Embryonic Hypotaurine Levels Contribute to Strain-Dependent Susceptibility in Mouse Models of Valproate-Induced Neural Tube Defects.

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address this challenge, we performed unbiased, whole embryo metabolomic screening of E8.5 mouse embryos from two inbred strains with differential susceptibility to VPA-induced NTDs. We identified metabolites of differential abundance between the two strains, both in response to VPA exposure and in the vehicle controls. Notable enriched pathways included lipid metabolism, carnitine metabolism, and several amino acid pathways, especially cysteine and methionine metabolism. There also was increased abundance of ω-oxidation products of VPA in the more NTD-sensitive strain, suggesting differential metabolism of the drug. Finally, we found significantly reduced levels of hypotaurine in the susceptible strain regardless of VPA status. Based on this information, we hypothesized that maternal supplementation with L-carnitine (400 mg/kg), coenzyme A (200 mg/kg), or hypotaurine (350 mg/kg) would reduce VPA-induced NTDs in the sensitive strain and found that administration of hypotaurine prior to VPA exposure significantly reduced the occurrence of NTDs by close to one-third compared to controls. L-carnitine and coenzyme A reduced resorption rates but did not significantly reduce NTD risk in the sensitive strain. These results suggest that genetic variants or environmental exposures influencing embryonic hypotaurine status may be factors in determining risk for adverse pregnancy outcomes when managing the health care needs of pregnant women exposed to VPA or other ASMs.

Effectiveness of Respondent-Driven Sampling for Conducting Health Studies Among Undocumented Immigrants at a Time of Heightened Immigration Enforcement.

This paper assessed the effectiveness of Respondent Driven Sampling (RDS) in recruiting undocumented Latinx immigrants for a prevalence health study at a time of heightened immigration enforcement. RDS was used to collect and analyze data from clinical interviews with 254 undocumented Latinx immigrant adults, enabling inference to a population of 22,000. 45% of the sample reported having a chronic medical condition. The desired sample size was achieved and exceeded with three initial recruits and 10 waves of recruitment across 9 weeks. There was substantial cross-group mixing for recruitment in terms of sex and recency of immigration, which facilitated the emergence of diversity within recruitment chains. Primary factors that contributed to effective recruitment were location, flexibility, on-site childcare, and detailed explanation of the recruitment process. RDS is an effective recruitment method to study the health of undocumented Latinx immigrants, which is essential to informing intervention and policy.

Undocumented immigrants and mental health: A systematic review of recent methodology and findings in the United States.

This study reviewed the methodology and findings of 44 peer-reviewed studies on psychosocial risk factors associated with mental health outcomes among undocumented immigrants (UIs) in the United States. Findings showed a considerable advancement over the past seven years in the methods and measures used in the included studies. Nonetheless, there is a need for continued methodological rigor, innovative study designs, greater diversity of samples, and in-depth exploration of constructs that facilitate resilience. Identifying avenues to reduce risk in this population is essential to inform intervention and advocacy efforts aimed at overcoming distress from the current U.S. anti-immigrant and socio-political climate.

Protective Factors to the Wellbeing of Undocumented Latinx Immigrants in the United States: A Socio-Ecological Approach.

Undocumented immigrants often experience multiple chronic stressors that over time can increase health risk. This qualitative study used data from 7 focus groups and 15 key informant interviews to identify relevant protective factors to the heath of undocumented immigrants in the U.S. Findings showed that at the individual level, undocumented immigrants rely primarily on motivation to cope with adversity, while also relying on family support and community cohesion at the interpersonal level. At the policy level, safe neighborhoods and non-stigmatizing environments, protection from abuse/exploitation, and activism were identified as protective factors. English proficiency was also identified as important.