Occipital-frontal Circumference Research Articles

Frequency of acute kidney injury in birth asphyxia at a Tertiary Care Hospital, Karachi.

ABSTRACT… Objective: To determine the frequency of acute kidney injury (AKI) in neonates presenting with birth asphyxia. Study Design: Cross-sectional study. Setting: Department of Pediatrics, National Institute of Child Health, Karachi. Period: December 2022 to May 2023. Material & Methods: A total of 159 neonates of both gender, aged between 7-28 days and having birth asphyxia were analyzed. Demographic features were recorded. The blood sample was collected in a sterile manner using 5 ml syringe and sent to the institutional laboratory for serum creatinine and electrolyte analysis. The frequency of AKI was noted. Results: In a total of 159 neonates, 95 (59.1%) were boys, The mean baseline serum urea and creatinine were 33.5±32.1 and 0.83±0.62 mg/dl respectively. AKI was noted in 65 (40.9%) neonates. Girls (p=0.035), relatively lower occipital frontal circumference (p=0.004), normal vaginal delivery (p<0.001), history of seizures (p<0.001), abnormal USG KUB (p<0.001), poor conscious level (p<0.001), higher birth asphyxia grading (p<0.001) and poor urine output (p<0.001) were linked with AKI. Mean baseline serum urea levels and serum creatinine levels were significantly raised among neonates who had AKI. Conclusion: The frequency of acute kidney injury among neonates having perinatal asphyxia was high. AKI was noted to have significant association with female gender, relatively lower occipital frontal circumference, normal vaginal delivery, history of seizures, abnormal ultrasonography findings, poor conscious level, higher birth asphyxia grading, and poor urine output at the time of admission.

The clinical and genotypic-phenotypic findings of mucopolysaccharidosis VI patients: an Iraqi single-study descriptive study.

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is a chronic illness that causes progressive enlargement, inflammation, or scarring of several tissues and organs until their collapse. In most cases, an infant with MPS VI shows no symptoms. The early signs and symptoms of MPS VI in children often develop in the first few months of life. MPS VI affects various systems in the body, including the skeletal, cardiac, and respiratory systems. The authors aim in our study to describe the clinical and genotypic-phenotypic findings of MPS VI patients in 'children Welfare Teaching Hospital, Medical City Complex.' The single-center study was conducted at the 'children Welfare Teaching Hospital, Medical City Complex' from November 2016 to May 2022. The research recruited 72 MPS VI patients from Iraq, all under 20. The authors investigated the sociodemographic characteristics, hematological lab results, gene-phenotype findings, and clinical features and evaluated the severity and progression of the MPS 6 disease. Seventy-two Iraqi MPS VI patients were involved in the study, and the average age of the study sample was 6.38±3.4 (0.3-19). The consanguinity rate was 94.4%. In the research, females comprised 56.9% of the patients, and the Z-scores for body mass index and occipital-frontal head circumference were -2.66 and 1.2. The fascial features at diagnosis, 'coarse facies' (90.3%), dysostosis multiplex (93%), short stature (94.4%), and recurrent respiratory infections (91.6%), were the most common clinical features among the enrolled patients. The most frequent mutation was (complementary DNA: c.753C>G, protein effect: p.(Tyr2*) or p.(Tyr251Term), and the codon cross-tabulation: premature stop codon, or homozygous stop nonsense mutation/exon N.3) (33/69 (47.82%)). Furthermore, a statistically significant correlation existed between lower weight and height readings and the progressed and severe stages of the MPS VI illness. As the first research in Iraq with a sufficient sample size of MPS VI patients, the investigation presented important clinical and gene-phenotype findings and revealed the necessity for enhancing the diagnosis of MPS VI, including the updated molecular analysis and monitoring the multisystem parameters, aberrant comorbidities, and the progression and severity.

A CAMK2B variant associated with tetralogy of Fallot, developmental delay, and growth retardation

CAMK2B encodes the beta-subunit of calcium/calmodulin-dependent protein kinase II (CAMKII), which is expressed mainly in the brain. Variants of CAMK2A and CAMK2B cause neurodevelopmental disorders, and CAMK2B alterations have been described in at least 14 patients with intellectual disability and developmental delay. Here, we describe a novel CAMK2B variant in a patient with tetralogy of Fallot (TOF), developmental delay, and growth retardation. The patient was a 2-year-old female. She was delivered at 36 weeks 6 days gestational age by caesarean section due to non-reassuring fetal status, with birth weight of 1680 g (−2.0 SD), birth length of 43.5 cm (−1.5 SD), and occipital-frontal head circumference (OFC) of 29.4 cm (−1.7 SD). Growth retardation, microcephaly, developmental delay, tetralogy of Fallot, and dysmorphic features were present. The patient controlled her head position at four months, rolled at six months, sat at 13 months, crawled at 18 months, and walked with support at 21 months. She began speaking words at 2 years old. Her dysmorphic features included a wide face, broad forehead, puffy eyelids, broad nasal base, broad and prominent philtrum, pointed chin, full cheeks, and prominent ears. A de novo missense CAMK2B variant (NM_172079.2:c.895A > G (p.Lys299Glu) NC_000007.14:g.44241708T > C (hg38)) was identified by proband exome sequencing and confirmed by Sanger sequencing. The variant was located at an autoregulatory segment and highly conserved among species. This patient displayed many of the physical features of CAMK2B-related neurodevelopmental disorder (NDD), but the TOF present in the current case is not a feature of patients with the NDD. Since a de novo CAMK2B (p.Leu443Val) variant has previously been found in a cohort of TOF, we conclude that CAMK2B variants may be associated with this specific cardiac defect.

Screening for fetal alcohol spectrum disorder in infants and young children.

Introduction: With an estimated prevalence of up to five percent in the general population, fetal alcohol spectrum disorders (FASD) are the most common neurodevelopmental disorder and more prevalent than autism. Early identification and subsequent early intervention have the potential to improve developmental trajectory of children with FASD. In addition, new research suggests supplementation with choline may ameliorate the developmental impairments associated with prenatal alcohol exposure. Availability of a screening tool with acceptable epidemiologic performance criteria may be clinical useful in identification of young children at increased risk for FASD. In this paper we describe the Early Fetal Alcohol Spectrum Disorder Screening Test (E-FAST) to identify young children at increased risk for an FASD. Methods: We developed the E-FAST dataset from previously published studies, comprised of 281 children under 5years of age, 180 (64.1%) were diagnosed with FASD and 101 (35.9%) were non-FASD. Analysis: The analysis identified seven useful variables (prenatal alcohol exposure, ADHD (Attention Deficit Hyperactivity Disorder), foster care or adopted, small OFC (occipital frontal circumference), communication impairments, impaired social skills, and cognitive deficits. All variables were categorized as yes/no for ease of use in a screening tool. Risk ratios for each of the seven indicators were estimated using two-way table analyses. Weights for each variable were estimated based on the relative strength of their odds ratios. Results: The average age was 2.7years of age (S.D. 1.29) and ranged from infant (6.4%) to 4years old (35.9%). Maternal alcohol use alone had a sensitivity of 0.97, specificity 0.65, and accuracy 0.86. For the combined seven variables, sensitivity was 0.94, specificity 0.74, and accuracy 0.87. Thus, the seven-item E-FAST screen had acceptable epidemiologic screening characteristics. Discussion: In the United States, up to 547 infants with FASD are born each day which far exceeds the capacity of multidisciplinary diagnostic clinics. During routine clinical management of infants and young children the use of an evidence-based screening tool provides a time efficient means to exclude large numbers of young children from further follow-up for FASD. Conversely, a positive screen identifies a smaller number of children at increased risk for FASD requiring more intensive evaluation and follow-up.

Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes.

Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. From June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year. Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < -2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < -2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = -0.08/illness-week, P = 0.06) and febrile illness (beta = -0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone ( P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12-15 months. These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.

Systematic Review on Individualized Versus Standardized Parenteral Nutrition in Preterm Infants.

The need for high quality evidence is recognized for optimizing practices of parenteral nutrition (PN). The purpose of the present systematic review is to update the available evidence and investigate the effect of standardized PN (SPN) vs. individualized PN (IPN) on protein intake, immediate morbidities, growth, and long-term outcome in preterm infants. A literature search was performed on articles published in the period from 1/2015 to 11/2022 in PubMed and Cochrane database for trials on parenteral nutrition in preterm infants. Three new studies were identified. All new identified trials were nonrandomized observational trials using historical controls. SPN may increase weight and occipital frontal circumference gain and lower the value of maximum weight loss. More recent trials suggest that SPN may easily increase early protein intake. SPN may reduce the sepsis incidence, but overall, no significant effect was found. There was no significant effect of standardization of PN on mortality or stage ≥2 necrotizing enterocolite (NEC) incidence. In conclusion SPN may improve growth through higher nutrient (especially protein) intake and has no effect on sepsis, NEC, mortality, or days of PN.

Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort.

Do twins conceived through assisted reproductive treatments (ART) grow differently from naturally conceived (NC) twins in early life? Assessments at 6-8 weeks old and at school entry show that ART twins conceived from frozen embryo transfer (FET) grow faster than both NC twins and ART twins conceived from fresh embryo transfer (ET). Singletons born from fresh ET grow more slowly in utero and in the first few weeks of life but then show postnatal catch-up growth by school age, compared to NC and FET babies. Evidence on early child growth of ART twins relative to NC twins is inconsistent; most studies are small and do not distinguish FET from fresh ET cycles. This cohort study included 13528 live-born twin babies conceived by ART (fresh ET: 2792, FET: 556) and NC (10180) between 1991 and 2009 in Scotland. The data were obtained by linking Human Fertilisation and Embryology Authority ART register data to the Scottish Morbidity Record (SMR02) and Scottish child health programme datasets. Outcome data were collected at birth, 6-8 weeks (first assessment), and school entry (4-7 years old) assessments. The primary outcome was growth, measured by weight at the three assessment points. Secondary outcomes were length (at birth and 6-8 weeks) or height (at school entry), BMI, occipital circumference, gestational age at birth, newborn intensive care unit admission, and growth rates (between birth and 6-8 weeks and between 6-8 weeks and school entry). All twins in the linked dataset (born between 1991 and 2009) with growth data were included in the analysis. To determine outcome differences between fresh ET, FET, and NC twins, linear mixed models (or analogous logistic regression models) were used to explore the outcomes of interest. All models were adjusted for available confounders: gestational age/child age, gender, maternal age and smoking, Scottish Index of Multiple Deprivation, year of treatment, parity, ICSI, and ET stage. In the primary birth weight models, the average birth weight of fresh ET twins was lower [-35 g; 95% CI: (-53, -16)g] than NC controls, while FET twins were heavier [71 g; 95% CI (33, 110) g] than NC controls and heavier [106 g; 95% CI (65, 146) g] than fresh ET twins. However, the difference between FET and NC twins was not significant when considering only full-term twins (≥37 weeks gestation) [26 g; 95% CI (-30, 82) g], while it was significantly higher in preterm twins [126 g; 95% CI (73, 179) g]. Growth rates did not differ significantly for the three groups from birth to 6-8 weeks. However, FET twins grew significantly faster from 6 to 8 weeks than NC (by 2.2 g/week) and fresh ET twins (by 2.1 g/week). By school entry, FET twins were 614 g [95% CI (158, 1070) g] and 581 g [95% CI (100, 1063) g] heavier than NC and fresh ET twins, respectively. Length/height and occipital frontal circumference did not differ significantly at any time point. Although the differences between ART and NC reflect the true ART effects, these effects are likely to be mediated partly through the different prevalence of mono/dizygotic twins in the two groups. We could not explore the mediating effect of zygosity due to the unavailability of data. The confounding variables included in the study were limited to those available in the datasets. Live-born twins from FET cycles are heavier at birth, grow faster than their fresh ET and NC counterparts, and are still heavier at school entry. This differs from that observed in singletons from the same cohort, where babies in the three conception groups had similar weights by school entry age. The results are reassuring on known differences in FET versus fresh ET and NC twin outcomes. However, FET twins grow faster and are consistently larger, and more ART twins depict catch-up growth. These may lead to an increased risk profile for non-communicable diseases in later life. As such, these twin outcomes require careful evaluation using more recent and comprehensive cohorts. This study was funded by the EU H2020 Marie Sklodowska-Curie Innovative Training Networks (ITN) grant Dohartnet (H2020-MSCA-ITN-2018-812660). The authors have no competing interests to declare. N/A.

To Learn, Try Teaching

To Learn, Try Teaching

Analysis of structural and functional central nervous system abnormalities associated with prenatal exposure to ethanol in children of primary school age

The article is presenting results of the third stage of the examination of primary school students for the identification and assessment of the severity of structural and functional abnormalities of the central nervous system (CNS) that arose in connection with perinatal exposure to ethanol — 77 children with previously identified delayed physical development of various degrees and characteristic dysmorphological disorders were examined. The identification of structural abnormalities to the CNS was carried out on the basis of assessing the correspondence of the occipital frontal circumference of the child’s head with the normative values for a specific sex and age, determination of functional abnormalities was carried out on the basis of an assessment of intellectual development based on the results of the Wechsler Intelligence Scale for Children and behavioral characteristics according to the Vineland Adaptive Behavior Scales.The presence of structural abnormalities to the CNS, manifested by a decrease in the occipital frontal circumference 2 or more standard deviations below the mean for the age norm, was revealed in 59 patients (77%). A serious functional disorder of the CNS, manifested by mild and moderate mental retardation, was found in 23 children (30%). Mild or moderate functional impairment of the CNS in the form of delayed cognitive development was found in 21 children (27%).Assessment of behavior and adaptive skills revealed a significant number of children (72%), whose adaptive behaviors were unfavorably different from the norm. The most common ones were: low concentration of attention — in 77%, increased anxiety and fear — in 65%, hyperactivity — in 60%, impulsivity — in 44%, outbursts of anger — in 43%, deceit and theft — in 40%, excessive dependence or codependency — in 38%, deliberate destruction of one’s own or someone else’s property — in 14% of children.Statistically significant inverse correlations of a high level of significance (p≤0.01) between indicators of nonverbal intelligence and maladaptive behavior were obtained. Inverse correlations between structural abnormalities of the CNS and nonverbal intelligence are presented at the tendency level.

Identification of Seminal Physical Features of Prenatal Alcohol Exposure by Child Psychologists

IntroductionPrenatal alcohol exposure (PAE) impacts an estimated 5% or more children born in the USA and is associated with life-long neuropsychological deficits. Early identification is essential but access to diagnostic evaluation is limited. This study reports on the effectiveness of training child psychologists to identify and measure the salient physical features of PAE.MethodsChildren, 8–13 years, were divided into two groups: (1) children meeting criteria for PAE (n = 46) and (2) typically developing controls without PAE (TD; n = 36). Child psychologists were trained to reliability measure height, weight, occipital frontal circumference (OFC), and the characteristic facial features of FASD independent of knowledge of PAE history.ResultsGroups differed significantly on meeting the diagnostic criteria proposed by Hoyme et al. (Pediatrics, 138:e20154256, 2016) on height, OFC, upper vermillion border, philtrum, and palpebral fissure length. They did not differ on weight. All children in the alcohol exposed group could be classified as meeting criteria for an FASD whereas none in the unexposed group met criteria.DiscussionThis study demonstrated that child psychologists, blind to PAE history, could be reliably trained to assess the physical features of children with PAE. Because early diagnosis and intervention is of paramount importance, we propose that inclusive diagnostic criteria for FASD and the use of psychologists and other allied health professionals, trained to screen for the diagnosis, should be expanded in clinical practice.

Primary microcephaly families mapped with different microcephalic genes by using whole exome sequencing; Insilco 3D Model's prediction of STIL, CENPJ, and CEP135 protein

BackgroundPrimary microcephaly (MCPH- OMIM 251200) is inherited from an autosomal recessive, heterogeneous, non-progressive, and neurodevelopmental disorder. It is considered by small occipital-frontal circumference (OFC) for a person's age and gender at birth. MethodsPrimary microcephaly affected consanguineous families (A, B, C, D) in various remote villages of Punjab, Pakistan were identified. Blood samples were collected followed by we used salting-out method for DNA extraction. WES (whole exome sequencing) was used to analyze the mutations and filtered variants that were confirmed by sanger sequencing. ResultsWhole-exome sequencing revealed a sequence variant c.453 + 5G > A in intron 5 of the STIL gene that generated a frameshift and truncated protein (p. Asp89Glyfs*8) by introducing a premature stop codon in family A. We have mapped a mutation in exon 2 (c.18delC) of the CENPJ gene in family B. This variant stopped the transcript synthesis by the premature introduction of the stop codon (p. Ser7Profs*2). The sequence variant in exon 23 (9557C > G) of the ASPM gene in family C, causing a sudden halted the translation process (p. Ser3186X). In family D revealed a variant in intron 11 (c.1473 + 1G > A) of the CEP135 gene caused a frameshift mutation (p. Glu417Glyfs*2) and terminated the protein synthesis, these variants were previously reported and our study supports them. However, no three-dimensional structure models of STIL, CENPJ, and CEP135 protein have been solved in the protein database. As a result, we predicted 3D protein models for the first time in this study by using Insilco technologies such as I TASSER, Swiss model, and phyre2. The validation of these protein models was done by using Ramachandran plot and SAVES server while refinement of the selected models was done by using Galaxy WEB server. In the Protein Model Database, the 3D model of STIL protein predicted and refined was submitted with the entry number PM0084074, whereas the 3D model of CENPJ protein was deposited with the accession number PM0084076. The 3D model of CEP135 protein was deposited in the Protein Model Database (PMDB – https://bioinformatics.cineca.it/PMDB/) with the accession number PM0084077. ConclusionsWe exposed DNA variants in primary microcephaly-affected individuals which impaired the expression of genes that are necessary to build a proper functioning of the brain. This study provides supporting evidence to the pathogenicity of previously reported mutations. Inslico protein models prediction provides functional exploration for clinicians and geneticists for establishing reliable diagnostic strategies for MCPH families.

Head Growth in Children With Perinatal Stroke

Source: Leong A, Floer A, Kirton A, et al. Head circumference trajectory in children with perinatal stroke [published online ahead of print March 8, 2021]. J Child Neurol. doi:10.1177/0883073821996103Investigators from Alberta Children’s Hospital, Calgary, Canada, conducted a retrospective cohort study to evaluate longitudinal head growth in children with perinatal stroke. Children with perinatal stroke were identified through a population-based research cohort of children with MRI-confirmed unilateral arterial perinatal stroke and who had follow-up of more than 12 months with the Pediatric Stroke Outcome Measure (PSOM), a validated measure of neurologic deficit and function. Participants included in this current study were ≤18 years old and had no other systemic conditions. Demographics were collected at the time of cohort enrollment.The primary predictor was occipital-frontal head circumference (OFC) as obtained from the medical record. OFC data at different ages from the same participant from birth to 18 years old were included. The primary outcome was neurologic deficit, as measured by the PSOM. The PSOM is scored on a 10-point scale, with higher scores representing worse deficits. Investigators generated sex-segregated OFC plots from birth to 18 years old using the 50th percentile OFC at every 2-week interval between birth and 6 months of age, 1-month intervals from 6 months to 2 years of age, and 6-month intervals from 2 to 18 years of age. Investigators also compared the 50th percentile OFC among participants at each interval to the 50th percentile OFC of healthy American children serving as controls using OFC data obtained from a separate database. Lastly, investigators assessed whether there were more participants with PSOM scores ≥1 who had OFCs at <50th percentile (vs ≥50th percentile).There were 315 OFC measurements from 102 participants with perinatal stroke included in analysis. Overall, 52% participants were male. There was a mean of 2.8 OFC measurements among female participants and 3.2 OFC measurements among male participants. Overall, 28% (N = 29) of participants had a PSOM score of 0.The OFC for female participants followed the OFC for female healthy controls until age 3 months, at which point the 50th percentile OFC for female participants became significantly smaller compared to healthy controls. This effect also was observed for male participants, but the divergence occurred later at 18 months. There were significantly more participants with an OFC <50th percentile (vs ≥50th percentile) who had PSOM scores ≥1 (87% vs 52%; P = 0.004).Investigators conclude that there is a deceleration in head growth in children with perinatal stroke and worse neurological outcomes among those with an OFC <50th percentile.Dr Candee has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Perinatal stroke is the most common cause of hemiplegic cerebral palsy, occurring in roughly 1/2,300 term births and 7/1,000 preterm births.1 It is most often the result of ischemic injury to brain tissue, which then leads to encephalomalacia, volume loss, and a decrease in OFC.2 Although acquired microcephaly has been shown to be associated with poor neurologic development across a variety of conditions, the current investigators are the first to look specifically at the impact of head growth (using OFC trajectory as a surrogate) on neurologic development in children with a history of perinatal stroke.3The results of the current study confirm the suspected hypothesis of the investigators, namely that head growth deceleration occurs in children with perinatal stroke, and that OFC <50th percentile is associated with a worse neurological outcome (as measured by PSOM). Interestingly, the timing of OFC divergence between the study population and healthy controls occurred much earlier for girls (eg, 3 months, vs 1 year for boys). The study findings are strengthened by the exclusion of “higher-risk” children with systemic conditions or other non-stroke neurologic diagnoses. They potentially are limited in that the collective data could be biased by over-representation of the more severely affected patients (who may have had more measurements).Perinatal stroke often goes unnoticed until 4-6 months of life, when motor asymmetry, early hand preference, or seizures become evident.1 While OFC is only a rough estimate of head size in a mobile infant and therefore highly subject to measurement error, it is an inexpensive, noninvasive tool that can enable primary care providers to detect perinatal stroke or its complications (eg, infantile spasms or cerebral palsy) sooner. OFC measurements also potentially could facilitate the connection of infants with earlier individualized support or therapeutic interventions for optimizing development.Head growth deceleration in children with perinatal stroke is associated with poor developmental outcome.Hats off to research with results that underscore the continued value of physical examination rather than newer health care technology.

Improving the rate of anthropometric measurements in the pediatric intensive care unit.

Malnutrition occurs in approximately 25% of pediatric intensive care patients and correlates with increased length of stay, prolonged ventilation, and mortality. Anthropometric measurements should be obtained at admission and throughout hospitalization to evaluate nutrition status. We aimed to increase documentation, reporting, and discussion of anthropometric measurements, including height/length, weight, and occipital frontal circumference (OFC) within 24 hours of admission and weekly. A multifaceted process improvement model was implemented over 1 month. Interventions included education, recruiting nurse champions, process mapping, new equipment, and formal discussion of nutrition status during rounds. A proportions hypothesis test compared frequency of anthropometric measures obtained during each study phase: preintervention, postintervention, and sustainment. In terms of admission metrics over respective study phases, the PICU had fluctuation in weights (91%, 98%, and 97%) and height (49%, 73%, and 71%) and increased rates in OFC (36%, 61%, and 65%). The cardiovascular intensive care unit (CVICU) had stable weights (100%, 100%, and 100%) and increased rates in height (87%, 94%, and 95%) and OFC (28%, 64%, and 86%), respectively. In terms of weekly metrics over study phases, the PICU had fluctuation in weights (91%, 89%, and 93%) and increased rates in heights (38%, 69%, and 76%) and OFC (45%, 76%, and 100%). The CVICU had increased rates in weights (98%, 100%, and 100%) and fluctuations in heights (50%, 83%, and 75%), and OFC (48%, 84%, and 75%). Interventions increased rates of measurements. During the sustainment phase, there was regression in rates, although these remained above baseline. Additional interventions may increase compliance and foster change in unit culture.

Growth of preterm very low birth weight infants discharged with weight of less than 1500grams

Early discharge of preterm very low birth weight (VLBW) infants is at times inevitable in low resource settings. The implication of such practice on the growth of this high-risk population is not known. We conducted a retrospective chart review to describe the growth of preterm VLBW infants discharged with a weight of less than 1500 g.ObjectivesTo describe the growth of discharged preterm VLBW infants over the first 12 weeks.MethodBetween June 2013 and January 2014; 164 discharged preterm VLBW infants were followed up for 3 months. Among the survivors (132), we identified 111 infant records for this study. Relevant data was entered in STATA for analysis. Growth percentiles were determined at approximately 4 weeks, 8 weeks, and 12 weeks post-discharge using the intergrowth 21st growth charts. Growth velocities were computed using the 2-point average weight model. Regression analysis was used to identify factors associated with growth failure. Growth failure was defined as occipital frontal circumference (OFC), weight, and length < 10th centile by 12 weeks post-discharge. P-value of < 0.05 was considered significant at a 95% confidence interval.ResultsAmong the study infants the median gestational age and weight at birth were 32 weeks (range 28-35 weeks) and 1250 g(range 850-1500 g) respectively; 60/111(54%) were Small for Gestational Age (SGA). The median discharge postmenstrual age (PMA) was 34 weeks (range 30-38 weeks) and weight was 1140 g (range 830-1490 g). The majority 88.2% had not recovered birth weight at discharge of whom 59.1% recovered by 2 weeks and 40.9% recovered between 2 and 4 weeks after discharge. By 12 weeks post-discharge the median PMA and weight were 46 weeks (range 37-51 weeks),and 3110 g (range 1750-5000 g) respectively, 38.7% of the infants had growth failure and 36.9% had OFC <3rd centile. Growth velocity < 15 g/kg/d in the first 4 weeks (OR 3.8, p 0.010) and subsequent 4 weeks (OR 2.5, p 0.049) post-discharge were independently associated with growth failure.ConclusionSlow birth weight recovery was observed and growth failure was prevalent by 12 weeks post-discharge with more than a third having severe microcephaly. Poor post-discharge growth velocity was associated with subsequent growth failure.RecommendationsGrowth velocity monitoring among preterm VLBW infants should be emphasized. The implication and interventions of this early growth failure needs to be explored.

Head circumference trajectory in children with perinatal stroke.

Background:Perinatal stroke is a leading cause of hemiparetic cerebral palsy and lifelong disability. Neurodevelopmental outcomes are difficult to predict and markers of long-term poor outcome continue to be investigated. Deceleration in growth of head circumference has been associated with worse developmental outcomes in neonatal brain injury. We hypothesized that perinatal stroke would result in decreased rates of head growth during childhood that would be associated with worse developmental outcomes.Methods:Patients with magnetic resonance imaging (MRI)–confirmed neonatal arterial ischemic stroke and arterial presumed perinatal ischemic stroke were identified from a population-based research cohort (Alberta Perinatal Stroke Project). Demographics and occipital-frontal circumference data were collected from medical records. Head growth was compared to typically developing control charts using a 2-tailed t test. The Fisher exact test was used to examine associations between Pediatric Stroke Outcome Measures (PSOM) scores and occipital-frontal head circumference.Results:Three hundred fifteen occipital-frontal head circumference measurements were collected from 102 patients (48 female, 54 male), over a median of 3.2 years (standard deviation = 5.18, range = 0-18.3). After 3 months for female patients and 1 year for male patients, occipital-frontal head circumference deviated and remained below normal growth trajectories (P < .05) with a large effect size (Cohen d >0.8). Poor outcome (PSOM ≥ 1) was associated with smaller occipital-frontal head circumference (P < .05).Conclusion:Head growth deceleration is observed in children with perinatal arterial ischemic stroke and is associated with poor outcome. Head circumference may be a tool to alert clinicians to the potential of abnormal neurologic outcome.

Respiratory effects of prolonged prednisolone use in infants with evolving and established Bronchopulmonary dysplasia

BackgroundCurrent literature focuses on systemic corticosteroids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants with limited data on use for pulmonary disease after the first month of life. Prednisolone may be a reasonable option for late treatment given its desirable pharmacologic properties and use in other pediatric disease states. AimsTo characterize a premature population that received an extended prednisolone course and determine the effect on respiratory and anthropometric outcomes over time. Study designSingle-center, retrospective study. SubjectsPreterm infants who received ≥30 days of prednisolone or methylprednisolone for treatment of respiratory complications following preterm birth. Outcomes measuresAssessment of pulmonary severity score (PSS), weight, length, and occipital frontal circumference weekly during the first 4 weeks of prednisolone and after discontinuation. ResultsThirty-four infants with a mean gestational age of 26.5 ± 2.5 weeks and birth weight of 846 ± 353 g were identified. Nine patients were on invasive mechanical ventilation and 25 patients were on non-invasive respiratory support at prednisolone initiation. Prednisolone was initiated at a mean post-menstrual age of 41.7 ± 5 weeks and a mean dose of 1.7 ± 0.6 mg/kg/day. A significant decrease in PSS was seen over time (p < 0.001) without rebound following discontinuation. Eleven patients decreased the mode of respiratory support during prednisolone treatment. No significant impact in anthropometric outcomes were identified. ConclusionProlonged prednisolone use was associated with a sustained decrease in PSS without adverse effects on growth measurements. These results suggest potential benefit of prednisolone on respiratory outcomes in a subset of preterm infants.

Uncomplicated intraventricular hemorrhage is not associated with lower estimated cerebral volume at term age.

Cerebral lesions detected using cerebral ultrasound (cUS) in very preterm infants are associated with increased risk for neurodevelopmental problems. However, uncomplicated intraventricular hemorrhage (IVH) has no consistent association with poor outcome. In this study we evaluate the effect of uncomplicated IVH on estimated brain volume at term-equivalent age (TEA), using a model based on measurements made from cUS. We studied 2 groups of preterm infants (<32 weeks' gestational age (GA)) up to and at TEA: (1) infants with uncomplicated grades 2 or 3 IVH, (2) infants with consistently normal scans. Estimated cerebral volumes at TEA were calculated using a previously described model based on linear measurements and compared between the 2 groups using independent groups t-test or the Mann-Whitney test; p-value <0.05 was considered significant. We assessed 95 preterm infants (18 with uncomplicated IVH and 71 with normal scans). GA and birth weight were lower in infants with uncomplicated IVH (26.8/28.7weeks, p<0.001, 944/1082g, p<0.05, respectively); occipital-frontal circumference at TEA was smaller in the IVH infants (34.2 vs 35.3cm, p<0.05). However, no significant differences at TEA were found for estimated cranial volume (383/411cc3), estimated cerebral volume (337/341cc3), Levene ventricular index (13.5/12.2mm) or thalamo-occipital distance (21.5/20.3mm). Statistical adjustment for the lower GA in the IVH group confirmed the absence of a significant difference in the findings. In summary, we found that estimated cerebral volume at TEA, based on measurements made at the bedside using cranial US, is not different between very preterm infants with consistently normal scans and those with uncomplicated grades 2 and 3 IVH.

Central catheter removal timing and growth patterns in preterm infants.

Early discontinuation of total parenteral nutrition (TPN) at 100 ml/kg/day of enteral feeds, compared with 140 ml/kg/day, led to significant delay in time to regain the birth weight in very low birth weight infants (birth weight < 1500 g, VLBW). Our aim was to compare the growth of infants in relation with timing of TPN discontinuation up to 2 years corrected gestational age (CGA). Posttrial follow-up study using review of paper medical records. Participants of the randomized controlled trial studying effect of early parenteral nutrition discontinuation on time to regain birth weight in VLBW infants were included. Growth parameters inclusive of weight, length, and occipital-frontal circumference (OFC) were collected. Z-scores were calculated at five predefined time points-birth, 0-11 weeks CGA, 12-35 weeks CGA, 36-60 weeks CGA, and 61-96 weeks CGA and compared for control and intervention groups. Regarding weight, we found lower mean Z-score in the intervention group between 0 and 11 weeks CGA, with larger difference in extremely low birth weight infants (birth weight < 1000 g, ELBW), but this did not reach the statistical significance. Regarding length, the same difference, slightly delayed to 35 weeks CGA was observed and reached statistical significance for ELBW infants between 12 and 35 weeks CGA. There was no difference in OFC mean Z-scores at any timepoint. The discontinuation of TPN at 100 ml/kg/day showed significantly lower Z-score for length in ELBW infants between 12 and 35 weeks CGA. There were no differences in Z-scores by 2 years CGA.

Whole-exome sequencing identifies homozygous mutation in TTI2 in a child with primary microcephaly: a case report

BackgroundPrimary microcephaly is defined as reduced occipital-frontal circumference noticeable before 36 weeks of gestation. Large amount of insults might lead to microcephaly including infections, hypoxia and genetic mutations. More than 16 genes are described in autosomal recessive primary microcephaly. However, the cause of microcephaly remains unclear in many cases after extensive investigations and genetic screening.Case presentationHere, we described the case of a boy with primary microcephaly who presented to a neurology clinic with short stature, global development delay, dyskinetic movement, strabismus and dysmorphic features. We performed microcephaly investigations and genetic panels. Then, we performed whole-exome sequencing to identify any genetic cause. Microcephaly investigations and genetic panels were negative, but we found a new D317V homozygous mutation in TELOE-2 interacting protein 2 (TTI2) gene by whole-exome sequencing. TTI2 is implicated in DNA damage response and mutation in that gene was previously described in mental retardation, autosomal recessive 39.ConclusionsWe described the first French Canadian case with primary microcephaly and global developmental delay secondary to a new D317V homozygous mutation in TTI2 gene. Our report also highlights the importance of TTI2 protein in brain development.

Endoscopic Third Ventriculostomy versus Ventriculo-Peritoneal Shunt for Infant Hydrocephalus

Introduction: Patients with hydrocephalus, which is the most pediatric neurological disorder, undergo Cerebrospinal fluid (CSF) diversion through third ventriculostomy or ventriculo-peritoneal shunt. Up to date, the optimal hydrocephalus treatment modality is not clear. Aim: We compared the outcome of endoscopic third ventriculostomy (ETV) versus ventriculo-peritoneal shunt (VP shunt) as a second surgical intervention in management of Infant hydrocephalus concerning success rate and complications. Patients and Methods: We conducted an observational study of 52 children with hydrocephalus (congenital or acquired) in whom CSF diversion was performed using either ETV or VP shunt in randomized control trial. Results: During the period examined, 52 children, 26 underwent ETV and 26 underwent VP shunt. The mean age was 11.0 ± 4.3 months in ETV and 11.3 ± 4.7 months in VP shunt. Postoperative infection in the ETV group was lower than in the VP shunt group (23.1% vs. 53.8% P = 0.045). Regarding operating time, In ETV group operation duration was 46.9 min and 64.3 min in the V-P shunt group (P = 0.13). There was no statistically significant difference between the two study groups regarding the rate of obstruction, change in occipital frontal circumference (OFC) or the need of revision surgery. One year survival for VP shunt group vs. ETV group was 46.2% vs. 65.4% respectively. Conclusion: ETV associated with lower rates of postoperative infection and shorter operation time with no significant difference in rates of obstruction, change in OFC and revision surgery in comparison to VP shunt.