Maternal worry of children contracting COVID-19 predicts vaccine uptake in young children in Vermont.

Background: Young children, 6 months to 4 years of age, were the last population for whom the COVID-19 vaccines became available and remain the group with the lowest uptake. Scarce information exists on drivers of vaccine uptake in young children. The relationship between parental perceived risk of infection and child COVID-19 vaccination is unknown. Objective: Examine the association between perceived risk of infection and early childhood vaccination. Methods: In June 2020, perinatal women in Vermont were enrolled in a longitudinal survey study assessing life changes during the pandemic. Surveys included worry of infection, Parents Attitude about Childhood Vaccines (PACV), intention to vaccinate children with the COVID-19 vaccine, and masking behaviors. Once vaccines became available, surveys also included child vaccination status. A demographic-adjusted stepwise logistic regression was conducted to assess the relationship of worry of infection and vaccine hesitancy on child vaccination status. Results: 85 women completed baseline and follow up surveys. Participants were highly adherent to adult COVID vaccines with 93 % at least partially vaccinated and only 3 % demonstrated general childhood vaccine hesitancy on the PACV. However, in this highly adherent population, only 61 % of young children are vaccinated. In univariate [OR = 7.35 95 % CI (2.70 to 20.02)] and demographic adjusted [OR = 6.03 95 % CI (1.30 to 27.90)] models, current worry about child infection was associated with higher odds of child vaccination. Previously established predictors, vaccine hesitancy [OR = 0.91 95 % CI (0.84 to 0.99)] and younger maternal age [OR = 1.33 95 % CI (1.07 to 1.65)] were again associated lower odds of child vaccination. Conclusion: Among vaccine adherent parents, worry of infection was a strong predictor of vaccine uptake. Continued efforts to articulate the potential morbidity of COVID in young children, along with established methods to address general vaccine hesitancy may aid in COVID vaccine uptake in this population.

Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products.

Cannabinoid use in all populations is increasing as legalization across the United States continues. Concerningly, there is a lack of caution provided by medical providers to pregnant individuals as to the impact the use of cannabinoids could have on the developing fetus. Research continues in both the preclinical and clinical areas, and is severely needed, as the potency of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has increased dramatically since the initial studies were completed. Thus far, clinical studies raise compelling evidence for short term memory deficits, impulse control issues, and attention deficiencies following prenatal cannabinoid exposure (PCE). These changes may be mediated through epigenetic modifications that not only impact the current offspring but could carry forward to future generations. While additional studies are needed, a pregnancy pause from cannabinoid products should be strongly recommended by providers to ensure the optimal health and well-being of our future generations.

Maternal perceived stress and infant behavior during the COVID-19 pandemic.

BACKGROUND: Maternal stress has negative consequences on infant behavioral development, and COVID-19 presented uniquely stressful situations to mothers of infants born during the pandemic. We hypothesized that mothers with higher levels of perceived stress during the pandemic would report higher levels of infant regulatory problems including crying and interrupted sleep patterns. METHODS: As part 6 sites of a longitudinal study, mothers of infants born during the pandemic completed the Perceived Stress Scale, the Brief Infant Sleep Questionnaire, and an Infant Crying survey at 6 (n = 433) and 12 (n = 344) months of infant age. RESULTS: Maternal perceived stress, which remained consistent at 6 and 12 months of infant age, was significantly positively correlated with time taken to settle infants. Although maternal perceived stress was not correlated with uninterrupted sleep length, time taken to put the infant to sleep was correlated. Perceived stress was also correlated with the amount of infant crying and fussiness reported at 6 months. CONCLUSIONS: Mothers who reported higher levels of perceived stress during the pandemic reported higher levels of regulatory problems, specifically at 6 months. Examining how varying levels of maternal stress and infant behaviors relate to overall infant developmental status over time is an important next step. IMPACT: Women giving birth during the COVID-19 pandemic who reported higher levels of stress on the Perceived Stress Scale also reported higher levels of infant fussiness and crying at 6 months old, and more disruptive sleep patterns in their infants at 6 months and 12 months old. Sleeping problems and excessive crying in infancy are two regulatory problems that are known risk factors for emotional and behavioral issues in later childhood. This paper is one of the first studies highlighting the associations between maternal stress and infant behaviors during the COVID-19 pandemic.

Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic.

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

Persistently low readiness to vaccinate young children against COVID among vaccine adherent mothers in Vermont, USA.

Young children (0-4 years) represent the next population in whom the SARS-CoV-2 (COVID) vaccine will be available. Addressing parental feelings about vaccination will be important to optimize uptake. In this study, online surveys were administered in 78 perinatal women in the Northeast United States (Vermont) between January and July 2021. Women reported vaccine intention by indicating their plans to have their child vaccinated. Response choices included vaccinate as soon as possible, vaccinate but not immediately, or no intention to vaccinate. Subsequently, women rated their readiness to vaccinate children if offered the COVID vaccine tomorrow on an 11-point scale from 0 (definitely not get the vaccine) to 10 (definitely get the vaccine). Factors influencing ratings were measured categorically. General vaccine hesitancy was measured with the Parent Attitudes about Childhood Vaccinations scale. While many individual participants changed readiness to vaccinate children between baseline and follow-up; readiness in the study cohort remained unchanged. Approximately 50% of participants were likely to have their young children vaccinated. Concerns about vaccine safety was the largest driver of hesitancy. Importantly, even in a cohort highly adherent to childhood vaccines, hesitancy toward general childhood vaccines predicted decreased readiness for young children to receive the COVID vaccine. Our data provide evidence that maternal attitudes about the COVID vaccine are not fixed but overall readiness remains low, that prior adherence to childhood vaccine schedules will not predict vaccine behavior related to the COVID vaccine, and that public health messaging should emphasize messaging targeting vaccine safety in children.

Prenatal cannabis exposure predicts attention problems, without changes on fMRI in adolescents.

OBJECTIVES: We hypothesized that prenatal cannabis exposure (PCE) would be associated with increased attention problems and altered neurocognition in young adolescents. METHODS: Data were obtained from the Adolescent Brain Cognitive Development (ABCD study®), a cohort of approximately 12,000 children. Presence or absence of PCE after knowledge of pregnancy was measured by caregiver report. All participants with PCE (N = 224) were included and compared to two control groups; those matched on tobacco and alcohol exposure and those without prenatal tobacco or alcohol exposures. Outcomes were measured with the ABCD baseline assessment when participants were 9-10 years old and included attention, internalizing, externalizing and total problems scales on the Child Behavior Checklist (CBCL). Teacher reports were used when available. Mixed effects modeling assessed the association between PCE and outcomes controlling for parental psychopathology, prematurity and socioeconomic status. For participants with available data, patterns of brain activity during three fMRI tasks (the Stop Signal Task measuring response inhibition, the Monetary Incentive Delay (MID) task measuring reward processing and the EN-Back task measuring working memory) were analyzed using Permutation Analyses of the Linear Model. RESULTS: Compared to both control groups, participants with PCE had significantly higher attention problems, externalizing, and total problem scores. PCE did not impact cognitive performance or patterns of brain activation during fMRI tasks. CONCLUSIONS: There are long-term associations between PCE and early adolescent attention and behavioral problems. These are not reflected in cognitive performance or task fMRI measures, a finding that is consistent with reports that fewer than half of children with ADHD have any specific cognitive deficit (Nigg et al., 2005; Willcutt et al., 2005). The young age of the sample may also relate to this finding and future investigation of neurodevelopmental trajectories of youth with PCE is warranted.

Behavioral coping phenotypes and associated psychosocial outcomes of pregnant and postpartum women during the COVID-19 pandemic.

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

Factors associated with parent views about participation in infant MRI research provide guidance for the design of the Healthy Brain and Child Development (HBCD) study.

PURPOSE: The National Institutes of Health announced the Healthy Brain and Child Development (HBCD) study to further understanding of infant brain development. This study examined perceptions and knowledge about research among the demographic groups to be studied in HBCD. METHOD: 1164 participants (n = 548 pregnant people and 616 mothers of infants < 12 months) completed anonymous, on-line surveys. Domains included research literacy, MRI knowledge, and attitudes about research incentives and biospecimen collection. Logistic regression was used to examine factors related to outcome variables. RESULTS: Knowledge of MRI safety was low and research literacy was high across participants. Likelihood of participation given various incentives differed between participants. Those with lower education were less likely to rate any items as increasing likelihood of participation. Substance use during pregnancy improved the model fit only for items about alternate visit structures (home and telephone visits) and confidentiality. CONCLUSION: Overall results support the feasibility of infant imaging studies, such as HBCD with respondents having high research literacy and interest in learning about their baby's development. Educating potential participants about MRI safety and providing flexible incentives for participation will improve the success of infant MRI studies.

Effects of depression, anxiety and screen use on adolescent substance use.

The current study examined relations between depression risk, anxiety risk, screen time and substance use among adolescents receiving SBIRT services. Between October 2018 and June 2020, 1701 youth ages 12 to 17 received SBIRT services (47% male, 24.2% non-white). SBIRT screening included the completion of the Patient Health Questionnaire for depression risk, Generalized Anxiety Disorder-7 item scale, a question on average amount of screen time daily, and the S2BI for substance use. Analyses included t-tests and chi-squares to examine demographic differences across variables, bivariate correlations among independent variables to assess for use within regression analyses, and stepwise linear regressions to examine relations between depression risk, anxiety risk, screen time and substance use. Analyses were examined using the full sample as well as those who scored positive for mild mental health symptoms. Median screen time was 3 to 4 h daily, 29% met criteria for mental health problems or risky substance use with high comorbidity of depression and anxiety risk. Findings demonstrated a significant risk of increased substance use associated with depression risk, severe anxiety risk, and screen time. Anxiety risk alone was not related to substance use risk when accounting for depression risk. Routine screening for depression, other mental health concerns, screen time and substance use is critical in supporting adolescent health and development, especially given comorbidity and their relative contributions. Interventions aimed at decreasing screen time, and identifying mental health problems may aid in decreasing substance use risk in adolescents.

Are we underestimating overweight and obesity prevalence in children?

OBJECTIVE: To objectively determine the prevalence of overweight and obesity in elementary school children in two rural counties in Vermont prior to implementing a community-based intervention. METHODS: School-based objective measures of body mass index (BMI) were obtained from 1,688 public school children in first, third, and fifth grades in two Northern Vermont counties in the Fall of 2017. RESULTS: Forty-one percentage of elementary school children were either overweight or obese, nearly double the estimated Vermont prevalence rate of 22.2%. Schools located in more rural areas showed higher levels of overweight and obesity in children than schools in less rural areas in these northern counties (p < .005). CONCLUSIONS: Indirect and self-reported measures of BMI may be underestimating the true prevalence of overweight and obesity particularly in more rural communities. POLICY IMPLICATIONS: Data presented here in which children were measured directly by trained study staff demonstrate that the prevalence of obesity among children in elementary school is alarmingly high. Accurate, ongoing BMI measurement surveillance is one tool to better understand both the current trends in childhood overweight and obesity and the effect of community and state interventions.

Evaluation and Management of Febrile Children: A Review.

IMPORTANCE: Management of febrile children is an intrinsic aspect of pediatric practice. Febrile children account for 15% of emergency department visits and outcomes range from the presence of serious bacterial infection to benign self-limited illness. OBSERVATIONS: Studies from 1979 to 2015 examining febrile infants and children were included in this review. Management of febrile infants younger than 90 days has evolved considerably in the last 30 years. Increased rates of Escherichia coli urinary tract infections, increasing resistance to ampicillin, and advances in viral diagnostics have had an effect on the approach to caring for these patients. Widespread vaccination with conjugate vaccines against Haemophilus influenzae and Streptococcus pneumoniae has virtually eliminated the concern for bacterial infections in children aged 3 to 36 months. Urinary tract infections still remain a concern in febrile infants of all ages. CONCLUSIONS AND RELEVANCE: Advances over the last 30 years allow for more precise risk stratification for infants at high risk of serious bacterial infection. With appropriate testing at the initial visit, much of the diagnostic testing and empirical treatment can be avoided for infants younger than 90 days. In the vaccinated child aged 3 to 36 months, the only bacterial infection of concern is urinary tract infection.

New Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy.

OBJECTIVE: The purpose of this article is to compare the recently published revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1) to the original guidelines (RECIST 1.0) for advanced non-small cell lung cancer (NSCLC) after erlotinib therapy and to evaluate the impact of the new CT tumor measurement guideline on response assessment. MATERIALS AND METHODS: Forty-three chemotherapy-naive patients with advanced NSCLC treated with erlotinib in a single-arm phase 2 multicenter open-label clinical trial were retrospectively studied. CT tumor measurement records using RECIST 1.0 that were generated as part of the prospective clinical trial were reviewed. A second set of CT tumor measurements was generated from the records to meet RECIST 1.1 guidelines. The number of target lesions, best response, and time to progression were compared between RECIST 1.1 and RECIST 1.0. RESULTS: The number of target lesions according to RECIST 1.1 decreased in 22 patients (51%) and did not change in 21 patients (49%) compared with the number according to RECIST 1.0 (p < 0.0001, paired Student's t test). Almost perfect agreement was observed between best responses using RECIST 1.1 and RECIST 1.0 (weighted kappa = 0.905). Two patients with stable disease according to RECIST 1.0 had progressive disease according to RECIST 1.1 criteria because of new lesions found on PET/CT. There was no significant difference in time to progression between RECIST 1.1 and RECIST 1.0 (p = 1.000, sign test). CONCLUSION: RECIST 1.1 provided almost perfect agreement in response assessment after erlotinib therapy compared with RECIST 1.0. Assessment with PET/CT was a major factor that influenced the difference in best response assessment between RECIST 1.1 and RECIST 1.0.

EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non-small cell lung carcinoma than FISH, CISH, and immunohistochemistry.

About 10% of patients with non-small cell lung carcinoma (NSCLC) respond to epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs). More than 75% of "responders" have activating mutations in EGFR. However, mutation analysis is not widely available, and proposed alternatives (in situ hybridization and immunohistochemical analysis) have shown inconsistent associations with outcome. Fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), immunohistochemical analysis, and DNA sequencing were compared in this study of 40 NSCLC samples from TKI-treated patients. Response rates were 12 of 19 in EGFR-mutant vs 1 of 20 EGFR wild-type tumors (P = .0001), 7 of 19 FISH+ vs 4 of 17 FISH- tumors (not significant [NS]), 5 of 16 CISH+ vs 6 of 21 CISH- tumors (NS), and 3 of 9 immunohistochemically positive vs 7 of 22 immunohistochemically negative tumors (NS). EGFR mutation was associated with improved progression-free survival (P = .0004). Increased copy number (FISH or CISH) and protein expression (immunohistochemical) did not independently predict outcome. Thus, EGFR sequence analysis was the only method useful for predicting response and progression-free survival following TKI therapy in NSCLC.

Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials.

PURPOSE: The impact of epidermal growth factor receptor (EGFR) and KRAS genotypes on outcomes with erlotinib or gefitinib therapy continues to be debated. This study combines patient data from five trials in predominantly Western populations to assess the impact of EGFR and KRAS mutations on first-line therapy with an EGFR-tyrosine kinase inhibitor (TKI) and compare clinical versus molecular predictors of sensitivity. EXPERIMENTAL DESIGN: Chemotherapy-naïve patients with advanced non-small cell lung cancer and known EGFR mutation status treated with erlotinib or gefitinib monotherapy as part of a clinical trial were eligible for inclusion. Patients received daily erlotinib (150 mg) or gefitinib (250 mg) until disease progression or unacceptable toxicity. Data were collected in a password-protected web database. Clinical outcomes were analyzed to look for differences based on EGFR and KRAS genotypes, as well as clinical characteristics. RESULTS: Patients (223) from five clinical trials were included. Sensitizing EGFR mutations were associated with a 67% response rate, time to progression (TTP) of 11.8 months, and overall survival of 23.9 months. Exon 19 deletions were associated with longer median TTP and overall survival compared with L858R mutations. Wild-type EGFR was associated with poorer outcomes (response rate, 3%; TTP, 3.2 months) irrespective of KRAS status. No difference in outcome was seen between patients harboring KRAS transition versus transversion mutations. EGFR genotype was more effective than clinical characteristics at selecting appropriate patients for consideration of first-line therapy with an EGFR-TKI. CONCLUSION: EGFR mutation status is associated with sensitivity to treatment with an EGFR-TKI in patients with advanced non-small cell lung cancer. Patients harboring sensitizing EGFR mutations should be considered for first-line erlotinib or gefitinib.

Treatment of peritoneal mesothelioma in pediatric patients.

Peritoneal mesothelioma is a rare and often aggressive malignancy, mostly affecting asbestos exposed adults. We present four pediatric peritoneal cases treated with a cisplatin-based doublet regimen, the standard of care in the systemic therapy of adult mesothelioma. Treatment was well tolerated, and three of these patients have achieved long-term survival. The fathers of three of the patients worked in the construction industry and may have been the source of indirect asbestos exposure.