Second Month Of Life Research Articles

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata

The effect and safety of prenatal and early life administration of paracetamol – routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10).Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60).This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established.

PP03.2 – 2683: Next generation sequencing allows the identification of NDUFS4 defect in a patient with fatal early Leigh syndrome and deficiencies in pyruvate dehydrogenase and multiple respiratory chain complexes

Objective Respiratory chain complex (RCC) I is the second most common biochemical abnormality causing Leigh syndrome (LS), an early-onset neurodegenerative disorder. NDUFS4 gene presents a hotspot of mutations leading to an inappropriate assembly of complex I. Our aim was to describe a 67-days-old female presenting with severe hypotonia, abnormal eye movements, lethargy, seizures and respiratory failure leading to death on day 5 of evolution. Plasma lactate was 5.83 mmol/L and amino acids and organic acids were normal. MRI showed swelling lesions in the basal ganglia and brainstem with restricted diffusion and a lactate peak on MRS. Methods Pyruvate dehydrogenase (PDH) and oxidation-reduction activity assays were performed in fibroblasts and muscle. Spectrophotometric assays of RCC were performed in muscle. Genetic analysis of nuclear genes involved in mitochondrial disorders was assessed by targeted exome sequencing using the TruSight One Sequencing Panel (Illumina). Results The patient showed a significative reduction in PDH activity in fibroblasts and muscle, with values of 0.22 mmol/min*mg prot (normal values 0.34–2.6) and 0.5 mmol/min*mg prot, (normal values 0.8–3.4) respectively, and reduced oxidation of pyruvate in fibroblasts. Muscle analysis of RCC showed a 50% reduction in the residual activity of CI and CIII compared to control. Muscle Q10 was low when related to cytrate synthase (2.18 nmol/U CS, reference values 2.7–8.4). Massive sequencing revealed a previously described homozygous mutation c.291delG (p. Trp97Ter) in NDUFS4 gene, which was further confirmed by Sanger sequencing. No disease-causing mutations were detected in the PDHc genes. Conclusion NDUFS4 defect in our patient led to a rapidly progressive and fatal Leigh encephalopathy in the second month of life. A combined defect in pyruvate metabolism and respiratory chain complexes was misleading; probably, mild Q10 deficiency was secondary to inappropriate assembly of complex I. Finally, NGS techniques allowed genetic diagnosis in our patient.

The HERC1 E3 Ubiquitin Ligase is essential for normal development and for neurotransmission at the mouse neuromuscular junction.

The ubiquitin-proteasome system (UPS) plays a fundamental role in protein degradation in neurons, and there is strong evidence that it fulfills a key role in synaptic transmission. The aim of the present work was to study the implication of one component of the UPS, the HERC1 E3 Ubiquitin Ligase, in motor function and neuromuscular transmission. The tambaleante (tbl) mutant mouse carries a spontaneous mutation in HERC1 E3 Ubiquitin Ligase, provoking an ataxic phenotype that develops in the second month of life. Our results show that motor performance in mutant mice is altered at postnatal day 30, before the cerebellar neurodegeneration takes place. This defect is associated with by: (a) a reduction of the motor end-plate area, (b) less efficient neuromuscular activity in vivo, and (c) an impaired evoked neurotransmitter release. Together, these data suggest that the HERC1 E3 Ubiquitin Ligase is fundamental for normal muscle function and that it is essential for neurotransmitter release at the mouse neuromuscular junction.

Factors associated with breastfeeding practice for at least six months in the state of Pernambuco, Brazil.

Despite the scientific consensus on the benefits that breastfeeding provides for the mother, the baby, the family and the environment, and also the recommendation to breastfeed exclusively for six months, this practice is far from being achieved. To analyze the factors associated with exclusive breastfeeding (EBF) for at least six month, as opposed to weaning up to the second month of life in the state of Pernambuco, Brazil. A case-control study of 124 cases (EBF for at least six months) matched for age and sex with 248 controls (weaning up to the second month of life). Cases and controls were drawn from the III State Health and Nutrition Survey. The exposure variables selected were maternal age and education, per capita income, housing zone, prenatal consultations, type of delivery, professional who assisted the delivery, and prenatal breastfeeding guidance. Logistic regression was applied to variables that showed a p-value < 0.2 in the bivariate analysis, and the variables with p-value < 0.05 were included in the final model. Of the eight groups of variables considered as possible predictors of EBF for at least six months, two remained as associated factors: maternal age between 20 - 35 years old, with odds ratio (OR) 2.5 and 95% confidence interval 95%CI 1.4 - 4.5; and maternal education of 5 - 8 years of schooling (OR 2.1; 95%CI 1.2 - 3.6). The study shows that mobilization of the public sector and stimulus to research is still needed for the success of EBF and for mother and child health.

Neonatal hyperthyroidism on rat heart: interrelation with nitric oxide and sex.

To clarify the mechanism mediating the effect of hyperthyroidism on cardiac function during the second month of life in rats. Male and female Sprague-Dawley rats were assigned to a control or to a triiodothyronine (T3)-treated group. Treatment of each group was started on the third day after birth. Control rats (Eut) received 0.9 NaCl [0.1ml/100g body weight (BW)] every second day during 60days and T3-treated rats (Hyper) received subcutaneous (SC) T3 injections every second day during 60days. Hyperthyroidism decreased left ventricle volume only in male rats. Female euthyroid rats presented higher atrial nitric oxide synthase (NOS) activity than male rats and hormonal treatment decreased this enzyme's activity in both sexes. Euthyroid male and female rats had similar atrial NOS protein levels, but females had higher caveolin (cav) 3 protein levels. T3 treatment increased this protein only in males. Female rats had lower ventricular NOS activity than male rats; hyperthyroidism increased NOS activity in both sexes but this effect was associated with lower cav 3 protein levels. Hyperthyroidism did not change cav 1 protein levels in both male and female rats. The results of this study demonstrating clinically relevant sex-related differences in the pathophysiology of the hyperthyroid heart have raised new questions regarding the mechanisms responsible for the observed differences. This study suggests that sex-related intrinsic factors such as nitric oxide may modulate the response to hyperthyroidism that leads to cardiovascular dysfunction.

Development of non-catecholaminergic sympathetic neurons in para- and prevertebral ganglia of cats

Expression of vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT) and calcitonin gene-related peptide (CGRP) in the sympathetic ganglia was investigated by immunohistochemistry in the superior cervical ganglion (SCG), stellate ganglion (SG) and celiac ganglion (CG) from cats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old and 2-month-old). Non-catecholaminergic TH-negative VIP-immunoreactive (IR) and nNOS-IR sympathetic ganglionic neurons are present from the moment of birth. In all studied age groups, substantial populations of VIP-IR (up to 9.8%) and nNOS-IR cells (up to 8.3%) was found in the SG, with a much smaller population found in the SCG (<1%) and only few cells observed in the CG. The percentage of nNOS-IR and VIP-IR neurons in the CG and SCG did not significantly change during development. The proportion of nNOS-IR and VIP-IR neuron profiles in the SG increased in first 20 days of life from 2.3±0.15% to 8.3±0.56% and from 0.3±0.05% to 9.2±0.83%, respectively. In the SG, percentages of nNOS-IR sympathetic neurons colocalizing VIP increased in the first 20 days of life. ChAT-IR and CGRP-IR neurons were not observed in the sympathetic ganglia of newborn animals and did not appear until 10 days after birth. In the SG of newborn and 10-day-old kittens, the majority of NOS-IR neurons were calbindin (CB)-IR, whereas in the SCG and CG of cats of all age groups and in the SG of 30-day-old and older kittens, the vast majority of NOS-IR neurons lacked CB. We conclude that the development of various non-catecholaminergic neurons in different sympathetic ganglia has its own time dynamics and is concluded at the end of the second month of life.

Traditional Oral Remedies and Perceived Breast Milk Insufficiency Are Major Barriers to Exclusive Breastfeeding in Rural Zimbabwe

Only 5.8% of Zimbabwean infants are exclusively breastfed for the first 6 mo of life despite substantial investment in exclusive breastfeeding (EBF) promotion throughout the country. We conducted a survey of 295 mothers of infants <6 mo of age who were recruited from rural immunization clinics and outreach sites in the Midlands Province of Zimbabwe. We explored infant feeding knowledge, beliefs and attitudes, and details regarding facilitators for EBF mothers and first foods fed by non-EBF mothers to identify and understand barriers to EBF. Among mothers of infants <1 mo, 1 to <2 mo, and 2–6 mo of age, 54%, 30%, and 12%, respectively, were practicing EBF. In adjusted multivariate analyses, EBF practice was positively associated with belief in the sufficiency of EBF (P = 0.05), belief in the avoidance of cooking oil feeding (a common traditional practice) in the first 6 mo (P = 0.001), and perceived pressure from others regarding infant feeding and traditional medicine use (P = 0.03). Psychosocial support and viewing breast milk as sufficient were reported as primary facilitators of EBF practice. Maternal responses to open-ended questions identified protection, nutrition, and crying as the main reasons for EBF interruption. During the first 2 mo of life, “protection feedings” using traditional oral remedies (such as cooking oil and water) to prevent or treat perceived illness, specifically colic and sunken/depressed fontanel, made up 78.5% of the non-breast milk feeds. From the second month of life, “nutrition feedings,” mainly of water and porridge, were given when mothers believed their breast milk was insufficient in quantity or quality to meet the hunger or thirst needs of their infants. Our findings underscore the importance of exploring cultural beliefs and practices as they pertain to infant feeding and care and present insights for designing and targeting EBF promotion interventions.

TWO-STAGE SURGICAL TREATMENT OF A CHILD OF ONE YEAR FROM CONGENITAL HEART DISEASE AND BILIARY CIRRHOSIS

Aim: Clinical case of successful two-stage surgical treatment of a 1-year-old child with congenital heart disease and biliary cirrhosis is represented in this article. At the fi rst day of life laparotomy was performed because of high intestinal obstruction. Kasai procedure and Roux-en-Y choledochojejunostomy were per- formed on 12 th day and at the end of second month of life, respectively. Liver biopsy showed the signs of biliary cirrhosis. At the same time ventricular septal defect and atrial septal defect with pulmonary hyper- tension were diagnosed. The fi rst step of treatment was the surgical septal defects closure. No complications during procedure, cardiopulmonary bypass and post-operative period were registered. There were no nega- tive effects on liver function after cardiac surgery. 11 months later living-donor liver transplantation was performed without any complications. Patient was discharged at 35 th post-transplant day with stable graft function.

Lipoprotein Lipase Deficiency: Clinical, Biochemical and Molecular Characteristics in Three Patients with Novel Mutations in the LPL Gene

Lipoprotein lipase (LPL) deficiency, caused by mutations in the LPL gene, is a rare autosomal recessive disorder manifesting in early childhood with recurrent abdominal pain, hepatosplenomegaly, acute pancreatitis, lipaemia retinalis and eruptive xanthomas. Typical laboratory findings are lactescent serum, extreme hypertriglyceridaemia and hypercholesterolaemia. The diagnostics is based on postheparin serum LPL assay and DNA analyses of the LPL gene. We report clinical, biochemical and molecular data of three children with LPL deficiency. One child manifested since the first week of life with recurrent abdominal pain (Patient 1), the second with abdominal distension and hepatosplenomegaly since the second month of life (Patient 3) and patient 2, asymptomatic younger brother of patient 1, was diagnosed in the first week of life. Lipaemia retinalis and splenomegaly were present in two symptomatic children, hepatomegaly in patient 3 and acute pancreatitis in patient 1. All children had lactescent serum, profound hypertriglyceridaemia (124 ± 25 mmol/l; controls &lt; 2.2), hypercholesterolaemia (22.8 ± 7.3 mmol/l, controls &lt; 4.2) and their LPL immunoreactive mass in serum did not increase after heparin injection. Molecular analyses revealed that both siblings are homozygous for novel mutation c.476C &gt; G in the LPL gene changing the conserved amino acid of the catalytic centre. The third patient is a compound heterozygote for mutations c.604G&gt;A and c.698A&gt;G in the LPL gene, both affecting highly conserved amino acids. We conclude that LPL deficiency must be considered in neonates and young infants with abdominal pain and hypertriglyceridaemia because early treatment might prevent development of life-threatening acute pancreatitis.

A 6-Month-Old Boy with Uncontrollable Dystonic Posture of the Neck

A6-month-old boy was admitted to the Department of Paediatrics, University of Chieti, Italy, with a 3-month history of uncontrollable dystonic posture of the neck. During the second month of life, the child began to present with a twisting of the neck to one side that persisted for 7 days, after which the abnormal position moved to the other side. The movements were not associated with vomiting, cyanosis, loss of consciousness, tonic or clonic movements, or a post-ictal state. The child’s personal medical history was otherwise unremarkable. Many different specialists, including orthopedic surgeons, otolaryngologists, orthoptists, and ophthalmologists, examined the child and found no evidence of pathology. The investigations included electroencephalograms, magnetic resonance imaging of the head, and X-ray and ultrasound of the neck, but showed no anomalous findings. On admission, physical examination revealed normal growth parameters, vital signs, and neurological findings. After sound stimulation, the child showed difficulty in turning his head to the opposite side and presented resistance to passive mobilization of the neck. A specialist in neurological evaluation demonstrated reduced reaction to the environment and a slight reduction of ocular motility due to torticollis. Laboratory investigations, including a complete blood count; blood electrolytes; serum pyruvate, lactate, and ammonium levels; and urine and blood amino acids, were within normal range. An occult blood test produced a negative result. A paroxysmal non-epileptic event was suspected and 24-hour pH metering revealed postprandial acid reflux of severe grade. Gastroesophageal ultrasound excluded the presence of hiatal hernia. Therapy with ranitidine (8 mg/kg per day) was started, after which symptoms rapidly improved and then disappeared completely within a few days. After 8 months of treatment with ranitidine, the treatment was ended and no problems have recurred. A 6-Month-Old Boy with Uncontrollable Dystonic Posture of the Neck

Severe phenotypes of SMARD1 associated with novel mutations of the IGHMBP2 gene and nuclear degeneration of muscle and Schwann cells

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive form of spinal muscular atrophy manifested in low birth weight, diaphragmatic palsy and distal muscular atrophy. Caused by a mutation in the IGHMBP2 gene, the disease is addressed here by reference to five Polish patients in which SMARD1 has been confirmed genetically. All presented a severe form of the disease and had evident symptoms during the second month of life; with four displaying weak cries, feeding difficulties and hypotonia from birth. Two were afflicted by severe dysfunction of the autonomic nervous system. Ultrastructural analysis of a muscle biopsy revealed progressive degeneration within the nuclei of the muscle cells and Schwann cells. Neuromuscular junctions were also defective. It proved possible to identify in our patients 6 novel IGHMBP2 mutations: three missense (c.595G>C, c.1682T>C and c.1794C>A), two nonsense (c.94C>T and c.1336C>T) and one in-frame deletion (c.1615_1623del). One nonsense mutation (c.429C>T) that had been described previously was also identified. Observation of our patients makes it clear that clinical picture is still the most important factor suggesting diagnosis of SMARD1, though further investigations concerning some of the symptoms are required. As the IGHMBP2 gene is characterized by significant heterogeneity, genetic counseling of affected families is rendered more complex. IGHMBP2 protein deficiency can lead to the degeneration of nuclei, in both muscle and Schwann cells.

Development of nNOS-positive neurons in the rat sensory and sympathetic ganglia

Neurochemical features in sympathetic and afferent neurons are subject to change during development. Nitric oxide (NO) plays a developmental role in the nervous system. To better understand the neuroplasticity of sympathetic and afferent neurons during postnatal ontogenesis, the distribution of neuronal NO synthase (nNOS) immunoreactivity was studied in the sympathetic para- and prevertebral, nodose ganglion (NG) and Th2 and L4 dorsal root ganglia (DRG) from female Wistar rats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old, 6-month-old, 1-year-old, and 3-year-old).nNOS-positive neurons were revealed in all sensory ganglia but not in sympathetic ones from birth onward. The percentage of nNOS-immunoreactive (IR) neurons increased during first 10days of life from 41.3 to 57.6 in Th2 DRG, from 40.9 to 59.1 in L4 DRG and from 31.6 to 38.5 in NG. The percentage of nNOS-IR neurons did not change in the NG later during development and senescence. However, in Th2 and L4 DRG the proportion of nNOS-IR neurons was high in animals between 10 and 30days of life and decreased up to the second month of life. In 2-month-old rats, the percentage of nNOS-IR neurons was 52.9 in Th2 DRG and 51.3 in L4 DRG. We did not find statistically significant differences in the percentage of nNOS-IR neurons between Th2 and L4 DRG and between young and aged rats.In NG and DRG of 10-day-old and older rats, a high proportion of nNOS-IR neurons binds isolectin B4. In newborn animals, only 41.3%, 45.3% and 28.4% of nNOS neuron profiles bind to IB4 in Th2, L4 DRG and NG, respectively. In 10-day-old and older rats, the number of sensory nNOS-IR neurons binding IB4 reached more than 90% in DRG and more than 80% in NG. Only a small number of nNOS-positive cells showed immunoreactivity to calcitonin gene-related peptide, neurofilament 200, calretinin. The information provided here will also serve as a basis for future studies investigating mechanisms of the development of sensory neurons.

Mothering Style and Infant Behavioral Development in Yunnan Snub-Nosed Monkeys (Rhinopithecus bieti) in China

Considerable variation in mothering styles is found among primate species, which may be directly related to species-typical differences in social structure, dominance style, patterns of infant development, and rates of intragroup aggression. We predicted that, as egalitarian Asian colobines, mothers of Yunnan snub-nosed monkeys (Rhinopithecus bieti) would adopt a mothering style characterized by low restrictiveness and low rejection. We followed six mother–infant dyads in a provisioned group of Rhinopithecus bieti inhabiting the Baimaxueshan National Nature Reserve, Yunnan, China, and collected 717.2 h of observational data on maternal care and infant development. In the first month after birth, infants were completely dependent on their mothers for nutrition and movement. They began to locomote clumsily during their second month of life. Mothers restricted the movements of their infants only during their first 2 mo of life. Maternal rejection occurred infrequently and never exceeded a mean of two events per hour for a given infant over any 1-mo period. Most rejections were mild, and did not result in a cessation of nursing. Infants were not weaned when they were 12 mo old. Our study offers support for the contention that females of Rhinopithecus bieti adopt a relaxed mothering style in caring for offspring during their first year of life.

Early Diet Impacts Infant Rhesus Gut Microbiome, Immunity, and Metabolism

Epidemiological research has indicated a relationship between infant formula feeding and increased risk of chronic diseases later in life including obesity, type-2 diabetes, and cardiovascular disease. The present study used an infant rhesus monkey model to compare the comprehensive metabolic implications of formula- and breast-feeding practices using NMR spectroscopy to characterize metabolite fingerprints from urine and serum, in combination with anthropometric measurements, fecal microbial profiling, and cytokine measurements. Here we show that formula-fed infants are larger than their breast-fed counterparts and have a different gut microbiome that includes higher levels of bacteria from the Ruminococcus genus and lower levels of bacteria from the Lactobacillus genus. In addition, formula-fed infants have higher serum insulin coupled with higher amino acid levels, while amino acid degradation products were higher in breast-fed infants. Increases in serum and urine galactose and urine galactitol were observed in the second month of life in formula-fed infants, along with higher levels of TNFα, IFN-γ, IL-1β, IL-4, and other cytokines and growth factors at week 4. These results demonstrate that metabolic and gut microbiome development of formula-fed infants is different from breast-fed infants and that the choice of infant feeding may hold future health consequences.

Congenital lobar emphysema surgical versus conservative management

Back ground: Congenital lobar Emphysema (CLE) is a rare yet serious condition which requires early detection and management, and usually present during infancy.&#x0D; Patients and methods: This retrospective study aimed to review and evaluate methods adopted for the management of congenital lobar emphysema cases and it aimed to report and to document any observation which might need further research. The study retrospectively reviewed medical records of 53 cases whom were admitted to the department of thoracic surgery-medical city teaching complex over a period of 4 years (from June 2005 to June 2010). All of them had been diagnosed and managed as cases of congenital lobar emphysema based on their clinical picture and radiologic examination.Objectives:&#x0D; Results: The commonest age group affected were infants in the second month of life(40 patients) (75.47%), 10 patients (18.86%) within the next 3 months, 2 cases (03.77%)were over 6months old and only one case (01.88%) was over 1y. The number of male patients in this study was higher than the female patients (38 versus 15) with a male to female ratio was 2.53:1. The affected lobes were left upper lobe in 39 patients (73.60%), right middle lobe in 9 patients (16.98%), right upper lobe in 3 cases (5.66%), and right upper and middle lobes in 2 cases (3.77). Postoperative complication encountered in 6 patients; chest infection (2 patients), bronchopleural fistula and empyema (2 patients), wound infection (1 patient), and postoperative atelectasis (1 patient). Each treated accordingly. No intraoperative mortality was recorded, yet postoperative mortality happened in 3 cases, two cases due to respiratory failure and other one due to septicaemia. The significant finding in this review was that, 8 cases out of the 53, during the period of observation and conservative management, they eventually developed complete clinical improvement of their signs and symptoms and complete resolution of their radiologic findings. All other patients (45) required surgical resection, were lobectomy was the commonest type of surgical resection (39 patients), combined lobectomy and wedge resection performed in (6) patients.&#x0D; Conclusions: A group of cases diagnosed with CLE can benefit from a period of observation and monitoring aiming for conservative management

Folliculogenesis, Ovulation and Endocrine Control of Oocytes and Embryos in the Dog

Reproductive physiology in dogs is quite unusual compared with that in other mammalian species. The peculiarities include the presence of numerous polyoocyte follicles, the ovulation of an immature oocyte (GV stage, non-fertilizable) and a peri-ovulatory period during which concentrations of circulating progesterone are particularly high. The aim of this review is to examine the unusual aspects of the reproductive physiology of dogs and how this relates to the clinical biology of this species.

Infantile Hemangioma Growth Peaks in Second Month of Life

Infantile Hemangioma Growth Peaks in Second Month of Life

Growth of Exclusively Breastfed and Self-Weaned Children of Greece Aged 0–36 Months

Breastfeeding is recognized as an important public health issue with substantial social and economic implications. Moreover, the growth of exclusively breastfed babies differs from that of their formula-fed counterparts. The purpose of this study was to evaluate the physical growth of exclusively breastfed and self-weaned boys and girls of Greece 0-36 months of age. The physical growth of children was monitored from birth up to 36 months of age. Body weight, length/height, and head circumference were recorded. The study population included 101 boys and 105 girls who were recruited consecutively from a private breastfeeding clinic in the second largest city of Greece and through La Leche League groups throughout the country during 2000 to 2005. All infants were exclusively breastfed for ≥ 6 months. Anthro software ( www.who.int/childgrowth/software/en/index.html ) was used to compare the data of our study population and the World Health Organization standards for weight, length/height, and head circumference for age. Male and female infants at 12 months had almost tripled their weight (192% and 190% increase, respectively) and had increased their length (height) by 48% and 47%, respectively, and head circumference had increased by 35% and 33%, respectively. In both sexes the relative length/height and the head circumference-for-age increase rates were higher from the first to the second month of life than at any other period. Long-term exclusively breastfed infants grow normally. Hence, no recommendations for the interruption of lactation and/or supplementation with formula are justified.

Ultrastructure of Neurons in the Caudal Mesenteric Ganglion in Kittens during Early Postnatal Ontogeny

Electron microscopic studies were performed to study the development of the neural elements of the sympathetic caudal mesenteric ganglion (CMG) in cats from the moment birth to the end of the second month of life. Non-simultaneous maturation of neurons and their terminals was seen; along with completely developed neurons, gliocytes, and synapses, neonatal kittens had numerous immature forms of these structures. In animals aged 14 days, the proportion of immature cells decreased, though neuron destruction was more frequent at this age. The CMG of animals of all age groups contained mostly axodendritic synapses, along with fewer axosomatic synapses. CMG ultrastructure in kittens became comparable with that in adult animals at age 60 days.

Etiology of Fever in Young Infants: A Reassessment

Source: Greenhow TL, Hung Y-Y, Herz AM. Changing epidemiology of bacteremia in infants aged 1 week to 3 months. Pediatrics. 2012; 129(3): e590– e596; doi: 10.1542/peds.2011-1546Investigators from Kaiser Permanente Northern California characterized the etiology of bacteremia in infants aged 1 week to 3 months by retrospectively reviewing the results of blood cultures (BC) obtained from a cohort of 160,818 full-term, previously healthy infants during a 5-year period (2005–2009). Cultures drawn from outpatients, in the emergency department, and within the first 24 hours of admission to the hospital were included. Excluded were infants with underlying medical problems and those born at <37 weeks estimated gestational age. Efforts were made to identify repeatedly positive cultures, which were counted as a single episode of bacteremia. Isolates such as coagulase-negative staphylococci, Micrococcus, and diphtheroids were defined as contaminants (3 children with viridans streptococci and 1 of enterococcal bacteremia were managed as infections).During the 5-year period 340 of 4,255 (8%) BCs were positive. Of these, 93 (2%) were clinically significant and 247 (6%) were considered contaminated. The incidence of true bacteremia was 0.57 per 1,000 live births in this cohort. Escherichia coli was the most common pathogen (56% of cases of bacteremia), followed by group B Streptococcus (GBS) (21%), Staphylococcus aureus (8%), and Streptococcus pneumoniae (3%). There were 3 cases of viridans streptococcal bacteremia, 2 cases each of Klebsiella and Salmonella bacteremia, and single cases of bacteremia due to Citrobacter, Enterococcus faecalis, Moraxella, and Streptococcus pyogenes. Of the 19 episodes of GBS bacteremia, 12 occurred between days 7 and 28, 6 in the second month of life, and 1 in the third month of life. For all other pathogens, there was no age-related pattern.A significantly higher proportion of contaminated BCs were drawn in the emergency department, compared to the outpatient or inpatient setting. Of the 48 infants with E coli bacteremia who had a urine culture (UC) performed, 47 (98%) had a concomitant urinary tract infection (UTI). Of the 38 such infants for whom a cerebrospinal fluid (CSF) culture was performed, 4 (11%) had concomitant meningitis. Of 17 infants with GBS bacteremia who had CSF culture performed, 5 (29%) had concomitant meningitis. There was 1 case of pneumococcal meningitis. Compared to nonbacteremic controls, bacteremic infants had a significantly higher average white blood cell count (13,820/μL vs 10,770/μL). Three of 52 (6%) of the E coli isolates were resistant to ampicillin and gentamicin.The authors conclude that empiric ampicillin treatment in the first 3 months of life may no longer be required, given the absence of Listeria infection and the observed antibiotic resistance in their cohort.Dr Tolan has disclosed no financial relationship relevant to this commentary. Dr. Tolan is on the Speaker’s Bureau for Novartis. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.This is the first study to address the incidence of bacteremia in infants 1 to 3 months of age since the advent of widespread pneumococcal conjugate vaccination. The most important finding is the prominence of UTI among serious bacterial infections (SBI) in this age group.1,2 Despite the striking occurrence of concomitant E coli UTI and bacteremia (98% when the urine was sampled), 4 infants with E coli bacteremia did not have UC performed. In fact, 11 (12%) of all the bacteremic infants did not have UC performed. Similarly, 32 (34.8%) of infants sick enough to have BC performed (and subsequently found to be bacteremic) did not have CSF cultures performed.The authors note the absence of Listeria infections in the study cohort, and suggest that empiric therapy for this organism may no longer be necessary. However, the rate of Listeria infection in the United States in 2009 was 0.05 cases per 100,000 persons aged ≤1 year.3 Thus, one would expect only 0.1 cases in their cohort over a 5-year span. Since the investigators excluded premature infants and those under 1 week of age, newborns with Listeria infections may have been missed.4 The results of this study, therefore, do not support a recommendation to discontinue empiric ampicillin therapy in the first months of life. However, assuring adequate treatment of E coli (including antibiotic-resistant strains) is of paramount importance in the management of SBI in this age group.The results described are likely generalizable to similar infants, but caution should be exercised when confronted with a febrile or ill-appearing infant born prematurely or having underlying medical conditions, for whom these data may be less applicable. In any event, the importance of UTI among infants with SBI in the first months of life is undeniable.