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Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children's Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates who were diagnosed at the Maternity and Children's Hospital (MCH), Bisha, Saudi Arabia, between 5 October 2020 and 5 November 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD = 6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25–1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38–2.19), LBW (aOR = 1.32, 95% CI: 1.06–1.66), and RDS (aOR = 1.57, 95% CI: 1.28–1.93) were significantly higher among neonates born to mothers with MDM. The types of DM were statistically significant in terms of their correlation with the following neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusions: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. The early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population. [ABSTRACT FROM AUTHOR]

Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates who were diagnosed at the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia, between 5 October 2020 and 5 November 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD = 6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25–1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38–2.19), LBW (aOR = 1.32, 95% CI: 1.06–1.66), and RDS (aOR = 1.57, 95% CI: 1.28–1.93) were significantly higher among neonates born to mothers with MDM. The types of DM were statistically significant in terms of their correlation with the following neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusions: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. The early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.

Aim: The neuronal mechanism linking the association between maternal diabetes mellitus (DM) and risk of attention deficit hyperactivity disorder (ADHD) symptoms and working memory deficits in children was investigated. Methods: A total of 6291 children (52% boys) born beyond 28 weeks of gestation were included and underwent brain magnetic resonance imaging scans at 9–10 years. Subcortical brain volumes were estimated from the T1‐weighted images. ADHD symptoms were assessed using factorial analysis of the Child Behaviour Checklist completed by parents/caregivers. Working memory performance was assessed with the NIH Toolbox. Results: Compared to unexposed children, those exposed to DM (n = 422) had smaller (β = −0.15, p = 0.001) volumes of pooled deep grey matter (GM). Regional analysis revealed smaller volumes of the caudate nucleus, putamen, thalamus and cerebellum but not of hippocampus. They also had altered cortico‐striatal white matter projection tracts. DM was not associated with working memory deficits or inattention, but with increased hyperactivity/impulsivity and Sluggish Cognitive Tempo symptoms in boys. This hyperactivity/impulsivity symptom in boys was partially mediated by smaller deep GM volume. Conclusion: Exposure to DM during pregnancy leads to altered deep GM development during late childhood in their offspring. This contributed to an increased risk of hyperactivity/impulsivity symptoms in boys. [ABSTRACT FROM AUTHOR]

Aim: Maternal pregestational diabetes mellitus (PGDM), type 1 or type 2, has been established as a potential risk factor for congenital heart disease (CHD). At the same time, the correlation between gestational diabetes mellitus (GDM) and increased risk of CHD has not been yet fully elucidated. The objective of this systematic review and meta-analysis (PROSPERO number: CRD42020182390) was to analyze the existing evidence on PGDM and to attempt to fill, to the best of our ability, the remaining knowledge gap in the association of GDM with CHD. Materials and methods: Two authors have independently searched the Pubmed/Medline, Scopus, Cochrane, Web of Science, and Theses Global databases with keywords and Boolean operators. The search yielded 9333 relevant articles, which were later screened for eligibility. Original peer-reviewed (case-control or cohort) studies were included if they were published in English between 1997 and 2020. Thirteen studies on mothers with PGDM and seven studies on mothers with GDM were finally included in our meta-analysis to investigate the association of maternal diabetes with the risk of delivering a child with CHD. The selected studies were all assessed for their methodological quality using the Newcastle–Ottawa scale. Associations with p < .05 were considered statistically significant. Results: Our meta-analysis (I² > 75%, total population: n = 12,461,586) of 79,476 women with PGDM and 160,893 with GDM produced an odds ratio of 3.48 (2.36–4.61) and 1.55 (1.48–1.61), respectively. Additionally, we did not find any noticeable difference in the risk for CHD among diabetic women living in the USA and Europe. Nevertheless, it still needs to be clarified, whether or not the gestational diabetic population includes undiagnosed women with preexisting diabetes, which might account for the increased risk of delivering a child with CHD in women classified as suffering from GDM. Conclusion: While both GDM and PGDM seem to significantly increase the risk of CHD in comparison with the general population, PDGM appears to have a greater association with CHD, being correlated with a 3.5-fold increase in the risk of malformation. Preconceptional and gestational diabetes care are, therefore, essential to mitigate the adverse effect of hyperglycemia on fetal heart formation during pregnancy. [ABSTRACT FROM AUTHOR]

Background and objective Cryptorchidism, or undescended testes (UDT), refers to the failure of one or both testicles to descend to their natural position in the scrotum of newborn males. The association of gestational diabetes with cryptorchidism has not been studied sufficiently. Hence, this study aimed to analyze the association between maternal diabetes and cryptorchidism and other associated anomalies among Jordanian male children. Methods We conducted a retrospective study involving women and their cryptorchid offspring over a 10-year period, between January 2010 and December 2019. The data were collected using a retrospective review of the hospital records and questionnaires administered via phone calls. We included all patients with cryptorchidism and excluded children with a diagnosis of disorders of sexual development. Results A total of 368 children with cryptorchidism were included, with 29 mothers suffering from gestational or type II diabetes at the time of pregnancy. About 25% of patients suffered from associated anomalies, the most common being genital anomalies, while hypospadias was the most common associated anomaly. We observed no differences in terms of the age of diagnosis or treatment of cryptorchidism between children born to diabetic and those born to nondiabetic mothers. Conclusions Diabetic mothers have a higher chance of having offspring with anomalies that might co-occur with cryptorchidism, particularly urogenital anomalies. Further research is needed to explore the link between maternal diabetes and these abnormalities. Screening for gestational diabetes is critical, and more extensive studies could provide clearer recommendations for screening protocols and early intervention., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethical Committee of School of Medicine, The University of Jordan issued approval 67/2019/6494. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abdullah et al.)

Background: Existing knowledge suggests that gestational diabetes mellitus was inconsistently associated with offspring allergic diseases. The aim of this study was to identify the association between maternal diabetes mellitus and the risk of offspring allergic diseases by systematic review. Methods: We searched and retrieved three databases (PubMed, Web of Science, and Cochrane Library) for articles on the association between maternal diabetes mellitus and offspring allergic diseases published before December 31, 2019. Stata software version 16.0 was used for statistical analysis. Results: Eight published studies were included in this meta‐analysis. The pooled effect estimates showed the association between maternal diabetes mellitus and allergic outcomes, including asthma (OR: 1.13, 95% CI: 1.01‐1.27), wheezing (OR: 1.13, 95% CI: 1.07‐1.21), and atopic dermatitis (OR: 1.43, 95% CI: 1.22‐1.57). Maternal diabetes mellitus was not associated with the risk of allergic sensitization, with a pooled effect estimate of 1.07 (95% CI: 0.45, 2.58). Conclusion: Maternal diabetes mellitus may increase the risk of allergic diseases in their children. However, this finding should be validated with future large‐sample epidemiological studies covering a wider spectrum of allergic diseases. [ABSTRACT FROM AUTHOR]

Abstract Congenital heart disease (CHD) is the most common anatomical malformation occurring live‐born infants and an increasing cause of morbidity and mortality across the lifespan and throughout the world. Population‐based observations have long described associations between maternal cardiometabolic disorders and the risk of CHD in the offspring. Here we review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD offspring with particular attention to mechanistic models of maternal‐fetal risk transmission and first trimester disturbances of fetal cardiac development. A deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHD by identifying at‐risk pregnancies, along with primary prevention of disease by improving preconception and prenatal treatment of at‐risk mothers.

Hyperglycemia during pregnancy is associated with fetal lung development disorders and surfactant protein (SP) deficiency. Here, we examined the role of FOXA2 and Akt signaling in fetal lung development during diabetic pregnancy. Sprague‐Dawley rats were injected with streptozocin (STZ) during pregnancy to induce diabetes (DM). DM‐exposed fetal lungs exhibited reduced numbers of alveoli, irregularities in the appearance and thickness of the alveolar septum, increased levels of glycogen and lipids in type II alveolar epithelial cells, fewer microvilli and mature lamellar bodies, and swollen mitochondria. SP‐B and SP‐C in DM amniotic fluid and DM lungs were lower than in the control group (P

The aim of this study was to evaluate the impact of pregestational diabetes mellitus (DM) on fetal cardiac function two-dimensional parameters using spectral and tissue Doppler. Pregnant women between 20 and 36 + 6 weeks gestation were divided into three groups: controls, type I DM, and type II DM. The right ventricle (RV) and left ventricle (LV) annular velocity peaks were measured using spectral (E, A) and tissue (E', A', S') Doppler. The myocardial performance index was calculated as (isovolumetric contraction time [ICT] + isovolumetric relaxation time [IRT])/ejection time using tissue (MPI') and the spectral Doppler (MPI). A general linear model, with fetal heart rate as a covariant, was used to evaluate the effect of DM on the fetal heart function assessment parameters. To assess the association of type I and II DM with adverse perinatal outcomes, Fisher's exact test was used. A receiver operating characteristic curve was used to determine the best cutoff for fetal cardiac function assessment parameters to identify the neonatal composite outcomes. The sample comprised 179 pregnant women. DM had significant effect on RV and LV A peak velocities (p = 0.026 and p = 0.011, respectively). LV ICT (p < 0.001) and LV MPI (p < 0.001) were significantly affected by maternal DM. Fetuses from pregnant women with type II DM showed significantly higher LV MPI (0.492 vs. 0.459, p = 0.006) and RV S' (7.2 vs. 6.44 cm/s, p = 0.024) than controls. Fetuses from type I DM pregnant women showed increase in cardiac parameters that evaluated the LV and RV diastolic function (LV IRT' p < 0.001 and RV MPI' p = 0.044). Type I and II DM were associated with adverse perinatal outcomes: neonatal intensive care unit stay (p < 0.0001), macrosomia (p < 0.0001), hyperbilirubinemia (p < 0.0001), and hypoglycemia (p < 0.0001). The LV MPI' showed significant but moderate sensitivity in identifying the composite neonatal outcomes (AUC: 0.709, 95% CI 0.629-0.780, p < 0.001). Tissue Doppler and MPI parameters can be useful to detect subclinical cardiac dysfunction in the fetal heart of pregestational DM pregnant women. [ABSTRACT FROM AUTHOR]

Purpose: A systematic review and meta-analysis was performed to assess the risk of congenital heart defects (CHDs) and its specific phenotypes associated with maternal diabetes mellitus (DM) including pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM).Methods: PubMed, Embase, Medline, Google Scholar, Cochrane Libraries, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Fulltext Database and China Biology Medicine disc were searched from the inception dates to 15 December 2018, to identify case-control or cohort studies assessing the association between maternal DM and risk of CHDs. The exposure of interest was maternal DM; the outcomes of interest were CHDs and its specific phenotypes. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analyses were performed to explore potential heterogeneity moderators.Results: Total 52 studies, which involved 259,917 patients with CHDs among 16,929,835 participants, were included for analysis. Overall, mothers with DM compared with those without DM had a significantly higher risk of CHDs in offspring [odds ratios (OR) = 2.71, 95% confidence intervals (CI) 2.28-3.23]. When data were restricted to different types of DM, a significantly increased risk of CHDs was observed among mothers with PGDM (OR = 3.18, 95% CI 2.77-3.65) and GDM (OR = 1.98, 95% CI 1.66-2.36). Our study suggested the risk of CHDs was significantly higher among mothers with PGDM than those with GDM. Additionally, this study suggested maternal DM was significantly associated with most phenotypes of CHDs; of these, double outlet of the right ventricle (OR = 10.89; 95% CI 8.77-13.53), atrioventricular septal defect (OR = 5.74; 95% CI 3.20-10.27) and truncus arteriosus (OR = 5.06; 95% CI 2.65-9.65) were identified as the first three of the most common phenotypes of CHDs associated with maternal DM.Conclusions: The maternal DM including PGDM and GDM are significantly associated with risk of CHDs and its most phenotypes. The PGDM seems to be more likely to cause CHDs in offspring than GDM. Further studies are needed to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Hyperglycemia from pregestational diabetes mellitus induces neural tube defects in the developing fetus. Folate supplementation is the only effective way to prevent neural tube defects; however, some cases of neural tube defects are resistant to folate. Excess folate has been linked to higher maternal cancer risk and infant allergy. Therefore, additional interventions are needed. Understanding the mechanisms underlying maternal diabetes mellitus–induced neural tube defects can identify potential targets for preventing such defects. Despite not yet being in clinical use, growing evidence suggests that microRNAs are important intermediates in embryonic development and can serve as both biomarkers and drug targets for disease intervention. Our previous studies showed that maternal diabetes mellitus in vivo activates the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in the developing embryo and that a high glucose condition in vitro reduces microRNA-322 (miR-322) levels. IRE1α is an RNA endonuclease; however, it is unknown whether IRE1α targets and degrades miR-322 specifically or whether miR-322 degradation leads to neural tube defects via apoptosis. We hypothesize that IRE1α can inhibit miR-322 in maternal diabetes mellitus–induced neural tube defects and that restoring miR-322 expression in developing neuroepithelium ameliorates neural tube defects. This study aimed to identify potential targets for preventing maternal diabetes mellitus–induced neural tube defects and to investigate the roles and relationship of a microRNA and an RNA endonuclease in mouse embryos exposed to maternal diabetes mellitus. To determine whether miR-322 reduction is necessary for neural tube defect formation in pregnancies complicated by diabetes mellitus, male mice carrying a transgene expressing miR-322 were mated with nondiabetic or diabetic wide-type female mice to generate embryos with or without miR-322 overexpression. At embryonic day 8.5 when the neural tube is not yet closed, embryos were harvested for the assessment of 3 miR-322 transcripts (primary, precursor, and mature miR-322), tumor necrosis factor receptor–associated factor 3 (TRAF3), and neuroepithelium cell survival. Neural tube defect incidences were determined in embryonic day 10.5 embryos when the neural tube should be closed if there is no neural tube defect formation. To identify which miR-322 transcript is affected by maternal diabetes mellitus and high glucose conditions, 3 miR-322 transcripts were assessed in embryos from dams with or without diabetes mellitus and in C17.2 mouse neural stem cells treated with different concentrations of glucose and at different time points. To determine whether the endonuclease IRE1α targets miR-322, small interfering RNA knockdown of IRE1α or overexpression of inositol-requiring transmembrane kinase/endoribonuclease 1α by DNA plasmid transfection was used to determine the effect of IRE1α deficiency or overexpression on miR-322 expression. RNA immunoprecipitation was performed to reveal the direct targets of inositol-requiring transmembrane kinase/endoribonuclease 1α. Maternal diabetes mellitus suppressed miR-322 expression in the developing neuroepithelium. Restoring miR-322 expression in the neuroepithelium blocked maternal diabetes mellitus–induced caspase-3 and caspase-8 cleavage and cell apoptosis, leading to a neural tube defect reduction. Reversal of maternal diabetes mellitus–inhibited miR-322 via transgenic overexpression prevented TRAF3 up-regulation in embryos exposed to maternal diabetes mellitus. Activated IRE1α acted as an endonuclease and degraded precursor miR-322, resulting in mature miR-322 reduction. This study supports the crucial role of the IRE1α–microRNA-TRAF3 circuit in the induction of neuroepithelial cell apoptosis and neural tube defect formation in pregnancies complicated by diabetes mellitus and identifies IRE1α and miR-322 as potential targets for preventing maternal diabetes mellitus–induced neural tube defects. [ABSTRACT FROM AUTHOR]

Hyperglycemia during pregnancy is associated with fetal lung development disorders and surfactant protein (SP) deficiency. Here, we examined the role of FOXA2 and Akt signaling in fetal lung development during diabetic pregnancy. Sprague‐Dawley rats were injected with streptozocin (STZ) during pregnancy to induce diabetes (DM). DM‐exposed fetal lungs exhibited reduced numbers of alveoli, irregularities in the appearance and thickness of the alveolar septum, increased levels of glycogen and lipids in type II alveolar epithelial cells, fewer microvilli and mature lamellar bodies, and swollen mitochondria. SP‐B and SP‐C in DM amniotic fluid and DM lungs were lower than in the control group (P < 0.05). DM lung nuclear FOXA2 was lower compared with the control group (P < 0.05), but p‐FOXA2 was higher (P < 0.05). In murine lung epithelial (MLE) 12 cells, p‐AKT levels were increased by high glucose/insulin, but decreased by the Akt inhibitor MK2206 (P < 0.05). Expression of nuclear FOXA2 was increased by MK2206 compared with the high glucose/insulin group (P < 0.05). These results suggest that maternal diabetes induces fetal lung FOXA2 phosphorylation through the Akt pathway, and also affects the maturation of alveolar epithelial cells and reduces levels of SP‐B and SP‐C in the fetal lungs. An Akt inhibitor reversed the changes in SP expression in vitro. [ABSTRACT FROM AUTHOR]

The caudal regression syndrome is defined as total or partial agenesis of the sacrum and lumbar spine, frequently associated with other developmental malformations (orthopedic, neurological, genito-urinary, gastrointestinal...). Prenatal diagnosis is possible through fetal ultrasound (US) and magnetic resonance imaging (MRI). A case of fetal caudal regression syndrome with omphalocele from a diabetic mother is presented, demonstrating the sonographic, MRI, CT and X-Ray features diagnostic. We will also discuss neonatal findings, risk factors and prognosis of this condition.

Aim The aim of this study was to retrospectively document the impact of hypertensive conditions in pregnancy and decidual arteriolopathy on the patterns of placental injury in maternal diabetes mellitus (MDM). Methods Among all 5248 > 20 weeks' placentas, the frequencies of 19 selected clinical and 24 placental phenotypes were compared between 287 MDM placentas and 4961 remaining placentas (control group [CG]) before and after further exclusion of 85 and 611 patients with hypertensive conditions (gestational hypertension, pre-eclampsia, chronic hypertension). Results Cesarean section rate, heavy placentas, decidual arteriolopathy, microscopic chorionic pseudocysts, and chorangiosis were more common in MDM than in the CG both before and after exclusion of hypertensive conditions. The frequencies of preuterine patterns of chronic hypoxic placental injury and plasma cell deciduitis became statistically significant only after exclusion of hypertensive conditions. Conclusion Hypertensive conditions of pregnancy may obscure the underlying preuterine placental hypoxic pattern in MDM placentas. Even in normotensive patients, decidual arteriolopathy, and shallow placental implantation significantly impact placental histomorphology in MDM. [ABSTRACT FROM AUTHOR]

Maternal diabetes mellitus induces an increased risk of congenital heart defects (CHD), however, the exact mechanisms are still not fully illustrated. In this study, diabetic pregnant C57BL/6 mice were induced by injection of streptozotocin before mating. Compared with the control normal mice, diabetic pregnant mice displayed significant changes of the exosomal miRNA contents in the blood, as revealed by RNA-seq analysis. Multiple of these miRNAs were found involved in cardiac development regulation. Moreover, fluorescence labeled exosomes and gold nanoparticles could cross the placenta barrier and infiltrated into the embryonic organs/tissues, including the heart, during embryonic development. Injection of diabetic maternal exosomes strikingly increased the risk of CHD in the normal recipient pregnant mice. Taken together, we could draw the conclusion that maternal exosomes in diabetes could cross the maternal-fetal barrier and contribute to the cardiac development deficiency possibly via miRNAs, providing new insights in CHD prevention and treatment. [ABSTRACT FROM AUTHOR]

Maternal diabetes mellitus is a significant risk factor for structural birth defects, including congenital heart defects and neural tube defects. With the rising prevalence of type 2 diabetes mellitus and obesity in women of childbearing age, diabetes mellitus-induced birth defects have become an increasingly significant public health problem. Maternal diabetes mellitus in vivo and high glucose in vitro induce yolk sac injuries by damaging the morphologic condition of cells and altering the dynamics of organelles. The yolk sac vascular system is the first system to develop during embryogenesis; therefore, it is the most sensitive to hyperglycemia. The consequences of yolk sac injuries include impairment of nutrient transportation because of vasculopathy. Although the functional relationship between yolk sac vasculopathy and structural birth defects has not yet been established, a recent study reveals that the quality of yolk sac vasculature is related inversely to embryonic malformation rates. Studies in animal models have uncovered key molecular intermediates of diabetic yolk sac vasculopathy, which include hypoxia-inducible factor-1α, apoptosis signal-regulating kinase 1, and its inhibitor thioredoxin-1, c-Jun-N-terminal kinases, nitric oxide, and nitric oxide synthase. Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid and myo-inositol. Dietary supplementation with fatty acids that restore lipid levels in the yolk sac lead to a reduction in diabetes mellitus-induced malformations. Although the role of the human yolk in embryogenesis is less extensive than in rodents, nevertheless, human embryonic vasculogenesis is affected negatively by maternal diabetes mellitus. Mechanistic studies have identified potential therapeutic targets for future intervention against yolk sac vasculopathy, birth defects, and other complications associated with diabetic pregnancies. [ABSTRACT FROM AUTHOR]

Background: Maternal diabetes is associated with increased teratogenic effects on fetuses; it affects the structure and functions of fetal heart and alters the fetal-placental circulation. Although several articles have demonstrated fetal cardiac malformation and defects in diabetic mothers, ventricular systolic and diastolic function has not been properly investigated, particularly in Iran. Objectives: The aim of this study was to assess ventricular function using tissue Doppler imaging (TDI) in fetuses of diabetic mothers compared with fetuses of non-diabetic mothers in the Iranian population. Patients and Methods: Twenty-one diabetic pregnantwomenat 28 weeks' gestation were enrolled as the case group, and 35 healthy pregnant women at the same gestation were considered as the control group. Fetal echocardiography, including TDI, was carried out for all cases. The variables measured by echocardiography were as follows: the systolic annular peak velocity (Sa), late-diastolic annular peak velocity (Aa), and diastolic annular peak velocity (Ea) waves on the lateral and septal walls of the left ventricle (LV) at the mitral valve annulus using TDI; mitral inflow E and A waves using pulse Doppler; and inter-ventricular septum thickness using two-dimensional (2D) echocardiography. Results: According to cut-off value of 6.3% for hemoglobin A1C (HbA1c), only one patient with HbA1c = 8 had uncontrolled diabetes. In 20 other patients with controlled diabetes, the mean HbA1c was 4.78 ± 1.22%. There was no significant difference between groups according to maternal age (29.24 ± 5.86 in the case group vs. 28.58 ± 4.42 in the control group, P = 0.6). No significant difference was found in the septal thicknesses between the two groups (P = 0.39). Moreover, there were no statistically significant differences between groups in terms of other echocardiography variables (P > 0.05). Conclusions: We did notfindsignificant differences in ventricular function or ventricular septal thickness in the fetuses of mothers whowere referred to our hospital with a previous diagnosis of diabetes mellituscompared with the fetuses of non-diabetic mothers. This could be due to early identification, appropriate treatment, and tightly controlled diabetes in our study population. It should be noted that only pregnant women who were being closely monitored by their gynecologist were referred to us, so there may be some bias in our case selection; moreover, only patients who have taken steps to control their diabetes, so that only one of them had an abnormal HbA1c level. Other possible reasons for our results are over-diagnosis of gestational diabetes by gynecologists and an inadequate number of participants in our study.

Myocardial hypertrophy and cardiac dysfunction frequently occur in newborns of diabetic mothers. The authors hypothesized that wall hypertrophy or disproportionate left ventricular wall thickness in newborns of diabetic mothers may affect both QT and QTc dispersion. This study aimed to assess whether left ventricular hypertrophy affects the QT variables of infants born to diabetic mothers. This prospective cross-sectional study was conducted with 47 consecutively selected neonates of gestational diabetic mothers and 30 healthy neonates born to healthy mothers. All the subjects were evaluated during the neonatal period. Electrocardiography with echocardiography was performed for the patients and the control subjects. The newborns of the diabetic mothers were classified according to septal thickness as group 1 (16 newborns with septal hypertrophy) or group 2 (31 newborns without septal hypertrophy). The study group consisted of three cohorts: groups 1, 2, and 3 (control group). Both QT and QTc dispersion were computed from a randomly selected beat as well as from an average beat derived from 12 beats included in a 10-s electrocardiography. A total of 16 infants (34 %) had a septal thickness of 6 mm or greater. The left ventricular end-systolic diameter in group 1 was smaller ( p = 0.0029) than in groups 2 and 3 ( p = 0.003). The interventricular septal thickness at end diastole (IVSTd) and the left ventricular posterior wall thickness at end diastole in group 1 were higher than in of groups 2 and 3. The QT and QTc dispersion intervals were longer in group 1 than in groups 2 and 3 ( p < 0.001), and a highly significant positive correlation was detected between IVSTd and QT dispersion ( r = 0.514, p = 0.042). Elevated QT and QTc dispersions may be risk factors for the development of arrhythmias in newborns of diabetic mothers. These patients may critically need systematic cardiac screening. [ABSTRACT FROM AUTHOR]

Abstract: Background: Fetal exposure to maternal diabetes mellitus (DM) is associated with high birth weight, congenital heart malformations, childhood adiposity, DM, hypertension and dyslipidemia. The long term cardiovascular consequences of fetal exposure to maternal DM during pregnancy and high birth weight are not known. Method: All individuals born in Sweden 1973–1988 (n=1,551,603) were included in the study. The Swedish Medical Birth Register was merged with the Swedish Prescribed Drug Register. The association between offspring's adult consumption of cardiovascular medication and i) maternal DM during pregnancy and ii) birth weight were analyzed. Follow up time ranged between 17 and 36years. Results: Offspring exposed to maternal DM in utero had an increased risk of non-malformation cardiovascular disease (NMCVD), odds ratio (OR) 1.46 (95% confidence interval (CI) 1.16–1.83). After also excluding offspring with insulin dependent DM, no increased risk of NMCVD was found, OR 1.19 (95% CI 0.92–1.55). No increased risk of NMCVD was found in offspring born large for gestational age, OR 1.02 (95% CI 0.96–1.08). An increased risk of NMCVD was found in offspring born small for gestational age, OR 1.29 (95% CI 1.24–1.35). Conclusions: Exposure to maternal DM during pregnancy was not associated with NMCVD in offspring at a maximum of 36years of follow up. Low birth weight was confirmed to be a risk factor for NMCVD while high birth weight was not. [Copyright &y& Elsevier]

Intellectual disability (ID) is a major public health condition that usually develops in utero and causes lifelong disability. Despite improvements in pregnancy and delivery care that have resulted in dramatic decreases in infant mortality rates, the incidence of ID has remained constant over the past 20 years. There may still be uncharacterized preventable causes of ID such as Diabetes Mellitus (DM). We used statewide individual level de-identified data for maternal and child pairs obtained by linking Medicaid claims, Department of Education, and Department of Disabilities and Special Needs data from 2000 to 2007 for all mother-child pairs with a minimum follow-up of 3-years post birth or until a diagnosis of ID. To ascertain the adjusted relationship between DM and ID, we fit a logistic regression model taking into account individual level clustering on mothers for multiple pregnancies using the population-averaged Generalized Estimating Equations method. Of the 162,611 eligible maternal and child pairs, 5,667 (3.49 %) of the children were diagnosed with ID between birth and 3-years of age. After adjustment for covariates the independent relationship between DM and ID was significant with odds ratio of 1.10 (1.01-1.12). On sub-analysis, patients with pre-pregnancy DM had the highest effect measure with an estimated odds ratio of 1.32 (0.84, 2.09), although this was not statistically significant. In this large cohort of mothers and children in South Carolina, we found a small but statistically significant increased risk for ID among children born to mothers with DM. Additional information about the association between maternal DM and risk of ID in children may lead to the development of effective preventive interventions on the individual and public health levels. [ABSTRACT FROM AUTHOR]

Aim: To determine the prevalence and types of intrapartum cardiotocography (CTG) patterns and investigate their relationship to moderate acidemia in term fetuses of diabetic mothers. Also, to assess if the combination of fetal electrocardiogram (FECG) and those CTG patterns strengthens the association with moderate acidemia. Material and methods: The material for this study is obtained from the Swedish randomized control trial and the European Union ST-analysis trial. We developed an analytical model for CTG patterns based on the progress in CTG changes, in a longitudinal periodic manner. The model was then combined with information regarding changes in ST interval that indicate threatening asphyxia, and the findings were analyzed to determine correlation with the presence of moderate acidemia at birth. Results: This study involved data of 413 diabetic mothers. A preterminal CTG was more common in the diabetes mellitus (DM) group (6/70, 8.6%) than in the gestational diabetes (GD) group (3/307, 1.0%; P=0.003). For diabetic mothers (i.e., DM+GD) with a normal CTG at the start of monitoring, the presence of FECG data indicating asphyxia significantly increased the likelihood of an umbilical artery pH<7.15 at birth [odds ratio (OR)=3.65, 95% confidence interval (CI)=1.33-10.05]. Among labors where the CTG was non-reassuring at the start of monitoring, no significant association was found between pH<7.15 and indication to intervene according to FECG information (OR=1.51, 95% CI=0.33-7.0). Conclusions: A preterminal CTG is more common in the fetuses of DM than GD mothers during labor. When CTG was normal at the start of recording, the addition of FECG information gave a significant add on information to predict moderate acidemia. [ABSTRACT FROM AUTHOR]

To determine whether there is a delay or reversal in switch mechanisms from embryonic (ε and ζ) to fetal (γ) hemoglobins accompanying the erythroblastosis in fetuses of diabetic mothers, and whether the increased erythroblast count in the fetal blood is associated with an increase in fetomaternal cell trafficking. In both fetal and maternal blood the median percentages of erythroblasts positive for γ-globin, ε-globin and ζ-globin chains were significantly higher in fetuses of diabetic mothers compared to controls (fetus, γ-globin, 76 vs. 64%, p < 0.0001; ε-globin, 4 vs. 0%, p < 0.0001; ζ-globin, 4 vs. 0%; p < 0.0001; mother, γ-globin, 14 vs. 1%, p < 0.0005; ε-globin, 0.25 vs. 0%, p < 0.0003; ζ-globin, 0.2 vs. 0%, p < 0.0003). The median percentage of cells with Y signals in maternal blood was also higher in diabetic pregnancies compared to normal controls (7.5 vs. 1%, p < 0.002). The findings suggest that the fetal erythroblastosis in diabetic pregnancies is accompanied by a delay in the switch from embryonic to fetal hemoglobin chains. In addition, it is associated with an increase in fetomaternal cell trafficking. [ABSTRACT FROM AUTHOR]

Objective To determine fetal left ventricular diastolic function as expressed by normalized left ventricular filling rate integral as well as conventional indices of transmitral blood flow in appropriate-for-gestational-age (AGA), small-for-gestational-age (SGA) and IDDM (insulin-dependent diabetes mellitus) fetuses during the third trimester of pregnancy. Design A cross-sectional study of fetal left ventricular filling using conventional parameters of transmitral blood flow. Subjects Twenty-five AGA fetuses (mean 32 weeks), 18 SGA fetuses (mean 32 weeks) and 15 fetuses associated with IDDM (mean 31 weeks). Methods Doppler measurements of mitral inflow velocity were converted to relative cumulative volume flow by integration at sequential time points along the velocity contour, producing a relative filling curve of the ventricle. The area under this curve was calculated to obtain the left ventricular filling rate integral. Results The left ventricular filling rate integral (I) for the complete diastole (E + A wave) was not significantly different between AGA and SGA fetuses but significantly lower in the IDDM fetus (p < 0.05) compared with the AGA fetus. Ie (E wave) was significantly lower and Ia (A wave) significantly higher in both SGA fetuses (p < 0.05) and IDDM fetuses (p < 0.01) compared with AGA fetuses. Conclusions There is a delay in left ventricular filling which may reflect changes in myocardial relaxation and possible reduction in passive ventricular filling as a result of chronic hypoxemia in the SGA fetus and altered in utero metabolic environment in the IDDM fetus. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is the most common anatomical malformation occurring live-born infants and an increasing cause of morbidity and mortality across the lifespan and throughout the world. Population-based observations have long described associations between maternal cardiometabolic disorders and the risk of CHD in the offspring. Here we review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD offspring with particular attention to mechanistic models of maternal-fetal risk transmission and first trimester disturbances of fetal cardiac development. A deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHD by identifying at-risk pregnancies, along with primary prevention of disease by improving preconception and prenatal treatment of at-risk mothers.

The caudal regression syndrome is defined as total or partial agenesis of the sacrum and lumbar spine, frequently associated with other developmental malformations (orthopedic, neurological, genito-urinary, gastrointestinal…). Prenatal diagnosis is possible through fetal ultrasound (US) and magnetic resonance imaging (MRI). A case of fetal caudal regression syndrome with omphalocele from a diabetic mother is presented, demonstrating the sonographic, MRI, CT and X-Ray features diagnostic. We will also discuss neonatal findings, risk factors and prognosis of this condition.

Maternal diabetes has adverse effects not only on oocyte quality but also on embryo development. However, it is still unknown whether the DNA imprinting in oocytes is altered by diabetes. By using streptozotocin (STZ)-induced and nonobese diabetic (NOD) mouse models we investigated the effect of maternal diabetes on DNA methylation of imprinted genes in oocytes. Mice which were judged as being diabetic 4 days after STZ injection were used for experiments. In superovulated oocytes of diabetic mice, the methylation pattern of Peg3 differential methylation regions (DMR) was affected in a time-dependent manner, and evident demethylation was observed on Day 35 after STZ injection. The expression level of DNA methyltransferases (DNMTs) was also decreased in a time-dependent manner in diabetic oocytes. However, the methylation patterns of H19 and Snrpn DMRs were not significantly altered by maternal diabetes, although there were some changes in Snrpn. In NOD mice, the methylation pattern of Peg3 was similar to that of STZ-induced mice. Embryo development was adversely affected by maternal diabetes; however, no evident imprinting abnormality was observed in oocytes from female offspring derived from a diabetic mother. These results indicate that maternal diabetes has adverse effects on DNA methylation of maternally imprinted gene Peg3 in oocytes of a diabetic female in a time-dependent manner, but methylation in offspring's oocytes is normal.