Diabetes has many adverse effects on pregnancy

Author: Dr Sorin Ioacara | Last update: November 18th, 2020

A newborn seen from the top of his head on blue hospital sheets, on a faint blue background.

Discover here: Fertility | Placenta | Pregnancy loss | Congenital malformation | Damage to the fetal pancreas | Impaired fetal growth | Premature birth | Hypoglycemia of the newborn

Diabetes has many adverse effects on pregnancy. Hypoxia and hyperinsulinemia are two standard features of pregnancy in women with diabetes. What do they mean? Hypoxia means a decrease in the blood oxygen level, while hyperinsulinemia implies an increase in the level of blood insulin.

Neonatal jaundice (yellowing of the baby) may be more severe due to a diabetes-associated increase in the number of red blood cells.

Up to 33% of newborns from mothers with diabetes have a thickening of the wall dividing the heart in left and right. This thickening decreases the heart’s efficiency. However, everything is usually transient and resolves spontaneously in time.

Decreased calcium and magnesium levels may accompany premature birth and mild asphyxia at birth.

Diabetes and fertility

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Diabetes is associated with several sexual development and fertility problems. Type 1 diabetes onset before puberty is responsible for a delay of the first menstruation, also called menarche. This lag can be significant in the case of poor metabolic control. The fertile period in women with diabetes is generally shorter, with a faster onset of menopause.

During the fertile period, amenorrhea can occur, i.e. the lack of menstruation. However, this usually occurs at glycosylated haemoglobin values above 9% (75 mmol/mol).

During pregnancy, glycosylated hemoglobin (HbA1c) evaluates the average blood glucose over the last two months. The reason is that during pregnancy, the mother’s blood changes faster. Besides, HbA1c is falsely low in pregnancy, frequently by up to one percentage point. Remember that you need two HbA1c values <7% (53 mmol/mol) three months apart to be able to start the conception of a baby safely.

Couple infertility is the lack of pregnancy after at least one year of trying. There may be a monthly menstrual cycle, but without getting a usable egg from the ovaries. This situation commonly occurs during periods of metabolic imbalance of type 1 diabetes. However, it may also happen under relatively reasonable control in type 2 diabetes associated with obesity and polycystic ovary syndrome.

Effects of diabetes on the placenta

A pregnant woman holds her belly with one hand and has baby shoes and her husband's hand in the other.

The adverse effects of maternal diabetes being present during pregnancy begin with a series of changes in the functioning or structure of the placenta. Vascular damage to the placenta can cause the flow of oxygen to the fetus to limit itself towards the end of pregnancy. The placenta of a pregnant woman with diabetes has more insulin receptors than usual. They will bind more insulin and facilitate the transfer of nutrients to the fetus. Consequently, the fetus will gain weight faster, often reaching over 4Kg at birth (macrosome).

The placenta secretes a series of hormones that contribute to a state of resistance to the action of insulin. This newly acquired insulin resistance can make the mother unable to consume its blood glucose.

Diabetes and pregnancy loss

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With a careful preparation for pregnancy by ensuring good metabolic control, the rate of pregnancy loss is similar to that of the general population without diabetes (15%). Good metabolic control means persistent HbA1c <7% (53 mmol/mol). If HbA1c is >7.5% (58 mmol/mol), the risk of pregnancy loss triples. In this case, the most common reason for pregnancy loss is the appearance of congenital malformations incompatible with survival. If the metabolic control is weak, it is better to postpone the pregnancy.

Pregnancy loss is more common in obese and older patients. This segment of women that is currently growing the most. If necessary, it also helps to lose weight along with improving metabolic control. This recommendation is especially true in type 2 diabetes. The risk of miscarriage is most significant in the first trimester and then gradually decreases as the birth deadline approaches. In conclusion, a good pregnancy preparation is essential for women with diabetes who want to have a baby.

Diabetes and birth defects

Colored chromosomes around two cells

Congenital malformations occur twice as often in pregnancies where a woman has diabetes. They can occur in up to 4% of these pregnancies. In specialized centres, where the care of the woman throughout the pregnancy is optimal, congenital malformations are the leading cause of illness or perinatal death.

The most common congenital malformations increased by diabetes are those of the heart and central nervous system. They are three times more common in the presence of diabetes. The lack of bone formation in the buttocks (sacral agenesia), although rare, is worst affected by the presence of diabetes. Diabetes increases its frequency of occurrence 200 times.

Metabolic control reduces the risk of malformations

An excellent metabolic control greatly diminishes the adverse effects of diabetes on pregnancy. There is a close relationship between the mother’s metabolic control during pregnancy and the risk of congenital disabilities in the baby.

The most important parameter monitored is glycosylated hemoglobin (HbA1c). It shows us the average blood sugar in the last two months (three months outside pregnancy). However, up to 25% of all genetic malformations still occur despite an optimal HbA1c during the first trimester of pregnancy. Optimal HbA1c values are below 7% (53 mmol/mol), but ideally <6.5% (48 mmol/mol).

This persistent risk of malformations means that it would be best if you carefully assessed blood glucose variability, even for low HbA1c levels. This assessment consists of glucose self-monitoring, ideally using a continuous blood glucose monitoring sensor.

Women with diabetes should seek care during pregnancy in qualified centres. Here, expert doctors will evaluate the glycemic rises after the meals and the possible presence of hypoglycemias. Intensified treatment of diabetes reduces the risk of congenital disabilities.

Diabetes and the fetal pancreatic development

A baby with blue eyes and a toy in his mouth

Insulin first appears in the fetal pancreas at seven weeks. At the end of the first trimester of pregnancy, the areas of the pancreas responsible for insulin secretion, also called the Langerhans Islands, are fully functional. If the blood sugar level in the mother’s blood is higher than typical, the excess sugar that reaches the fetus will lead to the activation of these areas of the pancreas. They will produce more insulin than usual.

This early “scheduling” of increased insulin secretion continues throughout pregnancy. An excellent metabolic control obtained at the end of the pregnancy, after an initial precarious period, will not lead to a decrease in insulin secretion from the child’s pancreas.

The reason is that it remains programmed in high secretion status, as previously learned. Insulin is an anabolic hormone, meaning that it helps the body grow faster. Consequently, there is an accelerated growth at the end of pregnancy, with adverse perinatal consequences.

The effects of diabetes on fetal growth

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In general, newborns of mothers with diabetes have a higher birth weight than those of mothers without diabetes. A higher than average birth weight is associated with trauma or even asphyxia during birth. Consequently, the risk for emergency cesarean section increases significantly. The child’s subsequent risk of developing obesity in childhood or as an adult also increases.

Insulin and other growth factors

Responsible for the accelerated fetal growth in the last trimester is the excess insulin in the child’s pancreas and the glucose and amino acids that come from the mother’s circulation. Some extra sugar from the mother’s blood will pass into the fetal circulation. Here, it stimulates local insulin secretion starting as early as week 13.

Fetal growth is also stimulated by insulin-like hormones called insulin growth factors 1 and 2 (IGF1 and IGF2). They are available in higher concentrations in pregnancies associated with diabetes.

Researchers managed to reduce the level of these growth factors in animals by various techniques. Consequently, the offsprings had a lower birth weight. This weight reduction at birth happened even if the babies came from mothers with experimentally induced diabetes.

Metabolic control and fetal growth

In the first trimester, glycosylated hemoglobin, which shows the average blood sugar in the last 2-3 months is an excellent predictor of excess weight at birth. If the mother does not have diabetes and still give birth to a child weighing >4000g (macrosome), she should know that this might highlight an increased risk for her of developing diabetes in the coming years. The presence of overweight accentuates this risk.

Diabetes and premature birth

A newborn seen from the top of his head on blue hospital sheets, on a blurred blue background.

Diabetes, regardless of its type, is associated with a five times higher risk of premature birth compared to the general population without diabetes. Premature birth means a delivery before 37 weeks, but after 24 weeks of pregnancy. The frequency of premature birth is similar in type 1 and type 2 diabetes. It is around 2.5% of all deliveries associated with diabetes.

Risk factors for premature birth in diabetes

Metabolic control throughout pregnancy significantly influences the risk of premature birth. This risk increases substantially as Hba1c rises above 7.5% (58 mmol/mol). Among the complications of diabetes, kidney damage (diabetic nephropathy) is a significant risk factor for premature birth.

In terms of lifestyle, the most harmful in this regard are smoking and obesity. Obesity most often accompanies type 2 diabetes and much less frequently type 1. The incidence of pregnancies with type 2 diabetes and obesity is unfortunately increasing alarmingly.

The excess glucose that comes from the mother, combined with the reflex secretion of insulin from the baby makes the baby’s tissues very metabolically active. The tissues consume an increased amount of oxygen to support this higher metabolic rate.

Sometimes the amount of oxygen that the placenta can provide is less than the demand from the baby. Under these conditions, hypoxia occurs, i.e. the lack of oxygen in the child’s blood. Also, the blood may become slightly more acidic than it should be, a condition called acidosis. Hypoxia and acidosis are responsible for a significant number of premature births in pregnancies associated with diabetes.

Glycosylated hemoglobin and premature birth

Hemoglobin transports the oxygen to the tissues. Blood glucose binds spontaneously to hemoglobin. So, a certain percentage of it will be loaded with glucose and is called glycosylated hemoglobin (HbA1c). Only about 6.5-7% of hemoglobin should be in the glycosylated state (loaded with glucose), while the rest non-glycosylated.

Glycosylated hemoglobin binds more closely the oxygen it carries to the tissues. Consequently, when it reaches its destination, glycosylated haemoglobin releases a lower amount of oxygen. Thus, it does not fulfil well its mission of oxygen transporter, and the tissues suffer.

Hypoglycemia of the newborn from a mother with diabetes

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During pregnancy, glucose passes from the maternal to the fetal circulation and stimulates the pancreatic beta cells to secrete as much insulin as possible. To cope with the ever-increasing need to produce as much insulin as possible, beta cells in the fetal pancreas begin to multiply. This cell multiplication is medically called hyperplasia.

Immediately after birth, the constant and massive flow of glucose from mother to child disappears. However, the insulin secretion in most pancreatic beta cells continues to stay at high levels. They trained daily for half a year to secrete as much insulin as possible. This insulin, which is excessively secreted by the newborn, prevents the liver from releasing the sugar it stores into the bloodstream.

The newborn has a lot of red blood cells (erythrocytes) in his blood. They rely on glucose to function. However, blood glucose is consumed quickly after birth, but not efficiently replaced by the liver. The reason is that there is too much insulin in circulation.

Decreased blood sugar after birth occurs in any newborn and is normal. When the blood sugar drops below 45 mg/dl (2.5 mmol/l), it is dangerous and is called neonatal hypoglycemia. Neonatal hypoglycemia occurs spontaneously in up to 50% of newborns from mothers with diabetes, in the absence of prevention.

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