IMPORTANCE Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. OBJECTIVE To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. DESIGN, SETTING, AND PARTICIPANTSIn this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge.EXPOSURES COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. MAIN OUTCOMES AND MEASURESThe primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity.RESULTS A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women withoutCOVID-19diagnosiswereenrolled,allwithbroadlysimilardemographiccharacteristics(mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with

Summary Reprogramming somatic cells to induced pluripotent stem cells (iPSCs), resets their identity back to an embryonic age, and thus presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson’s disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine-hydroxylase (TH) expression and enlarged mitochondria or Lewy body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models.

Human pluripotent stem cells (hPSCs) are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations, projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism and epilepsy. Here we demonstrate the highly efficient derivation of human cortical interneurons in a NKX2.1::GFP hESC reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes and migratory behaviors. Further differentiation in a murine cortical environment yields parvalbumin and somatostatin expressing neurons that exhibit synaptic inputs and electrophysiological properties of cortical interneurons. Our study defines the signals sufficient to model human ventral forebrain development in vitro and lays the foundation for studying cortical interneuron involvement in human disease pathology.

At the beginning of the COVID-19 pandemic, the extent of the risks of a COVID infection during pregnancy were unknown. During the start of the pandemic, there were only a few studies published comparing outcomes between pregnant women with and without COVID-19 infections. The INTERGROWTH-21st Consortium conducted a prospective, longitudinal, observational study (INTERCOVID), which assessed the association between COVID-19 and maternal/neonatal outcomes in pregnant women with a COVID-19 diagnosis compared with enrolled pregnant women without a COVID-19 diagnosis.This study enrolled patients from 43 hospitals in 18 different countries between March 2020 and October 2020. As a comparison group, the researchers enrolled 2 unmatched, consecutive, uninfected women immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care. Both women and neonates were followed until hospital discharge. COVID-19 was diagnosed by laboratory confirmation and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. The primary outcomes of the study were indices of maternal and severe neonatal/perinatal morbidity and mortality.In all, 706 pregnant women with a COVID-19 diagnosis and 1424 pregnant women without a COVID-19 diagnosis were enrolled. The women had broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Three hundred twentythree women were overweight early in pregnancy (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were more likely to have preeclampsia/eclampsia (relative risk [