Association between maternal prenatal depressive symptoms and offspring epigenetic aging at 3-5 weeks.

Epigenetic clocks are emerging as tools for assessing acceleration and deceleration of biological age during childhood. Maternal depression during pregnancy may affect the biological aging of offspring and related development. In a low-income cohort of mother-child dyads, we investigated the relationship between prenatal maternal depressive symptoms and infant epigenetic age residuals, which represent the deviation (acceleration or deceleration) that exists between predicted biological age and chronological age. The epigenetic age residuals were derived from a pediatric-specific buccal epithelial clock. We hypothesized that maternal depressive symptoms, both sub-clinical and elevated (clinical level), would be associated with estimated biological age deceleration in offspring during early infancy. We analyzed data from 94 mother-child dyads using the Edinburgh Postnatal Depression Scale (EPDS) and DNA methylation derived from offspring buccal cells collected at 3-5 weeks of age. There was a significant non-linear association between the EPDS score and epigenetic age residual (ß = -0.017, 95% confidence interval: -0.03,-0.01, P = <0.01). The results indicated that infants of mothers with sub-clinical depressive symptoms had the lowest infant epigenetic age residuals while infants of mothers with no-to-low depressive symptoms had the highest and experienced biological age acceleration. Maternal depressive symptoms may influence the biological aging of offspring living in poverty.

Association Between Maternal Adverse Childhood Experiences and Neonatal SCG5 DNA Methylation-Effect Modification by Prenatal Home Visiting.

Maternal childhood adversity and trauma may elicit biological changes that impact the next generation through epigenetic responses measured in DNA methylation (DNAm). These epigenetic associations could be modified by the early postnatal environment through protective factors, such as early childhood home visiting (HV) programs that aim to mitigate deleterious intergenerational effects of adversity. In a cohort of 53 mother-child pairs recruited in 2015-2016 for the Pregnancy and Infant Development Study (Cincinnati, Ohio), we examined the association between maternal adverse childhood experiences (ACEs) and neonatal DNAm in the secretogranin V gene (SCG5), which is important in neuroendocrine function. We examined prenatal HV as an effect modifier. Mothers completed a questionnaire on ACEs during pregnancy, and infant buccal samples were collected 1 month postpartum. Multivariable linear regression was used to examine the association between maternal ACEs and neonatal DNAm expressed as M-values averaged across 4 cytosine-phosphate-guanine dinucleotide sites. A higher number of maternal ACEs (>3) was associated with a 5.79-percentage-point lower offspring DNAm (95% confidence interval: -10.44, -1.14), and the association was modified by the number of home visits received during pregnancy. In a population of at-risk mother-child dyads, preliminary evidence suggests that maternal ACEs have a relationship with offspring SCG5 DNAm that differs by the amount of prenatal HV.

Opioid Requirement following Arthroscopic Knee Surgery: Are There Predictive Factors Associated with Long-Term Use.

The purpose of this study is to identify patterns of postoperative narcotic use and determine the impact of psychosocial and perioperative factors on postoperative opioid consumption following arthroscopic knee surgery. Fifty consecutive patients undergoing arthroscopic knee surgery were prospectively enrolled. Patients were contacted via telephone at 1 week postoperatively to report their pain level and opioid consumption. The patient was contacted again at 2 weeks, 4 weeks, and 90 days as necessary until opioid cessation, at which time the patient's plan for unused pills was inquired. Opioid consumption was compared using t-tests and one-way analysis of variance for demographic and surgical factors. Linear regression was used to determine whether the Pain Catastrophizing Scale (PCS), Resilience Scale (RS-11), International Knee Documentation Committee questionnaire, or patient-reported pain at 1 week predicted higher opioid consumption. The average morphine equivalent dose of opioid consumption was 142 mg. Sixty-four percent consumed less than 100 mg, and 68% discontinued opioid use by 1 week postoperatively. Seventy-four percent reported surplus pills, and 49% of those patients plans for pill disposal. Factors associated with higher consumption included undergoing a major procedure, having a regional anesthesia block, and higher area deprivation index score (p < 0.05). Higher PCS scores and reported average pain level at 1 week were predictive of higher opioid consumption (p < 0.05). In conclusion, a majority of patients undergoing outpatient knee surgery did not require the entirety of their narcotic prescription. The majority of patients consumed less than 100 mg of morphine equivalents and discontinued opioid use by 1 week postoperatively. Ligament reconstruction, living in an area with a higher index of deprivation, and higher score on the PCS were associated with greater opioid consumption. Overall, patient knowledge regarding opioid disposal was poor, and patients would likely benefit from additional education prior to surgery.

Associations Between Maternal Community Deprivation and Infant DNA Methylation of the SLC6A4 Gene.

Introduction: Poverty is negatively associated with health and developmental outcomes. DNA methylation (DNAm) has been proposed as a mechanism that underlies the association between adversity experienced by mothers in poverty and health and developmental outcomes in their offspring. Previous studies have identified associations between individual-level measures of stress and adversity experienced by a mother during pregnancy and infant DNAm. We hypothesized that independent of individual stresses, a mother's community-level deprivation while she is pregnant may also be associated with DNAm among the genes of her offspring that are related to stress response and/or development. Methods: Pregnant mothers (N = 53) completed assessments that measured stress, adversity, and mental health. To evaluate community-level deprivation, mothers' addresses were linked to census-level socioeconomic measures including a composite index of deprivation that combines multiple community-level indicators such as income and highest level of education received. Infant buccal cells were collected at about age 4 weeks to measure DNAm of candidate genes including NR3C1, SCG5, and SLC6A4, which are associated with the stress response and or social and emotional development. Multivariable models were employed to evaluate the association between maternal community deprivation and infant DNAm of candidate genes. Results: No significant associations were identified between maternal community-level deprivation and the methylation of NR3C1 or SCG5, however, maternal community-level deprivation was significantly associated with higher mean methylation across 8 CpG sites in SLC6A4. Conclusion: This study identified an association between community-level measures of deprivation experienced by a mother during pregnancy and DNAm in their offspring. These findings may have implications for understanding how the community context can impact early biology and potential function in the next generation.

Evaluation of Early Childhood Home Visiting to Prevent Medically Attended Unintentional Injury.

STUDY OBJECTIVE: We evaluated the influence of home visiting on the risk for medically attended unintentional injury during home visiting (0 to 3 years) and subsequent to home visiting (3 to 5 years). METHODS: A retrospective, quasi-experimental study was conducted in a cohort of mother-child pairs in Hamilton County, OH. The birth cohort (2006 to 2012) was linked to administrative home visiting records and data from a population-based injury surveillance system containing records of emergency department (ED) visits and hospitalizations. Cox proportional-hazard regression was used to compare medically attended unintentional injury risk (0 to 2, 0 to 3, and 3 to 5 years) in a home-visited group versus a propensity score-matched comparison group. The study population was composed of 2,729 mother-child pairs who received home visiting and 2,729 matched mother-child pairs in a comparison group. RESULTS: From birth to 2 years, 17.2% of the study population had at least one medically attended unintentional injury. The risk for medically attended unintentional injury from aged 0 to 2 and 0 to 3 years was significantly higher in the home-visited group relative to the comparison group (hazard ratio 1.17, 95% confidence interval 1.01 to 1.35; hazard ratio 1.15, 95% confidence interval 1.00 to 1.31, respectively). Additional injuries in the home-visited group were superficial, and the increased risk for medically attended unintentional injury was observed for ED visits and not hospitalizations. CONCLUSION: Home-visited children were more likely to have a medically attended unintentional injury from birth to aged 3 years. This finding may be partially attributed to home visitor surveillance of injuries or greater health care-seeking behavior. Implications and alternative explanations are discussed.

Plasma Concentrations of Ferritin in Early Pregnancy Are Associated with Risk of Gestational Diabetes Mellitus in Women in the Danish National Birth Cohort.

BACKGROUND: Evidence from experimental studies has demonstrated that higher than normal iron concentrations can lead to pancreatic ß cell dysfunction and impaired glucose metabolism. Studies on body iron stores in early pregnancy and subsequent gestational diabetes mellitus (GDM) risk are sparse. OBJECTIVE: Our objective was to determine whether biomarkers of body iron stores measured in early pregnancy are associated with GDM risk. METHODS: A case-control study of 350 GDM cases and 349 non-GDM controls was conducted in participants from the Danish National Birth Cohort. Blood was collected at a mean ± SD gestational age of 9.4 ± 3.2 wk. Plasma biomarkers of iron stores, including ferritin and soluble transferrin receptor (sTfR), were measured. Logistic regression was used to estimate the OR of GDM associated with quintiles of plasma biomarkers of body iron stores, controlling for maternal age, family history of diabetes, exercise in pregnancy, parity, and prepregnancy body mass index (BMI). RESULTS: Cases were older (mean ± SD age: 32.2 ± 4.3 compared with 29.9 ± 4.2 y) and had a higher BMI (in kg/m(2); mean ± SD: 28.7 ± 6.0 compared with 24.1 ± 4.6) than controls. Plasma concentrations of both ferritin and sTfR in early pregnancy were significantly higher in GDM cases than in controls [means ± SDs: 80.6 ± 56.0 compared with 71.8 ± 50.1 µg/L (P = 0.03) and 1.5 ± 0.7 compared with 1.4 ± 0.6 mg/L (P = 0.002) for ferritin and sTfR, respectively]. Ferritin was positively and significantly associated with GDM risk even after adjustment for major risk factors of GDM, including prepregnancy BMI. ORs across increasing quintiles of ferritin were 1.00 (reference), 1.25 (95% CI: 0.70, 2.22), 1.89 (95% CI: 1.06, 3.37), 0.82 (95% CI: 0.46, 1.48), and 2.34 (95% CI: 1.30, 4.21) (P-linear trend = 0.02). CONCLUSION: These findings suggest that plasma ferritin measured in early pregnancy is significantly and positively associated with GDM risk.