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ORIGINAL RESEARCH |
From the Department of Pediatrics, University of British Columbia, Vancouver, British Columbia; Centre for Community Health and Health Evaluation Research, Vancouver, British Columbia; Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia; and Department of Pediatrics, Memorial University of Newfoundland, St John’s, Newfoundland, Canada.
Address reprint requests to: Shoo K. Lee, MBBS, FRCPC, PhD, Coordinator, Canadian Neonatal Network, Canadian Neonatal Network Coordination Center, 4480 Oak Street, Room E-414, Vancouver, British Columbia V6H 3V4, Canada; E-mail: shool{at}interchange.ubc.ca.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: Logistic regression analysis was used to compare the risk-adjusted outcomes of 3769 singleton infants born at or before 32 weeks’ gestation, who were admitted to 17 Canadian NICUs during 1996–1997.
RESULTS: Outborn and inborn infants had significantly different gestational ages, perinatal risk factors (maternal hypertension, prenatal care, antenatal corticosteroid therapy, 5-minute Apgar score, delivery type, small for gestational age) and admission SNAP-II. Outborn infants were at higher risk of death (adjusted odds ratio [OR] 1.7, 95% confidence interval [CI] 1.2, 2.5), grade III or IV intraventricular hemorrhage (adjusted OR 2.2, 95% CI 1.5, 3.2), patent ductus arteriosus (adjusted OR 1.6, 95% CI 1.2, 2.1), respiratory distress syndrome (adjusted OR 4.8, 95% CI 3.6, 6.3), and nosocomial infection (adjusted OR 2.5, 95% CI 1.9, 3.3), even after adjusting for perinatal risks and admission illness severity.
CONCLUSIONS: Outborn infants were less mature and more ill than inborn infants at NICU admission. However, even after adjustment for perinatal risks and admission illness severity, inborn infants had better outcomes than outborn infants. Our results support in-utero transfer of high-risk pregnancies to a tertiary level facility.
Preterm infants are at high risk of mortality and morbidity.1 Outcomes of preterm infants were significantly improved with the introduction of neonatal intensive care units (NICUs) in the 1960s, regionalization of perinatal care in the 1970s, and introduction of artificial surfactant therapy in the 1980s.2–4 Regionalization resulted in increased emphasis on transfer of at-risk mothers to perinatal centers before delivery of the infant, instead of transferring infants after they were born.5,6 Yet, Lee et al1 reported that in 1996–1997, 20% of preterm infants admitted to Canadian NICUs were delivered outside tertiary centers (outborn).
Most previous studies reported higher survival rates of preterm and low birth weight infants born in tertiary perinatal centers (inborn) than infants born elsewhere (outborn).7,8 Compared with inborn infants, outborn infants also had higher rates of intraventricular hemorrhage, infection, hypothermia, pulmonary hypertension, hypoechogenic periventricular leucomalacia, and necrotizing enterocolitis.9,10 At age 2 years, inborn children with low birth weight showed higher rates of survival without impairment and lower prevalence of serious functional handicap.11,12 However, few of the previous studies adequately adjusted for perinatal factors. For example, two of four recent studies did not adjust for any perinatal risk factors9,10 and the other two only adjusted for birth weight and gestational age.7,8 None of the studies considered illness severity of the infant at the time of NICU admission, which has been shown to be predictive of neonatal outcomes.1 Consequently, their findings of higher mortality and morbidity among outborn infants might be due to differences in perinatal risks and illness severity of infants admitted to NICUs compared with inborn infants. In addition, the use of single hospital samples with limited sample size (range of n = 329 to 720) by many studies7,9,10 limit the generalizability of their results.
The objectives of this study were to examine the relationships between inborn or outborn status and neonatal morbidity and mortality among a large cohort of preterm infants admitted to 17 Canadian NICUs, after adjusting for perinatal risk factors and admission illness severity.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Trained research assistants prospectively abstracted patient information from the mothers’ and infants’ charts at each participating hospital on a daily basis. Details of data collection and management have been published.1 This study was approved by institutional review boards at all 17 sites.
Patient information included demographic information (sex), perinatal risk factors (gestational age, Apgar score at 5 minutes, small for gestational age, delivery type, maternal hypertension, presentation, antenatal corticosteroid therapy, and prenatal care), admission illness severity,15 and selected patient outcomes, including death during stay in the NICU. Study variables were defined according to the Canadian Neonatal Network SNAP (Score for Neonatal Acute Physiology) Project ABSTRACTor Manual. Gestational age was defined as the best obstetric estimate based on early prenatal ultrasound, obstetric examination, and obstetric history, unless the postnatal pediatric estimate of gestation differed from the obstetric estimate by more than 2 weeks. In that case, the best estimate of the attending neonatologist or the pediatric estimate of gestational age based on the Ballard score16 was used instead. An infant was defined as small for gestational age if the birth weight was less than the third percentile for gestational age according to the British Columbia provincial growth charts established by Whitfield17 in 1992. The Score for Neonatal Acute Physiology, Version II (SNAP-II)15 is a neonatal illness severity score calculated from six empirically weighted physiologic measurements (blood pressure, temperature, seizures, urine output, ratio of arterial oxygen tension to fraction of inspired oxygen, and serum pH) made during the first 12 hours of admission to the NICU. Chronic lung disease was defined as oxygen dependency at 36 weeks’ corrected gestational age for an infant who was born at less than 32 weeks’ gestation.18 Intraventricular hemorrhage was defined according to the criteria of Papile et al19 from cranial ultrasound performed before 14 days of life. Cranial ultrasounds were read by the radiologists at each site. Necrotizing enterocolitis was defined according to the criteria of Bell et al (stage 2 or higher).20 Primary infection was defined as positive single organism cultures from blood or cerebrospinal fluid taken within 48 hours of birth. Nosocomial infection was defined using blood and cerebrospinal fluid culture results according to the criteria of Freeman et al.21 Patent ductus arteriosus was defined as clinical diagnosis plus treatment with indomethacin, surgical ligation, or both. Respiratory distress syndrome was defined as presence of respiratory symptoms, such as grunting and chest retractions, typical chest X-ray findings or treatment with surfactant, and the need for mechanical ventilation for more than 24 hours.
SPSS for Windows 7.5 (SPSS Inc., Chicago, IL) was used for statistical analysis. We compared the incidence of mortality and major morbidity among inborn and outborn infants using 
2 analysis for categorical variables and the unpaired t test for continuous variables. For each outcome, we also used logistic regression analysis to compare the mortality and major morbidity rates of outborn and inborn infants, independent of perinatal risks and admission illness severity. In logistic regression models, the beta coefficient of a variable represents the logarithm odds ratio for the variable, adjusted for all other variables in the models. We used the Hosmer-Lemeshow method22 to test goodness of fit and assess deviations between the observed and expected number of infants with each outcome. A P value > .05 indicated no significant difference between the observed and expected values and therefore the fit of the model was acceptable.
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RESULTS |
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. Outborn infants were more likely to be of younger gestational age and have low (under 7) Apgar scores at 5 minutes but have high admission SNAP-II scores (at least 10) than inborn infants. Inborn infants were more likely to be small for gestational age and have a higher incidence of maternal hypertension, prenatal care, cesarean delivery, and antenatal steroid treatment, but lower incidence of noncephalic birth presentation than outborn infants.
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shows that outborn infants had significantly higher unadjusted incidence of mortality, severe (at least grade 3) intraventricular hemorrhage, chronic lung disease, patent ductus arteriosus, respiratory distress syndrome, and nosocomial infection than inborn infants. There was no significant difference in the incidence of necrotizing enterocolitis and primary infection.
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shows the results of multivariable logistic regression analysis. Differences in outcomes between outborn and inborn infants persisted even after adjustment for perinatal risks and admission SNAP-II score. The risk-adjusted odds ratio of death was 1.7 (95% confidence interval [CI] 1.2, 2.5) for outborn infants compared with inborn infants. The risk-adjusted odds ratios for grade 3 intraventricular hemorrhage or worse (odds ratio [OR] 2.2, 95% CI 1.5, 3.2), patent ductus arteriosus (OR 1.6, 95% CI 1.2, 2.1), respiratory distress syndrome (OR 4.8, 95% CI 3.6, 6.3), and nosocomial infection (OR 2.5, 95% CI 1.9, 3.3) were also higher among outborn than inborn infants. All models were well calibrated (P > .05 for Hosmer-Lemeshow goodness-of-fit test). Outborn or inborn status was not associated with higher adjusted risk for chronic lung disease, necrotizing enterocolitis, and primary infection. In this analysis, we excluded 1356 preterm infants born of multiple gestation (1185 inborn [27%] and 171 outborn [22%]), because including them would violate the statistical assumption of independence in statistical analyses. Nevertheless, inclusion of these multiple gestation infants in the study cohort yielded similar results (data not shown).
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DISCUSSION |
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There are many possible reasons for the improved outcomes of preterm birth at tertiary centers, including availability of laboratory, radiologic, and specialist medical support, and more adequate staffing and equipment to provide optimal care in the delivery room and nursery.11 Other factors that could be associated with the higher incidence of adverse outcomes among outborn infants include ineffectiveness of stabilization procedures before or during transport, delays in commencing assisted ventilation or use of surfactant, and delays in transport.11 In addition, transport itself is a stressor that can adversely affect infants.23 Better training in the care of mothers and infants at delivery, and improved staffing and equipment at community hospitals might improve outcomes of outborn infants. However, many community hospitals have low patient volumes, and it might be difficult to maintain staff competency in treatment of acute problems at birth. Innovative solutions, such as use of telemedicine facilities to access the expertise of tertiary level facilities, could help overcome some of these difficulties.
Although outborn infants were sicker than inborn infants, mothers of inborn infants had higher incidence of pregnancy complications, including maternal hypertension and multiple gestation. The higher incidence of pregnancy complications among inborn infants suggests that in utero transfer of high-risk pregnancies to tertiary level facilities does take place at Canadian hospitals to an appreciable extent. We also speculate that many outborn infants requiring NICU care are not born at community hospitals by choice but because of sudden and uncontrollable events that are outside the ability of physicians to control. Our findings of lower maturity (gestational age), lower rate of antenatal steroid use, and lower mean Apgar score at 5 minutes among outborn infants support this speculation. As regional transfer of predictably high-risk pregnancy improves, we would increasingly select sicker outborn infants as the product of poorly controlled or unexpected events in pregnancy. We therefore expect more severe illness among outborn infants.
In conclusion, outborn infants are different from inborn infants in perinatal risks and severity of illness at admission, and they have less favorable outcomes. Adjustment for perinatal risks and severity of illness at admission are necessary when making comparisons between inborn and outborn infants. Delivery of high-risk pregnancies at tertiary facilities is associated with improved outcomes. Improved maternal transport protocols which promote in utero transfer of patients, early use of antenatal steroids, and support for regionalized transport teams can further improve neonatal outcomes. Our findings are derived from regionalized NICUs serving 75% of the Canadian population and are generalizable to NICUs in Canada and potentially elsewhere.
We did not have detailed information on socioeconomic background, reasons and timing of maternal transport, resuscitation of infants and treatments given at delivery, time interval between infant birth and transport, or the transport stabilization process. These and potentially other unmeasured factors might confound our findings. Additional information on these factors would facilitate more in-depth analysis and provide insights into how we can design interventions to improve outcomes and reduce costs.
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Footnotes |
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Canadian Neonatal Network Coordinating Centre staff (Vancouver, BC): Li-Yin Chien, MPH, ScD; Joanna Sale, MSc; Herbert Chan, MSc; and Shawn Stewart.
This study was supported by Grant 40503 and Grant 00152 from the Medical Research Council of Canada. Additional funding was provided by the B.C.’s Children’s Hospital Foundation; Calgary Regional Health Authority; Dalhousie University Neonatal-Perinatal Research Fund; Division of Neonatology, Children’s Hospital of Eastern Ontario; Child Health Program, Health Care Corporation of St John’s; The Neonatology Program, Hospital for Sick Children; Lawson Research Institute; Midland Walwyn Capital Inc; Division of Neonatology, Hamilton Health Sciences Corporation; Mount Sinai Hospital; North York General Hospital Foundation; Saint Joseph’s Health Centre; University of Saskatchewan Neonatal Research Fund; University of Western Ontario; Women’s College Hospital.
Presented in part at the Annual Meeting of the Pediatric Academic Societies in Boston, Massachusetts in May 2000.
Received December 27, 2000. Received in revised form March 2, 2001. Accepted March 30, 2001.
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