduction of early mortality in preterm infants. Prospective studies are needed to validate these preliminary findings.
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http://dx.doi.org/10.1055/s-0035-1554797DOI Listing
November 2015

A randomised trial of re-feeding gastric residuals in preterm infants.

Arch Dis Child Fetal Neonatal Ed 2015 May 31;100(3):F224-8. Epub 2014 Dec 31.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Objective: To determine whether re-feeding of gastric residual volumes reduces the time needed to achieve full enteral feeding in preterm infants.

Design: Parallel-group randomised controlled trial with a 1:1 allocation ratio.

Setting: Regional referral neonatal intensive care unit.

Patients: 72 infants of gestational age 23(0/7) to 28(6/7) weeks receiving minimal enteral nutrition (<24 mL/kg/day) during the first week after birth.

Interventions: Infants were randomised to either be re-fed with gastric residual volumes (Re-feeding group) or receive fresh formula/human milk (Fresh-feeding group) whenever large gastric residual volumes were noted.

Main Outcome Measure: The primary efficacy end point was time to achieve full enteral feeding (≥120 mL/kg/day) after randomisation.

Results: The mean time to full enteral feeding was 10.0 days in the Re-feeding group and 11.3 days in the Fresh-feeding group (mean difference favouring re-feeding: -1.3 days; 95% CI -2.9 to 0.3; p=0.11). The composite safety end point of spontaneous intestinal perforation, surgical necrotising enterocolitis, or death occurred in 6 of 36 infants (17%) in the Re-feeding group versus 10 of 36 infants (28%) in the Fresh-feeding group (p=0.26).

Conclusions: Re-feeding gastric residual volumes in extremely preterm infants does not reduce time to achieve full enteral feeding. This trial suggests that re-feeding might be as safe as fresh feeding, but further research is needed, due to lack of sufficient statistical power in this study for safety analysis.

Trial Registration Number: NCT01420263NCT01420263.
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http://dx.doi.org/10.1136/archdischild-2014-307067DOI Listing
May 2015

Prophylactic indomethacin and intestinal perforation in extremely low birth weight infants.

Pediatrics 2014 Nov 27;134(5):e1369-77. Epub 2014 Oct 27.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama;

Objective: Prophylactic indomethacin reduces severe intraventricular hemorrhage but may increase spontaneous intestinal perforation (SIP) in extremely low birth weight (ELBW) infants. Early feedings improve nutritional outcomes but may increase the risk of SIP. Despite their benefits, use of these therapies varies largely by physician preferences in part because of the concern for SIP.

Methods: This was a cohort study of 15,751 ELBW infants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from 1999 to 2010 who survived beyond 12 hours after birth. The risk of SIP was compared between groups of infants with and without exposure to prophylactic indomethacin and early feeding in unadjusted analyses and in analyses adjusted for center and for risks of SIP.

Results: Among infants exposed to prophylactic indomethacin, the risk of SIP did not differ between the indomethacin/early-feeding group compared with the indomethacin/no-early-feeding group (adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.49-1.11). The risk of SIP was lower in the indomethacin/early-feeding group compared with the no indomethacin/no-early-feeding group (adjusted RR 0.58, 95% CI 0.37-0.90, P = .0159). Among infants not exposed to indomethacin, early feeding was associated with a lower risk of SIP compared with the no early feeding group (adjusted RR 0.53, 95% CI 0.36-0.777, P = .0011).

Conclusions: The combined or individual use of prophylactic indomethacin and early feeding was not associated with an increased risk of SIP in ELBW infants.
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http://dx.doi.org/10.1542/peds.2014-0183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533280PMC
November 2014

The value of Pa(CO2) in relation to outcome in congenital diaphragmatic hernia.

Am J Perinatol 2014 Nov 10;31(11):939-46. Epub 2014 Feb 10.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Postnatal assessment of disease severity is critical for analysis of mortality rates and development of future interventions in congenital diaphragmatic hernia (CDH).

Objective: The objective of this study was to stratify the risk of mortality based on arterial Paco 2.

Methods: Retrospective analysis of infants (n = 133) with CDH admitted to a regional extracorporeal membrane oxygenation (ECMO) center in two different periods: period I (1987-1996; n = 46) and period II (2002-2010; n = 87).

Results: The mortality rate (37%) was similar in both periods (p = 0.98). Paco 2 < 60 mm Hg in the first arterial blood gas (ABG) was an independent predictor of survival in both periods (p = 0.03). The predicted survival rate was 84% if initial Paco 2 was < 55 mm Hg. For infants with initial Paco 2 > 55 mm Hg treated with ECMO (n = 83), the predicted survival rate was 11% if the Paco 2 was > 88 mm Hg before the initiation of ECMO.

Conclusion: Paco 2, a surrogate of lung hypoplasia, may be useful for risk stratification in CDH. Paco 2 < 60 mm Hg in the first ABG may indicate milder pulmonary hypoplasia. A Paco 2 > 80 mm Hg in the first ABG and/or before ECMO may indicate severe pulmonary hypoplasia.
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http://dx.doi.org/10.1055/s-0034-1368088DOI Listing
November 2014

Oronasopharyngeal suction versus wiping of the mouth and nose at birth: a randomised equivalency trial.

Lancet 2013 Jul 3;382(9889):326-30. Epub 2013 Jun 3.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Wiping of the mouth and nose at birth is an alternative method to oronasopharyngeal suction in delivery-room management of neonates, but whether these methods have equivalent effectiveness is unclear.

Methods: For this randomised equivalency trial, neonates delivered at 35 weeks' gestation or later at the University of Alabama at Birmingham Hospital, Birmingham, AL, USA, between October, 2010, and November, 2011, were eligible. Before birth, neonates were randomly assigned gentle wiping of the face, mouth (implemented by the paediatric or obstetric resident), and nose with a towel (wipe group) or suction with a bulb syringe of the mouth and nostrils (suction group). The primary outcome was the respiratory rate in the first 24 h after birth. We hypothesised that respiratory rates would differ by fewer than 4 breaths per min between groups. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01197807.

Findings: 506 neonates born at a median of 39 weeks' gestation (IQR 38-40) were randomised. Three parents withdrew consent and 15 non-vigorous neonates with meconium-stained amniotic fluid were excluded. Among the 488 treated neonates, the mean respiratory rates in the first 24 h were 51 (SD 8) breaths per min in the wipe group and 50 (6) breaths per min in the suction group (difference of means 1 breath per min, 95% CI -2 to 0, p<0·001).

Interpretation: Wiping the nose and mouth has equivalent efficacy to routine use of oronasopharyngeal suction in neonates born at or beyond 35 weeks' gestation.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(13)60775-8DOI Listing
July 2013

Plastic bags for prevention of hypothermia in preterm and low birth weight infants.

Pediatrics 2013 Jul 3;132(1):e128-34. Epub 2013 Jun 3.

University of Alabama at Birmingham, Birmingham, AL 35249-7335, USA.

Background And Objectives: Hypothermia contributes to neonatal mortality and morbidity, especially in preterm and low birth weight infants in developing countries. Plastic bags covering the trunk and extremities of very low birth weight infants reduces hypothermia. This technique has not been studied in larger infants or in many resource-limited settings. The objective was to determine if placing preterm and low birth weight infants inside a plastic bag at birth maintains normothermia.

Methods: Infants at 26 to 36 weeks' gestational age and/or with a birth weight of 1000 to 2500 g born at the University Teaching Hospital in Lusaka, Zambia, were randomized by using a 1:1 allocation and parallel design to standard thermoregulation (blanket or radiant warmer) care or to standard thermoregulation care plus placement inside a plastic bag at birth. The primary outcome measure was axillary temperature in the World Health Organization-defined normal range (36.5-37.5°C) at 1 hour after birth.

Results: A total of 104 infants were randomized. At 1 hour after birth, infants randomized to plastic bag (n = 49) were more likely to have a temperature in the normal range as compared with infants in the standard thermoregulation care group (n = 55; 59.2% vs 32.7%; relative risk 1.81; 95% confidence interval 1.16-2.81; P = .007). The temperature at 1 hour after birth in the infants randomized to plastic bag was 36.5 ± 0.5°C compared with 36.1 ± 0.6°C in standard care infants (P < .001). Hyperthermia (>38.0°C) did not occur in any infant.

Conclusions: Placement of preterm/low birth weight infants inside a plastic bag at birth compared with standard thermoregulation care reduced hypothermia without resulting in hyperthermia, and is a low-cost, low-technology tool for resource-limited settings.
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http://dx.doi.org/10.1542/peds.2012-2030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691528PMC
July 2013

Histological characteristics of the fetal inflammatory response associated with neurodevelopmental impairment and death in extremely preterm infants.

J Pediatr 2013 Sep 8;163(3):652-7.e1-2. Epub 2013 May 8.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35249, USA.

Objective: To test the hypothesis that increasing severity of the fetal inflammatory response (FIR) would have a dose-dependent relationship with severe neurodevelopmental impairment or death in extremely preterm infants.

Study Design: We report 347 infants of 23-28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or neurodevelopmental impairment at the 18- to 22-month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1, phlebitis; stage 2, arteritis with or without phlebitis; stage 3, subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis).

Results: A FIR was detected in 110 placentas (32%). The rate of severe neurodevelopmental impairment/death was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs 35%; P < .05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with a higher rate of severe neurodevelopmental impairment/death (47% vs 23%; P < .05). After adjustment for confounding factors, only subacute necrotizing funisitis (risk ratio, 1.87; 95% CI, 1.04-3.35; P = .04) and chorionic plate vasculitis with thrombosis (risk ratio, 2.21; 95% CI, 1.10-4.46; P = .03) were associated with severe neurodevelopmental impairment/death.

Conclusion: Severe FIR, characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis, is associated with severe neurodevelopmental impairment/death in preterm infants.
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http://dx.doi.org/10.1016/j.jpeds.2013.03.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744601PMC
September 2013

Prospective analysis of pulmonary hypertension in extremely low birth weight infants.

Pediatrics 2012 Mar 6;129(3):e682-9. Epub 2012 Feb 6.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35249-7335, USA.

Objectives: Pulmonary hypertension is associated with bronchopulmonary dysplasia in extremely low birth weight (ELBW) infants and contributes to morbidity and mortality. The objective was to determine the prevalence of pulmonary hypertension among ELBW infants by screening echocardiography and evaluate subsequent outcomes.

Methods: All ELBW infants admitted to a regional perinatal center were evaluated for pulmonary hypertension with echocardiography at 4 weeks of age and subsequently if clinical signs suggestive of right-sided heart failure or severe lung disease were evident. Management was at discretion of the clinician, and infants were evaluated until discharge from the hospital or pre-discharge death occurred.

Results: One hundred forty-five ELBW infants (birth weight: 755 ± 144 g; median gestational age: 26 weeks [interquartile range: 24-27]) were screened from December 2008 to February 2011. Overall, 26 (17.9%) were diagnosed with pulmonary hypertension at any time during hospitalization (birth weight: 665 ± 140 g; median gestational age: 26 weeks [interquartile range: 24-27]): 9 (6.2%) by initial screening (early pulmonary hypertension) and 17 (11.7%) who were identified later (late pulmonary hypertension). Infants with pulmonary hypertension were more likely to receive oxygen treatment on day 28 compared with those without pulmonary hypertension (96% vs 75%, P < .05). Of the 26 infants, 3 died (all in the late group because of cor pulmonale) before being discharged from the hospital.

Conclusions: Pulmonary hypertension is relatively common, affecting at least 1 in 6 ELBW infants, and persists to discharge in most survivors. Routine screening of ELBW infants with echocardiography at 4 weeks of age identifies only one-third of the infants diagnosed with pulmonary hypertension. Further research is required to determine optimal detection and intervention strategies.
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http://dx.doi.org/10.1542/peds.2011-1827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289526PMC
March 2012

Psychosocial parental support programs and short-term clinical outcomes in extremely low-birth-weight infants.

J Matern Fetal Neonatal Med 2012 Jan 2;25(1):89-93. Epub 2011 Mar 2.

Department of Psychiatry, Miami Children's Hospital, Miami, FL 33155, USA.

Objective: To describe the association between an individualized psychosocial parental support (PPS) program and short-term clinical outcomes of extremely low-birth-weight (ELBW) infants admitted to the neonatal intensive care unit (NICU).

Methods: Medical records of ELBW infants (<1000 g) hospitalized in the NICU at Miami Children's Hospital between July 2006 and June 2008 were reviewed. Outborn infants admitted during their first 72 h of life and discharged home were included. Parents were divided in two groups according to their participation status in the PPS program. Neonatal outcomes in both groups were compared.

Results: Forty-one infants were included (n = 41). Mean gestational age was 26.7±2 weeks, and birth weight was 860±125 g. Median length of stay (LOS) was 96 days (quartile range: 76-112 days). PPS was provided to 33.3% of these infants' parents. The median LOS in the PPS group was significantly lower than in control group (86 vs. 99 days; p < 0.05). No other differences in short-term neonatal outcomes were found.

Conclusions: The addition of individualized psychosocial parent support programs to standard care in the NICU may reduce LOS in surviving infants discharged home. Further larger and randomized prospective studies are needed.
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http://dx.doi.org/10.3109/14767058.2011.557790DOI Listing
January 2012

Acute cerebellar ataxia in childhood: initial approach in the emergency department.

Emerg Med J 2010 Dec 26;27(12):956-7. Epub 2010 Jun 26.

Departamento de Infectologia, Hospital Infantil de Mexico Federico Gomez, Mexico, DF, Mexico.

Acute childhood ataxia is a relatively common presenting complaint in paediatric emergency settings. Because life-threatening causes of pure ataxia are rare in children, an approach in a stepwise fashion is recommended. Acute cerebellar ataxia is the most common cause of childhood ataxia, accounting for about 30-50% of all cases. Varicella is the most commonly associated virus. Post-varicella acute cerebellar ataxia (PVACA) is the most common neurological complication of varicella, occurring about once in 4000 varicella cases among children younger than 15 years of age, even in the postvaccine era. We describe an unimmunised child with PVACA to remind emergency physicians about its autoimmune pathogenesis. We also briefly discuss current controversies about the diagnostic approach and management.
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http://dx.doi.org/10.1136/emj.2009.079376DOI Listing
December 2010

A 7-year-old boy with acute onset of breathing difficulty.

Authors:
Ariel A Salas

Pediatr Emerg Care 2010 Feb;26(2):149-51

Department of Pediatrics, Hospital Agramont, La Paz, Bolivia.

Group A streptococcus (GAS) is a major bacterial pathogen affecting children globally. Approximately 15% of school-age children experience a symptomatic episode of GAS culture-positive pharyngitis each year. Although the incidence of invasive GAS disease under these circumstances is low (0.5%-2%), an increasing number of invasive GAS cases have been reported over the last 2 decades. This report describes a 7-year-old boy who, after being treated for GAS pharyngitis, developed a fatal streptococcal toxic shock syndrome.
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http://dx.doi.org/10.1097/PEC.0b013e3181d0a04eDOI Listing
February 2010

Significant weight loss in breastfed term infants readmitted for hyperbilirubinemia.

BMC Pediatr 2009 Dec 31;9:82. Epub 2009 Dec 31.

Division of Pediatrics, Caja Petrolera de Salud Clinic, 2525 Arce Ave, San Jorge, La Paz, Bolivia.

Background: Weight loss of greater than 7% from birth weight indicates possible feeding problems. Inadequate oral intake causes weight loss and increases the bilirubin enterohepatic circulation. The objective of this study was to describe the association between total serum bilirubin (TSB) levels and weight loss in healthy term infants readmitted for hyperbilirubinemia after birth hospitalization.

Methods: We reviewed medical records of breastfed term infants who received phototherapy according to TSB levels readmitted to Caja Petrolera de Salud Clinic in La Paz, Bolivia during January 2005 through October 2008.

Results: Seventy-nine infants were studied (64.6% were males). The hyperbilirubinemia readmission rate was 5% among breastfed infants. Term infants were readmitted at a median age of 4 days. Mean TSB level was 18.6 +/- 3 mg/dL. Thirty (38%) had significant weight loss. A weak correlation between TSB levels and percent of weight loss was identified (r = 0.20; p < 0.05). The frequency of severe hyperbilirubinemia (> 20 mg/dL) was notably higher among infants with significant weight loss (46.7% vs. 18.4%; p < 0.05). The risk of having severe hyperbilirubinemia was approximately 4 times greater for infants with significant weight loss (OR: 3.9; 95% CI: 1.4-10.8; p < 0.05).

Conclusions: Significant weight loss could be a useful parameter to identify breastfed term infants at risk of severe hyperbilirubinemia either during birth hospitalization or outpatient follow-up visits in settings where routine pre-discharge TSB levels have not been implemented yet.
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http://dx.doi.org/10.1186/1471-2431-9-82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806254PMC
December 2009

Haemophilusinfluenzae type b conjugate vaccine for preventing pneumonia in infants hospitalized for bronchiolitis: a case-control study.

Int J Infect Dis 2010 Jan 3;14(1):e68-72. Epub 2009 Jun 3.

Division of General Pediatrics, Clinica Caja Petrolera de Salud, 2525 Arce Ave., PO Box 3943, San Jorge, La Paz, Bolivia.

Background: Haemophilus influenzae type b (Hib) conjugate vaccine reduces the risk of pneumonia in infants.

Objective: To determine the effect of Hib conjugate vaccine (HibCV) on the prevention of pneumonia as a complication among infants hospitalized for bronchiolitis.

Methods: This record-based case-control study was conducted at The Children's Hospital "Dr. Ovidio Aliaga U" in La Paz, Bolivia during 2003 and 2004. Cases were infants hospitalized for bronchiolitis under 1 year of age who developed radiological pneumonia during hospitalization. Controls were patients who had good clinical progress without the use of antibiotics. Pneumonia was defined by alveolar consolidation on chest X-ray that justified the use of antibiotics.

Results: Eighty patients were studied (16 cases and 64 controls). Their median age was 4.5 months. Demographic and clinical features were similar in both groups, except for a higher proportion of vomiting (56.3% vs. 28.1%; p<0.05) in the case group. The percentage of unvaccinated infants was significantly higher in cases (68.8% vs. 26.6%; p<0.05) and the length of hospital stay longer (8.5+/-5.4 vs. 3.1+/-2.2 days; p<0.05). There was a strong association between unvaccinated infants and the occurrence of pneumonia as a complication (odds ratio 6.1, 95% confidence interval 1.8-20.1; p<0.01).

Conclusions: Unvaccinated infants admitted for bronchiolitis have a higher risk of radiologically confirmed pneumonia. Larger studies are needed to validate these results and reconsider the burden of Hib infection among infants in less developed countries.
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http://dx.doi.org/10.1016/j.ijid.2009.03.011DOI Listing
January 2010