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Human milk oligosaccharides (HMOs) have been positively associated with child neurodevelopment in some cohort studies. However, there is a lack of consistency in the association between HMOs and benefits to infants’ brains. Moreover, the quantification methods for HMOs have not yet been standardized. In this study, we developed a quantification method for evaluating eight HMOs (2′‐fucosyllactose [2′‐FL], 3′‐fucosyllactose [3′‐FL], 3′‐sialyllactose [3′‐SL], 6′‐sialyllactose [6′‐SL], lactosialyltetrasaccharide a [LSTa], lactosialyltetrasaccharide b [LSTb], lactosialyltetrasaccharide c [LSTc], and disialyllacto‐N‐tetraose [DSLNT]) in breast milk. After validating the method, we applied it to 1‐month breast milk samples (n = 150) from the Tohoku Medical Megabank Project Birth and Three‐Generation Cohort Study to assess HMO profiles in breast milk and their possible association with changes in head circumference z‐score (ΔHCZ) and neurodevelopmental scores of children (as measured by the Ages and Stages Questionnaire, Third Edition). The validation demonstrated that the method had relative standard deviation ≤ 12.7% of precision and 79.5–110.9% of accuracy. Using this method, eight HMO levels (2′‐FL, 0–4.74 mg/mL; 3′‐FL, 0.02–1.52 mg/mL; 3′‐SL, 0.07–0.32 mg/mL; 6′‐SL, 0.01–0.70 mg/mL; LSTa, 0.002–0.043 mg/mL; LSTb, 0.02–0.31 mg/mL; LSTc, 0.001–0.47 mg/mL; and DSLNT, 0.09–0.71 mg/mL [min–max, all participants]) and the ratio of low secretors (16.0%) in the Japanese cohort were obtained. The obtained HMO levels in breast milk were subjected to multivariate analysis to screen for HMOs showing a positive association with ΔHCZ and neurodevelopmental scores. The results proposed that ΔHCZ was positively associated with LSTb and 2′‐FL levels, whereas neurodevelopmental scores were positively associated with 2′‐FL levels (among all participants) and 3′‐SL and DSLNT levels (among secretor participants). This study showed that the developed method provides HMO profiles in Japanese breast milk, as well as additional information on the associations between specific HMOs and neurodevelopment, reinforcing the sum of evidence for the role of HMOs in the brain. [ABSTRACT FROM AUTHOR]

Broccoli (Brassica oleracea L. var. italica Plenck.) is nowadays one of the most important vegetable crops worldwide, with an increasing demand by the market, due to its high nutritional value. Based on the optimal temperature range, its cultivation in the temperate regions takes place from late summer to late spring. Broccoli cultivation nowadays faces many challenges, such as the profitable production throughout the year, as well as during conditions of an increased temperature, induced by the emerging climate change, as well as the possibility of introducing the cultivation to subtropical and tropical areas. The modern genotypes (F1 hybrids) differ significantly among themselves in terms of the requirements for the head's formation, which, however, has not been fully elucidated. In this direction, breeders have been developing programs internationally since the early 1990s, in order to create genotypes that will be adapted to temperatures higher than the optimal range, having, however, a relatively limited initial germplasm pool. The purpose of this review is to present extensively the temperature requirements in the broccoli crop production and to highlight the impacts of the emerging climate change. [ABSTRACT FROM AUTHOR]

IntroductionTo date cranial development has only been described by analyzing occipitofrontal circumference (OFC). More precise methods of determining head measurements have not been widely adopted. The use of additional measurements has the potential to better account for the three-dimensional structure of the head. Our aim was to put forward centile curves of such measurements for gestational age along with a compound head volume index.MethodsWe created generalized additive models for location, scale, and shape of two ear-to-ear distances (EED), transfontanellar (fEED) and transvertical (vEED), from birth anthropometric data. Same was done for OFC, crown-heel length, and birth weight to allow for comparison of our models with growth charts by Voigt et al. and Fenton and Kim.ResultsGrowth charts and tables of LMS parameters for fEED and vEED were derived from 6,610 patients admitted to our NICU and 625 healthy term newborns. With increasing gestational age EEDs increase about half as fast compared to OFC in absolute terms, their relative growths are fairly similar.DiscussionDifferences to the charts by Fenton and Kim are minute. Tape measurements, such as fEED or vEED can be added to routine anthropometry at little extra costs. These charts may be helpful for following and evaluating head sizes and growth of preterm and term infants in three dimensions.

Spontaneous intestinal perforation (SIP) and surgical necrotizing enterocolitis (NEC) are intestinal conditions requiring surgical intervention in preterm infants. We aimed to compare the head growth and neurodevelopment of preterm infants with SIP and surgical NEC. A retrospective single-center study was performed in preterm infants born at less than 32 weeks of gestation and who had undergone surgery for NEC or SIP. Data from the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) at 24 months of corrected age (CA) and the Korean Ages and Stages Questionnaire (K-ASQ) or Korean Developmental Screening Test (K-DST) at 36 months were collected. Among 82 eligible infants, 60 infants had surgical NEC, and 22 infants were diagnosed with SIP. Head growth was faster until CA 4 months in preterm infants with SIP than in those with surgical NEC. At 36 months, abnormal findings in the K-ASQ or K-DST were more prevalent in the NEC group than in the SIP group in the gross motor (48.2% vs. 0%, p = 0.015), fine motor (40.7% vs. 0%, p = 0.037), cognitive (55.6% vs. 12.5%, p = 0.047), and social domains (44.4% vs. 0%, p = 0.032). More studies evaluating the neurodevelopmental outcomes of preterm infants with surgical NEC and SIP are required. [ABSTRACT FROM AUTHOR]

Broccoli (Brassica oleracea L. var. italica Plenck.) is nowadays one of the most important vegetable crops worldwide, with an increasing demand by the market, due to its high nutritional value. Based on the optimal temperature range, its cultivation in the temperate regions takes place from late summer to late spring. Broccoli cultivation nowadays faces many challenges, such as the profitable production throughout the year, as well as during conditions of an increased temperature, induced by the emerging climate change, as well as the possibility of introducing the cultivation to subtropical and tropical areas. The modern genotypes (F1 hybrids) differ significantly among themselves in terms of the requirements for the head’s formation, which, however, has not been fully elucidated. In this direction, breeders have been developing programs internationally since the early 1990s, in order to create genotypes that will be adapted to temperatures higher than the optimal range, having, however, a relatively limited initial germplasm pool. The purpose of this review is to present extensively the temperature requirements in the broccoli crop production and to highlight the impacts of the emerging climate change.

Objective: Despite evidence for the prenatal onset of abnormal head growth in children with autism spectrum disorder (ASD), studies on fetal ultrasound data in ASD are limited and controversial.Method: We conducted a longitudinal matched case-sibling-control study on prenatal ultrasound biometric measures of children with ASD, and 2 control groups: (1) their own typically developed sibling (TDS) and (2) typically developed population (TDP). The cohort comprised 528 children (72.7% male), 174 with ASD, 178 TDS, and 176 TDP.Results: During the second trimester, ASD and TDS fetuses had significantly smaller biparietal diameter (BPD) than TDP fetuses (adjusted odds ratio for the z score of BPD [aORzBPD] = 0.685, 95% CI = 0.527-0.890, and aORzBPD = 0.587, 95% CI = 0.459-0.751, respectively). However, these differences became statistically indistinguishable in the third trimester. Interestingly, head biometric measures varied by sex, with male fetuses having larger heads than female fetuses within and across groups. A linear mixed-effect model assessing the effects of sex and group assignment on fetal longitudinal head growth indicated faster BPD growth in TDS versus both ASD and TDP in male fetuses (β = 0.084 and β = 0.100 respectively; p < .001) but not in female fetuses, suggesting an ASD-sex interaction in head growth during gestation. Finally, fetal head growth showed conflicting correlations with ASD severity in male and female children across different gestation periods, thus further supporting the sex effect on the association between fetal head growth and ASD.Conclusion: Our findings suggest that abnormal fetal head growth is a familial trait of ASD, which is modulated by sex and is associated with the severity of the disorder. Thus, it could serve as an early biomarker for ASD. [ABSTRACT FROM AUTHOR]

Landmark labeling in 3D head surfaces is an important and routine task in clinical practice to evaluate head shape, namely to analyze cranial deformities or growth evolution. However, manual labeling is still applied, being a tedious and time-consuming task, highly prone to intra-/inter-observer variability, and can mislead the diagnose. Thus, automatic methods for anthropometric landmark detection in 3D models have a high interest in clinical practice. In this paper, a novel framework is proposed to accurately detect landmarks in 3D infant's head surfaces. The proposed method is divided into two stages: (i) 2D representation of the 3D head surface; and (ii) landmark detection through a deep learning strategy. Moreover, a 3D data augmentation method to create shape models based on the expected head variability is proposed. The proposed framework was evaluated in synthetic and real datasets, achieving accurate detection results. Furthermore, the data augmentation strategy proved its added value, increasing the method's performance. Overall, the obtained results demonstrated the robustness of the proposed method and its potential to be used in clinical practice for head shape analysis. [ABSTRACT FROM AUTHOR]

Aim: The World Health Organization (WHO) published universal growth standards for children below five year of age in 2006. Traditionally, Swedish growth references have been used to monitor growth of children in Iceland, but it is not yet known how they compare with these reference charts.Methods: A total of 2128 longitudinal measurements of length or height, 2132 of weight and 2126 of head circumference between birth and four years of age were collected in 1996-2000 from 199 healthy children (53% boys) recruited at Landspitali University Hospital. Measurements were converted to z-scores using the WHO growth standards and Swedish growth references for further analysis with mixed-effects models.Results: Length or height, weight and in particular head circumference largely exceeded the WHO standards, with average z-scores that fluctuated between 0.5 and 1.5. Likewise, the proportion of children with a z-score larger than 2 SD increased about 10-fold. Icelandic children were longer and heavier than their Swedish peers during the first six months of life, but differences were less pronounced thereafter.Conclusion: The growth of Icelandic children deviated significantly from the WHO growth standards. Although more comparable to the Swedish references, significant differences were found, suggesting that a national growth reference would be more appropriate. [ABSTRACT FROM AUTHOR]

Background: Fetal growth may vary significantly in different congenital heart defects (CHDs).Objectives: To investigate prenatal growth of CHD fetuses and its correlation with classifications based upon expected oxygen delivery to the fetal brain or structural findings.Methods: Seventy-nine euploid fetuses with isolated CHD were recruited prospectively and categorized by the expected oxygen supply to the brain (low, intermediate, and high) or by the expected arterial mixing considering two categories (cyanotic or non-cyanotic). Biometry and Doppler were recorded, and Z-scores (Zs) calculated. Growth changes at different time points were analyzed and compared with 150 controls.Results: A total of 664 exams were performed on 229 fetuses. Median head circumference (HC) Zs were lower in all CHD fetuses from the second trimester onwards and in cyanotic CHD fetuses from the first onwards, with associated smaller abdominal circumference (AC) in the third trimester (first-trimester biparietal diameter Zs cyanotic: -1.3 [-2.36; -0.98], non-cyanotic -0.72 [-1.25; -0.6], p = 0.044, second-trimester HC Zs cyanotic: -1.47 [-2.3; -0.84]; non-cyanotic -0.45 [-0.83; -0.02], p < 0.0001; AC Zs cyanotic 0.0 [-0.44; 0.86]; non-cyanotic 0.65 [0.31; 1], p = 0.0006). Birth-weight centiles were smaller in CHDs (particularly in cyanotic) with no differences between categories of brain oxygen delivery.Conclusions: Fetuses with cyanotic CHD have fetal growth restriction, impaired head growth, yet normal posterior fossa dimensions and fetal-placental Doppler. [ABSTRACT FROM AUTHOR]

Aim: We describe the postnatal weight gain, linear and head growth trends of surviving preterm infants from 2005 to 2017.Methods: Multicentre cohort study, including surviving preterm infants <32 weeks (n = 21 084), from the Spanish Neonatal Network database, without major congenital malformations who were less than 50 weeks postmenstrual age at discharge. Outcomes were weight gain (g/kg/day), linear and head growth (cm/week) and changes in weight, length and head circumference z-scores from birth to discharge. The study period was divided into 2005-8, 2009-11, 2012-14 and 2015-17.Results: Weight gain, linear growth and head growth were slightly higher in 2015-2017 than in 2005-2008: 12.2 ± 2.6 to 13.1 ± 2.5 g/kg/day, 0.98 ± 0.6 to 1.03 ± 0.6 cm/week and 0.76 ± 0.2 to 0.77 ± 0.3 cm/week, respectively. It was associated with a decreased fall in weigh, length and head circumference z-scores from birth to discharge (-1.32 ± 0.9 to -1.01 ± 0.84, -1.38 ± 1.2 to -1.18 ± 1.2 and -0.41 ± 1.2 to -0.33 ± 1.3, respectively).Conclusion: Postnatal growth restriction remained a common complication of prematurity despite some increment over the last years. Growth disproportionality seemed to be worsening as weight gain was increased more than linear growth. [ABSTRACT FROM AUTHOR]

Population-based growth studies are important to demonstrate social, cultural, and medical milieu of the societies. The fact that there is no nationwide head circumference growth references of Turkish children is a significant deficiency. In this study, we aimed to create head growth references for 0-3-year-old children living in good conditions in Turkey. Within this scope, a total of 2061 infants and children with 1029 being boys and 1032 girls were examined in seven metropolitan city (Istanbul, Ankara, İzmir, Adana, Samsun, Diyarbakır, and Erzurum) in Turkey. LMS method was used to create percentile curves. According to the data obtained, it can be said that children of our country who grow in optimal and/or sub-optimal conditions have somewhat larger head circumference compared to their peers from the USA, but the difference is relatively low. Great similarity between the results of this study, which was conducted as multicenter, and previous reference studies performed in Istanbul is remarkable. [ABSTRACT FROM AUTHOR]

Vertebrates have unique head structures that are mainly composed of the central nervous system, the neural crest, and placode cells. These head structures are brought about initially by the neural induction between the organizer and the prospective neuroectoderm at early gastrula stage. Purinergic receptors are activated by nucleotides released from cells and influence intracellular signaling pathways, such as phospholipase C and adenylate cyclase signaling pathways. As P2Y receptor is vertebrate‐specific and involved in head formation, we expect that its emergence may be related to the acquisition of vertebrate head during evolution. Here, we focused on the role of p2ry4 in early development in Xenopus laevis and found that p2ry4 was required for the establishment of the head organizer during neural induction and contributed to head formation. We showed that p2ry4 was expressed in the head organizer region and the prospective neuroectoderm at early gastrula stage, and was enriched in the head components. Disruption of p2ry4 function resulted in the small head phenotype and the reduced expression of marker genes specific for neuroectoderm and neural border at an early neurula stage. Furthermore, we examined the effect of p2ry4 disruption on the establishment of the head organizer and found that a reduction in the expression of head organizer genes, such as dkk1 and cerberus, and p2ry4 could also induce the ectopic expression of these marker genes. These results suggested that p2ry4 plays a key role in head organizer formation. Our study demonstrated a novel role of p2ry4 in early head development. P2Y4 receptor is required for the formation of head organizer and function in the following induction process of neural and neural crest. We demonstrated a novel role of p2ry4 in early head development. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated if oral supplementation with the probiotic bacterium Lactobacillus reuteri DSM 17938 improved enteral feeding tolerance and growth rates in extremely low birthweight (ELBW) infants.Method: A randomised, double-blind, placebo-controlled trial comprising 134 ELBW (<1000 g) infants born before gestational week 28 + 0. Daily supplementation of L. reuteri (1.25 × 108 bacteria/day) or placebo started within 3 days and continued until gestational week 36 + 0. Primary outcome was feeding tolerance and secondary outcome growth rate calculated as z-score development.Results: Feeding tolerance was similar in the probiotic and placebo group. Time to full enteral feeds was 15 days in both groups. The z-score of the head circumference decreased in both groups from birth to day 28 of life, but it decreased less in the L. reuteri group compared to the placebo group: -1.2 SD (95% CI: -1.4 to -1.0) versus -1.7 SD (95% CI: -2.0 to -1.5; p = 0.001). Other growth parameters were similar in the study groups.Conclusion: Lactobacillus reuteri did not reduce time to reach full enteral feeds in ELBW infants. The L. reuteri supplemented infants, however, had a better growth rate of the head during the first month of life. [ABSTRACT FROM AUTHOR]

Background: Maternal smoking during pregnancy has been recognised as a detrimental factor associated with adverse perinatal outcomes; however, to date there is a dearth of information on how it affects post-natal head growth and shape. Aim: To assess the relationship between parental smoking exposure during pregnancy and head dimensions and shape at age 7-10 years in boys and girls. Methods: Body height and head length, breadth and circumference were measured. Birth weight and gestational age were obtained from the children's medical record books. Parental smoking habits during pregnancy and maternal educational attainment were obtained by a questionnaire. The relationship between exposure to parental smoking during pregnancy and head dimensions was evaluated using analysis of covariance implemented in the Generalized Linear Model, separately for each sex. Results: Maternal and parental smoking during pregnancy significantly altered head shape in boys by affecting head length, while neither head breadth nor circumference were affected. This phenomenon was not observed in girls. Conclusion: Smoking-induced chronic hypoxic effects on the growing foetus, indicated that both active and passive smoking during pregnancy seems to have persistent negative effects on children, going beyond foetal development and pre-natal growth restrictions. [ABSTRACT FROM AUTHOR]

The morphology of the head and pinna shape the spatial and frequency dependence of sound propagation that give rise to the acoustic cues to sound source location. During early development, the physical dimensions of the head and pinna increase rapidly. Thus, the binaural (interaural time and level differences, ITD and ILD) and monaural (spectral shape) cues are also hypothesized to change rapidly. Complex interactions between the size and shape of the head and pinna limit the accuracy of simple acoustical models (e.g. spherical) and necessitate empirical measurements. Here, we measured the cues to location in the developing guinea pig, a precocial species commonly used for studies of the auditory system. We measured directional transfer functions (DTFs) and the dimensions of the head and pinna in guinea pigs from birth (P0) through adulthood. Dimensions of the head and pinna increased by 87% and 48%, respectively, reaching adult values by ∼8 weeks (P56). The monaural acoustic gain produced by the head and pinna increased with frequency and age, with maximum gains at higher frequencies (>8 kHz) reaching values of 10–21 dB for all ages. The center frequency of monaural spectral notches also decreased with age, from higher frequencies (∼17 kHz) at P0 to lower frequencies (∼12 kHz) in adults. In all animals, ILDs and ITDs were dependent on both frequency and spatial location. Over development, the maximum ILD magnitude increased from ∼15 dB at P0 to ∼30 dB in adults (at frequencies >8 kHz), while the maximum low frequency ITDs increased from ∼185 μs at P0 to ∼300 μs in adults. These results demonstrate that the changes in the acoustical cues are directly related to changes in head and pinna morphology. [ABSTRACT FROM AUTHOR]

Precise control of neural progenitor transformation into neural crest stem cells ensures proper craniofacial and head development. In the neural progenitor pool, SoxB factors play an essential role as cell fate determinants of neural development, whereas during neural crest stem cell formation, Sox2 plays a predominant role as a guardian of the developmental clock that ensures precision of cell flow in the developing head. [ABSTRACT FROM AUTHOR]

Purpose: Folic acid supplementation during pregnancy has been associated with a reduced risk of common neurodevelopmental delays in the offspring. However, it is unclear whether low folate status has effects on the developing brain. We evaluated the associations of maternal folic acid supplementation and folate concentrations during pregnancy with repeatedly measured prenatal and postnatal head circumference in the offspring. Methods: Within a population-based prospective cohort, we measured maternal plasma folate concentrations at approximately 13 weeks of gestation (90 % range 10.5-17.2) and assessed folic acid supplementation by questionnaire (2001-2005). Up to 11 repeated measures of head circumference were obtained during foetal life (20 and 30 weeks of gestation) and childhood (between birth and age 6 years) in 5866 children (2002-2012). Results: In unadjusted models, foetal head growth was 0.006 SD (95 % CI 0.003; 0.009, P < 0.001) faster per week per 1-SD higher maternal folate concentration. After adjustment for confounders, this association was attenuated to 0.004 SD per week (95 % CI 0.000; 0.007, P = 0.02; estimated absolute difference at birth of 2.7 mm). The association was independent of overall foetal growth. No associations were found between maternal folate concentrations and child postnatal head growth. Preconceptional start of folic acid supplementation was associated with larger prenatal head size, but not with prenatal or postnatal head growth. Conclusions: Our results suggest an independent, modest association between maternal folate concentrations in early pregnancy and foetal head growth. More research is needed to identify whether specific brain regions are affected and whether effects of folate on foetal head growth influence children's long-term functioning. [ABSTRACT FROM AUTHOR]

To design high-quality head/face-related products for children, it is essential to be able to construct 3D geometric models of their head growth patterns and variations. However, compared to 3D anthropometric analysis of adults' heads, this is still an underexplored research area. This study developed a framework for modeling the 3D geometric growth patterns and sex-specific variations of children's heads. To analyze these variations, the entire heads of 793 children (395 females and 398 males) ages 5-17 were scanned, and one global and two sex-specific statistical shape models (SSMs) were constructed. The first principal component in these SSMs, contributing more than 65% to the total explained variations, was highly related to overall head sizes. To model growth patterns, expected average heads for different ages and per-vertex growth rates were computed. Our results showed that the entire female head basically reaches its mature size at age 13-14, whereas in males it continues to increase until age 16-17. This study therefore provides valuable references for children's head/face-related product design, including the development of a more accurate sizing system and improvements in product fit and function. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess head circumference (HC) growth and neurodevelopmental outcomes in very preterm-birth children after neonatal acute kidney injury (AKI)., Methods: This longitudinal follow-up cohort included 732 very preterm neonates of gestational age <31 weeks admitted to a tertiary center between 2008 and 2020. AKI was categorized as nonoliguric and oliguric AKI based on the urine output criteria during admission. We compared the differences in death, z scores of HC (zHC) at term-equivalent age (TEA) and at corrected ages of 6, 12, and 24 months, and the neurodevelopmental outcomes at corrected age of 24 months after neonatal nonoliguric and oliguric AKI., Results: Among the 154 neonates who developed AKI, 72 had oliguric AKI and 82 had nonoliguric AKI. At TEA, oliguric AKI, but not nonoliguric AKI, was independently associated with lower zHC than non-AKI (mean differences, -0.49; 95% confidence interval [CI], -0.92 to -0.06). Although the 3 groups were comparable in zHC at corrected ages of 6, 12, and 24 months, the oliguric AKI group, but not the nonoliguric AKI group, had a higher rate of microcephaly by corrected age of 24 months. In addition, the oliguric AKI group, but not the nonoliguric AKI group, was more likely to die (61% vs. 9%) and have neurodevelopmental impairment (41% vs. 14%) compare with the non-AKI group. After adjustment, oliguric (adjusted odds ratio [aOR], 8.97; 95% CI, 2.19-36.76), but not nonoliguric, AKI was associated with neurodevelopmental impairment., Conclusion: Neonatal oliguric AKI is associated with neurodevelopmental impairment in very preterm-birth children. Long-term head-size and neurodevelopmental follow-up after neonatal AKI is warranted., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Background: The contribution of growth parameters to the cognitive outcome of very low birth weight (VLBW)/very preterm (VP) infants is difficult to disentangle from other preterm-birth related factors.Aims: We hypothesized that long-term cognitive and motor outcome of VLBW/VP infants is most strongly associated with growth in head circumference after hospital discharge.Study Design: Single-centre prospective longitudinal study: anthropometric measures at different time points (birth, discharge, school-age).Subjects: 136 VLBW/VP infants (<32weeks gestation/birth weight<1.500g).Outcome Measures: Cognitive and motor function (Kaufman Assessment Battery for Children; Movement Assessment Battery for Children) at school-age (6.7-10.0years, mean=8.2).Results: In hierarchical multiple regression analyses, growth from birth to discharge significantly predicted cognitive outcome (weight: R2change=0.063, p=0.014; length: R2change=0.078, p=0.007; HC: R2change=0.050, p=0.030), as well as weight gain (R2change=0.096, p=0.001) and head growth (R2change=0.134, p<0.001) from discharge to school-age. While most growth parameters, especially those from birth to discharge, were significantly influenced by prenatal growth and immaturity related morbidity (R2=0.151 to 0.605, all p≤0.001), head growth after discharge was not (R2=0.029, p=0.461).Conclusions: Amongst all anthropometric measures, head growth between discharge and school-age is the best independent predictor for cognitive outcome in VLBW/VP infants. Determinants of head growth after discharge need further studies to identify targets for intervention. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the possible association between major neonatal morbidities and poor head growth from birth to discharge home in very-low-birthweight (VLBW) infants born preterm.Method: Population-based observational study comprising 12 992 infants (6340 male, 6652 female) of 24 to 32 weeks' gestation, and birthweight ≤1500g. Severe head growth failure (HGF) was defined as a decrease in head circumference z-score >2 z-scores, and moderate HGF as a decrease of 1 to 2 z-scores. Multinomial logistic regression analysis was applied to determine morbidities associated with HGF.Results: Severe HGF occurred in 4.5% and moderate HGF in 20.9% of infants. Each unit increase in head circumference z-score at birth was associated with increased odds for severe and moderate HGF (odds ratios [OR] 5.29, 95% confidence intervals [CI] 4.67-6.00, and OR 2.38, 95% CI 2.23-2.54 respectively). Both severe and moderate HGF were associated with respiratory distress syndrome (OR 2.03, 95% CI 1.58-2.62, and OR 1.66, 95% CI 1.48-1.85 respectively); bronchopulmonary dysplasia (OR 3.38, 95% CI 2.33-4.91, and OR 1.87, 95% CI 1.52-2.30 respectively); necrotizing enterocolitis (OR 2.89, 95% CI 2.04-4.09, and OR 1.72, 95% CI 1.38-2.16 respectively), and sepsis (OR 2.06, 95% CI 1.69-2.50, and OR 1.38, 95% CI 1.24-1.53 respectively).Interpretation: Major neonatal morbidities were associated with HGF in VLBW infants born preterm. Identification of whether this is a direct effect of these morbidities or mediated through nutritional or growth factors may enable interventions to improve postnatal head growth of infants born preterm. [ABSTRACT FROM AUTHOR]

Objectives: Congenital heart defects (CHDs) are reported to be associated with a smaller fetal head circumference (HC) and neurodevelopmental delay. Recent studies suggest that altered intrauterine brain hemodynamics may explain these findings. Our objectives were to evaluate the pattern of head growth in a large cohort of fetuses with various types of CHD, analyze these patterns according to the type of CHD and estimate the effect of cerebral hemodynamics with advancing gestation in the second and third trimesters.Methods: Singleton fetuses with an isolated CHD were selected from three fetal medicine units (n = 436). Cases with placental insufficiency or genetic syndromes were excluded. CHD types were clustered according to the flow and oxygen saturation in the aorta. Z-scores of biometric data were constructed using growth charts of a normal population. HC at different gestational ages was evaluated and univariate and multivariate mixed regression analyses were performed to examine the patterns of prenatal HC growth.Results: Fetuses with severe and less severe types of CHD demonstrated statistically significant HC growth restriction with increasing gestational age (slope of -0.017/day); however, there was no statistically significant effect of fetal hemodynamics on HC growth. Fetuses with CHD but normal brain oxygenation and normal aortic flow showed a significant decrease in HC growth (slope of -0.024/day). Only fetuses with isolated tetralogy of Fallot demonstrated a smaller HC z-score at 20 weeks of gestation (-0.67 (95% CI, -1.16 to -0.18)).Conclusions: Despite the decline in head growth in fetuses with a prenatally detected isolated CHD, HC values were within the normal range, raising the question of its clinical significance. Furthermore, in contrast to other studies, this large cohort did not establish a significant correlation between aortic flow or oxygen saturation and HC growth. Factors other than altered fetal cerebral hemodynamics may contribute to HC growth restriction with increasing gestational age, such as (epi)genetic or placental factors. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Brain development in early childhood is a key determinant of later cognition, social achievement and educational success. Head circumference (HC) measurements are a simple method to assess brain growth, yet reports of these measurements are uncommon in nutritional surveys of undernourished children. Objective: To evaluate HC measurements in a population of rural Nepali children and relate these measurements to demographics, health and diet. Methods: An observational study of head growth was nested within a longitudinal evaluation of a livestock-based agricultural intervention in rural Nepal. Between 538 and 689 children (aged 6 months to 8 years) were measured (height, weight, HC) at each of six survey visits. A total of 3652 HC measurements were obtained. Results were converted toZ-scores (WHO Anthro). Results: Mean head circumferenceZ-scores (HCZ) diminished progressively over the first 4 years of life; a decline of 30% occurred between 3 and 4 years of age (−1.73 to −2.45,P < 0.0001). Overall, 56% of HCZ were <−2. Gender-adjusted HCZ (but not other measurements) were significantly lower for girls than boys [mean (SD) −2.31 (1.0)vs−1.99 (0.094),P < 0.0001]; girls more often had microcephaly (61%vs50%,P < 0.0001). For children <3 years of age, HCZ were better in those who had eaten two or more animal-source foods (ASFs) within the previous 24 h [−1.69 (.05)vs−2.08 (0.10),P = 0.001] than in those who had eaten none or only one; HCZ correlated with the number of ASFs consumed (P < 0.001). Regression analyses demonstrated that the main determinants of HCZ were age, weight-for-ageZ-scores (WAZ) and gender; 43% of the variance in HCZ in younger children was explained by WAZ and ASF consumption. Conclusion: HCs reflect brain size in young children; brain size is linked to cognitive function. Poor head growth represents another facet of the ‘silent emergency’ of child undernutrition. Routine HCZ assessments may contribute to better understanding of the links between poverty and cognitive development. [ABSTRACT FROM AUTHOR]

Aim: This study examined the relationship between head growth and cognitive outcome at the age of five years in preterm infants born at less than 32 weeks of gestation from 2003 to 2009, as previous research has mostly focused on outcomes in toddlers.Methods: The head circumference of 273 very preterm infants born in Tyrol, Austria, was measured at birth, discharge, the corrected ages of three, 12 and 24 months and the chronological age of five years. Suboptimal head size was defined as a head circumference of more than one standard deviation below the mean. Full-scale intelligence quotient (IQ) at five years was determined using Wechsler Preschool and Primary Scales of Intelligence, third edition.Results: Infants with a suboptimal head size at the age of three months had a significantly lower median IQ than those with a normal head size (90 [20-122] versus 98 [20-138], p = 0.001) and from three months onwards they were more likely to exhibit cognitive delay.Conclusion: A suboptimal head size from the age of three months was consistently related to a 10% lower IQ, and this study adds further evidence that head growth failure, especially during the early postdischarge period, is related to impaired cognitive abilities. [ABSTRACT FROM AUTHOR]

Aim: This study compared postnatal growth patterns calculated using different reference data in a large cohort of very preterm infants.Methods: The weight, length and head circumference of 551 very preterm infants born in the Tyrol, Austria, between 2003 and 2011, were obtained at birth, discharge and the corrected ages of three, 12 and 24 months. Growth data are presented as Z-scores in relation to four reference populations: LMS growth by Pan et al., Fenton preterm growth charts, the Euro-Growth Study Group and the World Health Organization (WHO) Anthro programme.Results: We observed significant differences in mean weight Z-scores using the four reference populations, with the WHO data being the highest. The mean head circumference Z-scores also differed significantly at all time points. We observed a pronounced gap in the microcephaly rate, which was 10 times higher at the age of 24 months if the Pan data were used instead of the WHO data.Conclusion: Our findings revealed significant deviations between the interpretation of postnatal growth depending on the reference data used, with the most striking differences seen in head circumference. The choice of reference data, and particularly the conclusions drawn from the data, must be interpreted with utmost care. [ABSTRACT FROM AUTHOR]

The role of neural crest cells and the homeobox genes in the development of craniofacial development has been a topic of research which is now directing us towards a genetic control in the patterning of the craniofacial region. These genes with their genetic domination over the development and the patterning of the head and facial region, in fact, are found to be the regulators and thus the master genes of the head and face. This review article gives an overview of the role of neural crest cells and homeobox genes in the development of the craniofacial complex. [ABSTRACT FROM AUTHOR]

In light of the growing number of surviving children born very preterm, there is an increasing focus on their long-term outcomes in terms of growth, metabolic status, and neurocognitive development. Therefore, it is of importance to follow such children from birth onwards with the aim of identifying the causes of atypical development, developing preventative measures, and improving outcomes. Since such long-term follow-up needs to be conducted with the least possible burden, clinical investigations such as anthropometry and neurocognitive tests, if conducted rigorously, will continue to have a predominant role. The aim of this review is to discuss the complexity of longitudinal anthropometry in children born very preterm and to provide an overview of the main studies that have examined associations between growth, in particular head growth, and neurocognitive outcomes at around school age. [ABSTRACT FROM AUTHOR]

Objective: To review the literature investigating head size and examine head growth in relation to neurodevelopmental outcomes and neuroimaging data in the very preterm infant. Methods: Systematic literature review of studies published in the following databases: PubMed/Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health (CINAHL), and Excerpta Medica dataBASE (EMBASE). Studies in the English language published between January 2005 and August 2013 were examined. Subjects were infants born at #32 weeks of gestation. Main outcome measures included head growth, neurodevelopmental outcomes, and correlation between head size and neuroimaging. Results: Thirty-four articles comprising 9,394 infants met inclusion/exclusion criteria. Of these, 31 studies (6,592 subjects) report head growth data measured at two or more time points. Neurodevelopmental outcome at $2 years was reported by eleven studies (3,817 subjects). Nine studies (2,363 subjects) included neuroimaging data. Catch-up head growth was found to occur in the first year after birth. Poor nutrition was linked with poorer head growth. Small head size was associated with poor psychomotor and mental skills, higher rates of cerebral palsy, and autism. However, suboptimal head size at birth was not predictive of poor outcome, unless it persisted. Head size appears to correlate with brain volume at term. Associations between white matter abnormalities have been found by ultrasonography. In contrast, in magnetic resonance imaging (MRI) studies, gray matter seems to be the most susceptible to impairments during postnatal growth. Conclusion: Head growth in early neonatal life is of importance. Avoiding growth impairment during neonatal care may allow for optimal cortical development. Many factors impact upon early head growth, particularly appropriate nutrition. There is no clear correlation between neuroimaging and head growth and this is an area deserving future research. [ABSTRACT FROM AUTHOR]

Introduction A significant proportion of preterm infants have dolichocephaly and/or deformational plagiocephaly (DP) at term equivalent age. However, quantitative data on the clinical course after discharge is limited in these infants. Aims To quantify the individual course of cranial symmetry and proportion in infants born < 32 gestational weeks up to six months of corrected age (CA) and to investigate, whether measurements at discharge predict subsequent cranial deformations. Methods A total of 56 infants were examined at discharge, three and six months of CA. Cranial proportion and symmetry were quantified using a 3D laser scan method. Classification and prevalence data were obtained using age related reference values. Predictive value of DP at discharge regarding subsequent deformation was evaluated. Results Cranial Vault Asymmetry Index was 3.9% at discharge, 4.5% at three months and 3.7% at six months of CA. Prevalence of DP was 34% at discharge, 46% at three months and 27% at six months. Cranial Index was 71.4% at discharge and constantly increased over the examination period. Prevalence of dolichocephaly was high at discharge (77%) and subsequently decreased. While severe DP at discharge was predictive for a persistent deformation (PPV 0.78), 46% of infants without DP at discharge developed DP by six months of CA. Discussion Despite a high prevalence at discharge, the decreased prevalence of DP and dolichocephaly at six months of CA suggests an optimistic course. However, changes in head shape are hardly predictable for the individual infant. Thus, an accurate quantification should be part of neonatal follow-up programs. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) can emerge as a complication of placental dysfunction and increases the risk for neurodevelopmental delay. Marked elevations of umbilical artery (UA) Doppler resistance that set the stage for cardiovascular and biophysical deterioration with subsequent preterm birth characterize early-onset FGR. Minimal, or absent UA Doppler abnormalities and isolated cerebral Doppler changes with subtle deterioration and a high risk for unanticipated term stillbirth are characteristic for late-onset FGR. Nutritional deficiency manifested in lagging head growth is the most powerful predictor of developmental delay in all forms of FGR. Extremes of blood flow resistance and cardiovascular deterioration, prematurity and intracranial hemorrhage increase the risks for psychomotor delay and cerebral palsy. In late-onset FGR, regional cerebral vascular redistribution correlates with abnormal behavioral domains. Irrespective of the phenotype of FGR, prenatal tests that provide precise and independent stratification of risks for adverse neurodevelopment have yet to be determined. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The vertebrate head–trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head–trunk interface. [Copyright &y& Elsevier]

Abstract: Otx2 plays essential roles in each site at each step of head development. We previously identified the AN1 enhancer at 91kb 5' upstream for the Otx2 expressions in anterior neuroectoderm (AN) at neural plate stage before E8.5, and the FM1 enhancer at 75kb 5' upstream and the FM2 enhancer at 122kb 3' downstream for the expression in forebrain/midbrain (FM) at brain vesicle stage after E8.5. The present study identified a second AN enhancer (AN2) at 88kb 5' upstream; the AN2 enhancer also recapitulates the endogenous Otx2 expression in choroid plexus, cortical hem and choroidal roof. However, the enhancer mutants indicated the presence of another AN enhancer. The study also identified a third FM enhancer (FM3) at 153kb 5' upstream. Thus, the Otx2 expressions in anterior neuroectoderm and forebrain/midbrain are regulated by more than six enhancers located far from the coding region. The enhancers identified are differentially conserved among vertebrates; none of the AN enhancers has activities in caudal forebrain and midbrain at brain vesicle stage after E8.5, nor do any of the FM enhancers in anterior neuroectoderm at neural plate stage before E8.5. [Copyright &y& Elsevier]

Aim To determine if reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is explained by cigarette smoking or socio-economic deprivation. Design Retrospective cohort study. Setting Inner-city maternity unit in Scotland. Participants A total of 366 singleton infants of methadone-prescribed opioid-dependent mothers compared with the Scottish birth population ( n = 103 366) as a whole. Measurements Primary outcome measures were birth weight and head circumference. Findings In infants of methadone-prescribed opioid-dependent mothers mean birth weight was 259 g [95% confidence interval ( CI) 214-303 g; P < 0.0001] less, and mean head circumference 1.01 cm (95% CI 0.87-1.15 cm; P < 0.0001) less than in controls, allowing for gestation, cigarette smoking, area deprivation, infant sex and maternal age and parity. This represents an adjusted difference of −0.61 (95% CI −0.52-−0.71; P < 0.0001) Z-score in mean birth weight and −0.77 (95% CI −0.66-−0.89; P < 0.0001) Z-score in mean head circumference. Conclusions Reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is not fully explained by cigarette smoking, area deprivation, maternal age or parity. [ABSTRACT FROM AUTHOR]

Introduction: Whether parenteral nutrition benefits growth of very low birth weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement is unclear. Our aim was to examine this issue using data from Japan, where enteral feeding typically advances at a rapid rate. Methods: We studied 4005 hospitalized VLBW, very preterm (23–32 weeks' gestation) infants who reached full enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal Research Network Japan (2003–2007). Main outcomes were weight gain, head growth, and extra-uterine growth restriction (EUGR, measurement <10th percentile for postmenstrual age) at discharge. Results: 40% of infants received parenteral nutrition. Adjusting for maternal, infant, and institutional characteristics, infants who received parenteral nutrition had greater weight gain [0.09 standard deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05, 0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No statistically significant difference was seen in the proportion of infants with EUGR at discharge. SGA infants and infants who took more than a week until full feeding had larger estimates. Discussion: Even in infants who are able to establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition in the first weeks of life could lead to under nutrition, but infants who reached full feeding within one week benefit least. It is important to predict which infants are likely or not likely to advance on enteral feedings within a week and balance enteral and parenteral nutrition for these infants. [ABSTRACT FROM AUTHOR]

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