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Risk of Necrotizing Enterocolitis in Very-Low-Birth-Weight Infants with Isolated Atrial and Ventricular Septal Defects

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Risk of Necrotizing Enterocolitis in Very-Low-Birth-Weight Infants with Isolated Atrial and Ventricular Septal Defects Journal of Perinatology (2014) 34, 319–321 & 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp ORIGINAL ARTICLE Risk of necrotizing enterocolitis in very-low-birth-weight infants with isolated atrial and ventricular septal defects J Bain1,2, DK Benjamin Jr1,2, CP Hornik1,2, DK Benjamin3, R Clark4 and PB Smith1,2 OBJECTIVE: Necrotizing enterocolitis (NEC) is associated with a significant morbidity and mortality in premature infants. We sought to identify the frequency of NEC in very-low-birth-weight infants with isolated ventricular septal defects (VSDs) or atrial septal defects (ASDs) using a large multicenter database. STUDY DESIGN: We identified a cohort of infants with birth weight o1500 g cared for in 312 neonatal intensive care units (NICUs) managed by the Pediatrix Medical Group between 1997 and 2010. We examined the association between the presence of an ASD or a VSD with development of NEC using logistic regression to control for small-for-gestational age status, antenatal steroid use, antenatal antibiotic use, gestational age, sex, race, Apgar score at 5 min and method of delivery. RESULT: Of the 98 523 infants who met inclusion criteria, 1904 (1.9%) had an ASD, 1943 (2.0%) had a VSD and 146 (0.1%) had both. The incidence of NEC was 6.2% in infants without septal defects, 9.3% in those with an ASD, 7.8% in those with a VSD, and 10.3% in infants with both an ASD and a VSD. Compared with infants without septal defects, the adjusted odds ratios for developing NEC for each group—ASD alone, VSD alone and ASD with VSD—were 1.26 (95% confidence interval 1.07 to 1.49), 1.27 (1.07 to 1.51) and 1.79 (1.03 to 3.12), respectively. CONCLUSION: The presence of an ASD or a VSD was associated with NEC in this cohort of premature infants. Journal of Perinatology (2014) 34, 319–321; doi:10.1038/jp.2013.174; published online 16 January 2014 Keywords: necrotizing enterocolitis; atrial septal defect; ventricular septal defect INTRODUCTION METHODS Necrotizing enterocolitis (NEC) is a common and often fatal Study population complication of prematurity.1 Mortality associated with NEC Data were obtained from an administrative database that prospectively ranges from 15 to 30%.2–6 Survivors are at increased risk of captures information from daily progress notes generated by long-term morbidity, including short bowel syndrome, subsequent clinicians using a computer-assisted tool on all infants cared for intestinal strictures, neurodevelopmental impairment and growth by the Pediatrix Medical Group. Included in the data were diagnoses, delay.7 Physiologic states associated with the development of medications, gestational age, birth weight, method of delivery, Apgar score, sex, race and occurrence of NEC. The diagnosis of a septal defect NEC include: immature intestinal system, highly reactive inte- was made based on echocardiography results. We included all infants stinal immune system, altered microvascular environment admitted within the first 28 days of life with a birth weight of o1500 g including poor mesenteric blood flow and abnormal microbial who were discharged from 312 Pediatrix Medical Group neonatal intensive 8 colonization. care units (NICUs) in North America between 1997 and 2010. Exclusion Previous studies have identified term and near-term infants criteria were (1) death within the first 3 days of life, (2) treatment with with congenital heart disease as a risk factor for developing prostaglandins at any time before discharge, and (3) the presence of major NEC;9,10 however, they have not evaluated ventricular and atrial congenital anomalies (including infants with other structural heart septal defects (VSD and ASD) in isolation, but rather in association disease). with other congenital heart defects and in the surgical setting. VSD and ASD are the first and second most common congenital Definitions and statistical analysis heart defects, with a prevalence in the general population of For each infant, we identified the first episode of NEC occurring before 2.6/1000 and 1.6/1000, respectively.11 These defects may result in day of life (DOL) 120, including surgically or medically treated NEC. left-to-right shunting of blood, resulting in increased pulmonary We did not include those infants who had presumed or suspected NEC. blood flow, and a subsequent decrease in systemic, and thus We compared continuous and categorical variables between infants mesenteric blood flow. with a diagnosis of ASD, VSD, both ASD and VSD, or no cardiac septal Given the high prevalence of both VSD and ASD in infants, we defect. We used multivariable logistic regression models to evaluate the association between the presence of an ASD, a VSD, or both and the evaluated VSD and ASD as risk factors for NEC in premature infants diagnosis of medial or surgical NEC, controlling for the following using a large multicenter database. confounders present at birth: small-for-gestational age status, antenatal 1Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA; 2Department of Pediatrics, Duke University Medical Center, Duke University, Durham, NC, USA; 3Clemson University, Clemson, SC, USA and 4Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL, USA. Correspondence: Dr PB Smith, Department of Pediatrics, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715, USA. E-mail: [email protected] Received 1 July 2013; revised 31 October 2013; accepted 20 November 2013; published online 16 January 2014 Risk of NEC in infants with isolated ASD and VSD J Bain et al 320 steroid use, antenatal antibiotic use, gestational age, sex, race, Apgar RESULTS score at 5 min and method of delivery. We controlled for potential During the study period, 98 523 infants met our inclusion criteria site-specific effects using a fixed effect for site. Using a fixed effect model (Figure 1). Of these, 1904/98 523 (1.9%) had an ASD, 1943/98 523 that is conditioned on the NICU addresses the heterogeneity of baseline risk of outcomes in each individual NICU. We used Stata 12 (College (2.0%) had a VSD, and 146/98 523 (0.1%) had both an ASD and a Station, TX, USA) to analyze the data, and considered Po0.05 as VSD (Table 1). For infants with septal defect, the diagnosis was statistically significant. made on a median DOL 7 (interquartile range 3 to 26). The incidence of NEC in infants without cardiac septal defects was 5825/94 530 (6.2%); 3966/5825 (68.1%) of those episodes were medical NEC. Infants with an ASD had an incidence of 177/1904 (9.3%), 121/177 (68.4%) of which were medical NEC. Infants with a VSD had an incidence of 152/1943 (7.8%), and 107/152 (70.4%) of those episodes were medical NEC. Finally, infants with both an ASD and a VSD had an incidence of 15/146 (10.3%), 9/15 (60.0%) of which were medical NEC. The first episode of NEC occurred on DOL 21 (interquartile range 12 to 32), DOL 24 (14 to 37), DOL 22 (14 to 34) and DOL 18 (11 to 43) for infants without septal defects, infants with an ASD, infants with a VSD, and infants with an ASD and a VSD, respectively. Among infants who developed NEC, the incidence of surgical versus medical NEC did not differ between those with and without septal defects (P ¼ 0.75); it also did not differ across patients with different types of septal defects (P ¼ 0.69). Compared with infants without septal defects, the adjusted odds ratios for developing NEC for each group—ASD alone, VSD alone and ASD with VSD—were 1.26 (95% confidence interval 1.07 to 1.49), 1.27 (1.07 to 1.51) and 1.79 (1.03 to 3.12), respectively. DISCUSSION In our multicenter study, we observed that infants o1500 g birth Figure 1. Study population. ASD, atrial septal defect; DOL, day of life; weight with an ASD or a VSD were at increased risk of developing NEC, necrotizing enterocolitis; VSD, ventricular septal defect. NEC as compared with infants without septal defects. To date, no Table 1. Demographics No cardiac septal defect, N ¼ 94 530 (%) ASD, N ¼ 1904 (%) VSD, N ¼ 1943 (%) ASD þ VSD, N ¼ 146 (%) Gestational age, weeks p25 16 047 (17) 400 (21) 313 (16) 26 (18) 26–28 30 930 (33) 826 (43) 698 (36) 42 (29) 29–32 40 512 (43) 617 (32) 790 (41) 61 (42) 33–36 6721 (7) 52 (3) 135 (7) 17 (12) X37 291 (o1) 8 (o1) 7 (o1) 0 (0) Male 47 781 (51) 914 (48) 820 (42) 55 (38) Birth weight, g o750 15 587 (16) 447 (23) 353 (18) 30 (21) 750–999 21 189 (22) 539 (28) 492 (25) 36 (25) 1000–1499 57 754 (61) 918 (48) 1098 (57) 80 (55) SGA 22 588 (24) 413 (22) 528 (27) 55 (38) Apgar at 5 min 0–3 3327 (4) 84 (5) 80 (4) 9 (6) 4–6 14 031 (15) 330 (18) 329 (17) 26 (18) 7–10 75 368 (81) 1446 (78) 1493 (79) 107 (75) Race/ethnicity White 43 994 (48) 904 (49) 997 (53) 79 (57) Black 24 243 (27) 437 (24) 394 (21) 25 (18) Hispanic 18 257 (20) 371 (20) 386 (21) 28 (21) Other 4841 (5) 134 (7) 98 (5.2) 6 (4) Cesarean section 67 356 (72) 1433 (76) 1453 (75) 112 (78) Antenatal steroid exposure 68 973 (73) 1412 (74) 1426 (73) 111 (76) Antenatal antibiotic exposure 38 304 (41) 776 (41) 810 (42) 54 (37) Abbreviations: ASD, atrial septal defect; SGA, small-for-gestational age; VSD, ventricular septal defect. Journal of Perinatology (2014), 319 – 321 & 2014 Nature America, Inc.
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