Months In Infants Research Articles

A comparison of ultrasound-based testis volume with Prader orchidometry and stability of testis size relative to peers from birth to 28weeks.

Testis volume, an indicator of the reproductive development during minipuberty, is commonly measured by Prader orchidometer, despite ultrasound being the gold standard. Data are lacking on the longitudinal relationship between these two measures and on the stability of boys' relative testis size across infancy. To examine the relationship between ultrasound-based and orchidometer-based testis volume measurements and to assess the stability of relative testis size among individual boys in the study. The Infant Feeding and Early Development study is a longitudinal cohort of healthy infants recruited from hospitals in the Philadelphia area during 2010-2013. We measured testis size from birth to 28weeks in 147 infants using Prader orchidometry (nine study visits) and ultrasound (five study visits). We modeled testis growth, extracted predicted volumes for each boy on each day of the study, and ranked these volumes from smallest to largest. The average testis volume trajectory exhibited linear growth over the first 16weeks followed by slower growth and then a plateau. Prader orchidometry overestimated testis size by almost 3-fold, compared to ultrasound. A range of ultrasound volumes corresponded to each bead size (e.g., bead size of 1 cm3 corresponded to an ultrasound-based volume between 0.11 and 0.87 cm3). Infants changed rankings of median of 22 positions (of 147) across the entire 6-month follow-up. Infants' ranks near birth were highly correlated with their ranks at the end of the study. Consistent with other studies, we found wide variability in testis size during infancy and that Prader orchidometry overestimates testis size. When compared to ultrasound, orchidometry only crudely estimates testis size in this age group. Ultrasound-based volumes generally showed stability in relative testis size across infancy. Accurate measurement of testis size is difficult using orchidometry in infants. This highlights the need for ultrasound for accurate measurement, with a one-time measurement likely sufficient to determine relative testis size across the first 6 months of infancy.

Effects of exclusive breastfeeding on educational attainment and longitudinal trajectories of grade progression among children in a 13-year follow-up study in Malawi

The benefits of exclusive breastfeeding (EBF) for infant health and survival are well documented. However, its impact on educational outcomes has been contested and poorly researched in Africa. It has been hypothesised that positive associations reported in high-income countries can be attributed to residual confounding by socioeconomic status (SES). Our study investigated whether EBF duration in infancy is associated with educational attainment and age-for-grade attainment trajectories at school-age in rural Malawi. Longitudinal data on 1021 children at the Karonga demographic surveillance site in Malawi were analysed. Breastfeeding data were collected 3 months after birth and again at age one. The school grade of each child was recorded each year from age 6 until age 13. We calculated age-for-grade based on whether a child was at, over, or under the official expected age for a grade. Generalised estimating equations estimated the average effect of breastfeeding on age-for-grade. Latent class growth analysis identified age-for-grade trajectories, and multinomial logistic regression examined their associations with EBF. Maternal-child characteristics, SES, and HIV status were controlled. Overall, 35.9% of the children were exclusively breastfed for 6 months. Over-age for grade steadily increased from 9.6% at age 8 to 41.9% at age 13. There was some evidence that EBF for 6 months was associated with lower odds of being over-age for grade than EBF for less than 3 months (aOR = 0.82, 95%CI = 0.64–1.06). In subgroup analyses, children exclusively breastfed for 6 months in infancy were less likely to be over-age for grades between ages 6–9 (aOR = 0.64, 95%CI = 0.43–0.94). Latent class growth analysis also provided some evidence that EBF reduced the odds of falling behind in the early school grades (aOR = 0.66, 95%CI = 0.41–1.08) but not later. Our study adds to the growing evidence that EBF for 6 months has benefits beyond infant health and survival, supporting the WHO's recommendation on EBF.

Risk of visual axis opacification in infants with and without primary IOL implantation after congenital cataract surgery performed during the first 4 months of age

PurposeThe study evaluates the rate of postoperative formation of a pupillary membrane (PM) and posterior visual axis opacification (PVAO) in infants with and without primary IOL implantation during the first 4 months of infancy.MethodsMedical records for 144 eyes (101 infants) operated between 2005 and 2014 were evaluated. A posterior capsulectomy and anterior vitrectomy were performed. Primary IOL implantation was performed in 68 eyes, while 76 eyes were left aphakic. There were 16 bilateral cases in the pseudophakic group and 27 in the aphakic group. The follow-up period was 54.3 ± 21.05 months and 49.1 ± 18.60 months, respectively. Fisher’s exact test was used for statistical analysis. The two-sample t-test with equal variance was used to compare surgery age, follow-up period and time intervals of complications.ResultsThe mean age of surgery was 2.1 ± 0.85 months in the pseudophakic and 2.2 ± 1.01 months in the aphakic group. PM was diagnosed in 40% pseudophakic and 7% aphakic eyes. A second surgery for PVAO was performed in 72% pseudophakic and 16% aphakic eyes. Both were significantly higher in the pseudophakic group. In the pseudophakic group, the number of PVAO was significantly higher in infants operated before 8 weeks of age compared to surgery age 9–16 weeks. The frequency of PM was not age-dependent.ConclusionAlthough it remains feasible to implant an IOL during the primary surgery, even in very young infants, there should always be solid arguments for this decision since it puts the child at higher risk of repeated surgeries under general anaesthesia.

Capacity for Regulation of Energy Intake in Infancy

The capacity for regulation of energy intake (REI) to match energy needs is thought to contribute to differences in weight gain, and preventing excess infant weight gain is a priority. To determine capacity for REI across infancy. For this cohort study, a convenience sample of mother-infant dyads was recruited from the community in Michigan between 2015 and 2019. Inclusion criteria were healthy, full-term infants with weight appropriate for gestational age; biological mothers who were 18 years or older, English speaking, and a legal and custodial guardian; and infant having had consumed 2 oz or more in 1 feeding from an artificial nipple at least once per week. Infants were followed in the home setting with staff support for up to 12 months. Mother-infant dyads participated at infant age 1, 2.5, 5, 7, 10, and 12 months. In the intervention condition, mothers offered a feeding every hour for 6 hours. In the control condition, mothers fed infants as they typically would for 6 hours. Intake was recorded and kilocalories calculated. Capacity for REI was indexed as the difference in intake in kilocalories per kilogram of body weight (intervention minus control condition); a value of 0 indicated perfect REI. Maternal and infant characteristics were obtained by questionnaire, and anthropometry was measured. Using multiple imputation, the intercept and slope for difference in kilocalories per kilogram across the 6 age points were estimated using mixed models accounting for repeated measures within participants. Statistical analyses were conducted between September 2021 and February 2023. The sample included 175 infants (87 [49.71%] female, 88 [50.29%] male; 494 pairs of intervention and control conditions and 4630 feedings). The mean (SD) 12-month weight-for-age z score was 0.1 (0.8). Mean (SD) gestational age as 39.55 (1.05) weeks, and mean (SD) birth weight was 3.43 (0.41) kg. Mean (SD) breastfeeding duration for those who reported stopping by 12 months was 17.83 (12.03) weeks. As designed, the intervention (compared with control) condition included more feedings at shorter intervals. After collapsing the data across age points in a mixed model accounting for repeated measures within participants, the REI estimate at 1 month differed from 0. On average, infants ate 5.21 kcal/kg (95% CI, 2.89-7.54 kcal/kg) more in the frequent feeding intervention condition than in the ad lib feeding control condition. This difference did not significantly change over 12 months of infancy (REI slope = -0.01 kcal/kg per month; 95% CI, -0.02 to 0.03 kcal/kg per month). The study's findings suggested that, on average, when offered more frequent feedings, healthy, full-term infants may overeat. The results provide support for responsive feeding as a strategy for preventing excess infant weight gain.

A Systematic Review on the Efficacy and Safety of Alginate-based Liquid Formulations in Reducing Gastroesophageal Reflux in Neonates and Infants.

Neonates and infants experience gastroesophageal reflux as manifested through vomiting, reflux, and coughing. The complaint from many caregivers begins around the 2nd or 3rd month of life and subside around the 6th month of infancy. The standard of care has not been established and treatment options are limited owing to the pharmacological interventions that are deemed safe and effective. Alginate-based formulations, a widely used product in adults such as Gaviscon™, have been explored as another option to treat gastroesophageal reflux. To determine the safety and efficacy of alginate-based formulations in reducing symptoms of gastroesophageal reflux in neonates and infants. An electronic search was conducted for randomized control trials in MEDLINE via PubMed, Herdin Plus, Cochrane Central Register of Controlled Trials, SCOPUS, and Clinical Trials Registry. The search terms were "gastroesophageal reflux," "acid reflux," "neonates," "newborn," "infants," "baby," "babies,", and "alginate." Two review authors independently assessed the available full text articles and a third author intervened to settle the discussion. Two studies were identified and included in this study. Due to the difference in the period of measurement of the trials, a meta-analysis was not pursued. However, a systematic review was still conducted. The two studies suggest a significant improvement of symptoms with alginate-based liquid formulations as intervention. No significant adverse events have been noted making this treatment option generally safe for use in infants. There is insufficient evidence to conclude that alginate-based formulations ultimately help decrease gastroesophageal reflux in neonates and infants, but initial trials show promising results. There is also insufficient data to conclude the safety profile of this treatment option given the small sample.

Adherence to Canadian 24-Hour Movement Guidelines among infants and associations with development: a longitudinal study

BackgroundTo examine: 1) longitudinal adherence to the Canadian 24-Hour Movement Guidelines in a sample of infants and 2) associations between adherence to the guidelines over time and development.MethodsParticipants were 250 parent-infant dyads from the Early Movers project in Edmonton, Alberta. At 2, 4, and 6 months of age, physical activity, sedentary behaviour, sleep, and development were measured with a parental questionnaire that included items from the Ages & Stages Questionnaire (ASQ-3). Parents also reported the dates six major gross motor milestones were acquired during the first 18 months of life according to World Health Organization criteria. In a sub-sample (n = 93), movement behaviours were also measured with a time-use diary at 2, 4, and 6 months and gross motor development was measured by a physiotherapist using the Alberta Infant Motor Scale (AIMS) at 6 months. Guideline adherence was defined as: 1) ≥ 30 min/day of tummy time, 2) no screen time, some reading time, no restrained bouts > 1 h (time-use diary only), and 3) 14–17 h (2 months) or 12–16 h (4 and 6 months) of sleep per 24-h period. Generalized estimating equations were conducted as well as linear mixed models and linear regression models that adjusted for demographic characteristics.ResultsFew infants met the guidelines at all time-points (questionnaire: 2%; time-use diary: 0%). Infants that met a recommendation at 2 months, compared to those that did not, were 1.8–8.2 times more likely to meet that recommendation at subsequent time-points. Meeting more recommendations across time-points, according to both measures, was associated with a higher mean ASQ-3 gross motor score. Each additional time-point of tummy time recommendation adherence (questionnaire-measured) was associated with a 5–11-day earlier acquisition of independent sitting, crawling, and independent standing milestones. In the sub-sample, each additional time-point of guideline adherence was associated with a 16% higher AIMS score at 6 months.ConclusionsGuideline adherence was low across the first 6 months of infancy. Overall, meeting more recommendations over this period appeared important for gross motor development. Parents and caregivers should be targeted as early as possible with guideline dissemination and activation strategies to promote healthy infant development.

Latent profiles of maternal disrupted communication: Relations to affect and behaviour in early infancy.

Few studies have examined how mothering is organized in the first months of infancy, especially regarding risk-related interactions. Person-centred approaches, including latent profile analysis (LPA), add valuable insights about early parenting by identifying distinct profiles of interaction. First, this study aimed to identify profiles of disrupted maternal interaction during the Still-Face Paradigm among 181 mothers and their 3- to 8-month-old infants. Second, the study assessed how each maternal profile was related to infant affect and interactive behaviour. The LPA identified four profiles of maternal interaction: optimal, negative/intrusive, withdrawing and pervasively disrupted. The pervasively disrupted profile, in particular, has not been identified in past research. Each profile was associated with specific aspects of infant affect and behaviour. Recognition of disrupted behavioural profiles among at-risk mothers and infants in the early months could facilitate more precise tailoring of early interventions to the needs of mothers and infants with differing profiles of interactive risk.

Infant-Feeding Patterns and the Effects of Early Introduction to Formula and Solid Foods on Childhood Overweight or Obesity among 10-Years-Olds in a Low Socioeconomic Area of Lebanon: An Exploratory Analysis.

In Lebanon, there has been an alarming increase in childhood overweight and obesity. In addition, most mothers do not meet the WHO recommendation that infants should be introduced to formula or solids only during the second half of their first year. Because the study population, Burj Hammoud, which is a low socioeconomic district, is small, we performed an exploratory analysis of infant feeding patterns and the effects of introducing formula and solids within six months, respectively, on childhood overweight/obesity among 10-year-old children. A total of 101 mothers were recruited from seven intercommunity dispensaries located across the district. Descriptive, univariate and multivariate logistic regression analyses were performed. There were 86.1% infants initiating breastfeeding, 18% exclusively breastfeeding at 6 months of age, 67.1% and 52.6% starting formula and solids by 6 months, respectively, and 53.5% becoming overweight/obese by the age of 10 years. Working mothers were significantly less likely to introduce formula but not solids within the first six months of infancy. Based on two case-control studies, after controlling for maternal employment, there were 2.278- and 1.511-fold significantly higher odds of introducing solids and formula before the age of 6 months compared with after the age of 6 months, respectively, for the overweight/obese individuals among 10-year-olds. Future research should focus on conducting a larger study by incorporating other low socioeconomic regions to confirm these relationships.

Development and emergence of functional network asymmetry in 3- to 9-month-old infants

Cerebral asymmetry is a cardinal feature of functional organization in the human brain and an important biomarker of successful brain development. Studies have demonstrated that functional network asymmetries across hemispheres undergo significant development through childhood and adulthood. However, it remains unknown when such asymmetries of functional networks emerge and how they develop across the early months of infancy. To address this issue, we used multiple-channel functional near-infrared spectroscopy (fNIRS) imaging to record spontaneous brain activity in 66 healthy infants aged 3–9 months. We then adopted a graph-theory analysis approach to quantify the topological characteristics of hemispheric networks in each participant. Our results showed that infants aged 3 to 6 months old exhibited leftward asymmetries in local network efficiency, while infants aged 6 to 9 months old exhibited leftward asymmetries in global network efficiency. Importantly, the degree of leftward asymmetry in global network efficiency was increased over development from 3 to 9 months old, with a faster increase in the left hemisphere than in the right hemisphere. At the regional level, 3- to 6-month-old infants exhibited leftward asymmetries in functional connectivity strength (FCS) in the temporal cortex, whereas the FCS asymmetries were located in the temporal, frontal, and occipital cortexes for 6- to 9-month-old infants. Furthermore, the 6- to 9-month-old infants also exhibited leftward asymmetries in nodal efficiency around the frontal cortex. These combined findings demonstrate that functional asymmetric organization has emerged in early infancy, which could lay a critical foundation for the development of brain functions (e.g., language and social cognition functions) later in life.

Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics.

Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed. To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life. We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age. Cough severity, pulmonary exacerbations (PEx), respiratory cultures, and hospitalizations were collected at each CF center visit (every 1-2 months in infancy and quarterly thereafter). These data were used to construct the CFELD system and to classify lung disease into five categories: asymptomatic, minimal, mild, moderate, and severe. The most frequent manifestation of CF early lung disease was MD-reported PEx episodes, PEx hospitalizations, and positive Pseudomonas aeruginosa cultures. Parent-reported cough severity was correlated with the number of respiratory hospitalizations (r = 0.48, p < 0.0001). The distribution of CFELD categories was 10% asymptomatic, 17% minimal, 29% mild, 33% moderate, and 12% severe. The moderate and severe categories occurred threefold higher in pancreatic insufficient (PI, 49%) versus sufficient subjects (16%), p < 0.0001. In addition to PI, gastrointestinal and nutrition-related hospitalizations, plasma cytokines interleukin (IL)-6 and IL-10, duration of CFTR modulator therapy, and type of health insurance were significant predictors of CFELD scores. The CFELD scoring system is novel, allows systematic evaluation of lung disease prognosis early, and may aid in therapeutic decision-making particularly in the initiation of CFTR modulator therapy.

Evolution of Cortical Functional Networks in Healthy Infants.

During normal childhood development, functional brain networks evolve over time in parallel with changes in neuronal oscillations. Previous studies have demonstrated differences in network topology with age, particularly in neonates and in cohorts spanning from birth to early adulthood. Here, we evaluate the developmental changes in EEG functional connectivity with a specific focus on the first 2years of life. Functional connectivity networks (FCNs) were calculated from the EEGs of 240 healthy infants aged 0-2years during wakefulness and sleep using a cross-correlation-based measure and the weighted phase lag index. Topological features were assessed via network strength, global clustering coefficient, characteristic path length, and small world measures. We found that cross-correlation FCNs maintained a consistent small-world structure, and the connection strengths increased after the first 3months of infancy. The strongest connections in these networks were consistently located in the frontal and occipital regions across age groups. In the delta and theta bands, weighted phase lag index networks decreased in strength after the first 3months in both wakefulness and sleep, and a similar result was found in the alpha and beta bands during wakefulness. However, in the alpha band during sleep, FCNs exhibited a significant increase in strength with age, particularly in the 21-24months age group. During this period, a majority of the strongest connections in the networks were located in frontocentral regions, and a qualitatively similar distribution was seen in the beta band during sleep for subjects older than 3months. Graph theory analysis suggested a small world structure for weighted phase lag index networks, but to a lesser degree than those calculated using cross-correlation. In general, graph theory metrics showed little change over time, with no significant differences between age groups for the clustering coefficient (wakefulness and sleep), characteristics path length (sleep), and small world measure (sleep). These results suggest that infant FCNs evolve during the first 2years with more significant changes to network strength than features of the network structure. This study quantifies normal brain networks during infant development and can serve as a baseline for future investigations in health and neurological disease.

The effect of breastfeeding during infancy on arterial stiffness in young adults.

Breastfeeding has many benefits for health, also later in life. However, its effects on the cardiovascular system are still unclear. The aim of the present study was to evaluate the effect of exclusive breastfeeding as infants on arterial stiffness in young adults having no cardiovascular risk factors, using aortic pulse wave velocity, and brachial and aortic augmentation index. Eighty-six subjects were included in the study from similar socioeconomic status. 46 subjects who had received exclusive breastfeeding for the first 4-6 months in infancy (26 women, mean age 26.7±4 years) (group 1) and 40 subjects who had received exclusive breastfeeding for less than 3 months or had never been breast-fed (22 women, mean age: 28±3.8 years) (group 2) were recruited. Parameters of arterial stiffness (aortic pulse wave velocity, brachial and aortic augmentation index) were investigated using an arteriograph (TensioMed, Budapest, Hungary), which works on an ossilometric basis. A significant decrease in pulse wave velocity in the breast-fed group was detected compared to the non-breast-fed group (P<0.05) but no significant difference was detected for aortic and brachial augmentation index. In addition there was a significant relationship between breastfeeding duration and aortic pulse wave velocity. Breast milk intake in infancy reduces the risk of cardiovascular disease in young adults, independent of other cardiovascular risk factors. It seems that there is a negative relationship between the duration of breastfeeding and the risk reduction.

Vitamins A, D, E status as related to supplementation and lung disease markers in young children with cystic fibrosis.

The variable response to fat-soluble vitamin supplementation in young children with cystic fibrosis (CF), and factors contributing to this variability, remain under-investigated. To determine if recommended supplement doses normalize serum vitamins A (retinol), D (25-hydroxy-vitamin D, 25OHD), and E (α-tocopherol), and identify factors predictive of achieving sufficiency, in children with CF in the first 3 years of life. We studied 144 infants born during 2012-2017 and diagnosed with CF through newborn screening. Serum retinol, 25OHD, α-tocopherol and plasma cytokines interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were measured in early infancy and yearly thereafter. Vitamin supplement intakes and respiratory microbiology were assessed every 1-2 months in infancy and quarterly thereafter. The prevalence of vitamin D insufficiency (<30 ng/ml) at all ages combined was significantly higher (22%) compared to vitamin A (<200 ng/ml, 3%) and vitamin E (<5 µg/ml, 5%). All children were vitamin A sufficient by age 2 years. Vitamin E insufficiency was rare. Only 42% were early responders of vitamin D and 17% remain insufficient despite high supplement intakes. IL-6 was positively correlated, while IL-8, IL-10, and TNF-α were negatively correlated, with retinol and 25OHD. Multiple regression analysis revealed that supplement dose, season, α-tocopherol, pancreatic insufficiency, respiratory infections and IL-10 were significant predictors of 25OHD. Diagnosis through newborn screening coupled with supplementation normalized serum retinol and α-tocopherol in almost all infants with CF by age 3 years. However, response to vitamin D supplements in young children with CF occurred later and variably despite early and sustained supplementation.

Monthly measurement of child lengths between 6 and 27 months of age in Burkina Faso reveals both chronic and episodic growth faltering

ABSTRACTBackgroundLinear growth faltering is determined primarily by attained heights in infancy, but available data consist mainly of cross-sectional heights at each age.ObjectivesThis study used longitudinal data to test whether faltering occurs episodically in a few months of very low growth, which could potentially be prevented by timely intervention, or is a chronic condition with slower growth in every month of infancy and early childhood.MethodsUsing anthropometric data collected monthly between August 2014 and December 2016, we investigated individual growth curves of 5039 children ages 6–27 mo in Burkina Faso (108,580 observations). We evaluated growth-curve smoothness by level of attained length at ∼27 mo by analyzing variation in changes in monthly growth rates and using 2-stage regressions: 1) regressing each child's length on their age and extracting R2 to represent curve smoothness, initial length, and average velocity by age; and 2) regressing extracted parameters on individual-level attained length.ResultsShort children started smaller and remained on their initial trajectories, continuously growing slower than taller children. Growth between 9 and 11 mo was the most influential on attained length; for each 1-cm/mo increase in growth velocity during this period, attained length increased by 6.71 cm (95% CI: 6.59, 6.83 cm). Furthermore, a 0.01 increase in R2 from individual regression of length on age was associated with a 3.10-cm higher attained length (95% CI: 2.80, 3.41 cm), and having 2 consecutive months of slow growth (<15th centile relative to the sample) was associated with 1.7-cm lower attained length (95% CI: −1.80, −1.59 cm), with larger effects in younger children, suggesting that smoother growth patterns were also associated with higher attained length.ConclusionsChildren who experience extreme growth faltering are likely less resilient to systematic growth-limiting conditions as well as episodic insults to their growth.This trial was registered at clinicaltrials.gov as NCT02071563.

Abstract 16747: Rapidly Lethal Dilated Cardiomyopathy Secondary To Generalized Arterial Calcification Of Infancy

Case Presentation: A previously healthy 3-month-old infant presented with cardiorespiratory arrest, from which she was successfully resuscitated. A dilated cardiomyopathy with severely depressed systolic function was diagnosed. ECG showed high voltage QRS complexes and generalized alteration of repolarization. In the following 12 hours, she suffered 2 other cardiac arrests, recuperated with defibrillation. Hemodinamic stability was achieved but brain death was diagnosed 36 hours after the onset of symptoms. Autopsy showed striking calcification of the right and left coronary arteries, with narrowing of the arterial lumen, causing extensive subendocardial infarction. Calcification also affected the aorta, pulmonary arteries, thyroid, kidney and other splanchnic arteries. Generalized arterial calcification of infancy (GACI) was diagnosed and a genetic study found two biallelic variants in ABCC6 gene: p.Arg1114Cys and p.Trp38Ser, both previously described in elastic pseudoxanthoma (PXE), but not in GACI. Genotyping of the healthy parents confirmed genetic segregation with biallelic variants. Discussion: GACI is an extremely rare genetic disease characterized by widespread arterial calcification and narrowing of large and medium-sized vessels. The usual clinical presentation is heart failure in fetal life or in the first months of infancy. In most cases it is lethal, with death occurring within a few hours or days after the onset of symptoms, although clinical involvement is highly variable and cases with long survival have been described. GACI is an autosomal recessive disease secondary to biallelic variants in the ENPP1 gene (67% of cases) and in the ABCC6 gene (9%). The variants found in our patient had not been previously described in GACI, just in PXE, a much milder disease with usually normal lifespan. This case confirms that both entities reflect two extremes of a clinical spectrum of ectopic calcification instead of two different disorders. The aim of presenting this case is to remind clinicians of this rare etiology in neonates or infants with dilated cardiomyopathy. In case of death, autopsy should always be requested. When this condition is diagnosed, genetic study will be positive in 75% of cases, allowing prenatal counseling.

Coagulation parameters in the newborn and infant- the Copenhagen Baby Heart and COMPARE studies.

The coagulation system is not fully developed at birth and matures during the first months of infancy, complicating clinical decision making within hemostasis. This study evaluates coagulation parameters at birth and two months after birth, and tests whether cord blood can be used as a proxy for neonatal venous blood measurements. The Copenhagen Baby Heart Study (CBHS) and the COMPARE study comprise 13,237 cord blood samples and 444 parallel neonatal venous blood samples, with a two month follow-up in 362 children. Because coagulation parameters differed according to gestational age (GA), all analyses were stratified by GA. For neonatal venous blood, reference intervals for activated partial thromboplastin time (APTT) and prothrombin time (PT) were 28-43s and 33-61% for GA 37-39 and 24-38s and 30-65% for GA 40-42. Reference intervals for international normalized ratio (INR) and thrombocyte count were 1.1-1.7 and 194-409×109/L for GA 37-39 and 1.2-1.8 and 188-433×109/L for GA 40-42. Correlation coefficients between umbilical cord and neonatal venous blood for APTT, PT, INR, and thrombocyte count were 0.68, 0.72, 0.69, and 0.77 respectively, and the distributions of the parameters did not differ between the two types of blood (all p-values>0.05). This study describes new GA dependent reference intervals for common coagulation parameters in newborns and suggests that cord blood may serve as a proxy for neonatal venous blood for these traits. Such data will likely improve clinical decision making within hemostasis among newborn and infant children.

Adrenal steroids reference ranges in infancy determined by LC-MS/MS

Interpretation of the results of steroid hormone measurements is challenging at early infancy. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method provides a powerful tool for diagnosing steroidogenesis disorders. We aimed to develop normative data for a 14-steroid panel and four adrenal enzyme activity indices, determined by LC-MS/MS from 3 days to 6 months of age. Age- and sex-specific plasma steroid concentrations were calculated in 324 healthy full-term neonates and infants (151 females). Percentile curves were devised. Steroid ratios were evaluated as biomarkers of adrenal enzyme activities. The steroid profiles of four patients with adrenal enzyme deficiencies were included to test the diagnostic efficiency. Nine steroids showed age, but none showed sex specificity. The concentrations of progestins and androgens were higher at 7-14 days than at 3-7 days. After the first month, adrenal androgen concentrations decreased significantly. Adrenal enzyme activities changed towards increasing cortisol over the first 6 months. There were several-fold differences in diagnostic steroids and related adrenal enzyme activity indices between the patients and the healthy group. The majority of adrenal steroids show age-related variations in the neonatal period and early infancy. Our data will enable accurate interpretation of steroid measurements for etiologic diagnosis of disorders of steroidogenesis. LC-MS/MS method is capable of quantitating numerous analytes simultaneously, which provides an integrated picture of adrenal steroidogenesis in a small amount of sample. The development of LC-MS/MS-based normative data of steroid hormones in healthy infants is crucial to differentiate physiologic alterations from steroidogenic defects during the first 3-6 months of infancy. Previous studies had limitations due to the small numbers of samples available by sex and by age groups. Our detailed normative data and percentile curves will enable accurate interpretation of steroid measurements for etiologic diagnosis of disorders of steroidogenesis without the need for further invasive testing.

Systemic manifestations and treatment algorithm of food allergy

Food allergy or hypersensitivity can be defined as the presence of an observable immune secondary reaction to the administration of certain proteins that are present within the ingested foods. It has been previously estimated that around 2-10% of the general population suffer from IgE-mediated food allergy. Furthermore, identification of the manifestations is a key point to achieve appropriate evaluation and management of this condition. In this literature review, we aim to discuss the systemic manifestations and treatment algorithm for patients who suffer from a food allergy, according to the current evidence from studies in the literature. Gastrointestinal and skin-related manifestations have been reported to be the most common symptom. However, respiratory tract symptoms are also common and might severely deteriorate the affected patients. The development of severe anaphylaxis is also life-threatening with multiple organ affection. The appropriate management of food hypersensitivity is mainly based on the proper intervention from exposure to the related allergens. In addition, another appropriate management is early sensitization during the first few months of infancy to manage the symptoms of affected patients. Additionally, it should also be noted that most children usually develop tolerance, and the reported allergy to certain types of foods during childhood usually fades away by the age from 8 to12 years old and also during the period of adolescence. Future studies are needed to develop adequate management modalities with favorable safety and efficacy outcomes.

Dosage escalation of antenatal steroids in preterm twin pregnancies does not improve long-term outcome.

To analyze long-term effects of antenatal betamethasone (≤16mg, =24mg and >24mg) in preterm twins on infant and childhood morbidity. Retrospective cohort study among 198 preterm twins. Three follow up time points, including a total of 84 outcomes, were evaluated: first neonatal examination after birth and in the neonatal period up to 10days after birth using data from the clinic charts; examination from the 21st to the 24th month of life and examination from the 60th to the 64th months, using data from copies of the children's examination booklets sent back by the parents. Dosage-dependent and sex-specific long-term effects of antenatal betamethasone treatment on neonatal, infant and early childhood development and morbidity up to 5.3 years of age were analyzed. Dosage escalation of >24mg was not associated with improved neonatal, infant or early child hood outcome, independent of twin pair structure. In contrast, higher doses >24mg were significantly linked to increased rates of congenital infections (OR 5.867, 95% CI 1.895-18.167). Male sex as a factor was obvious for lower rates of apnea-bradycardia-syndrome in neonates, higher rates ofno free steps after 15months in infancy and highest rates of motor clumsiness in early childhood. Betamethasone dosage escalation >24mg in twins born between 23+5 and 33+6 weeks of gestation did not improve neonatal, infant or early childhood morbidity. In contrast, higher doses >24mg total dose resulted in significantly higher rates of congenital infections and are not recommended. For males, 24mg betamethasone appears to be the preferable dose.

Associations between KCNQ1 and ITIH4 gene polymorphisms and infant weight gain in early life.

An earlier meta-analysis of genome-wide association studies in Asian populations detected five novel body mass index-associated single-nucleotide polymorphisms (SNPs), including potassium voltage-gated channel subfamily Q member 1 (KCNQ1) (rs2237892), ALDH2/MYL2 (rs671, rs12229654), ITIH4 (rs2535633), and NT5C2 (rs11191580). Whether these SNPs take effect in early life, for example, affect infant rapid weight gain (RWG), is unclear. We obtained genomic DNA from 460 term infants with normal birth weight. RWG was defined as the change of weight-for-age standardized Z-score, calculated according to the Children Growth Standard released by the World Health Organization, from birth to 3 months of age >0.67. Using genetic models, associations between the candidate SNPs and infant RWG were examined, along with the interaction between the SNPs and the potential risk factors. RWG was presented in 225 of 460 infants. SNP rs2535633 and rs2237892 were associated with the risk of RWG. Both additive and multiplicative interaction effects were found between infant delivery mode and rs2237892. The negative association between the rs2237892 T allele and infant RWG was only observed in vaginally delivered infants. Obesity-related loci rs2535633 and rs2237892 are associated with infant RWG in the first 3 months of infancy. The relationship between rs2237892 and infant RGW might be moderated by cesarean delivery. Genetic predisposition is an essential aspect to understand infant weight gain. Obesity-related SNPs, rs2535633 and rs2237892, are associated with RWG in very early years of life. The negative association between rs2237892 T allele and RWG is only observed in infants delivered vaginally instead of cesarean section.