The birth prevalence of CHD declined from around 2005. Specifically, the prevalence of severe CHD was reduced by 3.4% per year from 2004 through 2009.

Prior genome-wide association studies for oral clefts have focused on clinic-based samples with unclear generalizability. Prior samples were also small for investigating effects by cleft type and exclusively studied isolated clefts (those occurring without other birth defects). We estimated the Reprints and permissions: sagepub.com/journalsPermissions.nav Corresponding Author: L.M. Moreno Uribe, Orthodontics-Dows Institute, University of Iowa, 401 DSB, Iowa City, IA 52242, USA. lina-moreno@uiowa.edu. * Authors contributing equally as senior authors. Author ContributionsL.M. Moreno Uribe, G.L. Wehby, contributed to conception, design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript; T. Fomina, H.K. Gjessing, M. Gjerdevik, contributed to data analysis, critically revised the manuscript; R.G. Munger, P.A. Romitti, M.M. Jenkins, K. Christensen, contributed to data acquisition, critically revised the manuscript; A.J. Wilcox, J.C. Murray, contributed to data acquisition and interpretation, critically revised the manuscript; R.T. Lie, contributed to conception, design, data acquisition, analysis, and interpretation, critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of the work.A supplemental appendix to this article is available online. HHS Public AccessAuthor manuscript J Dent Res. Author manuscript; available in PMC 2017 October 01. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript effects of 17 top loci on cleft types in both isolated and nonisolated cases in the largest consortium to date of European-descent population-based studies. Our analytic approach focused on a motherchild dyad case-control design, but it also allowed analyzing mother-only or child-only genotypes to maximize power. Our total sample included 1,875 cases with isolated clefts, 459 cases with nonisolated clefts, and 3,749 controls. After correcting for multiple testing, we observed significant associations between fetal single-nucleotide polymorphisms (SNPs) at IRF6, PAX7, 8q21.3, 8q24, KIAA1598-VAX1, and MAFB and isolated cleft lip only (CLO) and cleft lip and palate (CLP). Significant associations were observed between isolated CLO and fetal SNPs near TPM1 and NOG1 and between CLP and fetal SNPs at ABCA4-ARHGAP29, THADA, FOXE1, and SPRY2. Overall, effects were similar for isolated CLO and CLP, except for ABCA4-ARHGAP29. A protective effect was observed for the fetal NOG1 SNP on cleft palate only, opposite in direction to the effect on CLO. For most fetal SNPs, a dose-response allelic effect was observed. No evidence of parent-of-origin or maternal genome effects was observed. Overall, effect direction and magnitude were similar between isolated and nonisolated clefts, suggesting that several loci are modifiers of cleft risk in both isolated and nonisolated forms. Our results provide reliable estimates of the effects of top loci on risks of oral clefts in a population of European descent.

Obesity is an established risk factor for severe coronavirus disease 2019 , but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMIassociated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODSWe retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Sitespecific estimates were combined in a meta-analysis. RESULTSAmong 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15-1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03-1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74-1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONSIn adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.

NCT02026557.

The 1-year mortality of severe congenital heart defects among live births, 1994-2009, declined in Norway. The downward trend in mortality may be explained by a more frequent use of termination of affected pregnancies, and the reduced operative mortality of severe congenital heart defects.