Gynecology

Diabetes Mellitus

د. حسين محمد جمعه
اختصاصي الامراض الباطنة
البورد العربي
كلية طب الموصل
2012

Diabetes Mellitus

Insulin is not excreted into breast milk and is considered safe for use during breast-feeding.
Glyburide and glipizide are highly protein-bound (92 to 99 percent), second-generation sulfonylureas less likely to be displaced by other drugs and unlikely to pass into breast milk. If any of the sulfonylureas are used, it is important to monitor the nursing infant for signs of hypoglycemia, such as increased fussiness or somnolence.

The alpha-glucosidase inhibitors, are unlikely to be excreted into breast milk in clinically significant amounts.
Because of the potential for serious side effects (e.g., lactic acidosis, hepatotoxicity) in adults, it may be advisable to avoid the use of metformin (Glucophage) and thiazolidinediones
e.g., rosiglitazone ,pioglitazone
until more information is available on their use in breast-feeding.


Diabetes Mellitus
In pregnancy, the fetoplacental unit induces major metabolic changes, the purpose of which is to shunt glucose and amino acids to the fetus while the mother uses ketones and triglycerides to fuel her metabolic needs. These metabolic changes are accompanied by maternal insulin resistance, caused in part by placental production of steroids, a growth hormone variant, and placental lactogen. Although pregnancy has been referred to as a state of "accelerated starvation," it is better characterized as "accelerated ketosis.

" In pregnancy, after an overnight fast, plasma glucose is lower by 0.8–1.1 mmol/L (15–20 mg/dL) than in the nonpregnant state. This is due to the use of glucose by the fetus. In early pregnancy, fasting may result in circulating glucose concentrations in the range of 2.2 mmol/L (40 mg/dL) and may be associated with symptoms of hypoglycemia. In contrast to the decrease in maternal glucose concentration, plasma hydroxybutyrate and acetoacetate levels rise to two to four times normal after a fast.

Diabetes Mellitus in Pregnancy: Treatment

Preconception counseling and treatment are important for the diabetic patient contemplating pregnancy and can reduce the risk of congenital malformations and improve pregnancy outcome.

Folate supplementation reduces the incidence of fetal neural tube defects, which occur with greater frequency in fetuses of diabetic mothers. In addition, optimizing glucose control during key periods of organogenesis reduces other congenital anomalies including sacral agenesis, caudal dysplasia, renal agenesis, and ventricular septal defect.

Once pregnancy is established, glucose control should be managed more aggressively than in the nonpregnant state. In addition to dietary changes, this requires more frequent blood glucose monitoring and often involves additional injections of insulin or conversion to an insulin pump. Fasting blood glucose levels should be maintained at <5.8 mmol/L (<105 mg/dL) with no values >7.8 mmol/L (140 mg/dL).

Commencing in the third trimester, regular surveillance of maternal glucose control as well as assessment of fetal growth (obstetric sonography) and fetoplacental oxygenation (fetal heart rate monitoring or biophysical profile) optimizes pregnancy outcome. Pregnant diabetic patients without vascular disease are at greater risk for delivering a macrosomic fetus, and attention to fetal growth via clinical and ultrasound examinations is important.

Fetal macrosomia is associated with an increased risk of maternal and fetal birth trauma. Pregnant women with diabetes have an increased risk of developing preeclampsia, and those with vascular disease are at greater risk for developing intrauterine growth restriction, which is associated with an increased risk of fetal and neonatal death. Excellent pregnancy outcomes in patients with diabetic nephropathy and proliferative retinopathy have been reported with aggressive glucose control and intensive maternal and fetal surveillance.

Glycemic control may become more difficult to achieve as pregnancy progresses due to an increase in insulin resistance. Because of delayed pulmonary maturation of the fetuses of diabetic mothers, early delivery should be avoided unless there is biochemical evidence of fetal lung maturity. In general, efforts to control glucose and maintain the pregnancy until the estimated date of delivery result in the best overall outcome for both mother and newborn.

Gestational Diabetes

All pregnant women should be screened for gestational diabetes unless they are in a low-risk group. Women at low risk for gestational diabetes are those <25 years of age; those with a body mass index < 25 kg/m2, no maternal history of macrosomia or gestational diabetes, and no diabetes in a first-degree relative; and those not members of a high-risk ethnic group (African American, Hispanic, Native American).


A typical two-step strategy for establishing the diagnosis of gestational diabetes involves administration of a 50-g oral glucose challenge with a single serum glucose measurement at 60 min. If the plasma glucose is <7.8 mmol/L (<140 mg/dL), the test is considered normal. Serum glucose > 7.8 mmol/L (>140 mg/dL) warrants administration of a 100-g oral glucose challenge with serum glucose measurements obtained in the fasting state, and at 1, 2, and 3 h.

Normal values are plasma glucose concentrations <5.8 mmol/L (<105 mg/dL), 10.5 mmol/L (190 mg/dL), 9.1 mmol/L (165 mg/dL), and 8.0 mmol/L (145 mg/dL), respectively. Some centers have adopted more conservative criteria, using <7.5 mmol/L (<135 mg/dL) as the screening threshold, and values of <5.3 mmol/L (<95 mg/dL), <10 mmol/L (<180 mg/dL), <8.6 mmol/L (<155 mg/dL), and <7.8 mmol/L (<140 mg/dL) as the upper norms for a 3-h glucose tolerance test.

Pregnant women with gestational diabetes are at increased risk of preeclampsia, delivering infants who are large for their gestational age, and birth lacerations. Their fetuses are at risk of hypoglycemia and birth trauma (brachial plexus) injury.

Gestational Diabetes: Treatment

Treatment of gestational diabetes with a two-step strategy of dietary intervention followed by insulin injections if diet alone does not adequately control blood sugar [fasting glucose < 5.6 mmol/L (<100 mg/dL) and 2-h post-prandial <7.0 mmol/L (<126 mg/dL)] is associated with a decreased risk of birth trauma for the fetus.

More recently the use of the oral hypoglycemic agent glyburide has become popular for managing gestational diabetes refractory to nutritional management. More data on the safety and efficacy of glyburide for the management of gestational diabetes are needed before it supplants insulin as the treatment agent of choice.

For women with gestational diabetes, within the 10 years after the index pregnancy there is a 40% risk of being diagnosed with diabetes. All women with a history of gestational diabetes should be counseled about prevention strategies and evaluated regularly for diabetes.

Thyroid Disease

In pregnancy, the estrogen-induced increase in thyroxine-binding globulin causes an increase in circulating levels of total T3 and total T4. The normal range of circulating levels of free T4, free T3, and thyroid-stimulating hormone (TSH) remain unaltered by pregnancy.

The thyroid gland normally enlarges during pregnancy. Maternal hyperthyroidism occurs at a rate of ~2 per 1000 pregnancies and is generally well tolerated by pregnant women. Clinical signs and symptoms should alert the physician to the occurrence of this disease. Many of the physiologic adaptations to pregnancy may mimic subtle signs of hyperthyroidism.

Although pregnant women are able to tolerate mild hyperthyroidism without adverse sequelae, more severe hyperthyroidism can cause spontaneous abortion or premature labor, and thyroid storm is associated with a significant risk of maternal mortality.

Hyperthyroidism in Pregnancy: Treatment

Hyperthyroidism in pregnancy should be aggressively evaluated and treated. The treatment of choice is propylthiouracil. Because it crosses the placenta, the minimum effective dose should be used to maintain free T4 in the upper normal range. Methimazole crosses the placenta to a greater degree than propylthiouracil and has been associated with fetal aplasia cutis.


Gastrointestinal and Liver Disease
Up to 90% of pregnant women experience nausea and vomiting during the first trimester of pregnancy. Occasionally, hyperemesis gravidarum requires hospitalization to prevent dehydration, and sometimes parenteral nutrition is required.

Crohn's disease may be associated with exacerbations in the second and third trimesters. Ulcerative colitis is associated with disease exacerbations in the first trimester and during the early postpartum period. Medical management of these diseases during pregnancy is identical to the management in the nonpregnant state .

Exacerbation of gall bladder disease is commonly observed during pregnancy. In part this may be due to pregnancy-induced alteration in the metabolism of bile and fatty acids.

Intrahepatic cholestasis of pregnancy is generally a third-trimester event. Profound pruritus may accompany this condition, and it may be associated with increased fetal mortality. It has been suggested that placental bile salt deposition may contribute to progressive uteroplacental insufficiency. Therefore, regular fetal surveillance should be undertaken once the diagnosis of intrahepatic cholestasis is made. Favorable results with ursodiol have been reported.

Acute fatty liver is a rare complication of pregnancy. Frequently confused with the HELLP syndrome and severe preeclampsia, the diagnosis of acute fatty liver of pregnancy may be facilitated by imaging studies and laboratory evaluation. Acute fatty liver of pregnancy is generally characterized by markedly increased levels of bilirubin and ammonia and by hypoglycemia. Management of acute fatty liver of pregnancy is supportive; recurrence in subsequent pregnancies has been reported.

All pregnant women should be screened for hepatitis B. This information is important for pediatricians after delivery of the infant. All infants receive hepatitis B vaccine. Infants born to mothers who are carriers of hepatitis B surface antigen should also receive hepatitis B immune globulin as soon after birth as possible and preferably within the first 72 h. Screening for hepatitis C is recommended for individuals at high risk for exposure.

Infections

Bacterial Infections
Other than bacterial vaginosis, the most common bacterial infections during pregnancy involve the urinary tract .Many pregnant women have asymptomatic bacteriuria, most likely due to stasis caused by progestational effects on ureteral and bladder smooth muscle and later in pregnancy due to compression effects of the enlarging uterus. In itself, this condition is not associated with an adverse outcome of pregnancy. However, if asymptomatic bacteriuria is left untreated, symptomatic pyelonephritis may occur.

Indeed, ~75% of cases of pregnancy-associated pyelonephritis are the result of untreated asymptomatic bacteriuria. All pregnant women should be screened with a urine culture for asymptomatic bacteriuria at the first prenatal visit. Subsequent screening with nitrite/leukocyte esterase strips is indicated for high-risk women, such as those with sickle cell trait or a history of urinary tract infections. All women with positive screens should be treated.

Abdominal pain and fever during pregnancy create a clinical dilemma. The diagnosis of greatest concern is intrauterine amniotic infection. While amniotic infection most commonly follows rupture of the membranes, this is not always the case. In general, antibiotic therapy is not recommended as a temporizing measure in these circumstances. If intrauterine infection is suspected, induced delivery with concomitant antibiotic therapy is generally indicated.


Intrauterine amniotic infection is most often caused by pathogens such as Escherichia coli and group B streptococcus. In high-risk patients at term or in preterm patients, routine intrapartum prophylaxis of group B streptococcal (GBS) disease is recommended. Penicillin G and ampicillin are the drugs of choice. In penicillin-allergic patients, clindamycin is recommended.

For the reduction of neonatal morbidity due to GBS, universal screening of pregnant women for GBS between 35 and 37 weeks gestation with intrapartum antibiotic treatment of infected women is recommended.

Postpartum infection is a significant cause of maternal morbidity and mortality. While rare after vaginal delivery, postpartum endomyometritis develops in 5% of patients having elective repeat cesarean section and in 25% of patients after emergency cesarean section following prolonged labor.

Prophylactic antibiotics should be given to all patients undergoing cesarean section. As most cases of postpartum endomyometritis are polymicrobial, broad-spectrum antibiotic coverage with a penicillin, aminoglycoside, and metronidazole is recommended .

Most cases resolve within 72 h. Women who do not respond to antibiotic treatment for postpartum endomyometritis should be evaluated for septic pelvic thrombophlebitis. Imaging studies may be helpful in establishing the diagnosis, which is primarily a clinical diagnosis of exclusion

Patients with septic pelvic thrombophlebitis generally have tachycardia out of proportion to their fever and respond rapidly to intravenous administration of heparin.

All patients are screened prenatally for gonorrhea and chlamydial infections, and the detection of either should result in prompt treatment. Ceftriaxone and azithromycin are the agents of choice .

Viral Infections

Cytomegalovirus Infection
Viral infection in pregnancy presents a significant challenge. The most common cause of congenital viral infection in the United States is cytomegalovirus (CMV) (Chap. 175). As many as 50–90% of women of childbearing age have antibodies to CMV, but only rarely does CMV reactivation result in neonatal infection. More commonly, primary CMV infection during pregnancy creates a risk of congenital CMV.

No currently accepted treatment of CMV during pregnancy has been demonstrated to protect the fetus effectively. Moreover, it is impossible to predict which fetus will sustain life-threatening CMV infection.

Severe CMV disease in the newborn is characterized most often by petechiae, hepatosplenomegaly, and jaundice. Chorioretinitis, microcephaly, intracranial calcifications, hepatitis, hemolytic anemia, and purpura may also develop. CNS involvement, resulting in the development of psychomotor, ocular, auditory, and dental abnormalities over time, has been described.


Rubella
Rubella virus is a known teratogen; first-trimester rubella carries a high risk of fetal anomalies, though the risk decreases significantly later in pregnancy. Congenital rubella may be diagnosed by percutaneous umbilical blood sampling with the detection of IgM antibodies in fetal blood.

All pregnant women should be screened for their immune status to rubella. Indeed, all women of childbearing age, regardless of pregnancy status, should have their immune status for rubella verified and be immunized if necessary. The incidence of congenital rubella in the United States is extremely low.

Herpesvirus

The acquisition of genital herpes during pregnancy is associated with spontaneous abortion, prematurity, and congenital and neonatal herpes. A recent cohort study of pregnant women without evidence of previous herpes infection demonstrated that ~2% of the women acquired a new herpes infection during the pregnancy.

Approximately 60% of the newly infected women had no clinical symptoms. Infection occurred equally in all three trimesters. If herpes seroconversion occurred early in pregnancy, the risk of transmission to the newborn was very low. In women who acquired genital herpes shortly before delivery, the risk of transmission was high.

The risk of active genital herpes lesions at term can be reduced by prescribing acyclovir for the last 4 weeks of pregnancy to women who have had their first episode of genital herpes during the pregnancy.
Herpesvirus infection in the newborn can be devastating. Disseminated neonatal herpes carries with it high mortality and morbidity rates from CNS involvement.

It is recommended that pregnant women with active genital herpes lesions at the time of presentation in labor be delivered by cesarean section.

Parvovirus infection (human parvovirus B19) may occur during pregnancy. It rarely causes sequelae, but susceptible women infected during pregnancy may be at risk for fetal hydrops secondary to erythroid aplasia and profound anemia

HIV Infection

The predominant cause of HIV infection in children is transmission of the virus from the mother to the newborn during the perinatal period. Exposures, which increase the risk of mother-to-child transmission, include vaginal delivery, preterm delivery, trauma to the fetal skin, and maternal bleeding.

Additionally, recent infection with high maternal viral load, low maternal CD4+ T cell count, prolonged labor, prolonged length of membrane rupture, and the presence of other genital tract infections, such as syphilis or herpes, increase the risk of transmission. Breast-feeding may also transmit HIV to the newborn and is therefore contraindicated in most developed countries for HIV-infected mothers.


There is no clear evidence to suggest that the course of HIV disease is altered by pregnancy. There is also no clear evidence to suggest that uncomplicated HIV disease adversely impacts pregnancy other than by its inherent infection risk.

HIV Infection in Pregnancy: Treatment

The majority of cases of mother-to-child (vertical) transmission of HIV-1 occur during the intrapartum period. Mechanisms of vertical transmission include infection after rupture of the membranes and direct contact of the fetus with infected secretions or blood from the maternal genital tract.

Zidovudine (ZDV) administered during pregnancy and labor and to the newborn reduces the risk of vertical transmission by 70%. Cesarean section is associated with additional risk reduction compared to vaginal delivery, especially in women with a viral load >1000 copies/mL. Regardless of the mode of delivery, intrapartum ZDV should be provided.

Summary

Maternal mortality has decreased steadily during the past 70 years. The maternal death rate has decreased from nearly 600/100,000 live births in 1935 to 8/100,00 live births in 2002. The most common causes of maternal death in the United States today are, in decreasing order of frequency, pulmonary embolism, obstetric hemorrhage, hypertension, sepsis, cardiovascular conditions including peripartum cardiomyopathy, and ectopic pregnancy.

With improved diagnostic and therapeutic modalities as well as with advances in the treatment of infertility, more patients with medical complications will be seeking, and be in need of, complex obstetric care. Improving outcome of pregnancy in these women will be best obtained by assembling a team of internists, specialists in maternal-fetal medicine (high-risk obstetrics), and anesthesiologists to counsel these patients about the risks of pregnancy and to plan their treatment prior to conception.

The importance of preconception counseling cannot be overstated. It is the responsibility of all physicians caring for women in the reproductive age group to assess their patient's reproductive plans as part of their overall health evaluation.

Hematologic Disorders

Pregnancy has been described as a state of physiologic anemia. Part of the reduction in hemoglobin concentration is dilutional, but iron and folate deficiencies are the major causes of correctable anemia during pregnancy.

In populations at high risk for hemoglobinopathies hemoglobin electrophoresis should be performed as part of the prenatal screen. Hemoglobinopathies can be associated with increased maternal and fetal morbidity and mortality. Management is tailored to the specific hemoglobinopathy and is generally the same for both pregnant and nonpregnant women.

Prenatal diagnosis of hemoglobinopathies in the fetus is readily available and should be discussed with prospective parents either prior to or early in pregnancy.


Thrombocytopenia occurs commonly during pregnancy. The majority of cases are benign gestational thrombocytopenias, but the differential diagnosis should include immune thrombocytopenia and preeclampsia. Maternal thrombocytopenia may also be caused by catastrophic obstetric events such as retention of a dead fetus, sepsis, abruptio placenta, and amniotic fluid embolism.

Chronic renal disease

Complications depend on the degree of renal compromise .Mother has increased risk of pre-eclampsia which can be difficult to diagnose in the background or proteinurea and hypertension
Also associated with IUGR and preterm labour
Renal function and BP must be monitored as must fetal growth and development

Women on dialysis have impaired fertility and conception is not common.

When it does occur it has a very high rate of miscarriage and termination is often offered
When pregnancy does occur it is associated with pre-eclampsia, hypertension and volume overload

Diabetes and gestational diabetes

Increased insulin resistance during pregnancy due to the insulin antagonistic effects of human placental lactogen and cortisol
1-2% of pregnant women develop gestational diabetes
Risk factors include
Obesity
Family history
Previous baby >4.5kg
Previous unexplained stillborn
Previous congenital abnormality
Diabetes is defined as a fasting blood glucose >7.8mmol/L or a level of >11.1 postprandial (75g oral glucose challenge)