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BACKGROUND Intestinal disorders are common in very low-birthweight infants. The purpose of this study was to evaluate the impact of prophylactic oral Gastrografin® (diatrizoate acid) on meconium-related ileus (MRI) in extremely preterm infants. METHODS This was a retrospective case-control study of infants born extremely preterm at

BACKGROUND Although survival of preterm infants has improved, prematurity remains the second most frequent cause of death before 5 years of age in Romania. Data on the changing mortality of Romanian preterm infants born before 29 weeks of gestation have not been available. METHODS Outcomes of infants of gestational age 25-28 weeks born in 2007-2010 (n = 247) were compared with those born in 2011-2014 (n = 235). Data were analyzed from three tertiary neonatal intensive care centers. Mortality rates and major morbidities were compared between these two epochs. RESULTS Infants in the later epoch were more likely to have been born by cesarean section and had higher 1 and 5 min Apgar scores. Mortality rate decreased significantly with increasing gestational age at birth. Between the two epochs, the in-hospital mortality rate decreased from 65.6% to 29.4% (P

BACKGROUND Patent ductus arteriosus (PDA) is associated with increased morbidity and mortality in very low-birthweight (VLBW) preterm infants due to significant left-to-right shunting, which leads to pulmonary edema/hemorrhage, intracranial hemorrhage, acute renal failure and necrotizing enterocolitis. In this prospective study, echocardiography was carried out in VLBW preterm infants soon after birth and at the end of 72 h to evaluate the relationship between early ductal anatomic features and significant ductal shunt during follow up. METHODS Preterm infants with a gestational age ≤ 28 weeks, birthweight < 1000 g and who had ductal patency during the first 6-12 h of life underwent color Doppler echocardiograms through the first 3 days after birth. RESULTS Fifty-eight patients were enrolled. The DA remained open in 42 preterm infants (72.4%) and was hemodynamically significant in 36 (62%) at the end of 72 h postnatal age. The preterm infants with hemodynamically significant PDA (hsPDA) had shorter ductal length from aortic to pulmonary insertion and from ductal constriction to pulmonary insertion in the initial exam. Cut-offs for these lengths were 5.2 and 1.7 mm, respectively. These parameters had significant univariate correlation with ductal closure time after treatment. CONCLUSIONS Echocardiographic features such as short ductal length and short or absent ductal constriction area can be used to predict hsPDA for early decision making strategies in VLBW preterm infants.

Background Surgical intestinal disorders, such as necrotizing enterocolitis (NEC), focal intestinal perforation (FIP), and meconium-related ileus (MRI), are serious morbidities in very low-birthweight infants (VLBWI). The aim of this study was to compare the composite outcomes of death or neurodevelopmental impairment (NDI) in VLBWI with surgical intestinal disorders and assess independent risk factors for death and NDI at 18 months of corrected age. Methods A retrospective matched-cohort study was conducted at 11 institutes. We included VLBWI who had undergone laparotomy for NEC, FIP, and MRI. Two control subjects were chosen for every surgical patient and matched for gestational age and birthweight to form the comparison group. Death and neurodevelopmental outcome at 18 months of corrected age were evaluated. Results The number of infants in the NEC, FIP, MRI, and control groups was 44, 47, 42, and 261, respectively. In-hospital mortality was higher in infants with NEC and MRI relative to those in the control group (P < 0.001). The incidence rate for NDI at 18 months of corrected age was higher in infants with MRI relative to those in the control group (P = 0.021). On logistic regression analysis, low gestational age, male sex, small for gestational age, intraventricular hemorrhage, and MRI were associated with increased risk of death or NDI at 18 months of corrected age. Conclusions NEC and MRI were associated with in-hospital mortality, and MRI was associated with NDI or death at 18 months of corrected age.

Background The aim of this study was to investigate the relationship between plasma chitotriosidase activity, an inflammatory protein secreted mainly from macrophages, and neonatal morbidity and mortality in premature infants. Methods Cord blood chitotriosidase activity was studied in healthy control infants (53 term, group 1; 26 late preterm [33–37 gestational weeks], group 2) and 35 preterm infants (≤32 weeks; group 3). In group 3, consecutive samples at 3 h, 24 h, 72 h, 7 days, 14 days, and 36 weeks after conception were also analyzed. Group 3 was also evaluated for mortality, respiratory treatment and bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). Results Cord blood chitotriosidase activity was positively correlated with gestational age and birthweight. SNAPPE-II score was correlated with chitotriosidase activity at 24 h. Consecutive chitotriosidase activity for group 3 was non-significantly higher in infants who died in the early neonatal period. Higher chitotriosidase activity was observed in mechanically ventilated infants than infants treated with non-invasive assisted ventilation. BPD, PDA, IVH and ROP, but not NEC, were related to higher chitotriosidase activity, being significant at some of the time points. Conclusion Neonatal stress such as invasive ventilation may create a risk for the development of BPD, PDA, IVH, and ROP by increasing macrophage activation in preterm infants as reflected in the higher chitotriosidase activity. High chitotriosidase activity may also be associated with disease severity and mortality.

Background This study evaluated the benefit of Bifidobacterium bifidum OLB6378 (B. bifidum) in very low-birthweight (VLBW) infants (birthweight

Background Birth before 28 weeks of gestation is associated with high mortality and morbidity. The purpose of this study was to examine characteristics associated with in-hospital mortality and morbidity among extremely low-birthweight neonates admitted to three tertiary care centers in Romania. Methods The study was conducted in three Romanian hospitals with level-III neonatal intensive care units. We studied singleton live births at the established Romanian limit of viability (i.e., 25–28 weeks' gestational age) born between January 2007 and December 2010 (n = 227). Infants born in non-level-III facilities transferred to these three centers were included in our study (n = 39). Descriptive and multivariate statistical analyses were used to describe the population and examine outcomes and risk factors. Results During the study period, 62 neonates (27.3%) were delivered at 25 weeks, 56 (24.7%) were delivered at 26 weeks, 56 (24.7%) at 27 weeks, and 53 (23.3%) at 28 weeks. Overall in-hospital mortality was 65% (from 85% at 25 weeks to 35% at 28 weeks). The rates for major morbidities were necrotizing enterocolitis 8.8%, bronchopulmonary dysplasia 12.5%, and retinopathy of prematurity (stage higher than 2) 26.2%. Conclusions During 2007–2010, in-hospital survival of infants admitted to three neonatal intensive care units in Romania was 35% and ranged from 14% at 25 weeks to 64% at 28 weeks.

Background Intestinal perforation is known to correlate with neurodevelopmental outcome in very low-birthweight (VLBW) infants, and its two major causes are necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP). Infants with FIP are reported to have better neurodevelopmental outcome than infants with NEC, but outcome has not been compared with that in infants without diseases that require surgery. The aim of this study was to compare neurodevelopmental outcomes between FIP survivors and infants without diseases that require surgery. Methods Records of VLBW infants with FIP and infants without surgical diseases were retrospectively analyzed. Neurodevelopmental outcome was compared between eight infants with FIP and 24 case-matched control infants without surgical diseases using the Kyoto Scale of Psychological Development. Control group members were individually matched with FIP survivors for sex, gestational age, birthweight, and intraventricular hemorrhage (IVH) grade. Those with an episode of sepsis or severe IVH (grade 3–4) that occurred irrespective of FIP were excluded. Results Three FIP survivors and 12 infants without surgical diseases were classified as neurodevelopmentally normal (37.5% vs 50%, P = 0.69) at a corrected age of 18 months–3 years. All neurodevelopmentally normal FIP survivors were born at a gestational age ≥26 weeks. Conclusion Excluding the influence of sepsis or severe IVH, no significant difference was found in neurodevelopmental outcome between FIP survivors and infants without surgical diseases. None of the FIP infants born before 26 weeks of gestation, however, had normal neurodevelopment, suggesting that longer gestation might be needed to overcome the stress associated with FIP.

BACKGROUND: Lactobezoar is a compact mass of inspissated, undigested milk. Most often it is located in the stomach but it may also be located in other parts of the intestine. It is the most common type of bezoar in infancy. Reported herein are two cases of this rare condition mimicking necrotizing enterocolitis. METHOD: Data on two complicated cases of lactobezoar were retrospective analyzed. RESULTS: The first case involved a female infant, born at 37 weeks 2 days gestation with a birthweight of 3050 g, and multiple antenatal known congenital defects. Due to esophageal atresia she was given a gastrostomy on the second day of life. After 20 days of continuous feeding with formula feeding she developed food intolerance and clinical signs of a severe sepsis. On examination the abdomen was severely distended and tender at palpation. No palpable mass was noted at examination. Signs of hemodynamic instability and sepsis evolved. Plain abdominal X-ray showed a pneumatosis of the stomach matching necrotizing enterocolitis (NEC). During emergency laparotomy a gastric bezoar was seen and removed. The postoperative course was complicated by prolonged motility disturbance of the stomach. For a long time she was fed through a jejunostomy. The second case involved a female infant born at 26 weeks 4 days (birthweight 1040 g) who became progressively septic on the day 6 of life. On examination she had a tender and distended abdomen, and abdominal X-ray showed intra-abdominal air, consistent with a gastrointestinal perforation. On emergency laparotomy a perforation was seen at the back of the stomach, due to a lactobezoar, with only a little necrosis surrounding it. Surgical treatment consisted of extraction of the lactobezoar and closure of the perforation at the back of the stomach. Two days after the initial surgery, she developed a leakage of the suture anastomosis and another laparotomy was performed. A drain was left near the stomach. After 2 weeks she recovered quickly and feeding was initiated at day 21 with good outcome after 3 months. CONCLUSION: Factors associated with the development of lactobezoar are prematurity, low birthweight, disturbed gastric emptying, hypercaloric and hyperosmolaric milk compositions. It is important to realize that lactobezoar formation can occur in preterm and full-term infants, receiving either breast milk or formula, even when only minimal enteral feeding is given. Early recognition and treatment of this condition is critical. If a lactobezoar is not detected in an early phase, patients can deteriorate very quickly into a condition mimicking NEC.

Background: Delivery of premature infants outside tertiary care centers is not always preventable. The aim of this study was to compare rates of survival and common morbidities in extremely premature babies transported to a level III facility versus those born at the level III center. Methods: Retrospective chart review was performed on all neonates born at ≤ 28 weeks of gestation with birthweight ≤1500 g who were admitted to the Newborn Intensive Care Unit at Kapi‘olani Medical Center for Women and Children (KMCWC) between 1 January 2000 and 31 December 2005. Infants were divided into two groups, those born at KMCWC (Inborn) and those born at level I institutions and subsequently transported (Transport) to KMCWC. Results: A total of 394 neonates met the study criteria; 349 were inborn while 45 were transported. Survival rates were identical for both groups. However, the Transport group survivors displayed a significantly longer mean length of stay and higher rate of severe retinopathy of prematurity than those in the Inborn group (P≤ 0.01). Conclusion: Identical rates of survival in both groups suggest that community medical professionals are providing satisfactory care to stabilize critical neonates without reducing their chances of survival. However, increased length of stay and higher rate of retinopathy of prematurity in the Transport group suggest that differences in medical management during the first few hours of life may adversely affect outcomes.

Background: A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low-birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live-birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium-related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified. Methods: The histology of 13 ELBW neonates with intestinal perforation secondary to meconium-related ileus was reviewed, and the radiology of 33 cases of meconium-related ileus diagnosed on contrast enema was reviewed. Specimens obtained from 16 ELBW neonates without gastrointestinal disease served as age-matched controls for histological assessment. Results: The size of the ganglion cell nucleus in meconium-related ileus and in control subjects was 47.3 ± 22.0 µm2 and 37.8 ± 11.6 µm2, respectively, which was not significantly different. In all cases of meconium-related ileus, contrast enema demonstrated a microcolon or small-sized colon, with a gradual caliber change in the ileum and filling defects due to meconium in the ileum or colon, showing not-identical locations of caliber changes and filling defects. Conclusion: Morphological immaturity of ganglia was not suggested to be the pathogenesis of meconium-related ileus. Impaction of inspissated meconium is not the cause of obstruction, but the result of excessive water absorption in the hypoperistaltic bowel before birth, although the underlying mechanism responsible for the fetal hypoperistalsis remains unclear.

Although necrotizing enterocolitis (NEC) is a frequently encountered entity in premature infants in the neonatal intensive care unit, intussusception is extremely rare. Abdominal distension, bilious/non-bilious gastric residuals and bloody stool are the common clinical findings of both entities. Here we present three cases of intussusception misdiagnosed as NEC, two of which were complicated with intestinal perforation. Similar clinical findings of NEC and intussusception leads to misdiagnosis and delay in treatment, particularly in premature infants with intussusception.

Background: In extremely premature infants, the presence of a left-to-right shunt through a patent ductus arteriosus (PDA) increases the risks of pulmonary hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, renal failure, and chronic lung disease. Conservative management induces spontaneous ductus closure in

Background: Infants with severe congenital anomaly often need to undergo operation followed by antibiotic therapy. As a result they inevitably acquire abnormal intestinal microbiota, which cause severe infections such as necrotizing enterocolitis. Also, intestinal function deteriorates and their nutritional state is very poor. In order to prevent these situations probiotic therapy is proposed as an effective supporting treatment. Probiotic therapy were therefore applied to infants with severe congenital anomaly as early as possible to ascertain its efficacy. Methods: As probiotics, two bacteria were used: Bifidobacterium breve Yakult and Lactobacillus casei Shirota. Probiotic therapy was used in four infants with severe congenital anomaly as early as possible after surgery. Their intestinal microbiota and physical growth were followed through the treatment course. Results: Two patients suffered from meconium peritonitis with ileal atresia. One patient was born with complex anomalies (omphalocele, bladder exstrophy, myelomeningocele). The fourth patient suffered from complete urorectal septum malformation. The intestinal microbiota of these four patients was first induced to be probiotic dominant and finally changed to commensal anaerobe dominant that was similar to normal intestinal microbiota. Pathogenic bacteria were seldom detected. The patients' physical growth was excellent despite short bowel and pulmonary hypoplasia. Conclusion: Probiotic therapy was effective in inducing probiotic dominant intestinal microbiota and normal intestinal microbiota in infants with severe congenital anomalies. As a result their intestinal absorptive functions were activated and severe infections were completely prevented. All of the infants grew well despite their physical disadvantages.

Background: Neonatal gastric perforation (NGP) is a rare event and its etiology is still controversial. Although it has previously been described as spontaneous, recently some risk factors have been reported to be associated with the development of NGP including prematurity and nasal ventilation. The purpose of the present paper was to report and discuss etiology, clinical features, and outcome of the authors’ NGP cases over a 10 year period. Methods: Charts of five infants with NGP was reviewed in terms of gender, birthweight, gestational age, time of diagnosis, associated disease, site of perforation, type of surgery performed, and clinical outcome. Results: There were three boys and two girls with a mean birthweight and gestational age of 1650 g and 32 weeks, respectively. Three of them were premature. Mean perforation time was day 10 postnatally. Three infants had associated problems including prematurity, respiratory distress syndrome type 1, necrotizing enterocolitis, mechanical ventilator support, and one of them had tracheaesophageal fistula. Mothers of two out of these three infants had chorioamnionitis. One full-term infant received dexamethasone because of brain edema. Only one patient had no associated problem. Perforation occurred in the lesser curvature in three infants and in the greater curvature in two infants. Mortality rate was 60%. Conclusions: Contrary to previous literature, and similar to recent publications, it was found that essentially low-birthweight infants with tracheaesophageal fistula or chorioamnionitis and full-term babies on steroid therapy may have a risk for NGP, suggesting that an infant with contributing factors should be monitored more carefully for the development of NGP.

We report a case who was born with extremely low birth weight infant and had experienced abdominal operation for necrotizing enterocolitis, eventually developed ileus due to fatty acid calcium stones after giving human milk fortifier. He had developed necrotizing enterocolitis on day 30 of his age, such that we performed enterectomy and ileostomy. He could not tolerate enteral feeding fully, because intestinal fistula infection was repeated. Although we administered hindmilk, he grew up slowly and he suffered cholestasis as well. We performed end-to-end anastomosis to prevent fistula infections on day 87. After this operation, breast milk feeding volume was increased easily. However, we started to add HMF of half-strength on day 124, because his body weight gain remained very poor. And we confirmed to intensify the ratio of HMF full-strength on day 128. After that his abdomen had distended on day 131. As there is no effect of conservative therapy to occlusive ileus, we did emergency laparotomy on day 139. Intestinal calculi were impacted at anastomic portion. Although all stones were removed, he died on 144 days due to disseminated intravascular coagulation and renal failure. Calculi analysis revealed that all of them were fatty acid calcium stones. There is no report about like our case. We speculate that the construction of fatty acid calcium result from either high concentration of calcium/phosphorus or rapid increase in the fortification. We could have prevented this case happened by slower increment of fortification.

To study the effect of exchange transfusion on cytokine profiles in a patient with necrotizing enterocolitis, the levels of 12 cytokines and serum calprotectin were measured among exchange transfusion. A male extremely low birth weight infant was in non-compensated shock and diagnosed stage 3 necrotizing enterocolitis. Exchange transfusion was performed for critical condition, refractory hypotension and disseminated intravascular coagulation. After exchange transfusion, the patient's blood pressure increased and stabilized. Then an enterostomy was performed and revealed necrosis of the ascending colon. Of the cytokines examined, interleukin-8 and serum calprotectin were high before exchange transfusion and decreased after exchange transfusion.

The aim of this study was to investigate the differences in mean platelet volume (MPV) between neonates with and without neonatal respiratory distress syndrome (RDS). Eighty-three premature infants who were admitted to the neonatal intensive care unit were included in the study. Forty-four of these infants were diagnosed as having RDS and the other 39 infants were non-RDS patients. Infants born to mothers with pre-eclampsia, or a drug history that had negative effects on platelet count, perinatal hypoxia, sepsis and necrotizing enterocolitis were excluded. Blood collection was done on the first and third days of life. There were no demographic, gestational or platelet count differences between groups, but MPV was higher in RDS patients and this difference was statistically significant (P= 0.011). High platelet volumes in RDS patients is probably related to young platelet production and may be a result of increased platelet consumption in pulmonary damage due to RDS.

We succeeded in the early diagnosis of pneumoperitoneum in a low birth weight infant with neonatal necrotizing enterocolitis by transillumination. Transillumination is a simple and noninvasive technique which can be used in the evaluation in risk infants to detect pneumoperitoneum at the earliest possible time. In the large series of 296 neonates admitted to NICU over a period of 3 years, there was a sharp increase in the incidence of abdominal distension and/or intestinal bleeding with decreasing birth weight and gestation, indicating that neonatal necrotizing enterocolitis is dependent on the degree of prematurity. We therefore postulate that the disease could be termed “Enteropathy of Prematurity”. In infants with abdominal distension and/or intestinal bleeding, the routine use of transillumination may help the early detection of penumoperitoneum.