63 Commonly used antibiotics include penicillins, cephalosporins, and
nitrofurantoin. Antibiotic selection should be guided by antimicrobial susceptibility
testing. For coverage of the most common organism, E. coli, oral nitrofurantoin or
cephalexin is often used. E. coli resistance has been increasing to amoxicillin and
trimethoprim-sulfamethoxazole.
63,64 The antibiotic chosen should produce adequate
concentration in the urine, have a low resistance rate, and be safe to use during
pregnancy. A 7-day regimen of antibiotics should be used whenever possible.
recent WHO multicenter, randomized, noninferiority trial found a 7-day regimen with
nitrofurantoin was more effective than a 1-day regimen in treating pregnant women
with ASB, with bacteriologic cure rates of 86.2% and 75.7%, respectively.
Optimal antibiotics and duration of therapy have not been clearly identified and must
be individualized for each patient based on cultures and sensitivity results.
S.C., who likely has ASB, a 7-day course of nitrofurantoin is reasonable. At this
gestation age of 31 weeks, nitrofurantoin can still be used safely. There is a small
risk of hemolytic anemia in newborns when nitrofurantoin is used close to delivery.
Diabetes mellitus is the most common maternal medical complications during
pregnancy. Diabetes during pregnancy can be detected before or during pregnancy
and can be separated into two groups: (a) pregestational diabetes, which includes
women who have been diagnosed before pregnancy with either diabetes type 1 or
diabetes type 2, or (b) gestational diabetes mellitus (GDM), defined as carbohydrate
intolerance first detected during pregnancy.
More prevalent than pregestational diabetes, GDM accounts for more than 90% of
diabetes cases during pregnancy and affects approximately 6% to 7% of live births
It is estimated that 50% of women with GDM will go on to develop type
2 diabetes 22 to 28 years postpregnancy.
Pregestational diabetes accounts for the remaining 10% of cases. In the United
States, more than 8 million women have pregestational diabetes, affecting about 1%
71 Most women with pregestational diabetes have type 2
diabetes characterized by peripheral insulin resistance and relative insulin
69 The incidence of type 2 pregestational diabetes has been rapidly rising
in the past decade, most likely because of the increasing prevalence of obesity. In
contrast to type 2 diabetes, type 1 diabetes is characterized by complete insulin
deficiency resulting from autoimmune destruction of pancreatic β-cells.
0.5% of all pregnancies in the United States are complicated by type 1 diabetes.
Fluctuating glucose levels during the first trimester may be the first signs of
pregnancy for women with pregestational diabetes owing to increased insulin
resistance and reduced sensitivity to insulin action. Placental hormones (e.g., human
placental lactogen, progesterone, prolactin, placental growth hormone, and cortisol)
are thought to be responsible for the increase in insulin resistance during pregnancy.
The ACOG classifies diabetes in pregnancy according to the White classification,
modified to include gestational diabetes according to glycemic control. The White
classification relies on age at onset, duration of diabetes, and presence of vascular
complications for patient classification (Table 49-3).
QUESTION 1: K.H., a 27-year-old, 60-kg woman known to have type 1 diabetes since age 12, has married
glycosylated hemoglobin (Hgb A1c
) laboratory results are 134 mg/dL and 7.8%, respectively. Her BP is 145/94
the health of a child she would like to conceive?
Modified White Classification of Diabetes During Pregnancy
Class of Diabetes Age of Onset Duration
During pregnancy None Diet, exercise
During pregnancy None Diet, exercise plus
Class B Older than 20 years Less than 10 years None Insulin therapy
Class F At any age Any duration Nephropathy
Class H At any age Any duration Arteriosclerotic
Class R At any age Any duration Proliferative
Class T At any age Any duration Renal transplantation Insulin therapy
Perinatal mortality for infants of diabetic mothers has declined dramatically with
strict maternal metabolic control, improved fetal surveillance, and neonatal intensive
71 Fetal and neonatal mortality rates are approximately 2% to 4%, and the risk of
spontaneous abortion in patients with well-controlled type 1 diabetes is equal to that
72 The incidence of stillbirth is greatest after 36 weeks’
gestation in women with poor glycemic control, fetal macrosomia (see subsequent
discussion), maternal vascular disease, ketoacidosis, or preeclampsia.
The leading cause of perinatal mortality is major congenital anomalies that occur
in 9% to 14% of infants born to mothers with diabetes. The major malformations
observed include NTDs and other anomalies involving the cardiac, renal, and GI
systems, and rarely caudal regression syndrome.
66 Many congenital anomalies occur
during organogenesis, before the seventh week of gestation, when women are often
unaware that they are pregnant.
73 A direct correlation exists between higher Hgb A1c
levels and increased frequency of anomalies.
73 Women with elevated Hgb A1c values
during the time of conception have a significantly higher incidence of infants with
abomalies compared with women with Hgb A1c closer to the normal range of 4.0%
74 The risk of fetal anomalies increases dramatically to approximately 20%
associated with the same risk of anomalies as infants exposed to known teratogens
such as thalidomide, isotretinoin, or alcohol during organogenesis.
Macrosomia, defined as birth weight greater than 4 kg, is thought to be caused in
part by fetal hyperglycemia and hyperinsulinemia.
65 Fetal hyperglycemia occurs when
glucose crosses the placenta and subsequently stimulates fetal pancreatic β-cells to
release excessive insulin. Hyperinsulinemia promotes excessive fetal growth in
adipose tissue, causing disproportional fat concentration around the shoulders and
chest and doubling the risks of trauma (e.g., shoulder dystocia) during vaginal
Infants of diabetic mothers also are at increased risk for prolonged hypoglycemia
after delivery, respiratory distress syndrome (RDS), hypocalcemia, polycythemia,
and hyperbilirubinemia during the neonatal period.
K.H. should be informed that stringent preconception glycemic control is essential
for preventing early pregnancy loss and congenital malformations in the infant.
Tight glucose control, especially in the months before pregnancy and early in the first
trimester, will maximize her chance of having a healthy baby. She should be educated
before pregnancy about healthy practices she can institute now to improve a
CASE 49-2, QUESTION 2: K.H. wants to know what health risks she might incur from becoming pregnant
and what measures could minimize these risks?
A prepregnancy assessment, including a history and physical examination, is
necessary to determine the risks of or contraindications to pregnancy for K.H. She
should be evaluated for ischemic heart disease, neuropathies, or retinopathy, and her
renal status must be assessed.
71 Pregnancy can exacerbate the vascular complications
of diabetes. For instance, diabetic retinopathy can worsen if strict glycemic control is
implemented quickly in pregnant women with proliferative retinopathy; progression
to end-stage renal disease can occur in women with mild-to-moderate renal
insufficiency (e.g., serum creatinine >1.5 mg/dL or proteinuria >3 g/24 hours).
The presence of gastroparesis should be noted because it will make controlling her
Controlling K.H.’s diabetes before she becomes pregnant may benefit her
hypertension and neuropathies and will minimize maternal and fetal problems. Good
metabolic control of her diabetes can minimize progression of her diabetes.
CASE 49-2, QUESTION 3: What prepregnancy interventions relative to her general health and diabetes
should K.H. undertake before she attempts to become pregnant?
Pregestational care for K.H. should ideally begin 6 months before conception.
Recommendations for women with diabetes who want to conceive include suggesting
birth control methods until stringent glycemic control can be achieved, consulting a
dietitian to develop a patient-specific nutritional diet to attain healthy weight targets,
and implementing a self-monitoring blood glucose regimen.
levels close to normal) should be achieved months before conception to
minimize risks of major congenital anomalies. K.H.’s current regimen may not
achieve euglycemia (see Chapter 53, Diabetes Mellitus). Her insulin therapy should
be titrated to reduce her average blood glucose range from 90 to 120 mg/dL, targeting
an Hgb A1c of less than 6.5% without frequent episodes of hypoglycemia.
Additionally, K.H. should be started on prenatal vitamins containing at least 400 mcg
Her BP of 145/94 mm Hg is high and should be decreased to a diastolic BP of
about 80 mm Hg to minimize risks for preeclampsia (see Case 49-5, Question 6) or
exacerbation of her disorder. Many women with pregestational diabetes, such as
K.H., are likely on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin
receptor blocker for hypertension treatment or for renal protective effects. Before
pregnancy and during preconception planning, K.H. should be switched to another
antihypertensive (e.g., methyldopa, labetalol, or calcium-channel blockers) such as
methyldopa or labetalol because recent studies have observed possible increased
rates of congenital cardiac malformation associated with the use of ACEIs in the first
75 Further confirmatory studies are needed to define the risk of using ACEIs
during the first trimester. However, use of ACEIs is absolutely contraindicated
during the second and third trimesters of pregnancy.
TYPE 1 DIABETES TREATMENT IN PREGNANCY
CASE 49-2, QUESTION 4: After lowering her BP to 125/80 mm Hg with labetalol 200 mg PO twice daily
to 7.3%, K.H. discontinues her oral contraceptive and returns to the clinic 5 months later and
is noted to be about 4 weeks pregnant. How should her diabetes be managed at this time?
The overall goals of treatment of K.H.’s diabetes are to reduce the maternal and fetal
morbidity and mortality associated with diabetes. Treatment of diabetes (see Chapter
53, Diabetes Mellitus) should include dietary management, appropriate maternal
weight gain, insulin therapy to normalize glycemic control, and exercise.
The goals of dietary management for diabetes during pregnancy are directed at
ensuring fetal growth and development, appropriate maternal weight gain, and
normalizing maternal glucose concentrations. Patients often benefit from
individualized diets developed by a dietitian. Neonatal macrosomia has been
associated with high postprandial glucose levels; therefore, a reduction in
postprandial hyperglycemia is an important goal.
Blood Glucose and Glycosylated Hemoglobin Monitoring
K.H. should begin to self-monitor her blood sugars more intensively at fasting, before
meals, 1 hour postprandially, at bedtime, when she feels symptomatic hypoglycemia,
and at 3:00 AM to rule out dawn phenomenon versus Somogyi effect.
therapy is to maintain fasting glucose levels less than 90 mg/dL, premeal values of
less than 100 mg/dL, and 1-hour postprandial levels of 100 to 120 mg/dL.
glycemic control without incidence of hypoglycemic episodes, targeting Hgb A1c
levels in the normal range, is the goal. Adjusting therapy based on postprandial
glucose levels (as opposed to preprandial levels) can lower Hgb A1c
decrease the risk of macrosomia, neonatal hypoglycemia, and cesarean delivery. Hgb
levels can be drawn at each trimester to reveal the glycemic control during the
Insulin analogs (e.g., lispro, aspart, glargine) are genetically engineered by
recombinant DNA technology and usually differ by a few amino acids from human
insulin. Concerns about insulin analog use during pregnancy include placental drug
transfer and antibody formation.
77 The use of lispro (Humalog) and aspart (Novolog)
insulin during pregnancy is supported by several studies that found minimal passage
across the placenta, an absence of antibody formation, and no adverse maternal or
fetal effects. Although the rapid onset of insulin lispro and aspart can increase
adherence and patient satisfaction, it also may increase the incidence of
hypoglycemia. Insulin glargine (Lantus), a long-acting insulin analog, allows for
once-daily dosing and produces a peakless basal level of insulin. Only case reports
have examined the safety and efficacy of insulin glargine during pregnancy.
Glargine is usually reserved for very brittle and sensitive insulin-dependent type 1
diabetes patients. Neutral protamine Hagedorn (NPH) insulin is usually used twice
daily during pregnancy in lieu of insulin glargine as a basal insulin because it helps
to control fasting blood sugars better than a peakless basal insulin. Newer insulin
analogs such as insulin detemir (Levemir) and insulin glulisine (Apidra) have not yet
been adequately studied during pregnancy and should not be used until further studies
clarify their teratogenicity risk.
Glycemic control is most difficult to establish during the first trimester of
pregnancy because of the effect on blood sugars of maternal fluctuating hormones.
K.H.’s insulin regimen should be optimized by changing from insulin glargine to NPH
insulin (with a 1:1 ratio) to help better control her fasting blood sugars and instituting
a standard insulin lispro dosage before meals based on her carbohydrate intake.
Sliding-scale insulin therapy is rarely used during pregnancy.
commonly need to be monitored more strictly (every 2–4 days until glycemic control
is achieved) during the first trimester and adjusted usually upward every 2 to 3
TYPE 2 DIABETES TREATMENT IN PREGNANCY
routine physical examination. She is morbidly obese with a body mass index (BMI) of 49 kg/m
, which was 8.3%, was 2 months ago. Which medication and treatments should
Insulin is the hypoglycemic agent of choice during pregnancy because it does not
cross the placenta and has an established safety record for both mother and fetus. The
goal with insulin therapy is to imitate the glucose levels of a healthy pregnant woman.
Rapid glycemic control is of utmost importance during this critical period of
organogenesis when vital organs are developing.
Insulin requirements may vary, depending on the trimester. The first trimester is
characterized by unstable diabetes, followed by a stable period.
trimester, glucose and gluconeogenic substances in the blood are taken up by the
fetus, which can lead to a decrease in maternal insulin requirements and increased
episodes of hypoglycemia. On average, insulin dosages range from 0.7 to 0.8
units/kg/day in the first trimester.
If nausea and vomiting occurs during this time,
glycemic control may be unstable and should be monitored closely. At about 24
weeks’ gestation, insulin requirements begin to increase from 0.8 to 1 units/kg/day,
and insulin doses may need to be adjusted every 5 to 10 days.
continue to increase during the third trimester from 0.9 to 1.2 units/kg/day, which may
be twice as much as the prepregnancy dose, in part because of the placental
hormones (i.e., lactogen, prolactin, estrogen, and progesterone), which antagonize the
action of insulin. Weight-based dosing may not accurately assess the insulin
requirements in all pregnant women, especially in the obese population. Insulin
regimens must be individualized for each patient, taking into consideration their
educational level, compliance, and schedule constraints. Dosage adjustments must
take into account the level of activity, meal plan, and other factors (e.g., steroid use,
stress, infections) that may affect glucose control. Some women may be admitted into
the hospital in the first trimester to (a) rapidly gain glucose control, (b) accurately
assess their insulin requirements, and (c) institute an individualized insulin regimen
under careful monitoring of blood sugars.
An insulin regimen with three to four daily injections is most successful at
maintaining adequate glucose control. Biosynthetic human insulin (e.g., regular and
NPH insulin) is the usual treatment of choice in pregestational diabetes mellitus
because of its chemical, biologic, and immunologic equivalency to pancreatic human
38 These insulins have the most established safety profile during pregnancy,
but they require more stringent timing of meals during the day.
V.W. should be switched from her oral hypoglycemic agents to insulin therapy
with biosynthetic human regular insulin and NPH insulin. Metformin and glipizide
should be discontinued. The total daily insulin dosage can be calculated by taking
into account V.W.’s gestational age and actual body weight. Her total daily dose
equals 0.8 units/kg × 134 kg, or 107 units daily. Using three injections per day, her
dosage would be 47 units of NPH insulin plus 24 units of regular insulin SC 30
minutes before breakfast, 18 units of regular insulin SC 30 minutes before dinner, and
18 units SC of NPH insulin at bedtime. V.W.’s treatment plan needs to include
dietary management; appropriate counseling on maternal weight gain during
pregnancy given her morbid obesity; instructions on how to draw up, mix, and inject
her insulin therapy to normalize glycemic control; and moderate exercise and walking
20 to 30 minutes after each meal. She should be taught to inject only in the
subcutaneous abdomen area where insulin is best absorbed during pregnancy. V.W.
should also be given a glucometer and taught how to self-monitor her blood sugars 4
times daily, at fasting and 1 hour postprandially (after the last bite of food from each
meal) to target fasting blood glucose levels below 90 mg/dL and 1-hour postprandial
Oral Hypoglycemic use in Type 2 Diabetes during Pregnancy
Although oral hypoglycemic agents are used commonly to treat type 2 diabetes in
nonpregnant women, they are rarely used as
monotherapy during pregnancy. A switch to insulin therapy is recommended before
conception, if possible, or at the time the pregnancy is confirmed because many
patients have inadequate control with oral hypoglycemic agents.
started before conception, women should be strongly counseled to stay on oral
hypoglycemics to adequately control blood glucose until insulin therapy can be
implemented. Often, patients will discontinue oral hypoglycemics from fear of taking
any medication in pregnancy, resulting in hyperglycemia during the critical period of
The ACOG recommends that the use of oral hypoglycemics for the treatment of
type 2 diabetes during pregnancy be individualized until more safety and efficacy
66–71 There is limited experience with oral hypoglycemic use
in type 2 diabetes during pregnancy. Metformin, a biguanide, has been used during
pregnancy for hyperinsulinemic insulin resistance or in the treatment of infertility in
women with polycystic ovarian syndrome (see Chapter 50, Disorders Related to the
Menstrual Cycle). Women taking metformin should be switched to insulin therapy
unless specific circumstances (e.g., high insulin requirements during the second or
third trimester) warrant its use.
77. Studies have shown the sulfonylureas are inferior to
both insulin and metformin and increase risk for neonatal hypoglycemia.
CASE 49-3, QUESTION 2: Should an oral hypoglycemic be added to V.W.’s insulin regimen?
V.W. should remain on insulin therapy with three injections daily. Her insulin
regimen should be adjusted every 2 to 3 days until glycemic control is achieved and
targeted blood glucose levels are reached without significant hypoglycemia episodes.
Metformin should only be added if V.W.’s total daily insulin requirement exceeds
250 to 300 units. If metformin is added, insulin dosages should be decreased to at
least half the amount in anticipation of increased insulin sensitivity.
inches, 75 kg (prepregnancy weight), and her BMI is 30 kg/m
. At her regular prenatal visit, her obstetrician
recommends an oral glucose screening test for GDM. Her Hgb A1c was 5.8%. Although her mother has
diabetes, J.B. has had no glucosuria during pregnancy. Is J.B. at risk for GDM?
GDM is defined as carbohydrate intolerance that develops or is recognized during
pregnancy regardless of severity, necessity for treatment, time of onset, or
78 GDM occurs in about 7% (range, 1%–14%), and the
prevalence varies with the population and methods of detection.
noted in the offspring of affected women include macrosomia, hypocalcemia,
hypoglycemia, polycythemia, and jaundice. Women with GDM are more likely to
experience pregnancy-induced hypertensive disorders or require a cesarean delivery.
They also are at risk for type 2 diabetes later, and their children have an increased
risk for obesity and diabetes later in life.
Risk factors for GDM include age older than 25 years, obesity (BMI ≥25 kg/m2
family history of diabetes, previous delivery of an infant weighing more than 4 kg, a
history of a stillbirth, a history of glucose intolerance, or current glycosuria.
African-Americans, Hispanic, Asian, Native American, and Pacific Islander women
also are at increased risk for GDM.
J.B. is at risk for GDM because she is Asian and obese, and she has a family
history of diabetes. Her Hgb A1c at 26 weeks’ gestation was normal and ruled her out
for overt diabetes. J.B. should undergo the standard screening for gestational
diabetes with a 50-g, 1-hour glucose challenge. It is not essential for J.B. to fast
before this test. The diagnosis of GDM is important to the mother and the fetus
because of the increased risks of fetal hyperinsulinemia and macrosomia.
GESTATIONAL DIABETES MELLITUS TREATMENT
mg/dL. These results confirm that J.B. has GDM. How should she be managed?
J.B. requires extensive education about a gestational diabetes diet, use of a
glucometer, the signs and symptoms of hyperglycemia and hypoglycemia, and
treatment of low blood glucose. She should start to monitor her blood glucose 4 times
daily, at fasting and 1 hour after the end of each meal. She should return to the clinic
in 1 week for an assessment of her blood sugars to evaluate the need for medication
therapy (insulin versus glyburide treatment).
It is suggested that 60% to 85% of patients with GDM can control their glucose
with dietary modifications and regular exercise; however, management with
medications (insulin vs. oral hypoglycemics) should be initiated if dietary
management fails to maintain fasting plasma blood glucose concentrations at 95
mg/dL or less or to achieve a 1-hour postprandial plasma concentration of less than
74 Figure 49-3 outlines recommendations for screening and diagnosis of
dinner postprandial values are averaging 139 mg/dL. How should J.B. be managed at this time?
Treatment of GDM with insulin therapy is implemented similar to the treatment for
pregestational diabetes. An optimal insulin regimen for GDM has not been
determined. Similar dosing with a weight-based, split-mixed multidose regimen is
used. The insulin regimen must be tailored specifically to the needs of the woman to
successfully achieve target blood glucose levels.
More recently, the Metformin in Gestational Diabetes trial examined whether
metformin treatment could provide equivalent outcomes to insulin treatment. Women
with GDM at 20 to 33 weeks’ gestation were randomly assigned to open-label
treatment with metformin (titrated up to 2,500 mg with the option to add supplemental
insulin if glycemic control was not achieved) or to insulin treatment alone.
groups achieved similar primary outcomes (composite score of neonatal
morbidities), but 46% of the group allocated to metformin required supplemental
insulin therapy. Those requiring supplemental insulin were more obese and had
higher elevations of glycemic values at presentation. The results indicate that
metformin can be used during pregnancy for GDM, but will less likely be successful
as monotherapy in women with higher glucose levels.
reserved for patients with high insulin requirements (>300 units daily) in the second
38 More randomized trials are needed to further determine and to
better understand the role of oral hypoglycemic agents in pregnancy.
No comments:
Post a Comment
اكتب تعليق حول الموضوع