Optimizing Pregnancy for Intergenerational Health Benefits

Pregnancy is a critical period of body weight regulation for both mother and baby. Vital energy-sensing processes are established in utero that aid in nutrient storage and metabolic control later in life. Excessive weight gain during pregnancy and a surplus of maternal resources leads to preferential shuttling of nutrients and growth-promoting peptides across the placenta, resulting in fetal overgrowth — a well-established predictor of childhood obesity. Physical activity during pregnancy offers a safe and accessible way in which one can modify these intricate cellular networks across the maternal-placental-fetal interface to prevent dysregulation and optimize fetal birth weight. This commentary highlights the clinical utility of physical activity during pregnancy and provides practical recommendations as a way to ensure the best health and safety of mother, baby, and future generations.  Résumé La grossesse est une période critique de la régulation du poids corporel pour la mère et le bébé. Des processus vitaux de détection d’énergie sont établis in utero qui contribuent au stockage des nutriments et au contrôle métabolique plus tard dans la vie. Une prise de poids excessive pendant la grossesse et un surplus de ressources maternelles conduit à un transfert préférentiel des nutriments et des peptides favorisant la croissance à travers le placenta, entraînant une prolifération fœtale - un prédicteur bien établi de l’obésité infantile. L’activité physique pendant la grossesse offre un moyen sûr et accessible pour modifier ces réseaux cellulaires complexes à travers l’interface materno-placentaire-fœtal afin de prévenir le dérèglement et optimiser le poids de naissance fœtal. Ce commentaire met en évidence l’utilité clinique de l’activité physique pendant la grossesse et fournit des recommandations pratiques pour assurer la meilleure santé et sécurité de la mère, du bébé et des générations futures.

Addressing cultural, racial and ethnic discrepancies in guideline discordant gestational weight gain: a systematic review and meta-analysis

Objective To systematically review the literature and describe the discrepancies in achieving the 2009 Institute of Medicine (IOM) gestational weight gain (GWG) guidelines across cultures. Methods Ten databases were searched from inception to April 2018. Observational cohort studies were included that examined adult women; reported on a measure of culture; compared cultural groups, and reported on GWG. Articles were broken down into papers that used the current 2009 IOM GWG guidelines and those that used others. A meta-analysis was conducted for studies using the 2009 guidelines examining the prevalence of discordant GWG across cultural groups. Results The review included 86 studies. Overall, 69% of women experienced discordant GWG irrespective of culture. White women experienced excessive GWG most often, and significantly more than Asian and Hispanic women; Black women had a higher prevalence of excessive GWG than Hispanic and Asian women; however, this difference was not significant. Conclusions The majority of women experience excessive GWG, with White women experiencing this most often. Culturally diverse GWG guidelines are needed to individualize antenatal care and promote optimal maternal-fetal health outcomes across cultural groups

Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.

It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases6-8. This includes muscle biopsies from patients with undiagnosed rare muscle disorders6,9, and cultured fibroblasts from patients with mitochondrial disorders7. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution

Common sleep disorders in pregnancy: a review

In this review, we provide a comprehensive overview of common sleep disorders during pregnancy, including their characterization, prevalence, risk factors, and possible contribution to maternal and fetal outcomes. We conducted a quasi-systematic literature search of the MEDLINE database and identified 744 studies from 1991 through 2021, inclusive, that met our inclusion criteria. We synthesized the existing literature on sleep disorders during pregnancy and highlighted controversies, research gaps, and needed clinical developments. Our review covers a range of sleep disorders, including insomnia, obstructive sleep apnea, restless legs syndrome, and circadian rhythm disorders. We discuss the prevalence of these disorders in pregnancy and their potential impact on maternal and fetal health outcomes. We also explore the relationship between sleep disorders, pre-pregnancy comorbidities such as obesity, and pregnancy-related conditions such as gestational diabetes mellitus and preeclampsia. In addition to summarizing the existing literature on sleep disorders during pregnancy, we also highlight opportunities for further research in this area. We suggest that future studies should strive to employ validated and objective measurement tools for sleep disorders and prioritize utilization of longitudinal methods with participant follow-up through postpartum, mid-life, menopause, and beyond. We also put forward investigation into the impact of circadian rhythm disruption on reproductive physiology and early pregnancy outcomes as an area of important work. Overall, our review provides valuable insights on sleep and reproduction and into common sleep disorders during pregnancy and their potential impact on maternal and fetal health outcomes

The Atacama Cosmology Telescope: Microwave Intensity and Polarization Maps of the Galactic Center

We present arcminute-resolution intensity and polarization maps of the Galactic center made with the Atacama Cosmology Telescope (ACT). The maps cover a 32 deg$^2$ field at 98, 150, and 224 GHz with $\vert l\vert\le4^\circ$, $\vert b\vert\le2^\circ$. We combine these data with Planck observations at similar frequencies to create coadded maps with increased sensitivity at large angular scales. With the coadded maps, we are able to resolve many known features of the Central Molecular Zone (CMZ) in both total intensity and polarization. We map the orientation of the plane-of-sky component of the Galactic magnetic field inferred from the polarization angle in the CMZ, finding significant changes in morphology in the three frequency bands as the underlying dominant emission mechanism changes from synchrotron to dust emission. Selected Galactic center sources, including Sgr A*, the Brick molecular cloud (G0.253+0.016), the Mouse pulsar wind nebula (G359.23-0.82), and the Tornado supernova remnant candidate (G357.7-0.1), are examined in detail. These data illustrate the potential for leveraging ground-based Cosmic Microwave Background polarization experiments for Galactic science.Comment: 26 pages, 14 figures, accepted for publication in Ap

The Atacama Cosmology Telescope: Cosmology from cross-correlations of unWISE galaxies and ACT DR6 CMB lensing

We present tomographic measurements of structure growth using cross-correlations of Atacama Cosmology Telescope (ACT) DR6 and Planck CMB lensing maps with the unWISE Blue and Green galaxy samples, which span the redshift ranges $0.2 \lesssim z \lesssim 1.1$ and $0.3 \lesssim z \lesssim 1.8$, respectively. We improve on prior unWISE cross-correlations not just by making use of the new, high-precision ACT DR6 lensing maps, but also by including additional spectroscopic data for redshift calibration and by analysing our measurements with a more flexible theoretical model. An extensive suite of systematic and null tests within a blind analysis framework ensures that our results are robust. We determine the amplitude of matter fluctuations at low redshifts ($z\simeq 0.2-1.6$), finding $S_8 \equiv \sigma_8 (\Omega_m / 0.3)^{0.5} = 0.813 \pm 0.021$ using the ACT cross-correlation alone and $S_8 = 0.810 \pm 0.015$ with a combination of Planck and ACT cross-correlations; these measurements are fully consistent with the predictions from primary CMB measurements assuming standard structure growth. The addition of Baryon Acoustic Oscillation data breaks the degeneracy between $\sigma_8$ and $\Omega_m$, allowing us to measure $\sigma_8 = 0.813 \pm 0.020$ from the cross-correlation of unWISE with ACT and $\sigma_8 = 0.813\pm 0.015$ from the combination of cross-correlations with ACT and Planck. These results also agree with the expectations from primary CMB extrapolations in $\Lambda$CDM cosmology; the consistency of $\sigma_8$ derived from our two redshift samples at $z \sim 0.6$ and $1.1$ provides a further check of our cosmological model. Our results suggest that structure formation on linear scales is well described by $\Lambda$CDM even down to low redshifts $z\lesssim 1$.Comment: 73 pages (incl. 30 pages of appendices), 50 figures, 16 tables, to be submitted to ApJ. Watch G. S. Farren and A. Krolewski discuss the analysis and results under https://cosmologytalks.com/2023/09/11/act-unwis

Can We Modify the Intrauterine Environment to Halt the Intergenerational Cycle of Obesity?

Child obesity is a global epidemic whose development is rooted in complex and multi-factorial interactions. Once established, obesity is difficult to reverse and epidemiological, animal model, and experimental studies have provided strong evidence implicating the intrauterine environment in downstream obesity. This review focuses on the interplay between maternal obesity, gestational weight gain and lifestyle behaviours, which may act independently or in combination, to perpetuate the intergenerational cycle of obesity. The gestational period, is a crucial time of growth, development and physiological change in mother and child. This provides a window of opportunity for intervention via maternal nutrition and/or physical activity that may induce beneficial physiological alternations in the fetus that are mediated through favourable adaptations to in utero environmental stimuli. Evidence in the emerging field of epigenetics suggests that chronic, sub-clinical perturbations during pregnancy may affect fetal phenotype and long-term human data from ongoing randomized controlled trials will further aid in establishing the science behind ones predisposition to positive energy balance

Astro2020 APC White Paper: The MegaMapper: a z > 2 spectroscopic instrument for the study of Inflation and Dark Energy

MegaMapper is a proposed ground-based experiment to measure Inflation parameters and Dark Energy from galaxy redshifts at

A Spectroscopic Road Map for Cosmic Frontier: DESI, DESI-II, Stage-5

In this white paper, we present an experimental road map for spectroscopic experiments beyond DESI. DESI will be a transformative cosmological survey in the 2020s, mapping 40 million galaxies and quasars and capturing a significant fraction of the available linear modes up to z=1.2. DESI-II will pilot observations of galaxies both at much higher densities and extending to higher redshifts. A Stage-5 experiment would build out those high-density and high-redshift observations, mapping hundreds of millions of stars and galaxies in three dimensions, to address the problems of inflation, dark energy, light relativistic species, and dark matter. These spectroscopic data will also complement the next generation of weak lensing, line intensity mapping and CMB experiments and allow them to reach their full potential.Comment: Contribution to Snowmass 202