INTRODUCTION — Prior to the development of insulin in 1922, pregnancy in women with diabetes mellitus posed very high risks to both mother and fetus. Today, most women with diabetes can expect an excellent pregnancy outcome, similar to that of nondiabetic women. This improvement is largely due to better blood glucose control, which can be achieved with frequent daily glucose monitoring and insulin adjustment.
This topic review discusses care of women with type 1 or 2 diabetes during pregnancy, as well as fetal and newborn issues. It does not address gestational diabetes, which develops during pregnancy.
BLOOD GLUCOSE MANAGEMENT — High blood glucose levels early in pregnancy (especially a A1C above 8 percent or average blood glucose above 180 mg/dL (10 mmol/L)) increases the risk of miscarriage (show table 1). A1C is a blood test that measures the average blood glucose level. High blood glucose levels (eg, average blood glucose level of 180 mg/dL (10 mmol/L) or higher) in the last half of pregnancy and near delivery can cause the infant to be larger than normal (see "Ultrasound" below) and be at higher risk for complications after delivery (see "Newborn issues" below). Women with large infants are more likely to have a difficult vaginal birth or require delivery by cesarean section. Very high blood glucose levels (over 250 mg/dL (13.9 mmol/L)) late in pregnancy increases the risk of stillbirth. These complications occur less frequently when blood glucose levels are carefully controlled.
Glucose in the mother's blood crosses the placenta to help provide energy for the fetus; thus, maternal hyperglycemia (high blood glucose levels) leads to fetal hyperglycemia as well. In response to high glucose levels, the fetus produces large amounts of insulin, which lead to problems such as excessive fetal growth and low blood glucose levels after birth (see "Planning for delivery" below).
General measures Two to four insulin injections per day are recommended. Alternately, patients can use an insulin pump. For women with type 2 diabetes, insulin is not always required during pregnancy; when it is required, two injections per day will often provide acceptable blood gluose control. Women with diabetes need more insulin during pregnancy, especially during the last one-third of pregnancy (approximately 26 to 40 weeks of gestation) because the body becomes resistant to the actions of insulin as the pregnancy progresses. (See "Patient information: Diabetes type 1: Insulin treatment"). Frequent contact with health care providers is important for managing blood glucose levels and monitoring maternal and fetal health. The healthcare provider may want to review blood glucose levels and insulin doses one or more times per week; this can usually be done via telephone, e-mail, or fax. Oral hypoglycemic agents, specifically glyburide, have been used to manage gestational or type 2 diabetes in some women. These medications adequately control blood glucose levels, but large studies of their safety have not been performed. As a result, the American College of Obstetricians and Gynecologists and American Diabetes Association do not recommended their use during pregnancy at this time. Women who are taking these drugs when they become pregnant should speak with their healthcare provider. A nutritionist can help to plan a diet that provides the optimal number of calories, carbohydrate content, and distribution of snacks/meals throughout the day. The optimal calorie intake depends upon the woman's prepregnancy weight and activity level. Exercise is an excellent way to control weight and blood glucose levels. Most women who exercised before pregnancy can continue to do so during pregnancy at the same or a slightly reduced pace. Moderate intensity exercise, such as brisk walking, is recommended. Women who did not exercise previously may begin to exercise during pregnancy after consulting with their healthcare provider. Exercise intensity, type, and duration may need to be modified as the pregnancy progresses or if complications develop.
Target blood glucose levels — Frequent glucose monitoring is recommended during pregnancy, including testing before breakfast (while fasting) and before and after each meal. (See "Patient information: Self-blood glucose monitoring"). Target blood glucose levels during pregnancy are slightly lower than for persons with diabetes who are not pregnant. Goals are as follows: Fasting: 60 to 90 mg/dL (3.3 to 5 mmol/L) Preprandial (before meals): less than 100 mg/dL (5.5 mmol/L) One-hour postprandial (after meals): less than 130 to 140 mg/dL (7.2 to 7.7 mmol/L) Two-hour postprandial: less than 120 mg/dL (6.7 mmol/L)
A1C is usually done every four to six weeks. A1C at or near 6 percent (which corresponds to an average blood glucose of 120 mg/dL (6.7 mmol/L)) is recommended during pregnancy (show table 1). However, attempting to maintain this level can result in frequent episodes of hypoglycemia (low blood glucose), so A1C goals should be determined individually. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").
CARE DURING PREGNANCY — The care of diabetic women during pregnancy is a team effort involving an obstetrician and an endocrinologist or internist who oversees insulin management and medical care. Ideally, care should begin before a woman becomes pregnant so that medications can be adjusted if needed, folic acid supplementation can be started (at least 400 mcg per day is recommended, starting before conception) and other genetic issues may be fully addressed (show table 2). A summary of the testing recommended during pregnancy is shown in the table (show table 3).
Eye examination — Retinopathy causes abnormal, leaky blood vessels in the retina, the light sensitive tissue lining the back of the eye. Retinopathy can lead to vision problems, and even blindness in severe cases. Pregnancy can worsen diabetic retinopathy due to rapidly lowered blood glucose levels; which may occur when a person begins more frequent blood glucose monitoring and control measures. Changes in hormones, blood pressure, and blood flow in the retinal artery can also worsen retinopathy.
Thus, pregnant women with type 1 or 2 diabetes should have an eye examination by an ophthalmologist or optometrist during the first trimester (three months) of their pregnancy. Subsequent eye examinations during the pregnancy may be needed, depending upon the results of the initial examination. In most cases, eye examination is recommended every three months until delivery.
The impact of pregnancy on diabetic retinopathy is mild and temporary for most women; the retina usually returns to its prepregnancy condition within several months postpartum. Patients with severe retinopathy are more likely to experience progression and complications. Eye examinations before and during pregnancy, along with close monitoring and treatment (as needed) of retinopathy can minimize the risk of vision loss. Some experts have recommended cesarean delivery for women with retinopathy, although this is controversial; most women can attempt a vaginal delivery.
Blood pressure monitoring — Blood pressure may become elevated during pregnancy and should be measured frequently during visits with a diabetes specialist or obstetrician.
Gestational hypertension (high blood pressure during pregnancy) and preeclampsia are more common in women with diabetes. Blood pressure often improves in the first half of pregnancy, but returns to baseline or worsens in the second half. Medications to treat high blood pressure during pregnancy include methyldopa, calcium channel blocking agents, hydralazine, or beta blockers. However, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are not safe during pregnancy.
Preeclampsia is a condition that can occur in pregnancy that causes hypertension (blood pressure greater than 140/90) and proteinuria (protein in the urine). Fortunately, most cases are mild. In severe cases (eclampsia), seizure, stroke, heart failure, kidney damage, and rarely, maternal death can occur. Preeclampsia cannot be prevented; the only treatment is delivery of the baby. Women with moderately elevated blood pressure monitored for days or even weeks if preeclampsia develops prematurely; this may require hospitalization. Corticosteroids may be given to encourage the fetus's lungs to mature more rapidly. Steroids can significantly raise the mother's blood glucose levels, which requires a temporary increase in the insulin dose. (See "Patient information: Preeclampsia").
Kidney function monitoring — Pregnancy does not cause diabetes-related kidney disease (nephropathy), but it can worsen existing disease. Kidney function is monitored during pregnancy by urine dipstick testing for protein, which is usually performed at every visit. Other urine or blood tests may be ordered depending upon the individual's situation.
Nephropathy can cause other pregnancy complications, such as preeclampsia, preterm delivery, babies who are small for their age (intrauterine growth restriction (IUGR)), and a higher frequency of maternal hospitalization and cesarean delivery (show table 4). Women with retinopathy and kidney disease are at increased risk of having a small infant because blood flow to the placenta may be reduced.
If a woman develops worsening nephropathy during pregnancy, it is usually temporary and reverts to the prepregnancy condition within several months of delivery. Worsening nephropathy probably occurs because blood flow through the kidney increases by 50 percent during pregnancy, which increases the kidneys' workload. In addition, some women develop worsening hypertension or new pregnancy-induced hypertension, which further stresses the kidney.
Permanent kidney damage, including kidney failure, can occur, and is more common among women who have poorly controlled blood pressure or a serum creatinine (a blood test of kidney function) of 1.5 mg/dL or greater at the beginning of pregnancy. These women may require dialysis or kidney transplant sooner than a woman with severe chronic kidney disease who never becomes pregnant. (See "Patient information: Renal replacement therapy" and see "Patient information: Hemodialysis").
Ultrasound — Ultrasound examination of the fetus is recommended during the first trimester (before 13 weeks) if there is any uncertainty about the last menstrual period date or estimated due date. It is important that the due date is accurate because decisions about when to begin fetal testing and when to deliver the baby are based upon this date.
Ultrasound examination is recommended at 18 to 20 weeks gestation to screen for birth defects, and some experts recommend a fetal echocardiogram (an ultrasound of the fetus's heart) because of the increased incidence of heart defects among infants of diabetic mothers.
Ultrasound is also used to monitor the amount of amniotic fluid around the fetus; polyhydramnios is an abnormal increase in the amount of amniotic fluid. This condition is more common in women with diabetes than in women without diabetes. Polyhydramnios related to diabetes is usually mild and does not cause problems. If it becomes severe, maternal discomfort, uterine contractions, premature rupture of the membranes ("breaking the water"), and preterm delivery can occur. (See "Patient information: Preterm labor").
Ultrasound is also used to monitor the fetus's growth and development throughout the pregnancy. Macrosomia is a condition in which an infant weighs more than nine pounds or 4000 grams at term (at or beyond 37 weeks of pregnancy), and is more common in women with diabetes. High fetal insulin levels, which can develop in response to elevated maternal blood glucose levels, contribute to an infant's weight since insulin stimulates fetal growth.
Macrosomia occurs in 15 to 45 percent of diabetic pregnancies, compared to 10 percent in the nondiabetic population. Macrosomic infants are at higher risk of being injured during delivery and are more likely to require cesarean delivery because the infant's shoulders may be difficult to deliver through a woman's pelvis (called shoulder dystocia). Shoulder dystocia occurs in 1 out of 4 macrosomic births in women with diabetes (show table 5).
Screening for birth defects — Birth defects are more common in women with elevated blood glucose levels before and during the early weeks of pregnancy. There is no particular birth defect caused by maternal diabetes, though most occur by the seventh week of pregnancy. In older studies, the frequency of birth defects was approximately 8 to 13 percent among diabetic women, compared to 2 to 4 percent in the nondiabetic population. However, more recent studies have demonstrated that tight blood glucose control prior to becoming pregnant greatly reduces the risk of birth defects to a level similar to women who do not have diabetes.
First or second trimester screening for birth defects such as spina bifida and Down syndrome is recommended (to all women, not just those with diabetes). Women with diabetes are not at increased risk for having a baby with a chromosomal abnormality, such as Down's syndrome, but they are at increased risk of having a baby with a neural tube defect (eg, spina bifda). These tests are used for screening (as opposed to diagnosis), and cannot determine with certainty if a baby has these problems. If the test is abnormal, an ultrasound examination and/or amniocentesis may be performed to determine if the abnormality is actually present. (See "Patient information: First trimester and integrated screening for Down syndrome" and see "Patient information: Second trimester screening for Down syndrome" and see "Patient information: Amniocentesis").
Fetal testing — Close monitoring of the fetus is recommended in the third trimester, including weekly to twice-weekly nonstress testing. This is done by monitoring the baby's heart rate with a small device that is placed on the mother's abdomen. The device uses sound waves (ultrasound) to measure the baby's heart rate over time, usually for 20 to 30 minutes. Normally, the baby's baseline heart rate should be between 110 and 160 beats per minute and should increase above its baseline by at least 15 beats per minute for 15 seconds when the baby moves.
The test is considered reassuring (called "reactive") if two or more fetal heart rate increases are seen within a 20 minute period. Further testing may be needed if these increases are not observed after monitoring for 40 minutes.
PLANNING FOR DELIVERY — A woman and her obstetrician may decide to schedule the date of her delivery (either an induction of labor or Cesarean section), especially if there are risk factors, such as poor blood glucose levels, nephropathy, worsening retinopathy, hypertension or preeclampsia, or limited or excessive fetal growth. If delivery before the due date is planned, an amniocentesis to determine fetal lung maturity may be needed, depending on the individual's situation and the fetus's gestational age. (See "Patient information: Amniocentesis").
If the fetus appears to be very large (based upon ultrasound measurements), a woman and her obstetrician should consider cesarean delivery to avoid possible trauma from shoulder dystocia. The American College of Obstetricians and Gynecologists recommends that a woman and her physician consider a planned Cesarean delivery if the estimated fetal weight (by ultrasound measurement) is greater than 4500 grams (9 lbs, 14 oz).
Waiting for labor to start on its own is reasonable if blood glucose levels are well-controlled and the mother and fetus are without problems. However, extending pregnancy beyond 40 to 41 weeks of gestation is generally not recommended; some practitioners routinely induce labor between 39 and 40 weeks in all women with type 1 or 2 diabetes.
The risk of stillbirth for pregnant women with carefully controlled diabetes is about the same as women without diabetes: less than 1 percent. The newborn mortality (death) rate in infants of diabetic women is slightly higher than in nondiabetics (2 versus 1 percent). This is due to a higher rate of serious birth defects, premature births, and breathing problems (respiratory distress syndrome) in infants of diabetic mothers.
INFANT CARE
Newborn issues — The infant of the diabetic mother is at risk for several problems in the newborn period, such as low blood glucose levels (less than 30 mg/dL (1.7 mmol/L)), jaundice, breathing problems, too many red blood cells (polycythemia), low calcium level, and heart problems. These problems are more common when the mother's blood glucose levels have been elevated during the pregnancy. Most of these problems resolve within a few hours or days of delivery. Infants of diabetic mothers are often evaluated in a special care nursery to monitor for these potential problems.
Infants of mothers with diabetes are at higher risk of breathing difficulties, especially if the infant is born earlier than 39 weeks of gestation. This is due to a delay in lung maturation, which appears to be more common in infants of women with diabetes. The risk of respiratory problems is highest when maternal blood glucose levels have been elevated near the time of delivery.
Inheritance of diabetes — The children of diabetic parents have a higher risk for developing the same type of diabetes. In one study, the risk of type 1 diabetes in the child was 1.3 percent (if the mother was diabetic) or 6.1 percent (if the father was diabetic). The risk of type 2 diabetes in children is 10 to 15 times higher (than children of nondiabetic parents) if one parent has type 2 diabetes. (See "Patient information: Diabetes mellitus, type 1" and see "Patient information: Diabetes mellitus, type 2").
AFTER DELIVERY CARE — Postpartum (after delivery) care for a woman with diabetes is similar to that for women without diabetes. However, it is important to pay close attention to blood glucose levels because insulin requirements are highly variable in the immediate postpartum period; some women require little or no insulin. Insulin requirements usually return to near-prepregnancy levels within 48 hours.
Breastfeeding — Breastfeeding is strongly encouraged, and benefits both the infant and the mother. Insulin requirements may be lower while breastfeeding, and frequent blood glucose monitoring is important to prevent severe hypoglycemia. Approximately 400 additional calories are required each day while breastfeeding. Breastfeeding for longer than three months can aid in maternal weight loss and provides significant short and long-term benefits to the infant.
Adequate amounts of human milk meet all the nutritional requirements of an infant during the first six months of life. Exclusive breastfeeding (without formula supplementation) is recommended for the first six months after birth, and partial breastfeeding is recommended for at least 12 months, and thereafter for as long as mutually desired. The World Health Organization recommends that partial breastfeeding continue for up to two years, and beyond.
SUMMARY Most women with diabetes can expect an excellent pregnancy outcome as a result of improvements in blood glucose control; this requires frequent daily glucose testing and insulin adjustment. Women with diabetes who have elevated blood glucose levels before or during pregnancy are more likely to have complications, including miscarriage, stillbirth, a large baby that requires cesarean delivery, or worsening of existing kidney function or retinopathy. Frequent visits with a healthcare provider are recommended to monitor blood glucose levels and blood pressure, eye and kidney health, and also to monitor the health of the developing baby. Target blood glucose levels during pregnancy are as follows: A!C level: less than 6 (show table 1), fasting blood glucose: 60 to 90 mg/dL (3.3 to 5 mmol/L), before meals: less than 100 mg/dL (5.5 mmol/L), one hour after meals: less than 130 to 140 mg/dL (7.2 to 7.7 mmol/L), two-hours after meals: less than 120 mg/dL (6.7 mmol/L). A woman and her obstetrician may decide to schedule the date of her delivery (either an induction of labor or Cesarean section), especially if there are risk factors, such as poor blood glucose levels, nephropathy, worsening retinopathy, hypertension or preeclampsia, or limited or excessive fetal growth. Waiting for labor to start on its own is reasonable if blood glucose levels are well-controlled and the mother and fetus are without problems. However, extending pregnancy beyond 40 to 41 weeks of gestation is generally not recommended If the fetus appears to be very large (based upon ultrasound measurements), a woman and her obstetrician should consider cesarean delivery to avoid possible trauma from shoulder dystocia. The infant of the diabetic mother is at risk for several problems in the newborn period, such as low blood glucose levels (less than 30 mg/dL [1.7 mmol/L]), jaundice, too many red blood cells (polycythemia), low calcium level, and heart problems. These problems are more common when the mother's blood glucose levels have been elevated during the pregnancy. Most of these problems resolve within a few hours or days of delivery. Infants of diabetic mothers are often evaluated in a special care nursery to monitor for these potential problems. Postpartum (after delivery) care for a woman with diabetes is similar to that for women without diabetes. However, insulin requirements are highly variable in the immediate postpartum period; some women require little or no insulin. Insulin requirements usually return to near-prepregnancy levels within 48 hours. Breastfeeding is strongly encouraged, and benefits both the infant and the mother. Insulin requirements may be lower while breastfeeding, and frequent blood glucose monitoring is important to prevent severe hypoglycemia. Approximately 400 additional calories are required each day while breastfeeding. Breastfeeding for longer than three months can aid in maternal weight loss and provides significant short and long-term benefits to the infant.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Diabetes and Digestive and Kidney Diseases
(www.niddk.nih.gov/)
American Diabetes Association (ADA)
(800)-DIABETES (800-342-2383)
(www.diabetes.org)
The Endocrine Society
(www.endo-society.org)
The Hormone Foundation
(www.hormone.org/public/diabetes.cfm, available in English and Spanish)
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2. Bernasko, J. Contemporary management of type 1 diabetes mellitus in pregnancy. Obstet Gynecol Surv 2004; 59:628.
3. Preconception care of women with diabetes. Diabetes Care 2004; 27 Suppl 1:S76.
4. Gabbe, SG, Graves, CR. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003; 102:857.
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