Download Diabetes with Pregnancy

Diabetes with Pregnancy
Classifying Diabetes
Diabetes mellitus is generally classified into the following
categories: type 1 or insulin-dependent diabetes mellitus, type 2
or noninsulin-dependent diabetes mellitus, and gestational
diabetes mellitus (GDM). Approximately 10% of all individuals
with diabetes mellitus have type 1 diabetes. Beta cell
destruction, with resulting insulin deficiency, is the hallmark of
this disorder. Onset is generally before the age of 30 years, and
as a result, this type of diabetes is frequently encountered in
women of childbearing age. It is estimated that type 1 diabetes
complicates approximately 0.2% of all pregnancies in the
United States annually.
Type 2 diabetes is the most common form of the disease,
affecting nearly 90% of all individuals with diabetes. Type 2
diabetes is characterized by defects in both insulin action and
secretion. It typically is seen in individuals over the age of 40
years and therefore in the past was felt to be uncommon in
women of childbearing age. However, in recent years, the
incidence of type 2 diabetes has been increasing steadily among
younger individuals, and data from the National Maternal and
Infant Health Survey indicates that type 2 diabetes complicates
0.3% of all pregnancies in the United States. Gestational
diabetes mellitus is defined as carbohydrate intolerance of
variable severity with onset or first recognition during the index
pregnancy.
If the abnormality in glucose tolerance persists after pregnancy,
the patient's diagnosis is revised to type 1, type 2, or impaired
glucose tolerance (IGT).
Gestational Diabetes Mellitus
GDM is a common problem that complicates approximately 5%
of all pregnancies in the United States. The likelihood of
developing GDM is significantly increased among certain
subgroups, including individuals with a positive family history
of type 2 diabetes, advancing maternal age, obesity, and.
1
nonwhite ethnicity. Excess risks for both GDM and IGT have
been demonstrated in black, Hispanic, and Native American
women as well as in women from the Indian subcontinent and
the Middle East.
Screening and Diagnosis for Gestational Diabetes
Mellitus
Screening should be performed between 24 and 28 weeks
gestation, although women with significant risk factors may
benefit from being screened earlier in pregnancy. A 50-g
glucose challenge test is performed without regard to the time of
day or interval since the last meal. Venous plasma glucose is
measured 1 hour later, with a value of ≥140 mg/dL indicating
the need for a 3-hour 100-g oral glucose tolerance test (OGTT).
The OGTT is performed after an overnight fast and 3 days of an
unrestricted carbohydrate diet. A fasting blood glucose level is
drawn, and a 100-g glucose load is then administered. Plasma
glucose levels are drawn 1, 2, and 3 hours following ingestion of
the glucose solution. Diagnosis requires that at least two of the
four glucose levels of the OGTT meet or exceed the upper limits
of normal.
The evaluation of glucose intolerance during pregnancy may
be made by using a one-step approach or 2-hour 75-g OGTT.
This approach is considered most applicable in high-risk
populations.
Women with GDM should be evaluated at the first postpartum
visit by a 2-hour OGTT using a 75-g load. Greater than 90% of
women will convert to normal glucose tolerance following
delivery. However, studies indicate that the risk for overt
diabetes may be as high as 20% to 50% in this population.
Long-term annual follow-up is therefore indicated. GDM is
influenced greatly by body weight, with the highest rate
occurring in obese patients.
2
Maternal Complications
Despite improvements in pregnancy outcomes, women with
both GDM and pre-GDM are at greater risk for a number of
pregnancy-related as shown in the table.
TABLE 15.1 Pregnancy Complications in Diabetes
Maternal
Preterm labor
Infectious morbidities
Hydramnios
Hypertensive disorders
Worsening of diabetic retinopathy
Fetal/Neonatal
Stillbirth
Congenital malformations
Altered fetal growth
Metabolic abnormalities
Hypoglycemia
Hypocalcemia
Polycythemia
Hyperbilirubinemia
Cardiomyopathy
RDS
Long Term
Childhood obesity
Neuropsychologic defects
Diabetes
RDS, respiratory distress syndrome.
Current data would seem to indicate that pregnancy is an
independent risk factor for diabetic retinopathy. Therefore all
women with type 1 diabetes for 5 years or more or type 2
diabetes at diagnosis require a thorough dilated ophthalmologic
evaluation.
However, diabetic nephropathy is the complication of diabetes
that is most likely to affect pregnancy outcomes. There are
increased risks for pregnancy-induced hypertension and/or a
3
progression of already existing hypertension, intrauterine
growth retardation resulting in small-for-gestational-age infants,
preterm deliveries secondary to fetal distress, and a 10-fold
increase in the incidence of stillbirth over women with diabetes
but without nephropathy. Preeclampsia is the most frequent,
serious complication of maternal nephropathy, with implications
for both mother and fetus.
Neonatal Complications
The offspring of women with diabetes remain at increased risk
for a number of complications, which includes congenital
anomalies, fetal macrosomia, respiratory distress syndrome
(RDS), and metabolic abnormalities as well as long-term
sequelae.
Perinatal Mortality
The two major causes of perinatal mortality are unexplained
fetal death and congenital malformations. The causes of
unexpected death are not well understood. In animal models,
sustained hyperglycemia has been associated with increased
insulin secretion, elevated fetal oxygen consumption, acidosis,
and death. It has been postulated that fetal polycythemia and
increased platelet aggregation could explain the increased
incidence of intravascular thrombosis in infants of diabetic
mothers and that thrombotic episodes could be the underlying
cause for late unexplained intrauterine deaths.
Approximately 40% of perinatal deaths that occur among infants
of women with diabetes can be attributed to malformations.
Diabetes mellitus is one of the most common maternal
conditions that results in anomalous offspring. The frequency of
major congenital anomalies is increased two- to threefold over
the general population.
4
The most frequent types of malformations involve
1-the central nervous system 2-cardiovascular3-gastrointestinal,
4-genitourinary 5-and skeletal systems, with cardiac
malformations being the most common.
The defects most often associated with diabetes occur during
organogenesis before 7 weeks gestation. As a result, the
management goal for diabetic pregnancies has become the
establishment and maintenance of near euglycemia beginning
with the preconceptual period and continuing throughout
gestation.
Altered Fetal Growth
Macrosomia is a classic hallmark of the pregnancy complicated
by diabetes and is reported to occur in 20% to 25% of
pregnancies complicated by diabetes. Macrosomia is defined as
excessive birth weight (>90%) for gestational age or as a birth
weight >4000 g. Increased adiposity is the primary cause of the
increased birth weight seen in the offspring of diabetic women.
Numerous studies have established a relationship between the level
of maternal glucose control and macrosomia. Mothers of macrosomic
infants usually have significantly elevated plasma glucose levels
at term, indicating increased glucose availability to the fetus,
with hyperinsulinemia a likely intermediate step, during the
third trimester.
Other factors associated with an increased risk for fetal
macrosomia include 1-increased maternal weight, 2-increased
parity,3- previous delivery of a macrosomic infant,
4-and insulin requirements >80 U per day.
Macrosomic fetuses have higher perinatal and neonatal
mortality and morbidity rates. Approximately 10% of infants
weighing over 4,500 g at birth will require admission to a
neonatal intensive care nursery. In addition, the reported
perinatal mortality is two to five times higher in this group of
children than in average-sized children. Delivery of a
5
macrosomic infant is dangerous because of the risk for birth
trauma to the head and neck. Fetal asphyxia and meconium
aspiration may occur as a result of prolonged labor secondary to
unrecognized cephalopelvic disproportion and shoulder
dystocia.
At the other extreme, women with type 1 diabetes also are at
increased risk for delivering a small-for-gestational-age infant.
In general, the risk of growth retardation increases with the
severity of the mother's clinical diabetes. Vascular
complications, such as retinopathy and nephropathy, are
believed to be associated with uteroplacental insufficiency in
pregnant women with diabetes. Poor maternal renal function,
hypertension, and placental lesions have all been associated with
intrauterine growth retardation in the offspring of diabetic
mothers. However, more recent evidence suggests that the
growth retardation may be related to disturbances in maternal
fuels during organogenesis.
Metabolic Abnormalities
Hypoglycemia occurs when plasma glucose levels fall below 35
mg/dL in the term infant and 25 mg/dL in the preterm infant.
The incidence of hypocalcemia also is significantly increased in
the infants of women with diabetes. Hypocalcemia generally
occurs in association with hyperphosphatemia and occasionally
with hypomagnesemia. Neonatal hypocalcemia is defined as a
calcium level at or below 7 mg/dL. Serum calcium levels
usually are lowest on the second or third day of life.
Polycythemia is defined as a venous hematocrit that exceeds
65% and is reported to occur in one third of neonates born to
diabetic women. Polycythemia is believed to occur as a result of
chronic intrauterine hypoxia, which leads to an increase in
erythropoietin and consequently results in an increase in red cell
production. Neonates born to women with diabetes also have a
higher incidence of hyperbilirubinemia as compared with
6
nondiabetic controls. Neonatal hyperbilirubinemia develops in
approximately 20% to 25% of cases.
Other Infant Morbidities
Offspring born to women with diabetes mellitus also are at
increased risk of developing various hypertrophic types of
cardiomyopathies and congestive heart failure.
RDS is another common complication associated with
diabetes.
Preconception Care
Care of women with type 1 or type 2 diabetes ideally begins
before conception. Although numerous clinical trials have
demonstrated that strict glycemic control prior to and during
early gestation can reduce the rate of structural defects, the vast
majority of women with diabetes still seek medical care only
after they learn they are pregnant. Consequently, the rate of
congenital malformations in infants of mothers with diabetes has
continued to remain significantly higher than that of the general
population.
Diabetes Management
The main goal of management for pregnancies complicated by
either gestational diabetes or pre-GDM is to achieve and/or
maintain euglycemia throughout gestation. The treatment
approach requires a combination of diet, exercise, intensive
insulin regimens, oral medications, and daily multiple blood
glucose determinations.
Diet
Diet therapy is the cornerstone of diabetes management in
pregnancy, just as it is in the nonpregnant state.. Most experts
advocate an additional intake of 300 to 400 kcal per day to meet
the needs of pregnancy. Recommendations regarding total
7
caloric intake often are based on the mother's pregravid
weight—30 kcal/kg of body weight per day for normal weight
women with diabetes, 40 kcal/kg per day for underweight
women, and 24 kcal/kg per day for overweight women.
Exercise
Although exercise has been demonstrated to be beneficial in
nopregnant individuals, evidence regarding the risk and/or
benefits of either periodic or regular exercise in pregnant
women with diabetes is limited.
Pharmacologic Therapy
The goal of insulin therapy is to achieve blood glucose levels
that are nearly identical to those observed in healthy pregnant
women. Therefore, multiple injections of insulin usually are
required in women with preexisting diabetes. Human insulin is
the least immunogenic of all insulins and is exclusively
recommended in pregnancy. Insulin requirements may change
dramatically throughout the various stages of gestation. In the
first trimester, the maternal insulin requirement is approximately
0.7 U/kg of body weight per day. This is increased in the third
trimester to 1.0 U/kg per day.
Monitoring Metabolic Status
Self-Monitoring of Blood Glucose
Self-monitoring of blood glucose by has become the mainstay of
management for pregnancies complicated by diabetes mellitus.
Blood glucose measurements should be obtained at least 4 times
a day (fasting and 1 to 2 hours after meals) in women with
GDM and 5 to 7 times a day in women with preexisting
diabetes. In addition to this regular monitoring, patients also
8
should test whenever they feel symptoms of either
hyperglycemia or hypoglycemia. Detailed record keeping is
useful to help identify glucose patterns. Daily urine ketone
testing should be performed to ensure early identification of the
development of starvation ketosis or ketoacidosis. Ketone
testing also should be performed any time the blood glucose
level exceeds 200 mg/dL, during illness, or when the patient is
unable to eat.
TABLE 15.3 Monitoring the Diabetic Pregnancy
Maternal Surveillance
Self blood glucose monitoring four to seven times daily
A1C
Urinary ketones
Blood pressure
Retinal and renal status (for women with preexisting diabetes)
Fetal Surveillance
Level II ultrasound and fetal echocardiogram (for women with
preexisting diabetes)
Serial assessment (4–6 wk) of fetal growth
Daily fetal movement counting
Weekly NST or BPP
NST, nonstress test; BPP, biophysical profile.
Blood glucose levels are measured in both the fasted and
postprandial states. Current recommendations are that whole
blood glucose levels should not exceed 95 mg/dL in the fasted
state and 120 mg/dL after meals.
Fetal Assessment
All pregnancies that are complicated by diabetes require
additional fetal evaluation and assessment, Ultrasonography
provides the clinician with essential information about the fetus
and its development. A first-trimester scan should be performed
to date the pregnancy and establish viability. Evaluation
9
includes a targeted ultrasound to survey general fetal anatomy
and fetal echocardiography at approximately 20 to 22 weeks
gestation. In addition, the maternal serum alpha-fetoprotein
screening test should be performed between 16 and 18 weeks
gestation because of the increased risk of neural tube defects.
Since women with diabetes are at risk for fetal growth
aberrations, frequent ultrasound scans are recommended to
identify states of altered growth. Ultrasound examinations
should be performed at 4- to 6-week intervals during the second
and third trimesters of pregnancy to assess not only fetal growth
but amniotic fluid volume as well.
Fetal death is more common in pregnancies complicated by
diabetes than in the general population. The goal of antepartum
surveillance is avoidance of intrauterine death by early detection
of fetal compromise. The nonstress test (NST) has become the
preferred antepartum fetal heart rate test for screening the fetal
condition in pregnancies complicated by diabetes. The NST
evaluates the presence of accelerations from the baseline fetal
heart rate. An alternative fetal test is the fetal biophysical profile
(BPP), which also is utilized to evaluate the significance of a
nonreactive NST. Because the BPP employs ultrasound, it
permits evaluation of amniotic fluid volume and may detect
major fetal malformations in patients who have not been studied
earlier in pregnancy. Maternal evaluation of fetal movement
counts also should be integrated into the surveillance program.
Women with diabetes are instructed to count fetal movements
beginning as early as 28 weeks gestation. Although the falsepositive rate is high, the technique is inexpensive and simple
and augments the total antepartum surveillance program.
Most perinatal centers institute a program of weekly fetal
monitoring beginning at 32 to 34 weeks gestation. Since fetal
death is more common in women with poor glycemic control,
hydramnios, fetal macrosomia, hypertension, or vasculopathy,
these women receive twice weekly NST testing. Patients with
diet-controlled GDM who maintain normal fasting and
postprandial glucose levels are probably at low risk for an
intrauterine death and are not tested as early or frequently.
10
However, women with GDM and chronic hypertension, a
previous history of stillbirth, and preeclampsia and those who
require insulin therapy receive more intense surveillance.
Timing and Mode of Delivery
It is generally accepted that if a pregnant diabetic patient is in
good metabolic control and is receiving fetal surveillance on a
regular basis, delivery may be safely delayed until term or the
onset of spontaneous labor. Women with poor metabolic
control, worsening hypertensive disorders, fetal macrosomia,
growth retardation, or polyhydramnios may be electively
delivered after fetal lung maturity has been confirmed. If an
elective delivery is planned before 38 weeks gestation,
amniocentesis should be performed for confirmation of fetal
lung maturity. Fetal lung maturation is better predicted by the
amniotic fluid phosphatidylglycerol content than by the
lecithin:sphingomyelin ratio.
Cesarean section should be performed on most diabetic patients
with an estimated fetal weight of greater than 4,500 g to prevent
shoulder dystocia and birth trauma. Management should be
individualized for patients with an estimated fetal weight
between 4,000 and 4,500 g. The decision is based on the size of
the pelvis and progress of labor as well as the patient's obstetric
history. A history of shoulder dystocia often is an indication for
repeat cesarean section.
During labor and delivery, good blood glucose control should be
maintained to prevent neonatal hypoglycemia. Blood glucose
levels should be maintained at a level below 100 mg/dL with the
use of an insulin infusion. After delivery, insulin requirements
tend to dramatically fall as a result of the significant decrease in
level of placental hormones. Once the patient is able to eat
regular meals, she should receive subcutaneous insulin at
approximately one half of her prepregnancy dose.
Conclusion
The diagnosis of diabetes mellitus during pregnancy has certain
implications for the well-being of both the mother and the fetus.
11
Advances in medical and obstetric care have dramatically
improved the outlook for women with diabetes and their
offspring. However, both mother and child remain at increased
risk for a number of complications. Research indicates that the
majority of these complications are associated with
hyperglycemia. The achievement and maintenance of euglyemia
has therefore become the major focus of management.
Dr. Naser Malas.
12