[PERIOPERATIVE MANAGEMENT OF AN ADOLESCENT GIRL WITH SEVERE FACTOR XI DEFICIENCY AND INHIBITORS].

INTRODUCTION: Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by injury-related hemorrhage, mostly associated with surgical procedures at sites noted for high fibrinolytic activity. Severe FXI deficiency is defined when the FXI level is lower than 15-20 IU/dL. Perioperative prophylactic treatment for high-bleeding-risk surgery in patients with severe FXI deficiency is based on fresh frozen plasma (FFP) transfusions or FXI concentrate (where available). Exposure to FFP and to FXI concentrate may lead to the development of inhibitory antibodies against FXI. This phenomenon occurs mostly in patients with very severe FXI deficiency (baseline FXI <1IU/dL) and is associated with an increased risk of substantial perioperative bleeding, unresponsive to FXI replacement. Thus, in individuals with severe FXI deficiency, routine testing for the presence of inhibitory antibodies against FXI is recommended. We present a 17-year-old adolescent patient with very severe FXI deficiency, who developed an inhibitor to FXI following FFP exposure associated with neurosurgery for medulloblastoma. Prophylactic treatment for subsequent invasive procedures consisted of single low dose (10 mcg/kg) recombinant activated factor VII (rFVIIa) and tranexamic acid (Hexakapron). The procedures were performed uneventfully, with no hemorrhagic or thrombotic complications. In patients with very severe FXI deficiency, the development of inhibitory antibodies following plasma replacement therapy comprises a rare and challenging occurrence. The formulation of a safe and effective evidence-based protocol for hemostatic support in these patients requires multi-center collaboration.

Syndromes predisposing to leukemia are a major cause of inherited cytopenias in children.

Prolonged cytopenias are a non-specific sign with a wide differential diagnosis. Among inherited disorders, cytopenias predisposing to leukemia require a timely and accurate diagnosis to ensure appropriate medical management, including adequate monitoring and stem cell transplantation prior to the development of leukemia. We aimed to define the types and prevalences of the genetic causes leading to persistent cytopenias in children. The study comprises children with persistent cytopenias, myelodysplastic syndrome, aplastic anemia, or suspected inherited bone marrow failure syndromes, who were referred for genetic evaluation from all pediatric hematology centers in Israel during 2016-2019. For variant detection, we used Sanger sequencing of commonly mutated genes and a custom-made targeted next-generation sequencing panel covering 226 genes known to be mutated in inherited cytopenias; the minority subsequently underwent whole exome sequencing. In total, 189 children with persistent cytopenias underwent a genetic evaluation. Pathogenic and likely pathogenic variants were identified in 59 patients (31.2%), including 47 with leukemia predisposing syndromes. Most of the latter (32, 68.1%) had inherited bone marrow failure syndromes, nine (19.1%) had inherited thrombocytopenia predisposing to leukemia, and three each (6.4%) had predisposition to myelodysplastic syndrome or congenital neutropenia. Twelve patients had cytopenias with no known leukemia predisposition, including nine children with inherited thrombocytopenia and three with congenital neutropenia. In summary, almost one third of 189 children referred with persistent cytopenias had an underlying inherited disorder; 79.7% of whom had a germline predisposition to leukemia. Precise diagnosis of children with cytopenias should direct follow-up and management programs and may positively impact disease outcome.

Tramadol Treatment for Chemotherapy-induced Mucositis Pain in Children.

Mucositis, a painful and debilitating condition, is a common side effect of chemotherapy. The role of tramadol in the treatment of mucositis in pediatric patients has not yet been determined. In this retrospective study, we evaluate whether tramadol as single agent achieved a reduction of pain intensity among oncologic children admitted for mucositis. In total, 34 of 54 (63%) episodes were treated with tramadol alone and achieved adequate pain relief. Tramadol's side effects were mild and manageable.

Neutrophil Elastase Activity as a Surrogate Marker for Neutrophil Extracellular Trap Formation following Hematopoietic Stem Cell Transplantation.

Impaired neutrophil extracellular trap (NET) formation compromises the host defense after engraftment following hematopoietic stem cell transplantation (HSCT) despite adequate neutrophil counts. The aims of the present study were to determine reference ranges for the activity of key enzymes of NET formation-neutrophil elastase (NE) and myeloperoxidase (MPO)-in a healthy population and to unravel the recovery dynamics of NET formation over time following HSCT, along with NE and MPO enzymatic activities. Reference ranges of NE and MPO activity were derived from 50 healthy volunteers. During 2017 to 2018, 11 consecutive pediatric patients undergoing allogeneic or autologous HSCT were recruited at a single referral center for pediatric hemato-oncology. Patients were followed for up to 1 year following engraftment. The mean reference value was 7.5 ± .4 mU for NE activity and 2.17 ± .4 U for MPO activity in the healthy population, and enzymatic activity of MPO was significantly higher in males. At 3 weeks following neutrophil engraftment, all study participants demonstrated extremely low enzymatic NE activity, whereas MPO activity was above the lower normal reference range at all time points. Reduced NE activity corresponded to the inability to form NETs. Neutrophil function improved over time, but partial impairment persisted for 7 months following transplantation. The ability of neutrophils to form NETs was significantly impaired for 3 weeks after engraftment in the setting of HSCT, exposing patients to bacterial infections. NE activity might serve as a surrogate marker for the capacity of neutrophils to form NETs.

Neutrophil extracellular traps in pediatric inflammatory bowel disease.

Neutrophil extracellular traps (NETs) are fibers composed of chromatin and neutrophil proteins released by activated neutrophils. NETs trap and kill microbes, activate dendritic and T cells, and are implicated in autoimmune and vascular diseases. The pathogenesis of inflammatory bowel disease (IBD) is multifactorial and characterized by chronic active mucosal inflammation with controversial contribution of neutrophils. Our aim is to describe the involvement of NETs in pediatric IBD. We retrospectively examined biopsies from the small bowel and colon of children at diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). The biopsies were labeled for neutrophil elastase, myeloperoxidase, DNA, chromatin and histones in order to identify NETs. Samples of two children with normal colonoscopy served as controls. Twelve patients (5 boys) were included, 6 with CD and 6 with UC. Their average age was 12.2 years (range 5-16). NETs were found in all samples from patients and not in the samples from the two controls. This is the first demonstration of the presence of NETs in biopsies taken from the small bowel and colon of pediatric patients with IBD. More studies are needed in order to identify the role of NETs in CD/UC pathogenesis.

Significant correlation between peripheral blood CD34+ cell count in children prior to aphaeresis and CD34+ cell yield following aphaeresis: A single-center experience.

Numerous adults' studies demonstrated that preaphaeresis CD34+ cells significantly correlate with the number of CD34+ cells collected by the aphaeresis procedure. Equivalent studies in children are scarce. We studied retrospectively 92 aphaeresis procedures performed following chemotherapy (44) or in steady state (48) in 60 pediatric patients (40 males, 20 females), median age of 7.5 years. Aphaeresis procedures were performed using a SPECTRA Optica (TERUMOBCT) continuous flow cell separator. CD34+ cell concentrations were assessed using flow cytometry. A highly significant correlation between peripheral CD34 cell count on the day of aphaeresis and CD34 cell yield per kg (R2  = .824, P < .0001) was demonstrated. A higher preaphaeresis CD34 cell count was demonstrated in patients with higher preaphaeresis white blood cell count, in patients with brain tumors, and in patients who received chemotherapy as part of their mobilization protocol. A threshold number of 20 peripheral CD34+ cell/µL was found to predict harvesting of 3 × 106 stem cells/kg, and 30 peripheral CD34+ cell/µL for harvesting of 5 × 106 stem cells/kg. This significant correlation between peripheral CD34 cell count and CD34 cell yield, and the threshold number of peripheral CD34 found to predict adequate harvesting can be useful in planning the optimal time for aphaeresis in children.

Lessons From an Outbreak of Varicella Infection in Pediatric Hemato-oncology Patients.

BACKGROUND: Immunocompromised patients exposed to varicella may experience significant morbidity and a 7% mortality rate. Management and outcome of an outbreak of varicella infection among hospitalized pediatric hemato-oncology patients using the guidelines of the American Academy of Pediatrics Committee on Infectious Diseases are presented. METHODS: This retrospective study describes an outbreak of varicella infection between February 2011 and June 2011. Data were retrieved from the patients' files. Positive polymerase chain reaction results for varicella zoster virus from vesicular skin lesions were used for the diagnosis of varicella infection. RESULTS: Twelve pediatric hemato-oncology patients experienced 13 episodes of varicella infection, 11 underwent 1 episode each and 1 patient had 2 episodes. All exposed patients without immunity received varicella zoster immune globulins or intravenous immunoglobulin and were isolated as recommended by the guidelines. Infected patients received intravenous acyclovir. One patient with acute lymphoblastic leukemia at induction chemotherapy died. All the other patients survived. CONCLUSIONS: Our experience in the management of hospitalized immunocompromised patients exposed to varicella was that a positive IgG serology did not confer protection after exposure to varicella infection and thus can not serve as a marker for immunity. Unlike the isolation period sufficient for immunocompetent patients, crusted lesions can be contagious and thus require extended isolation for immunocompromised patients. Patients receiving rituximab are at greater risk of having persistent or recurrent disease. Studies with a larger sample size should be performed to better assess the management of immunocompromized patients exposed to varicella.

Reduced Neutrophil Elastase Activity and Neutrophil Extracellular Traps in Pediatric Acute Myeloid Leukemia May Increase the Rate of Infections.

Data on the production of neutrophil extracellular traps (NETs) in leukemia patients are scant. Phagocytosis, hydrogen peroxide, neutrophil elastase and myeloperoxidase enzymatic activity as well as NETs formation were studied in 10 pediatric acute lymphoblastic leukemia and 7 pediatric acute myeloid leukemia (AML) patients after induction chemotherapy. Median neutrophil elastase activity and NETs formation were lower in AML versus acute lymphoblastic leukemia (41% vs. 90%, P=0.005 and 51% vs. 94%, P=0.008, respectively). AML patients had more episodes of febrile neutropenia during the first 2 blocks of treatment (100% vs. 40%, P=0.011) and a trend for more invasive bacterial and fungal infections.

Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients.

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life-threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD). Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long-term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28-36, 2017. © 2016 Wiley Periodicals, Inc.

Combined plerixafor and granulocyte colony-stimulating factor for harvesting high-dose hematopoietic stem cells: Possible niche for plerixafor use in pediatric patients.

PB is a source of HSC, especially for autologous HCT in solid tumors. However, there is a risk of failing to achieve the target number of SC after mobilization with growth factors alone in patients who were heavily pretreated with chemotherapy or those in need for tandem transplants. SC were harvested from seven pediatric patients with solid tumors who were in need of autologous HCT following combination GCSF and plerixafor. Six of them received plerixafor after failing to achieve enough SC with GCSF only, while the seventh patient received the combined protocol upfront. All seven patients achieved the target number of SC according to their treatment protocol. There were no adverse events. All patients underwent autologous HCT using the harvested HSC and achieved full engraftment. A protocol for harvesting autologous HCT using GCSF and plerixafor is feasible and safe in children with solid tumors who had been heavily pretreated with chemotherapy or needed tandem transplants.

A proposed role for neutrophil extracellular traps in cancer immunoediting.

Upon activation, neutrophils release fibers composed of chromatin and neutrophil proteins termed neutrophil extracellular traps (NETs). NETs trap and kill microbes, activate dendritic cells and T cells, and are implicated in autoimmune and vascular diseases. Given the growing interest in the role of neutrophils in cancer immunoediting and the diverse function of NETs, we searched for NETs release by tumor-associated neutrophils (TANs). Using pediatric Ewing sarcoma (ES) as a model, we retrospectively examined histopathological material from diagnostic biopsies of eight patients (mean ± SD age of 11.5 ± 4.7 years). TANs were found in six patients and in two of those we identified NETs. These two patients presented with metastatic disease and despite entering complete remission after intensive chemotherapy had an early relapse. NETs were not identified in the diagnostic biopsies of two patients with localized disease and two with metastatic disease. This study is the first to show that TANs in ES are activated to make NETs, pointing to a possible role of NETs in cancer.

Lessons learned from phagocytic function studies in a large cohort of patients with recurrent infections.

BACKGROUND: There is a paucity of data on the relationship between demographic characteristics, specific clinical manifestations, and neutrophil dysfunction, guiding physicians to decide which clinical signs and symptoms are a code for an underlying phagocytic disorder. METHODS: The data over a 21-year period of all adult and pediatric patients referred to our Laboratory for Leukocyte Functions with recurrent pyogenic infections were analyzed. Neutrophil function studies included chemotaxis, superoxide production (SOP), bactericidal activity (BA), and specific studies in case of suspected primary phagocytic disorder (PPD). RESULTS: Neutrophil dysfunction was found in 33.6% of 998 patients; chemotaxis in 16.6%, SOP in 6%, and BA in 24.5%. The younger the patient and the more organ systems involved, the greater the probability of finding phagocytic impairment. Impaired chemotaxis correlated with recurrent aphthous stomatitis, infections associated with elevated IgE, and purulent upper respiratory tract infections. Impaired SOP and BA correlated with deep-seated abscesses, recurrent lymphadenitis, sepsis, and bone and joint and central nervous system infections. PPDs were identified in 5.7%, chronic granulomatous disease in 4.8%, neutrophil glucose-6-phosphate dehydrogenase deficiency in 0.3%, leukocyte adhesion deficiency type 1 in 0.4%, and myeloperoxidase deficiency in 0.2%. Phagocytic evaluation contributed to the diagnosis of hyperimmunoglobulin-E syndrome (n = 21) and Chediak-Higashi syndrome (n = 3). CONCLUSIONS: PPDs are identified in 5.7% of patients with recurrent pyogenic infections; in the remainder, phagocytic dysfunction may be related to deleterious effects of persistent infection, drug consumption, or disorders not yet established.

Pediatric chronic rhinosinusitis histopathology: differences and similarities with the adult form.

OBJECTIVE: To compare the histopathology and immunohistochemistry of pediatric and adult chronic rhinosinusitis (CRS). STUDY DESIGN: Cross-sectional study. SETTING: University-affiliated hospital. PATIENTS AND METHODS: Inflamed sinus-mucosal samples of 16 children (mean age, 11.6 ± 2.9 years) with refractory CRS who underwent endoscopic sinus surgery were studied. Twenty-nine diagnosis-matched adults served as controls. Study analysis covered sinus computed tomography (CT) scores, general pathologic features, eosinophil and T-lymphocyte population, and thickness and integrity of the epithelium. RESULTS: Children had a lower CT score than adults did (P = .005). The inflammatory response of the children, which differed greatly from that of adults, was dominated by cellular infiltration of the lamina propria with chronic inflammatory cells and fibrosis (8/16 had extensive fibrosis); eosinophils were scanty. Adult CRS was characterized by polypoid mucosa and eosinophilia (type A) or glandular hyperplasia (type B). Extensive fibrosis was shown in adult type-B patients (7/13). Assessment of eosinophils in the lamina propria showed marginal statistical significance between children and adults (P = .065). This difference was accentuated when pediatric and adult type A were compared (14.6 ± 25.3 vs 121.5 ± 174.2 cell/mm(2); P = .043). Complete epithelial shedding was less significant in children (9.4% ± 8.2% vs 25.4% ± 15.1%; P < .001). The number of lamina propria and epithelial T lymphocytes was similar. CONCLUSIONS: The marked differences in the inflammatory response of children and adults with CRS may attest to different pathophysiologic pathways. The significantly reduced epithelial shedding in children is probably associated with diminished tissue eosinophilia. Extensive fibrosis was found in half of adult type-B patients; similar findings were found in children.

Blood sampling through peripheral venous catheters is reliable for selected basic analytes in children.

OBJECTIVE: The goal was to determine the interchangeability of peripheral venous catheter (PVC) and venipuncture blood sampling (BS). METHODS: Paired blood samples from hospitalized children were obtained through venipuncture and from existing PVCs, following discard of 2 mL of blood. Comparisons of 9 complete blood count indices (white and red blood cell counts, hemoglobin and hematocrit levels, mean corpuscular volume, mean corpuscular hemoglobin level, red blood cell distribution width, platelet count, and mean platelet volume) and 5 basic chemical analysis indices (sodium, potassium, glucose, chloride, and urea levels) were performed, and hemolysis was documented. RESULTS: Irrespective of gauge, blood samples were obtained successfully from 40 (85.1%) of 47 PVCs, with no abnormal hemolysis. BS through venipuncture took longer than BS from PVCs (175.8 +/- 229.6 vs 104.5 +/- 53.4 seconds; P = .053) and was associated with significantly more distress/crying (73.1% vs 0%; P < .001). There were no significant differences between venipuncture and PVC samples (paired t test). Twenty-one (6%) of 348 pairs analyzed with the Clinical Laboratory Improvement Amendment standards fell outside the range of acceptable variance (8 of 21 aberrations were attributed to glucose measurements). Bland-Altman analysis indicated that, with the exclusion of glucose measurements, BS from PVCs is reliable, with 29 (6.5%) of 448 pairs exceeding the limits of agreement. Of those, 9 cases were clinically significant, but none would have altered clinical management. CONCLUSIONS: PVC sampling was shown to be a pain-reducing method that can be used for children for selected basic analytes. The findings for glucose were unreliable.

Gastric emptying time of oral contrast material in children and adolescents undergoing abdominal computed tomography.

OBJECTIVES: : Considering the hazards of pulmonary aspiration of oral contrast material (OCM) during general anesthesia, we investigated the gastric emptying time (GET) of OCM in children and adolescents undergoing abdominal computed tomography (CT). PATIENTS AND METHODS: : Included in the study were 101 consecutive patients ages 3.1 to 17.9 years (mean age 12.2 +/- 3.3 years), who underwent contrast-enhanced abdominal CT for suspected acute appendicitis (n = 90), abdominal trauma (n = 10), or suspected ileus (n = 1). Oral iodinated ioxithalamate was given for bowel opacification. Background data (age, sex, weight, chronic diseases, and medication intake), time of initiation and completion of OCM, and time of CT scanning were recorded. To estimate the GET of OCM, CT images were reviewed to examine whether the stomach was empty or full of OCM at the time of imaging. RESULTS: : The Kaplan-Meier curve showed that 75% of the patients had OCM in the stomach 48 +/- 5.2 minutes after its completion, 50% after 74 +/- 7.9 minutes, and 25% after 135 +/- 32.5 minutes; 1 patient still had OCM after 162 minutes. Except for the length of time taken to drink the contrast material (< or =90 minutes was associated with slower empting of the stomach; log rank, P = 0.03), GET of OCM was not correlated with sex (P = 0.16), age (P = 0.15), weight (P = 0.13), or type of diagnosis (P = 0.41). CONCLUSIONS: : Given the variability of GET of OCM and if clinically feasible, we advocate waiting at least 3 hours between completion of OCM ingestion and general anesthesia induction.

The effect of aerobic exercise on neutrophil functions.

PURPOSE: Intense exercise bouts are associated with a reduction of immune function and increased susceptibility to infections. Neutrophils act as a first line of defense to eliminate infectious agents and are also involved in muscle tissue inflammatory response to exercise. Intensive exercise suppresses several neutrophil functions including chemotaxis. The study investigates the pathophysiological mechanisms of impaired chemotaxis after submaximal aerobic exercise. METHODS: Twenty-three healthy physically active adult males were tested before and 24 h after 30 min of treadmill running at 75% VO2max. N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophil migration, polarization, adherence, expression of adhesion molecules (CD11b/CD18), and chemotactic receptor (C5aR) were assessed preexercise and postexercise. RESULTS: Neutrophil chemotaxis and polarization were found to be impaired 24 h postexercise. Adherence was impaired 24 h postexercise as well, but the expression of the adhesion molecule CD11b/CD18 was not affected. Further, the availability of the C5aR was found to be unaffected 24 h postaerobic exercise. CONCLUSIONS: The pathophysiological mechanism of the impaired chemotaxis is likely related to the impaired postexercise neutrophil adherence and polarization but not to changes in the chemotactic receptor availability.

Transfusion-related acute lung injury following intravenous anti-D administration in an adolescent.

Transfusion-related acute lung injury (TRALI) is associated with administration of all plasma containing blood products. We present a 14-year-old adolescent diagnosed with idiopathic thrombocytopenic purpura who developed acute respiratory insufficiency compatible with TRALI within 5 hr following intravenous anti-D. Full blown noncardiogenic pulmonary edema was noted after 9 hr. Mechanical ventilation was not required and the patient made a full recovery after 36 hr. Analysis of the anti-D preparation revealed reactivity against the neutrophil FcgammaRIIIb. A postinfusion serum sample contained antibodies against class I human HLA-A11 antigen. Clinicians should consider TRALI in patients developing unexplained dyspnea after receiving intravenous anti-D.

Widespread use of soy-based formula without clinical indications.

OBJECTIVES: In view of reports of the growing popularity of soy-based formula for infants, we examined soy consumption and its possible overuse during early infancy in central Israel. METHODS: Mothers of 1,803 infants aged 2, 4, 6 and 12 months attending well-baby clinics participated in a telephone survey covering background data, rate, duration, and pattern of soy-based formula use and the reasons for its initiation. The reasons were grouped into those based on the recommendations of the medical personnel and those based on mothers' initiative, and evaluated according to infants' age at soy-based formula initiation (0 to 1, 2 to 4 and 5 to 12 months). The symptoms that prompted soy-based formula use were assessed quantitatively. RESULTS: The rate of soy-based formula use was 10.4% at 2 months and 31.5% at 12 months (P<0.001); 70.6%+/- 2.7% of the infants were given soy for>6 months. Regardless of infants' age, the role of the mothers in the decision to use soy-based formula was greater than that of the medical personnel, and increased significantly with age (chi for trend=0.018). A suspicion of cow's milk allergy was responsible for only 10.9% (7/64) of all soy initiations in infants aged 5 to 12 months. In all ages, occasional symptoms, mainly diarrhea (33.3%) and colic (19.8%), were the leading cause for recommending soy-based formula by medical personnel, whereas the personal preference without clinical justification was the leading cause among mothers. CONCLUSIONS: The use of soy-based formula in central Israel is extensive and continues for long periods, with rates far beyond clinical indications. Mothers play a greater role than medical personnel in the decision to initiate soy-based formula.

Breast-feeding patterns in Central Israel.

BACKGROUND: The rate of breast-feeding in Israel has increased over the last two decades but is still lower than rates in other developed countries that have taken an active role in promoting breast-feeding. OBJECTIVE: To determine breast-feeding patterns and the association between sociodemographic characteristics and breast-feeding in the Tel Aviv district. METHODS: The mothers of infants aged 2, 4, 6 and 12 months, attending 59 well-baby clinics in the Tel Aviv district, were interviewed by telephone. Singleton infants who weighed less than 2,000 g and multiple-gestation infants were excluded from the study. The questions covered background data, sociodemographic characteristics of the family, and breast-feeding practices. Stepwise logistic regression was used to analyze the association between breast-feeding and various sociodemographic characteristics. RESULTS: Altogether, 78.5% of the mothers (1,307/1,665) initiated breast-feeding. The rate of breast-feeding at 2, 4, 6 and 12 months was 55.8, 36.8, 29.9 and 11.8%, respectively. Only 35.8% of the infants at 2 months and 11.2% at 6 months were exclusively breast-fed. The mean duration of breast-feeding was 5.2 +/- 0.2 months. Grand multiparas (> or = 5 children) had a significantly higher rate of breast-feeding than women with one to four children (P < 0.001). More likely to breast-feed for 2 weeks or longer were women married to Yeshiva students (odds ratio = 5.3), women with > or = 13 years education (OR = 2.1), and women on maternity leave (OR = 1.6). The predictors for breast-feeding for 6 months or longer were similar. CONCLUSIONS: Although the rate of breast-feeding initiation in central Israel was 78.5%, only 29.9% of the mothers continue to breast-feed for 6 months. Already at a young age, an appreciable number of breast-fed infants receive infant formula. Breast-feeding promotion should focus on less educated women, homemakers, and families with one to four children.