Trends and risk factors associated with stillbirths: a case study of the Navrongo War Memorial Hospital in Northern Ghana

Maternal and Child health remains at the core of global health priorities transcending the Millennium Development Goals into the current era of Sustainable Development Goals. Most low and middle-income countries including Ghana are yet to achieve the required levels of reduction in child and maternal mortality. This paper analysed the trends and the associated risk factors of stillbirths in a district hospital located in an impoverished and remote region of Ghana.; Retrospective hospital maternal records on all deliveries conducted in the Navrongo War Memorial hospital from 2003-2013 were retrieved and analysed. Descriptive and inferential statistics were used to summarise trends in stillbirths while the generalized linear estimation logistic regression is used to determine socio-demographic, maternal and neonatal factors associated with stillbirths.; A total of 16,670 deliveries were analysed over the study period. Stillbirth rate was 3.4% of all births. There was an overall decline in stillbirth rate over the study period as stillbirths declined from 4.2% in 2003 to 2.1% in 2013. Female neonates were less likely to be stillborn (Adjusted Odds ratio = 0.62 and 95%CI [0.46, 0.84]; p = 0.002) compared to male neonates; neonates with low birth weight (4.02 [2.92, 5.53]) and extreme low birth weight (18.9 [10.9, 32.4]) were at a higher risk of still birth (p<0.001). Mothers who had undergone Female Genital Mutilation had 47% (1.47 [1.04, 2.09]) increase odds of having a stillbirth compared to non FGM mothers (p = 0.031). Mothers giving birth for the first time also had a 40% increase odds of having a stillbirth compared to those who had more than one previous births (p = 0.037).; Despite the modest reduction in stillbirth rates over the study period, it is evident from the results that stillbirth rate is still relatively high. Primiparous women and preterm deliveries leading to low birth weight are identified factors that result in increased stillbirths. Efforts aimed at impacting on stillbirths should include the elimination of outmoded cultural practices such as FGM

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated

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

New susceptibility loci associated with kidney disease in type 1 diabetes

WOS:000309817900008Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.Peer reviewe

Prevalence and adverse obstetric outcomes of female genital mutilation among women in rural Northern Ghana

Female genital mutilation (FGM) is commonly practiced in sub-Saharan Africa and results in adverse pregnancy outcomes among affected women. This paper assessed the prevalence and effects of FGM on pregnancy outcomes in a rural Ghanaian setting.; We analyzed 9306 delivery records between 2003 and 2013 from the Navrongo War Memorial Hospital. Multivariable logistic regression analyses were used to determine the effects of FGM on pregnancy outcomes such as stillbirth, birth weight, postpartum haemorrhage, caesarean and instrumental delivery. We also assessed differences in the duration of stay in the hospital by FGM status.; A greater proportion of mothers with FGM (24.7%) were older than 35 years compared with those without FGM (7.6%). FGM declined progressively from 28.4% in 2003 to 0.6% in 2013. Mothers with FGM were nearly twice as likely to have caesarean delivery (adjusted odds ratios = 1.85 with 95%CI [1.72, 1.99]) and stillbirths (1.60 [1.21, 2.11]) compared with those without. Similarly, they had a 4-fold increased risk of post-partum haemorrhage (4.69 [3.74, 5.88]) and more than 2-fold risk lacerations/episiotomy (2.57 [1.86, 3.21]) during delivery. Average duration of stay in the hospital was higher for mothers with FGM from 2003 to 2007.; Despite significant decline in prevalence of FGM, adverse obstetric outcomes are still high among affected women. Increased public health education of circumcised women on these outcomes would help improve institutional deliveries and heighten awareness and prompt clinical decisions among healthcare workers. Further scale-up of community level interventions are required to completely eliminate FGM

Efficacy and Safety of Renal Tubule Cell Therapy for Acute Renal Failure

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF