Potentially modifiable risk and protective factors affecting mental and emotional wellness in pregnancy.

Introduction: Impaired mental and emotional wellness often co-occurs with prenatal substance use, and both affect infant socio-emotional, cognitive, language, motor, and adaptive behavioral outcomes. Guided by the modified biopsychosocial framework, this study examined the role of common substance exposures during pregnancy (i.e., alcohol and cannabis), socio-cultural factors (social support during pregnancy, adverse childhood experiences), and reproductive health factors on maternal mental health (MMH). Methods: Data were obtained from a prospective cohort study-Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH-2), and included 202 pregnant persons. Alcohol and cannabis exposures were assessed through repeated prospective interviews and a comprehensive battery of drug and ethanol biomarkers. MMH outcomes were evaluated during the third trimester through the Perceived Stress Scale, Edinburgh Depression Scale, Generalized Anxiety Disorders-7, and Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders. Univariate and multivariable linear regression models evaluated significant predictors of MMH. Results: Results of multivariable analysis indicate that both maternal adverse childhood experiences and alcohol exposure, even at low-to-moderate levels, during pregnancy were associated with poorer scores for most MMH measures, while higher level of social support and Spanish as the primary language at home (as a proxy of enculturation) had protective effects (all p's < 0.05). Conclusion: These findings highlight the importance of assessing substance use, including periconceptional alcohol exposure, and mental health in pregnant persons as closely related risk factors which cannot be addressed in isolation. Our findings also emphasize a strong protective effect of socio-cultural factors on maternal mental and emotional wellbeing-a strong precursor to maternal-infant bonding and infant neurodevelopment.

Dose-response effect of prenatal alcohol exposure on perinatal outcomes.

BACKGROUND: A better understanding of the effects of lower levels of prenatal alcohol exposure (PAE), as a common exposure, is needed. The goal of this study was to examine the effects of mild-moderate PAE and episodic binge drinking on perinatal outcomes. METHODS: The data were obtained from three prospective cohorts with a combined sample of 281 participants: 125 with PAE and 156 without PAE. Alcohol-related measures included the Alcohol Use Disorders Identification Test, timeline follow-back questionnaires (covering the periconceptional period, mid-gestation, and late gestation), and biomarkers. Absolute alcohol per day (AAD) and per drinking day (AADD), number of binge episodes, and maximum number of drinks in a 24-h period were estimated. Perinatal outcomes included gestational age and anthropometric measures. Data were analyzed using correlation and multivariable regression analysis. RESULTS: Among women with PAE, average alcohol consumption across the periconceptional period and pregnancy was 0.37 oz ± 0.74 AA/day (~5 drinks/week). After adjusting for tobacco co-exposure and sociodemographic characteristics, significant associations between all alcohol measures and gestational age at delivery were observed, including cumulative measures of AAD (ß = -0.58; 95% CI: -0.98; -0.17) and AADD (ß = -0.58; 95% CI: -0.90; -0.26) during pregnancy and the periconceptional period. A significant association between the maximum number of drinks in a 24-h period and birth length percentile (ß = -0.70; 95% CI: -1.36; -0.04) was observed in the final model. PAE was associated with lower birth weight percentile in univariate analyses only. CONCLUSIONS: Results of this study demonstrate a negative association between mild-moderate PAE and episodic binge drinking with gestational age at delivery and birth length percentile after controlling for other factors. Robust negative effects of PAE, including in the periconceptional period before pregnancy recognition, on duration of gestation highlight the need for primary prevention efforts aimed at PAE in persons of reproductive age.

Impact of low-level prenatal alcohol exposure and maternal stress on autonomic regulation.

BACKGROUND: Prenatal alcohol exposure (PAE) impacts the neurodevelopment of the fetus, including the infant's ability to self-regulate. Heart rate variability (HRV), that is, the beat-to-beat variability in heart rate, is a non-invasive measurement that can indicate autonomic nervous system (ANS) function/dysfunction. METHODS: The study consisted of a subset of our ENRICH-2 cohort: 80 participants (32 PAE and 48 Controls) who had completed three visits during pregnancy. The participants completed a comprehensive assessment of PAE and other substances throughout pregnancy and assessments for stress, anxiety, and depression in the third trimester. At 24 h of age, infant HRV was assessed in the hospital during the clinically indicated heel lance; 3- to 5-min HRV epochs were obtained during baseline, heel lancing, and recovery episodes. RESULTS: Parameters of HRV differed in infants with PAE compared to Controls during the recovery phase of the heel lance (respiratory sinus arrhythmia (RSA) and high-frequency (HF), p < 0.05). Increased maternal stress was also strongly associated with abnormalities in RSA, HF, and low-frequency / high-frequency (LF/HF, p's < 0.05). CONCLUSIONS: Alterations in ANS regulation associated with PAE and maternal stress may reflect abnormal development of the hypothalamic-pituitary-adrenal axis and have long term implications for infant responsiveness and self-regulation. IMPACT: Previous studies have focused on effects of moderate to heavy prenatal alcohol exposure (PAE) on autonomic dysregulation, but little is known about the effects of lower levels of PAE on infant self-regulation and heart rate variability (HRV). Prenatal stress is another risk factor for autonomic dysregulation. Mild PAE impacts infant self-regulation, which can be assessed using HRV. However, the effect of prenatal stress is stronger than that of mild PAE or other mental health variables on autonomic dysregulation.

The effect of the COVID-19 pandemic on substance use patterns and physiological dysregulation in pregnant and postpartum women.

BACKGROUND: The SARS-CoV-2/COVID-19 pandemic has been associated with increased stress levels and higher alcohol use, including in pregnant and postpartum women. In the general population, alcohol use is associated with dysregulation in the autonomic nervous system (ANS), which is indexed by heart rate variability (HRV). The objectives of this study were to: (1) characterize changes in substance use during the SARS-CoV-2/COVID-19 pandemic via a baseline self-report survey followed by mobile ecological momentary assessment (mEMA) of substance use; and (2) examine the associations between momentary substance use and ambulatory HRV measures in pregnant and postpartum women. METHODS: Pregnant and postpartum women were identified from the ENRICH-2 prospective cohort study. Participants were administered a baseline structured phone interview that included the Coronavirus Perinatal Experiences (COPE) survey and ascertained the prevalence of substance use. Over a 14-day period, momentary substance use was assessed three times daily, and HRV measurements were captured via wearable electronics. Associations between momentary substance use and HRV measures (root mean square of successive differences [RMSSD] and low frequency/high frequency [LF/HF] ratio) were examined using a mixed effects model that included within-subject (WS) and between-subject (BS) effects and adjusted for pregnancy status and participant age. RESULTS: The sample included 49 pregnant and 22 postpartum women. From a combination of a baseline and 14-day mEMA surveys, 21.2% reported alcohol use, 16.9% reported marijuana use, and 8.5% reported nicotine use. WS effects for momentary alcohol use were associated with the RMSSD (ß = -0.14; p = 0.005) and LF/HF ratio (ß = 0.14; p = 0.01) when controlling for pregnancy status and maternal age. No significant associations were observed between HRV measures and instances of marijuana or nicotine use. CONCLUSIONS: These findings highlight the negative effect of the SARS-CoV-2/COVID-19 pandemic on the psychological health of pregnant and postpartum women associated with substance use, and in turn, ANS dysregulation, which potentially puts some women at risk of developing a substance use disorder.

Impulsivity and Alcohol Use during Pregnancy and Postpartum: Insights from Novel Methodological Approaches within the Context of the COVID-19 Pandemic.

Impaired emotion regulation and impulsivity have been linked to substance use. This study evaluated the association between emotion regulation difficulties-specifically impulsivity-and substance use within the context of the COVID-19 pandemic among pregnant (n = 49) and postpartum (n = 20) women. Participants from a prospective cohort ENRICH-2 completed a baseline phone survey of COVID-19-related experiences and impulsivity followed by a 14-day (3x/day) mobile ecological momentary assessment (mEMA) of impulsivity and substance use. Between-subject (BS) and within-subject (WS) associations for baseline impulsivity and momentary impulsivity with respect to substance use were examined using mixed effects models. At the BS level, momentary impulsivity scores that were higher than the overall group average were positively associated with subsequent momentary reports of marijuana use (ß = 1.25; p = 0.04) when controlling for pregnancy status and COVID-19-related stress. At the WS level, momentary impulsivity scores that were higher than an individual's average score were positively associated with subsequent reports of momentary alcohol use (ß = 0.08; p = 0.04). This research supports the idea that impulsivity varies based on individual situations, such as stress associated with the COVID-19 pandemic, and may be an important correlate of substance use in pregnant and postpartum women. Future research might consider investigation of additional factors, which may serve to moderate or mediate the relationship between impulsivity and substance use.

Early developmental trajectory of children with prenatal alcohol and opioid exposure.

BACKGROUND: With significant increases in opioid use/misuse and persistent high prevalence of prenatal alcohol exposure (PAE), identifying infants at risk for long-term developmental sequelae due to these exposures remains an urgent need. This study reports on developmental outcomes in young children from a prospective cohort, ENRICH-1, which recruited pregnant women and followed up maternal-infant pairs. METHODS: Subjects were assigned to four study groups based on prenatal use of medications for opioid use disorder (MOUD), PAE, MOUD+PAE, and unexposed controls (UC). Mixed effects modeling was used to evaluate changes in the Bayley Scales of Infant Development-III (BSID-III) Cognitive, Language, and Motor scores between 6 and 20 months. RESULTS: There was a significant three-way interaction (MOUD-by-PAE-by-Time) with respect to the BSID-III Cognitive (p = 0.045) and Motor (p = 0.033) scales. Significant changes between the two evaluations were observed for MOUD group in Cognitive and Language scores; for PAE group in Cognitive, Language, and Motor scores, and for MOUD+PAE group in Language scores after adjusting for child sex and family socio-economic status. The developmental scores for the UC remained stable. CONCLUSION: Observed decline in neurodevelopmental scores during the first 2 years of life emphasizes the importance of a longitudinal approach when evaluating children with prenatal polysubstance exposure. IMPACT: BSID-III scores were stable during the first 2 years of life for unexposed children. BSID-III scores declined for children with prenatal exposures to alcohol and/or opioids. Standard developmental tests may not be sensitive enough during the first year of life. Findings emphasize the need for repeated evaluations of children who are at high risk.

Effects of prenatal opioid and alcohol exposures on immune and serotonin factors in human placenta.

PURPOSE: Opioids and alcohol impact critical serotonin (5-HT) function in the developing placenta and fetus through the actions of immune proinflammatory factors. Yet, possible convergent effects of opioids and alcohol on human placental toll-like receptor 4 (TLR4) activation and subsequent 5-HT homeostasis remain entirely unknown. The purpose of this study was to examine the effect of prenatal exposure to opioids with or without prenatal alcohol exposure (PAE) on the expression of key placental immune and serotonin signaling factors in human placental tissue obtained from a well-characterized prospective cohort. METHODS: Data were collected from a subset of participants enrolled in the prospective pre-birth Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH-1) cohort. Women were recruited and classified into four study groups: 1) PAE (n = 20); 2) those taking medications for opioid use disorder (MOUD; n = 28), 3) concurrent PAE and MOUD (n = 20); and 4) controls (HC; n = 20) based on prospective, repeated self-report, and biomarker analysis. Placenta samples underwent tissue processing to identify mRNA for TLR4, nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), serotonin transporter (SERT), tryptophan hydroxylase (TPH1), indoleamine 2,3-Dioxygenase 1 (IDO) as well as protein concentrations of TLR4, IL-1ß, TNF-α, SERT. To consider the association between study group and mRNA/protein expression of our targets, multivariable regression models were developed with inclusion of a priori selected covariates. RESULTS: There was a significant negative association between PAE and SERT mRNA (ß = -0.01; p < 0.01) and a positive association with TPH1 mRNA expression (ß = 0.78; p < 0.05). In addition, there was a negative association between MOUD and TNF-α protein expression (ß = -0.12; p < 0.05). CONCLUSIONS: This study provides the first evidence that PAE may inhibit SERT expression while simultaneously promoting increased TPH1 protein expression in human placenta. This may result in increased 5-HT in fetal circulation known to affect neurodevelopment. Our data suggest that opioids and alcohol may disturb the bidirectional, dynamic interaction between the placental immune and serotonin system. Given the implication for brain development and health across the life-span further investigation of these critical mechanisms in well-defined cohorts is required.

The Curse of Curves: Sex Differences in the Associations Between Body Shape and Pain Expression.

This study examines the associations between objective and subjective measurements and impressions of body shape and cold pressor pain reporting in healthy adults. On the basis of sexual selection theory (SST), we hypothesized that body characteristics that are universally preferred by the opposite sex-specifically, lower waist-to-hip ratios (WHR) in women and higher shoulder-to-hip ratios (SHR) in men-and characteristics (e.g., proportion of body fat in women) that infer attractiveness differently across cultures will correspond to higher experimental pain reporting in women and lower pain reporting in males. A convenience sample of young adults (n = 96, 58 females, 18-24 years; mean age = 19.4) was measured for body mass index (BMI), WHR, SHR, and subjective body impressions (SBI), along with cold pressor pain reporting. The findings showed that BMI was positively associated with WHR and less-positive SBI in both sexes. Consistent with SST, however, only BMI and WHR predicted variability in pain expression in women, whereas only SHR predicted variability in men. Subjective body impressions were positively associated with SHR among males and unrelated to WHR among females, yet only females showed a positive association between SBI and higher pain reporting. The findings suggest that sexually selected physical characteristics (WHR and SHR) and culturally influenced somatic (BMI) and psychological (SBI) indicators of attractiveness correspond with variability in pain reporting, potentially reflecting the general tendency for people to express clusters of sexually selected and culturally influenced traits that may include differential pain perception.

Experimenter Effects on Pain Reporting in Women Vary across the Menstrual Cycle.

Background. Separate lines of research have shown that menstrual cycling and contextual factors such as the gender of research personnel influence experimental pain reporting. Objectives. This study examines how brief, procedural interactions with female and male experimenters can affect experimentally reported pain (cold pressor task, CPT) across the menstrual cycle. Methods. Based on the menstrual calendars 94 naturally cycling women and 38 women using hormonal contraceptives (M age = 19.83, SD = 3.09) were assigned to low and high fertility groups. This assignment was based on estimates of their probability of conception given their current cycle day. Experimenters (12 males, 7 females) engaged in minimal procedural interactions with participants before the CPT was performed in solitude. Results. Naturally cycling women in the high fertility group showed significantly higher pain tolerance (81 sec, d = .79) following interactions with a male but not a female experimenter. Differences were not found for women in the low fertility or contraceptive groups. Discussion. The findings illustrate that menstrual functioning moderates the effect that experimenter gender has on pain reporting in women. Conclusion. These findings have implications for standardizing pain measurement protocols and understanding how basic biopsychosocial mechanisms (e.g., person-perception systems) can modulate pain experiences.