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Necrotizing enterocolitis.

Improvement in survival rates of low birth-weight infants particularly in the neonatal intensive care units of India appears to be accompanied by frequent recognition of Necrotizing enterocolitis (NEC) among early survivors. As the philosophy and practice of advanced care for tiny infants becomes more acceptable and affordable in the country, a steady increase in survival of such infants is predictable. However there is growing concern in India that NEC could become a significant contributor to morbidity and mortality in the future. NEC is currently regarded as the most common acquired gastrointestinal emergency in the newborn period, and the outcome of this disease is universally poor. Improved understanding of the pathophysiology and pathogenesis of this condition is required for formulating optimal principles of prevention and management.

Enterocolitis, Necrotizing↗

Jejunal blind loop 10 years after neonatal necrotizing enterocolitis.

A 10-year-old girl presented with abdominal distension and vomiting due to a jejunojejunal bowel fistula, forming a blind loop. This was related to neonatal necrotizing enterocolitis (NEC) in her first few weeks of life, which was followed by apparently a full recovery. We would like to raise awareness of possible long-term gastrointestinal sequelae in children who have had NEC.

Child↗

Heparin-binding epidermal growth factor-like growth factor reduces intestinal apoptosis in neonatal rats with necrotizing enterocolitis.

PURPOSE: We have previously demonstrated that enterally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF) decreases the incidence and severity of necrotizing enterocolitis (NEC) in a neonatal rat model. Because apoptosis contributes to gut barrier failure in this model, the aim of this study was to investigate the effect of HB-EGF on apoptosis during the development of NEC. METHODS: NEC was induced in neonatal rats by exposure to hypoxia, hypothermia, hypertonic formula feeding (HHHTF) plus enteral administration of lipopolysaccharide (LPS). Fifty-one neonatal rats were randomly divided into the following groups: (1) breast-fed (BF), (2) HHHTF + LPS, and (3) HHHTF + LPS with HB-EGF (600 microg/kg) added to the formula. NEC was evaluated using a standard histological scoring system. Apoptotic cells in intestinal tissues were detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and by active caspase 3 immunohistochemical staining. RESULTS: The incidence of NEC in the HHHTF + LPS group was higher than that in the BF group (65% vs 0%, P < .05). With administration of HB-EGF, the incidence of NEC significantly decreased to 23.8% (P < .05). The median TUNEL and active caspase 3 scores in the HHHTF + LPS group were higher than those in the BF group (1.9 vs 0.9 and 1.75 vs 0.6, respectively, P < .05). The median TUNEL and active caspase 3 scores were significantly decreased in the HHHTF + LPS + HB-EGF group compared with the HHHTF + LPS group (1.24 vs 1.9 and 1.0 vs 1.75, respectively, P < .05). CONCLUSION: HB-EGF reduces the incidence of NEC in a neonatal rat model in part by decreasing apoptosis. These results support the use of HB-EGF-based clinical regimens for the treatment of NEC.

Animals↗

Plasma intestinal fatty acid binding protein in neonates with necrotizing enterocolitis: a pilot study.

BACKGROUND/PURPOSE: Intestinal fatty acid-binding protein (IFABP) is found within cells at the tip of the intestinal villi, an area commonly injured when necrotizing enterocolitis (NEC) occurs. This study was undertaken to determine if measuring IFABP concentrations in the bloodstream early in the course of NEC would differentiate patients by severity before clinical findings made it clear who had stage 3 NEC and who had milder stages. METHODS: Three plasma samples from newborn infants evaluated for NEC were obtained at symptom onset and after 8 and 24 hours. IFABP concentration was measured by radioimmunoassay. Infants were classified by the final and most severe stage of NEC, and IFABP levels were compared between groups at each sampling. RESULTS: IFABP was detectable in blood samples from all 7 infants with stage 3 NEC compared with 3 of 24 with stages 1 or 2 NEC. Elevated plasma IFABP concentrations were detectable before clinical staging could be made in 5 of the 7 subjects with stage 3 NEC. CONCLUSION: IFABP may be a specific marker for early identification of severe NEC.

Biomarkers↗

Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted age.

OBJECTIVE: Extremely low birth weight (ELBW; < or =1000 g) infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP) are treated surgically with either initial laparotomy or peritoneal drain placement. The only published data comparing these therapies are from small, retrospective, single-center studies that do not address outcomes beyond nursery discharge. The objective of this study was to conduct a prospective, multicenter, observational study to (1) develop a hypothesis about the relative effect of these 2 therapies on risk-adjusted outcomes through 18 to 22 months in ELBW infants and (2) to obtain data that would be useful in designing and conducting a successful trial of this hypothesis. METHODS: A prospective, cohort study was conducted at 16 clinical centers within the National Institute of Child Health and Human Development Neonatal Research Network. To assist in risk adjustment, the attending pediatric surgeon recorded the preoperative diagnosis and intraoperative diagnosis and identified infants who were considered to be too ill for laparotomy. Predefined measures of short- and longer-term outcome included (1) either predischarge death or prolonged parenteral nutrition (>85 days) after enrollment and (2) either death or neurodevelopmental impairment on a standardized examination at 18 to 22 months' adjusted age. RESULTS: Severe NEC or IP occurred in 156 (5.2%) of 2987 ELBW infants; 80 were treated with initial drainage, and 76 were treated with initial laparotomy. By 18 to 22 months, 78 (50%) had died; 112 (72%) had died or were shown to be impaired. Outcome was worse in the subgroup with NEC. Laparotomy was never performed in 76% (28 of 36) of drain-treated survivors. CONCLUSIONS: Drainage was commonly used, and outcome was poor. Our findings, particularly the risk-adjusted odds ratio favoring laparotomy for death or impairment, indicate the need for a large, multicenter clinical trial to assess the effect of the initial surgical therapy on outcome at > or =18 months.

Child Development↗

Endothelin-1 in human intestine resected for necrotizing enterocolitis.

OBJECTIVES: We asked if the tissue concentration of the potent vasoconstrictor endothelin-1 (ET-1) is greater in areas of human preterm intestine that demonstrate histologic evidence of necrotizing enterocolitis (NEC) when compared with relatively healthy areas within the same resection specimen. We then evaluated if ET-1 participates in hemodynamic regulation within intestinal subserosal arterioles harvested from portions of human preterm intestine that demonstrate NEC. STUDY DESIGN: Human preterm intestine resected for NEC was divided into three zones based on proximity to the perforation (zone 1 most proximal, zone 3 most distal). Histologic evidence of NEC was determined in each zone (normal = 0, advanced necrosis = 6). The tissue concentration of ET-1 was determined by enzyme-linked immunosorbent assay within intestinal homogenates prepared from each zone. Arteriolar hemodynamics were determined in vitro on subserosal arterioles harvested from different zones. Arteriolar flow rate, diameter, and resistance were determined at pressure gradients (DeltaP) of 20 and 40 mmHg under control conditions and again after blockade of endothelin ET A receptors with BQ610 (10 -9 mol/L). RESULTS: The tissue concentration of ET-1 (pg/mg protein) and histologic score in the three zones were: zone 1: 84 +/- 14, 5.5 +/- 0.3; zone 2: 99 +/- 12, 4.7 +/- 0.4, and zone 3: 33 +/- 9, 0.8 +/- 0.6, respectively (M +/- SD, n = 10 resection specimens, P < .05, zone 3 vs zones 1 and 2). Zone 2 arterioles demonstrated significantly lower flow rate and diameter and increased resistance under control conditions than zone 3 arterioles when DeltaP was either 20 or 40 mmHg (n = 7, P < .05). Treatment with BQ610 had no effect on zone 3 arterioles but significantly vasodilated zone 2 arterioles, increasing flow rate and vessel diameter, and decreasing vascular resistance (n = 7, P < .05). CONCLUSIONS: The tissue concentration of ET-1 is greater in human preterm intestine that demonstrates histologic evidence of NEC. Arterioles harvested from intestine exhibiting histologic evidence of NEC demonstrate vasoconstriction when compared with arterioles from relatively healthy intestine in the same resection specimen. This vasoconstriction was reversed by blockade of endothelin ET A receptors.

Arterioles↗

Hyperglycemia is associated with increased morbidity and mortality rates in neonates with necrotizing enterocolitis.

BACKGROUND PURPOSE: An association between hyperglycaemia and poor outcome has been reported in critically ill adults and children. The authors investigated the incidence of hyperglycemia in infants with necrotizing enterocolitis (NEC) and the relationship between glucose levels and outcome in these infants. METHODS: All glucose measurements (n = 6508) in 95 neonates with confirmed NEC admitted to the surgical intensive care unit (ICU) were reviewed. Maximum glucose concentration during admission (Gmax) was determined for each infant and correlated with outcome. Eleven infants in whom treatment was withdrawn within 24 hours owing to unsalvageable panintestinal NEC were excluded from the analysis. RESULTS: Glucose levels ranged from 0.5 to 35.0 mmol/L and 69% of infants became hyperglycemic (>8 mmol/L) during their admission. Thirty-two infants died. Mortality rate tended to be higher in infants with Gmax greater than 11.9 mmol/L compared with those with Gmax less than 11.9 mmol/L, and late (>10 days admission) mortality rate was significantly higher in these infants (29% v, 2%; P =.0009). Median length of stay was 9.3 days. Linear regression analysis indicated that Gmax was significantly related to length of stay (P <.0001). CONCLUSIONS: Hyperglycemia is common in infants with NEC admitted to the ICU and is associated with an increase in late mortality and longer intensive care stay. Aggressive glycemic control may improve outcome in this group of infants.

Birth Weight↗

Human torovirus: a new virus associated with neonatal necrotizing enterocolitis.

AIM: Toroviruses have been associated with gastroenteritis in both animals and humans. The aim of this study was to examine the fecal excretion of torovirus in infants with necrotizing enterocolitis (NEC). METHODS: We reviewed all infants with NEC admitted to our tertiary care NICU over a 5-y period who had stool specimens sent for microbial culture and virology. Infants in the NICU during the same period with diagnoses other than NEC served as controls. RESULTS: Forty-four infants with NEC stages I-III were identified, and pathogenic organisms were identified in 27 (61%). Toroviruses were identified in stool cultures in 48% of patients with NEC, and 17% of the non-NEC controls (p<0.001). There was no significant difference in illness severity or mortality between the torovirus-positive and -negative infants with NEC. CONCLUSION: Torovirus should be added to the list of infectious agents associated with NEC in newborn infants. The exact role torovirus plays in the etiology and progression of NEC warrants further investigation.

Case-Control Studies↗

Maternal hypertensive disorders are an independent risk factor for the development of necrotizing enterocolitis in very low birth weight infants.

OBJECTIVE: The purpose of this study was to compare complications and outcome of preterm neonates weighing < or =1,500 g who developed necrotizing enterocolitis (NEC) to neonates without NEC. STUDY DESIGN: During January, 1995 to December, 1998, 211 live preterm neonates were born with birth weight < or =1,500 g. A cross sectional prospective study was designed and two groups were defined: 17 neonates who developed NEC and 194 without NEC. Multiple logistic regression analysis was performed to determine independent risk factors for the development of NEC. RESULTS: The prevalence of NEC was 8% (17/211). The following complications were found to be significantly higher among mothers of neonates with NEC: mild pre-eclampsia (11.8 vs. 2.6%, p=0.04); severe pre-eclampsia (35.5 vs. 12.9%, p=0.01); chronic hypertension (29.4 vs. 5.7%, p<0.001) and low birth weight (968 +/- 233 vs. 1,123 +/- 257 g, p=0.02). In contrast, mean maternal age, mean gestational age at delivery and parity were not significantly different between the groups. A multivariate analysis including the following factors: maternal hypertensive disorders, pregestational diabetes mellitus, birth weight and gestational age at delivery, found only maternal hypertensive disorders to be independent risk factors for NEC (OR=5.21, 95% CI 1.64-16.58). CONCLUSIONS: Maternal hypertension is an independent risk factor for the development of NEC in preterm neonates weighing <1,500 g. Thus, maternal vascular disorders may play an important role in the pathophysiology of NEC.

Adult↗

Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants.

OBJECTIVE: We sought to determine if an association exists between the use of histamine-2 receptor (H2) blockers and the incidence of necrotizing enterocolitis (NEC) in infants of 401 to 1500 g in birth weight. STUDY DESIGN: Data from the National Institute of Child Health and Human Development Neonatal Research Network very low birth weight (401-1500 g) registry from September 1998 to December 2001 were analyzed. The relation between the diagnosis of NEC (Bell stage II or greater) and antecedent H2-blocker treatment was determined by using case-control methodology. Conditional logistic regression was implemented, controlling for gender, site of birth (outborn versus inborn), Apgar score of < 7 at 5 minutes, and postnatal steroids. RESULTS: Of 11072 infants who survived for at least 12 hours, 787 (7.1%) developed NEC (11.5% of infants 401-750 g, 9.1% of infants 751-1000 g, 6.0% of infants 1001-1250 g, and 3.9% of infants 1251-1500 g). Antecedent H2-blocker use was associated with an increased incidence of NEC (P < .0001). CONCLUSIONS: H2-blocker therapy was associated with higher rates of NEC, which is in agreement with a previous randomized trial of acidification of infant feeds that resulted in a decreased incidence of NEC. In combination, these data support the hypothesis that gastric pH level may be a factor in the pathogenesis of NEC.

Case-Control Studies↗

[Post-necrotizing enterocolitis stenosis of the colon associated with cytomegalovirus infection. Description of a clinical case].

We report a case of an infant with a post-necrotizing enterocolitis stenosis, resolved with operative measures. The histologic finding of Cytomegalovirus in the resected sigmoid colon rise the question if the intestinal stricture was the proper consequence of a primary enteric viral infection or a superinfection in a transitory immunodeficiency after the acute phase of necrotizing enterocolitis.

Colonic Diseases↗

Evaluation of hexosaminidase activity as a potential biochemical marker in serum for necrotizing enterocolitis.

The presence of increased serum activity of the lysosomal hydrolase hexosaminidase has been suggested to be potentially useful in the diagnosis of neonatal necrotizing enterocolitis (NEC). In the present study, serum activity of hexosaminidase was measured in 19 neonates with NEC and compared to developmental patterns of enzyme activity determined in 61 neonates without NEC. Infants with NEC were studied at intervals starting at the onset of disease and continuing until 6 weeks after diagnosis. In normal infants, serum activity of hexosaminidase increases with increasing gestational and postnatal ages. However, infants with NEC had relatively lower serum hexosaminidase activity than these control infants of similar gestational and postnatal ages. Necrotizing enterocolitis is not associated with increased serum activity of hexosaminidase.

Enterocolitis, Pseudomembranous↗

Plasma cytokine levels in necrotizing enterocolitis.

Plasma concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (> 10 pg/ml) in 71% samples with a mean of 48 pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL-6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage III (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p = 0.001). Postoperative plasma IL-6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ml, p = 0.79). We conclude that plasma concentration of IL-6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti-cytokine therapy in NEC.

Biomarkers↗

Necrotizing enterocolitis in full-term infants: case-control study and review of the literature.

OBJECTIVE: To examine the increasing number of full-term infants at our hospital exhibiting necrotizing enterocolitis (NEC) in order to characterize these cases and to discover common risk factors. METHODS: Medical charts were reviewed for all full-term infants (gestational age > 36 weeks) that were born in our institution during a 5-year period (from January 1, 1998 to December 31, 2002) and that developed definite NEC. Data regarding the rate of Cesarean section (CS) in our institution over the study period and five years prior to the study was also recorded. RESULTS: During the 5 years of the study, 14 full-term infants were found to have NEC. The incidence of NEC in full-term infants increased from 0.16 to 0.71 per 1000 live births in the 5-year period. Mean birth weight was 2829 g. All the NEC infants except one were delivered by CS, and all of them were fed either with a mixture of breast milk and formula or entirely by formula. Seven of the infants (50%) had no major known risk factors predisposing them for NEC. Mean age of disease onset was very early (4.1 days) in most of the infants (12 infants), and the colon was the main NEC site. The short-term outcome was favorable in all but one case, which required explorative laparotomy for intestinal perforation. The number of infants born by CS has been steadily increasing, and was almost three times greater during the study period in comparison to the preceding years. CONCLUSIONS: The etiology of NEC in the full-term population seems to differ from the etiology for the preterm group in its intestinal location and in the timing of its onset. The increase in the rate of CS over the years might be related to the concurrent increase in NEC, and this relationship should be further investigated.Journal

Case-Control Studies↗

Intestinal O2 consumption in necrotizing enterocolitis: role of nitric oxide.

We tested the hypothesis that inducible isoform of nitric oxide synthase (iNOS)-derived nitric oxide (NO) inhibits oxygen consumption (VO2) in human intestine resected for necrotizing enterocolitis (NEC). Each NEC resection specimen was divided into two sections based on histologic appearance: healthy or diseased. Intestine removed from infants for reasons other than NEC was used as control. The tissue injury score (0-6, with 6 indicating complete necrosis) was 0.4 +/- 0.2 in control tissue, 1.2 +/- 0.4 in NEC-healthy tissue, and 4.6 +/- 0.5 in NEC-diseased tissue. Prominent iNOS staining was present in villus enterocytes in NEC-healthy tissue but not in the other tissue types. Intestinal VO2 (per direct oximetry, in nM O2/min/g) was significantly greater in control tissue than in NEC-healthy or NEC-diseased tissues. Accumulation of NO into buffer bathing intestinal slices (in nM NO/microL/g) was greater in NEC-healthy tissue than control or NEC-diseased tissues. The specific iNOS antagonist L-Nomega-(1-iminoethyl)-lysine (L-NIL) reduced buffer NO concentration 76% and increased VO2 by 90% in NEC-healthy tissue; however, L-NIL had no effect on NO or VO2 in control or NEC-diseased tissue. Addition of exogenous NO via S-nitroso-N-acetylpenicillamine depressed VO2 in NEC-healthy and control tissues but not NEC-diseased tissue. A significant correlation was present between buffer NO concentration and VO2 in NEC-healthy tissue. We conclude that iNOS-derived NO suppresses VO2 in intestine resected for NEC that demonstrates a relatively normal histology on light microscopy.

Animals↗

Gastric residuals and their relationship to necrotizing enterocolitis in very low birth weight infants.

OBJECTIVE: To determine the characteristics of gastric residuals in very low birth weight (VLBW; <or=1500 g birth weight) infants with and without necrotizing enterocolitis (NEC). METHODS: Case-control study compared 51 VLBW infants who had proven NEC (pneumatosis intestinalis, portal venous gas, and/or perforation; excluding spontaneous gastrointestinal perforations) with 102 control subjects (without suspected or proven NEC) who were matched for birth weight, gestational age, race, and sex and were born January 1996 to December 2001. The age in days at diagnosis of NEC was identified in infants with NEC, and feeding characteristics were recorded for the previous 6 days. Feeding characteristics were recorded for control subjects for the corresponding time period. RESULTS: The median birth weight was 822 g and median gestational age was 26 weeks in both groups. Feeds were started on the fifth day, with a planned increase to full feeds over 10 days (median) in both groups. Median time to full feeds was 13 days in both groups. Median age of onset of NEC was day 24. The total residuals as a percentage of total feed volume (the primary outcome), maximum residual in the previous 6 days, maximum residual as a percentage of the feed, maximum residuals over the 6 days, and the percentage of feeds with residuals were higher in the NEC group. The maximum residual (median [25th-75th centiles]) was as follows: control subjects: 2 mL per feed (0.5-3.5) or 14% of a feed (4-33); NEC group: 4.5 mL per feed (1.5-9.8) or 40% of a feed (24-61). The total residuals as percentage of feeds and the average of maximum residuals increased in the NEC group from the first 3 days to the 3 days before diagnosis of NEC, but a similar increase was not noted for control subjects. CONCLUSIONS: VLBW infants who developed NEC had more gastric residuals. However, there was overlap with the normal control subjects. Of the gastric residual data, the maximum residual seems to be the best predictor for NEC in the subsequent days.

Birth Weight↗

Resection and primary anastomosis is a valid surgical option for infants with necrotizing enterocolitis who weigh less than 1000 g.

HYPOTHESIS: Primary anastomosis following intestinal resection is a valid surgical option in the treatment of infants with necrotizing enterocolitis (NEC) who weigh less than 1000 g. DESIGN: Retrospective case series. SETTING: Tertiary neonatal surgery referral center. PATIENTS: All infants with confirmed NEC weighing less than 1000 g admitted to our intensive care unit over 4 years. INTERVENTION: For infants requiring laparotomy and intestinal resection, primary anastomosis was performed whenever the clinical condition permitted. MAIN OUTCOME MEASURES: Short- and long-term survival, length of intensive care unit stay, and complications. RESULTS: Fifty-one infants with NEC who weighed less than 1000 g were admitted during the study period. Twelve infants underwent intestinal resection and primary anastomosis (median weight at surgery, 0.83 kg; range, 0.6-0.96 kg). One infant developed recurrent NEC, requiring further surgery, but there were no anastomotic leakages and no strictures. The median postoperative stay on our intensive care unit was 14 days (range, 2-49 days). All 12 infants survived their episode of acute NEC, and 8 are alive, with a median follow-up of 34.2 months (range, 4.7-48.4 months). Only 1 death was related to NEC. During the same period, 14 infants underwent intestinal resection and stoma formation. Ten survived the acute episode, and 6 are alive at a median follow-up of 24.0 months (range, 13.1-33.9 months). The median postoperative intensive care unit stay was 18 days (range, 2-74 days). Necrotizing enterocolitis-related complications occurred in 8 of these infants. CONCLUSIONS: The outcome of infants with NEC who weigh less than 1000 g and undergo primary anastomosis is comparable to that of infants treated using alternative techniques. It is, therefore, a valid surgical option in selected infants. The mortality in this group of infants is high.

Anastomosis, Surgical↗

Maternal cocaine abuse resulting in necrotizing enterocolitis. An experimental study in a rat model. II. Results of perfusion studies.

During the last decade, several publications have appeared associating the maternal use of cocaine and subsequent development of necrotizing enterocolitis (NEC). In 1994, the effects of cocaine in pregnant rats had been reported by this group: a significant decrease in the number of live births, mean birth weight and mean placental weight. In addition, histopathologic examinations revealed severe inflammation and degenerative vascular changes in the uterus and placenta. Severe histopathologic changes resembling NEC such as focal necrosis, necrobiosis, and hemorrhagic inflammatory changes in the gastrointestinal tract of the embryos were also reported. The aim of the second part of this study was to assess the hemodynamic effects of cocaine HCI in pregnant rats and the results of perfusion studies in the uterus, placenta, and fetuses to determine a relation between the dose of drug, hemodynamic changes, and degree of histopathologic findings. Forty-seven Wistar albino rats and 91 rat fetuses were studied: group A (pregnant rats), 16 rats and 91 rat fetuses, group B (nonpregnant rats), 31 rats. Each group was divided into subgroups of cocaine-abused and non-cocaine-abused rats. In each group 2-3 mCi technetium Tc-99m methoxyisobutyl-isonitryl (Sesta MIBI) was injected into the tail vein. Radioactivity counts per g tissue (cps/g) in the uterus, placenta, and fetus were assessed by gamma counter. Cocaine 75 mg/kg per day severely decreased the perfusion of the uterus, placenta, and fetuses. These impairments were statistically significant. In lower doses (30-50 mg/kg per day) no statistically significant changes were observed in the perfusion of the uterus and placenta, but a significant decrease in fetal perfusion was seen. In group B, no significant changes in the perfusion of the uterus due to cocaine were seen. Thus, maternal cocaine abuse results in a reduction in perfusion of the uterus, placenta, and fetus. There was a dose-dependent correlation between the perfusion changes and the development of NEC-like histopathologic changes: the higher the cocaine dose received by the mother, the higher the level of placental and fetal injury. We suggest that perinatal cocaine exposure should be considered a high risk for development of NEC in rat fetuses and embryos. For this reason, infants with a history of possible maternal cocaine abuse or positive urinary cocaine metabolites have to be followed very carefully for NEC.

Animals↗