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In this study we sought to ascertain a critical threshold of the degree of prematurity and long-term digestive morbidity of the offspring. A population-based cohort analysis was conducted, comparing long-term incidence of digestive morbidity in infants born preterm. Cases were divided into four groups according to the extremity of prematurity. Digestive morbidity included hospitalizations involving a predefined set of ICD9 codes. A Kaplan–Meier survival curve was constructed to compare cumulative incidence of digestive morbidity. A Cox proportional hazards model was used to control for confounders. During the study period 220,563 patients met the inclusion criteria. Offspring born preterm had significantly more hospitalizations due to digestive morbidity compared to term offspring. The Kaplan–Meier survival curve demonstrated significant higher cumulative incidence of long-term digestive morbidity of the offspring with decreasing gestational age (Log rank p

Leflunomide, an inhibitor of pyrimidine synthesis, is used for the treatment of rheumatic diseases, which are prevalent in women of childbearing age. Due to the very long half-life of the active metabolite, its mechanism of action and the teratogenicity observed in animal studies at doses similar to or lower than human therapeutic doses on a weight basis, it is recommended that women stop the treatment before conception and a drug elimination procedure be performed. However, unintended gestational exposures may occur, posing challenges in risk assessment. In order to address the safety of leflunomide in unintended exposures in pregnancy, we performed a critical review of human studies. We located 13 publications in Medline and Embase, which reported on 222 pregnancies with known outcomes exposed to leflunomide preconception and/or during pregnancy. Among the 169 live births, there were eight congenital malformations with no consistent pattern of anomalies. These studies collectively showed no significant difference in the rates of malformations between exposed and unexposed pregnancies. At present, accumulating human data do not point toward leflunomide as a potent human teratogen, which may inform risk assessment of unintended gestational exposure to leflunomide.

This study was aimed to assess the association between the use of epidural analgesia during labor and mother-infant bonding.A cross-sectional study.Maternity ward at Soroka University Medical Center during 2020.Women who delivered a singleton live-born infant vaginally in their immediate post-partum period.Women completed questionnaires. 25 items post-partum bonding questionnaire (PBQ) to assess mother-infant bonding (A high score on the PBQ indicates impaired mother-infant bonding) and the Edinburgh postnatal depression scale (EPDS) questionnaire to assess risk for post-partum depression.The study used PBQ questionnaire and four sub-scales to assess mother-infant bonding and the EPDS questionnaire to assess risk for post- partum depression. Generalized linear regression models (gamma) were constructed to examine the association between epidural analgesia and mother-infant bonding total score and impaired bonding sub- scale, while adjusting for confounders Additional information such as pregnancy complications and sociodemographic data was drawn from women's medical records.A total of 234 women were included in the final analysis, of them 126 (53.8%) delivered with epidural analgesia. The total PBQ score was significantly lower among women who received epidural analgesia compared to women without epidural analgesia (7.6 vs. 10.2, p = 0.024), demonstrating a better mother -infant bonding. Using two multivariable linear regression models, controlling for confounders such as maternal age and educational status, epidural analgesia during labor was independently associated with a better mother -infant bonding total score and better impaired bonding sub-scale score (Beta coefficient-0.252, 95% CI -0.5; -0.006, p = 0.045 and Beta coefficient - 0.34, 95% CI -0.52; -0.08, p = 0.01 for mother-infant bonding total score and sub-scale score, respectively). No differences in post-partum depression risks were found between the groups (EDPS≥13, 5.7% vs. 13%, p = 0.058).Our study demonstrated better mother -infant bonding among women delivering with epidural analgesia.

To evaluate perinatal outcomes and long-term neurological morbidity of offspring to mothers with a history of ectopic pregnancy. In this retrospective study, perinatal outcomes and long-term neurological morbidity of offspring were assessed among mothers with a history of ectopic pregnancy, either medically or surgically treated. The study groups were followed until 18 years of age for neurological-related morbidity. For perinatal outcomes, generalized estimated equation (GEE) models were used to control for confounders. A Kaplan–Meier survival curve was used to compare cumulative neurological morbidity incidence and Cox proportional hazards model was conducted to control for confounders. A total of 243,682 mothers were included; 1424 mothers (0.58%) had a previous ectopic pregnancy, of which 25.6% (n = 365) were treated medically, and 74.3% (n = 1059) were treated surgically. Using GEE models, controlling for confounders, both surgically and medically treated ectopic pregnancies were noted as independent risk factors for preterm delivery in the subsequent pregnancies. Maternal history of surgically treated ectopic pregnancy was also independently associated with cesarean delivery. Offspring to mothers with previous ectopic pregnancy had comparable rates of long-term neurological morbidity. In the Cox proportional hazards model, controlling for confounders, being born to a mother with a history of previous ectopic pregnancy was not found to be independently associated with long-term neurological morbidity of offspring. Maternal history of ectopic pregnancy is independently associated with preterm delivery. However, offspring of mothers with a history of ectopic pregnancy are not at an increased risk for long-term neurological morbidity.

Drug allergy is associated with adverse short-term perinatal outcomes such as caesarian delivery and preterm delivery. The aim of the present study was to determine whether being born to a mother with known drug allergy increases the risk for long-term dermatological morbidity of the offspring. A population-based cohort study, comparing long-term dermatological morbidity of offspring to mothers with and without known drug allergy, was conducted. Dermatological morbidity was assessed up to the age of 18 years according to a predefined set of ICD-9 codes associated with hospitalization of the offspring. A Kaplan-Meier survival curve was used to compare cumulative incidence of long-term dermatological morbidity, and a Cox proportional hazards model was constructed to control of confounders. During the study period, 243,682 deliveries met the inclusion criteria, of them 4% (n = 9756) were of mothers with known drug allergy. Offspring born to mothers with known drug allergy had higher rates of long-term dermatological morbidity Likewise, the cumulative incidence of long-term dermatological morbidity was higher as compared with those without known drug allergy (Kaplan-Meier log-rank P = .021). Using a Cox proportional hazards model, controlling for confounders, being born to a mother with known drug allergy was found to be an independent risk factor for long-term dermatological morbidity of the offspring (adjusted HR 1.2, 95% CI 1.03-1.33, P = .016). Being born to a mother with known drug allergy is independently associated with higher risk for long-term dermatological morbidity of the offspring.

Substance use during pregnancy is associated with obstetrical and fetal complications. Though use of some substances is discontinued during pregnancy, use of others persists. Our goal was to characterize substance-specific use and patterns of use throughout pregnancy among vulnerable women who attended an early intervention program for women with substance use issues. Through retrospective analyses of client records (1995–2016; N = 470), results indicated that the greatest number of women continued use of tobacco and cannabis for the duration of pregnancy (n = 232; 84.4% and n = 102; 60.0%, respectively), while the proportion of women continuing opioid use was relatively high (n = 33; 57.9%). Relapse rates were high for women who initially attempted to discontinue use of cocaine, crack cocaine, and heroin. Results can inform intervention and treatment by indicating which substances are more difficult to discontinue, as well as substances associated with high rates of relapse.

Lamotrigine is used in pregnancy to control epilepsy and mood disorders. The reproductive safety of this widely used drug remains undefined and may represent a significant public health concern.We aimed to perform a systematic review and meta-analysis of existing knowledge related to malformation rates and maternal-neonatal outcomes after in utero exposure to monotherapy with lamotrigine.Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters) from database inception to July 2016; no language or date restrictions were applied. All publications of clinically relevant outcomes of pregnancies following in utero exposure to lamotrigine were included in this systematic review and meta-analysis.A total of 21 studies describing immediate pregnancy outcomes and rates of congenital malformations fulfilled the inclusion criteria. Compared with disease-matched controls (n = 1412, total number of patients) and healthy controls (n = 774,571, total number of patients), in utero exposure to lamotrigine monotherapy was found to be associated with significantly decreased rates of inborn defects (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.62-2.16 and OR 1.25; 95% CI 0.89-1.74, respectively). Rates of miscarriages, stillbirths, preterm deliveries, and small for gestational age (SGA) neonates were not found to have been increased after in-utero exposure to LTG compared to the general population. Similarly, in utero exposure to lamotrigine monotherapy was not found to be associated with increased rates of inborn defects compared with in utero exposure to carbamazepine, and lamotrigine was found to be statistically significantly less teratogenic than valproic acid (n = 12,958 and 10,748; OR 0.84; 95% CI 0.68-1.03 and OR 0.32; 95% CI 0.26-0.39, respectively).No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.

A 4-year-old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with a recall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.

Objectives This study aimed to describe the epidemiology and clinical burden of unintended carbon monoxide (CO) poisoning among children in the Negev region of southern Israel. Methods This was a cross-sectional retrospective study of CO poisoning patients admitted to Soroka University Medical Center in 2011 through 2015. Results Overall, 43 cases of CO poisoning were recorded among children younger than 18 years. Five patients died, all upon admission. Poisoning due to smoke "per se" and due to CO emitted from heating devices were responsible for 28 (65.1%) and 14 (32.6%) cases, respectively. Eight (18.6%) patients suffered from convulsions, and 13 (43.3%) of 30 evaluable patients complained of headaches. Twenty-two (51.2%) were found unconscious in the field, and 7 (16.3%) were unconscious at examination at the emergency department. The average carboxyhemoglobin level on admission was 10.5% ± 10.4% (level ranging from 0.1% to 46.2%). Treatment included oxygen in 34 patients (79%) and hyperbaric oxygen therapy in 8 patients (19%). No differences were found between Bedouin and Jewish children in sex, age, residence area, source of CO poisoning, symptoms severity, and need for hyperbaric oxygen therapy. More patients with exposure to water heating devices were older than 4 years, lived in villages, and were diagnosed as having loss of consciousness in the field compared with those exposed to smoke inhalation. Conclusions Carbon monoxide poisoning in children is frequent in southern Israel. Education about prevention, implementation of safer standards for home heating systems, and government supervision are required management strategies to decrease the CO poisoning incidence in southern Israel.

Siblings of non-consanguineous Jewish-Ethiopian ancestry presented with congenital axial hypotonia, weakness of the abducens nerve, psychomotor developmental delay with brain ventriculomegaly, variable thinning of corpus callosum and cardiac septal defects. Homozygosity mapping identified a single disease-associated locus of 3.5 Mb on chromosome 3. Studies of a Bedouin consanguineous kindred affected with a similar recessive phenotype identified a single disease-associated 18 Mb homozygosity locus encompassing the entire 3.5 Mb locus. Whole exome sequencing demonstrated only two homozygous mutations within a shared identical haplotype of 0.6 Mb, common to both Bedouin and Ethiopian affected individuals, suggesting an ancient common founder. Only one of the mutations segregated as expected in both kindreds and was not found in Bedouin and Jewish-Ethiopian controls: c.1404A>G, p.[*468Trpext*6] in CCDC174. We showed that CCDC174 is ubiquitous, restricted to the cell nucleus and co-localized with EIF4A3. In fact, yeast-two-hybrid assay demonstrated interaction of CCDC174 with EIF4A3, a component of exon junction complex. Knockdown of the CCDC174 ortholog in Xenopus laevis embryos resulted in poor neural fold closure at the neurula stage with later embryonic lethality. Knockdown embryos exhibited a sharp reduction in expression of n-tubulin, a marker for differentiating primary neurons, and of hindbrain markers krox20 and hoxb3. The Xenopus phenotype could be rescued by the human normal, yet not the mutant CCDC174 transcripts. Moreover, overexpression of mutant but not normal CCDC174 in neuroblastoma cells caused rapid apoptosis. In line with the hypotonia phenotype, the CCDC174 mutation caused depletion of RYR1 and marked myopathic changes in skeletal muscle of affected individuals.

Breast milk contains not only nutrients for the infant, but also various substances the mother is exposed to, including drugs and chemicals such as heavy metals, environmental pollutants, and nonmedicinal substances, which may compromise infant neurodevelopment. However, knowledge on the impact of these substances in milk on infant neurodevelopment is limited because most of these exposures continue throughout pregnancy and lactation, making it difficult to separate prenatal from postnatal effects. Moreover, concentrations of these substances in milk are low and breastfeeding has been repeatedly shown to be associated with tangible health benefits in the mother and infant, including favorable neurocognitive development. These factors pose significant challenges in study design and interpretation, but research efforts have been made, nonetheless. Overall, available evidence points toward the lack of major detrimental effects of these substances in milk on infant neurodevelopment.

Background Substance use during pregnancy is a major public health concern, stemming from potential physical and psychosocial harms to both the mother and child. Purpose To understand women’s experiences using substances during pregnancy and the reasons that women continue and/or discontinue using substances. Methods Focus groups were conducted with women who attended an early intervention program for pregnant or parenting women with substance use issues. Results Women identified that external and internal stressors, feelings of guilt and low-self efficacy, and a lack of understanding of the scientific and medical consequences of substance use contributed to their continued substance use. Conversely, women highlighted the importance of high self-efficacy and the quality of relationships when trying to make positive changes to their substance use during pregnancy. Conclusions Recommendations are proposed for easier access to and more comprehensive services. Healthcare professionals and service providers should offer non-judgmental care by building high-quality relationships with pregnant women with substance use issues, to increase these women’s self-efficacy and empower them to discontinue substance use.

Lamotrigine is used in pregnancy to control epilepsy and mood disorders. The reproductive safety of this widely used drug remains undefined and may represent a significant public health concern. We aimed to perform a systematic review and meta-analysis of existing knowledge related to malformation rates and maternal–neonatal outcomes after in utero exposure to monotherapy with lamotrigine. Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters) from database inception to July 2016; no language or date restrictions were applied. All publications of clinically relevant outcomes of pregnancies following in utero exposure to lamotrigine were included in this systematic review and meta-analysis. A total of 21 studies describing immediate pregnancy outcomes and rates of congenital malformations fulfilled the inclusion criteria. Compared with disease-matched controls (n = 1412, total number of patients) and healthy controls (n = 774,571, total number of patients), in utero exposure to lamotrigine monotherapy was found to be associated with significantly decreased rates of inborn defects (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.62–2.16 and OR 1.25; 95% CI 0.89–1.74, respectively). Rates of miscarriages, stillbirths, preterm deliveries, and small for gestational age (SGA) neonates were not found to have been increased after in-utero exposure to LTG compared to the general population. Similarly, in utero exposure to lamotrigine monotherapy was not found to be associated with increased rates of inborn defects compared with in utero exposure to carbamazepine, and lamotrigine was found to be statistically significantly less teratogenic than valproic acid (n = 12,958 and 10,748; OR 0.84; 95% CI 0.68–1.03 and OR 0.32; 95% CI 0.26–0.39, respectively). No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.

Background The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents. Methods Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy. Results A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap. Conclusion This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner.

Pediatric drug research is gradually becoming more and more accepted as the norm for assessing whether a drug is safe and efficacious for infants and children. The process of informed consent and assent for these trials presents a major challenge. The aim of this review is to map historical, ethical and legal aspects relevant to the challenges of informed consent in the setting of pediatric drug research. The impact of age, level of maturity and life circumstances on the process of obtaining informed consent as well as the relations between consent and assent are discussed. There appears to be a lack of regulatory clarity in the area of pediatric clinical trials; while numerous statements have been made regarding children's rights to autonomy and their ability to care for themselves and for younger ones, the ever changing status of adolescence is still difficult to translate to informed consent. This may delay scientific and clinical advancement for children who are at the very junction of being independent and not needing parental permission. Obtaining consent and assent for pediatric clinical trials is a delicate matter, as both parent and child need to agree to participate. The appropriate transfer of information to guardians and the children, especially concerning potential risks and benefits, is at the heart of informed consent, as it serves to protect both patient and physician. As many adults lack health literacy, one must ensure that guardians receive relevant information at a level and in forms they can understand regarding the trials their children are asked to participate in.

Fetal Alcohol Spectrum Disorder (FASD) affects an estimated 1% of all children born in North America. FASD is a chronic disorder impacting many systems of care. Only a minority of these children exhibit the pathognomonic facial features of Fetal alcohol syndrome (FAS) that include short palpebral fissures, smooth philtrum and thin upper lip. Hence, in the majority of affected individuals FASD is a diagnosis of exclusion. The differential diagnosis of both the dysmorphological and neurobehavioral aspects of FASD is wide. This review aims to provide the pediatrician with information concerning the differential diagnosis of FASD and to discuss genetic testing that might be relevant to the assessment.

The Northern region of the Negev desert is an endemic area of organophosphate and carbamate intoxications in Bedouin children. Most victims are intoxicated by drinking the poisonous material kept by the parents in soft drink bottles. Signs and symptoms of intoxication are commonly known and generally include various effects on the central nervous system, usually a decreased level of consciousness in children, cholinergic muscarinic (sweating, rhinorrhea, miosis, vomiting) and nicotinic (weakness) effects. Specific therapy includes Atropine Sulphate and Oximes. PURPOSE AND RESULTS: To describe the course of disease of four (out of 47) children admitted to the Division of Pediatrics with organophosphate or carbamate poisoning during a two-year period. The four children 3-17 years of age ingested the poisonous material: organophosphate chlorpyrifos (2 children); carbamate methomyl (one child) and an unidentified compound in another child. Three of the four patients ingested the poison in a suicide attempt. All 4 children suffered from severe and uncommon complications, including severe respiratory failure from different etiologies. In addition, two of the four suffered from a neurological deficit causing prolonged disability. Three had renal failure necessitating hemofiltration in one case. One child had severe hemodynamic failure and arrhythmias necessitating, among other therapy, the insertion of a temporary pace maker. Two children had (laboratory) pancreatitis. One of the children with severe respiratory failure died after 38 days of extracorporeal membrane oxygenation.Intoxications by anticholinesterase compounds are not uncommon among Bedouin children in the Negev. This public health threat should be prevented and completely eradicated by the health authorities. Severe intoxication, especially in cases arising after suicide attempts, wherein the amount of the poisonous material is large, may be complicated by life threatening, multi-organ failure during and after the initial phase of poisoning and may progress into prolonged disability and death.

BACKGROUND: Acute kidney injury as a direct complication of organophosphate poisoning has rarely been described and its etiology is unclear. CASE: A 17-year-old adolescent girl was admitted to the pediatric intensive care unit after a suicidal attempt with chlorpyrifos, an organophosphate insecticide compound. The patient developed acute kidney injury followed by renal failure, necessitating renal replacement therapy. She was treated with continuous venovenous hemofiltration with full resolution of her renal function. CONCLUSIONS: Organophosphate poisoning can lead to renal failure, which, with proper treatment, may be reversible but, if left unattended, might aggravate the clinical course of the disease. Physicians should be aware of this rare complication. Language: en

Bacterial infections are a major threat to pediatric oncology patients with fever and neutropenia. Current management consists of empiric broad-spectrum antibiotics and prompt medical evaluation. Local bacterial susceptibility rates were published in 2005, and the local protocol (piperacillin and amikacin) was established as an adequate empiric treatment with -100% efficiency against the common pathogens in our pediatric hemato-oncology ward.To characterize the spectrum of bacteria isolated from blood cultures at the pediatric hemato-oncology ward between 2008- 2010, and to evaluate the current protocol.A prospective study, conducted in the pediatric hemato-oncologic ward among hospitalized children (2 months - 18 years) with fever and neutropenia. Blood cultures from peripheral blood and central lines were obtained from all patients at admission. Bacterial resistance to various antimicrobial agents was determined.During 2008-2010, 195 admissions (105 children) due to fever and neutropenia were recorded. Approximately 30% of all blood cultures were positive for a pathogen with -50% Gram positive bacteria mostly CONS. The most prevalent Gram negative bacteria were acinetobacter and klebsiella spp. Candida species were isolated from 7% of positive cultures. Susceptibility rates for the current empiric antimicrobial regimen were about 90%. CONS bacteremia rate increased from 4% in 2000-2002 to 29% in 2008-2010 (p0.01).The currently applied empiric antimicrobial protocol is an optimal first line regimen, considering the susceptibility of the most common pathogens. Judicious use of carbapenems for gram negative bacteria and glycopeptides or other novel antimicrobial agents in cases of CONS bacteremia is required.

Organophosphate and carbamate are mainly used to kill insects, thereby protecting livestock, crops, homes and communities. Yet, these compounds also convey great danger. OP and CRB poisoning is an important clinical problem, often life-threatening, especially in the pediatric population in rural areas where reaching a physician or hospital on time is difficult. We present a summary of accumulated toxicological knowledge as well as clinical and laboratory experience from a medical center serving a relatively vast rural area and pediatric population. We stress the importance of knowing how to recognize the classic signs of OP and CRB poisoning and when it is appropriate to investigate for such poisoning even in the absence of those signs. Like any medical emergency, OP and CRB poisoning requires prompt resuscitation and use of antidotes. Atropine, oxygen and fluids are the mainstay of therapy. Oximes, which were found useful in some cases of OP poisoning and useless in some cases of CRB poisoning, are absolutely safe as empiric treatment, which is often needed since the major differential diagnosis of OP poisoning is CRB poisoning, which is clinically indistinguishable. We hope that continuing research will offer further insights into the management of such events, and we are confident that improved medical management of OP and CRB poisoning will result in a reduction of morbidity and other complications associated with intensive care procedures and hospitalization.