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.

Variación del perímetro cefálico en prematuros menores de 34 semanas expuestos a corioamnionitis histológica / Variation of head circumference variation in preterm infants less than 34 weeks to histologic chorioamnionitis

RESUMEN Objetivo : Analizar las variaciones del perímetro cefálico (PC) en prematuros menores de 34 semanas expuestos a corioamnionitis histológica (CAH), y observados hasta los 2 años de edad corregida. Material y métodos : Estudio de cohorte secundaria de dos estudios prospectivos. Los datos correspondieron a mediciones del PC al nacimiento, a las 40 semanas y a los 2 años de edad corregida. La variación del PC se analizó en los prematuros con y sin exposición a CAH. La CAH se analizó de acuerdo con los subtipos subcorionitis/corionitis, corioamnionitis y corioamnionitis más funisitis. Resultados : De 91 prematuros incluidos, el 41,8 % (38/91) tuvo CAH. El promedio del PC al nacimiento fue de 27,7 cm (percentil 31,2) en los expuestos y de 28,3 cm (percentil 42,1) en los no expuestos (p = 0,039); a las 40 semanas y a los 2 años, los promedios fueron similares. El subtipo corioamnionitis estuvo asociado con un menor PC (p < 0,05). La menor edad gestacional al nacer (p < 0,005) se relacionó con una mayor velocidad de crecimiento craneal. La CAH y el retardo de crecimiento intrauterino (RCIU) fueron los factores determinantes del menor PC en las tres edades evaluadas, y la sepsis confirmada solo tuvo lugar a las 40 semanas. Conclusiones : Los prematuros menores de 34 semanas expuestos a la CAH tuvieron menor percentil de PC al nacimiento; se observó recuperación del percentil de PC a las 40 semanas; y, finalmente, el subtipo corioamnionitis se relacionó con un menor PC a los 2 años de edad corregida. El factor RCIU potencia esta asociación en las tres edades y la sepsis solo a las 40 semanas. Se recomienda realizar futuros estudios para confirmar estos hallazgos.

SUMMARY Objective : To analyze the variations of head circumference (HC) in preterm infants, born with less than 34 weeks of gestation, exposed to histologic chorioamnionitis (CAH), and observed until 2 years of corrected age. Materials and methods : This is a cohort study derived from two prospective studies. The analyzed data corresponded to HC measures obtained from the subjects at three points: birth, 40 weeks, and 2 years of corrected age. The subjects were classified in two groups: exposed and not exposed to CAH. Preterm infants with CAH were divided according to its subtype in chorioamnionitis, subchorionitis and chorioamnionitis plus funisitis. Results : Out of 91 preterm infants included in the study. 41.8% (38/91) presented CAH. At birth, the average measure of HC in exposed infants was 27.7 cm (31,2 percentile), while in not exposed infants it was 28.3 cm. (42,1 percentile). At 40 weeks and at 2 years, the average measures were similar. The CAH chorioamnionitis subtype was found to be associated with PC growth retardation (p<0,05). A lesser gestational age (p=0.005) was related with greater cranial growth speed. Conclusions : Newborns younger than 34 weeks exposed to CAH had lower HC percentile at birth. We observed a recovery of HC at 40 weeks. The chorioamnionitis subtype was related to lower HC at 2 years of corrected age. Intrauterine growth restriction (IUGR) enhanced this association at these three points, while sepsis did so only at 40 weeks. Further research is required to confirm these findings.

Maternal plasma transforming growth factor-β1 (TGF-β1) and newborn size: the Araraquara Cohort Study

Abstract Objective To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. Methods This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. Results Maternal plasma TGF-β1 concentration was inversely associated with newborn weight (β= -43.0; p= 0.012), length (β= -0.16, p= 0.028), head circumference (β= -0.13, p= 0.004), ponderal index (β= -0.32, p= 0.011) and fat-free mass (β= -0.05, p= 0.005). However, the association persisted just for head circumference (β= -0.26; p= 0.030) and ponderal index (β= - 0.28; p= 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. Conclusions Maternal plasma TGF-β1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-β1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Exposure to ultra-processed foods during pregnancy and ultrasound fetal growth parameters.

Periconceptional maternal ultra-processed food (UPF) consumption impairs embryonic growth. Impacts of exposure to UPF on distinct components of fetal growth in late pregnancy are unknown. We investigated the influence of frequency of UPF consumption during pregnancy on fetal head circumference (HC), abdominal circumference (AC) and femur length (FL). This study included 417 live-born singleton pregnancies prospectively followed-up since the antenatal period in the MINA-Brazil Study, with an available ultrasound scan at >24 gestational weeks. Frequency of food groups consumption in the previous month was categorised as no/monthly, weekly or daily. Ultrasound scans were conducted at 27·8 (sd: 1·7) gestational weeks. HC, AC and FL z-scores were calculated for gestational age using the INTERGROWTH-21st Project standards. Simultaneous-quantile regression models were fitted at the 10th, 50th and 90th percentiles of the distribution of each ultrasound parameter according to UPF consumption, with adjustment for potential confounders. Participants were aged on average 24·7 (sd: 6·5) years, 44·8 % were primiparous, and 26·9 % and 24·9 %, respectively, had weekly and daily UPF consumption. Compared with no/monthly intake, daily UPF consumption impaired HC across its distribution, with significant effect sizes varying from -0·24 to -0·40 z-score. Weekly UPF consumption decreased HC at the 90th percentile by -0·39 z-score (95 % CI: -0·78, -0·01) and FL at the 50th percentile by -0·32 z-score (95 % CI: -0·60, -0·04). No association was noted with AC. Frequency of UPF consumption was negatively associated with skeletal components of fetal growth in late pregnancy. Infant body composition may benefit from healthy food practices since pregnancy.

Association of Postnatal Growth Changes and Neurodevelopmental Outcomes in Preterm Neonates of <29 Weeks' Gestation.

OBJECTIVE: To examine associations between weight and head circumference (HC) changes and neurodevelopment in preterm infants. STUDY DESIGN: This retrospective cohort study of Canadian Neonatal Network and Canadian Neonatal Follow-Up Network sites included preterm infants born 2010-2018. Logistic regression and model diagnostics evaluated relationships between changes in z score and velocity of weight and HC from birth to discharge from a tertiary neonatal intensive care unit, discharge to 18-24 months corrected age (CA), and birth to 18-24 months CA and significant cognitive/motor impairment at 18-24 months CA classified using a Bayley Scales of Infant and Toddler Development-Third Edition cognitive or motor composite score <70. RESULTS: In total, 4530 infants (53.0% male) with a mean (SD) gestational age of 26.3 (1.4) weeks and birth weight of 920 (227) g were included. Weight and HC changes were associated with lower odds of significant cognitive/motor impairment including an OR of 0.87 (95% CI: 0.83, 0.91; P < .001) for a 1-g/d increase in weight from discharge to 18-24 months CA and 0.81 (95% CI: 0.75, 0.88; P < .001) for a 1-unit increase in HC z score from birth to 18-24 months CA. Associations were not statistically significant in morbidity-free neonates. Weight and HC gains poorly discriminated between infants with and without significant cognitive/motor impairment (areas under the receiver operating characteristic curve of <0.64). No growth measure had a clinically useful balance of sensitivity and specificity. CONCLUSIONS: Weight and HC changes were associated with significant cognitive/motor impairment but had poor discriminatory capability. Neonatal morbidities may make a larger contribution than postnatal growth to neurodevelopment.

Measuring head circumference using visual impressions or cross-sectional volumetric imaging: a comparison.

BACKGROUND: Head circumference (HC) correlates with brain growth and development. However, radiologists typically use their visual impressions to evaluate head dimensions, which is a purely subjective assessment. OBJECTIVE: The first objective of this paper was to analyze whether it is possible to obtain HC measurements by CT and MRI cross-sectional volumetric imaging using parameters similar to the tape measurement method, which is considered the gold standard. The second objective was to determine the most accurate method for characterizing head size: visual impression or imaging measurement. MATERIALS AND METHODS: Children who underwent HC measurement by tape and with volumetric imaging exams were selected from the Paulo Niemeyer State Brain Institute, Brazil. Two radiologists classified the children's heads using their visual impressions and by direct measurement on imaging. We used anatomical parameters similar to the tape measurement method and appropriate head growth charts and compared the absolute values obtained. RESULTS: The concordance between tape and imaging ranged 52.3-72.7% for visual impression (kappa 0.27-0.55), ≥ 95.5% for CT and ≥ 93.1% for MRI (kappa ≥ 0.92 and ≥ 0.88, respectively). Intraclass correlation coefficients ≥ 0.997 and ≥ 0.996, absolute technical error measurements of 0.20-0.31 cm and 0.24-0.29 cm, and relative technical error measurements of 0.49-0.73% and 0.58-0.70% were evidenced in the intra- and inter-rater evaluations, respectively. The means between the methods were not significantly different (P > 0.05), with high values of Pearson correlation coefficient (≥ 0.99) and Lin concordance correlation coefficient (≥ 0.99). CONCLUSION: Head circumference values obtained by cross-sectional volumetric imaging are similar to those obtained using the tape measurement method (gold standard), with high repeatability and reproducibility. Head size characterization by visual impression is less accurate than head circumference measurement by imaging and plotting the values obtained on World Health Organization normative charts.

Maternal plasma transforming growth factor-ß1 (TGF-ß1) and newborn size: the Araraquara Cohort Study.

OBJECTIVE: To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. METHODS: This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. RESULTS: Maternal plasma TGF-ß1 concentration was inversely associated with newborn weight (ß = -43.0; p = 0.012), length (ß = -0.16, p = 0.028), head circumference (ß = -0.13, p = 0.004), ponderal index (ß = -0.32, p = 0.011) and fat-free mass (ß = -0.05, p = 0.005). However, the association persisted just for head circumference (ß = -0.26; p = 0.030) and ponderal index (ß = - 0.28; p = 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. CONCLUSIONS: Maternal plasma TGF-ß1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-ß1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Breastfeeding practices and head circumference in young children: a systematic review

ABSTRACT OBJECTIVE To review observational studies on the association between breastfeeding (BF) practices and head circumference (HC) of children < 2 years old. METHODS A systematic review was conducted using the following electronic databases of health sciences: PubMed, Latin American and Caribbean Literature in Health Sciences (Lilacs), Web of Science and Scopus. We selected observational studies published in any language from January 01, 2010 to November 19, 2021, from different populations that investigated the association between BF practice and HC among healthy children < 2 years old. Titles and abstracts were screened independently by two evaluators. RESULTS From the 4,229 articles identified, 24 were included in this review: 6 cross-sectional, 17 longitudinal, and 1 case-control. The studies varied in their definition of the variables for BF and in reporting its practice, frequency, duration, and feeding method. Regarding HC, the authors analyzed the mean differences, abnormal values (z-score above + 2SD or below -2SD according to the World Health Organization (WHO) growth standards, 2007), and longitudinal growth parameters. The findings of this review suggest that BF may have a positive relationship with HC at the beginning of life. CONCLUSIONS Our findings suggest that BF, especially exclusive BF, may play a protective role against abnormal HC values in young children. However, more robust evidence with standardized BF indicators and WHO growth standards (2007) are required.

Human milk microbial species are associated with infant head-circumference during early and late lactation in Guatemalan mother-infant dyads.

Human milk contains abundant commensal bacteria that colonize and establish the infant's gut microbiome but the association between the milk microbiome and head circumference during infancy has not been explored. For this cross-sectional study, head-circumference-for-age-z-scores (HCAZ) of vaginally delivered breastfed infants were collected from 62 unrelated Mam-Mayan mothers living in eight remote rural communities in the Western Highlands of Guatemala during two stages of lactation, 'early' (6-46 days postpartum, n = 29) or 'late' (109-184 days postpartum, n = 33). At each stage of lactation, infants were divided into HCAZ ≥ -1 SD (early: n = 18; late: n = 14) and HCAZ < -1 SD (early: n = 11; late: n = 19). Milk microbiome communities were assessed using 16S ribosomal RNA gene sequencing and DESeq2 was used to compare the differential abundance (DA) of human milk microbiota with infant HCAZ subgroups at both stages of lactations. A total of 503 ESVs annotated 256 putative species across the 64 human milk samples. Alpha-diversity using Chao index uncovered a difference in microbial community richness between HCAZ ≥ -1 SD and HCAZ < -1 SD groups at late lactation (p = 0.045) but not at early lactation. In contrast, Canonical Analysis of Principal Coordinates identified significant differences between HCAZ ≥ -1 SD and HCAZ < -1 SD at both stages of lactation (p = 0.003); moreover, 26 milk microbial taxa differed in relative abundance (FDR < 0.05) between HCAZ ≥ -1 SD and HCAZ < -1 SD, with 13 differentially abundant at each lactation stage. Most species in the HCAZ ≥ -1 SD group were Streptococcus species from the Firmicutes phylum which are considered human colonizers associated with human milk whereas the HCAZ < -1 SD group at late lactation had more differentially abundant taxa associated with environmentally and 'potentially opportunistic' species belonging to the Actinobacteria genus. These findings suggest possible associations between brain growth of breastfed infants and the milk microbiome during lactation. Importantly, these data provide the first evidence of cross talk between the human milk microbiome and the infant brain that requires further investigation.

Evaluación de la antropometría en neonatos sanos. No todas las medidas son relevantes / Anthropometry assesment in healthy neonates. Not all measurements are relevant

Resumen Las medidas antropométricas se han usado para evaluar el crecimiento fetal y neonatal, además de determinar factores de riesgo de forma temprana. Clásicamente se han tomado el peso, talla, perímetro cefálico, torácico y abdominal. Son usadas para establecer condiciones como peso bajo o elevado para la edad gestacional, y con base en esto poder definir riesgos tempranos y tardíos. Otra medida sumamente importante es el perímetro cefálico, misma que determina neonatos con potencial riesgo neurológico. Estas tres medidas son clave como parte de la evaluación inicial neonatal, además de que se incluyen en el seguimiento del crecimiento y desarrollo infantil. No obstante, otras mediciones rutinarias como el perímetro torácico y abdominal, en neonatos con adaptación espontánea y exploración física normal (neonatos sanos), puede que aporten poco acerca del estado de salud neonatal. Estas últimas medidas no forman parte de los parámetros de seguimiento del crecimiento infantil, ni cuentan con gráficas de percentiles extrapolables para género y edad gestacional. Todas estas medidas están condicionadas por múltiples factores como genética, raza y nutrición, entre otros. Es momento de analizar las medidas rutinarias al momento del nacimiento de neonatos sanos, y priorizar las extrapolables a implicaciones clínicas relevantes.

Abstract Anthropometric measurements are used to assess fetal and neonatal growth and determine early risk factors. Classically, weight, height, head circumference, thoracic and abdominal circumference are the usual measures. They are used to identify conditions such as low or high weight for gestational age and, based on this, to determine early and late risks. Another important measurement is head circumference, which determines neonates with potential neurological risk. These three measures are key as part of the initial neonatal evaluation, and they are also a part of the child's growth monitoring and development. However, other routine measurements such as chest and abdominal circumferences, in newborns with spontaneous adaptation and normal physical examination (healthy neonates) may provide little information about the neonatal health status. These last measurements are not part of the child growth monitoring parameters, nor do they have percentile graphs that can be extrapolated to gender and gestational age. All these measures are conditioned by multiple factors such as genetics, race, and nutrition, among others. It is time to analyze routine measures at the time of birth of healthy newborns and prioritize those that can be extrapolated to relevant clinical implications.

A prospective cohort study of head circumference and its association with neurodevelopmental outcomes in infants and young children in rural Guatemala.

Microcephaly, an anthropometric marker of reduced brain volume and predictor of developmental disability, is rare in high-income countries. Recent reports show the prevalence of microcephaly to be much higher in lower resource settings. We calculated the prevalence of microcephaly in infants and young children (n = 642; age range = 0.1-35.9 months), examined trends in occipitofrontal circumference (OFC) growth in the year after birth and evaluated the relationship between OFC and performance on the Mullen Scales of Early Learning (MSEL) in rural Guatemala. Multivariable regression analyses adjusted for age were performed: (1) a model comparing concurrent MSEL performance and OFC at all visits per child, (2) concurrent OFC and MSEL performance by age group, and (3) OFC at enrollment and MSEL at final visit by age group. Prevalence of microcephaly ranged from 10.1% to 25.0%. OFC z-score decreased for most infants throughout the first year after birth. A significant positive association between continuous OFC measurement and MSEL score suggested that children with smaller OFC may do worse on ND tests conducted both concurrently and ∼1 year later. Results were variable when analyzed by OFC cutoff scores and stratified by 6-month age groups. OFC should be considered for inclusion in developmental screening assessments at the individual and population level, especially when performance-based testing is not feasible.

Birth Characteristics Among Children Diagnosed with Neurofibromatosis Type 1 and Tuberous Sclerosis.

OBJECTIVE: To evaluate whether children with neurofibromatosis type 1 (NF1) and tuberous sclerosis have different birth characteristics compared with the general population. STUDY DESIGN: We identified all individuals born in Sweden between 1973 and 2014 from the nationwide Medical Birth Register for whom information on both biological parents was available (n = 4 242 122). Individuals with NF1 and individuals with tuberous sclerosis were identified using data from Swedish population-based health data registers. Using logistic regression models, we assessed the associations between these 2 neurocutaneous syndromes and birth characteristics in a cohort that included 1804 subjects with NF1 and 450 with tuberous sclerosis. RESULTS: Children with NF1 and tuberous sclerosis were significantly more likely to be born preterm and via cesarean delivery. In addition, children with NF1 were also more likely to be born with other birth characteristics, such as short length, a large head circumference, and a low Apgar score. Moreover, children with NF1 had an increased odds of being born with a high birth weight or large for gestational age (OR, 1.61; 95% CI, 1.42-1.82 and OR, 1.82; 95% CI, 1.60-2.06, respectively). CONCLUSION: Children with NF1 and tuberous sclerosis differ from the general population in terms of several birth characteristics, with the strongest associations observed for high birth weight and large for gestational age in individuals with NF1.

Hereditary hypophosphatemic rickets and craniosynostosis.

BACKGROUND: Craniosynostosis is an underdiagnosed complication associated with hypophosphatemic rickets. The study aims to describe the clinical and auxological characteristic of children with hypophosphatemic rickets and craniosynostosis, describe the usual treatment, and compare the characteristics with those of children without craniosynostosis. METHODS AND PATIENTS: An observational and retrospective cohort study was conducted. Clinical notes and cranial images were reviewed. Out of 96 children, only the 50 patients who had skull images were included. RESULTS: Out of 50 patients, 26 (15 males) had craniosynostosis (52%). No differences were observed in birth size, age, height, body proportions, alkaline phosphatase, serum phosphate, or percent tubular reabsorption of phosphate at first appointment among children with or without craniosynostosis. Among patients with craniosynostosis, dolichocephaly was prevalent. The sagittal suture was affected in all patients with craniosynostosis, with 19 of 26 children (73%) affected with isolated scaphocephaly. Pan-sutural craniosynostosis was present in 7 children (27%). None of the children had microcephaly, 7 of them presented macrocephaly and, in the remaining subjects, head circumference was normal. Five patients had undergone at least 1 cranial remodeling surgery. One patient with craniosynostosis was diagnosed with a Chiari I malformation. Molecular characterization of PHEX gene was performed in 14 cases. CONCLUSIONS: Craniosynostosis is an underdiagnosed complication of hypophosphatemic rickets. Many patients with normal head size and growth may go undiagnosed, thus it is important to consider this association for early diagnosis and possible surgical treatment. A multidisciplinary approach is necessary for a correct long-term follow-up.

Association between exposure to air pollution during intrauterine life and cephalic circumference of the newborn.

It has been observed that air pollution can affect newborn health due to the negative effects of pollutants on pregnancy development. However, few studies have evaluated the impact of maternal exposure to urban air pollution on head circumference (HC) at birth. Reduced head growth during pregnancy may be associated with neurocognitive deficits in childhood. The objectives of this study were to evaluate the association between maternal exposure to air pollution and HC at birth and to provide context with a systematic review to investigate this association. This was a prospective study of low-risk pregnant women living in São Paulo, Brazil. Exposure to pollutants, namely, nitrogen dioxide (NO2) and ozone (O3), was measured during each trimester using passive personal samplers. We measured newborn HC until 24 h after birth. We used multiple linear regression models to evaluate the association between pollutants and HC while controlling for known determinants of pregnancy. To perform the systematic review, four different electronic databases were searched through November 2018: CENTRAL, EMBASE, LILACS, and MEDLINE. We selected longitudinal or transversal designs associating air pollution and HC at birth. Two reviewers evaluated the inclusion criteria and risk of bias and extracted data from the included papers. Thirteen studies were selected for the systematic review. We evaluated 391 patients, and we did not observe a significant association between air pollution and HC. Regarding the systematic review, 13 studies were selected for the systematic review, 8 studies showed an inverse association between maternal exposure to pollutants and HC, 4 showed no association, and one observed a direct association. In the city of São Paulo, maternal exposure to pollutants was not significantly associated with HC at birth. The systematic review suggested an inverse association between air pollution and HC at birth.

Association between brain morphology and electrophysiological features in Congenital Zika Virus Syndrome: A cross-sectional, observational study.

BACKGROUND: Intrauterine infection with the Zika virus (ZIKV) has been connected to severe brain malformations, microcephaly, and abnormal electrophysiological activity. METHODS: We describe the interictal electroencephalographic (EEG) recordings of 47 children born with ZIKV-derived microcephaly. EEGs were recorded in the first year of life and correlated with brain morphology. In 31 subjects, we tested the association between computed tomography (CT) findings and interictal epileptiform discharges (IED). In eighteen, CTs were used for correlating volumetric measurements of the brainstem, cerebellum, and prosencephalon with the rate of IED. FINDINGS: Twenty-nine out of 47 (62%) subjects were diagnosed as having epilepsy. Those subjects presented epileptiform discharges, including unilateral interictal spikes (26/29, 90%), bilateral synchronous and asynchronous interictal spikes (21/29, 72%), and hypsarrhythmia (12/29, 41%). Interestingly, 58% of subjects with clinical epilepsy were born with rhombencephalon malformations, while none of the subjects without epilepsy showed macroscopic abnormalities in this region. The presence of rhombencephalon malformation was associated with epilepsy (odds ratio of 34; 95% CI: 2 - 654). Also, the presence of IED was associated with smaller brain volumes. Age-corrected total brain volume was inversely correlated with the rate of IED during sleep. Finally, 11 of 44 (25%) subjects presented sleep spindles. We observed an odds ratio of 0·25 (95% CI: 0·06 - 1·04) for having sleep spindles given the IED presence. INTERPRETATION: The findings suggest that certain CT imaging features are associated with an increased likelihood of developing epilepsy, including higher rates of IED and impaired development of sleep spindles, in the first year of life of CZVS subjects. FUNDING: This work was supported by the Brazilian Federal Government through a postdoctoral fellowship for EBS (Talented Youth, Science without Borders), an undergraduate scholarship for AJR (Institutional Program of Science Initiation Scholarships, Federal University of Rio Grande do Norte, Brazil), by International Centre for Genetic Engineering and Biotechnology (CRP/BRA18-05_EC) and by CAPES (Grant number 440893/2016-0), and CNPq (Grant number 88881.130729/2016-01).

Measurement error, microcephaly prevalence and implications for Zika: an analysis of Uruguay perinatal data.

BACKGROUND AND OBJECTIVE: The Zika virus outbreak has drawn attention to microcephaly, whose definition is based on head circumference measuring below a percentile or number of SDs below the mean. The objective of this analysis was to assess how differences in measurement precision might affect prevalence and trends of microcephaly. METHODS: Data from all births in Uruguay during 2010-2015 were obtained from the Perinatal Information System. The prevalence of births with microcephaly was calculated based on head circumference measurement at birth applying the INTERGROWTH-21st standards for sex and gestational age, and compared by method of ascertaining gestational age. RESULTS: Rounding and digit preference was observed: 74% of head circumference measurements were reported as a whole centimetre value. The prevalence of births varied substantially by the criterion used to define microcephaly (<3 SD, <2 SD, <3rd percentile for gestational age) and could be halved or doubled based on adding or subtracting a half-centimetre from all reported head circumference measurements. If 4 days were added to gestational age calculations, rather than using completed gestational weeks (without days) for gestational age reporting, the prevalence was 1.7-2 times higher. DISCUSSION: Rounding in measurement of head circumference and reporting preferences of gestational age may have contributed to a lower prevalence of microcephaly than expected in this population. Differences in head circumference measurement protocols and gestational age dating have the potential to affect the prevalence of babies reported with microcephaly, and this limitation should be acknowledged when interpreting head circumference data collected for surveillance.

Fetal Heart Defects and Measures of Cerebral Size.

OBJECTIVES: To estimate the association between fetal congenital heart defects (CHDs) and measures of brain size throughout pregnancy, from the end of the first trimester to birth. STUDY DESIGN: The cohort consisted of all fetuses scanned in Western Denmark in 2012 and 2013. Anthropometric measures in fetuses with isolated CHDs diagnosed within 12 months after birth were compared with those in the fetuses without CHDs. Z-scores standardized to gestational age were calculated for first trimester biparietal diameter, second trimester head circumference, fetal weight, birthweight, head circumference, and placental weight. RESULTS: We obtained data from 63 349 pregnancies and identified 295 fetuses with isolated CHDs (major n = 145; minor n = 150). The first trimester mean biparietal diameter Z-scores were not different between those with and those without CHDs. The head circumference mean Z-score difference was -0.13 (95% CI, -0.24 to -0.01; P = .03) in the second trimester and -0.22 (95% CI, -0.35 to -0.09; P < .001) at birth. Fetuses with univentricular physiology or tetralogy of Fallot showed the most pronounced compromise in cerebral size. CONCLUSIONS: Our results suggest that the brain alterations inducing an increased risk of impaired neurodevelopment in children with CHDs begin during pregnancy. Although fetuses with univentricular physiology or tetralogy of Fallot exhibited the most pronounced compromise in cerebral size, we recommend neurodevelopmental follow-up for all children with CHDs.

Impact of anthropometric nutritional parameters on the university selection test in Chile: A multifactorial approach.

OBJECTIVES: Scholastic achievement (SA) is a multifactorial problem that depends on factors related to the child, the child's family, and the educational system. The aim of this study was to quantify the relative impact of significant variables at the beginning of high school during 2010 (first grade of high school [1 HSG]) on 2013 university selection test (Prueba de Seleccion Universitaria [PSU]) outcomes, both in language scholastic achievement (LSA) and mathematics scholastic achievement (MSA), when students graduated from high school (4 HSG). This was done at the time of university admission with a multicausal approach. The purpose was to confirm the hypothesis that the level of educational establishment SA, intellectual ability, sex, parental schooling levels, and head circumference for age Z-score at the onset of high school are the most relevant parameters associated with 2013 PSU outcomes, both in LSA and MSA. METHODS: A representative, proportional, and stratified sample of 671 children of both sexes who enrolled in 1 HSG in 2010 (mean age: 14.8 ± 0.6 y) participated in the study. Nutritional, intellectual, brain developmental, cardiovascular risk, socio-to-economic, demographic, and educational variables were quantitated. SA was assessed at 4 HSG with the 2013 PSU tests. Data were analyzed with SAS software. RESULTS: Educational establishment SA, intellectual ability, maternal schooling, and age Z-score were the most relevant parameters to explain LSA (R2 = 0.493; P < 0.0001) and MSA variance in addition to sex (male), but only in MSA (R2 = 0.600; P < 0.0001). CONCLUSIONS: These findings confirm the hypothesis and can be useful to support nutritional, health, and educational planning.

Infant growth faltering linked to subclinical mastitis, maternal faecal-oral contamination, and breastfeeding.

Infant growth faltering occurs in breastfed infants <6 months of age. The possibility that maternal health status contributes to this growth faltering is underexplored. We investigated whether (a) subclinical mastitis (SCM), an asymptomatic inflammation of the breast, (b) maternal intestinal nematode and protozoan infections, indicators of faecal-oral contamination, or (c) poor breastfeeding practices increased the odds of stunting (length-for-age z-score < -2SD), underweight (weight-for-age z-score < -2SD), or low head circumference (head circumference-for-age z-score < -2SD) in breastfed infants in rural indigenous communities in Guatemala. Mother-infant dyads (n = 105) were subdivided into those with and without SCM (milk Na:K ratio > 0.6). Maternal and infant anthropometry were measured at the time of breast milk collection. Maternal stool samples were examined for the presence of intestinal nematodes and protozoa. Questionnaires were used to characterize breastfeeding practices (exclusivity and frequency) and support, hygiene (latrine use and household faucet), and infant diarrhoea. SCM occurred in 14% of women and was associated with increased odds of infant stunting (odds ratio [OR] = 4.3; confidence interval [CI] [1.1, 15.8]), underweight (OR = 9.2; CI [1.8, 48.0]), and low head circumference (OR = 15.9; CI [2.6, 96.9]). Maternal pathogenic protozoa and nematodes were uncommon (<4%), but nonpathogenic protozoa were common (e.g., Entamoeba coli [39%]). Entamoeba coli increased the likelihood (OR = 3.3; CI [1.02, 10.6]) of low head circumference, whereas higher breastfeeding frequency lowered its odds (OR = 0.74, CI [0.56, 0.97]). Prevention of SCM may improve early infant growth, but public health measures that increase breastfeeding frequency and reduce faecal-oral contamination may be required to minimize low head circumference.

Docosahexaenoic acid levels in erythrocytes and their association with the University Selection Test Outcomes in Chile.

The aim of this study was to quantitate the relative impact of DHA and AA levels in erythrocytes, anthropometric parameters and socio-economic status of school-age children, of both genders, graduated from high school in Chile, on the scholastic achievement in the University Selection Test (Prueba de Selección Universitaria, PSU) both language scholastic achievement (LSA) and mathematics scholastic achievement (MSA). A representative sample of 671 school-age young graduated from high school in 2013, 550 and 548 of them took the PSU for LSA and MSA, respectively. Only school-age young with high (n = 91) and low (n = 69) SA in both tests were considered. A total of 122 school-age children agreed to participate in the study and were divided as follows: Group 1: high PSU outcome (n = 70; males n = 48) and Group 2: low PSU outcome (n = 52; males n = 23). Data were analyzed by means of SAS software. Independently of gender, DHA, socio-economic status and head circumference-for-age Z-score were the most relevant parameters explaining both LSA (R2 = 0.650; p < 0.0001) and MSA outcomes (R2 = 0.700; p < 0.0001). These results can be useful for nutrition, health and education planning, in order to protect children starting from an early age and thus increase their school outcomes.