Fetal heart rate during a maternal grand mal epileptic seizure

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Skin Autofluorescence in Young Adult Offspring of Women with Type 1 Diabetes : A Cross-Sectional Case-Control Study

Introduction: Offspring born to women with type 1 diabetes pregnancies have an elevated risk for early-onset obesity and type 2 diabetes compared with offspring born to women without diabetes. Skin autofluorescence (SAF) is a marker of accumulated advanced glycation end products (AGEs) and it has been shown to predict type 2 diabetes, cardiovascular disease, and mortality in the general population. The aim of this study was to evaluate whether maternal type 1 diabetes influences the SAF value in young adult offspring. Methods: This cross-sectional case-control study included 78 offspring of women with type 1 diabetes (cases) and 85 control participants (controls). All study participants, aged 18-23 years, were invited to participate in a clinical assessment including laboratory tests and questionnaires. SAF was assessed using the AGE reader from the dominant forearm of each participant. Results: The mean SAF value did not differ between the cases (1.61 [standard deviation (SD) 0.37]) arbitrary units [AU]) and the controls (1.64 [SD 0.41] AU) (p = 0.69). After adjusting for glycated hemoglobin A(1c), body fat percentage, smoking, and season the mean SAF value did not differ between the cases and the controls (p = 0.49) but differed between men and women (p = 0.008), without any interaction observed (p = 0.78). Conclusion: SAF values did not differ between the young adult offspring of women with type 1 diabetes and offspring born to mothers without diabetes. Surprisingly, young adult women showed higher SAF values than men in both case and control groups.Peer reviewe

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes : a case-control study

Background Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. Methods This is a case-control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18-23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student's t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. Results We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, Hb(A1c), and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD +/- 1.2) m/s than in controls 6.2 (SD +/- 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. Conclusions We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.Peer reviewe

The genomics of preterm birth: from animal models to human studies

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A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

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Genetic Associations with Gestational Duration and Spontaneous Preterm Birth

BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0x10(-8)) or an association with suggestive significance (P<1.0x10(-6)) in the discovery set. RESULTS In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.Peer reviewe

Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study

Aims/hypothesis: The aim of this prospective nationwide study was to examine antenatal pregnancy care and pregnancy outcomes in women with type 1 and type 2 diabetes, and to describe changes since 2002/2003. Methods: This national population-based cohort included 3036 pregnant women with diabetes from 155 maternity clinics in England and Wales who delivered during 2015. The main outcome measures were maternal glycaemic control, preterm delivery (before 37 weeks), infant large for gestational age (LGA), and rates of congenital anomaly, stillbirth and neonatal death. Results: Of 3036 women, 1563 (51%) had type 1, 1386 (46%) had type 2 and 87 (3%) had other types of diabetes. The percentage of women achieving HbA1c < 6.5% (48 mmol/mol) in early pregnancy varied greatly between clinics (median [interquartile range] 14.3% [7.7–22.2] for type 1, 37.0% [27.3–46.2] for type 2). The number of infants born preterm (21.7% vs 39.7%) and LGA (23.9% vs 46.4%) were lower for women with type 2 compared with type 1 diabetes (both p < 0.001). The prevalence rates for congenital anomaly (46.2/1000 births for type 1, 34.6/1000 births for type 2) and neonatal death (8.1/1000 births for type 1, 11.4/1000 births for type 2) were unchanged since 2002/2003. Stillbirth rates are almost 2.5 times lower than in 2002/2003 (10.7 vs 25.8/1000 births for type 1, p = 0.0012; 10.5 vs 29.2/1000 births for type 2, p = 0.0091). Conclusions/interpretation: Stillbirth rates among women with type 1 and type 2 diabetes have decreased since 2002/2003. Rates of preterm delivery and LGA infants are lower in women with type 2 compared with type 1 diabetes. In women with type 1 diabetes, suboptimal glucose control and high rates of perinatal morbidity persist with substantial variations between clinics

Mapping a New Spontaneous Preterm Birth Susceptibility Gene, IGF1R, Using Linkage, Haplotype Sharing, and Association Analysis

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HS1, a Lyn Kinase Substrate, Is Abnormally Expressed in B-Chronic Lymphocytic Leukemia and Correlates with Response to Fludarabine-Based Regimen

In B-Chronic Lymphocytic Leukemia (B-CLL) kinase Lyn is overexpressed, active, abnormally distributed, and part of a cytosolic complex involving hematopoietic lineage cell-specific protein 1 (HS1). These aberrant properties of Lyn could partially explain leukemic cells’ defective apoptosis, directly or through its substrates, for example, HS1 that has been associated to apoptosis in different cell types. To verify the hypothesis of HS1 involvement in Lyn-mediated leukemic cell survival, we investigated HS1 protein in 71 untreated B-CLL patients and 26 healthy controls. We found HS1 overexpressed in leukemic as compared to normal B lymphocytes (1.38±0.54 vs 0.86±0.29, p<0.01), and when HS1 levels were correlated to clinical parameters we found a higher expression of HS1 in poor-prognosis patients. Moreover, HS1 levels significantly decreased in ex vivo leukemic cells of patients responding to a fludarabine-containing regimen. We also observed that HS1 is partially localized in the nucleus of neoplastic B cells. All these data add new information on HS1 study, hypothesizing a pivotal role of HS1 in Lyn-mediated modulation of leukemic cells’ survival and focusing, one more time, the attention on the BCR-Lyn axis as a putative target for new therapeutic strategies in this disorder