Research Spotlights: February 2021

Marijuana use may impair a woman’s fertility

The prevalence of marijuana use continues to rise, with self-reported use nearly doubling among women of reproductive age over the last 20 years, likely due to increasing perceptions of overall safety and acceptability. A recent study, supported by the Intramural Research Program of the NICHD and other funders, investigated if there were differences in conception rates among women who use marijuana compared to those who do not. Currently, there is a paucity of research on the safety of marijuana use during critical windows of pregnancy establishment. Prior research based on self-reported marijuana use suggests that use is not associated with changes in conception rates; however, self-reported use may underestimate actual use due to stigma surrounding drug use.

To address these questions, this study examined a cohort of women in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial that is investigating preconception low-dose aspirin on pregnancy outcomes in four US medical centers (Pennsylvania, New York, Utah and Colorado; 2006–2012) who were trying to conceive after experiencing one or two prior miscarriages (n=1228, ages 18-40 years old, 93.8% Caucasian ethnicity). Women participated in the study for up to 6 months while attempting to become pregnant and throughout pregnancy if conception occurred. In addition to relying on self-reported use of marijuana, this study also included longitudinal assessment of marijuana use via daily urine samples during the time periods of preconception and early pregnancy. In this study, 62 women (5%) tested positive for marijuana or self-reported marijuana use before conception. Of the women who became pregnant, 1.3% used marijuana during the first eight weeks of pregnancy.

Women who used marijuana while trying to conceive were around 40% less likely to conceive per monthly cycle than non-users. By the end of the study, a smaller proportion of marijuana users became pregnant (42%) compared to non-users (66%). The groups did not differ in miscarriage rates. All results were similar after adjusting for parity, income, employment, and stress and after excluding women who smoked cigarettes, used alcohol, or reported any other drug use in the previous year.

Animal studies have shown that marijuana can impact hormone levels and ovulation. Therefore, the researchers also measured reproductive hormones to determine if cannabis use was also associated with changes in hormones, leading to decreased conception probability. Women who used marijuana tended to have a higher risk of missed ovulation and significantly higher levels of luteinizing hormone, which is central to menstrual and ovulatory function, as compared to non-users.

This study indicates that marijuana use during conception and early pregnancy may impair fertility, potentially due to changes in hormone levels and menstrual cycle function, adding to the limited data on the safety of marijuana use during the critical windows of preconception and early pregnancy. However, this study was limited in that it captured a small population of marijuana users in a population that was already experiencing fertility difficulties, without also considering the male partner’s marijuana use and fertility. This study highlights the potential effects of marijuana on fertility and the need for more research on the effects of marijuana on reproductive health.

Mumford SL, Flannagan KS, Radoc JG, Sjaarda LA, Zolton JR, Metz TD, Plowden TC, Perkins NJ, DeVilbiss EA, Andriessen VC, Purdue-Smithe AC, Kim K, Yisahak SF, Freeman JR, Alkhalaf Z, Silver RM, Schisterman EF 2021. Cannabis use while trying to conceive: a prospective cohort study evaluating associations with fecundability, live birth and pregnancy loss. Hum Reprod. doi: 10.1093/humrep/deaa355

Vaccine uptake in sparse verses dense communities

Community vaccinations have been a proven method of saving lives. A study funded by grants from the NIAID, NIDA, and NIMH investigated the specific motivations that individuals consider when deciding to vaccinate. Individuals decide to vaccinate for various reasons, such as the density of the community, cost to vaccinate, and risk of infection, but motivation to vaccinate for the benefit of others (prosocial benefits) has not yet been explored. Previous research indicates that more dense populations are often more social and more likely to spread infection and often seek vaccination to protect others. Prosocial benefits are beliefs that could potentially motivate individuals to vaccinate based on the concern that their action would impact others.

The aim of this study is to understand how prosocial concerns motivate vaccination in sparse and dense communities. The authors hypothesized that more populated communities may have greater perceived impact of vaccination because vaccinating may prevent more disease, while less dense communities may have greater perceived impact of vaccination because individuals feel a sense of unique contribution.

To test these hypotheses, three studies were conducted, two of which were controlled experiments to determine causality by manipulation of social density and prosocial concern. A longitudinal survey measured vaccination behavior during the 2018-2019 flu season, which considered individual differences for prosocial concern for vaccination and examined the extent to which prosocial concern influenced vaccination across varying levels of social density. The two follow up experiments examined interaction effects on intentions to vaccinate for flu and COVID-19 and the effects of prosocial concern.

The first longitudinal study examined a nationally diverse sample of adults living in the United States (n=2,490) during 2018-2019 across six time points. The dependent variable was whether participants received the vaccine at any point during the flu season. Zip codes for each individual participant were used to determine the county and state and calculate proportion of urban land. To form the prosocial concern index, questions assessed the level of concern of infecting others such as family or friends if the individual did not get the flu vaccine at timepoint one. Regression analyses were used to test the impact of prosocial concern on vaccination rates across various levels. Logistic regression showed a consistently higher likelihood of vaccination when prosocial concern was higher. Prosocial concern had a larger positive effect on vaccination when participants resided in non-metropolitan areas (z= -2.18, P=0.03, 95% CI: -0.70, -0.05), lower population dense areas (z= -2.29, P=0.02, 95% CI: -0.45, -0.08) and regions with lower proportion of urban land area (z=-3.35, P<0.001, 95% CI: -0.23. -0.06)

Study two was a 2X2 factorial design which recruited workers (n=240) in the United States to complete an online consumer health survey to examine whether greater influence of prosocial concern on vaccination in sparser environments is mediated by perceived impact, on prosocial concern. The factorial ANOVA yielded a significant positive interaction between social density and prosocial concern on vaccination intention (P =0.03, 95% CI: 0.11, 1.95). A significant positive interaction was found between social density and prosocial concern on perceived impact (P=0.03, 95% CI: 0.07, 1.76). Low density participants with prosocial concern had stronger intention to vaccinate.

Study three included a nationally representative sample of adults (n=560), randomly assigned to 2X2 factorial design. Participants read an article about a COVID-19 vaccine discussion with Dr. Anthony Fauci and then indicated their intentions to vaccinate to positively impact their community. A significant positive interaction was found between social density and prosocial concern on perceived impact (P=0.03, 95% CI: 0.06, 1.23). Intentions to vaccinate in low density conditions were stronger (P=0.003) among participants characterized as having prosocial concerns (M=5.59, SD=1.75) than participants characterized as having individual concern (M=4.92. SD=1.96).

Taken together, these findings suggest that both rural and urban individuals are equally concerned with the well-being of community members, however rural members perceived their action to have a greater impact. The findings from this study may help close the gap between urban and rural disparities in vaccination by utilizing the prosocial impact as an evidence-based communication strategy for rural populations that experience low vaccination rates.

Jung, H. and Albarracín, D., 2021. Concerns for others increases the likelihood of vaccination against influenza and COVID-19 more in sparsely rather than densely populated areas. Proceedings of the National Academy of Sciences, 118(1).

Prenatal stress may increase children’s disease risk, especially in Black women

Our environment can cause changes to our biology and result in an increased risk for a multitude of diseases and disorders. In a study funded by the NHLBI and NIEHS, researchers investigated whether changes to the prenatal environment due to maternal stress impacted children’s mitochondrial function and ultimately neurobehavioral development.

Although prenatal stress has long been studied for its impact on maternal and offspring physiology and function, cumulative stress and trauma exposure to a mother before conception is likely to have a lasting impact on the mother’s physiological response to stress. Preconception stress can impact offspring development by mutating the child’s mitochondrial DNA, leading to mitochondrial dysfunction, which is associated with childhood conditions such as asthma, obesity, attention deficit hyperactivity disorder, and autism. Individuals’ exposure levels of lifetime stressors and physiological stress response have been shown to vary by race which may indicate that the resulting changes in offspring outcomes may also vary by race.

In this study, placenta samples were received from 365 mothers (Black, 40%; Hispanic, 19%; multiracial, 8%) and underwent whole mitochondrial DNA sequencing in order to evaluate specific mutations. Maternal lifetime exposure to stressful events such as sexual assault, incarceration, serious injury, physical or mental illness, family hardship, and interpersonal violence was assessed during the second trimester using the validated Life Stressor Checklist-Revised, although questions considered time periods as early as the mother’s own childhood. Multivariable regression was used to look at maternal lifetime stress in relation to the number of gene mutations in the placenta mitochondrial genome. Racial/ethnic differences were examined by cross-product terms and contrast statements.

Women experiencing more psychosocial stress over their lifetime exhibited a higher number of placental mitochondrial mutations. The strongest association between stress exposure was observed among Black women. While white women also demonstrated this association, Hispanic women did not. In fact, Hispanic women exposed to stress had fewer placental mitochondrial DNA mutations.

One explanation for why Black women had the strongest association between stress and mitochondrial mutations is that Black women are already at an increased risk for many diseases such as obesity, diabetes, and certain cancers, so the effects of psychosocial stress may exacerbate this resulting in a further increase in risk for developing stress-related diseases. On the other hand, the reverse association of stress to mitochondrial mutations seen in Hispanic women may be explained by the epidemiological phenomenon called “Hispanic paradox” that has documented better health and lower mortality in Hispanic people relative to non-Hispanic white people despite greater risk and lower socioeconomic status for Hispanics. It is also possible that the negative effects of stress in Hispanic populations may be attenuated by other sociocultural dynamics specific to Hispanics, resulting in better outcomes.

This is the first study to examine and report an association between maternal lifetime psychosocial stress exposure and an increase in placental mitochondrial mutations. The results of this study indicate that stress on an expectant mother could affect her offspring’s chance of developing certain diseases and provide insight as to why certain children may be more vulnerable to developing complex conditions linked to environmental exposures. In addition, it provides evidence of the racial/ethnic differences in mutational load on offspring development and resulting chronic disease disparities.

Brunst KJ, Zhang L, Zhang X, Baccarelli AA, Blooquist T, Wright RJ 2021. Associations Between Maternal Lifetime Stress and Placental Mitochondrial DNA Mutations in an Urban Multiethnic Cohort. Biol Psychiatry, doi: 10.1016/j.biopsych.2020.09.013.