Neuromuscular and cardiovascular phenotypes in paediatric titinopathies: a multisite retrospective study.

BACKGROUND: Pathogenic variants in TTN cause a spectrum of autosomal dominant and recessive cardiovascular, skeletal muscle and cardioskeletal disease with symptom onset across the lifespan. The aim of this study was to characterise the genotypes and phenotypes in a cohort of TTN+paediatric patients. METHODS: Retrospective chart review was performed at four academic medical centres. Patients with pathogenic or truncating variant(s) in TTN and paediatric-onset cardiovascular and/or neuromuscular disease were eligible. RESULTS: 31 patients from 29 families were included. Seventeen patients had skeletal muscle disease, often with proximal weakness and joint contractures, with average symptom onset of 2.2 years. Creatine kinase levels were normal or mildly elevated; electrodiagnostic studies (9/11) and muscle biopsies (11/11) were myopathic. Variants were most commonly identified in the A-band (14/32) or I-band (13/32). Most variants were predicted to be frameshift truncating, nonsense or splice-site (25/32). Seventeen patients had cardiovascular disease (14 isolated cardiovascular, three cardioskeletal) with average symptom onset of 12.9 years. Twelve had dilated cardiomyopathy (four undergoing heart transplant), two presented with ventricular fibrillation arrest, one had restrictive cardiomyopathy and two had other types of arrhythmias. Variants commonly localised to the A-band (8/15) or I-band (6/15) and were predominately frameshift truncating, nonsense or splice-site (14/15). CONCLUSION: Our cohort demonstrates the genotype-phenotype spectrum of paediatric-onset titinopathies identified in clinical practice and highlights the risk of life-threatening cardiovascular complications. We show the difficulties of obtaining a molecular diagnosis, particularly in neuromuscular patients, and bring awareness to the complexities of genetic counselling in this population.

Prenatal and postpartum care during the COVID-19 pandemic: An increase in barriers from early to mid-pandemic in the United States.

BACKGROUND: The COVID-19 pandemic led to changes in the provision of pregnancy and postpartum care. The purpose of this study was to describe changes in access to prenatal and postpartum care over time, from early in the pandemic (July 2020) to mid-pandemic (January 2021) and to explore socioeconomic and COVID-19-related economic factors associated with experiencing barriers to care. METHODS: We recruited two cross sections of women and birthing people in the US in July 2020 (N = 4645) and January 2021 (N = 3343) using Facebook and Instagram Ads. RESULTS: Three out of four women in the prenatal period and four out of five women in the postpartum period reported barriers to scheduling a visit. The likelihood of not having a visit (OR = 4.44, 95% CI 2.67-7.40), being unable to schedule a visit (OR = 2.73, 95% CI 1.71-4.35), and not being offered visits (OR = 4.26, 95% CI 2.32-7.81) increased over time. Participants were more likely to report barriers attending scheduled prenatal or postpartum appointments over time (OR = 2.72, 95% CI 2.14-3.45). Women who experienced more economic impacts from COVID-19 were older, less educated, and were Black, Indigenous, or a person of color, and were more likely to have barriers to attending appointments. CONCLUSIONS: Certain subgroups are more at risk during COVID-19, and around 9 months into the pandemic, women were not only still facing barriers to care, but these had been amplified. Additional research using other data sources is needed to identify and ameliorate barriers and inequalities in access to prenatal and postpartum care that appear to have persisted throughout the pandemic.

Contraceptive care in the United States during the COVID-19 pandemic: A social media survey of contraceptive access, telehealth use and telehealth quality.

OBJECTIVES: To examine demographic, socioeconomic, and regional differences in contraceptive access, differences between telehealth and in-person contraception visits, and telehealth quality in the United States during the COVID-19 pandemic. STUDY DESIGN: We surveyed reproductive-age women about contraception visits during the COVID-19 pandemic via social media in July 2020 and January 2021. We used multivariable regression to examine relationships between age, racial/ethnic identity, educational attainment, income, insurance type, region, and COVID-19 related hardship, and ability to obtain a contraceptive appointment, telehealth vs in-person visits, and telehealth quality scores. RESULTS: Among 2031 respondents seeking a contraception visit, 1490 (73.4%) reported any visit, of which 530 (35.6%) were telehealth. In adjusted analyses, lower odds of any visit was associated with Hispanic/Latinx and Mixed race/Other identity (aOR 0.59 [0.37-0.94], aOR 0.36 [0.22-0.59], respectively), the South, Midwest, Northeast (aOR 0.63 [0.47-0.85], aOR 0.64 [0.46-0.90], aOR 0.52 [CI 0.36-0.75], respectively), no insurance (aOR 0.63 [0.43-0.91]), greater COVID-19 hardship (aOR 0.52 [0.31-0.87]), and earlier pandemic timing (January 2021 vs July 2020 aOR 2.14 [1.69-2.70]). Respondents from the Midwest and South had lower odds of telehealth vs in-person care (aOR 0.63 [0.44-0.88], aOR 0.54 [0.40-0.72], respectively). Hispanic/Latinx respondents and those in the Midwest had lower odds of high telehealth quality (aOR 0.37 [0.17-0.80], aOR 0.58 [0.35-0.95], respectively). CONCLUSIONS: We found inequities in contraceptive care access, less telehealth use for contraception visits in the South and Midwest, and lower telehealth quality among Hispanic/Latinx people during the COVID-19 pandemic. Future research should focus on telehealth access, quality, and patients' preferences. IMPLICATIONS: Historically marginalized groups have faced disproportionate barriers to contraceptive care, and telehealth for contraceptive care has not been employed equitably during the COVID-19 pandemic. Though telehealth has the potential to improve access to care, inequitable implementation could exacerbate existing disparities.

Prioritizing patient experience: Validation of the person-centered contraceptive counseling measure as a performance measure.

OBJECTIVE: A performance measure assessing how often patients experience patient-centered contraceptive counseling can inform quality improvement in contraceptive care and enable efforts to enhance equity in the provision of this care. We sought to test the validity and reliability of the Person-Centered Contraceptive Counseling (PCCC) measure as a performance measure, in preparation for application for endorsement from the National Quality Forum. STUDY DESIGN: We combined data from two research studies, a statewide quality improvement assessment, and a dedicated data collection effort at nine sites, all collected between 2009 and 2019 at 22 total sites in the United States, to evaluate the validity and reliability of the four-item PCCC measure aggregated at the provider and facility level. We scored the PCCC dichotomously as a "top-box" score of 20 versus less than 20. We assessed reliability using the Spearman-Brown coefficient, and validity by comparing scores on the PCCC to aggregated scores on single-item measures of patient satisfaction. RESULTS: We included 22 facilities and 34 providers in the analyses. The average PCCC top-box score by provider and facility was 81% and 79%, respectively. We found adequate reliability with panel sizes of 20-50. PCCC scores were strongly associated with the single-item measures of satisfaction. There were notable disparities by race/ethnicity and language (Spanish vs English) in PCCC scores. DISCUSSION: The PCCC is a valid and reliable performance measure for use at the provider and facility level. The development and use of the measures of patient experience, like the PCCC, is critical for prioritizing patient-centeredness in reproductive health care. IMPLICATIONS: The PCCC measure can facilitate the identification of gaps and disparities in patient-centered contraceptive counseling and enable quality improvement to promote quality, equitable contraceptive care. Using this measure provides the opportunity to enhance patient experience of care and build trust between contraceptive providers and the communities they serve.

Quality of prenatal and postpartum telehealth visits during COVID-19 and preferences for future care.

BACKGROUND: At the start of the COVID-19 pandemic, telehealth practices for pregnancy-related care were rapidly implemented. Telehealth for pregnancy-related care is likely to continue after the pandemic. In order for health systems and clinicians to provide person-centered pregnancy-related care via telehealth, it is critical to understand patients' telehealth experiences and their preferences regarding the use of telehealth moving forward. OBJECTIVE: This study aimed to describe perceived quality of prenatal and postpartum telehealth visits during COVID-19 and to examine the association between telehealth quality during the pandemic and future telehealth preferences. STUDY DESIGN: We used data from of an online sample of US women aged 18 to 45 years seeking reproductive health care during COVID-19. Two cross-sections of survey data were collected in July 2020 and January 2021. This analysis included those who sought prenatal (n=1496) or postpartum (n=482) care during the pandemic. Among those who had a prenatal or postpartum telehealth visit, we used multivariable logistic regression to examine the association between a measure of perceived telehealth quality and openness to future telehealth visits, adjusting for sociodemographic characteristics. RESULTS: A total of 57.5% of prenatal and 52.9% of postpartum respondents had a telehealth appointment. Respondents agreed with most statements about the quality of their telehealth appointments, with ≥80% reporting that they were convenient, easy, safe, and provided good information. Lower-ranked quality items were related to visits feeling personal and the patient feeling cared for. A total of 35.2% of prenatal (n=816) and 43.3% of postpartum (n=231) respondents expressed openness to telehealth visits in the future. Prenatal and postpartum respondents reporting higher telehealth quality had increased odds of being open to telehealth in the future (prenatal: adjusted odds ratio, 1.2; 95% confidence interval, 1.2-1.3; postpartum: adjusted odds ratio, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSION: Prenatal and postpartum respondents with better telehealth experiences were more likely to express openness to telehealth in the future, although most preferred future in-person visits. As pregnancy-related telehealth continues, it is important to offer appointment options that match patient preferences, especially populations that face barriers in access to care, and to explore ways to personalize care and support positive patient-provider relationships.

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum.

An Initiative "that you do for one person": Identifying Barriers and Facilitators to Implementing an Immediate Postpartum LARC Initiative in Florida Hospitals.

INTRODUCTION: In the United States (U.S.), perinatal quality improvement collaboratives have pursued implementing immediate postpartum long-acting reversible contraception (LARC) initiatives to increase people's access to contraception and support their fertility desires. This process evaluation aimed to identify barriers and facilitators to implementing an immediate postpartum LARC initiative in Florida. METHODS: Data collection included in-depth qualitative assessments (i.e., interviews, small focus group discussions) with hospitals in pre- and early stages of the implementation process. Snowball sampling was used to recruit participants. Interviews were conducted in-person or via Zoom or phone and were audio-recorded and transcribed verbatim. Four of the five domains within the Consolidated Framework for Implementation Research (e.g., process, intervention characteristics, inner and outer settings) informed the study design and data collection/analysis. RESULTS: Fourteen staff of diverse job roles from five hospitals participated. Factors that facilitated implementation were the strength of the evidence, relative advantage, internal and external networks, and engaging staff. Barriers to implementation included billing and reimbursement and needing significant support from external networks to progress through implementation phases. DISCUSSION: Findings suggest that depending on the task or phase, multiple factors work in tandem to serve as implementation barriers and facilitators. Additionally, evaluating hospitals' progress at the pre- and early implementation phases was critical for quickly finding solutions and benefited other hospitals in different stages. As this initiative requires substantial support, health systems should create and sustain a culture of excellence and efficiency to facilitate implementing initiatives that improve care quality.

Georgia state spinal muscular atrophy newborn screening experience: Screening assay performance and early clinical outcomes.

The purpose of this study is to provide the results of the newborn screening (NBS) program for Spinal Muscular Atrophy (SMA) in the state of Georgia to determine disease incidence, time to diagnosis and treatment, and early outcomes. NBS for SMA was performed using real time PCR assays from February 2019 through February 2020 in a pilot phase of screening. This method continued as part of our official state panel, and here we describe the pilot period as well as the first year of standard screening through February 2021. Medical records of infants with a positive NBS were reviewed for time to confirmation and neurologic evaluation, SMN2 copy number, clinical information, and treatment. Descriptive statistics were applied. Of the 301,418 samples screened, there were 15 true positive (eight males) and 24 false positive cases. One patient was missed due to human error early in the pilot phase and presented after symptom onset. The incidence of SMA in Georgia is approximately 1 in 18,840 births per year. After the pilot phase, the false positive rate was found to be so low that all patients who test positive were immediately referred to neurology for further care. Four patients died prior to intervention. Ten patients received intervention. Gene therapy was the preferred treatment. One patient was lost to follow-up; another was clinically followed. In conclusion, trends for treated patients show improved or stable motor function. Long-term follow-up will help determine the durability of treatment.

Community perspectives on pharmacist-prescribed hormonal contraception in rural California.

OBJECTIVES: In the United States, numerous states have enabled pharmacists to prescribe hormonal contraception. Little research focuses on the perspectives of potential users of this service in rural communities. This study sought to describe awareness of, interest in, acceptability of, and support for pharmacist-prescribed contraception in a rural California county. STUDY DESIGN: We conducted a community-based survey in 2019-20 in Tulare County, California. Researchers partnered with community members to design, implement, and analyze the survey. We recruited respondents who were ages 15 to 44 and assigned female sex at birth, using passive community-based approaches, social media advertisements, and social networks. Analyses focused on 177 respondents with a potential future need for contraception. RESULTS: Thirty-one percent of respondents were aware that pharmacists could prescribe hormonal contraception in California, with more accurate knowledge among older respondents (p = 0.015). After receiving brief educational information about pharmacist-prescribed contraception, respondents expressed high levels of support and acceptability: they perceived pharmacist-prescribed contraception to be safe, time saving, and more convenient. Respondents were more comfortable talking about contraception with traditional contraceptive care providers compared to asking pharmacists questions about contraception. Fifty-seven percent were somewhat or very interested in obtaining contraception from a pharmacist, with higher levels of interest among those who preferred to use a different method. CONCLUSION: Awareness of pharmacist-prescribed contraception in a rural California community was low, though people are supportive of and interested in utilizing this service. This research suggests that increased availability of pharmacist-prescribed contraception could support individuals' reproductive self-determination and address gaps in access. IMPLICATIONS: Despite limited awareness of pharmacist-prescribed contraception, interest in using and community support for this service was high in a rural California community. This analysis suggests that increased availability of pharmacist-prescribed contraception could support reproductive self-determination and address access barriers, particularly for people whose contraceptive needs are not currently being met.

Coercion and non-consent during birth and newborn care in the United States.

In the United States, Black, Indigenous, and People of Color (BIPOC) experience more adverse health outcomes and report mistreatment during pregnancy and birth care. The rights to bodily autonomy and consent are core components of high-quality health care. To assess experiences of coercion and nonconsent for procedures during perinatal care among racialized service users in the United States, we analyzed data from the Giving Voice to Mothers (GVtM-US) study. METHODS: In a subset analysis of the full sample of 2700, we examined survey responses for participants who described the experience of pressure or nonconsented procedures or intervention during perinatal care. We conducted multivariable logistic regression analyses by racial and ethnic identity for the outcomes: pressure to have perinatal procedures (eg, induction, epidurals, episiotomy, fetal monitoring), nonconsented procedures performed during perinatal care, pressure to have a cesarean birth, and nonconsented procedures during vaginal births. RESULTS: Among participants (n = 2490), 34% self-identified as BIPOC, and 37% had a planned hospital birth. Overall, we found significant differences in pressure and nonconsented perinatal procedures by racial and ethnic identity. These inequities persisted even after controlling for contextual factors, such as birthplace, practitioner type, and prenatal care context. For example, more participants with Black racial identity experienced nonconsented procedures during perinatal care (AOR 1.89, 95% CI 1.35-2.64) and vaginal births (AOR 1.87, 95% CI 1.23-2.83) than those identifying as white. In addition, people who identified as other minoritized racial and ethnic identities reported experiencing more pressure to accept perinatal procedures (AOR 1.55, 95% CI 1.08-2.20) than those who were white. DISCUSSION: There is a need to address human rights violations in perinatal care for all birthing people with particular attention to the needs of those identifying as BIPOC. By eliminating mistreatment in perinatal care, such as pressure to accept services and nonconsented procedures, we can help mitigate long-standing inequities.

Reimagining Preexposure Prophylaxis Provision for Women in the United States.

Structural determinants of health drive inequities in the acquisition of human immunodeficiency virus (HIV) and the use of preexposure prophylaxis (PrEP) for HIV prevention among cisgender women in the United States. However, current PrEP clinical guidance and implementation paradigms largely focus on individual behaviors and characteristics, resulting in missed opportunities to improve PrEP access, and the implicit transferring of prevention work from health systems to individuals. In this viewpoint article, we outline ways to apply a structural lens to clinical guidance and PrEP implementation for women and propose areas for future work.

Health literacy needs and preferences for a technology-based intervention to improve college students' sexual and reproductive health.

Objective: To explore health literacy needs and preferences for a technology-based intervention (app) to improve sexual and reproductive health (SRH) among college students.Participants: In Spring 2019, in-depth interviews were conducted with 20 participants (10 male, 10 female) from a large, public university.Methods: Interview guide was developed based on Integrated Model of Health Literacy domains and Diffusion of Innovation constructs. Data were analyzed in MaxQDA using applied thematic analysis.Results: Dominant themes included accessing health information and services, evaluating options to make decisions, intervention utility and characteristics, and the emergent theme of credibility. Specific topics included accessing STI testing, contraceptive decision making, information on human papillomavirus (HPV) and the HPV vaccine, patient-provider communication, app design and function elements, and modifying the app to meet the SRH needs of diverse college students.Conclusions: Findings identified areas where an app could address college students' SRH literacy, ultimately improving SRH outcomes among this population.Supplemental data for this article can be accessed online at https://doi.org/10.1080/07448481.2022.2040517 .

Predictors of COVID-19 Vaccination Likelihood Among Reproductive-Aged Women in the United States.

OBJECTIVES: Vaccination for COVID-19 is an effective method of preventing complications; however, studies suggest that public attitudes toward the vaccine are heterogeneous. The objective of our study was to identify predictors for low likelihood of COVID-19 vaccination among women in the United States and determine whether reasons for low intention were modified by race, ethnicity, or other characteristics to better understand the factors that shape attitudes toward the COVID-19 vaccine and help inform multilevel interventions. METHODS: In January 2021, we used social media to recruit a cross-section of reproductive-aged women in the United States (N = 5269). Our primary outcome was self-reported low vaccination likelihood (responses of unlikely or very unlikely on a 5-item scale). Our secondary outcome was concerns influencing vaccination decision that participants selected from a list of 19 items. We estimated multivariable logistic regression models and controlled for respondents' sociodemographic characteristics. RESULTS: Overall, race and ethnicity, educational attainment, health insurance type, annual household income, partnership status, and US region were associated with low vaccine likelihood. The adjusted odds of reporting low likelihood were 1.83 (95% CI, 1.45-2.32) times greater among non-Hispanic Black than among non-Hispanic White participants. Among pregnant or postpartum participants, breastfeeding status was the strongest predictor (adjusted odds ratio = 2.77; 95% CI, 2.02-3.79). CONCLUSIONS: Vaccine hesitancy and concerns may exacerbate existing COVID-19 health disparities in racial and ethnic groups and highlight the need to target messaging to specific populations, including pregnant and breastfeeding women, because these populations are at high risk for COVID-19 complications.

Exploring the impact of mifepristone's risk evaluation and mitigation strategy (REMS) on the integration of medication abortion into US family medicine primary care clinics✰,✰✰.

OBJECTIVES: In 2000, the United States' Food and Drug Administration (FDA) approved mifepristone for medication abortion. In this article, we explore how the Risk Evaluation and Mitigation Strategy (REMS) criteria for mifepristone specifically impede family physicians' ability to provide medication abortion in primary care settings. STUDY DESIGN: We conducted 56 qualitative interviews with a national sample of family physicians across the US who were not opposed to abortion. We examined how the REMS criteria for mifepristone impact family physicians' ability to provide medication abortion. RESULTS: Of the 56 interviews conducted, 23 participants (41%) raised the REMS criteria as a barrier to providing medication abortion in primary care. These participants reported the REMS added a layer of bureaucratic complexity that made it difficult for family physicians to navigate, even when trained, to provide abortion care. These family physicians described 2 predominant ways the REMS impede their ability to provide medication abortion: (1) The REMS require substantial involvement of clinic administration, who can be unsupportive; (2) The complexity of navigating the REMS results in physicians and clinic administration in primary care viewing medication abortion as not worth the effort, since it is only a small component of services offered in primary care. CONCLUSION: Removing the REMS could simplify integration of medication abortion into primary care, which could meet patient preferences, improve access, and reduce abortion stigma. The FDA's revised REMS criteria may ease administrative burden but will likely maintain key barriers to integrating medication abortion into family physicians' practice. IMPLICATIONS: Our study highlights that the REMS criteria are barriers to family physicians' ability to integrate medication abortion into their primary care practices. The FDA's removal of in person dispensing criteria may provide some impetus for trained family physicians to integrate medication abortion into their scope of practice but the revised REMS criteria maintain key barriers to broader adoption.

Understanding young Black women's socialisation and perceptions of sexual and reproductive health.

Although sexual and reproductive health inequities acutely and disproportionately affect Black women in the USA, there are few studies that consider the sociocultural context in which Black women transition to adulthood and develop their sexuality. The objective of this study was to describe the lived realities of young Black women to elucidate how the sociocultural context informs their current perceptions of sexual and reproductive health. We conducted phenomenological interviews with 22 Black women aged 18-29 years to elicit their life stories. The main categories identified in the findings include how the sociocultural environment informs the self-concept; how the sociocultural environment informs early learning about sexual health; and how together these experiences inform women's development of a sexual self-concept. Three main groupings of experiences were identified relative to women's sexual self-concept: fear-based disease and pregnancy prevention; a deeper understanding of bodies and sexuality beyond disease and pregnancy prevention; and sexual pleasure and fulfilment as a priority. To address ongoing sexual and reproductive health inequities that particularly disadvantage young Black women, health systems and interventions should address the sociocultural contexts in which young Black women develop and manage their sexual health.

"My 9 to 5 Job Is Birth Work": A Case Study of Two Compensation Approaches for Community Doula Care.

With the increased policy emphasis on promoting doula care to advance birth equity in the United States, there is a vital need to identify sustainable and equitable approaches for compensation of community doulas, who serve clients experiencing the greatest barriers to optimal pregnancy-related outcomes. This case study explores two different approaches for compensating doulas (contractor versus hourly employment with benefits) utilized by SisterWeb San Francisco Community Doula Network in San Francisco, California. We conducted qualitative interviews with SisterWeb doulas in 2020 and 2021 and organizational leaders in 2020. Overall, leaders and doulas reported that the contractor approach, in which doulas were paid a flat fee per client, did not adequately compensate doulas, who regularly attend trainings and provide additional support for their clients (e.g., referrals to promote housing and food security). Additionally, this approach did not provide doulas with healthcare benefits, which was especially concerning during the COVID-19 pandemic. As hourly, benefited employees, doulas experienced a greater sense of financial security and wellbeing from receiving consistent pay, compensation for all time worked, and benefits such as health insurance and sick leave, allowing some to dedicate themselves to birth work. Our study suggests that efforts to promote community doula care must integrate structural solutions to provide appropriate compensation and benefits to doulas, simultaneously advancing birth equity and equitable labor conditions for community doulas.

Lessons Learned from Longer Acting Reversible Contraception Applied to Longer Acting HIV Prevention Technologies.

PURPOSE OF REVIEW: This review describes lessons learned from longer acting contraception and employs a reproductive justice lens to inform expansion of emerging HIV prevention technologies. RECENT FINDINGS: Reproductive justice is a framework that advocates for the promotion of universal sexual and reproductive freedoms, particularly among historically marginalized communities. This framework takes a holistic view of individuals and sees the interconnections between sexual health, reproductive health, and overall health. Employing a sexual and reproductive justice perspective is essential to understanding and helping to mitigate the role intersecting structural, sexual, and reproductive oppressions, including those demonstrated through promotion of longer acting contraception, and can critically inform rollout of future prevention technologies, such as longer acting HIV pre-exposure prophylaxis. This review highlights the need for researchers, clinicians, and policymakers to apply lessons learned from contraception and specifically focuses on principles of reproductive justice to offer expanding HIV prevention options.

Biallelic loss-of-function variants in the splicing regulator NSRP1 cause a severe neurodevelopmental disorder with spastic cerebral palsy and epilepsy.

PURPOSE: Alternative splicing plays a critical role in mouse neurodevelopment, regulating neurogenesis, cortical lamination, and synaptogenesis, yet few human neurodevelopmental disorders are known to result from pathogenic variation in splicing regulator genes. Nuclear Speckle Splicing Regulator Protein 1 (NSRP1) is a ubiquitously expressed splicing regulator not known to underlie a Mendelian disorder. METHODS: Exome sequencing and rare variant family-based genomics was performed as a part of the Baylor-Hopkins Center for Mendelian Genomics Initiative. Additional families were identified via GeneMatcher. RESULTS: We identified six patients from three unrelated families with homozygous loss-of-function variants in NSRP1. Clinical features include developmental delay, epilepsy, variable microcephaly (Z-scores -0.95 to -5.60), hypotonia, and spastic cerebral palsy. Brain abnormalities included simplified gyral pattern, underopercularization, and/or vermian hypoplasia. Molecular analysis identified three pathogenic NSRP1 predicted loss-of-function variant alleles: c.1359_1362delAAAG (p.Glu455AlafsTer20), c.1272dupG (p.Lys425GlufsTer5), and c.52C>T (p.Gln18Ter). The two frameshift variants result in a premature termination codon in the last exon, and the mutant transcripts are predicted to escape nonsense mediated decay and cause loss of a C-terminal nuclear localization signal required for NSRP1 function. CONCLUSION: We establish NSRP1 as a gene for a severe autosomal recessive neurodevelopmental disease trait characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.

COVID-19's impact on contraception experiences: Exacerbation of structural inequities in women's health.

INTRODUCTION: Structural inequities may impact the relationship between COVID-19 and access to contraception. METHODS: In July 2020 and January 2021, we used social media to survey 2 samples of women of reproductive age who had not been surgically sterilized and were not currently pregnant about their experiences seeking contraception. We explore whether experiences differed for people experiencing social and/or economic disadvantage due to COVID-19, using multivariable logistic regression to control for age, education and income. RESULTS: In July 2020, 51.5% of respondents who sought contraception (total N = 3064) reported barriers to care compared to 55.3% in January 2021 (total N = 2276). A larger percent (14% in July 2020 and 22% in Jan 2021) reported not using their preferred method of contraception due to COVID-19. Individuals experiencing income loss (OR = 1.61, 95% CI 1.27-2.04 early in the COVID-19 pandemic and OR = 1.58, 1.21-2.06 mid COVID-19 pandemic) and hunger (OR = 1.73, 1.24-2.40 early and OR = 2.02, 1.55-2.64 mid-COVID-19 pandemic) were more likely to report they would be using a different method if not for COVID-19, compared to respondents without income loss or hunger. CONCLUSIONS: COVID-19 has complicated access to contraception, especially for disadvantaged populations. IMPLICATIONS: Efforts are needed to ensure access to contraception despite the COVID-19 epidemic, especially for disadvantaged populations.

Modesty and Security: Attributes Associated with Comfort and Willingness to Engage in Telelactation.

The objectives were to identify conditions under which mothers may be willing to use telelactation and explore associations between participant characteristics, willingness, and beliefs regarding telelactation use. Mothers 2-8 weeks postpartum were recruited from two Florida maternal care sites and surveyed to assess demographics, breastfeeding initiation, and potential telelactation use. Analyses included descriptive statistics and logistic regression models. Of the 88 participants, most were white, married, earned less than USD 50,000 per year, had access to technology, and were willing to use telelactation if it was free (80.7%) or over a secure server (63.6%). Fifty-six percent were willing to use telelactation if it involved feeding the baby without a cover, but only 45.5% were willing if their nipples may be seen. Those with higher odds of willingness to use telelactation under these modesty conditions were experienced using videochat, white, married, and of higher income. Mothers with security concerns had six times the odds of being uncomfortable with telelactation compared to mothers without concerns. While telelactation can improve access to critical services, willingness to use telelactation may depend on conditions of use and sociodemographics. During the COVID-19 pandemic and beyond, these findings offer important insights for lactation professionals implementing virtual consultations.