Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1 General references Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1)... read more ).
Gestational diabetes (diabetes that begins during pregnancy [ 2 General references Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1)... read more ]) can develop in overweight, hyperinsulinemic, insulin-resistant women or in thin, relatively insulin-deficient women. Gestational diabetes occurs in at least 5% of all pregnancies, but the rate may be much higher in certain groups (eg, Mexican Americans, American Indians, Asians, Indians, Pacific Islanders). Women with gestational diabetes are at increased risk of type 2 diabetes in the future.
Guidelines for managing diabetes mellitus during pregnancy are available from the American College of Obstetricians and Gynecologists (ACOG [ 1 General references Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1)... read more , 2 General references Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1)... read more ]).
Risks of diabetes during pregnancy
Diabetes during pregnancy increases fetal and maternal morbidity and mortality. Neonates are at risk of respiratory distress, hypoglycemia Neonatal Hypoglycemia Hypoglycemia is difficult to define in neonates but is generally considered a serum glucose concentration 40 mg/dL ( 2.2 mmol/L) in symptomatic term neonates, 45 mg/dL ( 2.5 mmol/L) in asymptomatic... read more , hypocalcemia Neonatal Hypocalcemia Hypocalcemia is a total serum calcium concentration 8 mg/dL ( 2 mmol/L) in term infants or 7 mg/dL ( 1.75 mmol/L) in preterm infants. It is also defined as an ionized calcium level 3.0 to 4... read more , hyperbilirubinemia Neonatal Hyperbilirubinemia Jaundice is a yellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration). The serum bilirubin level required to cause jaundice varies with... read more , polycythemia, and hyperviscosity.
Poor control of preexisting (pregestational) or gestational diabetes during organogenesis (up to about 10 weeks gestation) increases risk of the following:
Major congenital malformations
Poor control of diabetes later in pregnancy increases risk of the following:
Fetal macrosomia Large-for-Gestational-Age (LGA) Infant Infants whose weight is > the 90th percentile for gestational age are classified as large for gestational age. Macrosomia is birthweight > 4000 g in a term infant. The predominant cause is maternal... read more (usually defined as fetal weight > 4000 grams or > 4500 grams at birth)
However, gestational diabetes can result in fetal macrosomia even if blood glucose is kept nearly normal.
1. Committee on Practice Bulletins—Obstetrics: ACOG Practice Bulletin No. 201: Clinical management guidelines for obstetrician-gynecologists: Pregestational diabetes mellitus. Obstet Gynecol 132 (6):e228–e248, 2018. doi: 10.1097/AOG.0000000000002960
2. Committee on Practice Bulletins—Obstetrics: ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol 131 (2):e49–e64, 2018. doi: 10.1097/AOG.0000000000002501
Diagnosis of Diabetes Mellitus in Pregnancy
Oral glucose tolerance test (OGTT) or a single plasma glucose measurement (fasting or random)
Most experts recommend that all pregnant women be screened for gestational diabetes Laboratory testing . An OGTT is usually recommended, but the diagnosis can probably be made based on a fasting plasma glucose of > 126 mg/dL (> 6.9 mmol/L) or a random plasma glucose of > 200 mg/dL (> 11 mmol/L).
The recommended screening method has 2 steps. The first is a screening test with a 50-g oral glucose load and a single measurement of the glucose level at 1 hour. If the 1-hour glucose level is > 130 to 140 mg/dL (> 7.2 to 7.8 mmol/L), a second, confirmatory 3-hour test is done using a 100-g glucose load (see table Glucose Thresholds for Gestational Diabetes Using a 3-hour Oral Glucose Tolerance Test ).
Most organizations outside the US recommend a single-step, 2-hour test.
Treatment of Diabetes Mellitus in Pregnancy
Tight control of blood glucose
Management of complications
Preconception counseling and optimal control of diabetes before, during, and after pregnancy minimize maternal and fetal risks, including congenital malformations. Because malformations may develop before pregnancy is diagnosed, the need for constant, strict control of glucose levels is stressed to women who have diabetes and who are considering pregnancy (or who are not using contraception).
To minimize risks, clinicians should do all of the following:
Involve a diabetes team (eg, physicians, nurses, nutritionists, social workers) and a pediatrician
Promptly diagnose and treat complications of pregnancy, no matter how trivial
Plan for delivery and have an experienced pediatrician present
Ensure that neonatal intensive care is available
In regional perinatal centers, specialists in management of diabetic complications are available.
Treatment can vary, but some general management guidelines are useful (See tables Management of Type 1 Diabetes During Pregnancy Management of Type 1 Diabetes Mellitus* During Pregnancy , Management of Type 2 Diabetes During Pregnancy Management of Type 2 Diabetes Mellitus* During Pregnancy , and Management of Gestational Diabetes During Pregnancy Management of Gestational Diabetes During Pregnancy ).
Women with type 1 or 2 should monitor their blood glucose levels at home. During pregnancy, normal fasting blood glucose levels are about 76 mg/dL (4.2 mmol/L).
Goals of treatment are
Fasting blood glucose levels at < 95 mg/dL (< 5.3 mmol/L)
2-hour postprandial levels at ≤ 120 mg/dL (≤ 6.6 mmol/L)
No wide blood glucose fluctuations
Glycosylated hemoglobin (HbA1c) levels at < 6.5%
Insulin is the traditional drug of choice because it cannot cross the placenta and provides more predictable glucose control; it is used for types 1 and 2 diabetes and for some women with gestational diabetes. Human insulin is used if possible because it minimizes antibody formation. Insulin antibodies cross the placenta, but their effect on the fetus is unknown. In some women with long-standing type 1 diabetes, hypoglycemia does not trigger the normal release of counterregulatory hormones (catecholamines, glucagon, cortisol, and growth hormone); thus, too much insulin can trigger hypoglycemic coma without premonitory symptoms. All pregnant women with type 1 should have glucagon kits and be instructed (as should family members) in giving glucagon if severe hypoglycemia (indicated by unconsciousness, confusion, or blood glucose levels < 40 mg/dL [< 2.2 mmol/L]) occurs.
Pearls & Pitfalls
Oral hypoglycemic drugs (eg, glyburide) are being increasingly used to manage diabetes in pregnant women because of the ease of administration (pills compared to injections), low cost, and single daily dosing. Several studies have shown that glyburide is safe during pregnancy and that it provides control equivalent to that of insulin for women with gestational diabetes. For women with type 2 diabetes before pregnancy, data for use of oral drugs during pregnancy are scant; insulin is most often preferred. Oral hypoglycemics taken during pregnancy may be continued postpartum during breastfeeding, but the infant should be closely monitored for signs of hypoglycemia.
Management of complications
Although diabetic retinopathy, nephropathy, and mild neuropathy are not contraindications to pregnancy, they require preconception counseling and close management before and during pregnancy.
Retinopathy requires that an ophthalmologic examination be done every trimester. If proliferative retinopathy is noted at the first prenatal visit, photocoagulation should be used as soon as possible to prevent progressive deterioration.
Nephropathy, particularly in women with renal transplants, predisposes to pregnancy-induced hypertension. Risk of preterm delivery is higher if maternal renal function is impaired or if transplantation was recent. Prognosis is best if delivery occurs ≥ 2 years after transplantation.
Congenital malformations of major organs are predicted by elevated HbA1c levels at conception and during the first 8 weeks of pregnancy. If the level is ≥ 8.5% during the 1st trimester, risk of congenital malformations is significantly increased, and targeted ultrasonography and fetal echocardiography are done during the 2nd trimester to check for malformations ( 1 Treatment reference Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy ( 1)... read more ). If women with type 2 diabetes take oral hypoglycemic drugs during the 1st trimester, fetal risk of congenital malformations is unknown (see table Drugs With Adverse Effects During Pregnancy Some Drugs With Adverse Effects During Pregnancy ).
Labor and delivery
Certain precautions are required to ensure an optimal outcome.
Timing of delivery depends on fetal well-being. Women are told to count fetal movements during a 60-minute period daily (fetal kick count) and to report any sudden decreases to the obstetrician immediately. Antenatal testing Fetal Monitoring Labor consists of a series of rhythmic, involuntary or medically induced contractions of the uterus that result in effacement (thinning and shortening) and dilation of the uterine cervix. The... read more is begun at 32 weeks; it is done earlier if women have severe hypertension or a renal disorder or if fetal growth restriction is suspected. Amniocentesis to assess fetal lung maturity may be necessary for women with the following:
Obstetric complications in past pregnancies
Inadequate prenatal care
Uncertain delivery date
Poor glucose control
Poor adherence to therapy
Type of delivery is usually spontaneous vaginal delivery at term. Risk of stillbirth and shoulder dystocia increases near term. Thus, if labor does not begin spontaneously by 39 weeks, induction is often necessary; also, delivery may be induced between 37 to 39 weeks without amniocentesis if adherence to therapy is poor or if blood glucose is poorly controlled. Dysfunctional labor, fetopelvic disproportion, or risk of shoulder dystocia may make cesarean delivery necessary.
Blood glucose levels are best controlled during labor and delivery by a continuous low-dose insulin infusion. If induction is planned, women eat their usual diet the day before and take their usual insulin dose. On the morning of labor induction, breakfast and insulin are withheld, baseline fasting plasma glucose is measured, and an IV infusion of 5% dextrose in 0.45% saline solution is started at 125 mL/hour, using an infusion pump. Initial insulin infusion rate is determined by capillary glucose level. Insulin dose is determined as follows:
Initially: 0 units for a capillary level of < 80 mg/dL (< 4.4 mmol/L) or 0.5 units/hour for a level of 80 to 100 mg/dL (4.4 to 5.5 mmol/L)
Thereafter: Increased by 0.5 units/hour for each 40-mg/dL (2.2-mmol/L) increase in glucose level over 100 mg/dL up to 2.5 units/hour for levels > 220 mg/dL (> 12.2 mmol/L)
Every hour during labor: Measurement of glucose level at bedside and adjustment of dose to keep the level at 70 to 120 mg/dL (3.8 to 6.6 mmol/L)
If the glucose level is significantly elevated: Possibly additional bolus doses
For spontaneous labor, the procedure is the same, except that if intermediate-acting insulin was taken in the previous 12 hours, the insulin dose is decreased. For women who have fever, infection, or other complications and for obese women who have type 2 and have required > 100 units of insulin/day before pregnancy, the insulin dose is increased.
After delivery, loss of the placenta, which synthesizes large amounts of insulin antagonist hormones throughout pregnancy, decreases the insulin requirement immediately. Thus, women with gestational diabetes and many of those with type 2 require no insulin postpartum. For women with type 1, insulin requirements decrease dramatically but then gradually increase after about 72 hours.
During the first 6 weeks postpartum, the goal is tight glucose control. Glucose levels are checked before meals and at bedtime. Breastfeeding is not contraindicated but may result in neonatal hypoglycemia if oral hypoglycemics are taken. Women who have had gestational diabetes should have a 2-hour oral glucose tolerance test with 75 g of glucose at 6 to 12 weeks postpartum to determine whether diabetes has resolved.
1. Miller E, Hare JW, Cloherty JP, et al: Elevated maternal hemaglogin A1c in early pregnancy and major congenital anomalies in infants of diabetic mothers. N Engl J Med 304 (22):1331–1334, 1981. doi: 10.1056/NEJM198105283042204
Diabetes in pregnancy increases risk of fetal macrosomia, shoulder dystocia, preeclampsia, cesarean delivery, stillbirth, and, if preexisting or gestational diabetes is poorly controlled during organogenesis, major congenital malformations and spontaneous abortion.
Screen all pregnant women for gestational diabetes using an oral glucose tolerance test.
Involve a diabetes team if available, and aim to keep fasting blood glucose levels at < 95 mg/dL (< 5.3 mmol/L) and 2-hour postprandial levels at ≤ 120 mg/dL (≤ 6.6 mmol/L).
Begin antenatal testing at 32 weeks and deliver by 39 weeks.
Adjust insulin dose immediately after delivery of the placenta.
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