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1. Characterizing the extent human milk folate is buffered against maternal malnutrition and infection in drought‐stricken northern Kenya

   https://doi.org/10.1002/ajpa.24603  

   Fujita, Masako ; Wander, Katherine ; Tran, Tin ; Brindle, Eleanor ( August 2022 , American Journal of Biological Anthropology)

   Folate is an essential nutrient fundamental to human growth and development. Human milk maintains high folate content across the maternal folate status range, suggesting buffering of milk folate with prioritized delivery to milk at the expense of maternal depletion. We investigated whether and how the extent of this buffering may diminish under prolonged nutritional and/or disease stress, while taking into consideration infants' varying vulnerability to malnutrition‐related morbidity/mortality.

   A cross‐sectional study analyzed milk specimens from northern Kenyan mothers (n = 203), surveyed during a historic drought and ensuing food shortage. Multiple regression models for folate receptor‐α (FOLR1) in milk were constructed. Predictors included maternal underweight (BMI < 18.5), iron‐deficiency anemia (hemoglobin <12 g/dl and dried‐blood‐spot transferrin receptor >5 mg/L), folate deficiency (hyperhomocysteinemia, homocysteine >12 or 14 μmol/L), inflammation (serum C‐reactive protein >5 mg/L), infant age and sex, and mother‐infant interactions.

   In adjusted models, milk FOLR1 was unassociated with maternal underweight, iron‐deficiency anemia and inflammation. FOLR1 was positively associated with maternal folate deficiency, and inversely associated with infant age. There was interaction between infant age and maternal underweight, and between infant sex and maternal folate deficiency, predicting complex changes in FOLR1.

   Our results suggest that mothers buffer milk folate against their own nutritional stress even during a prolonged drought; however, the extent of this buffering may vary with infant age, and, among folate‐deficient mothers, with infant sex. Future research is needed to better understand this variability in maternal buffering of milk folate and how it relates to folate status in nursing infants.

    

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2. Neurobehavioral outcomes of neonatal asymptomatic congenital cytomegalovirus infection at 12-months

   https://doi.org/10.1186/s11689-024-09533-0  

   Stoyell, Sally M. ; Elison, Jed T. ; Graupmann, Emily ; Miller, Neely C. ; Emerick, Jessica ; Ramey, Elizabeth ; Sandness, Kristen ; Schleiss, Mark R. ; Osterholm, Erin A. ( April 2024 , Journal of Neurodevelopmental Disorders)

   Congenital cytomegalovirus (cCMV) is the most common congenital viral infection in the United States. Symptomatic infections can cause severe hearing loss and neurological disability, although ~ 90% of cCMV infections are asymptomatic at birth. Despite its prevalence, the long-term neurobehavioral risks of asymptomatic cCMV infections are not fully understood. The objective of this work was to evaluate for potential long-term neurobehavioral sequelae in infants with asymptomatic cCMV.

   Infants with cCMV were identified from a universal newborn cCMV screening study in a metropolitan area in the midwestern United States. Asymptomatic infants with cCMV were enrolled in a longitudinal neurodevelopmental study (N = 29). Age- and sex-matched healthy control infants (N = 193) were identified from the Baby Connectome Project (BCP), a longitudinal study of brain and behavioral development. The BCP sample supplemented an additional group of healthy control infants (N = 30), recruited from the same participant registry as the BCP specifically for comparison with infants with asymptomatic cCMV. Neurobehavioral assessments and parent questionnaires, including the Mullen Scales of Early Learning, the Repetitive Behavior Scales for Early Childhood (RBS-EC), and the Infant Toddler Social Emotional Assessment (ITSEA) were administered at 12 months of age. Neurobehavioral scores were compared between infants with asymptomatic cCMV and all identified healthy control infants.

   Infants with asymptomatic cCMV performed equivalently compared to healthy control infants on the neurobehavioral measures tested at 12 months of age.

   These results indicate that at 12 months of age, infants with asymptomatic cCMV are not statistically different from controls in a number of neurobehavioral domains. Although follow-up is ongoing, these observations provide reassurance about neurobehavioral outcomes for infants with asymptomatic cCMV and inform the ongoing discussion around universal screening. Additional follow-up will be necessary to understand the longer-term outcomes of these children.

    

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3. Infant eating behaviors and Milk feeding independently predict infant size

   https://doi.org/10.1002/ajhb.23678  

   Barrett, Katherine J. ; Thompson, Amanda L. ( September 2021 , American Journal of Human Biology)

   This study investigates the association of infant eating behaviors with infant size, and if those associations are mediated by infant feeding.

   Mothers with infants less than 12 months of age and living in Central North Carolina were enrolled (N = 61). Data were collected at baseline and at 3‐ and 6‐month follow up visits. Modified constructs from the Baby Eating Behavior Questionnaire (BEBQ) and Child Eating Behavior Questionnaire (CEBQ) measured parents' perceptions of infant eating behaviors related to food approach (enjoyment of food, and food responsiveness) and food avoidance (food fussiness, satiety responsiveness, and slowness in eating). Linear mixed effects models tested longitudinal associations among infant eating behavior ratings, infant feeding (breastfeeding intensity, timing of introduction of complementary foods), and anthropometry (weight, length, and weight‐for‐length z‐scores). Path analyses were stratified by age and tested for direct and indirect effects of mothers' ratings of infant eating behaviors and infant feeding on infant anthropometry.

   Linear mixed models showed that general appetite was associated with higher weight‐for‐age, and satiety responsiveness was associated with lower length‐for‐age. Path analyses showed that infant milk feeding did not mediate associations. Breastfeeding intensity was independently associated with lower weight‐ and length‐for‐agez‐scores. Age at complementary feeding initiation was associated with lower length‐for‐agez‐scores.

   Associations between parental perceptions of general appetite, satiety responsiveness, and infant weight and length are observed early in life. These findings suggest that parental perceptions of infant eating behaviors may contribute to the early developmental programming of later health outcomes.

    

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4. Population Pharmacokinetics of Phenobarbital in Neonates and Infants on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy

   https://doi.org/10.1002/jcph.1743  

   Thibault, Céline ; Massey, Shavonne L. ; Abend, Nicholas S. ; Naim, Maryam Y. ; Zoraian, Alexandra ; Zuppa, Athena F. ( September 2020 , The Journal of Clinical Pharmacology)

   The objective of this study was to describe the pharmacokinetics (PK) of intravenous phenobarbital in neonates and infants on extracorporeal membrane oxygenation (ECMO) and to provide dosing recommendations in this population. We performed a retrospective single‐center PK study of phenobarbital in neonates and infants on ECMO between January 1, 2014, and December 31, 2018. We developed a population PK model using nonlinear mixed‐effects modeling, performed simulations using the final PK parameters, and determined optimal dosing based on attainment of peak and trough concentrations between 20 and 40 mg/L. We included 35 subjects with a median (range) age and weight of 14 days (1–154 days) and 3.4 kg (1.6–8.1 kg), respectively. A total of 194 samples were included in the analysis. Five children (14%) contributing 30 samples (16%) were supported by continuous venovenous hemodiafiltration (CVVHDF). A 1‐compartment model best described the data. Typical clearance and volume of distribution for a 3.4–kg infant were 0.038 L/h and 3.83 L, respectively. Clearance increased with age and CVVHDF. Although on ECMO, phenobarbital clearance in children on CVVHDF was 6‐fold higher than clearance in children without CVVHDF. In typical subjects, a loading dose of 30 mg/kg/dose followed by maintenance doses of 6–7 mg/kg/day administered as divided doses every 12 hours reached goal concentrations. Age did not impact dosing recommendations. However, higher doses were needed in children on CVVHDF. We strongly recommend therapeutic drug monitoring in children on renal replacement therapy (excluding slow continuous ultrafiltration) while on ECMO.

    

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5. Quantifying latent social motivation and its associations with joint attention and language in infants at high and low likelihood for autism spectrum disorder

   https://doi.org/10.1111/desc.13336  

   Stallworthy, Isabella C. ; Berry, Daniel ; Davis, Savannah ; Wolff, Jason J. ; Burrows, Catherine A. ; Swanson, Meghan R. ; Grzadzinski, Rebecca L. ; Botteron, Kelly ; Dager, Stephen R. ; Estes, Annette M. ; et al ( October 2022 , Developmental Science)

   Social motivation—the psychobiological predisposition for social orienting, seeking social contact, and maintaining social interaction—manifests in early infancy and is hypothesized to be foundational for social communication development in typical and atypical populations. However, the lack of infant social‐motivation measures has hindered delineation of associations between infant social motivation, other early‐arising social abilities such as joint attention, and language outcomes. To investigate how infant social motivation contributes to joint attention and language, this study utilizes a mixed longitudinal sample of 741 infants at high (HL = 515) and low (LL = 226) likelihood for ASD. Using moderated nonlinear factor analysis (MNLFA), we incorporated items from parent‐report measures to establish a novel latent factor model of infant social motivation that exhibits measurement invariance by age, sex, and familial ASD likelihood. We then examined developmental associations between 6‐ and 12‐month social motivation, joint attention at 12–15 months, and language at 24 months of age. On average, greater social‐motivation growth from 6–12 months was associated with greater initiating joint attention (IJA) and trend‐level increases in sophistication of responding to joint attention (RJA). IJA and RJA were both positively associated with 24‐month language abilities. There were no additional associations between social motivation and future language in our path model. These findings substantiate a novel, theoretically driven approach to modeling social motivation and suggest a developmental cascade through which social motivation impacts other foundational skills. These findings have implications for the timing and nature of intervention targets to support social communication development in infancy.

   We describe a novel, theoretically based model of infant social motivation wherein multiple parent‐reported indicators contribute to a unitary latent social‐motivation factor.

   Analyses revealed social‐motivation factor scores exhibited measurement invariance for a longitudinal sample of infants at high and low familial ASD likelihood.

   Social‐motivation growth from ages 6–12 months is associated with better 12−15‐month joint attention abilities, which in turn are associated with greater 24‐month language skills.

   Findings inform timing and targets of potential interventions to support healthy social communication in the first year of life.

    

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