The trajectory of head circumference and neurodevelopment in very preterm newborns during the first two years of life: a cohort study.

OBJECTIVE: To evaluate the growth trajectory of head circumference and neurodevelopment, and to correlate head circumference with cognitive, language, and motor outcomes during the first two years. METHOD: Prospective cohort study in a tertiary hospital including 95 newborns under 32 weeks or 1500 g. Neonates who developed major neonatal morbidities were excluded. The head circumference was measured at birth, at discharge, and at term-equivalent age, 1, 3, 5, 12, 18, and 24 months of corrected age, and the Bayley Scales (Bayley-III) were applied at 12, 18 and 24 months of corrected age to assess cognitive, language and, motor domains. Scores below 85 were classified as mild/moderate deficits and scores below 70 as severe deficits. The association between head circumference Z score and Bayley scores was assessed using Pearson's correlation. The study considered a significance level of 0.05. RESULTS: There was a decrease of -0.18 in the head circumference Z score between birth and discharge and the catch-up occurred between discharge and 1 month (an increase of 0.81 in the Z score). There was a positive correlation between head circumference and Bayley scores at 18 months. There was also a positive correlation between head circumference at discharge and at 5 months with the three domains of the Bayley. CONCLUSION: Serial measurements of head circumference provide knowledge of the trajectory of growth, with early catch-up between discharge and 1 month, as well as its association with neurodevelopment. Head circumference is therefore a valuable clinical marker for neurodevelopment, especially in very preterm newborns.

Argentine reference charts for head circumference from birth to 19 years of age. / Referencias argentinas de perímetro cefálico desde el nacimiento hasta los 19 años.

Introduction. Head circumference (HC) is an indicator of brain growth; growth charts are necessary to determine normal or pathological variations. Objectives. To present the first Argentine HC reference charts between birth and 19 years of age and to compare them with the Nellhaus charts, which have been used in our country to date. Population and methods. These references were developed based on combined data from the National Survey on Nutrition and Health of 2018 and cross-sectional studies conducted between 2004 and 2007 in the provinces of Buenos Aires and La Pampa, which included 8326 healthy children and adolescents. Growth curves were adjusted using the LMS method. To assess the differences between these reference charts and the Nellhaus charts, at different ages, the 2nd, 50th, and 98th percentiles were plotted. Results. HC showed a variable increase in size with age, which was greater in the first years of life, and a slight increase at puberty. The values for the 98th percentile of the Argentine reference charts werehigher than those of the Nellhaus charts at all ages. The values for the 2nd percentile of the national reference were lower than those of the Nellhaus charts during the first 2 years of life, similar between 3 and 7 years of age, and higher after this age. Conclusions. The Argentine curves adequately describe the growth pattern of HC. The differences found with the Nellhaus charts may be attributed to secular changes.

Introducción. El perímetro cefálico (PC) es un indicador del crecimiento cerebral y es necesario contar con referencias de crecimiento que permitan determinar variaciones normales o patológicas. Objetivos. Presentar las primeras referencias argentinas de perímetro cefálico entre el nacimiento y los 19 años, y compararlas con las referencias de Nellhaus, utilizadas en nuestro país hasta la actualidad. Población y métodos. Para la construcción de estas referencias, se combinaron datos de la Encuesta Nacional de Nutrición y Salud 2018 y estudios transversales realizados entre 2004 y 2007 en las provincias de Buenos Aires y La Pampa, que incluyeron 8326 niños, niñas y adolescentes sanos. Las curvas de crecimiento fueron ajustadas con el método LMS. Para evaluar la magnitud de las diferencias entre estas referencias y las de Nellhaus, a diferentes edades, se graficaron los centilos 2, 50 y 98. Resultados. El PC mostró un incremento de tamaño variable con la edad, de mayor magnitud en los primeros años de vida, y un ligero incremento en la pubertad. Los valores del centilo 98 de las referencias argentinas fueron mayores que los de Nellhaus en todas las edades. Los valores del centilo 2 de la referencia nacional fueron menores que los de Nellhaus durante los primeros 2 años de vida, similares entre los 3 y 7 años, y mayores a partir de esta edad. Conclusiones. Las curvas argentinas describen adecuadamente el patrón de crecimiento del PC. Las diferencias halladas con la referencia de Nellhaus pueden atribuirse a cambios seculares.

Head circumference at birth and postnatal growth trajectory in vulnerable groups from Argentina.

OBJECTIVES: To investigate the association between the anthropometric status at birth and brain and bone growth during the first year of life. According to the brain-sparing hypothesis, we expect catch-up to be faster in head circumference (HC) than in body length. METHODS: This is a longitudinal design that included Argentinian infants under 12 months of age with at least three anthropometric records. We classified study participants into four growth status categories according to z-scores for HC (HCZ) and length (LAZ) at birth, with z-score = -2 as a threshold. We used the Count model to describe growth trajectories in HC and length in the first year of life according to the growth status at birth. Recovery indicator for HC and length was taken as the time until the predicted growth trajectory surpassed the threshold curve predicted by z-score = -2 for age. RESULTS: Growth models included 3399 infants. There were significant differences in the growth parameters between groups in all cases (p < 0.05). Within the group with a low HCZ and a low LAZ at birth, HC recovery was faster than length. In the case of a low z-score for only one of the variables, newborns with a low HCZ recovered faster than individuals born with a low LAZ. CONCLUSIONS: The postnatal growth pattern in HC and length is associated with the growth status of HC and length at birth. As we hypothesized, the fastest postnatal recovery occurs for HC in cases of intrauterine delayed growth.

A tridimensional atlas of the developing human head.

The evolution and development of the head have long captivated researchers due to the crucial role of the head as the gateway for sensory stimuli and the intricate structural complexity of the head. Although significant progress has been made in understanding head development in various vertebrate species, our knowledge of early human head ontogeny remains limited. Here, we used advanced whole-mount immunostaining and 3D imaging techniques to generate a comprehensive 3D cellular atlas of human head embryogenesis. We present detailed developmental series of diverse head tissues and cell types, including muscles, vasculature, cartilage, peripheral nerves, and exocrine glands. These datasets, accessible through a dedicated web interface, provide insights into human embryogenesis. We offer perspectives on the branching morphogenesis of human exocrine glands and unknown features of the development of neurovascular and skeletomuscular structures. These insights into human embryology have important implications for understanding craniofacial defects and neurological disorders and advancing diagnostic and therapeutic strategies.

Annelid functional genomics reveal the origins of bilaterian life cycles.

Indirect development with an intermediate larva exists in all major animal lineages1, which makes larvae central to most scenarios of animal evolution2-11. Yet how larvae evolved remains disputed. Here we show that temporal shifts (that is, heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. We performed chromosome-scale genome sequencing in the annelid Owenia fusiformis with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids. We found that trunk development is deferred to pre-metamorphic stages in the feeding larva of O. fusiformis but starts after gastrulation in the non-feeding larva with gradual metamorphosis of Capitella teleta and the direct developing embryo of Dimorphilus gyrociliatus. Accordingly, the embryos of O. fusiformis develop first into an enlarged anterior domain that forms larval tissues and the adult head12. Notably, this also occurs in the so-called 'head larvae' of other bilaterians13-17, with which the O. fusiformis larva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in head larvae, facilitated larval evolution in Bilateria. This diverges from prevailing scenarios that propose either co-option9,10 or innovation11 of gene regulatory programmes to explain larva and adult origins.

Emergence of heart and branchiomeric muscles in cardiopharyngeal mesoderm.

Branchiomeric muscles of the head and neck originate in a population of cranial mesoderm termed cardiopharyngeal mesoderm that also contains progenitor cells contributing to growth of the embryonic heart. Retrospective lineage analysis has shown that branchiomeric muscles share a clonal origin with parts of the heart, indicating the presence of common heart and head muscle progenitor cells in the early embryo. Genetic lineage tracing and functional studies in the mouse, as well as in Ciona and zebrafish, together with recent experiments using single cell transcriptomics and multipotent stem cells, have provided further support for the existence of bipotent head and heart muscle progenitor cells. Current challenges concern defining where and when such common progenitor cells exist in mammalian embryos and how alternative myogenic derivatives emerge in cardiopharyngeal mesoderm. Addressing these questions will provide insights into mechanisms of cell fate acquisition and the evolution of vertebrate musculature, as well as clinical insights into the origins of muscle restricted myopathies and congenital defects affecting craniofacial and cardiac development.

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment.

The early life microbiome plays critical roles in host development, shaping long-term outcomes including brain functioning. It is not known which initial infant colonizers elicit optimal neurodevelopment; thus, this study investigated the association between gut microbiome succession from the first week of life and head circumference growth (HCG), the earliest validated marker for neurodevelopment. Fecal samples were collected weekly from a preterm infant cohort during their neonatal intensive care unit stay and subjected to 16S rRNA gene sequencing for evaluating gut microbiome composition, in conjunction with clinical data and head circumference measurements. Preterm infants with suboptimal HCG trajectories had a depletion in the abundance/prevalence of Bacteroidota and Lachnospiraceae, independent of morbidity and caloric restriction. The severity of gut microbiome depletion matched the timing of significant HCG pattern separation between study groups at 30-week postmenstrual age demonstrating a potential mediating relationship resultant from clinical practices. Consideration of the clinical variables indicated that optimal infant microbiome succession is primarily driven by dispersal limitation (i.e., delivery mode) and secondarily by habitat filtering (i.e., antibiotics and enteral feeding). Bacteroidota and Lachnospiraceae are known core taxa of the adult microbiome, with roles in dietary glycan foraging, beneficial metabolite production and immunity, and our work provides evidence that their integration into the gut microbiome needs to occur early for optimal neurodevelopment.

Dinámica relacionada con la edad de parámetros antropométricos craneofaciales y su asociación con el tipo de oclusión dental en seres humanos de ambos géneros de: 17 a 24 años / Age-related dynamics of craniofacial anthropometric parameters and their association with the type of dental occlusion in humans of both genders aged 17­24 years

El propósito del estudio fue analizar la dinámica de los cambios relacionados con la edad de las estructuras craneofaciales de acuerdo con los parámetros antropométricos en hombres y mujeres de 17 a 24 años, y determinar la correlación, definida por análisis antropométrico, entre las formas de morfología craneofacial y los tipos de anomalías dento-maxilares. Materiales y métodos: Se realizó un examen antropométrico de 851 individuos (418 hombres y 433 mujeres) de 17 a 24 años y la evaluación de 45 mediciones entre puntos de referencia de tejidos blandos. Además, se realizó una valoración odontológica general, que incluyó la clasificación de las anomalías dentomaxilares. Resultados: Se detectó que el ancho de la cabeza, el largo de la cabeza, así como el ancho de la mandíbula y el ancho morfológico facial en las hembras alcanzan valores máximos de crecimiento a la edad de 20 años. Además, se obtuvieron datos que indicaron la continuación del crecimiento de los parámetros antropométricos craneofaciales mencionados anteriormente en los hombres durante el período de transición de la adolescencia a la edad adulta. Conclusión: la mordida profunda distal es la anomalía dento-maxilar (DMAn) más común en hombres y mujeres bielorrusos de 17 a 24 años. Junto con esto, la frecuencia de ocurrencia de maloclusión de mordida profunda distal en individuos con morfología craneofacial dolicocefálica es mayor en hombres y mujeres en comparación con otras formas de morfología craneofacial. La mordida profunda distal se acompaña de la disminución de los parámetros antropométricos de la altura facial, en comparación con la mordida mesial y abierta en la que hay un aumento estadístico. Además, se observa una disminución estadística en el valor de la profundidad facial inferior en individuos diagnosticados con mordida distal, en comparación con individuos con mordida mesial y normal. Estos resultados obtenidos del análisis antropométrico podrían ser útiles en el diagnóstico de anomalías dentofaciales y dento-maxilares, y en la simulación de resultados de tratamiento estéticamente estables.

The purpose of the study was to analyze the dynamics of age-related changes of craniofacial structures according to anthropometric parameters in males and females aged 17­24 years, and to determine the correlation, defined by anthropometric analysis, between forms of craniofacial morphology and the type of dento-maxillary anomalies. Materials and Methods: An anthropometric examination of 851 individuals (418 males and 433 females) aged 17­24 years and the evaluation of 45 measurements between soft tissue landmarks was performed. In addition, general dental assessment was conducted, which included the classification of the dento-maxillary anomalies. Results: It was detected that the head width, head length, as well as the mandible width, and the morphological facial width in females reach growth peak values at the age of 20 years. Furthermore, data was obtained which indicated growth continuation of the stated above craniofacial anthropometric parameters in males during the transitional period from adolescence to adulthood. Conclusion: Distal deep bite is the most commonly prevailed dento-maxillary anomalies (DMAn) in Belarusian men and women aged 17­24 years. Along with this, the frequency of distal deep bite malocclusion occurrence in individuals with dolichocephalic craniofacial morphology is higher in men and women when compared to other forms of craniofacial morphology. Distal deep bite is accompanied by the decrease of facial height anthropometric parameters, when compared to mesial and open bite in which there is a statistical increase. Moreover, a statistical decrease in the value of the inferior facial depth is observed in individuals diagnosed with distal bite, when compared to individuals with mesial and normal bite. These obtained results from anthropometric analysis could be useful in diagnosis of dentofacial and dento-maxillary anomalies, and in the simulation of aesthetically stable treatment results

Comparative Aspects of Annelid Regeneration: Towards Understanding the Mechanisms of Regeneration.

The question of why animals vary in their ability to regenerate remains one of the most intriguing questions in biology. Annelids are a large and diverse phylum, many members of which are capable of extensive regeneration such as regrowth of a complete head or tail and whole-body regeneration, even from few segments. On the other hand, some representatives of both of the two major annelid clades show very limited tissue regeneration and are completely incapable of segmental regeneration. Here we review experimental and descriptive data on annelid regeneration, obtained at different levels of organization, from data on organs and tissues to intracellular and transcriptomic data. Understanding the variety of the cellular and molecular basis of regeneration in annelids can help one to address important questions about the role of stem/dedifferentiated cells and "molecular morphallaxis" in annelid regeneration as well as the evolution of regeneration in general.

Clinical Evaluation of 16-Week Supplementation with 5HMO-Mix in Healthy-Term Human Infants to Determine Tolerability, Safety, and Effect on Growth.

Human milk oligosaccharides (HMOs) are complex sugars that occur naturally in human breast milk and provide many beneficial functions. Most formula products lack HMOs or contain only the most abundant HMO, 2'-fucosyllactose; however, benefits of HMOs come from multiple sugars. We therefore developed a mixture of five HMOs (5HMO-Mix) mimicking the natural concentrations of the top five HMOs (5.75 g/L total, comprising 52% 2'-fucosyllactose, 13% 3-fucosyllactose, 26% lacto-N-tetraose, 4% 3'-sialyllactose, and 5% 6'-sialyllactose) representing the groups of neutral, neutral-fucosylated, and sialylated HMOs. We conducted the first multicenter, randomized, controlled, parallel-group clinical study assessing the safety, tolerability, and effect on growth of formula containing the 5HMO-Mix in healthy infants. We enrolled 341 subjects aged ≤14 days; 225 were randomized into groups fed either with infant formula containing 5HMO-Mix (5HMO-Mix) or infant formula without HMOs (IF) for 4 months, with the others exclusively breastfed. There were no differences in weight, length, or head circumference gain between the two formula groups. The 5HMO-Mix was well tolerated, with 5HMO-Mix and breastfed infants producing softer stools at a higher stool frequency than the control formula group. Adverse events were equivalent in all groups. We conclude that the 5HMO-Mix at 5.75 g/L in infant formula is safe and well tolerated by healthy term infants during the first months of life.

Extensive Study of Breast Milk and Infant Growth: Protocol of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF).

Growth and nutrition during early life have been strongly linked to future health and metabolic risks. The Cambridge Baby Growth Study (CBGS), a longitudinal birth cohort of 2229 mother-infant pairs, was set up in 2001 to investigate early life determinant factors of infant growth and body composition in the UK setting. To carry out extensive profiling of breastmilk intakes and composition in relation to infancy growth, the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) was established upon the original CBGS. The strict inclusion criteria were applied, focusing on a normal birth weight vaginally delivered infant cohort born of healthy and non-obese mothers. Crucially, only infants who were exclusively breastfed for the first 6 weeks of life were retained in the analysed study sample. At each visit from birth, 2 weeks, 6 weeks, and then at 3, 6, 12, 24, and 36 months, longitudinal anthropometric measurements and blood spot collections were conducted. Infant body composition was assessed using air displacement plethysmography (ADP) at 6 weeks and 3 months of age. Breast milk was collected for macronutrients and human milk oligosaccharides (HMO) measurements. Breast milk intake volume was also estimated, as well as sterile breastmilk and infant stool collection for microbiome study.

Maternal bisphenol urine concentrations, fetal growth and adverse birth outcomes: A population-based prospective cohort.

BACKGROUND: Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. METHODS: In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. RESULTS: An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth. CONCLUSIONS: Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.

High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants.

BACKGROUND: Human milk is the best enteral nutrition for preterm infants. However, human milk, given at standard recommended volumes, is not adequate to meet the protein, energy, and other nutrient requirements of preterm or low birth weight infants. One strategy that may be used to address the potential nutrient deficits is to give a higher volume of enteral feeds. High volume feeds may improve nutrient accretion and growth, and in turn may improve neurodevelopmental outcomes. However, there are concerns that high volume feeds may cause feed intolerance, necrotising enterocolitis, or complications related to fluid overload such as patent ductus arteriosus and chronic lung disease. This is an update of a review published in 2017. OBJECTIVES: To assess the effect on growth and safety of high versus standard volume enteral feeds in preterm or low birth weight infants. In infants who were fed fortified human milk or preterm formula, high and standard volume feeds were defined as > 180 mL/kg/day and ≤ 180 mL/kg/day, respectively. In infants who were fed unfortified human milk or term formula, high and standard volume feeds were defined as > 200 mL/kg/day and ≤ 200 mL/kg/day, respectively. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 6) in the Cochrane Library; Ovid MEDLINE (1946 to June 2020); Embase (1974 to June 2020); and CINAHL (inception to June 2020); Maternity & Infant Care Database (MIDIRS) (1971 to April 2020); as well as previous reviews, and trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared high versus standard volume enteral feeds for preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. The primary outcomes were weight gain, linear and head growth during hospital stay, and extrauterine growth restriction at discharge. MAIN RESULTS: We included two new RCTs (283 infants) in this update. In total, we included three trials (347 infants) in this updated review. High versus standard volume feeds with fortified human milk or preterm formula Two trials (283 infants) met the inclusion criteria for this comparison. Both were of good methodological quality, except for lack of masking. Both trials were performed in infants born at < 32 weeks' gestation. Meta-analysis of data from both trials showed high volume feeds probably improves weight gain during hospital stay (MD 2.58 g/kg/day, 95% CI 1.41 to 3.76; participants = 271; moderate-certainty evidence). High volume feeds may have little or no effect on linear growth (MD 0.05 cm/week, 95% CI -0.02 to 0.13; participants = 271; low-certainty evidence), head growth (MD 0.02 cm/week, 95% CI -0.04 to 0.09; participants = 271; low-certainty evidence), and extrauterine growth restriction at discharge (RR 0.71, 95% CI 0.50 to 1.02; participants = 271; low-certainty evidence). We are uncertain of the effect of high volume feeds with fortified human milk or preterm formula on the risk of necrotising enterocolitis (RR 0.74, 95% CI 0.12 to 4.51; participants = 283; very-low certainty evidence). High versus standard volume feeds with unfortified human milk or term formula One trial with 64 very low birth weight infants met the inclusion criteria for this comparison. This trial was unmasked but otherwise of good methodological quality. High volume feeds probably improves weight gain during hospital stay (MD 6.2 g/kg/day, 95% CI 2.71 to 9.69; participants = 61; moderate-certainty evidence). The trial did not provide data on linear and head growth, and extrauterine growth restriction at discharge. We are uncertain as to the effect of high volume feeds with unfortified human milk or term formula on the risk of necrotising enterocolitis (RR 1.03, 95% CI 0.07 to 15.78; participants = 61; very low-certainty evidence). AUTHORS' CONCLUSIONS: High volume feeds (≥ 180 mL/kg/day of fortified human milk or preterm formula, or ≥ 200 mL/kg/day of unfortified human milk or term formula) probably improves weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes. A large RCT is needed to provide data of sufficient quality and precision to inform policy and practice.

Disrupted eye and head development in rainbow trout with reduced ultraviolet (sws1) opsin expression.

Visual opsins are proteins expressed by retinal photoreceptors that capture light to begin the process of phototransduction. In vertebrates, the two types of photoreceptors (rods and cones) express one or multiple opsins and are distributed in variable patterns across the retina. Some cones form opsin retinal gradients, as in the mouse, whereas others form more demarcated opsin domains, as in the lattice-like mosaic retinas of teleost fishes. Reduced rod opsin (rh1) expression in mouse, zebrafish, and African clawed frog results in lack of photoreceptor outer segments (i.e., the cilium that houses the opsins) and, in the case of the mouse, to retinal degeneration. The effects of diminished cone opsin expression have only been studied in the mouse where knockout of the short-wavelength sensitive 1 (sws1) opsin leads to ventral retinal cones lacking outer segments, but no retinal degeneration. Here we show that, following CRISPR/Cas9 injections that targeted knockout of the sws1 opsin in rainbow trout, fish with diminished sws1 opsin expression exhibited a variety of developmental defects including head and eye malformations, underdeveloped outer retina, mislocalized opsin expression, cone degeneration, and mosaic irregularity. All photoreceptor types were affected even though sws1 is only expressed in the single cones of wild fish. Our results reveal unprecedented developmental defects associated with diminished cone opsin expression and suggest that visual opsin genes are involved in regulatory processes that precede photoreceptor differentiation.

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.

High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants.

BACKGROUND: In-hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering. For preterm infants who cannot be fed maternal or donor breast milk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs) or long chain triglycerides (LCTs) may be chosen to support nutrient utilization and to improve growth. MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervous system development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant's short-term growth remain unclear. This is an update of a review originally published in 2002, then in 2007. OBJECTIVES: To determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula.  SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included all randomized and quasi-randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short-term growth of preterm (< 37 weeks' gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition. DATA COLLECTION AND ANALYSIS: The review authors assessed each study's quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We identified 10 eligible trials (253 infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, or blinding. We found no evidence of differences in short-term growth parameters when high and low MCT formulas were compared. As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of -0.21 g/kg/d (95% confidence interval (CI) -1.24 to 0.83; 6 studies, 118 infants; low-certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d (95% CI -5.93 to 5.93; 1 study, 18 infants; very low-certainty evidence), finding an average weight gain of 20 ± 5.9 versus 20 ± 6.9 g/d for high and low MCT groups, respectively. We found that length gain showed no difference between low and high MCT formulas, with a typical MD of 0.10 cm/week (95% CI -0.09 to 0.29; 3 studies, 61 infants; very low-certainty evidence). Head circumference gain also showed little to no difference during the intervention period, with an MD of -0.04 cm/week (95% CI -0.17 to 0.09; 3 studies, 61 infants; low-certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference (2 studies, 32 infants; very low-certainty evidence). There are conflicting data (5 studies) as to formula tolerance, with 4 studies reporting narrative results of no observed clinical difference and 1 study reporting higher incidence of signs of gastrointestinal intolerance in high MCT formula groups. There is no evidence of effect on the incidence of necrotizing enterocolitis (NEC), based on small numbers in two trials. Review authors found no studies addressing long-term growth parameters or neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: We found evidence of very low to low certainty suggesting no differences among short-term growth data for infants fed low versus high MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short-term growth outcomes or have fewer adverse effects. Further studies are necessary because the results from included studies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence.

Single-cell reconstruction with spatial context of migrating neural crest cells and their microenvironments during vertebrate head and neck formation.

The dynamics of multipotent neural crest cell differentiation and invasion as cells travel throughout the vertebrate embryo remain unclear. Here, we preserve spatial information to derive the transcriptional states of migrating neural crest cells and the cellular landscape of the first four chick cranial to cardiac branchial arches (BA1-4) using label-free, unsorted single-cell RNA sequencing. The faithful capture of branchial arch-specific genes led to identification of novel markers of migrating neural crest cells and 266 invasion genes common to all BA1-4 streams. Perturbation analysis of a small subset of invasion genes and time-lapse imaging identified their functional role to regulate neural crest cell behaviors. Comparison of the neural crest invasion signature to other cell invasion phenomena revealed a shared set of 45 genes, a subset of which showed direct relevance to human neuroblastoma cell lines analyzed after exposure to the in vivo chick embryonic neural crest microenvironment. Our data define an important spatio-temporal reference resource to address patterning of the vertebrate head and neck, and previously unidentified cell invasion genes with the potential for broad impact.

Head circumference in infants with nonopiate-induced neonatal abstinence syndrome.

BACKGROUND: No relationship has been reported between nonopiate neonatal abstinence syndrome (NAS) and anthropometric indices, including head circumference (HC). The purpose of this study was to determine the relationship between maternal nonopioid drug use and HC at birth in neonates with NAS. METHODS: This retrospective observational study included neonates born between January 1, 2010 and March 31, 2019, whose mothers had been taking antipsychotic, antidepressant, sedative, or anticonvulsant medications. The outcome measures were HCs of NAS infants and controls. RESULTS: Of 159 infants, 33 (21%) were diagnosed with NAS. There was no maternal opioid use among mothers during pregnancy. The HCs in the NAS group were significantly smaller than those in the control group. The median z-scores for HC at birth were -0.20 and 0.29 in the NAS group and the control group, respectively (P = .011). The median HCs at birth were 33.0 and 33.5 cm in the NAS group and the control group, respectively. Multivariate analysis revealed that maternal antipsychotic drug use and selective serotonin reuptake inhibitors were independently associated with NAS (P < .001 and P = .004, respectively). Notably, benzodiazepine use and smoking were not independent risk factors. CONCLUSIONS: The results suggest an association between maternal antipsychotic drug use and NAS, which was further associated with decreased HC. Careful monitoring of maternal drug use should be considered to improve fetal outcomes.

Comparing Caliper versus Computed Tomography Measurements of Cranial Dimensions in Children.

OBJECTIVES/HYPOTHESIS: We have found no study assessing the accuracy of caliper cranium measurements compared to computed tomography (CT) measurements of the head. The objective of this study was to assess the reliability of caliper measurements in comparison to CT measurements. STUDY DESIGN: Retrospective chart review. METHODS: This study includes all patients evaluated for head shape abnormality between 2010 and 2019 at a single academic medical center. Eighty-nine patients who had CT head scans were identified, and their caliper measurements of anterior-posterior and transverse head dimensions were documented. RESULTS: There was no statistically significant difference between the CT and caliper measurements. CONCLUSION: Caliper measurements are a simple and reliable way to assess cranial vault proportionality with growth after cranial vault reconstruction. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:773-775, 2021.