The effects of oral clefts on hospital use throughout the lifespan

<p>Abstract</p> <p>Background</p> <p>Oral clefts are one of the most common birth defects worldwide. They require multiple healthcare interventions and add significant burden on the health and quality of life of affected individuals. However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan.</p> <p>Methods</p> <p>We estimate two-part regression models for hospital admission and length of stay for several age groups up to 68 years of age. The study employs unique secondary population-based data from several administrative inpatient, civil registration, demographic and labor market databases for 7,670 individuals born with oral clefts between 1936 and 2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random sample of the total birth population from 1936 to 2002.</p> <p>Results</p> <p>Oral clefts significantly increase hospital use for most ages below 60 years by up to 233% for children ages 0-10 years and 16% for middle age adults. The more severe cleft forms (cleft lip with palate) have significantly larger effects on hospitalizations than less severe forms.</p> <p>Conclusions</p> <p>The results suggest that individuals with oral clefts have higher hospitalization risks than the general population throughout most of the lifespan.</p

Psychiatric Diagnoses in Individuals with Non-Syndromic Oral Clefts:A Danish Population-Based Cohort Study

The aim of this study was to investigate the risk of psychiatric diagnoses in individuals with non-syndromic oral clefts (OC) compared with individuals without OC, including ages from 1 to 76 years.Linking four Danish nationwide registers, we investigated the risk of psychiatric diagnoses at Danish psychiatric hospitals during the period 1969-2012 for individuals born with non-syndromic OC in Denmark 1936-2009 compared with a cohort of 10 individuals without OC per individual with OC, matched by sex and birth year. The sample included 8,568 individuals with OC, observed for 247,821 person-years, and 85,653 individuals without OC followed for 2,501,129 person-years.A total of 953 (11.1%) of the individuals with OC (9.6% for cleft lip (CL), 10.8% for cleft lip and palate (CLP) and 13.1% for cleft palate (CP)) and 8,117 (9.5%) in the comparison group had at least one psychiatric diagnosis. Cox proportional hazard regression model revealed that individuals with OC had significantly higher risk of a psychiatric diagnosis (hazard ratio (HR) = 1.19, 95% CI: 1.12-1.28). When examining cleft type, no difference was found for CL (HR = 1.03, 95% CI: 0.90-1.17), but CLP was associated with a small increased risk (HR = 1.13, 95% CI: 1.01-1.26), whereas individuals with CP had the largest increased risk (HR = 1.45, 95% CI: 1.30-1.62). The largest differences were found in schizophrenia-like disorders, mental retardation and pervasive developmental disorders, but we found no increased risk of mood disorders and anxiety-related disorders.Individuals with non-syndromic OC had significantly higher risk of psychiatric diagnoses compared with individuals without OC. However, the elevated risk was observed for individuals with CLP and CP but not for individuals with CL and the absolute risk increase was modest

Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins

IntroductionPregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (MZ) and dizygotic (DZ) twins, as this allowed us to describe the age-relationship of PAPP-A, and to test the hypothesis that serum PAPP-A concentrations are genetically determined. As PAPP-A is functionally related to stanniocalcin-2 (STC2), an endogenous PAPP-A inhibitor, we included measurements on STC2 as well as IGF-I and IGF-II.MethodsThe twin cohort contained 596 subjects (250 MZ twins, 346 DZ twins), whereof 33% were males. The age ranged from 73.2 to 94.3 (mean 78.8) years. Serum was analyzed for PAPP-A, STC2, IGF-I, and IGF-II by commercial immunoassays.ResultsIn the twin cohort, PAPP-A increased with age (r=0.19; P&lt;0.05), whereas IGF-I decreased (r=-0.12; P&lt;0.05). Neither STC2 nor IGF-II showed any age relationship. When analyzed according to sex, PAPP-A correlated positively with age in males (r=0.18; P&lt;0.05) and females (r=0.25; P&lt;0.01), whereas IGF-I correlated inversely in females only (r=-0.15; P&lt;0.01). Males had higher levels of PAPP-A (29%), STC2 (18%) and IGF-I (19%), whereas serum IGF-II was 28% higher in females (all P&lt;0.001). For all four proteins, within-pair correlations were significantly higher for MZ twins than for DZ twins, and they demonstrated substantial and significant heritability, which after adjustment for age and sex averaged 59% for PAPP-A, 66% for STC2, 58% for IGF-I, and 52% for IGF-II.DiscussionThis twin study confirms our hypothesis that the heritability of PAPP-A serum concentrations is substantial, and the same is true for STC2. As regards the age relationship, PAPP-A increases with age, whereas STC2 remains unchanged, thereby supporting the idea that the ability of STC2 to inhibit PAPP-A enzymatic activity decreases with increasing age

Studies of Metabolic Phenotypic Correlates of 15 Obesity Associated Gene Variants

Genome-wide association studies have identified novel BMI/obesity associated susceptibility loci. The purpose of this study is to determine associations with overweight, obesity, morbid obesity and/or general adiposity in a Danish population. Moreover, we want to investigate if these loci associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms.15 gene variants in 14 loci including TMEM18 (rs7561317), SH2B1 (rs7498665), KCTD15 (rs29941), NEGR1 (rs2568958), ETV5 (rs7647305), BDNF (rs4923461, rs925946), SEC16B (rs10913469), FAIM2 (rs7138803), GNPDA2 (rs10938397), MTCH2 (rs10838738), BAT2 (rs2260000), NPC1 (rs1805081), MAF (rs1424233), and PTER (rs10508503) were genotyped in 18,014 middle-aged Danes.Five of the 15 gene variants associated with overweight, obesity and/or morbid obesity. Per allele ORs ranged from 1.15-1.20 for overweight, 1.10-1.25 for obesity, and 1.41-1.46 for morbid obesity. Five of the 15 variants moreover associated with increased measures of adiposity. BDNF rs4923461 displayed a borderline BMI-dependent protective effect on type 2 diabetes (0.87 (0.78-0.96, p = 0.008)), whereas SH2B1 rs7498665 associated with nominally BMI-independent increased risk of type 2 diabetes (1.16 (1.07-1.27, p = 7.8×10(-4))).Associations with overweight and/or obesity and measures of obesity were confirmed for seven out of the 15 gene variants. The obesity risk allele of BDNF rs4923461 protected against type 2 diabetes, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI

Increased prevalence of congenital heart defects in monozygotic and dizygotic twins

Background— Smaller studies and many case series reports indicate that congenital heart defects may be more common in monochorionic twins than in dichorionic twins and singletons. Methods and Results— We investigated congenital heart defect occurrence in all twins and 5% of all singletons born in Denmark in 1977–2001 and followed through 2006 by linking the Danish Twin Registry and Statistics Denmark registers including the National Medical Birth Register and the Danish National Patient Register. Among 41 525 twin individuals, a total of 584 twins (1.4%) had a congenital heart defect registered in the Danish National Patient Register, whereas the corresponding numbers for singletons were 648 of 74 473 (0.87%; P &lt;0.001; ie, a 63% [95% confidence interval, 45–82%] increased risk for congenital heart defect for twins). Patent ductus arteriosus and coarctation of aorta occurred &gt;3 times as often in twins as in singletons, at 3.9 (95% confidence interval, 2.6–5.8) and 3.1 (95% confidence interval, 1.5–6.4), respectively. The increased occurrence in twins was also found in sensitivity analyses including only inpatients or only surgically treated cases regardless of whether preterm patent ductus arteriosus was included. We were not able to demonstrate a higher risk for congenital heart defect among monozygotic twins compared with dizygotic twins, and the congenital heart defect occurrence was also increased in dizygotic twins, who are all dichorionic. Conclusions— Congenital heart defect is more common in twins than in singletons, and the increased occurrence is not restricted to monochorionic twins. Intrauterine surveillance and a postnatal comprehensive cardiac assessment for both twins may be considered regardless of chorionicity and zygosity. </jats:sec

Ethnic Variation in Oral Cleft Occurrence in Denmark 1981–2002

Objective To examine differences in oral cleft (OC) occurrence based on maternal only and parental country of origin in Denmark from 1981 to 2002. Methods Data on all live births from the Danish Medical Birth Register from 1981 to 2002 were linked with the Danish Facial Cleft Database. Cleft cases were categorized into isolated and nonisolated cleft lip with or without palate (CL/P) and cleft palate only (CP). Birth prevalence was calculated as cases per 1,000 live born children by maternal country of origin, world region, and mixed parental groups. Results We identified 3094 OC cases among 1,319,426 live births. Danish-born women had an OC birth prevalence of 2.38 with a 95% confidence interval (CI) (2.29–2.47) and foreign-born women a significant lower prevalence of 2.01 (CI, 1.77–2.27). This difference was explained by a lower isolated CL/P birth prevalence among foreign-born women of 0.97 (CI, 0.81–1.16) versus 1.35 (CI, 1.28–1.41). No significant differences were seen for the remaining subtypes. Parents with the same foreign country of origin had a lower overall OC (1.63; CI, 1.35–1.94) and isolated CL/P (0.76; CI, 0.57–0.99) birth prevalence than Danish-born parents. This was not the case for any of the mixed parental groups. Overall and subtype prevalence rates varied according to maternal categories of world region. Conclusion In this study we found differences in OC occurrence among all live births in the Danish population based on maternal country of origin from 1981 to 2002. Danish-born women had higher OC and isolated CL/P birth prevalence compared with foreign-born women. </jats:sec