Ram Mazkereth

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.

Growth restriction as a determinant of outcome in preterm discordant twins.

OBJECTIVE: To estimate the influence of intrauterine growth restriction (IUGR) on the outcome of preterm discordant twins. METHODS: Medical records of preterm twins born at 24–34 weeks of gestation between 1995 and 2000 were reviewed. Significant discordancy was defined as more than 15% difference in birth weight. Small for gestational age (SGA) was defined as birth weight less than 10th percentile, according to a twin-adjusted gestational age nomogram. The smaller twins of 96 discordant twin pairs were evaluated. The SGA-discordant group included the smaller twin of a discordant pair who was also SGA (n = 46); the appropriate-for-gestational-age (AGA)-discordant group included the smaller twin of a discordant pair who was appropriate for gestational age (n = 50). RESULTS: Maternal age, incidence of maternal hypertension, antenatal steroids, and gestational age at delivery were similar between groups. Delivery for suspected fetal compromise complicated significantly more pregnancies in the SGA-discordant group than in the AGA-discordant group (45.6% versus 16%, P = .005), as did respiratory distress syndrome (RDS) (37% versus 8%, P < .05) and intraventricular hemorrhage (21.7% versus 6%, P = .024). Mortality or severe neonatal morbidity (defined as severe RDS, intraventricular hemorrhage grades 3–4, or necrotizing enterocolitis) were significantly higher among neonates in the SGA-discordant group than in the AGA-discordant group (19.5% versus 6%, P = .04). The risk for major morbidity was 7.7-fold greater in the SGA-discordant than in the AGA-discordant group, adjusted for gestational age. CONCLUSION: Growth restriction in preterm discordant twins is associated with a 7.7-fold increased risk for major neonatal morbidity. Therefore, discordant twins with IUGR require closer monitoring than discordant twins without IUGR. LEVEL OF EVIDENCE: II-2

Mode of delivery of twin gestation with very low birthweight: is vaginal delivery safe?

OBJECTIVE The purpose of this study was to determine whether planned vaginal delivery is associated with increased risk of perinatal death and morbidity in twin pregnancies that are complicated by a very low birthweight of the second twin. STUDY DESIGN We conducted a retrospective cohort study of twin pregnancies in which the second twins birthweight was ≤1500 g. One hundred ninety-three twin gestations met the study criteria; patients were classified into 2 groups according to the planned mode of delivery: (1) cesarean delivery (n = 142) and (2) vaginal delivery (n = 51). In the vaginal delivery group, 21 pairs were in cephalic-cephalic presentation at the time of delivery; 28 pairs were cephalic-noncephalic, and 2 pairs were noncephalic-noncephalic. Composite adverse neonatal outcome was defined as the presence of neonatal death, respiratory distress syndrome, sepsis, necrotizing enterocolitis, or intraventricular hemorrhage grade 3-4. RESULTS Trial of vaginal delivery was successful for both twins in 90.5% of cephalic-cephalic twins and 96.4% in cephalic-noncephalic twins. The rate of intraventricular hemorrhage was significantly higher in the vaginal delivery group (29.4% vs 8.5%, respectively; P = .013; adjusted odds ratio [OR], 3.65; 95% confidence interval [CI], 1.32-10.1). The increased risk of intraventricular hemorrhage in the vaginal delivery groups was evident in both twin A (17.6% vs 7.0%; P = .029) and twin B (15.7% vs 4.9%; P = .014); however, these differences were not significant after adjustment for possible confounders (twin A: adjusted OR, 1.79; 95% CI, 0.58-5.55; twin B: adjusted OR, 2.13; 95% CI, 0.63-7.25). In addition, subgroup analysis revealed that both cephalic-cephalic and cephalic-noncephalic twins who were delivered vaginally had increased risk for intraventricular hemorrhage. There were no significant differences between the cesarean and vaginal delivery groups in the rates of Apgar score <7 at 5 minutes, arterial cord pH <7.1, composite adverse neonatal outcome, and neonatal mortality rate. However, the rate of respiratory distress syndrome was significantly lower in the vaginal delivery group (66.7% vs 69%; P = .042; OR, 0.34; 95% CI, 0.12-0.96). CONCLUSION Vaginal delivery of very low birthweight twins is associated with an increased risk of intraventricular hemorrhage, regardless of presentation. Because of the small sample size and the retrospective cohort design, large prospective randomized studies are needed.

Carina Angle Measurements for Diagnosis of Patent Ductus Arteriosus in Preterm Infants

Background: Bedside diagnosis of patent ductus arteriosus (PDA) continues to be important, especially when echocardiography is not readily available. Objective: The aim of our study was to evaluate whether measurement of left main bronchus displacement portrayed on a chest X-ray as a widened carina angle (CA) may support the presumptive diagnosis of PDA. Methods: Displacement of the left bronchus was assessed by measuring the angle between the two main bronchi at the level of the carina in 47 infants with PDA and 73 with no evidence of ductus, all born before 32 weeks of gestation. Results: The PDA group had a significantly wider CA (99.9 ± 12.1°) compared to the no-ductus group (72.9 ±15.7°; p < 0.001). Resolution of the PDA resulted in closure of the CA (62.3 ± 10.8°). We observed a significant and positive association between an increased CA measurement and PDA occurrence (OR = 1.7, 95% CI = 1.4–2.1). A CA cutoff point of 90° had the highest sensitivity (85%) and specificity (85%) for indicating the presence of PDA. Conclusions: Measurement of the CA is an easily accessible and reliable tool that may assist in establishing the diagnosis of PDA.

Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer

Summary Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation. We find that induction of endogenous NO production by enterocytes with supplements that upregulate ASL expression and complement its substrates results in improved epithelial integrity and alleviation of colitis and of inflammation-associated colon cancer.

Growth parameters of discordant preterm twins during the first year of life.

Abstract Objective: To evaluate and compare growth parameters (weight, length and head circumference) of discordant preterm twins during the first year of life. Methods: Retrospective data were collected on 78 pairs of >10% discordant preterm twins. Data regarding short-term neonatal outcome were recorded. Growth parameters were recorded at birth and again at 1 year of age, as collected by phone interview. Results: At 1 year of age, the gap was significantly reduced between the group of smaller twins and the group of larger twins on all the parameters studied. Discordance in weight decreased from a mean of 22% at birth (calculated from the weight of the larger twin) to 8.9%, in length from 6.5% to 2.5% and in head circumference from 5.5% to 1.3% at 1 year of age. While length and head circumference (HC) z-scores improved in both the large and the small siblings, weight z-score decreased significantly among the large twins and decreased mildly among the small twins. Conclusions: The gaps in growth parameters between the smaller twins of preterm discordant twins and their larger siblings are significantly reduced during the first year of life. The impact of the differential growth patterns between the two siblings should be further evaluated.

Weight loss and bronchopulmonary dysplasia in very low birth weight infants.

Our objective was to evaluate the extent of weight loss in very low birth weight (VLBW) preterm infants and to discover how weight loss and other variables correlate with bronchopulmonary dysplasia (BPD). We conducted an observational study of 387 VLBW preterms, gestational age (GA) < 33 weeks, in a single institution over a period of 5 years. The mean weight loss of AGA infants was significantly greater than that of SGA infants. In AGA infants, GA, z-score, weight loss, and male sex were found to correlate with BPD. After adjustments were made for GA and birth weight, each 10% loss of body weight increasesd the risk for developing BPD by a factor of 2.7. We concluded that excessive weight loss does not prevent BPD in VLBW preterms and presumably should be prevented. Controlled fluid restriction resulting in milder weight loss is probably the right choice.

“Golden Hour” quality improvement intervention and short-term outcome among preterm infants

ObjectiveTo evaluate the impact of a quality improvement intervention during the first hour of life (“Golden Hour”) on short-term preterm neonatal outcome.Study designA comprehensive protocol designed for initial stabilization and treatment of preterm infants that included cord blood sampling, use of a dedicated resuscitation room and improved team communication using Crew Resource Management tools. The infants admitted before and after implementation of the protocol were retrospectively compared in a matched case-control design.ResultsThere were 194 infants in the intervention group and 194 controls. Admission temperatures improved significantly from a mean of 35.26 °C to 36.26 °C (P < 0.001), and late-onset sepsis and bronchopulmonary dysplasia rates lowered significantly (P = 0.035 and P = 0.028, respectively) in the intervention group. There was trend towards reduction in early blood transfusion and ventilation duration.ConclusionsA “Golden Hour” quality improvement intervention was of significant benefit for preterm neonates. Further follow-up to assess long-term effects is warranted.

Internal and External Resources and the Adjustment of Parents of Premature Infants

Studies have shown premature birth and infant hospitalization to be associated with increased levels of parental distress. Internal and external psychological resources have been found to mitigate distress among persons coping with stressful medical events. The current study evaluated psychological resources and distress in 87 parents (57 mothers and 30 fathers) to whom an infant was born prematurely and hospitalized in the NICU of a large tertiary medical center. Parents were administered standardized measures of internal (problem-solving skills) and external (total spousal support, adequacy of spousal support) psychological resources and of psychological distress (depression, posttraumatic symptoms, and mood). Findings indicated that higher levels of problem-solving skills and more adequate spousal support, but not total spousal support, were related to lower levels of parental distress. Adequacy of spousal support and parents’ problem-solving skills accounted for 18% of the variance in overall mood and 13.8% of the variance in posttraumatic stress symptoms. A significant two-way interaction was found between adequacy of spousal support and problem-solving skills such that individuals with better problem-solving skills reported better overall mood independent of the adequacy of spousal support they receive. However, for individuals with poor problem-solving skills, the adequacy of the spousal support they receive was a significant factor in determining their overall mood. The theoretical and clinical implications of these findings are discussed in terms of the accessibility of these resources to assessment and their potential for change via existing intervention approaches.

Neonatal isolated rectal bleeding and the risk of hypersensitivity syndromes

Objective:When rectal bleeding occurs in an otherwise asymptomatic child, it can be classified as isolated rectal bleeding (IRB). Among the different etiologies suggested for IRB, one of the most common is a hypersensitivity reaction of the bowel mucosa to digested antigens. The objective of this study was to assess the long-term outcomes and the risk of developing hypersensitivity syndromes among infants following an IRB event.Study Design:A historical prospective comparative study was carried out. The study compared 77 infants who were born at the Sheba Medical Center in Israel during the period 2002 to 2009 and who experienced a neonatal IRB event to 77 infants with the same gestational age, but without IRB. Data were obtained from hospital records and from phone interviews with the parents regarding hypersensitivity syndrome between the ages of 3 and 10 years.Result:The IRB group was not at an increased risk of developing a hypersensitivity syndrome or gastrointestinal symptoms compared to the control group. Longer duration of breast-feeding was found to be related to a lower incidence of hypersensitivity symptoms.Conclusion:An IRB event in the neonatal period does not increase the risk of developing hypersensitivity syndromes or food allergies during childhood.