Accelerated epigenetic clock aging in maternal peripheral blood and preterm birth.

BACKGROUND: Epigenetic clocks use CpG DNA methylation to estimate biological age. Acceleration is associated with cancer, heart disease, and shorter life span. Few studies evaluate DNA methylation age and pregnancy outcomes. AgeAccelGrim is a novel epigenetic clock that combines 7 DNA methylation components. OBJECTIVE: This study aimed to determine whether maternal biological aging (via AgeAccelGrim) is associated with early preterm birth. STUDY DESIGN: A prospective cohort of patients with singleton pregnancies and at high risk of spontaneous preterm birth delivering at a tertiary university hospital were included in this study. Genome-wide CpG methylation was measured using the Illumina EPIC BeadChip (Illumina, Inc, San Diego, CA) from maternal blood samples obtained at <28 weeks of gestation. AgeAccelGrim and its 7 DNA methylation components were estimated by the Horvath DNA methylation age online tool. Positive values are associated with accelerated biological aging, whereas negative values are associated with slower biological aging relative to each subject's age. The primary outcome was preterm birth at <34 weeks of gestation (any indication). The secondary outcomes were preterm birth at <37 and <28 weeks of gestation. AgeAccelGrim was analyzed as a continuous variable and in quartiles. Exploratory analyses evaluated each of the 7 DNA methylation components included in the composite AgeAccelGrim. Data were analyzed by chi-square test, t test, rank-sum test, logistic regression (controlling a priori for maternal age, cell counts, low socioeconomic status, and gestational age at the time of sample collection), and Kaplan-Meier survival analyses. The log-rank test was used to test the equality of the survival functions. RESULTS: Overall, 163 patients met the inclusion criteria. Of the patients, 48%, 39%, and 21% delivered at <37, <34, and <28 weeks of gestation, respectively. The median AgeAccelGrim was -0.35 years (interquartile range, -2.24 to 1.31) for those delivering at term. Those delivering preterm had higher AgeAccelGrim values that were inversely proportional to delivery gestational age (preterm birth at <37 weeks of gestation: +0.40 years [interquartile range: -1.21 to +2.28]; preterm birth at <34 weeks of gestation: +0.51 years [interquartile range: -1.05 to +2.67]; preterm birth at <28 weeks of gestation: +1.05 years [interquartile range: -0.72 to +2.72]). Estimated DNA methylation of the 7 epigenetic clock component values was increased among those with preterm birth at <34 weeks of gestation, although the differences were only significant for DNA methylation of plasminogen activation inhibitor 1. In regression models, AgeAcccelGrim was associated with an elevated risk of preterm birth with increasing magnitude for increasing severity of preterm birth. For each 1-year increase in the AgeAccelGrim value (ie, each 1-year increase in biological age compared with chronologic age), the adjusted odds of preterm birth were 11% (adjusted odds ratio, 1.11; 95% confidence interval, 1.00-1.24), 13% (adjusted odds ratio, 1.13; 95% confidence interval, 1.01-1.26), and 18% (adjusted odds ratio, 1.18; 95% confidence interval, 1.04-1.35) higher for preterm birth at <37, <34, and <28 weeks of gestation, respectively. Similarly, individuals with accelerated biological aging (≥75th percentile AgeAccelGrim) had more than double the odds of preterm birth at <34 weeks of gestation (adjusted odds ratio, 2.36; 95% confidence interval, 1.10-5.08) and more than triple the odds of preterm birth at <28 weeks of gestation (adjusted odds ratio, 3.89; 95% confidence interval, 1.61-9.38). The adjusted odds ratio for preterm birth at <37 weeks of gestation was 1.73 but spanned the null (adjusted odds ratio, 1.73; 95% confidence interval, 0.81-3.69). In Kaplan-Meier survival analyses, those in the highest AgeAccelGrim quartile delivered the earliest (log-rank P value of <.001). CONCLUSION: Accelerated biological aging was associated with preterm birth among high-risk patients. Future research confirming these findings and elucidating factors that slow biological aging may improve birth outcomes.

Physical activity and pregnancy outcomes: an expert review.

This expert review aimed to assess current literature on the effect and tracking of physical activity during pregnancy and associated outcomes. Self-reported physical activity may be inaccurate given the subjective nature of the questionnaires. The accelerometer ActiGraph is considered the "gold standard" to objectively measure physical activity. However, other more user-friendly wearable devices are now widely available and may accurately track physical activity. Conclusive data from both validated activity questionnaires and accelerometers indicate that physical activity is safe during pregnancy. In addition, studies of physical activity during pregnancy that evaluate pregnancy outcomes have found reduced risks of preterm birth, preeclampsia, and gestational diabetes mellitus and improved mental health among individuals who regularly engage in physical activity. In the United States, approximately 48% of pregnant individuals gain more than the recommended amount of weight during pregnancy; excessive gestational weight gain is associated with an increased risk of maternal and fetal complications, including preterm birth, preeclampsia, and gestational diabetes mellitus, and corresponding higher adverse short- and long-term maternal and offspring health outcomes. Although physical activity is safe during pregnancy and may reduce excessive gestational weight gain and resultant pregnancy complications, further research is needed to determine the frequency and duration of specific types of physical activity during pregnancy. Providers should encourage physical activity before and during pregnancy and educate patients regarding the benefits and safety of physical activity.

Engaging family members in maternal, infant and young child nutrition activities in low- and middle-income countries: A systematic scoping review.

The influence of fathers, grandmothers and other family members on maternal, infant and young child nutrition practices has been well documented for decades, yet many social and behavioural interventions continue to reach only mothers. While recent guidelines recommend involving fathers, grandmothers and other family members in maternal and child nutrition, we lack a comprehensive review of interventions that have engaged them. This scoping review aimed to address this gap by describing social and behavioural interventions to engage family members in maternal and child nutrition in low- and middle-income countries. We systematically searched PubMed, Scopus, Web of Science, Global Health and CINAHL for peer-reviewed studies meeting inclusion criteria. We screened 6,570 abstracts, evaluated 179 full-text articles, and included 87 articles from 63 studies. Studies reported a broad range of approaches to engage fathers, grandmothers and other family members to support maternal nutrition (n = 6); breastfeeding (n = 32); complementary feeding (n = 6) and multiple maternal and child nutrition practices (n = 19). Interventions were facility and community based; included individual and group-based interpersonal communication, community mobilization, mass media and mHealth; and reached mothers and family members together or separately. Most interventions were located within the health sector; rare exceptions included nutrition-sensitive agriculture, social protection, early child development and community development interventions. Few interventions addressed gender norms, decision-making, and family dynamics or described formative research or theories informing intervention design. These diverse studies can shed light on innovative programme approaches to increase family support for maternal and child nutrition.

Exposure to toxic metals and per- and polyfluoroalkyl substances and the risk of preeclampsia and preterm birth in the United States: a review.

Preeclampsia and preterm birth are among the most common pregnancy complications and are the leading causes of maternal and fetal morbidity and mortality in the United States. Adverse pregnancy outcomes are multifactorial in nature and increasing evidence suggests that the pathophysiology behind preterm birth and preeclampsia may be similar-specifically, both of these disorders may involve abnormalities in placental vasculature. A growing body of literature supports that exposure to environmental contaminants in the air, water, soil, and consumer and household products serves as a key factor influencing the development of adverse pregnancy outcomes. In pregnant women, toxic metals have been detected in urine, peripheral blood, nail clippings, and amniotic fluid. The placenta serves as a "gatekeeper" between maternal and fetal exposures, because it can reduce or enhance fetal exposure to various toxicants. Proposed mechanisms underlying toxicant-mediated damage include disrupted placental vasculogenesis, an up-regulated proinflammatory state, oxidative stressors contributing to prostaglandin production and consequent cervical ripening, uterine contractions, and ruptured membranes and epigenetic changes that contribute to disrupted regulation of endocrine and immune system signaling. The objective of this review is to provide an overview of studies examining the relationships between environmental contaminants in the US setting, specifically inorganic (eg, cadmium, arsenic, lead, and mercury) and organic (eg, per- and polyfluoroalkyl substances) toxicants, and the development of preeclampsia and preterm birth among women in the United States.

Mixed-Methods Systematic Review of Behavioral Interventions in Low- and Middle-Income Countries to Increase Family Support for Maternal, Infant, and Young Child Nutrition during the First 1000 Days.

Fathers, grandmothers, and other family members' influence on maternal, infant, and young child nutrition (MIYCN) is widely recognized, yet synthesis of the effectiveness of engaging them to improve nutrition practices during the first 1000 d is lacking. We examined the impact of behavioral interventions to engage family members in MIYCN in low- and middle-income countries through a mixed-methods systematic review. We screened 5733 abstracts and included 35 peer-reviewed articles on 25 studies (16 with quantitative and 13 with qualitative data). Most quantitative studies focused on early breastfeeding, primarily engaging fathers or, less often, grandmothers. Most found positive impacts on exclusive breastfeeding rates and family members' knowledge and support. The few quantitative studies on complementary feeding, maternal nutrition, and multiple outcomes also suggested benefits. Qualitative themes included improved nutrition behaviors, enhanced relationships, and challenges due to social norms. Interventions engaging family members can increase awareness and build support for MIYCN, but more rigorous study designs are needed. This systematic review is registered at PROSPERO as CRD42018090273, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=90273.

Serological survey of British sheep flocks for evidence of exposure to ovine pestiviruses.

Ovine pestiviruses have the potential to reduce productivity in the British sheep flock. However, their prevalence and impact are currently poorly understood. This study aimed to estimate the exposure to pestiviruses in adult breeding ewe stock. Blood samples collected for metabolic profiling before lambing were tested using an ELISA that detected antibodies raised to both bovine viral diarrhoea virus and Border disease virus. A group of 15 animals were tested per flock. A total of 34 farms were tested, of which 13 had at least one seropositive animal. In those positive flocks between one and nine of the animals tested antibody-positive. Positive flocks were identified in all regions of Great Britain. This work suggests that exposure to ovine pestiviruses is widespread, and that it is timely to investigate flock-level prevalence and possible production impacts of endemic infection.

Quantitative analysis of antibiotic usage in British sheep flocks.

The aim of this study was to examine the variation in antibiotic usage between 207 commercial sheep flocks using their veterinary practice prescribing records. Mean and median prescribed mass per population corrected unit (mg/PCU) was 11.38 and 5.95, respectively and closely correlated with animal defined daily dose (ADDD) 1.47 (mean), 0.74 (median) (R2=0.84, P<0.001). This is low in comparison with the suggested target (an average across all the UK livestock sectors) of 50 mg/PCU. In total, 80 per cent of all antibiotic usage occurred in the 39 per cent of flocks where per animal usage was greater than 9.0 mg/PCU. Parenteral antibiotics, principally oxytetracycline, represented 82 per cent of the total prescribed mass, 65.5 per cent of antibiotics (mg/PCU) were prescribed for the treatment of lameness. Oral antibiotics were prescribed to 49 per cent of flocks, 64 per cent of predicted lamb crop/farm. Lowland flocks were prescribed significantly more antibiotics than hill flocks. Variance partitioning apportioned 79 per cent of variation in total antibiotic usage (mg/PCU) to the farm level and 21 per cent to the veterinary practice indicating that veterinary practices have a substantial impact on overall antimicrobial usage. Reducing antibiotic usage in the sheep sector should be possible with better understanding of the drivers of high usage in individual flocks and of veterinary prescribing practices.

Survey of prevalence and investigation of predictors and staining patterns of the split upper eyelid defect in Hebridean sheep.

The split upper eyelid defect (SUED) is a congenital defect of the upper eyelid thought to be exclusive to multihorned sheep. Eleven flocks with a high proportion of multihorned Hebridean sheep were visited in 2011. Statistical analysis was performed generating Pearson's chi-squared analysis, as well as (1) logistic regression, (2) ordinal logistic regression and (3) linear regression models. Four hundred and seventy-three pure-bred Hebridean sheep and one crossbred lamb were examined. Of all the multihorned animals inspected in 2011, 9.7 per cent of adults had evidence of SUED in one or more eyelids, with 17.6 per cent of lambs presented with one or more eyelid affected. Having five or more horns was protective in the linear regression model on eye-level data (p=0.045). Forward-facing horns were consistently associated with a 'worst' eye score in the eye-level data, with an odds ratio (OR) as high as 9.4 when compared with a base of backward-facing horns (p=0.002). Eyes positive for SUED were significantly more likely to be rose bengal stain-positive in all four analysis, including multilevel mixed effect ordered logistic regression (p<0.001, OR 149.3). A novel lesion was identified during the course of the study, with 3.4 per cent of lambs presented with dermoid. SUED was also identified in a crossbred animal. Further work is needed to quantify the exact cost to animals with unilateral or bilateral SUED with subtle and production cost of SUED.