Pediatrix Medical Group BabySteps and the Clinical Data Warehouse

Pediatrix Medical Group BabySteps and the Clinical Data Warehouse Pediatrix Medical Group Reese H Clark MD Dan Ellsbury MD Alan Spitzer MD Duke Clinical Research Institute Brian Smith MD MPH MHS Danny Benjamin MD PhD MPH

Pediatrix Medical Group Pediatrix Medical Group 1200 neonatologists 278 NICUs 33 states 20-25% of infants admitted to NICUs in the US

Pediatrix Electronic Medical Record (EMR) Launched in 1996 BabySteps - proprietary system developed by Pediatrix Clinical documentation system used to create clinical notes Used across 278 Pediatrix sites Data collected daily until discharge. Used for research, education, and quality improvement

Pediatrix Electronic Medical Record (EMR) Clinical Data Warehouse Data transferred daily from BabySteps > 600,000 infants 11,000,000 patient days Reports on aspects of care, morbidities and mortality at individual centers Queried by FDA, NIH, and academic neonatology programs.

BabySteps to Research Database

Variables in Research Database Demographics Inborn status Birth weight Gestational age Sex Race/ethnicity Admit year Apgar scores Maternal variables Maternal age Maternal serologies Delivery type Duration of rupture of membranes Medications (antibiotics, steroids)

Variables in Research Database Diagnoses Congenital anomalies Necrotizing enterocolitis Spontaneous intestinal perforation Patent ductus arteriosus/ligation Intraventricular hemorrhage Chronic lung disease Labs Lab values chemistries, LFTs, hematology Culture results Respiratory Support FiO2

Variables in Research Database Therapeutics Drug name Start/stop day Feedings Type Start/stop days Volume Outcomes Mortality Day of discharge Discharge growth parameters

Publications Diagnosis Ansong, et al. Group B streptococcal meningitis: cerebrospinal fluid parameters in the era of intrapartum antibiotic prophylaxis. Early Hum Dev 2009. Benjamin, et al. Empirical therapy for neonatal candidemia in very low birth weight infants. Pediatrics 2003. Cohen-Wolkowiez, et al. Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures. J Perinatol 2007. Garges, HP, et al. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters? Pediatrics 2006. Greenberg, et al. Traumatic lumbar punctures in neonates: test performance of the cerebrospinal fluid white blood cell count. Pediatr Infect Dis J 2008. Lenfestey, et al. Predictive value of cerebrospinal fluid parameters in neonates with intraventricular drainage devices. J Neurosurg 2007. Smith, et al. A comparison of neonatal Gram-negative rod and Gram-positive cocci meningitis. J Perinatol 2006. Smith, et al. Meningitis in preterm neonates: importance of cerebrospinal fluid parameters. Am J Perinatol 2008. Nutrition Bloom, et al. Improving growth of very low birth weight infants in the first 28 days. Pediatrics 2003. Clark, Interneonatal intensive care unit variation in growth rates and feeding practices in healthy moderately premature infants. J Perinatol 2005. Clark, et al. Extrauterine growth restriction remains a serious problem in prematurely born neonates. Pediatrics 2003. Olsen, et al. New intrauterine growth curves based on United States data. Pediatrics. Powers, Site of care influences breastmilk feedings at NICU discharge. J Perinatol 2003.

Publications Epidemiology Abrams, et al. Hydrops fetalis: a retrospective review of cases reported to a large national database and identification of risk factors associated with death. Pediatrics 2007. Benjamin, et al. Mortality following blood culture in premature infants: increased with Gram-negative bacteremia and candidemia, but not Gram-positive bacteremia. Journal of Perinatology 2004. Benjamin, et al. Postconception age and other risk factors associated with mortality following Gram-negative rod bacteremia. J Perinatol 2004. Clark, et al. Prevalence of gastroschisis and associated hospital time continue to rise in neonates who are admitted for intensive care. J Pediatr Surg 2009. Cohen-Wolkowiez, et al. Early and late onset sepsis in late preterm infants. Pediatr Infect Dis J 2009. Garite, et al. JA Intrauterine growth restriction increases morbidity and mortality among premature neonates. Am J Obstet Gynecol 2004. Garite, et al. Twins and triplets: the effect of plurality and growth on neonatal outcome compared with singleton infants. Am J Obstet Gynecol 2004. Guthrie, et al. Necrotizing enterocolitis among neonates in the United States. J Perinatol 2003. Laughon, et al. Rising birth prevalence of gastroschisis. J Perinatol 2003. Paranka, et al. Are very low birth weight infants born at high altitude at greater risk for adverse outcomes? J Pediatr 2001. Perfect Sychowski, et al. Home apnea monitor use in preterm infants discharged from newborn intensive care units. J Pediatr 2001. Singh, et al. Meconium aspiration syndrome remains a significant problem in the NICU: outcomes and treatment patterns in term neonates admitted for intensive care during a ten-year period. J Perinatol 2009. Thomas, et al. A new look at intrauterine growth and the impact of race, altitude, and gender. Pediatrics 2000. Walker, et al. Elevation in plasma creatinine and renal failure in premature neonates without major anomalies: terminology, occurrence and factors associated with increased risk. J Perinatol

Publications Drug Safety Attridge. PV New insights into spontaneous intestinal perforation using a national data set (3): antenatal steroids have no adverse association with spontaneous intestinal perforation. J Perinatol 2006. Attridge. New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure. J Perinatol 2006. Attridge. New insights into spontaneous intestinal perforation using a national data set: (2) two populations of patients with perforations. J Perinatol 2006. Clark. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics 2006. Farkouh. Antenatal magnesium exposure and neonatal demise. Am J Obstet Gynecol 2001. Thorp. Does antenatal steroid therapy affect birth weight and head circumference? Obstet Gynecol 2002. Thorp. Effect of antenatal and postnatal corticosteroid therapy on weight gain and head circumference growth in the nursery. Obstet Gynecol 2002. Yoder. Time-related changes in steroid use and BPD in preterm infants. Pediatrics 2009. Clark. Patience is a virtue in the management of gastroesophageal reflux. J Pediatr 2009.

Publications - Effectiveness Clark, et al. A comparison of the outcomes of neonates treated with 2 different natural surfactants. J Pediatr 2001. Laughon, et al. Treatment strategies to prevent or close a PDA in preterm infants and outcomes. J Perinatol 2007. Laughon, et al. R Treatment strategies to prevent or close a patent ductus arteriosus in preterm infants and outcomes. J Perinatol 2007

Publications - Prescribing Arnold. Variability in vancomycin use in newborn intensive care units determined from data in an electronic medical record. Infect Control Hosp Epidemiol 2008. Clark. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 2006. Clark. The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit. J Perinatol Linn. Increasing supplemental thyroid hormone use among premature infants born at 23 to 32 weeks gestation. Am J Perinatol

Prescribing Practices Rank Medication name Days exposed Rank Medication name Days exposed 1 Ampicillin 186,799 7 Beractant 36,410 2 Gentamicin 171,388 8 Metoclopramide 27,541 3 Cefotaxime 55,455 9 Dopamine 25,839 4 Caffeine 48,814 10 Ranitidine 23,905 5 Furosemide 47,278 11 Indomethacin 20,605 6 Vancomycin 44,218 12 Dexamethasone 20,398 Clark, Pediatrics, 2006.

Comparative Effectiveness Antibiotic Selection: 1st 3 days of Life Clark RH, Pediatrics, 2006

Comparative Effectiveness Adjusted OR for death for cefotaxime vs. gentamicin = 1.5 [1.4, 1.7] Clark RH, Pediatrics, 2006

Percent of Discharges Cefotaxime Use 20 Cefotaxime (Day 0,1or 2) Cefotaxime (Day 3 to 7) Cefotaxime Start Day >7th day Any Report of Cefotaxime 15 10 5 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 Year of Discharge

Ongoing Therapeutics Projects using Pediatrix Clinical Data Warehouse Outcomes by antifungal following Candida infections Safety of antifungals liver function tests Outcomes following use of ibuprofen vs. indomethacin for treatment of PDA Blood culture and antimicrobial timing Neonatal Therapeutics and Incorporation of Best Practices

FDA questions - Regarding your database/network/system.. How specific is your demographic information? Can you document therapeutic use and indication? Can you document hospitalizations due to AEs? Can you identify AEs to drugs, dose, schedule, formulation and route? Can you determine con meds? Can you determine OTC meds in patients who reported an AE? At the origin of the AE, what type of physician did the patient see? Where was the AE reported? Is there verification of cause of death? Will you be able to know the distribution of AEs across age subpopulations? Is there comparative pediatric AE reporting in adult vs. non-adult facilities? yes yes n/a yes yes n/a yes yes no yes no

FDA questions - Does your database/network/system Have staff that routinely monitors, investigates and verifies specific AEs? Investigates the cause of AEs through epidemiologic or genomic studies? Automatically detects AEs through criteria that trigger an investigation? Link data to EMRs? Record age of patients with great granularity? Record growth data (weight, height, head circumference)? Record birth history of patients? Record AEs in high-level terms, preferred terms, low-level terms? Register a unique patient identifier that permits long-term data analysis? Record costs of visits to hospitals, clinics, or ED? Record costs of treating AEs? no no no no yes yes yes no yes* no yes*