
Haresh KirpalaniThe Children's Hospital of Philadelphia | CHOP
Haresh Kirpalani
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Publications (313)
Background
Bronchopulmonary dysplasia (BPD) affects up to half of extremely preterm infants, and is associated with adverse long-term respiratory, neurodevelopmental, and educational sequelae and costly health service and family economic outcomes. The NICHD Neonatal Research Network Hydrocortisone for Bronchopulmonary Dysplasia (BPD) Trial evaluate...
Importance
Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants.
Objective
To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC amo...
Background
Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchron...
Missing outcome data in clinical trials may jeopardize the validity of the trial results and inferences for clinical practice. Although sick and preterm newborns are treated as a captive patient population during their stay in the NICUs, their long-term outcomes are often ascertained after discharge. This greatly increases the risk of attrition. We...
Aim
Infants and children who require specialized medical attention are admitted to neonatal and pediatric intensive care units (ICUs) for continuous and closely supervised care. Overnight in-house physician coverage is frequently considered the ideal staffing model. It remains unclear how often this is achieved in both pediatric and neonatal ICUs i...
Importance
Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes.
Objective
To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue satura...
Objectives:
Inhaled nitric oxide (iNO) is an effective pulmonary vasodilator. However, the efficacy of iNO in former premature infants with established bronchopulmonary dysplasia (BPD) has not been studied. This study aimed to determine the efficacy of iNO in reducing pulmonary artery pressure in infants with severe BPD as measured by echocardiogr...
Background:
Nasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. Nasal intermittent positive pressure ventilation (NIPPV) can augment NCPAP by delivering ventilator breaths via nasal prongs.
Objectives:
Primary objective To determine the effects of management with NIPPV versus N...
Background:
Nasal continuous positive airway pressure (NCPAP) is a strategy to maintain positive airway pressure throughout the respiratory cycle through the application of a bias flow of respiratory gas to an apparatus attached to the nose. Early treatment with NCPAP is associated with decreased risk of mechanical ventilation exposure and might r...
Evidence‐based medicine has changed clinical practice by incorporating data from randomised controlled trials (RCTs). While some biases in RCTs are well recognised, we discuss some less acknowledged. Selection bias may arise in the consent stage. Industry‐funded studies more often report a positive outcome. Post‐hoc changes of outcome measures and...
Introduction:
Lung biopsy is infrequently performed in the population of infants with severe bronchopulmonary dysplasia (BPD). Yet, its presentation may overlap with other infant diffuse lung diseases, including those within the spectrum of childhood interstitial lung diseases (chILD). Lung biopsy might differentiate between these entities or iden...
Introduction:
Low pressure nasal continuous positive airway pressure (nCPAP) has long been the mainstay of non-invasive respiratory support for preterm neonates, at a constant distending pressure of 5-8 cmH2O. When traditional nCPAP pressures are insufficient, other modes including nasal intermittent positive pressure ventilation (NIPPV) are used....
Introduction Lung biopsy is infrequently utilized in the population of infants with severe bronchopulmonary dysplasia (BPD). Yet, its presentation may overlap with other infant diffuse lung diseases, including those within the spectrum of childhood interstitial lung diseases (chILD). Lung biopsy might differentiate between these entities, or discer...
Importance
Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.
Objective
To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age.
Design, Setting, and Participants
This cohort study is a secondary analysis...
Objective:
Survival rates of extremely premature infants are rising, but changes in neurodevelopmental impairment (NDI) rates are unclear. Our objective was to perform a systematic review of intrainstitutional variability of NDI over time.
Design:
Systematic review and meta-analysis.
Data sources:
Ovid MEDLINE, Embase, PubMed, Cochrane Library...
Importance
The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials.
Objective
To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal st...
Objective
To measure within-subject changes in ventilation/perfusion (V′/Q′) mismatch in response to a protocol of individualised nasal continuous positive airway pressure (CPAP) level selection.
Design
Single-arm, non-randomised, feasibility trial.
Setting
Three centres in the Children’s Hospital of Philadelphia neonatal care network.
Patients...
Introduction:
Approximately, one in ten infants is born preterm or requires hospitalization at birth. These complications at birth have long-term consequences that can extend into childhood and adulthood. Timely detection of developmental delay through surveillance could enable tailored support for these babies and their families. However, the pos...
Background:
Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined.
Methods:
A prospective study of ELBW preterm infants utilized NIRS monito...
Continuous distending pressure (CDP) is a pressure applied to the airways throughout the respiratory cycle. This chapter focuses on the non-invasive use of CDP using continuous positive airway pressure (CPAP). The underlying pathophysiology of treated conditions, indications and potential harms related to CPAP are discussed. Devices and interfaces...
This chapter covers methods of assisted ventilation without an endotracheal tube in the trachea and using interfaces either just at the nares or sealing the entire nose with a mask. These methods can deliver positive pressure throughout the respiratory cycle with additional intermittent increases in the airway pressure. This additional intermittent...
Background:
Preterm infants are at risk of lung atelectasis due to various anatomical and physiological immaturities, placing them at high risk of respiratory failure and associated harms. Nasal continuous positive airway pressure (CPAP) is a positive pressure applied to the airways via the nares. It helps prevent atelectasis and supports adequate...
( Neonatology. 2019;115:406–410)
Practices for the transfusion for preterm infants vary widely between centers and there is a lack of consensus on the best approach. There is only a small amount of randomized controlled trial (RCT) evidence available, but 2 larger trials comparing high and low hemoglobin transfusion levels will report their finding...
Objective
To characterize respiratory function monitor (RFM) measurements of sustained inflations and intermittent positive pressure ventilation (IPPV) delivered non-invasively to infants in the Sustained Aeration of Infant Lungs (SAIL) trial and to compare vital sign measurements between treatment arms.
Study design
We analyzed RFM data from SAIL...
( N Engl J Med . 2020;383:2639–2651)
Extremely-low birthweight infants are commonly treated with packed red-cell transfusions to treat low hemoglobin, but transfusion protocols vary. Randomized control trial (RCT) evidence is limited, and more evidence is needed to evaluate low and high hemoglobin thresholds in terms of complications. This study, i...
Background
Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.
Methods
We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6...
Objectives
To measure between-center variation in loop diuretic use for infants developing severe bronchopulmonary dysplasia (BPD) in United States children’s hospitals, and to compare mortality and age at discharge among infants from low versus high use centers.
Study design
We performed a retrospective cohort study of preterm infants <32 weeks g...
Objective
To identify sociodemographic and clinical factors associated with withholding or withdrawing life-sustaining treatment (WWLST) for extremely low gestational age neonates.
Design
Observational study of prospectively collected registry data from 19 National Institute of Child Health and Human Development Neonatal Research Network centres o...
Objectives:
Overnight physician staffing in the ICU has been recommended by the Society of Critical Care Medicine and the Leapfrog Consortium. We conducted a survey to review practice in the current era and to compare this with results from a 2006 survey.
Design:
Cross-sectional survey.
Setting:
Canadian adult ICUs.
Participants:
ICU directo...
Objectives:
To evaluate the survival and neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants at 18 to 26 months with early hypoxemic respiratory failure (HRF). We also assessed whether African American infants with early HRF had improved outcomes after exposure to inhaled nitric oxide (iNO).
Methods:
ELBW infants ≤10...
Objectives
To compare the number of intermittent hypoxia events before and after packed red blood cell (pRBC) and non-pRBC transfusions in very low birth weight infants, and to compare the time spent with saturations of ≤85% before and after transfusions in the same population.
Study design
This prospective observational study was conducted from A...
Importance
Most preterm infants require respiratory support to establish lung aeration after birth. Intermittent positive pressure ventilation and continuous positive airway pressure are standard therapies. An initial sustained inflation (inflation time >5 seconds) is a widely practiced alternative strategy.
Objective
To conduct a systematic revie...
The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study showed that the addition of postnatal weight gain to birth weight and gestational age detects similar numbers of infants with ROP, but requires examination of fewer infants.
To determine the incremental cost-effectiveness of screening with G-ROP compared with conventional screening....
Objective:
To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).
Study design:
We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of post...
Rationale:
Bronchopulmonary dysplasia (BPD) is a heterogenous condition with poorly characterized disease subgroups.
Objectives:
To define the frequency of three disease components: moderate-severe parenchymal disease, pulmonary hypertension (PH), or large airway disease, in a referral cohort of preterm infants with severe BPD. The association b...
Extreme prematurity is associated with an increased risk to develop bronchopulmonary dysplasia (BPD). Severe BPD is associated with a significant long-term burden for the affected infant, families and society. Currently there are limited prevention and treatment options. Regenerative approaches using mesenchymal stromal cells (MSC) are associated w...
This article explores the validity of the Sustained Aeration Inflation for Infant Lungs (SAIL) randomized controlled clinical trial. The SAIL trial enrolled 460 infants out of a planned 600, but the trial was stopped early for harm. We ask here, whether there were any threats to validity in the trial as conducted. We then explore what design elemen...
Objective
Compare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia.
Design
N-of-1 multiple crossover trials with individual patient and pooled data analyses.
Setting
Level IV intensive care nursery.
Patients
Infants receiving positive airway pressure between 36 and 55 wee...
Reducing the risk of primary noninvasive ventilation failure in extremely low birthweight infants is linked to reducing bronchopulmonary dysplasia. In a secondary analysis of randomized data, we identified that failure rates and time to failure were similar for nasal intermittent positive pressure ventilation vs nasal continuous positive airway pre...
Objective:
To identify the number of cumulative medication exposures and most frequently used medications in infants with severe BPD.
Study design:
We performed a retrospective cohort study in infants with severe BPD admitted to United States children's hospitals. We measured cumulative medication exposures in individual subjects and between-cen...
Objective:
To evaluate neurodevelopmental outcomes of preterm infants with need for Child Protective Services (CPS) supervision at hospital discharge compared with those discharged without CPS supervision.
Study design:
For infants born at <27 weeks of gestation between 2006 and 2013, prospectively collected maternal and neonatal characteristics...
Differences in preterm birth rates between black and white women are the largest contributor to racial disparities in infant mortality. In today’s age of precision medicine, analysis of the genome, epigenome, metabolome, and microbiome has generated interest in determining whether these biomarkers can help explain racial disparities. We propose tha...
Objectives:
We aimed to determine the accuracy and validity of the Ultrasonic Cardiac Output Monitor (USCOM) measurements of cardiac output (CO) compared to echocardiography in newborn infants, and the inter-rater agreement of USCOM measurements.
Methods:
In a single-center study we prospectively evaluated neonates undergoing an echocardiographi...
Background:
The natural history and optimal management of a patent ductus arteriosus (PDA) among infants with established severe bronchopulmonary dysplasia (sBPD) remains uncertain.
Objectives:
To describe the characteristics of PDA present at ≥36 weeks' postmenstrual age (PMA) and the effects of late surgical PDA closure in a referral cohort of...
Continuous positive airway pressure (CPAP), noninvasive intermittent positive pressure ventilation (NIPPV), and heated humidified high-flow nasal cannula (HHFNC) are modes of noninvasive respiratory support used in neonatal practice. These modes of noninvasive respiratory support may obviate mechanical ventilation, prevent extubation failure, and r...
Background:
Premature infants with severe bronchopulmonary dysplasia (sBPD) are at risk of pulmonary hypertension (PH). Serum brain natriuretic peptide (BNP) is used to predict disease severity in adult PH. Its diagnostic utility in sBPD-associated PH is unknown.
Objective:
The aim of this paper was to determine the accuracy of BNP, against echo...
Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity.
Objectives: To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define diseas...
Currently the question of whether to maintain a higher hemoglobin level by transfusing more liberally, as opposed to a more restrictive strategy with lower hemoglobin maintenance levels, has not been answered. We review summarized conclusions of a Cochrane systematic review and meta-analysis of 614 infants in 4 randomized controlled trials (RCT) po...
Rationale
Infants with severe bronchopulmonary dysplasia (sBPD) and airway obstruction may develop dynamic hyperinflation and intrinsic positive end‐expiratory pressure (PEEPi), which impairs patient/ventilator synchrony.
Objectives
To determine if PEEPi is present in infants with sBPD during spontaneous breathing and if adjusting ventilator PEEP...
Objective:
To assess decisional conflict and knowledge about prematurity among mothers facing extreme premature delivery when the counseling clinicians were randomized to counsel using a validated decision aid compared with usual counseling.
Study design:
In this randomized trial, clinicians at 5 level III neonatal intensive care units in the US...
Importance
Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations.
Objective
To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or...
Background:
Conventional mechanical ventilation (CMV) is a common therapy for neonatal respiratory failure. While CMV facilitates gas exchange, it may simultaneously injure the lungs. Positive end-expiratory pressure (PEEP) has received less attention than other ventilation parameters when considering this benefit-risk balance. While an appropriat...
Objective:
We studied decision making regarding inhaled nitric oxide (iNO) in preterm infants with Pulmonary Hypertension (PH).
Study design:
We asked members of the AAP-Society of Neonatal-Perinatal Medicine and Division-Chiefs to select from three management options- initiate iNO, engage parents in shared decision making or not consider iNO in...
Background: It is unknown whether observational studies comparing laparotomy versus peritoneal drainage for surgical treatment of necrotizing enterocolitis (NEC) in preterm infants differ from randomized controlled trials (RCTs) of the same interventions. Further, in the absence of sufficient RCT evidence, it is uncertain how best to use existing o...
Objective:
To assess parents' views of their children's health-related quality of life (HRQoL) and the association between neonatal morbidities and HRQoL in children with severe bronchopulmonary dysplasia (BPD) who survived to 18-36 months of corrected age.
Study design:
Study population included infants born <32 weeks of gestational age with se...
Objective:
To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight.
Study design:
This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33...
Objectives
This study tested the hypothesis that longer duration of any type of respiratory support is associated with an increased rate of death or neurodevelopmental impairment (NDI) at 18‐22 months.
Methods
Retrospective cohort study using the Generic Database of NICHD Neonatal Research Network from 2006 to 2010. Infants were born at <27 weeks...
Objective How Latino parents perceive and understand antenatal counseling for extreme prematurity, < 26 weeks of gestational age (GA), is not clear. We aim to characterize Latino parental perceptions of antenatal counseling in order to construct and validate a Spanish decision-aid (SDA) to improve parental knowledge of prematurity after antenatal c...
Objectives
To examine growth, sedation needs, and participation in developmental activities before and after tracheostomy among infants with severe bronchopulmonary dysplasia.
Methods
Retrospective analysis of infants born at <32 weeks’ gestation or birth weights <1500 g with severe BPD who underwent tracheostomy placement between January 1, 2010...
To describe balloon catheter occlusion of hyperinflated portions of lung. In six eligible infants, imaging showed severe air trapping from hyperinflated lobes of lung. To determine if surgical removal of the lobe would improve pulmonary function, a catheter was inserted with bedside bronchoscopy. With the balloon inflated, the patient's gas exchang...
Aim:
To assess in children with severe bronchopulmonary dysplasia at a corrected age of 18-36 months: 1)Neonatal follow-up clinic attendance rates; 2)Parent-identified reasons for difficulty attending neonatal follow-up.
Methods:
Mixed methods study utilizing semi-structured phone interviews with parents of infants eligible for follow-up with se...
Objective:
To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies.
Study design:
Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 we...
Objectives:
To describe the frequency and extent of delivery room resuscitation and evaluate the association of delivery room resuscitation with neonatal outcomes in moderately preterm (MPT) infants.
Study design:
This was an observational cohort study of MPT infants delivered at 290/7 to 336/7 weeks' gestational age (GA) enrolled in the Neonata...
Background:
To develop and test a decision aid for counseling parents of children with bronchopulmonary dysplasia (BPD).Local problem:Parental education about complex conditions is not standardized and communication and understanding may not be adequate.
Methods:
Semi-structured interviews were conducted with 33 neonatal clinicians and 12 parent...
Objective:
To test the hypothesis that significant positive end-expiratory pressure (PEEP) level variation exists between neonatal centers.
Study design:
We performed a secondary analysis cohort study of the Nasal Intermittent Positive-Pressure Ventilation trial. Our study population was extremely low birth weight infants requiring mechanical ve...
Background
Congenital diaphragmatic hernia (CDH) is commonly associated with pulmonary hypoplasia and pulmonary hypertension (PH). PH associated with CDH (CDH-PH) is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO) possibly due to right and left ventricular dysfunction. Milrinone is an intraven...
Shared decision-making is a recent priority in neonatology. However, its implementation is at an early stage. Decision aids are tools designed to assist in shared decision-making. They help patients competently participate in making healthcare decisions. There are limited studies in neonatology on the formal use of decision aids as used in adult me...
Objective:
To assess the impact of the latest randomized controlled trial (RCT) to each systematic review (SR) in Cochrane Neonatal Reviews.
Study design:
We selected meta-analyses reporting the typical point estimate of the risk ratio for the primary outcome of the latest study (n=130), mortality (n=128) and the mean difference for the primary...
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of "high" (> 5 cmH2O) vs "low" (≤ 5 cmH2O) initial NCPAP pressure levels in preterm VLBW infants receiving NCPAP a) for initial respiratory support following birth and neonatal resuscitation or b) following MV and endotracheal extubation. ©...