Temporal relation between pubertal development and peer victimization in a prospective sample of US adolescents.

Peer victimization typically peaks in early adolescence, leading researchers to hypothesize that pubertal timing is a meaningful predictor of peer victimization. However, previous methodological approaches have limited our ability to parse out which puberty cues are associated with peer victimization because gonadal and adrenal puberty, two independent processes, have either been conflated or adrenal puberty timing has been ignored. In addition, previous research has overlooked the possibility of reverse causality-that peer victimization might drive pubertal timing, as it has been shown to do in non-human primates. To fill these gaps, we followed 265 adolescents (47% female) prospectively across three-time points (Mage : T1 = 9.6, T2 = 12.0, T3 = 14.4) and measured self-report peer victimization and self- and maternal-report of gonadal and adrenal pubertal development on the Pubertal Development Scale. Multilevel modeling revealed that females who were further along in adrenal puberty at age 9 were more likely to report peer victimization at age 12 (Cohen's d = 0.25, p = .005). The relation between gonadal puberty status and peer victimization was not significant for either sex. In terms of the reverse direction, the relation between early peer victimization and later pubertal development was not significant in either sex. Overall, our findings suggest that adrenal puberty status, but not gonadal puberty status, predicted peer victimization in females, highlighting the need to separate gonadal and adrenal pubertal processes in future studies.

Impact of the COVID-19 pandemic on infant feeding practices in the United States: Food insecurity, supply shortages and deleterious formula-feeding practices.

The coronavirus disease 2019 (COVID-19) pandemic increased food insecurity among US households, however, little is known about how infants, who rely primarily on human milk and/or infant formula, were impacted. We conducted an online survey with US caregivers of infants under 2 years of age (N = 319) to assess how the COVID-19 pandemic impacted breastfeeding, formula-feeding and household ability to obtain infant-feeding supplies and lactation support (68% mothers; 66% White; 8% living in poverty). We found that 31% of families who used infant formula indicated that they experienced various challenges in obtaining infant formula, citing the following top three reasons: the formula was sold out (20%), they had to travel to multiple stores (21%) or formula was too expensive (8%). In response, 33% of families who used formula reported resorting to deleterious formula-feeding practices such as diluting formula with extra water (11%) or cereal (10%), preparing smaller bottles (8%) or saving leftover mixed bottles for later (11%). Of the families who fed infants human milk, 53% reported feeding changes directly as a result of the pandemic, for example, 46% increased their provisioning of human milk due to perceived benefits for the infant's immune system (37%), ability to work remotely/stay home (31%), concerns about money (9%) or formula shortages (8%). Fifteen percent of families who fed human milk reported that they did not receive the lactation support they needed and 4.8% stopped breastfeeding. To protect infant food and nutrition security, our results underscore the need for policies to support breastfeeding and ensure equitable and reliable access to infant formula.

Detection of SMN1 to SMN2 gene conversion events and partial SMN1 gene deletions using array digital PCR.

Proximal spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an early-onset motor neuron disease characterized by loss of α-motor neurons and associated muscle atrophy. SMA is caused by deletion or other disabling mutations of survival motor neuron 1 (SMN1) but retention of one or more copies of the paralog SMN2. Within the SMA population, there is substantial variation in SMN2 copy number (CN); in general, those individuals with SMA who have a high SMN2 CN have a milder disease. Because SMN2 functions as a disease modifier, its accurate CN determination may have clinical relevance. In this study, we describe the development of array digital PCR (dPCR) to quantify SMN1 and SMN2 CNs in DNA samples using probes that can distinguish the single nucleotide difference between SMN1 and SMN2 in exon 8. This set of dPCR assays can accurately and reliably measure the number of SMN1 and SMN2 copies in DNA samples. In a cohort of SMA patient-derived cell lines, the assay confirmed a strong inverse correlation between SMN2 CN and disease severity. We can detect SMN1-SMN2 gene conversion events in DNA samples by comparing CNs at exon 7 and exon 8. Partial deletions of SMN1 can also be detected with dPCR by comparing CNs at exon 7 or exon 8 with those at intron 1. Array dPCR is a practical technique to determine, accurately and reliably, SMN1 and SMN2 CNs from SMA samples as well as identify gene conversion events and partial deletions of SMN1.

Mothers are more sensitive to infant cues after breastfeeding compared to bottle-feeding with human milk.

The belief that breastfeeding promotes maternal bonding is widely held by both the public and professional health organizations. Yet to our knowledge, all research examining the link between breastfeeding and maternal behavior in humans has been correlational, limiting our ability to draw causal conclusions. In many mammals, the hormone prolactin, which is central to milk production, rises in response to each breastfeeding session and promotes maternal sensitivity, yet there is a dearth of research in human mothers. To fill these research gaps, we randomly assigned 28 breastfeeding mothers to either breastfeed in the lab or feed their infants previously expressed breastmilk in a bottle before participating in a video-recorded free play session with their infant. Plasma prolactin was measured 40 min after the start of the feeding session and video observations were coded for maternal sensitivity. We found that women randomly assigned to breastfeed were more sensitive to infant cues than women randomly assigned to bottle-feed. Prolactin levels did not differ between feeding groups, although prolactin was positively correlated with maternal sensitivity. Our results suggest that feeding milk directly from the breast (compared to bottle-feeding) increases maternal sensitivity towards infants, at least in the short term.

Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia.

BACKGROUND: Preterm infants with bronchopulmonary dysplasia (BPD) have lifelong increased risk of respiratory morbidities associated with environmental pathogen exposure and underlying mechanisms are poorly understood. The resident immune cells of the lung play vital roles in host defense. However, the effect of perinatal events associated with BPD on pulmonary-specific immune cells is not well understood. METHODS: We used a double-hit model of BPD induced by prenatal chorioamnionitis followed by postnatal hyperoxia, and performed a global transcriptome analysis of all resident pulmonary immune cells. RESULTS: We show significant up-regulation of genes involved in chemokine-mediated signaling and immune cell chemotaxis, and down-regulation of genes involved in multiple T lymphocyte functions. Multiple genes involved in T cell receptor signaling are downregulated and Cd8a gene expression remains downregulated at 2 months of age in spite of recovery in normoxia for 6 weeks. Furthermore, the proportion of CD8a+CD3+ pulmonary immune cells is decreased. CONCLUSIONS: Our study has highlighted that perinatal lung inflammation in a double-hit model of BPD results in short- and long-term dysregulation of genes associated with the pulmonary T cell receptor signaling pathway, which may contribute to increased environmental pathogen-associated respiratory morbidities seen in children and adults with BPD. IMPACT: In a translationally relevant double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia, we identified pulmonary immune cell-specific transcriptomic changes and showed that T cell receptor signaling genes are downregulated in short term and long term. This is the first comprehensive report delineating transcriptomic changes in resident immune cells of the lung in a translationally relevant double-hit model of BPD. Our study identifies novel resident pulmonary immune cell-specific targets for potential therapeutic modulation to improve short- and long-term respiratory health of preterm infants with BPD.

Human milk as "chrononutrition": implications for child health and development.

Human biology follows recurring daily rhythms that are governed by circadian cues in the environment. Here we show that human milk is a powerful form of "chrononutrition," formulated to communicate time-of-day information to infants. However, 85% of breastfed infants in the US consume some milk that does not come directly from the breast but is pumped and stored in advance of feeding. Expressed milk is not necessarily circadian-matched (e.g., an infant might drink breastmilk pumped in the evening on the following morning). Ingesting mistimed milk may disrupt infants' developing circadian rhythms, potentially contributing to sleep problems and decreased physiological attunement with their mothers and environments. Dysregulated circadian biology may compromise infant health and development. Despite wide-ranging public health implications, the timing of milk delivery has received little empirical study, and no major pediatric or public health organization has issued recommendations regarding the circadian-matching of milk. However, potential adverse developmental and health consequences could be ameliorated by simple, low-cost interventions to label and circadian-match stored milk. The current paper reviews evidence for human milk as chrononutrition and makes recommendations for future research, practice, and policy.

Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons.

Topoisomerase 1 (TOP1) poisons like camptothecin (CPT) are currently used in cancer chemotherapy but these compounds can have damaging, off-target effects on neurons leading to cognitive, sensory and motor deficits. To understand the molecular basis for the enhanced sensitivity of neurons to CPT, we examined the effects of compounds that inhibit TOP1-CPT, actinomycin D (ActD) and ß-lapachone (ß-Lap)-on primary cultured rat motor (MN) and cortical (CN) neurons as well as fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts but transcript levels are reduced in all cell types after treatment with CPT. Microarray analysis was performed to identify differentially regulated transcripts in MNs in response to a brief exposure to CPT. Pathway analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. Immediate-early genes like Fos, Egr-1 and Gadd45b were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cell types treated with CPT; Egr-1, Gadd45b and Dyrk3 transcript levels, however, increased in CPT-treated MNs and CNs but decreased in CPT-treated fibroblasts. These transcripts may represent new targets for the development of therapeutic agents that mitigate the off-target effects of chemotherapy on the nervous system.

Paternal uniparental disomy with segmental loss of heterozygosity of chromosome 11 are hallmark characteristics of syndromic and sporadic embryonal rhabdomyosarcoma.

Costello syndrome (CS) arises from a typically paternally derived germline mutation in the proto-oncogene HRAS, and is considered a rasopathy. CS results in failure-to-thrive, intellectual disabilities, short stature, coarse facial features, skeletal abnormalities, congenital heart disease, and a predisposition for cancer, most commonly embryonal rhabdomyosarcoma (ERMS). The goal of this study was to characterize CS ERMS at the molecular level and to determine how divergent it is from sporadic ERMS. We characterized eleven ERMS tumors from eight unrelated CS patients, carrying paternally derived HRAS c.34G>A (p.Gly12Ser; 6) or c.35G>C (p.Gly12Ala; 2) mutations. Loss of heterozygosity (LOH) was evaluated in all CS ERMS by microarray and/or short tandem repeat (STR) markers spanning the entire chromosome 11. Eight CS ERMS tumors displayed complete paternal uniparental disomy of chromosome 11 (pUPD11), whereas two displayed UPD only at 11p and a second primary ERMS tumor showed UPD limited to 11p15.5, the classical hallmark for ERMS. Three sporadic ERMS cell lines (RD, Rh36, Rh18) and eight formalin fixed paraffin embedded (FFPE) ERMS tumors were also analyzed for RAS mutations and LOH status. We found a higher than anticipated frequency of RAS mutations (HRAS or NRAS; 50%) in sporadic ERMS cell lines/tumors. Unexpectedly, complete uniparental disomy (UPD11) was observed in five specimens, while the other six showed LOH extending across the p and q arms of chromosome 11. In this study, we are able to clearly demonstrate complete UPD11 in both syndromic and sporadic ERMS. © 2016 Wiley Periodicals, Inc.

Biological and psychosocial predictors of postpartum depression: systematic review and call for integration.

Postpartum depression (PPD) adversely affects the health and well being of many new mothers, their infants, and their families. A comprehensive understanding of biopsychosocial precursors to PPD is needed to solidify the current evidence base for best practices in translation. We conducted a systematic review of research published from 2000 through 2013 on biological and psychosocial factors associated with PPD and postpartum depressive symptoms. Two hundred fourteen publications based on 199 investigations of 151,651 women in the first postpartum year met inclusion criteria. The biological and psychosocial literatures are largely distinct, and few studies provide integrative analyses. The strongest PPD risk predictors among biological processes are hypothalamic-pituitary-adrenal dysregulation, inflammatory processes, and genetic vulnerabilities. Among psychosocial factors, the strongest predictors are severe life events, some forms of chronic strain, relationship quality, and support from partner and mother. Fully integrated biopsychosocial investigations with large samples are needed to advance our knowledge of PPD etiology.

The Interrelationship between Stress, Sugar Consumption and Depression.

Depression is a leading cause of disability in the United States. Previous research has shown that added sugar consumption and stress are both risk factors for depression. Despite evidence that stress predicts added sugar consumption, and both affect the HPA axis, no research has explored how stress, added sugar consumption and depression are related. In this study, we investigated the possible effects of total added sugar and sugar-sweetened beverage consumption on depression, as well as their potential interactions with chronic stress. Measures of sugar consumption, chronic stress and depression were taken in an adult community sample at two time points. We hypothesized that high sugar consumption would predict more depression even after stress was statistically adjusted for, but that stress would moderate the relationship between added sugar consumption and depressive symptoms, amplifying the effect. We found that both total sugar consumption and sugar-sweetened beverage consumption at baseline predicted depressive symptoms one month later. However, only sugar-sweetened beverage consumption was a significant predictor of depression after controlling for stress, possibly because stress is related to diet quality. Stress did not moderate the relationship between added sugar consumption and depressive symptoms. These results suggest that stress should be included in future research on sugar and depression.

Impact of FADS genotype on polyunsaturated fatty acid content in human milk extracellular vesicles: A genetic association study.

BACKGROUND: Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk. METHODS: Milk was obtained from a cohort of mothers (N = 70) at 2-4 weeks of lactation. SNPs in the FADS gene locus were determined using pyrosequencing for rs174546 in FADS1 and rs174575 in FADS2. Quantitative lipidomic analysis of polyunsaturated fatty acids in human milk and extracellular vesicles from human milk was completed by gas chromatography-mass spectrometry. RESULTS: The rs174546 and rs174575 genotypes were independent predictors of the arachidonic acid content in extracellular vesicles. The rs174546 genotype also predicted eicosapentaenoic acid and docosahexaenoic acid in extracellular vesicles. The reduced content of long-chain polyunsaturated fatty acids in extracellular vesicles in human milk may be due to lower fatty acid desaturase activity in mothers who are carriers of the A allele in rs174546 or the G allele in rs174575. CONCLUSION: The polyunsaturated fatty acid composition of milk extracellular vesicles is predicted by the FADS genotype. These findings yield novel insights regarding extracellular vesicle content and composition that can inform the design of future research to explore how lipid metabolites impact the bioavailability of human milk extracellular vesicles.

Mothers' prenatal distress accelerates adrenal pubertal development in daughters.

Human life history schedules vary, partly, because of adaptive, plastic responses to early-life conditions. Little is known about how prenatal conditions relate to puberty timing. We hypothesized that fetal exposure to adversity may induce an adaptive response in offspring maturational tempo. In a longitudinal study of 253 mother-child dyads followed for 15 years, we investigated if fetal exposure to maternal psychological distress related to children's adrenarche and gonadarche schedules, assessed by maternal and child report and by dehydroepiandrosterone sulfate (DHEA-S), testosterone, and estradiol levels. We found fetal exposure to elevated maternal prenatal psychological distress predicted earlier adrenarche and higher DHEA-S levels in girls, especially first-born girls, and that associations remained after covarying indices of postnatal adversity. No associations were observed for boys or for gonadarche in girls. Adrenarche orchestrates the social-behavioral transition from juvenility to adulthood; therefore, significant findings for adrenarche, but not gonadarche, suggest that prenatal maternal distress instigates an adaptive strategy in which daughters have earlier social-behavioral maturation. The stronger effect in first-borns suggests that, in adverse conditions, it is in the mother's adaptive interest for her daughter to hasten social maturation, but not necessarily sexual maturation, because it would prolong the duration of the daughter allomothering younger siblings. We postulate a novel evolutionary framework that human mothers may calibrate the timing of first-born daughters' maturation in a way that optimizes their own reproductive success.

Does breastfeeding offer protection against maternal depressive symptomatology?: A prospective study from pregnancy to 2 years after birth.

Mothers who breastfeed typically exhibit lower levels of depressive symptomatology than mothers who do not. However, very few studies have investigated the directionality of this relationship. Of the prospective studies published, all but one focus exclusively on whether maternal depression reduces rates of subsequent breastfeeding. This study again examines this relationship, but also the reverse-that breastfeeding might predict lower levels of later depression. Using multilevel modeling, we investigated the relationship between breastfeeding and self-reported depressive symptomatology in 205 women followed prenatally and at 3, 6, 12, and 24 months after birth. Consistent with previous research, women with prenatal depressive symptomatology weaned their infants 2.3 months earlier, on average, than women without such symptomatology. We also found, however, that women who breastfed more frequently at 3 months postpartum showed greater subsequent declines in depressive symptomatology over time compared to women who breastfed less frequently, resulting in lower absolute levels of depressive symptoms by 24 months postpartum, controlling for important confounds. In sum, these findings are consistent with a bidirectional association between breastfeeding and depression, with prenatal depression predicting less breastfeeding soon after birth and breastfeeding predicting declines in maternal depression up to 2 years after birth. We discuss mechanisms that could potentially explain these associations and avenues for future research.

Nutritional factors and cross-national postpartum depression prevalence: an updated meta-analysis and meta-regression of 412 studies from 46 countries.

Background: Postpartum depression (PPD) is the most common complication associated with childbirth and can lead to adverse outcomes for both mothers and their children. A previous meta-analysis found that PPD prevalence varies widely across countries. One potential underexplored contributor to this cross-national variation in PPD is diet, which contributes to mental health and varies significantly around the world. Here, we sought to update the global and national estimates of PPD prevalence using systematic review and meta-analysis. Further, we examined whether cross-national variation in PPD prevalence is associated with cross-national variation in diet using meta-regression. Methods: To estimate national rates of PPD prevalence, we conducted an updated systematic review of all papers reporting PPD prevalence using the Edinburgh Postnatal Depression Scale between 2016-2021 and combined our findings with a previous meta-analysis of articles published between 1985-2015. PPD prevalence and methods were extracted from each study. Random effects meta-analysis was used to estimate global and national PPD prevalence. To examine dietary predictors, we extracted data on sugar-sweetened beverage, fruit, vegetable, total fiber, yogurt, and seafood consumption from the Global Dietary Database. Random effects meta-regression was used to test whether between-country and within-country variation in dietary factors predicted variation in PPD prevalence, controlling for economic and methodological variables. Results: 412 studies of 792,055 women from 46 countries were identified. The global pooled prevalence of PPD was 19.18% (95% confidence interval: 18.02 to 20.34%), ranging from 3% in Singapore to 44% in South Africa. Countries that consumed more sugar-sweetened beverages (SSBs) had higher rates of PPD (Coef. = 0.325, p = 0.044, CI:0.010-0.680); Moreover, in years when higher rates of sugar-sweetened beverages were consumed in a country, there were correspondingly higher rates of PPD in that country (Coef. = 0.129, p = 0.026, CI: 0.016-0.242). Conclusion: The global prevalence of PPD is greater than previous calculations, and drastically varies by country. Sugar-sweetened beverage consumption explained some of the national variation in PPD prevalence.

Randomized controlled trial to prevent postpartum depressive symptomatology: An infant carrier intervention.

BACKGROUND: There is a need for effective interventions to reduce symptomatology of postpartum depression. The objective of this study was to test whether providing an ergonomic infant carrier would reduce postpartum depression symptomatology. METHODS: A randomized two-arm, parallel-group trial with 100 participants was conducted between February 2018 and June 2019 in a low-income community. At 30-weeks' gestation, 50 participants were randomly assigned to receive an ergonomic infant carrier and instructions on proper use (intervention group), and 50 participants were assigned to a waitlist (control group). Participants tracked the extent of their infant carrier use and completed the Edinburgh Postpartum Depression Scale (EPDS) to assess postpartum depression symptomatology at 6-weeks postpartum. RESULTS: Participants in the intervention group reported using an infant carrier significantly more often than the control group (ß = 2.69, SE = 0.347, p < .001, 95 % CI = 2.08-3.41). The intervention group reported fewer depressive symptoms at 6-weeks postpartum than the control group (ß = -0.541, p = .042). LIMITATIONS: The sample size was relatively small and thus our results may not be generalizable to the general population. CONCLUSION: Infant carrying may be a cost-effective intervention to reduce postpartum depression symptomatology. Large-scale studies are warranted to further examine the efficacy and cost-effectiveness of providing carriers as an intervention to reduce postpartum depression symptomatology. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov id: NCT04376021. Data Sharing Statement: Deidentified individual participant data will not be made available because we did not obtain permission to share individual data. CLINICAL TRIAL REGISTRATION NUMBER: NCT0437602; https://beta. CLINICALTRIALS: gov/study/NCT04376021.

The Intestinal Tract Brush Border in Young Children Uniformly Expresses Guanylate Cyclase C.

The present study examined staining of guanylate cyclase C (GCC/GUCY2C) in the small and large intestines of children younger than age 7 years. Normal intestinal tissue from children aged 0 to 7 years was stained using GCC, uroguanylin, and villin antibodies and scored for staining intensity. A subset underwent quantitative real-time polymerase chain reaction. Data were analyzed using t test of independent means, descriptive statistics, and logistic regression. Four hundred sixty-four specimens underwent immunohistochemistry; 291 specimens underwent real-time polymerase chain reaction. GCC, villin, and uroguanylin were detected across age groups and anatomic sites. No significant differences were identifiable across age groups. GUCY2C and uroguanylin mRNA was detected in all samples, with no variability of statistical significance of either target-to-villin normalization between any age cohorts. A gradient of expression of GCC across age groups does not seem to exist.

Maternal prenatal cortisol trajectories predict accelerated growth in infancy.

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)1 at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth mixture modeling (GGMM)2 and then used to predict child growth patterns using multilevel modeling. Infants of mothers who had flat cortisol trajectories, characterized by relatively high cortisol in early gestation that plateaus by mid-gestation, experienced more rapid increases in BMIP from birth to 6 months, and had higher BMIPs at 3 and 6 months, than infants whose mothers had the typical slow cortisol rise over gestation, or steep (rapidly accelerating) trajectories. These results suggest that it is not just the total amount of maternal cortisol in pregnancy that shapes early infant growth, but instead the timing and trajectory of prenatal cortisol exposure. To better understand the early origins of obesity risk, future research is needed to investigate the factors that shape mothers' prenatal cortisol trajectories.

Parental factors that impact the ecology of human mammary development, milk secretion, and milk composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 1.

The goal of Working Group 1 in the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to outline factors influencing biological processes governing human milk secretion and to evaluate our current knowledge of these processes. Many factors regulate mammary gland development in utero, during puberty, in pregnancy, through secretory activation, and at weaning. These factors include breast anatomy, breast vasculature, diet, and the lactating parent's hormonal milieu including estrogen, progesterone, placental lactogen, cortisol, prolactin, and growth hormone. We examine the effects of time of day and postpartum interval on milk secretion, along with the role and mechanisms of lactating parent-infant interactions on milk secretion and bonding, with particular attention to the actions of oxytocin on the mammary gland and the pleasure systems in the brain. We then consider the potential effects of clinical conditions including infection, pre-eclampsia, preterm birth, cardiovascular health, inflammatory states, mastitis, and particularly, gestational diabetes and obesity. Although we know a great deal about the transporter systems by which zinc and calcium pass from the blood stream into milk, the interactions and cellular localization of transporters that carry substrates such as glucose, amino acids, copper, and the many other trace metals present in human milk across plasma and intracellular membranes require more research. We pose the question of how cultured mammary alveolar cells and animal models can help answer lingering questions about the mechanisms and regulation of human milk secretion. We raise questions about the role of the lactating parent and the infant microbiome and the immune system during breast development, secretion of immune molecules into milk, and protection of the breast from pathogens. Finally, we consider the effect of medications, recreational and illicit drugs, pesticides, and endocrine-disrupting chemicals on milk secretion and composition, emphasizing that this area needs much more research attention.

Prenatal antibiotic exposure in pregnancy and early childhood socioemotional development.

Background: Antibiotic exposure in pregnancy is associated with reduced microbiome diversity in the infant gut. Given that recent research has shown that early microbiome health can impact child socioemotional development, we examined the relationship between prenatal antibiotic exposure in pregnancy and childhood socioemotional developmental outcomes using a large, nationally representative longitudinal dataset. Methods: A sample of 4800 diverse families were assessed from the population cohort of the Growing Up in New Zealand Study (GUiNZ), which prospectively follows children starting in the last trimester of pregnancy into early childhood. Socioemotional development was measured using a composite score derived from seven commonly used socioemotional tasks administered between 9 months and 4.5 years of child age, addressing emotional expression understanding, regulation of emotions and behavior, and social problem solving and relationship skills. A national comprehensive pharmaceutical database was used to determine children's prenatal antibiotic exposure. Multivariate linear regressions models were used to examine the effects of the timing (trimester) and dosage (number of courses) of prenatal antibiotic exposure on socioemotional development, with and without statistically adjusting for confounding factors addressing maternal health, socioeconomic status, maternal age, and child sex. Results: In unadjusted analyses, antibiotic exposure was inversely associated with child socioemotional development. However, after statistically adjusting for important confounds, socioemotional development was not associated with prenatal antibiotic exposure at any dosage or trimester of pregnancy (all ß ≤ -0.02). Conclusion: Prenatal antibiotic exposure does not appear to impact early childhood socioemotional development. Maternal health and sociodemographic factors are confounded with antibiotic exposure and socioemotional development, a fact that should be considered in future research examining the effects of prenatal antibiotic exposure on child health. These findings may be reassuring to families who are concerned about the long-term effects of antibiotics in pregnancy on child health outcomes.

The IgA in milk induced by SARS-CoV-2 infection is comprised of mainly secretory antibody that is neutralizing and highly durable over time.

Approximately 10% of infants infected with SARS-CoV-2 will experience COVID-19 illness requiring advanced care. A potential mechanism to protect this population is passive immunization via the milk of a previously infected person. We and others have reported on the presence of SARS-CoV-2-specific antibodies in human milk. We now report the prevalence of SARS-CoV-2 IgA in the milk of 74 COVID-19-recovered participants, and find that 89% of samples are positive for Spike-specific IgA. In a subset of these samples, 95% exhibited robust IgA activity as determined by endpoint binding titer, with 50% considered high-titer. These IgA-positive samples were also positive for Spike-specific secretory antibody. Levels of IgA antibodies and secretory antibodies were shown to be strongly positively correlated. The secretory IgA response was dominant among the milk samples tested compared to the IgG response, which was present in 75% of samples and found to be of high-titer in only 13% of cases. Our IgA durability analysis using 28 paired samples, obtained 4-6 weeks and 4-10 months after infection, found that all samples exhibited persistently significant Spike-specific IgA, with 43% of donors exhibiting increasing IgA titers over time. Finally, COVID-19 and pre-pandemic control milk samples were tested for the presence of neutralizing antibodies; 6 of 8 COVID-19 samples exhibited neutralization of Spike-pseudotyped VSV (IC50 range, 2.39-89.4ug/mL) compared to 1 of 8 controls. IgA binding and neutralization capacities were found to be strongly positively correlated. These data are highly relevant to public health, not only in terms of the protective capacity of these antibodies for breastfed infants, but also for the potential use of such antibodies as a COVID-19 therapeutic, given that secretory IgA is highly in all mucosal compartments.