Children Of Diabetic Mothers Research Articles

Cardiac Manifestations in Children of Diabetic Mothers and Fathers.

Diabetic individuals of reproductive age face higher risks of poor pregnancy outcomes and abnormal fetal development. Approximately 4.5% of women of reproductive age have diabetes, with non-Hispanic Black women having the highest prevalence of 15%. Research on the impact of paternal diabetes on offspring cardiac anomalies is limited, but it may interact with metabolic syndrome to increase long-term health risks. Infants of diabetic parents are more likely to develop cyanotic and acyanotic heart defects, hypertrophic cardiomyopathy, and subsequently other cardiovascular issues. Fetal hyperinsulinemia, caused by maternal hyperglycemia, contributes to these conditions through oxidative stress, impaired heart development, and cardiac remodeling. Long-term risks include diabetes, arrhythmias, pulmonary hypertension, heart failure, and early-onset cardiovascular disease. Treatment options are limited, often requiring surgery for severe conditions. Prevention focuses on tight glycemic control, a balanced diet, avoiding teratogens (nicotine, alcohol, or drugs), and using technology like continuous glucose monitors and insulin pumps, along with pregnancy screening and monitoring protocols. Understanding the effects of parental diabetes on offspring's cardiac health is crucial for early intervention, prevention, and improved maternal-fetal care, ultimately reducing the burden of congenital heart defects and long-term cardiovascular complications.

Caudal Regression Syndrome

Background: Caudal Regression Syndrome is an infrequent congenital malformation of the vertebral spine’s lower segments characterized by a truncated medullar cone and aplasia or hypoplasia of the sacrum. Specifically, sacral agenesis represents an incidence of 0.01 to 0.05 of every newborn. Among the main risk factors are elevated glycosylated hemoglobin, hormonal imbalance, and lipid protein metabolic disorder. A correlation has been established between anomalous pregnancies and congenital malformations in newborns, with a prevalence of 5 to 10% in children of diabetic mothers, with an incidence of 1 per 350 cases, representing a 200% rise over the general population. Objective: To report an extremely uncommon epidemiologically rare case of Caudal Regression Syndrome, characterized by caudal musculoskeletal involvement. Clinical case: a 27-year-old female in her 34th week of gestation during her second pregnancy presented to the high specialty, high-risk pregnancy consultation with a background of glycemia of 205mg/dl, glycosylated hemoglobin percentage (%HbA1c) of 10.1%, and estimated average glucose levels of 243mg/dl. The patient arrived at the emergency room during active labor with premature membrane rupture, both deciding factors for pregnancy termination. The outcome was a sole female live product with a vertebral spine interrupted approximately by T10, non-palpable iliac crests, sacrum, and coccyx, and shortening of hypotrophied inferior extremities. Conclusion: successful prevention in the early diagnosis of malformations during pregnancy requires strict prenatal control for any pregnant woman with metabolic risk factors. The first prenatal consultation presents an opportunity to perform diabetic screening. If diagnosed, follow-up procedures such as ultrasounds at a second level of medical care should be performed for the timely detection of congenital malformations associated with high levels of glycemia.

Neurodevelopment at Two Years of Age in Newborn Infants of Diabetic Mothers

Introduction: The lack of brain maturity caused by hyperglycemia in children of diabetic mothers has repercussion on language, fine and gross motor skills and cerebral palsy, which seem to have a higher incidence due to an adverse intrauterine environment, characterized by hyperglycemia, maternal hypoglycemia, vascular abnormalities and hypoxemia, which profoundly affect neurodevelopment. Objective: To describe neurodevelopment at two years of age of newborns born to diabetic mothers, who were admitted to the Pediatric Follow-up service of the National Institute of Perinatology in Mexico. Material and Methods: It is a retrospective, observational, longitudinal, analytical study of a cohort of newborns born to diabetic mothers, at two years of age, from 1990-2010. Two hundred and forty four infants plus a 51control group met the criteria for admission to the Pediatric Follow-up service and had the evaluations from the different services. Statistic analysis; means, medians, frequencies, ANOVA, Ch2, SPSS version 21. Results: 295 infants met the criteria and four groups were formed; 1) control group, 2) diabetes mellitus type 1, 3) diabetes mellitus type 2 and 4) gestational diabetes. Perinatal morbidity was higher for the type 2 diabetes mellitus group, but the presence of cerebral palsy was higher in mothers with gestational diabetes 8.3%, the Bayley II assessment was lower for type 1 diabetes mellitus, problems of decreased language for the different groups. Conclusion: There is a relationship between infants of diabetic mothers and the presence of neurodevelopmental problems, mainly cerebral palsy in gestational diabetes, Bayley II with normal mental and low motor scales.

Dapagliflozin Mitigated Elevated Disomic and Diploid Sperm in a Mouse Model of Diabetes and Recover the Disrupted Ogg1, Parp1, and P53 Gene Expression.

Increases in numerical chromosomal syndromes were observed in children of diabetic mothers. However, the effects of diabetes on male reproduction, specifically numerical chromosomal aberrations (aneuploidy), have not been studied. Furthermore, despite the increasing use of dapagliflozin for diabetes treatment, no data exists on its ability to affect aneuploidy levels in germ cells. Thus, our investigation aimed to evaluate the effects of diabetes on spontaneous sperm aneuploidy and whether treatment with dapagliflozin influences the frequency of aneuploidy in the sperm of an experimental diabetic animal model. Our findings show that dapagliflozin has no aneugenic effects on the meiotic stages of spermatogenesis. In contrast, diabetes raised the frequency of aneuploidy, and dapagliflozin administration decreased the elevated levels of disomic and diploid sperm. The level of oxidative stress was markedly increased in diabetic mice, but were reduced by dapagliflozin treatment. Furthermore, the expression of some of DNA repair genes was disrupted in diabetic animals, whereas dapagliflozin therapy restored these disruptions and significantly enhanced DNA repair. Thus, dapagliflozin may effectively ameliorate diabetes-induced aneugenic effects on male meiosis and treating diabetic patients with dapagliflozin may effectively mitigate the transmission of diabetes-induced chromosomal defects to offspring.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers

Motor Developmental Outcomes in Children Exposed to Maternal Diabetes during Pregnancy: A Systematic Review and Meta-Analysis.

Studies on the association of maternal diabetes with motor development in children provide inconsistent findings. We searched MEDLINE/PubMed, EMBASE, Emcare, PsycINFO, and Google Scholar databases for primary observational, case–control, or cohort studies that report on the motor development of children exposed to maternal diabetes during pregnancy. Quality appraisal and data extraction were performed independently and in duplicate. A meta-analysis of summary measures was performed using random-effect models. Eighteen studies were identified for inclusion, however, only 13 were included in the meta-analysis. Exposure to maternal diabetes during pregnancy was associated with a lower pooled motor development in children and a decrease in both gross and fine motor development. Among all other factors, pre-existing diabetes and other gestational comorbidities, such as hypertension and obesity, or low socioeconomic status, also affect child development. Therefore, among children of diabetic mothers, those with other gestational comorbidities or pre-existing diabetes were more likely to be at risk developmentally.

Hipokalcemija novorođenčeta usled transfuzije eritrocita - prikaz slučaja

Introduction: Hypocalcemia in preterm infants could occurs as early or late. Causes of late onset of hypocalcaemia: maternal vitamin D deficiency, metabolic syndromes, congenital abnormalities, iatrogenic (transfusion, bicarbonate therapy, phototherapy, antibiotics). Case report: The authors describe the occurrence of late hypocalcemia following transfusion of erythrocytes to the second newborn from a twin pregnancy born prematurely in the 32/33 week of gestation. Mother is diabetic and has hypertension, edema, hypothyroidism, and preeclampsia during pregnancy. Due to the detected pyelectasis in newborn, prophylactic use of cephalexin was introduced. At the end of the first month of life, anemia appear indicating a transfusion. The infant received 50 ml an O+ leukodepleted RBC transfusion. Immediately after transfusion was completed, there is a short-term deterioration of the general condition. Cyanosis, stiffness, trismus, and bradycardia appear within a few seconds. DAT was negative, bilirubin in the reference range. After transfusion, laboratory, echosonographic examination, neurological examination, EEG and ECG showed normal results. It was concluded that the adverse reaction was probably caused by transfusion. Conclusion: In preterm infants, hypocalcaemia may occur during transfusion due to citrate overload. Children of diabetic mothers, on antibiotic and photo therapy are at higher risk of developing hypocalcemia. Future studies should evaluate incidence rate of adverse transfusion reactions in newborns.

Persistent Aortic Stiffness and Left Ventricular Hypertrophy in Children of Diabetic Mothers

Persistent Aortic Stiffness and Left Ventricular Hypertrophy in Children of Diabetic Mothers

Cardiomyopathy and cardiac function in fetuses and newborns of diabetic mothers

Cardiomyopathy and cardiac function in fetuses and newborns of diabetic mothers

Sex differences in offspring neurodevelopment, cognitive performance and microglia morphology associated with maternal diabetes: Putative targets for insulin therapy

Sex differences in offspring neurodevelopment, cognitive performance and microglia morphology associated with maternal diabetes: Putative targets for insulin therapy

Volumetric investigation of the hippocampus in rat offspring due to diabetes in pregnancy–A stereological study

Volumetric investigation of the hippocampus in rat offspring due to diabetes in pregnancy–A stereological study

Maternal Diabetes Mellitus as a Risk Factor for High Blood Pressure in Late Childhood.

Intrauterine fetal conditions can have lifelong cardiovascular effects. The impact of maternal diabetes mellitus on children's cardiovascular profile is not well established. The goal of this study was to explore the association between maternal diabetes mellitus and offspring's blood pressure (BP) ≤10 years of age. Generation XXI is a prospective birth cohort, which enrolled 8301 mother-offspring pairs, including 586 (7.1%) children of diabetic mothers. The associations between maternal diabetes mellitus and BP at 4, 7, and 10 years of age was modeled using linear regression. A mixed-effects model was built to assess differences in BP variation over time. Path analysis was used to quantify effects of potential mediators. Maternal diabetes mellitus was associated with higher BP in offspring at the age of 10 (systolic: β, 1.48; 95% CI, 0.36-2.59; and diastolic: β, 0.86; 95% CI, 0.05-1.71). This association was independent of maternal perinatal characteristics, and it was mediated by child's body mass index and, to a lesser extent, by gestational age, type of birth, and birth weight (indirect effect proportion, 73%). No significant differences in BP were found at 4 and 7 years of age. Longitudinal analysis showed an accelerated systolic BP increase on maternal diabetes mellitus group (β, 1.16; 95% CI, 0.03-2.28). These finding were especially relevant in males, suggesting sex differences in the mechanisms of BP prenatal programing. Our results provide further evidence that maternal diabetes mellitus is associated with high BP late in childhood, demonstrating a significant role of child's body mass in the pathway of this association.

Left ventricular mass in offspring of diabetic mothers: at 5–7 years old

Newborns of mothers with diabetes have increased risk for cardiac left ventricular (LV) hypertrophy. Diabetic pregnancy is also associated with in increased risk for obesity and hypertension, as well as for later cardiovascular morbidity and mortality. This study aimed to examine the connection between being the offspring from a diabetic pregnancy and having hypertension and obesity to the increased risk to have left ventricular mass (LVM) and altered LV geometry in childhood. We conducted a retrospective cohort study on 23 offspring of diabetic mothers and 23 sex- and age-matched control children at the age of 5–7 years. LVM and LV geometry were assessed using M-mode echocardiography and indexed for height2.7. Data analyses were adjusted for birth weight, current overweight/obesity status and blood pressure. Prevalence of increased LVM/height2.7 was higher in children of diabetic mothers, i.e. 43.5 vs. 8.7% in the control group (RR (95% CI) 5.0 (1.2–20.4), p = 0.007). The association between maternal diabetes and increased LVM persisted after adjustment for age, sex, birth weight, current overweight/obesity status and blood pressure, with regression coefficient of (95% CI) 5.7 (1.4–10.1), p = 0.01. Together, maternal diabetes, overweight/obesity status and blood pressure contributed 50% to the increase. Results showed that children of diabetic mothers were more likely to have altered LV geometry (RR (95% CI) 6.0 (1.5–23.9), p < 0.001). Maternal diabetes is a risk factor for increased LVM and altered LV geometry in childhood.

Maternal and paternal family history of diabetes in second-degree relatives and metabolic outcomes at age 5–6 years: The ABCD Study

Maternal and paternal family history of diabetes in second-degree relatives and metabolic outcomes at age 5–6 years: The ABCD Study

Intrauterine fetal demise with caudal regression syndrome, a case report

Background: The causes of intrauterine fetal demise are varied and not entirely well-understood. Multiple observational studies have shown that both perinatal and infant mortality rates are increased in children of diabetic mothers when compared to those of nondiabetic mothers. Case: We present a case involving a 22-year-old G4P0120 with poorly controlled type 1 diabetes mellitus and a complex medical history including two first trimester fetal losses, and second trimester intrauterine fetal demise who presented during the second trimester for care and was found to have a fetus with ultrasound findings consistent with caudal regression syndrome. When she presented in labor at term intrauterine fetal demise was identified. Discussion: Infants and fetuses of diabetic mothers are at a higher risk for congenital anomalies, one of which is the potentially devastating caudal regression syndrome. However, it appears that this risk may be lowered with strict glycemic control both before and during pregnancy.

Associations of growth patterns and islet autoimmunity in children with increased risk for type 1 diabetes: a functional analysis approach.

Several studies indicate associations between early growth and type 1 diabetes (T1D). However, it remains an open question whether these findings can be translated to typical growth patterns associated with increased risk for T1D-associated islet autoimmunity. We analyzed pooled data from 2236 children followed up in two large prospective German birth cohorts with a genetically increased risk for T1D including 18 564 measurements of height and weight, which were transformed to sex- and age-specific standard deviation scores (SDS). A total of 191 children developed any islet autoantibodies, 101 multiple islet autoantibodies. We applied a model-based clustering technique to derive typical height and body mass index (BMI) growth patterns, stratified for maternal T1D status. These patterns were used to predict islet autoimmunity in logistic regression models, adjusted for potential confounders. Growth patterns were not associated with islet autoimmunity in the whole dataset and in children of diabetic mothers, respectively. In children of non-diabetic mothers ,however, islet autoimmunity was associated with rapidly increasing BMI SDS values until the age of 3 yr [adjusted odds ratio (95% confidence interval): 2.02 (1.03, 3.73) for development of any islet autoantibodies) and with consistently above average height SDS values [odds ratio: 2.21 (1.15, 4.17)]. In contrast, a pattern of high height SDS values at birth followed by a decrease to average values after 3 yr was associated with a reduced rate of islet autoimmunity [odds ratio: 0.16 (0.01, 0.62)]. Early growth patterns may be associated with T1D-related islet autoimmunity risk in children of non-diabetic mothers.

MATERNAL DIABETES MELLITUS AND ITS IMPACT ON CHILD NEURODEVELOPMENT; SYSTEMATIC REVIEW

at present, diabetes has become a global health problem. The consequences that entails, both short and long term, do more studies and knowledge necessary for detection, control and treatment. Moreover, its prevalence is increasing in both the general population and pregnant women. Numerous effects and complications have been reported in infants of diabetic mothers, such as fetal macrosomia, hypoglycemia and increased risk of developing obesity. This condition could have negative effects on the neurological development of the child and could affect his intellectual capacity and increase cognitive impairment. to analyze the studies which have investigated in the relationship between diabetes mellitus during pregnancy and its impact on child neurodevelopment short and long-term. we performed a systematic search and 20 specific articles on the subject selected would be selected following the PRISMA guidelines. in the studies consulted include a large methodological variety in both instruments and cognitive assessment scales, as in the age at which the sample is studied. However, most researchers conclude that maternal diabetes can have consequences for the child, both short and long-term. A higher rate of obesity, impaired glucose tolerance, cardiovascular and metabolic disorders and neurodevelopmental impairment is also described, which increase the neurobehavioral disorders and intellectual disability. most of the studies are agree in describing neurodevelopmental disorders in children of diabetic mothers, both in cognition and in the specific areas related to expressive language, social relations, graphical skills and psychomotor development. Other research has linked maternal diabetes with an increased incidence of autism spectrum disorders such as hyperactivity, attention deficits and schizophrenia.

Functional and Anatomic Consequences of Diabetic Pregnancy on Memory in Ten-Year-Old Children.

Pregnancies complicated by diabetes mellitus impair offspring memory functions during infancy and early childhood. The purpose of this study was to investigate the long-term consequences of such pregnancies on memory and memory-related brain regions in 10-year-old children. Nineteen children of diabetic mothers (CDMs) and 35 children of nondiabetic mothers participated in this 10-year follow-up study. Memory performance was assessed using a continuous recognition memory task during which children made old/new judgments in response to pictures of concrete and abstract objects presented after different lags or delays. In addition, the volume of the hippocampal formation (HF) was measured using high-resolution structural images. At 10 years of age, recognition memory performance of CDMs did not differ from children of nondiabetic mothers. Similarly, the volume of the HF did not differ between groups. However, the size of the HF in CDMs predicted the time those children needed to provide accurate responses in the continuous recognition memory task. CDMs do not show memory impairments by 10 years of age, despite evidence for such impairments early in life. However, subtle differences in underlying neural processes may still be present. These results have important implications for long-term cognitive development of CDMs.

Abstract P252: Effect of Maternal Diabetes on Fetal Programming of Vascular Remodeling Mechanisms in Adult Rats

Modifications of the intra-uterine environment are now recognized as an important cause of fetal stress. Leading to several responses such as loss of structure/function and pre-emptive adaptations to an adverse post-natal environment, and finally to adult diseases. It has been demonstrated that children of diabetic mothers have an increased risk of developing cardiovascular diseases (i.e. hypertension) during adulthood. Blood vessels are able to reorganize their structure in response to physiological alteration of blood flow or pathological stimuli. Constrictive vascular remodeling is currently associated with the occurrence of cardiovascular diseases. Thus, our objective was to study vascular remodeling in case of in utero exposure to maternal diabetes. This is in order to investigate the effect of intra-uterine environment perturbations on vascular fetal programming. We have developed an animal model of rats exposed in utero to moderated maternal hyperglycemia (DMO), which developed an hypertension around 6 months of age. We analyzed structure of elastic and resistance arteries (internal diameter, MCSA, intima-media thickness and remodeling parameters) in absence or presence of established hypertension in male DMO compared to controls (CMO) (at 3 and 18 months of age). Moreover, by in vivo sequential ligation of mesenteric arteries, we have studied vascular remodeling of resistance arteries in response to low (LF), normal (NF) or high flow (HF). In old DMO, we did not observe any vascular remodeling induced by hypertension neither in aorta nor in mesenteric arteries. This could be related to the increase of smooth muscle cell attachments that we observed. Moreover, after 1 or 3 weeks of mesenteric arteries ligation, DMO did not exhibit any constrictive remodeling in LF although expansive remodeling in HF is maintained. Interestingly, we measured an increase of eNOS activity and GP91 in LF arteries of theses animals although transglutaminase-2 protein expression was not modified. Our results demonstrate that in utero exposure to maternal diabetes induce modification of vascular remodeling mechanisms in adulthood. Absence of vascular response could be a pre-emptive adaptation to fetal programmed-hypertension in these animals.

Renal echo-3D and microalbuminuria in children of diabetic mothers: a preliminary study.

Maternal diabetes has assumed epidemic relevance in recent years and animal studies have provided some evidence that it may cause abnormalities in renal development and a reduction in nephron endowment in the offspring; however, human data are lacking. The renal cortex contains ∼95% of the glomeruli and its volume could be taken as a surrogate measure of glomerular number; based on this assumption, we measured renal cortex volume and in addition, microalbuminuria in a homogeneous sample of 42 children of diabetic (pregestational, n = 13, and gestational, n = 29) mothers, compared with 21 healthy children born of non-diabetic mothers. The offspring of diabetic mothers showed a significant reduction of renal cortex volume and higher albumin excretion compared with controls, possibly attributable to a reduction in the number of nephrons and the difference was statistically significant (P < 0.001). Although further studies on a larger sample are necessary, our preliminary findings suggest that maternal diabetes may affect renal development with sequelae later in life, requiring closer monitoring and follow-up. Furthermore, the importance of strict maternal diabetes management and control must be emphasized.