Progress in the effect of maternal diabetes on the kidney development in offspring / 国际儿科学杂志

Maternal diabetes not only affects the mother′s own health but also has a significant influence on offspring.Adverse prenatal and intrauterine condition can influence fetal kidney development, which may increase the risk of kidney disease in the adulthood.This article reveiws the impact of maternal diabetes on kidney structure and function.Maternal diabetes can increase the risk of congenital anomalies of the kidney and urinary tract(CAKUT)and impair early and long-term renal function of offspring.In addition, this article reveiws the research progress of the potential mechanisms of how maternal diabetes affects kidney development including oxidative stress, key signal pathway changes of kidney development and epigenetic changes.

Glycemic and nonglycemic mechanisms of congenital malformations in hyperglycemic pregnancies: a narrative review

ABSTRACT Congenital malformations are more frequently found among children born to mothers with diabetes than in the background population. There are several complex mechanisms involved in the development of congenital malformations in the offspring of mothers with hyperglycemia, such as the overexpression of glucose transporters (GLUTs) 1 and 2, the increased activity of the hexosamine biosynthetic pathway and the reduced expression of the PAX3 gene with a consequent increase in p53 protein expression. These alterations can lead to increased glucose and free radical concentrations in the embryo, thus promoting the process of apoptosis and causing malformation. The most frequent malformations found in the offspring of mothers with diabetes are heart and neural tube defects, urinary tract and kidney malformations, and cleft lip with or without cleft palate. Strict glycemic control should be obtained before and during pregnancy, aiming to avoid or minimize the risk of congenital malformations in the offspring. Beyond hyperglycemia, several factors may also be associated with increased risks of malformations in the offspring of these women, such as obesity, multiple pregnancies, advanced maternal age, folic acid deficiency, use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, assisted reproduction techniques, and exposure to different types of environmental pollutants.

Caudal regression syndrome: A rare case report with review of the literature

Caudal regression syndrome is a very rare neural tube disorder, in which the caudal vertebral column and spinal cord develop abnormally, causing substantial sensory and motor deficits, primarily in the legs. An abnormality in the spinal cord and nerve roots interacts with a section of lumbar, lumbosacral, or coccygeal spinal dysgenesis or agenesis. Here, we present a rare case of caudal regression syndrome in a 3-year-old male child who was brought to the pediatrics department with a serious complaint of urine dribbling since infancy. The infant was discovered with spina bifida, lumbar scoliosis, and cavus deformity in both feet during a routine health check. For which, a neurological opinion was taken. Plain X-ray revealed a partial sacral agenesis, MRI revealed anterior and posterior nerve roots of cauda equina divided into two bundles of fibers due to abnormal path. The lower back and both gluteal areas were underdeveloped. On the basis of radiological findings, a diagnosis of the syndrome was confirmed.

Maternal diabetes: A potential risk factor of congenital hearing loss

@#Objective. The purpose of this study is to identify the incidence rate of 'refer' result in neonates born to diabetic mothers and to determine the association of maternal diabetes and the initial 'refer' result. Methods. This was a retrospective cross-sectional study which included neonates who had hearing screening test using transient-evoked otoacoustic emissions test (TEOAE) on both ears at the Philippine General Hospital Ear unit during three weeks. We obtained the demographic characteristics, presence/absence of maternal diabetes, and OAE results. Results. Among the 150 neonates, ten were born to diabetic mothers, with an age range of 2-8 days old. Forty percent of neonates of diabetic mothers had an initial 'refer' result compared with 7.9% of nondiabetic mothers' neonates. After logistic regression analysis, there is a significant association between maternal diabetes and initial 'refer' result in OAE with a p-value <0.05. If the mother is diagnosed with diabetes (gestational/pre-gestational), the odds of having an initial 'refer' result in the hearing screening is 2x higher. The odds can range from 2-43 times. Conclusion. The incidence rate of an initial 'refer' result in neonates of diabetic mothers is 40%. There is a significant association between maternal diabetes and the initial 'refer' result in the OAE test.

Diabetes materna y trastornos del neurodesarrollo en los hijos / Maternal diabetes and neurodevelopmental disorders in offspring

Resumen La diabetes durante el embarazo se asocia a un mayor riesgo perinatológico para los niños. Este puede reducirse significativamente con un control glucémico adecuado en estadios tempranos de la gestación. En la última década nuevos estudios han mostrado los efectos deletéreos de la diabetes materna en la salud de los hijos a largo plazo, como las alteraciones del neurodesarrollo y los efectos sobre el pronóstico educacional y ocupacional. Las mismas pueden ser clasificadas, desde el punto de vista clínico-diagnóstico en tres grupos principales: trastornos del aprendizaje y del desarrollo intelectual, trastorno por déficit de atención e hiperactividad y trastornos del espectro autista. El presente trabajo tiene como objetivo realizar una actualización no sistemática de la evidencia más reciente en el tema y comprender los mecanismos subyacentes que provocan el daño, con el fin de desarrollar estrategias preventivas.

Abstract Diabetes during pregnancy is associated with adverse effects on offspring perinatal outcomes. These could be reduced significantly with an adequate glycemic control in early stages of gestation. In the last decade, new studies have shown the effects of maternal diabetes in the long-term health of the offspring, like impaired neurodevelopment and its impact on educational and occupational outcome. This can be classified, from the clinical and diagnostic perspective, in three main groups: learning and cognitive disorders, attention deficit hyperactivity disorder and autism spectrum disorders. This paper has the objective to give a non-systematic upgrade of the current evidence on the subject, and to understand the underlying mechanisms of adverse neurodevelopmental outcomes which in turn may lead to strategies for its prevention.

Life Without Limbs: Tetra-amelia

Amelia is defined as the complete absence of the skeletal parts of a limb. Tetra- amelia, is the absence of all thefour limbs is a very rare condition with an incidence range of 1.5–4/100,000 births. Many factors causingvarious limb defects are genetic, environmental (teratogens), vascular compromise by amniotic bands andconditions like oligohydraminos and maternal diabetes. Point mutation in the WNT gene plays a major role incausing limb defects.

Sirenomelia: A Detailed Fetal Autopsy Study.

Sirenomelia also known as mermaid syndrome, characterized by fused lower limbs, is a lethal and rare congenital abnormality. This is an extreme example of caudal regression syndrome caused by vascular steal of single umbilical artery. Sirenomelia is found approximately one in 100,000 live births and is usually fatal because of complications associated with pulmonary hypoplasia, abnormal development of the kidneys and urinary bladder. Most of the cases are associated with maternal diabetes and single umbilical artery. We report a case of sirenomelia terminated at 21weeks of gestation due to multiple congenital abnormalities. Antenatal scan of a25-year old primi revealed a single live fetus of 21 weeks gestation with severe olighydramnios, non-visualization of kidneys and bladder and lower part of the spine. This pregnancy was terminated and the specimen sent to the department of anatomy for fetal autopsy. On external examination,a tail like rudimentary single midline lower limb without foot was noted. There were no external genitalia and anal orifice. Internal examination revealed hypoplastic lungs, atrial septal and ventricular septal defects, aberrant right subclavian artery, hypoplastic abdominal aorta distal to the single umbilical artery, complete agenesis of urinary system, rectal agenesis and rudimentary indeterminate gonads. We would like to discuss the clinical features, etio- pathogenesis and review of literature of sirenomelia. Early diagnosis and termination of this lethal congenital anomaly results in minimizing the trauma related to the termination of pregnancy at advanced gestation.

Protective effect of Cissus quadrangularisLinn. on diabetes induced delayed fetal skeletal ossification.

Background: Delayed fetal skeletal ossification is one of the known complications of maternal diabetes. Objective: The present study was designed to evaluate the protective role of petroleum ether extract of Cissus quadrangularis (PECQ) on diabetes‑induced delayed fetal skeletal ossification. Materials and Methods: Female Wistar rats were rendered diabetic with streptozotocin (STZ, 40 mg/kg, intraperitonial) before mating. After confirmation of pregnancy, the pregnant rats were divided into three groups: normal control group, diabetic control group, and diabetic + CQ group. The diabetic + CQ group pregnant rats were treated with PECQ (500 mg/kg body weight) throughout their gestation period. Immediately after delivery, pups were collected from all three groups and processed for alizarin red S–alcian blue staining in order to examine the pattern of skeletal ossification. Results: Fewer ossification centers and decreased extent of ossification of forelimb and hindlimb bones were observed in the neonatal pups of diabetic control group as compared to those in the normal control group. PECQ pretreatment significantly restored the ossification centers and improved the extent of ossification of forelimb and hindlimb bones in the neonatal pups of diabetic + CQ group as compared to those in the diabetic control group. Conclusions: The results suggested that PECQ treatment is effective against diabetes‑induced delayed fetal skeletal ossification. However, further studies on the isolation and characterization of active constituents of PECQ, which can cross the placental barrier and are responsible for the bone anabolic activity are warranted.

Prenatally programmed hypertension: role of maternal diabetes

Epidemiological and experimental studies have led to the hypothesis of the fetal origin of adult diseases, suggesting that some adult diseases might be determined before birth by altered fetal development. Maternal diabetes subjects the fetus to an adverse environment that has been demonstrated to result in metabolic, cardiovascular and renal impairment in the offspring. The growing amount of obesity in young females in developed and some developing countries should contribute to increasing the incidence of diabetes among pregnant women. In this review, we discuss how renal and extrarenal mechanisms participate in the genesis of hypertension induced by a diabetic status during fetal development.

A Case of Caudal Regression Syndrome Diagnosed by Prenatal Ultrasonography / 대한산부인과학회지

Caudal regression syndrome is rare malformative syndrome characterized by lower vertebral agenesis, accompanied by abnormalities of the pelvis, lower extremities and urogenital malformation. Although the cause is not clear, hyperglycemia during the organogenesis may be important teratogen. Strict evaluation of diabetes and its control in preconception and early pregnancy are important to prevent this malformation. And ultrasonography in the first trimester should be recommended for early detection of this syndrome. We report a case of caudal regression syndrome detected by prenatal ultrasonography of the gestational diabetic mother.