Congenital abdominal wall defects and cryptorchidism : a population-based study

Purpose Several studies have reported high prevalence of undescended testis (UDT) among boys with congenital abdominal wall defects (AWD). Due to rarity of AWDs, however, true prevalence of testicular maldescent among these boys is not known. We conducted a national register study to determine the prevalence of UDT among Finnish males with an AWD. Methods All male infants with either gastroschisis or omphalocele born between Jan 1, 1998 and Dec 31, 2015 were identified in the Register of Congenital Malformations. The data on all performed operations were acquired from the Care Register for Health Care. The register data were examined for relevant UDT diagnosis and operation codes. Results We identified 99 males with gastroschisis and 89 with omphalocele. UDT was diagnosed in 10 (10.1%) infants with gastroschisis and 22 (24.7%) with omphalocele. Majority of these required an operation; 8/99 (8.1%) gastroschisis and 19/89 (21.3%) omphalocele patients. UDT is more common among AWD patients than general population with the highest prevalence in omphalocele. Conclusions Cryptorchidism is more common among boys with an AWD than general population. Furthermore, omphalocele carries significantly higher risk of UDT and need for orchidopexy than gastroschisis. Due to high prevalence testicular maldescent, careful follow-up for UDT is recommended.Peer reviewe

Extended spectrum penicillins reduce the risk of omphalocele : A population-based case-control study

Peer reviewe

Long-term hospital admissions and surgical treatment of children with congenital abdominal wall defects: a population-based study

Congenital abdominal wall defects, namely, gastroschisis and omphalocele, are rare congenital malformations with significant morbidity. The long-term burden of these anomalies to families and health care providers has not previously been assessed. We aimed to determine the need for hospital admissions and the requirement for surgery after initial admission at birth. For our analyses, we identified all infants with either gastroschisis (n=178) or omphalocele (n=150) born between Jan 1, 1998, and Dec 31, 2014, in the Register of Congenital Malformations. The data on all hospital admissions and operations performed were acquired from the Finnish Hospital Discharge Register between Jan 1, 1998, and Dec 31, 2015, and compared to data on the whole Finnish pediatric population (0.9 million) live born 1993-2008. Patients with gastroschisis and particularly those with omphalocele required hospital admissions 1.8 to 5.7 times more than the general pediatric population (p<0.0001). Surgical interventions were more common among omphalocele than gastroschisis patients (p=0.013). At the mean follow-up of 8.9 (range 1.0-18.0) years, 29% (51/178) of gastroschisis and 30% (45/150) of omphalocele patients required further abdominal surgery after discharge from the neonatal admission.Conclusion: Patients with gastroschisis and especially those with omphalocele, are significantly more likely than the general pediatric population to require hospital care. Nevertheless, almost half of the patients can be treated without further surgery, and redo abdominal surgery is only required in a third of these children. What is Known: • Gastroschisis and omphalocele are congenital malformations with significant morbidity • There are no reports on the long-term need for hospital admissions and surgery in these children What is New: • Patients with abdominal wall defects are significantly more likely than the general pediatric population to require hospital care • Almost half of the patients can be treated without further surgery, and abdominal redo operations are only required in a third of these children.<br

High incidence of inguinal hernias among patients with congenital abdominal wall defects: a population-based case-control study

The aim of this nationwide population-based case-control study was to assess the incidence of inguinal hernia (IH) among patients with congenital abdominal wall defects. All infants born with congenital abdominal wall defects between Jan 1, 1998, and Dec 31, 2014, were identified in the Finnish Register of Congenital Malformations. Six controls matched for gestational age, sex, and year of birth were selected for each case in the Medical Birth Register. The Finnish Hospital Discharge Register was searched for relevant diagnosis codes for IH, and hernia incidence was compared between cases and controls. We identified 178 infants with gastroschisis and 150 with omphalocele and selected randomly 1968 matched, healthy controls for comparison. Incidence of IH was significantly higher in gastroschisis girls than in matched controls, relative risk (RR) 7.20 (95% confidence interval [CI] 2.25-23.07). In boys with gastroschisis, no statistically significant difference was observed, RR 1.60 (95% CI 0.75-3.38). Omphalocele was associated with higher risk of IH compared to matched controls, RR 6.46 (95% CI 3.90-10.71), and the risk was equally elevated in male and female patients.Conclusion: Risk of IH is significantly higher among patients with congenital abdominal wall defects than in healthy controls supporting hypothesis that elevated intra-abdominal pressure could prevent natural closure of processus vaginalis. Parents should be informed of this elevated hernia risk to avoid delays in seeking care. We also recommend careful follow-up during the first months of life as most of these hernias are diagnosed early in life.</p

Extended spectrum penicillins reduce the risk of omphalocele: A population-based case-control study

Background: Omphalocele is a major congenital anomaly associated with significant morbidity and mortality. Regardless, the influence of maternal use of prescription drugs on the risk of omphalocele has only been addressed in a handful of studies. The aim of this study was to assess the influence of maternal risk factors and prescription drugs in early pregnancy on the risk of omphalocele.Methods: We performed a nationwide register-based case-control study in Finland. The analysis is based on the Finnish Register of Congenital Malformations and Drugs and Pregnancy databases, both upheld by the Finnish Institute for Health and Welfare. All omphalocele cases were identified between Jan 1, 2004, and Dec 31, 2014. Five age-matched controls from the same geographical region were randomly selected for each case. The main outcome measures were maternal risk factors for omphalocele. Our analysis compared the maternal characteristics and the use of prescription drugs during the first trimester of pregnancy between case and control mothers.Results: Mothers of 359 omphalocele cases were compared with 1738 randomly selected age and area-matched mothers of healthy infants between 1 January 2014 and 31 December 2014. Both maternal obesity (BMI ≥30) and diabetes increased the risk for omphalocele, and their co-occurrence accumulated this risk (aOR 5.06, 95% Cl 1.19-21.4). Similarly, history of multiple miscarriages was an independent risk factor (2.51, 1.16-5.43). The oral use of extended spectrum penicillins during the first trimester of pregnancy had a significant, protective influence (0.17, 0.04-0.71). These analyses were adjusted for sex, parity, and risk factors reported above. No significant changes in risk were observed with any other medication used during the first trimester.Conclusion: In conclusion, these findings may suggest that extended spectrum penicillins in the first trimester reduces the risk of omphalocle formation. Additionally, consistent with earlier studies, previous repeated miscarriages, maternal obesity, and diabetes were significant risk factors for omphalocele.</p

Immediate sequential bilateral cataract surgery : A 13-year real-life report of 56 700 cataract operations

Background/aims: To assess the frequency of immediate sequential bilateral cataract surgery (ISBCS) and endophthalmitis during 13-year period in Tays Eye Centre, Tampere University Hospital, Tampere, Finland. Methods: All cataract surgeries performed between 1 January 2008 and 31 December 2020, and all endophthalmitis cases during the same period were searched from electronic patient records. Numbers and frequencies of ISBCS, and complications, including endophthalmitis and vitreous loss, were recorded and compared with unilateral operations. Results: The study included 56 700 cataract surgeries in 34 797 patients of whom 39% (n=13 445) had ISBCS. The median age of the patients was 75 (IQR 68-80, range 0.08-99) years at the time of surgery. The proportion of ISBCS patients increased from 4.2% in 2008 to 46% in 2020. Vitreous loss occurred in 480 (0.9%) of cataract surgeries. There were no postoperative endophthalmitis after cataract surgery (n=0) during the 13-year period. Conclusion: The proportion of patients undergoing ISBCS increased from 4.2% in 2008 to 46% in 2020. No endophthalmitis were found to be associated with ISBCS.publishedVersionPeer reviewe

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations