Gestational diabetes mellitus is an abnormal glucose tolerance that occurs or is first detected during pregnancy, its incidence varies from country to country but is on the rise, and GDM can cause many adverse effects on both the mother and child in the near and distant future.
1, GDM on the recent maternal effects
(1) Hypertensive disease in pregnancy – preeclampsia
Schneider et al. reported that GDM is an independent risk factor for the development of preeclampsia, and age, first birth, and multiple pregnancies are common risk factors for both, and pre-pregnancy body mass index (BMI) is an important monitoring indicator for the occurrence of both. To study the relationship between the severity of GDM and preeclampsia, scholars at home and abroad have conducted long-term, large-sample investigations: the incidence of preeclampsia increased significantly with increasing fasting glucose and glycosylated hemoglobin values; the study also found that high pre-pregnancy BMI and rapid weight gain during pregnancy were independent risk factors for the development of GDM with preeclampsia. Therefore, good glycemic and weight control during pregnancy can reduce the incidence of preeclampsia.
(2) Excessive amniotic fluid
The incidence of excessive amniotic fluid is 10 times higher than that of non-diabetic pregnant women, and the mechanism of its occurrence is still unclear. Early studies suggested that the hyperglycemic state of the fetus leads to hyperosmolar diuresis, resulting in increased urination of the fetus, and the increased concentration of glucose in the amniotic fluid causes hyperosmolarity, resulting in excessive amniotic fluid. Recently, it has been proposed that intra-amniotic transit is an important mode of amniotic fluid transport, and water channel proteins (APQs) expressed in the placenta are involved in water transport across biological membranes and may play an important role in maternal and fetal fluid exchange; the expression of AQP8 and AQP9 in amniotic membrane and placental tissue is high in the group with high amniotic fluid in GDM, while the difference between AQP8 and AQP9 in the group with normal amniotic fluid and the control group is not statistically significant Therefore, it was hypothesized that the high expression of AQP8 and AQP9 in amniotic and placental tissues in GDM patients may only play an important compensatory regulatory role in the abnormal amniotic fluid volume in GDM, but not be the cause of the abnormal amniotic fluid volume in GDM. Nevertheless, the study of water channel proteins still provides a new idea for the treatment of excessive amniotic fluid.
(3) Cesarean delivery
It is not an indication for cesarean delivery per se, but it indirectly increases the rate of cesarean delivery because of the tendency to combine other obstetric diseases and the high incidence of giant babies. In recent years, the cesarean delivery rate of GDM has gradually increased, and the cesarean delivery rate of GDM pregnant women with fasting glucose >5.8mmol/L in the glucose tolerance test is significantly higher than that of pregnant women with fasting glucose <5.8mmol/L. In GDM pregnant women with fasting glucose >5.8mmol/L, glucose tolerance level and maternal weight are independent risk factors for cesarean delivery. In addition, the cesarean delivery rate in GDM pregnant women with well-controlled glucose was significantly lower than that in the group with uncontrolled glucose. Therefore, the control of glucose level and maternal weight gain during pregnancy is important for the reasonable return of delivery mode.
2. Recent effects of GDM on the offspring
(1) Fetal overgrowth
The incidence of gigantism in pregnant women with GDM without glycemic control is high. The elevated fasting glucose, pregnancy weight gain, family history of diabetes and history of delivery of gigantism in pregnant women with GDM are the main risk factors for the occurrence of gigantism, and maternal serum triacylglycerol level may be an independent predictor for the occurrence of gigantism, so the monitoring of fasting glucose, lipid level and pregnancy weight gain should be paid attention to during pregnancy. The traditional view is that the hyperglycemia-hyperinsulin theory, the mechanism of which is that maternal blood glucose is transported to the fetus through the placenta, and fetal hyperglycemia stimulates the proliferation and hypertrophy of pancreatic B cells and increases insulin secretion, thus triggering hyperinsulinemia, promoting amino acid uptake, protein synthesis and inhibiting lipolysis, leading to the occurrence of macrosomia. In recent years, it has been shown that the placental transport and surrogate fetal insulin-like growth factor-1 system affects intrauterine fetal growth and metabolism, leading to the development of macrosomia. Fetal growth restriction is also of concern and may be related to inadequate nutritional intake due to over-controlled diet in pregnant women with GDM.
(2) Preterm birth
The correlation between GDM and preterm delivery is not uniform, but it is recognized that increased blood glucose levels during pregnancy increase the risk of spontaneous preterm delivery, and glycemic control reduces the risk of preterm delivery. the severity of GDM is associated with preterm delivery: the incidence of preterm delivery is significantly higher in diabetic pregnant women with poor glycemic control than in diabetic pregnant women with good glycemic control, and the incidence of preterm delivery is higher in diabetic pregnant women with GDM requiring insulin therapy than in those requiring diet therapy alone.
(3) Perinatal mortality
The hyperglycemia of pregnant women with GDM affects the blood oxygen supply to the fetus and placenta, and the hyperglycemia and hyperinsulinemia of the fetus increase the oxygen consumption of the body, causing intrauterine hypoxia, and in serious cases, the fetus may die in utero; if the ketoacidosis is complicated by poor glycemic control, the fetal mortality rate will be high. Perinatal prognosis, termination of pregnancy at 39 weeks of gestation can significantly reduce the stillbirth rate and neonatal mortality.
(4) Shoulder obstructed labor and birth injury
The fetus with GDM has a disproportionate body shape during growth, the trunk grows more rapidly than the head, and fat tends to be distributed on the back of the shoulder. Therefore, even a fetus with normal weight may still have a difficult shoulder delivery. In addition, the high incidence of gigantism in GDM fetuses further leads to an increased risk of obstructed shoulder delivery: the risk of obstructed shoulder delivery is 3.6 times higher in GDM gigantics. In addition to the increased risk of labor tear and postpartum hemorrhage, obstructed shoulder delivery also predisposes to neonatal asphyxia, neonatal brachial plexus injury, clavicle fracture and intracranial hemorrhage, and the occurrence of these neonatal complications is related to the weight of the newborn, the duration of shoulder delivery and the number of delivery techniques used.
(5) Other neonatal complications
Due to the presence of hyperinsulinemia, GDM increases the risk of neonatal hypoglycemia, the occurrence of which is closely related to maternal blood glucose levels at the time of delivery in the neonatal period in the offspring of pregnant women with GDM. In addition, GDM can also lead to neonatal hyperbilirubinemia, neonatal respiratory distress syndrome, erythrocytosis and other complications, the pathophysiological basis for the pathogenesis of persistent hyperglycemia and hyperinsulinemia, hyperinsulinemia leads to reduced synthesis of fetal lung surface active substances, increased incidence of neonatal respiratory distress syndrome; cause increased metabolism and oxygen consumption of the body, prone to chronic hypoxia, stimulating fetal The increase in hematopoiesis outside the bone marrow, the increase in erythropoiesis, and the massive destruction of erythrocytes after delivery lead to hyperbilirubinemia.
3, GDM on the maternal long-term impact
GDM pregnant women are a high prevalence of diabetes, Damm et al. found after follow-up of 241 cases of diet-controlled GDM pregnant women from 1978 to 1985, 6 years after delivery 3.7; women with type 1 diabetes, 14.5; with type 2 diabetes, 19.5; combined with abnormal glucose tolerance or abnormal fasting glucose, while no diabetic patients were found in the control group, only 5.3; combined with abnormal glucose tolerance or abnormal fasting glucose. Subsequently, Feig et al. investigated 659,164 non-pregnant diabetic women from 1995-2001, and found that the incidence of type 2 diabetes in pregnant women with GDM at 9 months postpartum was 3.7 and 18.9 at 9 years postpartum, whereas the incidence of type 2 diabetes in women in the normoglycemic group at 9 years postpartum was only 1.95, controlling for age, number of births, After controlling for confounding factors such as age, birth, residence, and income status, GDM was the most significant risk factor for the development of diabetes mellitus in the postpartum period. Kim et al. reported that the incidence of developing type 2 diabetes in pregnant women with GDM increased from 2.6 to more than 70 with increasing follow-up time from 6 weeks postpartum to 28 years postpartum. Early studies suggested that the development of type 2 diabetes in pregnant women with GDM is only related to family genetic factors, but maternal age, postpartum obesity, repeat pregnancy, and severity of GDM are also high-risk factors for the development of type 2 diabetes, and the early onset of gestational hyperglycemia and high oral glucose tolerance test (OGTT) 2h and 3h values affect the occurrence of postpartum glucose metabolism abnormalities in GDM that may develop into type 2 diabetes. In the high-risk group of diabetes such as obese and those with family history, exercise can delay the occurrence of diabetes, and exercise + diet control can reduce the risk of developing type 2 diabetes by 30 to 50; potentially. GDM also increases the risk of metabolic syndrome in the postpartum period, and the risk of metabolic syndrome in GDM patients is 3 times higher than that in the normal population.
4, GDM on the long-term effects of offspring
In the 1990s, David Barker pointed out through a series of epidemiological studies that the nutritional status during pregnancy will have an important impact on the occurrence of cardiovascular abnormalities, abnormal glucose metabolism, obesity and other diseases in the offspring, that is, the “fetal origin of adult diseases theory”. As research in this field progressed, it was confirmed that genetic and intrauterine environmental factors not only affect fetal development in utero, but also produce continuous functional and structural changes that lead to a series of diseases in adulthood, and this theory has gradually transitioned and improved into the DOHaD theory, which suggests that we should pay more attention to nutrition and health during pregnancy in order to provide early prevention of chronic diseases that affect adult health. As a result, the adverse effects of GDM on the offspring in the distant future have also received increasing attention in recent years.
(1) History of obesity GDM
Maternal offspring are at increased risk of obesity: compared to mothers who developed diabetes postnatally and never had comorbid diabetes, offspring of GDM mothers had significantly higher mean BMI from birth to adulthood, and Lowlor et al [6] found in a study of 280,866 male singleton births that maternal GDM would result in increased mean BMI in male offspring at age 18 years compared to offspring of non-GDM mothers, and The same differences existed between siblings, which also suggests that the effect of GDM on offspring BMI is mainly related to intrauterine hyperglycemia and less related to the living environment. It is unclear whether glycemic control during pregnancy reduces the risk of obesity in the offspring. Although treatment of mild GDM can reduce the incidence of macrosomia, it does not improve the BMI of offspring at the age of 4 to 5 years.
(2) Type 2 diabetes mellitus
The risk of diabetes mellitus in the offspring of pregnant women with GDM at the age of 19-27 years is 8 times higher than that of the offspring of normal pregnant women; the insulin resistance index of the offspring of pregnant women with GDM is higher than that of the offspring of normal pregnant women, indicating that even if the offspring do not have abnormal glucose tolerance, they may have combined insulin dysfunction, and the mechanism of abnormal glucose metabolism in the offspring may be related to the intrauterine hyperglycemic environment. The mechanism of abnormal glucose metabolism in the offspring may be related to insulin resistance caused by the intrauterine hyperglycemic environment and damage to B cells in the offspring.
(3) Cardiovascular diseases
In addition to diabetes mellitus and metabolic syndrome, cardiovascular diseases are also highly prevalent in the offspring of pregnant women with GDM, including high blood pressure and cardiac injury. Systolic blood pressure is higher in the offspring of GDM pregnant women compared to the offspring of non-GDM pregnant women, but this may be related to the greater susceptibility of GDM offspring to obesity and may also be due to the hyperglycemic and hyperinsulinemic state of the offspring affecting the kidneys, leading to an increased incidence of nephrogenic hypertension.Chu et al [9] reported altered cardiac anatomy and function in GDM fetuses, including thickening of the ventricular wall, increased fetal blood circulation, and Diastolic and ventricular hypofunction, of which changes in Tei index were detected earliest, and changes in the right ventricle were greater than those in the left ventricle. Good glycemic control during pregnancy in pregnant women with GDM can delay the gestational weeks of fetal heart injury, but cannot change the extent of lesions. The ventricular structure of infants with GDM can be partially restored at 60-90 d of birth, but there is still some distance to complete recovery, and there are still no studies to clarify the exact time of recovery. Epidemiological studies with large samples have shown that the incidence of coronary heart disease is significantly higher in the offspring of diabetic mothers.
(4) Motor and neurological dysfunction
GDM not only affects maternal and fetal health during pregnancy, but also the maternal and offspring are at risk of developing type 2 diabetes and metabolic syndrome in the long term. metabolic syndrome and other diseases at increased risk, forming a vicious circle that will probably lead to more and more people with the disease. Therefore, early screening, early detection and early diagnosis of high-risk groups, as well as effective glucose monitoring and control will help to reduce the occurrence of various complications of GDM and better protect the safety of mother and child.