Spontaneous Intestinal Perforation in Extremely Low Birth Weight Infants: Association with Indometacin Therapy and Effects on Neurodevelopmental Outcomes at 18–22 months Corrected Age
Spontaneous intestinal perforation (SIP) is associated with the use of postnatal glucocorticoids and indometacin in extremely low birth weight (ELBW) infants. The authors hypothesised: 1) an association of SIP with the use of antenatal steroids (ANS) and indometacin either as prophylaxis for intraventricular hemorrhage (IVH) (P Indo) or for treatment of PDA (Indo/PDA) and 2) an increased risk of death or abnormal neurodevelopmental outcomes in infants with SIP at 18-22 months corrected age.
The authors retrospectively identified ELBW infants with SIP in the Neonatal Research Network's generic database. Unadjusted analysis identified the differences in maternal, neonatal and clinical variables between infants with and without SIP. Logistic regression analysis identified the adjusted OR for SIP with reference to ANS, P Indo and Indo/PDA. Neurodevelopmental outcomes were assessed among survivors at 18-22 months corrected age.
Indo/PDA was associated with an increased risk of SIP (adjusted OR 1.61; 95% CI 1.25 to 2.08), while P Indo and ANS were not. SIP was independently associated with an increased risk of death or neurodevelopmental impairment (NDI) (adjusted OR 1.85; 95% CI 1.32 to 2.60) and NDI among survivors (adjusted OR 1.75, 95% CI 1.20 to 2.55).
Indometacin used for IVH prophylaxis and ANS were not associated with the occurrence of SIP in ELBW infants. Indometacin used for treatment of symptomatic PDA was however associated with an increased risk of SIP. ELBW infants with SIP have an increased risk of poor neurodevelopmental outcomes.
Available from: PubMed Central
- "The reported complications include pulmonary bleeding, NEC, intestinal perforation, renal failure, and thrombocytopenia, especially in low-birth-weight preterm neonates. Therefore, prostaglandin synthetase inhibitors are used with great caution for VLBW infants and may even worsen already compromised intestinal blood flow in the presence of a hemodynamically significant PDA . "
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ABSTRACT: This study aimed to determine whether primary surgical closure of patent ductus arteriosus (PDA) is a risk factor for morbidity and mortality compared with secondary surgical ligation. The study enrolled 178 very-low-birth-weight infants. The surgical group included 34 patients who did not respond to pharmacologic intervention and eventually required ligation of their PDA as well as 35 patients who underwent direct ligation because of contraindications to the use of oral ibuprofen. The overall outcomes for the primary and secondary ligation groups were compared. The outcome during hospitalization showed no statistically significant difference in terms of morbidity and mortality between the two groups. The group that had primary ligation for PDA experienced more complications associated with premature birth such as lower gestational age and birth weight. The two groups did not differ significantly in terms of overall outcomes.
Pediatric Cardiology 12/2013; 35(5). DOI:10.1007/s00246-013-0854-6 · 1.31 Impact Factor
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Spontaneous intestinal perforation (SIP) has been recognized as a distinct disease entity. This study sought to quantify mortality associated with laparotomy confirmed SIP and to compare it to mortality of laparotomy confirmed necrotizing enterocolitis (NEC).
Data were prospectively collected on 177,618 very low birth weight (VLBW, 401-1500 g) neonates born between January 2006 and December 2010 admitted to U.S hospitals participating in the Vermont Oxford Network (VON). SIP was defined at laparotomy as a focal perforation of the intestine without features suggestive of NEC or other intestinal abnormalities. The primary outcome was in-hospital mortality.
At laparotomy, 2,036 (1.1%) neonates were diagnosed with SIP and 4,076 (2.3%) with NEC. Neonates with laparotomy confirmed SIP had higher mortality (19%) than infants without NEC or SIP (5%, P = 0.003). However, laparotomy confirmed SIP patients had significantly lower mortality than those with confirmed NEC (38%, P < 0.0001). Mortality in both NEC and SIP groups decreased with increasing birth weight and mortality was significantly higher for NEC than SIP in each birth weight category. Indomethacin and steroid exposure were more frequent in the SIP cohort than the other two groups (P < 0.001).
In VLBW infants, the presence of laparotomy confirmed SIP increases mortality significantly. However, laparotomy confirmed NEC mortality was double that of SIP. This relationship is evident regardless of birth weight. The variant mortality of laparotomy confirmed SIP versus laparotomy confirmed NEC highlights the importance of differentiating between these two diseases both for clinical and research purposes.
Journal of Pediatric Surgery 01/2013; 49(8). DOI:10.1016/j.jpedsurg.2013.11.051 · 1.39 Impact Factor
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The aim of the study was to determine whether longitudinal measurements of fecal S100A12, a damage-associated molecular pattern protein, which is released from neutrophils or monocytes under stress, can detect very-low-birth-weight (VLBW) infants at risk for intestinal distress apart from necrotizing enterocolitis.
This prospective study included 46 VLBW infants with intestinal distress and 49 reference patients. Meconium and stool samples were collected prospectively on alternate days for 4 weeks, and fecal S100A12 was measured by enzyme-linked immunosorbent assay.
Gestational age and weight at birth were significantly lower in patients with intestinal distress when compared to unaffected reference infants. Median levels of fecal S100A12 were significantly higher in patients with intestinal distress at onset of disease and before compared with unaffected reference infants. Median levels of fecal S100A12 declined steadily to baseline levels within 2 weeks after disease onset. The ideal cutoff value for identifying patients with intestinal distress within 7 days before disease onset was 60 μg/kg (sensitivity 0.73; specificity 0.55).
Fecal S100A12 levels are increased in VLBW infants with intestinal distress; however, the potential for S100A12 as an early biomarker is largely limited by overlaps between values of infants with intestinal distress and the reference population.
Journal of pediatric gastroenterology and nutrition 04/2013; 144(5). DOI:10.1097/MPG.0b013e3182946eb2 · 2.63 Impact Factor
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