Improving Parental Health Literacy in Primary Caregivers of 0- to 3-Year-Old Children Through a WeChat Official Account: Cluster Randomized Controlled Trial.

Background: Parental health literacy is important to children's health and development, especially in the first 3 years. However, few studies have explored effective intervention strategies to improve parental literacy. Objective: This study aimed to determine the effects of a WeChat official account (WOA)-based intervention on parental health literacy of primary caregivers of children aged 0-3 years. Methods: This cluster randomized controlled trial enrolled 1332 caregiver-child dyads from all 13 community health centers (CHCs) in Minhang District, Shanghai, China, between April 2020 and April 2021. Participants in intervention CHCs received purposefully designed videos via a WOA, which automatically recorded the times of watching for each participant, supplemented with reading materials from other trusted web-based sources. The contents of the videos were constructed in accordance with the comprehensive parental health literacy model of WHO (World Health Organization)/Europe (WHO/Europe). Participants in control CHCs received printed materials similar to the intervention group. All the participants were followed up for 9 months. Both groups could access routine child health services as usual during follow-up. The primary outcome was parental health literacy measured by a validated instrument, the Chinese Parental Health Literacy Questionnaire (CPHLQ) of children aged 0-3 years. Secondary outcomes included parenting behaviors and children's health outcomes. We used the generalized linear mixed model (GLMM) for data analyses and performed different subgroup analyses. The ß coefficient, risk ratio (RR), and their 95% CI were used to assess the intervention's effect. Results: After the 9-month intervention, 69.4% (518/746) of caregivers had watched at least 1 video. Participants in the intervention group had higher CPHLQ total scores (ß=2.51, 95% CI 0.12-4.91) and higher psychological scores (ß=1.63, 95% CI 0.16-3.10) than those in the control group. The intervention group also reported a higher rate of exclusive breastfeeding (EBF) at 6 months (38.9% vs 23.44%; RR 1.90, 95% CI 1.07-3.38) and a higher awareness rate of vitamin D supplementation for infants younger than 6 months (76.7% vs 70.5%; RR 1.39, 95% CI 1.06-1.82). No significant effects were detected for the physical score on the CPHLQ, breastfeeding rate, routine checkup rate, and children's health outcomes. Furthermore, despite slight subgroup differences in the intervention's effects on the total CPHLQ score and EBF rate, no interaction effect was observed between these subgroup factors and intervention factors. Conclusions: Using a WHO literacy model-based health intervention through a WOA has the potential of improving parental health literacy and EBF rates at 6 months. However, innovative strategies and evidence-based content are required to engage more participants and achieve better intervention outcomes.

Early-emerging combinatorial thought: Human infants flexibly combine kind and quantity concepts.

Combinatorial thought, or the ability to combine a finite set of concepts into a myriad of complex ideas and knowledge structures, is the key to the productivity of the human mind and underlies communication, science, technology, and art. Despite the importance of combinatorial thought for human cognition and culture, its developmental origins remain unknown. To address this, we tested whether 12-mo-old infants (N = 60), who cannot yet speak and only understand a handful of words, can combine quantity and kind concepts activated by verbal input. We proceeded in two steps: first, we taught infants two novel labels denoting quantity (e.g., "mize" for 1 item; "padu" for 2 items, Experiment 1). Then, we assessed whether they could combine quantity and kind concepts upon hearing complex expressions comprising their labels (e.g., "padu duck", Experiments 2-3). At test, infants viewed four different sets of objects (e.g., 1 duck, 2 ducks, 1 ball, 2 balls) while being presented with the target phrase (e.g., "padu duck") naming one of them (e.g., 2 ducks). They successfully retrieved and combined on-line the labeled concepts, as evidenced by increased looking to the named sets but not to distractor sets. Our results suggest that combinatorial processes for building complex representations are available by the end of the first year of life. The infant mind seems geared to integrate concepts in novel productive ways. This ability may be a precondition for deciphering the ambient language(s) and building abstract models of experience that enable fast and flexible learning.

The Effect of Prenatal Docosahexaenoic Acid Supplementation on Offspring Fat Mass and Distribution at 24 Months Old.

Background: Excessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist. Objectives: This study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex. Methods: Infants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines. Results: For total FM, there was a significant main effect for the DHA dose (P = 0.03); however, the dose by GWG status was nonsignificant (P = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose (P = 0.01) was detected for central FM. However, no interaction was detected (P = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose. Conclusions: Greater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.

Causes and Risk Factors of Vitamin B12 Deficiency at the Bookends of Life, From Infancy to Old Age.

The causes and risk factors of vitamin B12 deficiency are many and varied. Importantly, they vary considerably across the lifespan, from infancy to old age. The complexity of the physiology of vitamin B12 bespeaks the myriad of possible causes of deficiency and possible disruptions of its functional integrity. These lead ultimately to the pathobiological effects witnessed in deficiency of this fascinating micronutrient. This brief overview of the multiplicity of mechanisms that can result in vitamin B12 deficiency, and the panoply of its manifestations explores the underlying reasons for the protean presentations of the disease. As the human organism progresses through the chronology and milestones of age, various susceptibility factors arise resulting from the interplay of environmental and genetic factors. Acting independently and in concert, these factors produce the common denominator of vitamin B12 deficiency. However, the rate at which such deficiency develops and the way in which it presents clinically vary widely, subject to such influences as genetic variability, end-organ susceptibility, and concomitant micronutrient status. Some examples of unusual cases of vitamin B12 deficiency are described. Much has been learned about the last of the numbered vitamins in almost a century. Much yet remains to be discovered.

Association of early parent-child separation with depression, social and academic performance in adolescence and early adulthood: a prospective cohort study.

OBJECTIVE: The present study aimed to investigate the long-term effects of parent-child separation during infancy and early childhood on depression, social relationships including parent-child and peer relationships, and academic performance during adolescence and early adulthood. METHODS: Data from the China Family Panel Studies (CFPS) were analyzed, which included a sample of 3829 children aged 4-15 years from 25 provinces over a period of 8 years. The study examined the association between early parent-child separation and outcomes related to depression, social and academic performance, comparing outcomes between individuals with and without early separation experiences. A series of subgroup analyses were conducted to further explore these associations. RESULTS: Parent-child separation lasting 3 months or longer was found to be associated with moderate to severe levels of depression and impaired social relationships during adolescence and early adulthood, particularly among males, adolescents, urban dwellers, and those with less educated mothers. Children who experienced parent-child separation for 3 months or longer showed a positive correlation between separation duration and depression. Short-term separations under 3 months did not show this association. The duration of separation also had a negative correlation with parent-child and peer relationships, as well as academic performance. CONCLUSION: Early parent-child separation has significant adverse effects on the mental health, social and academic performance of adolescents and early adulthood, especially among males, adolescents, urban residents, and those with lower maternal education. The severity of depression was found to be related to the duration of separation, highlighting the importance of minimizing separation to less than 3 months for children under the age of 3. These findings underscore the critical role of early parental care and the need for targeted interventions for high-risk populations.

Development of nitroalkene-based inhibitors to target STING-dependent inflammation.

Stimulator of Interferon Genes (STING) is essential for the inflammatory response to cytosolic DNA. Despite that aberrant activation of STING is linked to an increasing number of inflammatory diseases, the development of inhibitors has been challenging, with no compounds in the pipeline beyond the preclinical stage. We previously identified endogenous nitrated fatty acids as novel reversible STING inhibitors. With the aim of improving the specificity and efficacy of these compounds, we developed and tested a library of nitroalkene-based compounds for in vitro and in vivo STING inhibition. The structure-activity relationship study revealed a robustly improved electrophilicity and reduced degrees of freedom of nitroalkenes by conjugation with an aromatic moiety. The lead compounds CP-36 and CP-45, featuring a ß-nitrostyrene moiety, potently inhibited STING activity in vitro and relieved STING-dependent inflammation in vivo. This validates the potential for nitroalkene compounds as drug candidates for STING modulation to treat STING-driven inflammatory diseases, providing new robust leads for preclinical development.

Neonatal Physical Growth Predicts Electroencephalography Power in Rural South African Children.

Anthropometric measures at birth, indexing prenatal growth, are associated with later cognitive development. Children in low- and middle-income countries (LMIC) are at elevated risk for impaired prenatal and early postnatal growth and enduring cognitive deficits. However, the associations of neonatal physical growth with neural activity are not well-characterized in LMIC contexts, given the dearth of early childhood neuroimaging research in these settings. The current study examined birth length, weight, and head circumference as predictors of EEG relative power over the first three years of life in rural Limpopo Province, South Africa, controlling for postnatal growth and socioeconomic status (SES). A larger head circumference at birth predicted lower relative gamma power, lower right hemisphere relative beta power, and higher relative alpha and theta power. A greater birth length also predicted lower relative gamma power. There were interactions with timepoints such that the associations of birth head circumference and length with EEG power were most pronounced at the 7-month assessment and were attenuated at the 17- and 36-month assessments. The results identify birth head circumference and length as specific predictors of infant neural activity within an under-resourced context.

Learning phonetic categories in infancy: The role of word-context information.

Identifying the type of mechanisms at the core of phonetic categorization remains a central subject of research in infant language learning. Amongst different theories, one is that infants compute distributional information of phonemes based on their surrounding sounds (i.e., word context) such that phonemes that appear in different word contexts are more likely to be discriminated and categorized separately than phonemes that appear in similar word contexts. Following the procedure of Feldman et al. (2013a), we investigated the role of contextual information in the acquisition of phonetic categories in 8-month-old infants, using a non-native vowel contrast (English /ɒ/-/ʌ/). In Experiment 1, we established lack of discrimination of the non-native contrast without prior exposure to it. In Experiment 2, we manipulated the type of exposure prior to testing: half of the infants were exposed to minimal pair carriers (words that differ by one phoneme only; e.g., lituh and litoh), and the other half of the infants were exposed to non-minimal pair carriers (words formed by different phonemes; e.g., lituh and nutoh). All infants were tested for discrimination of the contrast (tuh vs. toh) presented as alternating (e.g., tuh-toh-tuh-toh) and non-alternating trials (e.g., tuh-tuh-tuh), as in Experiment 1. Infants in both conditions looked on average longer at alternating rather than non-alternating trials, suggesting that they discriminated the /ɒ/-/ʌ/ contrast after a brief exposure to the vowels embedded into words. Crucially, discrimination occurred regardless of whether words were minimal pair carriers or non-minimal pair carriers. A cross-experiment comparison revealed that infants showed different patterns of looking times based on whether they were exposed to the contrast before testing (Experiment 2) or not (Experiment 1). Our study shows that any type of word context helps infants to re-establish discrimination of non-native contrasts once sensitivity has been lost. These findings aid to better understand how the speech input modulates learning mechanisms during the establishment of phonetic categories in the first year of postnatal life.

Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

Role of High Flow Nasal Cannula as a Novel Therapy for Treatment of Severe Obstructive Sleep Apnea in a Child With Neuroendocrine Hyperplasia of Infancy: A Case Report and Review of Literature.

Neuroendocrine hyperplasia of infancy is a rare form of pediatric interstitial lung disease presenting with hypoxemia, tachypnea, retractions, and persistent pulmonary crackles in the first year of life. As these children frequently require supplemental oxygen therapy and demonstrate nighttime hypoxemia, there is a concern for an increased prevalence of sleep-disordered breathing in this population, including obstructive sleep apnea. As untreated sleep-disordered breathing is associated with adverse developmental outcomes for children, it is essential to promptly diagnose and treat. However, treatment of obstructive sleep apnea is often challenging in children. In this report, we describe a case of a child diagnosed with neuroendocrine hyperplasia of infancy at 12 months of age who was subsequently found to have severe obstructive sleep apnea that persisted despite adenotonsillectomy. As continuous positive airway pressure was not well tolerated, the patient was initiated on a high-flow nasal cannula at nighttime, which resulted in improvement of his sleep apnea and daytime functioning with better adherence to treatment. Our case illustrates the importance of screening for sleep-disordered breathing in patients with neuroendocrine hyperplasia of infancy, as well as the utility of a high-flow nasal cannula as a novel, effective treatment for pediatric obstructive sleep apnea.

Corrigendum: Differential effects of attachment security on visual fixation to facial expressions of emotion in 14-month-old infants: an eye-tracking study.

[This corrects the article DOI: 10.3389/fpsyg.2024.1302657.].

Leveraging technological advances to assess dyadic visual cognition during infancy in high- and low-resource settings.

Caregiver-infant interactions shape infants' early visual experience; however, there is limited work from low-and middle-income countries (LMIC) in characterizing the visual cognitive dynamics of these interactions. Here, we present an innovative dyadic visual cognition pipeline using machine learning methods which captures, processes, and analyses the visual dynamics of caregiver-infant interactions across cultures. We undertake two studies to examine its application in both low (rural India) and high (urban UK) resource settings. Study 1 develops and validates the pipeline to process caregiver-infant interaction data captured using head-mounted cameras and eye-trackers. We use face detection and object recognition networks and validate these tools using 12 caregiver-infant dyads (4 dyads from a 6-month-old UK cohort, 4 dyads from a 6-month-old India cohort, and 4 dyads from a 9-month-old India cohort). Results show robust and accurate face and toy detection, as well as a high percent agreement between processed and manually coded dyadic interactions. Study 2 applied the pipeline to a larger data set (25 6-month-olds from the UK, 31 6-month-olds from India, and 37 9-month-olds from India) with the aim of comparing the visual dynamics of caregiver-infant interaction across the two cultural settings. Results show remarkable correspondence between key measures of visual exploration across cultures, including longer mean look durations during infant-led joint attention episodes. In addition, we found several differences across cultures. Most notably, infants in the UK had a higher proportion of infant-led joint attention episodes consistent with a child-centered view of parenting common in western middle-class families. In summary, the pipeline we report provides an objective assessment tool to quantify the visual dynamics of caregiver-infant interaction across high- and low-resource settings.

Spindle cell lesions with oncogenic EGFR kinase domain aberrations: expanding the spectrum of protein kinase-related mesenchymal tumors.

EGFR aberrations are reported in a subset of myofibroblastic lesions with kinase domain duplication (EGFR-KDD) and exon 20 mutations being assigned to infantile fibrosarcomas (IFS), mesoblastic nephroma and fibrous hamartoma of infancy (FHI), respectively. In this retrospective study, we correlated molecular findings with histomorphology of 14 myofibroblastic lesions harboring such genetic changes identified by NGS. We additionally performed DNA methylation profiling (DNAmp) and immunohistochemistry. Lesions were from 10 males and 4 females with a mean age of 3 years (range, 0.3 -14) and occurred subcutaneously in the upper limbs (n = 5), lower limbs (n = 3), back/thorax (n = 5), and the nasal cavity (n = 1). Eleven were cured by surgery, including one relapsed case. Two patients were lost to follow-up. One case was very recent, and the patient was biopsied. Histologically, the lesions showed a wide spectrum varying from classic FHI (n=9) to IFS (n=1) or lipofibromatosis-like tumors (LFT-like) (n=2) or dermatofibrosarcoma protuberans-like (DFSP-like) (n=1) to a predominantly-myxoid spindle cell lesion (n=1). Immunohistochemically, all neoplasms stained with CD34, while S100 was positive in 2/14. EGFR expression was observed in 9/10 cases. Molecularly, the IFS and one LFT-like harbored EGFR-KDD, while an exon 20 mutation was identified in all FHI, one LFT-like and in the DFSP-like and predominantly myxoid spindle cell lesion. By DNAmp, all but two cases formed a well-defined cluster, demonstrating that these lesions are also epigenetically related. In conclusion, EGFR kinase domain aberrations found in FHI, IFS, LFT-like, DFSP-like and a spindle cell lesion with a predominant myxoid stroma of children and adolescents show that these neoplasms with a broad morphological spectrum belong to the group of protein kinase-related lesions with a distinct epigenetic signature. Molecular analyses, including DNAmp, help to identify and characterize this emerging category and become mandatory when targeted treatment is considered.

Reconsidering the nature of threat in infancy: Integrating animal and human studies on neurobiological effects of infant stress.

Early life stress has been associated with elevated risk for later psychopathology. One mechanism that may contribute to such long-term risk is alterations in amygdala development, a brain region critical to stress responsivity. Yet effects of stress on the amygdala during human infancy, a period of particularly rapid brain development, remain largely unstudied. In order to model how early stressors may affect infant amygdala development, several discrepancies across the existing literatures on early life stress among rodents and early threat versus deprivation among older human children and adults need to be reconciled. We briefly review the key findings of each of these literatures. We then consider them in light of emerging findings from studies of human infants regarding relations among maternal caregiving, infant cortisol response, and infant amygdala volume. Finally, we advance a developmental salience model of how early threat may impact the rapidly developing infant brain, a model with the potential to integrate across these divergent literatures. Future work to assess the value of this model is also proposed.

An update of the development of motor behavior.

This primer describes research on the development of motor behavior. We focus on infancy when basic action systems are acquired-posture, locomotion, manual actions, and facial actions-and we adopt a developmental systems perspective to understand the causes and consequences of developmental change. Experience facilitates improvements in motor behavior and infants accumulate immense amounts of varied everyday experience with all the basic action systems. At every point in development, perception guides behavior by providing feedback about the results of just prior movements and information about what to do next. Across development, new motor behaviors provide new inputs for perception. Thus, motor development opens up new opportunities for acquiring knowledge and acting on the world, instigating cascades of developmental changes in perceptual, cognitive, and social domains. This article is categorized under: Cognitive Biology > Cognitive Development Psychology > Motor Skill and Performance Neuroscience > Development.

Infant Care: Predictors of Outdoor Walking, Infant Carrying and Infant Outdoor Sleeping.

BACKGROUND: Although spending time outdoors is beneficial for development, little is known about outdoor time during infancy. The aim of this study was to assess frequencies and durations of (1a) outdoor walking and carrying in mother-infant dyads and (1b) infant outdoor sleeping in a stationary cot or pram. We furthermore aimed to identify associations of (2a) outdoor walking and carrying and (2b) infant outdoor sleeping, with infant, maternal and environmental sample characteristics. METHODS: An online survey was distributed among mothers of 0- to 12-month-old infants. Initially, 1453 mothers were recruited, of which 1275 were included in the analyses. With respect to (1a) the outcomes of interest were: mother-infant dyads' total weekly duration of walking in minutes, frequency of walking on weekdays, as well as weekends, and the frequency of using an infant carrier during walks, as well as the daily duration of carrying in hours (indoors and outdoors together). With respect to (1b) the outcome variables were: placing the infant outdoors to sleep (yes/no), the total weekly duration of outdoor sleeping and the weekly frequency of outdoor sleeping. For aim 2, associations of the outcome variables with infant (i.e., age), maternal (i.e., working status) and environmental (i.e., house type) sample characteristics were assessed. RESULTS: Mother-infant dyads engaged in walks for a total weekly duration of 201 min, for approximately one to three walks over weekdays (Monday through Friday), as well as one to three walks on the weekend. The infant carrier was used by 22% of mothers at least half of the time during outdoor walks, and 18% reported a daily duration of infant carrying of one hour or more. Among other associations, infant and maternal enjoyment of outdoor walking correlated positively with the duration as well as the frequency of walking during weekdays and during the weekend. Furthermore, employed mothers walked for a shorter duration and less frequently on weekdays as compared to mothers on maternity leave or mothers without a paid job. The availability of nearby recreational areas correlated positively with the weekly duration and frequency of walks. The infant carrier was used more frequently during outdoor walks if more than one child lived in the household. Infant carrying during outdoor walks was also related to infant behavior at night. Roughly a third of the mothers (29%) regularly had their infant sleep outdoors for a weekly duration of four hours and a weekly frequency of approximately one to two times. Younger infants, infants of mothers with higher education and infants living in detached houses were more likely to be placed outdoors to sleep. DISCUSSION: We identified associations of infant, maternal and environmental characteristics with outdoor time spent during infancy. These results lay the foundation for future research on the effects of the outdoors on child development as well as on facilitators and barriers for caregivers.

Emergence of locomotor behaviors: Associations with infant characteristics, developmental status, parental beliefs, and practices in typically developing Brazilian infants aged 5 to 15 months.

Independent locomotion provides autonomy for infants, drastically changing their relationship with their surroundings. From a dynamic systems perspective, the interaction between environment, tasks, and organismic constraints leads to the emergence of new behaviors over time. This 6-month longitudinal study aimed to verify associations between the emergence of locomotor behaviors and infants' characteristics, developmental status, parental beliefs, and practices. This observational study remotely assessed 37 full-term Brazilian infants aged 5 to 15 months, divided into two groups (G1: 5 to 11 months, n = 19; and G2: 9 to 15 months, n = 18). The motor developmental status of infants was closely associated with the emergence of behaviors (p < 0.05). Infants in G2 whose parents agreed with the statement "In typically developing infants, motor development occurs naturally and there is no need to actively stimulate it" started to walk later than those whose parents disagreed. Infants whose parents expected them to walk around 10-11 months walked earlier compared to those expected to walk after 11 months (G2, p = 0.011). Infants in G2 with a high frequency of staying in the supine position started to walk, both with and without support, later than those with a low frequency (p < 0.05). For infants in G1 with a high frequency of playing on the floor, locomotion (p = 0.041) and crawling on hands-and-knees (p = 0.007) started sooner compared to those with a low frequency. Staying in the cradle more frequently was related to a later emergence of supported walk (p = 0.046) among infants in G2. The emergence of locomotor behaviors is associated with motor developmental status, the surfaces where the infant plays, and body position. Parental beliefs and expectations influence how infants are stimulated and, consequently, the emergence of independent walking.

Serum biomarkers in neuroendocrine cell hyperplasia of infancy.

BACKGROUND: Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease of unknown origin associated with hyperplasia of pulmonary neuroendocrine cells (PNECs). Diagnosis is based on the characteristic clinical picture and typical radiological imaging, and, in some cases, on lung biopsies. To date, no biochemical indicators of the disease have been identified. AIM: We aimed to determine biomarkers that could be useful in the management of children diagnosed with NEHI. METHODS: Patients with NEHI and healthy children were enrolled. Concentrations of serum biomarkers secreted by PNECs (calcitonin gene-related peptide and gastrin-releasing peptide) and biomarkers of the destruction of alveolar capillary membrane (surfactant proteins A and D [SP-A and SP-D]; glycoprotein Krebs von den Lungen-6 [KL-6]; metalloproteinases 7 and 9 [MMP-7 and MMP-9]; tissue inhibitor of metalloprotease 1) were measured. RESULTS: Fifty-two children with NEHI and 23 healthy children were included in the study. The median age of children with NEHI was 3.9 years. There were no differences in serum levels of biomarkers secreted by PNECs between groups. KL-6 levels were significantly higher in children with NEHI than in healthy ones (median 119.6 vs. 92.1 U/mL, p = 0.003); however, concentrations of KL-6 were low in both groups. No significant differences existed between groups for the remaining biomarkers associated with the destruction of the alveolar-capillary membrane. CONCLUSIONS: Measurement of serum biomarkers released by PNECs and those associated with the destruction of the alveolar-capillary membrane does not appear to be useful in the management of children with NEHI.