Real-world diagnostic potential of bacterial biomarkers of canine periodontitis.

Introduction: The objective of this study was to investigate the diagnostic potential of bacterial biomarkers by comparing the performance of molecular detection assays with clinical assessments of dog's oral health performed by veterinarians. Methods: Supragingival and subgingival plaque samples were collected from 127 client-owned dogs, pre-booked for procedures under general anesthesia, visiting veterinary practices in the United States. DNA was extracted and bacterial biomarkers quantified using quantitative polymerase chain reaction. Gingivitis and periodontitis were recorded by a trained clinician using the Weighted Gingivitis Periodontitis Score which involved assessing the buccal surfaces of 18 teeth while under general anesthesia. Intraoral dental radiographs of the left and right mandibular first molar teeth were also obtained. These data were then used to establish the diagnostic performance of the molecular assay to detect periodontitis. Results: An initial conscious, visual oral examination performed by the veterinarian identified 67.7% of dogs as having periodontitis, but examination under general anesthesia indicated a higher proportion (86.6%). Analysis of supragingival plaque samples collected by veterinarians from conscious and unconscious dogs demonstrated the assay had an accuracy of 77.7 to 80.9%, a sensitivity of 77.6 to 81.0%, and a specificity of 80.0%. Discussion: Use of this molecular screening tool in conscious dogs has the potential to improve early periodontal disease detection and support veterinary decision making, ultimately improving the oral health of dogs and consequently their quality of life.

Assessment of salivary cortisol dynamics in an infantry training exercise: a pilot study.

INTRODUCTION: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment. METHOD: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry. RESULTS: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ2=0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively. CONCLUSIONS: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting.

Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.

BACKGROUND: Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding. METHODS: We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant's effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects. RESULTS: The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy. CONCLUSIONS: Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.

The dynamic theory of reasoned action: evidence for a reverse causal process in the context of WHO handwashing guidelines.

OBJECTIVE: This study provided a first empirical test of the Reverse Dynamic Theory of Reasoned Action (RDTRA) developed by Boster et al. DESIGN: In a longitudinal experiment, 169 participants were exposed to a WHO handwashing-guidelines behavioural induction, followed by an immediate posttest and a follow-up one week later. MAIN OUTCOME MEASURES: The study measured attitudes and norms about WHO handwashing guidelines, as well as self-reported handwashing behaviour. RESULTS: The experimental induction produced variance in self-reported handwashing behaviour, allowing a test of the RDTRA using path analysis and structural equation modelling (SEM). Results were consistent with the RDTRA, with a positive effect of behaviour on both the attitude and norm coupled with excellent model fit. Results were inconsistent with behaviour as an outcome of attitudes and norms in this context. CONCLUSION: For health behaviours, such as the WHO handwashing technique, initial behavioural adoption may promote subsequent shaping of attitudes and perceived norms. Boundary conditions for this effect may include the degree of spontaneity and consent involved in behaviour adoption.

Approaches to screening for hyperglycaemia in pregnant women during and after the COVID-19 pandemic.

AIM: To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA1c , during the COVID-19 pandemic. METHODS: Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004-2008; 826 consecutive gestational diabetes pregnancies, 2014-2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large-for-gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver-operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA1c performance. RESULTS: Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver-operating characteristic curve for both criteria 0.81 (95% CI 0.79-0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver-operating characteristic curve 0.75 (95% CI 0.65-0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver-operating characteristic curve 0.92 (95% CI 0.85-0.98)] and HbA1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75-0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77-0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2-5.4 mmol/l (sensitivity 18-41%; specificity 97-98%). CONCLUSIONS: Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.

Is there an increased risk of perinatal mental disorder in women with gestational diabetes? A systematic review and meta-analysis.

AIM: Gestational diabetes (GDM) and mental disorder are common perinatal morbidities and are associated with adverse maternal and child outcomes. While there is a relationship between type 2 diabetes and mental disorder, the relationship between GDM and mental disorder has been less studied. We conducted a systematic review and meta-analysis of the prevalence of mental disorders in women with GDM and their risk for mental disorders compared with women without GDM. METHODS: Published, peer-reviewed literature measuring prevalence and/or odds of GDM and perinatal mental disorders was reviewed systematically. Risk of bias was assessed using a checklist. Two independent reviewers were involved. Analyses were grouped by stage of peripartum, i.e. antepartum at the time of GDM diagnosis and after diagnosis, and in the postpartum. RESULTS: Sixty-two studies were included. There was an increased risk of depressive symptoms in the antenatal period around the time of diagnosis of GDM [odds ratio (OR) 2.08; 95% confidence interval (CI) 1.42, 3.05] and in the postnatal period (OR 1.59; 95% CI 1.26, 2.00). CONCLUSIONS: Given the potential relationship between GDM and perinatal mental disorders, integration of physical and mental healthcare in women experiencing GDM and mental disorders could improve short- and long-term outcomes for women and their children.

Positive adaptation of HPA axis function in women during 44 weeks of infantry-based military training.

BACKGROUND: Basic military training (BMT) is a useful model of prolonged exposure to multiple stressors. 8-12 week BMT is associated with perturbations in the hypothalamic-pituitary-adrenal (HPA) axis which could predispose recruits to injury and psychological strain. However, characterisations of HPA axis adaptations during BMT have not been comprehensive and most studies included few if any women. METHODS: We studied women undertaking an arduous, 44-week BMT programme in the UK. Anxiety, depression and resilience questionnaires, average hair cortisol concentration (HCC), morning and evening saliva cortisol and morning plasma cortisol were assessed at regular intervals throughout. A 1-h dynamic cortisol response to 1 µg adrenocorticotrophic hormone-1-24 was performed during weeks 1 and 29. RESULTS: Fifty-three women (aged 24 ± 2.5 years) completed the study. Questionnaires demonstrated increased depression and reduced resilience during training (F 6.93 and F 7.24, respectively, both p < 0.001). HCC increased from 3 months before training to the final 3 months of training (median (IQR) 9.63 (5.38, 16.26) versus 11.56 (6.2, 22.45) pg/mg, p = 0.003). Morning saliva cortisol increased during the first 7 weeks of training (0.44 ± 0.23 versus 0.59 ± 0.24 µg/dl p < 0.001) and decreased thereafter, with no difference between the first and final weeks (0.44 ± 0.23 versus 0.38 ± 0.21 µg/dl, p = 0.2). Evening saliva cortisol did not change. Fasting cortisol decreased during training (beginning, mid and end-training concentrations: 701 ± 134, 671 ± 158 and 561 ± 177 nmol/l, respectively, p < 0.001). Afternoon basal cortisol increased during training while there was a trend towards increased peak stimulated cortisol (177 ± 92 versus 259 ± 13 nmol/l, p = 0.003, and 589 ± 164 versus 656 ± 135, p = 0.058, respectively). DISCUSSION: These results suggest a normal stress response in early training was followed quickly by habituation, despite psychological and physical stress evidenced by questionnaire scores and HCC, respectively. There was no evidence of HPA axis maladaptation. These observations are reassuring for women undertaking arduous employment.

Transforming mental well-being for people with diabetes: research recommendations from Diabetes UK's 2019 Diabetes and Mental Well-Being Workshop.

AIMS: To identify key gaps in the research evidence base that could help to improve the mental well-being of people with diabetes, and to provide recommendations to researchers and research funders on how best to address them. METHODS: A 2-day international research workshop was conducted, bringing together research experts in diabetes and in mental health, people living with diabetes and healthcare professionals. RESULTS: The following key areas needing increased financial investment in research were identified: understanding the mechanisms underlying depression; understanding the multifactorial impact of social stigma; improving the language used by healthcare professionals; supporting people who find it difficult to engage with their diabetes; supporting significant others; supporting people with diabetes and eating disorders; improving models of care by learning from best practice; the potential benefits of screening and managing diabetes distress in routine diabetes care pathways; primary prevention of mental health issues at the time of diagnosis of diabetes; establishing the effectiveness of diabetes therapies on mood and other mental health issues; and understanding the impact of current diabetes technologies on mental health. Research recommendations as to how to address each of these priority areas were also developed. CONCLUSIONS: This inaugural position statement outlines recommendations to address the urgent unmet need related to the mental well-being of people living with diabetes, and calls on the research community and funders to develop research programmes and strategies to reduce this need.

Risk of heat illness in men and women: A systematic review and meta-analysis.

BACKGROUND: Heat illness (HI) is a growing global concern; its incidence has risen dramatically across the world in recent years. The individual factors whereby elevated core temperature produces HI are not well-understood. Given known physiological differences between men and women pertaining to temperature regulation, we hypothesized that women would be at increased risk of HI than men. OBJECTIVES: We aimed to determine the relative risk of HI in women compared with men through an exhaustive literature review and meta-analysis. METHODS: We search PubMed and Ovid Medline databases from inception to Apr 2017. Search terms included all permutations of sex and heat illness (including heatstroke and exertional heat illness) with no language restrictions. We included adult or adolescent human data reporting comparable male and female HI rates. One reviewer identified and screened titles and abstracts. Two independent reviewers applied eligibility criteria. Disagreements were resolved with a third reviewer. RESULTS: Of 5888 articles identified by searches, 36 were included in the systematic review and 22 in the meta-analysis. The mean (standard deviation) quality score was 3.31(1.25)/5. Overall the rate among women was consistently lower than men across the lifespan. The male: female pooled IRR was 2.28 (p < 0.001, 95% CI: 1.66-3.16). There was modest heterogeneity (between-studies variance (τ2) = 0.02). The rates did not differ significantly when corrected for severity or occupation. DISCUSSION: The rate of HI was significantly increased in men compared with women. Risk for HI might be conferred by psychological and behavioral factors rather than physiological ones. Further research is required to delineate which groups are at greatest risk, leading to the development of mitigation strategies against HI. OTHER: No funding was received. The authors acknowledge the support of the UK Women in Ground Close Combat Review. The Study was registered with PROSPREO CRD42017064739.

Maternal antenatal daytime sleepiness and child neuropsychiatric and neurocognitive development.

BACKGROUND: The prevalence of sleep problems among pregnant women is over 50%, and daytime sleepiness is among the most common sleep problems. Previous studies have associated antenatal sleep problems with adverse maternal health and neonatal outcomes, but the consequences of antenatal sleep problems and particularly daytime sleepiness on child psychological development have not been assessed prospectively. METHODS: In this prospective cohort study including 111 mother-child dyads, we examined the associations of maternal daytime sleepiness during pregnancy, assessed at 17 and 28 weeks of gestation using the Epworth Sleepiness Scale, with child neuropsychiatric problems and neuropsychological development, assessed with mother-rated questionnaires and individually administered neuropsychological tests, at child age 2.6-5.7 years (mean = 4.3 years). RESULTS: Independently of sociodemographic and perinatal covariates and maternal depressive and anxiety symptoms during and/or after pregnancy, maternal antenatal daytime sleepiness was associated with increased total [unstandardized regression coefficient (B) = 0.25 standard deviation (s.d.) units; 95% confidence interval (CI) 0.01-0.48] and internalizing (B = 0.25 s.d.s: 95% CI 0.01-0.49) psychiatric problems and ADHD symptoms (B = 0.27 s.d.s: 95% CI 0.04-0.50) in children, and with poorer executive function, particularly in the areas of attention, working memory and inhibitory control (B = -0.39 s.d.s: 95% CI -0.69 to -0.10). CONCLUSIONS: Maternal antenatal daytime sleepiness carries adverse consequences for offspring psychological development. The assessment of sleep problems may be an important addition to standard antenatal care.

Bioactive components in human milk are differentially associated with rates of lean and fat mass deposition in infants of mothers with normal vs. elevated BMI.

OBJECTIVE: To model breastfed infant growth and body composition patterns over the first 4 months with multiple bioactive components of human milk (HM) and clinical factors (including maternal BMI status), which are related to growth. METHODS: Longitudinal observation of infant growth and body composition from 0 to 4 months among 41 predominantly breastfed infants (25 mothers of Normal-weight and 16 mothers with overweight/obesity). Fasted morning HM samples were collected at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin, cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight-for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and %fat gain were modelled controlling for clinical covariates. RESULTS: HM insulin negatively associated with WLZ trajectory among infants of NW mothers (P = 0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM glucose (P < 0.001) was associated with slower rates of infant FFM gain. Infants of mothers with OW/Ob exhibited slower rates of FFM gain. HM protein, adiponectin and insulin concentrations, and n-6:n-3 ratio were all significant predictors in the model of infant fat mass gain (P < 0.03). Any amount of formula supplementation was associated with faster fat gain (P = 0.002). The model of %fat gain was similar to that of fat mass gain, excepting HM adiponectin was not a significant covariate, and a trend for maternal OW/Ob to correlate with faster %fat gain (P = 0.056). CONCLUSIONS: Bioactive components in HM may contribute to regulation of partitioning of body composition, and these contributions may differ between mothers of normal-weight vs. with OW/Ob.

Activity behaviors in lean and morbidly obese pregnant women.

Interventions to increase physical activity in pregnancy are challenging for morbidly obese women. Targeting sedentary behaviors may be a suitable alternative to increase energy expenditure. We aimed to determine total energy expenditure, and energy expended in sedentary activities in morbidly obese and lean pregnant women. We administered the Pregnancy Physical Activity Questionnaire (nonobjective) and the Actical accelerometer (objective) to morbidly obese (BMI ≥ 40 kg/m²) and lean (BMI ≤ 25 Kg/m²) pregnant women recruited in early (<24 weeks), and late (≥24 weeks) gestation. Data are mean (SD). Morbidly obese pregnant women reported expending significantly more energy per day in early (n = 140 vs 109; 3198.4 (1847.1) vs 1972.3 (10284.8) Kcal/d, P < .0001) and late (n = 104 vs 64; 3078.2 (1356.5) vs 1947.5 (652.0) Kcal/d, P < .0001) pregnancy, and expended significantly more energy in sedentary activities, in early (816.1 (423.5) vs 540.1 (244.9) Kcal/d, P < .0001) and late (881.6 (455.4) vs 581.1 (248.5) Kcal/d, P < .0001) pregnancy, than lean pregnant women. No differences were observed in the proportion of energy expended sedentary between lean and morbidly obese pregnant women. The greater total energy expenditure in morbidly obese pregnant women was corroborated by Actical accelerometer in early (n = 14 per group, obese 1167.7 (313.6) Kcal; lean 781.1 (210.1) Kcal, P < .05), and in late (n = 14 per group, obese 1223.6 (351.5) Kcal; lean 893.7 (175.9) Kcal, P < .05) pregnancy. In conclusion, non-objective and objective measures showed morbidly obese pregnant women expended more energy per day than lean pregnant. Further studies are needed to determine whether sedentary behaviors are a suitable target for intervention in morbidly obese pregnancy.

Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Brain Development in Fetuses of Mothers with Diabetes: A Case-Control MR Imaging Study.

BACKGROUND AND PURPOSE: Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of brain metabolism (1H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured. MATERIALS AND METHODS: Women with singleton pregnancies with diabetes (n = 26) and healthy controls (n = 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks' gestation. RESULTS: Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for 1H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean [SD]) in the fetal brain in women with diabetes compared with controls (1.74 [0.79] versus 1.79 [0.64], P = .81; and 0.78 [0.28] versus 0.94 [0.36], P = .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 [0.11] versus 0.53 [0.10], P = .04). There was no difference in mean [SD] anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 [0.12] versus 1.16 [0.08], P = .96; 1.54 [0.16] versus 1.59 [0.20], P = .56; and 1.49 [0.23] versus 1.52 [0.23], P = .89, respectively) or volume of the cerebrum (243.0 mL [22.7 mL] versus 253.8 mL [31.6 mL], P = .38). CONCLUSIONS: Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted.

Reproductive dysfunction and associated pathology in women undergoing military training.

INTRODUCTION: Evidence from civilian athletes raises the question of whether reproductive dysfunction may be seen in female soldiers as a result of military training. Such reproductive dysfunction consists of impaired ovulation with or without long-term subfertility. METHODS: A critical review of pertinent evidence following an extensive literature search. RESULTS: The evidence points towards reduced energy availability as the most likely explanation for exercise-induced reproductive dysfunction. Evidence also suggests that reproductive dysfunction is mediated by activation of the hypothalamic-pituitary-adrenal axis and suppression of the hypothalamic-pituitary-gonadal axis, with elevated ghrelin and reduced leptin likely to play an important role. The observed reproductive dysfunction exists as part of a female athletic triad, together with osteopenia and disordered eating. If this phenomenon was shown to exist with UK military training, this would be of significant concern. We hypothesise that the nature of military training and possibly field exercises may contribute to greater risk of reproductive dysfunction among female military trainees compared with exercising civilian controls. We discuss the features of military training and its participants, such as energy availability, age at recruitment, body phenotype, type of physical training, psychogenic stressors, altered sleep pattern and elemental exposure as contributors to reproductive dysfunction. CONCLUSIONS: We identify lines of future research to more fully characterise reproductive dysfunction in military women and suggest possible interventions that, if indicated, could improve their future well-being.

Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans suggest increased vulnerability in females: a systematic review.

Fetal glucocorticoid overexposure is a key mechanism linking early development with later-life disease. In humans, low birth weight associates with increased fasting cortisol, hypothalamic-pituitary-adrenal (HPA) axis reactivity, and with cardiovascular risk and cognitive decline. As there are sex differences in these adult diseases, we hypothesized that there may be sex differences in programming of the HPA axis in response to prenatal stressors. We conducted a systematic review following Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched Embase, MEDLINE and Web of Science from inception to 31 October 2016. We included studies related to sex differences, prenatal exposures and HPA axis. We excluded studies investigating specific disease states. The 23 included studies investigated the consequences of low birth weight, preterm birth and maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology and offspring HPA axis function in early life and later life. Female offspring exposed to stressors had increased HPA axis reactivity compared with males. Furthermore, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with changes in the expression of 11ß-hydroxysteroid dehydrogenase enzymes in response to maternal glucocorticoid exposure or asthma. Among males there was some evidence of altered diurnal cortisol secretion. We conclude that although there is some evidence of male vulnerability leading to altered diurnal cortisol secretion, the female HPA axis is more vulnerable to programming, particularly in terms of its reactivity; this suggests a mechanism underlying sex differences in later-life diseases.

Prenatal exposure to very severe maternal obesity is associated with adverse neuropsychiatric outcomes in children.

BACKGROUND: Prenatal maternal obesity has been linked to adverse childhood neuropsychiatric outcomes, including increased symptoms of attention deficit hyperactivity disorder (ADHD), internalizing and externalizing problems, affective disorders and neurodevelopmental problems but few studies have studied neuropsychiatric outcomes among offspring born to very severely obese women or assessed potential familial confounding by maternal psychological distress. METHOD: We evaluated neuropsychiatric symptoms in 112 children aged 3-5 years whose mothers had participated in a longitudinal study of obesity in pregnancy (50 very severe obesity, BMI ⩾40 kg/m2, obese class III and 62 lean, BMI 18.5-25 kg/m2). The mothers completed the Conners' Hyperactivity Scale, Early Symptomatic Syndrome Eliciting Neurodevelopmental Clinical Examination Questionnaire (ESSENCE-Q), Child's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ), and Child Behavior Checklist (CBCL) to assess child neuropsychiatric symptoms. Covariates included child's sex, age, birthweight, gestational age, socioeconomic deprivation levels, maternal age, parity, smoking status during pregnancy, gestational diabetes and maternal concurrent symptoms of anxiety and depression assessed using State Anxiety of Spielberger State-Trait Anxiety Index (STAI) and General Health Questionnaire (GHQ), respectively. RESULTS: Children exposed to prenatal maternal very severe obesity had significantly higher scores in the Conners' Hyperactivity Scale; ESSENCE-Q; total sleep problems in CSHQ; hyperactivity, conduct problems and total difficulties scales of the SDQ; higher externalizing and total problems, anxious/depressed, aggressive behaviour and other problem syndrome scores and higher DSM-oriented affective, anxiety and ADHD problems in CBCL. Prenatal maternal very severe obesity remained a significant predictor of child neuropsychiatric problems across multiple scales independent of demographic factors, prenatal factors and maternal concurrent symptoms of anxiety and depression. CONCLUSIONS: Prenatal maternal very severe obesity is a strong predictor of increased neuropsychiatric problems in early childhood.