Long-term endocrine disorders in children born from pregnancies conceived following fertility treatments.

BACKGROUND: Despite the endocrine basis of several infertility etiologies, data on long-term endocrine consequences in offspring conceived following fertility treatments remain limited. AIM: To determine the risk of long-term endocrine disorders among children born after in-vitro fertilization (IVF) and ovulation induction (OI) as compared with spontaneous pregnancies. STUDY DESIGN, SUBJECTS, AND OUTCOME MEASURES: A population-based cohort study including all singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center was performed. Hospitalization rates up to the age of 18 years involving endocrine disorders were compared between children delivered following pregnancies achieved by IVF, OI, and spontaneous pregnancies. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence. A Cox regression model was used to control for confounders. RESULTS: During the study period, 242,187 singleton deliveries met the inclusion criteria; 1.0% were following IVF (n = 2603), 0.7% following OI (n = 1721), and the remaining (n = 237,863) were following spontaneous conceptions. Hospitalizations up to the age of 18 years involving endocrine disorders were comparable in children delivered following IVF (0.4%), OI (0.8%) and spontaneous pregnancies (0.5%; p = 0.09). The Kaplan-Meier survival curve demonstrated comparable cumulative incidence of endocrine morbidity following IVF and OI (log-rank p = 0.30). Using the Cox regression model while controlling for confounders, no significant association was noted between IVF (adjusted HR = 0.95, CI 0.51-1.87), or OI (adjusted HR = 1.32, CI 0.78-2.24) conceived pregnancies, and long-term pediatric endocrine morbidity. CONCLUSIONS: Singletons conceived via fertility treatment do not appear to be at an increased risk for long-term endocrine disorders.

Low Apgar score in term newborns and long-term infectious morbidity: a population-based cohort study with up to 18 years of follow-up.

Since introduced, the Apgar score has remained the most widespread predictor for neonatal morbidity and mortality. We aimed to investigate the association between low 5-min Apgar score and long-term infectious pediatric morbidity. A population-based cohort analysis was performed comparing total and specific subtypes of infectious morbidity leading to hospitalization among term newborns with normal (≥ 7) and low (< 7) 5-min Apgar scores, born between 1999 and 2014 at a single tertiary regional hospital. Infectious morbidity included hospitalizations involving a pre-defined set of infection-related ICD-9 codes. A Kaplan-Meier survival curve was constructed to compare cumulative infectious morbidity incidence and a Cox proportional hazards model to adjust for confounders. The long-term analysis of 223,335 children (excluding perinatal death cases) yielded 585 (0.3%) infants with low 5-min Apgar scores. The rate of infection-related hospitalizations was 9.8% and 12.4% among newborns with normal and low 5-min Apgar scores, respectively (p = 0.06). Adjusting for maternal age, gestational age, hypertension, diabetes, cesarean delivery, and fertility treatments, the association proved to be statistically significant (adjusted HR = 1.28; 95% CI 1.01-1.61).Conclusion: Term infants with low 5-min Apgar scores may be at an increased risk for long-term pediatric infectious morbidity.What is Known:• Though not meant to be a prognostic tool for long-term morbidity, studies assessing the correlation between low Apgar score and long-term outcomes were and are being performed, reporting significant associations with many outcomes-such as cerebral palsy (CP), ophthalmic disorders, GI disorders, and several types of malignancies.• Yet, an association between low Apgar scores and future health remains a matter of controversy.What is New:• Our work shows that a low 5-min Apgar score is independently associated with long-term pediatric infection-related hospitalizations among term singleton newborns.

Group B Streptococcus maternal colonization and respiratory infections in the offspring: lessons learned from an analysis of a population-based cohort with 18-year follow-up.

OBJECTIVE: Group B Streptococcus (GBS) early onset disease is a major cause for neonatal morbidity and mortality. We aimed to determine whether maternal GBS and the associated intrapartum antibiotic prophylaxis impacts pediatric long-term respiratory infectious morbidity. STUDY DESIGN: A population-based cohort study was conducted, during the years 1991-2013, comparing the incidence of hospitalizations due to common respiratory infections (RI) in offspring of mothers with and without GBS. Univariate analysis and a Cox proportional hazard model were used to estimate un-adjusted and adjusted hazard ratios for pediatric RI risk. RESULTS: During the study period, 173,757 term vaginal deliveries took place, of which 2.4% (4252) were diagnosed as GBS + gravidas. In univariate and multivariate analyses for the entire study period, RI risk was increased in exposed offspring. In a sensitivity analysis investigating study periods with different health policies, both GBS diagnosis rates and pediatric infectious respiratory morbidity rates increased over time, but with no independent association between the two. CONCLUSION: When analyzing large data sets spanning over long time periods, a special attention must be paid to account for healthcare trends, to avoid erroneous conclusions, as demonstrated here.

Vacuum Extraction in Preterm Deliveries and Long-Term Neurological Outcome of the Offspring.

BACKGROUND: Concern exists regarding a possible harmful impact of vacuum extraction on the preterm newborn. We aimed to evaluate the long-term pediatric neurodevelopmental outcomes of the preterm offspring after vacuum extraction. METHODS: A population-based cohort analysis was performed comparing the risk for long-term neurological morbidity (up to age 18 years) in preterm (less than 37 completed weeks of gestation) children born via following three delivery modes: vacuum extraction, spontaneous delivery, and Caesarean delivery performed during the second stage of labor. A Kaplan-Meier survival curve was used to compare the cumulative neurological morbidity in all groups. A Cox proportional hazards model was used to control for confounders. RESULTS: During the study period 11,662 preterm newborns met the inclusion criteria, 97.2% (n = 11,338) of which were born via spontaneous vaginal delivery, 2.3% (n = 267) underwent vacuum extraction, and 0.5% (n = 57) were delivered by Caesarean section during the second stage of labor. Gestational age at delivery median (range) was 36 (29 to 36) weeks for vacuum extractions, 36 (23 to 36) for spontaneous vaginal delivery, and 35 (29 to 36) for Caesarean delivery within second stage of labor. Total pediatric hospitalizations involving neurological diagnoses were comparable between the groups as were the cumulative incidences of total neurological morbidity in the survival curves (log rank P = 0.723). In the Cox regression model, vacuum delivery in preterm newborns was not found to be associated with later pediatric neurological hospitalizations. CONCLUSIONS: Vacuum extraction performed on preterm newborns does not appear to be independently associated with severe long-term neurological morbidity, as reflected by later pediatric hospitalizations.

Apgar score and long-term respiratory morbidity of the offspring: a population-based cohort study with up to 18 years of follow-up.

The objective of this study is to investigate whether a significant association exists between low 5-min Apgar scores (< 7) and respiratory morbidity of the offspring. A population-based cohort analysis was performed comparing subtypes of respiratory morbidity leading to hospitalizations among children (up to age 18 years) stratified by their 5 min Apgar scores. Data were collected from two databases of a regional tertiary center. All singleton deliveries occurring between 1991 and 2014 were included in the analysis. A Kaplan-Meier survival curve was constructed to compare cumulative respiratory-related hospitalization incidence and a Cox proportional hazards model to control for confounders. Deliveries (238,622) met the inclusion criteria. Low 5-min Apgar scores were recorded in 742 (0.3%) newborns. Incidence of respiratory hospitalizations was higher among the low 5 min Apgar score group (7.3 vs. 4.8% in the normal [≥ 7] 5 min Apgar score group; OR = 1.5, 95%CI 1.2-2.0, p = 0.003). Association remained significant in the Cox model (aHR = 1.4, 95%CI 1.1-1.9, p = 0.01). Incidence of respiratory-related hospitalizations in preterm born offspring was higher among the low vs. the normal 5 min Apgar score groups (13.4 vs. 7.2%, OR = 2.0, 95%CI 1.2-3.1 , p = 0.008). Association remained significant in the multivariable analysis (aHR = 1.6, 95%CI 1.1-2.5, p = 0.03). The survival curves demonstrated significantly higher cumulative respiratory morbidity in the low Agar score group for the entire cohort and for the preterm born subgroup.Conclusion: Newborns, of any gestational age, with low 5 min Apgar scores appear to be at an increased risk for pediatric respiratory morbidity. What is Known: • Apgar score is a method for assessment of the medical condition of a newborn, and of the need for medical intervention and/or resuscitation. Studies assesing the correlation between low Apgar score and short or long term outcomes report a sgnificant correlation with different outcomes including neurological development and more. As two of its five components (color and respiratory effort) are utilizing the respiratory status, low Apgar scoreis associated with a higher risk for immedisate respiratory morbidity. What is New: • Low Apgar score increases the chances for several long-term respiratory-related morbidities, independent of gestational age and other obstetrical circumstances.

Small for gestational age as an independent risk factor for long-term pediatric gastrointestinal morbidity of the offspring.

OBJECTIVE: The concept of neonatal programming has begun to emerge as an important component of adult health. Scarce data exist regarding perinatal risk factors for long-term gastrointestinal (GI) morbidity of the offspring. We aimed to evaluate the association between birthweight (BW) at term and long-term pediatric GI morbidity. STUDY DESIGN: A population-based cohort analysis was performed, comparing the risk of long-term GI morbidity (up to the age of 18 years) in children delivered at term according to their BW. The study included all term deliveries occurring between 1991 and 2014 at a single regional tertiary medical center. Multiple gestations and fetuses with congenital malformations were excluded. BW was subdivided into: small for gestational age (small for gestational age (SGA) - BW ≤ 5th centile), appropriate for gestational age (AGA -5th centile < BW < 95th centile), and large for gestational age (LGA - BW ≥95th centile). Hospitalizations up to the age of 18 years involving GI morbidity were evaluated, using a predefined set of ICD-9 codes, as recorded in the hospital files. A Kaplan-Meier survival curve was used to compare cumulative GI morbidity incidence. A Cox proportional hazards model was constructed to control for confounders. RESULTS: During the study period, 225,600 term singleton deliveries met the inclusion criteria. Of them, 4.6% (n = 10,415) were SGA and 4.3% (n = 9796) were LGA. During the 18-years follow-up period, 11,791 (5.2%) children were hospitalized with GI morbidity. Hospitalizations were significantly more common in the SGA group, as compared with the AGA and LGA groups (6.6 versus 5.2 versus 4.5%, respectively, p < .001) Specifically, inflammatory bowel disease, celiac, hernia, hepatitis, and cholecystitis, were more common in the SGA group. The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of gastrointestinal morbidity in the SGA group (log rank p < .001). In the Cox proportional hazards model, controlled for relevant clinical confounders, SGA BW was found to be an independent risk factor for long-term GI morbidity (adjusted HR = 1.23, 95%CI 1.14-1.33, p < .001). CONCLUSIONS: SGA offspring are at an increased and independent risk for long-term pediatric GI morbidity.

Low Apgar scores in term newborns and long-term gastro-intestinal morbidity: a population-based cohort study with up to 18 years of follow-up.

INTRODUCTION: Low Apgar scores (<7) measured at age 5 minutes can predict short-term infant morbidity and mortality. Although an association exists between low Apgar scores and neuropsychological disorders, other childhood disorders were not thoroughly studied. We aimed to study the possible association between low 5-minute Apgar scores in term newborns and their long-term childhood gastrointestinal (GI) morbidity. METHODS: A population-based cohort analysis was performed comparing total and different subtypes of GI-related pediatric hospitalizations among newborns with normal (≥7) and low (<7) 5-minute Apgar scores. The analysis included all term singletons born between the years 1999 and 2014 at a single tertiary regional medical center. Infants with congenital malformations, multiple gestations, and all perinatal deaths were excluded from the analysis. GI-related morbidities included hospitalizations involving a predefined set of ICD-9 codes, as recorded in the hospital computerized files. A Kaplan-Meier survival curve was constructed to compare the cumulative GI morbidity, and a Cox proportional hazards model was used to adjust for confounders. RESULTS: The study population, including 223 244 term singletons, was followed for an average of 10.02 ± 6.0 years (0-18 years, median 10.25) following discharge from birth hospitalization. Low 5-minute Apgar scores were recorded in 585 (0.3%) newborns. Incidence of GI-related hospitalizations was higher among the low versus the normal 5-minute Apgar score group (7.4 versus 5.2%; 8.6/1000 person years (PY) versus 5.2/1000 PY, respectively; p = .02; odds ratio =1.66, 95%CI 1.36-1.96). The association remained significant and independent while adjusting for gestational age, fetal weight, offspring gender, maternal age, maternal smoking, hypertension, and diabetes (Adjusted HR =1.57, 95%CI 1.16-2.12, p = .003). CONCLUSIONS: Low 5 minutes Apgar score is associated with an increased risk for long-term pediatric GI morbidity of the offspring. Our results suggest that Apgar scores can be used as a possible predictor for long-term pediatric morbidities and thus may necessitate appropriate surveillance in this vulnerable group of children.

Long-Term Cardiovascular Morbidity in Children Born Following Fertility Treatment.

OBJECTIVE: To determine the risk of long-term cardiovascular disease (CVD) among children born following in vitro fertilization (IVF) and compared with spontaneous pregnancies. STUDY DESIGN: A population-based cohort study including all singleton deliveries occurring between 1991and 2014 at a tertiary medical center was performed. Hospitalizations up to the age of 18 years involving CVD were evaluated in children delivered following IVF, ovulation induction, and spontaneous pregnancies. CVD included valvular disorders, hypertension, arrhythmias, rheumatic disease, cardiomyopathy, ischemic heart disease, and heart failure. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence, and a Cox regression model controlled for confounders. RESULTS: During the study period, 242 187 singleton deliveries met the inclusion criteria; 1.1% following IVF (n = 2603), and 0.7% following ovulation induction (n = 1721). Hospitalizations up to the age of 18 years involving CVD (n = 1503) were comparable in children delivered following IVF (0.6%), ovulation induction (0.7%), and spontaneous pregnancies (0.6%; P = .884). No significant difference in the cumulative incidence of CVD was noted between the groups (log rank P = .781). Controlling for maternal age, gestational age, birthweight, maternal diabetes, and hypertensive disorders in pregnancy, fertility treatment was not noted as a risk factor for long-term pediatric CVD (IVF adjusted hazard ratio 1.05, 95% CI 0.63-1.74, P = .86; ovulation induction adjusted hazard ratio 0.97, CI 95% 0.55-1.71, P = .92). CONCLUSIONS: Singletons conceived via fertility treatments do not appear to be at an increased risk of long-term pediatric CVD.

Term Elective Cesarean Delivery and Offspring Infectious Morbidity: A Population-Based Cohort Study.

BACKGROUND: Studies have found associations between delivery mode and offspring long-term health. We aimed to study the possible association between delivery mode and the risk for long-term infectious diseases of the offspring during a follow-up period of up of 18 years. METHODS: A population-based cohort analysis was performed comparing different subtypes of infectious morbidity leading to hospitalization among children, based on delivery mode (vaginal vs. elective cesarean). Data on pregnancy course and outcome, delivery mode and later offspring hospitalizations were available from a single tertiary center. All singleton uncomplicated deliveries and pregnancies between the years 1991 and 2014 were included in the analysis. Kaplan-Meier and multivariable Weibull survival models were applied to adjust for differences in follow-up time between the study groups and confounders. RESULTS: During the study period, 138,910 newborns met the inclusion criteria: 13,206 (9.5%) were delivered by elective cesarean delivery, and 125,704 (91.5%) were delivered vaginally. During the follow-up period (median: 10.22 years), 13,054 (9.4%) were hospitalized (at least once) with infectious morbidity: 12.0% and 9.1% among the cesarean and vaginally delivered children, respectively (Relative Risk: 1.36; 95% confidence interval: 1.28-1.43; incidence density rates for first hospitalization were 15.22/1000 person-years and 9.06/1000 person-years among cesarean and vaginally delivered children, respectively; Kaplan-Meier log rank P < 0.001). The association between cesarean delivery and long-term pediatric infectious morbidity remained significant in the multivariable model, controlling for confounding variables (adjusted hazard ratio: 1.18; 95% confidence interval: 1.11-1.25; P < 0.001). CONCLUSIONS: Children delivered by elective cesarean section are at an increased risk for hospitalization with pediatric infectious morbidity when compared with vaginally delivered children.

Infertility Treatments and Long-Term Neurologic Morbidity of the Offspring.

OBJECTIVE: To determine the risk of long-term neurologic morbidity among children (up to 18 years) born following in vitro fertilization (IVF) or ovulation induction (OI) treatments as compared with spontaneously conceived. STUDY DESIGN: A population-based cohort analysis was performed, including data from the perinatal computerized database on all singleton infants born at the Soroka University Medical Center (SUMC) between the years 1991 and 2014. This perinatal database was linked and cross-matched with the SUMC computerized dataset of all pediatric hospitalizations. RESULTS: Neurologic morbidity was significantly more common in IVF (3.7%) and OI (4.1%) offspring as compared with those following spontaneous pregnancies (3.1%; p = 0.017). In particular, attention deficit/hyperactivity disorders and headaches were more common in the OI group and sleep disorders in the IVF group, whereas autism and cerebral palsy were comparable between the groups. In the Weibull multivariable analysis, while controlling for maternal age, preterm delivery, birthweight centile, maternal diabetes, and hypertensive disorders, IVF (adjusted hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.14-1.71; p = 0.001), but not OI (adjusted HR: 1.17' 95% CI: 0.92-1.48; p = 0.196), was noted as an independent risk factor for long-term pediatric neurologic morbidity. CONCLUSION: IVF offspring appear to be at an increased risk of long-term neurologic morbidity up to 18 years of age.

Elective cesarean delivery at term and the long-term risk for respiratory morbidity of the offspring.

Maternal morbidity is associated with cesarean deliveries. However, new evidence suggests that short- and long-term neonatal morbidity is also associated. This includes respiratory morbidity with conflicting results. To determine whether mode of delivery has an impact on the long-term risk for respiratory morbidity in the offspring, a population-based cohort analysis was conducted including all singleton term deliveries occurring between 1991 and 2014 at a single tertiary medical center. A comparison was performed between children delivered via elective cesarean delivery (CD) and those delivered vaginally. Multiple gestations and fetuses with congenital malformations were excluded from the analysis as were all cases of urgent CDs. Pediatric hospitalizations involving respiratory morbidity of offspring up to the age of 18 years were evaluated. A Kaplan-Meier survival curve was used to compare cumulative respiratory morbidity incidence and a Cox regression model to control for confounders. During the study period, 132,054 term deliveries met the inclusion criteria; 8.9% were via elective CDs (n = 11,746) and 91.1% (n = 120,308) were vaginal deliveries. Hospitalizations of the offspring involving respiratory morbidity were significantly more common in offspring delivered by CDs (5.2 vs. 4.3% in vaginal deliveries, p < 0.001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory morbidity in the elective CD group (log rank p < 0.001). In a Cox proportional hazards model, while controlling for maternal age, gestational age, and birthweight, CD exhibited a significant and independent association with long-term respiratory morbidity of the offspring (adjusted hazard ratio = 1.22 (CI, 1.12-1.33), p < 0.001).Conclusion: Elective cesarean delivery at term is a significant risk factor for long-term pediatric respiratory morbidity of the offspring. What is Known: • Cesarean delivery is a major surgery with known possible complications. • Cesarean delivery has possible immediate complications for the newborn including respiratory complications. What is New: • Our study shows more long term respiratory morbidity in the CD group including asthma and obstructive sleep apnea. • Different possible explanations have been proposed including exposure to maternal flora during vaginal delivery and the stress hormones secreted during contractions and delivery.

The new Israeli PA.

Israel launched its new physician assistant profession with its first class of students, who were graduated in October 2017. The program is run by the Ministry of Health's Training and Development Department. This first course was focused on emergency medicine and the plan is to expand to anesthesiology and pathology in the near future.

Elective Cesarean Delivery at Term and the Long-Term Risk for Neurological Morbidity of the Offspring.

OBJECTIVE: The study's objective was to determine whether mode of delivery has an impact on the long-term risk for neurologic morbidity of the offspring. MATERIALS AND METHODS: This population-based cohort analysis included all term singleton deliveries between 1991 and 2014. The study population was divided into two study group: elective cesarean deliveries (CD) versus vaginal deliveries (VD). Urgent cesarean deliveries, pregnancy, and delivery complications including preeclampsia and gestational diabetes were excluded. The evaluation of cumulative neurological hospitalization rate over time was performed with a Kaplan-Meier survival analysis and Cox proportional hazards models were used to study the independent association between mode of delivery and neurological morbidity while controlling for potential confounders. RESULTS: During the study period 132,054 deliveries met the inclusion criteria, 11,746 CD (8.9%), and 120,308 (91.1%) VD. A total of 3,626 neurological hospitalizations were documented with 2.70% (3,244) in the VD group as compared with 3.25% (382) in the CD group. The survival curves showed higher cumulative hospitalization rates in the CD as compared with the VD group (p ≤ 0.001). The Cox analysis demonstrated CD to be an independent risk factor for pediatric neurological hospitalizations (p < 0.001). CONCLUSION: Term elective CD is an independent risk factor for neurological morbidity of the offspring.

Cesarean Delivery and Childhood Malignancies: A Single-Center, Population-Based Cohort Study.

Rising rates of cesarean deliveries worldwide prompt the evaluation of long-term morbidity to the offspring. In this retrospective cohort study, we evaluated whether cesarean delivery influences the development of childhood malignancies. We identified an association of cesarean delivery with acute lymphoblastic leukemia in children, suggesting prudence in the recommendation of cesarean delivery for nonmedically indicated cases.

Maternal history of recurrent pregnancy loss is associated with increased risk for long-term pediatric gastrointestinal morbidity in the offspring.

PROBLEM: Recurrent pregnancy loss (RPL) potentially involves an abnormal maternal inflammatory response. We investigated whether children of mothers with a history of RPL are at an increased risk for childhood gastrointestinal (GI) morbidity, with a specific focus on inflammatory bowel diseases (IBD). METHOD OF STUDY: A population-based cohort analysis comparing the risk for long-term GI morbidity in children born to mothers with and without a history of RPL. Gastrointestinal (GI) morbidity included hospitalizations involving a pre-defined set of ICD-9 codes. RESULTS: During the study period, 242 186 newborns met the inclusion criteria; 5% of which were offspring to mothers with a history of RPL. Gastrointestinal morbidity was significantly more common in the RPL group (6.6% vs 5.3%). Specifically, offspring to mothers with a history of RPL had significantly higher rates of IBD (2.1% vs 1.7%). CONCLUSION: Maternal history of RPL is associated with an increased risk for pediatric GI morbidity in the offspring.

Fertility treatments and pediatric neoplasms of the offspring: results of a population-based cohort with a median follow-up of 10 years.

OBJECTIVE: Studies have questioned the long-term health effects of offspring conceived after fertility treatments. METHODS: We aimed to evaluate whether an association exists between mode of conception (in vitro fertilization, ovulation induction, or spontaneous pregnancy) and neoplasm risk (both benign and malignant tumors) among the offspring; we observed the offspring for up to 18 years. STUDY DESIGN: A population-based cohort analysis was performed that compared the risk for neoplasms among children (up to the age of 18 years) based on mode of conception. Neoplasm diagnoses were based on hospital records of the same single tertiary center in the region. All singletons born during from 1991-2013 and discharged alive were included in the study. Offspring with congenital malformations were excluded from the analysis. Kaplan-Meier survival curves were constructed to compare cumulative neoplasms incidence; multivariable survival analyses were used to control for confounders that included gestational age, pregnancy complications, and maternal factors. RESULTS: During the study period, 242,187 newborn infants met the inclusion criteria: 2603 (1.1%) were conceived after in vitro fertilization; 1721 (0.7%) were conceived after ovulation induction treatments, and 237,863 (98.3%) were conceived spontaneously. During the follow-up period (median, 10.55 years), 1498 neoplasms(0.6%) were diagnosed. Incidence density rate for neoplasms was higher among children conceived either after in vitro fertilization (1.5/1000 person years) or ovulation induction treatments (1.0/1000 person years), as compared with naturally conceived children (0.59/1000 person years; Kaplan-Meier log rank, P<.001). The association between in vitro fertilization and total pediatric neoplasms and the association between any fertility treatments and malignancies remained significant; we controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age (adjusted hazard ratio, 2.48; 95% confidence interval, 1.71-3.50; and adjusted hazard ratio, 1.96; 95% confidence interval, 1.14-3.36, for all neoplasms and all malignancies, respectively). CONCLUSION: Children conceived after fertility treatments are at an increased risk for pediatric neoplasms.

Partial enteral nutrition with a Crohn's disease exclusion diet is effective for induction of remission in children and young adults with Crohn's disease.

BACKGROUND: Exclusive enteral nutrition is effective for inducing remission in active pediatric Crohn's disease. Partial enteral nutrition (PEN) with free diet is ineffective for inducing remission, suggesting that the mechanism depends on exclusion of free diet. We developed an alternative diet based on PEN with exclusion of dietary components hypothesized to affect the microbiome or intestinal permeability. METHODS: Children and young adults with active disease defined as a pediatric Crohn's disease activity index >7.5 or Harvey-Bradshaw index ≥4 received a 6-week structured Crohn's disease exclusion diet that allowed access to specific foods and restricted exposure to all other foods, and up to 50% of dietary calories from a polymeric formula. Remission, C-reactive protien, and erythrocyte sedimentation rate were reevaluated at 6 weeks. The primary endpoint was remission at 6 weeks defined as Harvey-Bradshaw index ≤3 for all patients and pediatric Crohn's disease activity index <7.5 in children. RESULTS: We treated 47 patients (mean age, 16.1 ± 5.6 yr; 34 children). Response and remission were obtained in 37 (78.7%) and 33 (70.2%) patients, respectively. Mean pediatric Crohn's disease activity index decreased from 27.7 ± 9.4 to 5.4 ± 8 (P < 0.001), Harvey-Bradshaw index from 6.4 ± 2.7 to 1.8 ± 2.9 (P < 0.001). Remission was obtained in 70% of children and 69% of adults. Normalization of previously elevated CRP occurred in 21 of 30 (70%) patients in remission. Seven patients used the diet without PEN; 6 of 7 obtained remission. CONCLUSIONS: Dietary therapy involving PEN with an exclusion diet seems to lead to high remission rates in early mild-to-moderate luminal Crohn's disease in children and young adults.

Role reversal method for treatment of food refusal associated with infantile feeding disorders.

OBJECTIVES: Infantile feeding disorders (IFDs) are common causes of food refusal and failure to thrive, and are frequently encountered by primary care physicians and specialists. We have published the Wolfson criteria for IFD, which have eased the approach to the diagnosis of IFDs. Along with and complementary to the Wolfson criteria, we have also developed the role reversal treatment method for IFD, which has been briefly described earlier. The aim of this study was to validate the role reversal treatment method on a cohort of infants diagnosed as having IFD and to present a detailed description of this method for the first time. METHODS: Parents of infants and children diagnosed as having IFD were invited to participate in the study; they were handed over a questionnaire comprising 6 categories of questions related to patient and parents behaviors, attitudes, and perceptions, which was completed at initiation and at the end of treatment. Full response was defined as improved normative feeding, cessation of abnormal parental feeding, and improved or normal growth patterns. A partial response was defined as success with two-third categories. RESULTS: We enrolled 38 patients, and 32 patients completed the study. Improved feeding occurred in 78%, full recovery was documented in 53% of infants by 6 months, and partial response was observed in another 25%. All forms of pathological feeding improved significantly (mechanistic, nocturnal, persecutory, forced feeding, and distraction). CONCLUSIONS: The role reversal treatment method is a simple and effective approach to the treatment of food refusal associated with IFD.

Eosinophilic esophagitis: an immune-mediated esophageal disease.

Eosinophilic esophagitis (EoE) is an emerging disease defined by esophageal dysfunction, by typical endoscopic findings and by abnormal eosinophilic inflammation within the esophagus. Eosinophilic accumulation in the esophagus occurs as a result of esophageal overexpression of pro-inflammatory mediators, including T cells and mast cells, cytokines such as interleukin (IL)-13, IL-5 and IL-15, as well as chemoattractants (eotaxin and transforming growth factor-ß1, fibroblast growth factor and the newly characterized gene--thymic stromal lymphopoietin, which is a key regulator of allergic sensitization initiation). The role of allergy, particularly food allergy in EoE is indisputable, as elimination diet is a proven commonly used treatment for the disease. However, unlike classical immediate IgE-mediated reaction to allergen, EoE is associated with an altered immune response, characterized by a combination of IgE-mediated and non-IgE-mediated mechanisms. In this review, we aim to discuss the many typical aspects of EoE as opposed to other entities involving the esophagus, with focusing on the aberrant immune-mediated key players contributing to the pathogenesis of this unique disease.

Abnormal liver transaminases and conjugated hyperbilirubinemia at presentation of acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. While hepatitis is a well-known complication during the treatment phase of ALL, the association of abnormal liver biochemistries at initial presentation of leukemia is poorly described. The aim of this study is to examine the prevalence and assess the clinical impact of hepatitis at diagnosis in children with ALL. PROCEDURE: All children diagnosed with ALL at BC Children's Hospital between 2001 and 2006 were included. Charts were reviewed and data recorded to a computerized spreadsheet. Descriptive statistical analyses were performed. RESULTS: One hundred forty-seven ALL patients were identified. Over one third of patients had abnormal liver transaminase values (AST and/or ALT). Of the patients with abnormal transaminases, (52%) had ALT elevations twice the upper limit of normal. Risk factors for elevated transaminases included a high WBC count at diagnosis, older age, bulky disease, and T-cell leukemia. Conjugated hyperbilirubinemia was observed in 3.4% of subjects. Of these cases, 60% received steroids prior to induction chemotherapy and all had rapid resolution of their hyperbilirubinemia to normal levels. CONCLUSIONS: Elevated transaminases are common at initial presentation of ALL and are likely due to hepatic injury from leukemic infiltrates. Conjugated hyperbilirubinemia at presentation may require treatment modification and dose reduction. A short course of steroids prior to initiation of induction chemotherapy appears to result in rapid resolution of the hyperbilirubinemia with subsequent ability to provide full dosing of induction chemotherapy.