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Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins. Cox regression was used to estimate associations between EDs and ADHD or ASD, and mediation analysis was used to assess the effects of intermediate mood or anxiety disorders. Polygenic scores (PGSs) were used to investigate the genetic association between anorexia nervosa (AN) and ADHD or ASD. Significantly increased risk for any ED was observed following an ADHD [hazard ratio = 1.97, 95% confidence interval = 1.75-2.22] or ASD diagnosis [2.82, 2.48-3.19]. Mediation analysis suggested that intermediate mood or anxiety disorders could account for 44-100% of the association between ADHD or ASD and ED. Individuals with a full sibling or maternal halfsibling with ASD had increased risk of AN [1.54, 1.33-1.78; 1.45, 1.08-1.94] compared to those with siblings without ASD. A positive association was found between ASD-PGS and AN risk [1.06, 1.02-1.09]. In this study, positive phenotypic associations between EDs and ADHD or ASD, mediation by mood or anxiety disorder, and a genetic association between ASD-PGS and AN were observed. These findings could guide future research in the development of new treatments that can mitigate the development of EDs among individuals with ADHD or ASD., Competing Interests: Conflict of interest Dr. Bulik is an author and royalty recipient from Pearson. D.D. had received speaker fee from Medici Nordic. The remaining authors declare no conflict of interest.

Background: The pathophysiology of obstructive sleep apnea in pregnancy remains poorly understood and studies examining the effect of treatment with positive airway pressure on pregnancy have been limited., Objective: This study aimed to perform a randomized controlled trial of positive airway pressure treatment for obstructive sleep apnea in pregnancy., Study Design: Participants with a body mass index ≥30 kg/m 2 underwent polysomnography at 14 to 20 weeks' gestation (visit 1) and those with obstructive sleep apnea (apnea-hypopnea index ≥5 but <50) were enrolled. In phase 1, participants were randomized to autotitrating positive airway pressure vs sham positive airway pressure; in phase 2, the sham arm was replaced with a sleep hygiene control. Participants returned at 28 to 31 weeks' gestation (visit 2). The mean arterial blood pressure, uterine artery Doppler pulsatility index, endoglin, soluble FMS-like tyrosine kinase 1 levels, and placental growth factor levels were measured, as well as fasting glucose and insulin to calculate insulin resistance (homeostatic model assessment for insulin resistance). The primary outcome was a composite of the uterine artery Doppler pulsatility index, soluble FMS-like tyrosine kinase 1 to placental growth factor ratio, and the homeostatic model assessment for insulin resistance. For secondary analyses, each outcome variable was analyzed independently. Adherence to treatment was examined., Results: A total of 241 participants completed visit 1, and 89 (37%) had an apnea-hypopnea index between 5 and 50. Of the those, 51 participants were randomized in phase 1 and 38 in phase 2. There was no significant difference in our primary outcome by treatment group. In secondary analyses, the uterine artery Doppler pulsatility index was lower in participants on autotitrating positive airway pressure when compared with sleep hygiene controls. Otherwise, there were no differences in the mean arterial blood pressure, angiogenic markers, or metabolic markers in phase 1, phase 2, or across the entire study. The overall adherence to autotitrating positive airway pressure therapy was low, but the mean use was greater in phase 2 (0.3±0.6 hours/night vs 1.3±2.3 hours/night; P=.10). For those on active therapy, fasting glucose values decreased as adherence increased., Conclusion: This randomized controlled trial of autotitrating positive airway pressure in pregnancy did not find any differences in a composite primary cardiometabolic risk profile between the treatment groups. Higher autotitrating positive airway pressure adherence was associated with lower fasting glucose levels. The use of a sham positive airway pressure control arm in phase1 may have negatively impacted adherence to active treatment., (Copyright © 2022. Published by Elsevier Inc.)

Study Objectives: To evaluate the impact of sleep-disordered breathing (SDB) on vascular, angiogenic and metabolic analytes in pregnancy., Methods: Participants with a body mass index ≥30 kg/m 2 underwent polysomnography at 14-20 weeks gestation (visit 1). Participants with SDB (defined as an apnea-hypopnea index ≥5 events/h) were then enrolled in a separate trial. SDB-negative participants returned for a polysomnogram at 28-31 weeks (visit 2) and were recategorized as persistent-negative SDB or new-onset SDB. Mean arterial blood pressure, mean uterine artery Doppler pulsatility index, endoglin, soluble Feline McDonough Sarcoma-like tyrosine kinase 1, placental growth factor, and the homeostatic model assessment for insulin resistance were measured after each visit. Our primary outcome was a composite of uterine artery Doppler pulsatility index, soluble FMS-like tyrosine kinase 1/placental growth factor ratio, and homeostatic model assessment for insulin resistance. For secondary analyses, each outcome variable was analyzed independently., Results: A total of 242 and 130 participants completed visit 1 and visit 2, respectively. Newly diagnosed SDB was present in 37% of individuals at visit 1 and 31% of individuals at visit 2. No significant differences in our composite outcome vector were observed in individuals with and without SDB at either visit. In our secondary analysis, mean arterial blood pressure (88.7 ± 7.3 mm Hg vs 85.4 ± 7.1 mm Hg, P = .04) and fasting glucose (92.4 ± 15.2 mg/dL vs 86.6 ± 11.5 mg/dL, P = .05) were higher in participants with early pregnancy SDB. These associations were not observed for new-onset SDB. No associations were observed between uterine artery Doppler pulsatility index and angiogenic markers and SDB in pregnancy., Conclusions: SDB in early pregnancy was not associated with our composite primary outcome but was associated with higher mean arterial blood pressure and fasting glucose. The pathophysiologic changes that occur in pregnant individuals with SDB and how they lead to an increased risk of preeclampsia and gestational diabetes remain poorly understood., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP); URL: https://clinicaltrials.gov/ct2/show/NCT02086448; Identifier: NCT02086448., Citation: Onslow ML, Wolsk J, Wisniewski S, et al. The association between sleep-disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity. J Clin Sleep Med . 2023;19(1):97-109., (© 2023 American Academy of Sleep Medicine.)

Heterogeneity, frequent diagnostic fluctuation across presentations, and global concerns with the absence of effective treatments all encourage science that moves the field toward individualized or precision medicine in eating disorders. We review recent advances in psychiatric genetics focusing on genome-wide association studies (GWAS) in eating disorders. Given that the only eating disorder to be the subject of GWAS to date is anorexia nervosa, we review anorexia GWAS and enumerate the prospects and challenges of a genomics-driven approach towards personalized intervention in eating disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: A common challenge in medicine, exemplified in the analysis of biomarker data, is that large studies are needed for sufficient statistical power. Often, this may only be achievable by aggregating multiple cohorts. However, different studies may use disparate platforms for laboratory analysis, which can hinder merging., Methods: Using circulating placental growth factor (PlGF), a potential biomarker for hypertensive disorders of pregnancy (HDP) such as preeclampsia, as an example, we investigated how such issues can be overcome by inter-platform standardization and merging algorithms. We studied 16,462 pregnancies from 22 study cohorts. PlGF measurements (gestational age ⩾20 weeks) analyzed on one of four platforms: R&D Systems, AlereTriage, RocheElecsys or AbbottArchitect, were available for 13,429 women. Two merging algorithms, using Z-Score and Multiple of Median transformations, were applied., Results: Best reference curves (BRC), based on merged, transformed PlGF measurements in uncomplicated pregnancy across six gestational age groups, were estimated. Identification of HDP by these PlGF-BRCs was compared to that of platform-specific curves., Conclusions: We demonstrate the feasibility of merging PlGF concentrations from different analytical platforms. Overall BRC identification of HDP performed at least as well as platform-specific curves. Our method can be extended to any set of biomarkers obtained from different laboratory platforms in any field. Merged biomarker data from multiple studies will improve statistical power and enlarge our understanding of the pathophysiology and management of medical syndromes., (Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: Maternal obesity is associated with increased risk of large-for-gestational-age (LGA) and small-for-gestational-age (SGA) births. Both are related to childhood obesity. This study considers that the patterns of gestational weight gain (GWG) may help to disentangle these competing risks., Methods: Patterns of GWG were characterized among a cohort of women with overweight or obesity (n = 651). Polytomous logistic regression models were tested for associations between GWG patterns and birth weight outcomes: SGA (<10th) and LGA (>90th percentile)., Results: Rates of SGA were higher than those for LGA (14.9% vs. 7.8%). Four GWG patterns were identified: consistently high (29%), early adequate/late high (33%), consistently adequate (18%), and consistently low (20%). Risk of LGA was highest in women with consistently high GWG (adjusted odds ratio [OR] 4.62 [1.53, 13.96]), and risk was elevated, but with lower magnitude, among women with early adequate/late high gains (OR 3.07 [1.01, 9.37]). High GWG before 20 weeks, regardless of later gain, was related to LGA. Low gain before 20 weeks accompanied by high gain later may be associated with reduced SGA risk (0.55 [0.29, 1.07])., Conclusions: The pattern of weight gain during pregnancy may be an important contributor to or marker of abnormal fetal growth among women with overweight or obesity., (© 2015 The Obesity Society.)

Background: A small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome., Methods: We analyzed the DNA methylation status of approximately 27,000 CpG sites in placental tissues in a massively parallel fashion using an oligonucleotide microarray. Follow up analysis of DNA methylation at specific CpG loci was performed using the Epityper MassArray approach and high-throughput bisulfite sequencing., Results: Preeclampsia-specific DNA methylation changes were identified in placental tissue samples irrespective of gestational age of delivery. In addition, we identified a group of CpG sites within specific gene sequences that were only altered in early onset-preeclampsia (EOPET) although these DNA methylation changes did not correlate with altered mRNA transcription. We found evidence that fetal gender influences DNA methylation at autosomal loci but could find no clear association between DNA methylation and gestational age., Conclusion: Preeclampsia is associated with altered placental DNA methylation. Fetal gender should be carefully considered during the design of future studies in which placental DNA is analyzed at the level of DNA methylation. Further large-scale analyses of preeclampsia-associated DNA methylation are necessary.

Introduction: Circulating angiogenic factors are potential markers for preeclampsia, but heterogeneous studies have failed to identify precise predictive/diagnostic properties. The Global CoLaboratory is investigating how to merge published data of angiogenic factors for meta-analysis on an individual sample basis., Objective: To amalgamate pregnancy angiogenic factor studies, investigate diagnostic and predictive properties of these markers in preeclampsia and placenta-related pregnancy complications, and to test if measures from disparate platforms can be standardised. This is the first report using PlGF measures to diagnose preeclampsia., Methods: Data were derived from 15 cohorts, within and outside the CoLaboratory network. Women were classified as either case (confirmed diagnosis of preeclampsia at sampling) or non-case (no preeclampsia at sampling). Individual PlGF measurements from four different analytical platforms were used, along with transformations of the data (e.g. log-transformations, transformations to a baseline platform). Transformed measurements were standardised both for specific platforms and globally, stratifying on gestational age. Different statistical techniques were compared., Results: The database currently contains 1442 cases and 11,512 non-cases, which were used to define an algorithm to merge PlGF measurements from different platforms. Non-case distributions were used to standardise case results. Diagnostic PlGF measurements in relation to preeclampsia will be presented and confirm feasibility., Conclusions: Future studies can extend this approach to other angiogenic factors, prediction as well as diagnosis and to other placenta-related disorders., (Copyright © 2013. Published by Elsevier B.V.)

Introduction: Endotoxin activates innate immunity, decreases insulin sensitivity and is associated with obesity. Recent data indicates that subclinical endotoxemia is associated with inflammation in obese women in late pregnancy., Objectives: The objective of this study was to quantify circulating endotoxin across pregnancy in lean and obese women, and assess the relationship between endotoxin and markers of inflammation and insulin sensitivity., Methods: Endotoxin was measured in sterile maternal EDTA plasma samples from 24 lean pregnant women (BMI=22.4±1.9kg/m(2)) and 45 obese pregnant women (BMI= 32.6±2.1kg/m(2)), and 6 non-pregnant women. Samples were collected at 10.5±3.1, 21.3±4.6 and 35.2±2.1weeks gestation. Endotoxin was quantified using the PyroGene Recombinant Factor C endotoxin detection assay from LONZA, inter-assay variability <10%. IL-6, myloperoxidase, uric acid, triglycerides, insulin and glucose were also measured. Statistical analysis was by repeated measures ANOVA and students t-test as appropriate. Correlation analysis was performed using Pearson product moment correlation coefficient. Statistical significance was accepted at p<0.05., Results: Endotoxin was significantly increased in both lean (10.4±5.3EU/ml) and obese (9.1±5.3EU/ml) pregnant women compared to non-pregnant women (4.3±2.6EU/ml, p<0.05). Endotoxin increased significantly across pregnancy in both lean and obese pregnant women (p<0.001), but was not different between these groups (table). Endotoxin was not associated with adiposity, IL-6, myloperoxidase, uric acid, triglycerides or insulin sensitivity as assessed by homeostasis model of insulin resistance (HOMA). Data are mean±SD. Repeated measures ANOVA p<0.001., Conclusion: Circulating endotoxin increases significantly during pregnancy, but endotoxin is not associated with markers of systemic inflammation or insulin resistance. Pregnancy may represent a condition of metabolic endotoxemia, however the causes and biologic activity of these increasing levels of endotoxin are unclear., (Copyright © 2012. Published by Elsevier B.V.)

Objective: Women who deliver preterm infants may be at increased risk for cardiovascular disease, perhaps related to dyslipidemia., Study Design: In a nested case control study of women with spontaneous preterm birth, cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were evaluated. Lipid concentrations and gestational changes, as well as risk for preterm birth, were evaluated in women who delivered <34 (n = 23), >or=34-<37 (n = 67), and >or=37 weeks (n = 199)., Results: High cholesterol or triglycerides or=34-<37 weeks, respectively. Overweight women who delivered <34 weeks had particularly elevated early pregnancy concentrations of cholesterol and low-density lipoprotein; lean women with moderate preterm birth had elevated triglycerides. There was a reduced triglyceride response in the first half of pregnancy among women who delivered <34 weeks., Conclusion: Our results indicate the presence of dyslipidemia in women with spontaneous preterm birth.