Anticonvulsants and drugs for neurological disease

The use of anticonvulsant drugs in pregnancy presents unique challenges to clinicians and their patients. The need for control of maternal epilepsy must be balanced with the fetal and neonatal risks associated with anticonvulsant drugs. Anticonvulsant drugs may have potential effects on embryogenesis, neurological development, growth and subsequent paediatric progress. Drug selection and dose adjustment must be appropriate and based on a combination of known maternal and fetal risks as well as the clinical status of the patient. Overall, no one drug can be specifically recommended but monotherapy with most of the recognized first-line drugs will result in a satisfactory outcome. Polytherapy is associated with an increase in congenital malformations and should be avoided if possible. It is possible that newer second-line agents, for example, gabapentin, may be safer as add-on therapy.Neurological disorders such as migraine, and the less common conditions of myasthenia gravis and multiple sclerosis, may require the use of drugs which have not been well studied in pregnancy. Information is provided about the use of drugs to control symptoms and prevent disease progression in these disorders during pregnancy.     

Obesity and diabetes: A recipe for obstetric complications.

The prevalence of obesity has been increasing worldwide and has reached epidemic proportions in the United States, where well over 20% of the population have a body mass index (BMI) within the obese range. Obesity is associated with a wide spectrum of obstetric and perinatal complications, including increased risks of fetal mortality and morbidity, congenital malformations, maternal hypertensive disorders, gestational diabetes, excessive fetal growth and cesarean delivery. The odds ratios for these risks increase in direct correlation with the severity of obesity, and are significant even among women who are overweight without meeting criteria for obesity. Although obesity is closely associated with diabetes which, in itself, is associated with similar perinatal complications, diabetes and obesity are independent risk factors for adverse pregnancy outcome. Moreover, improving glycemic control in the pregnant woman with diabetes may mitigate the additive adverse effects of diabetes and obesity on pregnancy outcome.     

Identification of fetal problems associated with anticonvulsant usage and maternal epilepsy.

This article reviews the general approach for assessing teratogenic risks related to fetal exposure, concentrating on the specific patterns associated with anticonvulsant usage and maternal epilepsy. Major anomalies that might be detected prenatally are presented, as well as the patterns of minor anomalies (syndromes) that might be detected at birth or later. Each of the specific drugs used in the treatment of epilepsy is reviewed in detail. In addition, recent information concerning genetically determined variations in the metabolism of antiepileptic drugs is discussed in light of how genetic factors might relate to teratogenicity.     

Drugs used in hypertensive diseases in pregnancy

PURPOSE OF REVIEW: This review will summarize results derived from the most recent publications on the use of drugs in women with hypertensive diseases in pregnancy. RECENT FINDINGS: There is consensus that severe hypertension should be treated without delay to reduce maternal risks of acute cerebrovascular complications. There is no consensus that antihypertensive drugs improve maternal or fetal outcome in mild to moderate hypertension. Evidence exists that antihypertensive drugs may halve the risk of severe hypertension in pregnancy. No proof exists that antihypertensive drugs reduce perinatal mortality or development of preeclampsia, and such drugs have not been associated with improved fetal growth. Clinical trials indicate non-consistent data concerning antihypertensive treatment on antenatal rate of hospitalization, proteinuria at delivery and neonatal respiratory distress syndrome. Hydralazine has for many years been regarded as the first drug of choice for treatment of severe hypertension in pregnancy. Recent findings indicate that the calcium antagonist nifedipine might be a better alternative. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists should be discontinued due to fetotoxicity. The beta1-selective adrenoceptor blocker atenolol in the first trimester is associated with low birth weight. SUMMARY: Large randomized controlled trials are urgently needed to determine whether antihypertensive therapy in pregnancy results in greater benefit than risks for mother and fetus.     

Excessive Gestational Weight Gain

Excessive gestational weight gain (GWG) is associated with an increasing incidence of maternal and neonatal complications, including hypertensive disorders of pregnancy, fetal macrosomia, and increased cesarean birth rates. In the United States, it is recommended that health care providers use an individualized approach to counsel a woman about pregnancy weight gain goals that is based on the woman's initial body mass index (BMI) and to track GWG throughout the pregnancy by evaluating maternal weight at each visit. Studies have shown that women entering pregnancy with a higher BMI are at increased risk for excessive GWG and postpartum weight retention. Research also demonstrates an increased risk of childhood obesity in children born to women with excessive GWG. Specific counseling about exercise and diet, as well as technology and motivational interviewing, are some tools prenatal care providers can use that have been shown to be effective in reducing excessive GWG. This article reviews the current research regarding maternal and neonatal risks associated with excessive GWG, as well as the interventions that have demonstrated promise for addressing this problem.     

Contraception for women with chronic medical conditions

Chronic medical conditions can complicate maternal and fetal health during pregnancy, making unintended or mistimed pregnancy problematic. The use of highly effective reversible contraceptives is important for women with health issues, yet sometimes those same illnesses make the contraceptives themselves less effective or less safe. We review the evidence surrounding contraceptive use by women with six common medical conditions: systemic lupus erythematosus, diabetes mellitus, anticonvulsant use for epilepsy or mood disorder, HIV infection, migraine headache, and obesity. In some instances it is not possible to make a risk-free contraceptive choice, yet pregnancy may be even riskier. Good clinical judgment and patient counseling must be exercised.     

Obesity and diabetes: A recipe for obstetric complications

The prevalence of obesity has been increasing worldwide and has reached epidemic proportions in the United States, where well over 20% of the population have a body mass index (BMI) within the obese range. Obesity is associated with a wide spectrum of obstetric and perinatal complications, including increased risks of fetal mortality and morbidity, congenital malformations, maternal hypertensive disorders, gestational diabetes, excessive fetal growth and cesarean delivery. The odds ratios for these risks increase in direct correlation with the severity of obesity, and are significant even among women who are overweight without meeting criteria for obesity. Although obesity is closely associated with diabetes which, in itself, is associated with similar perinatal complications, diabetes and obesity are independent risk factors for adverse pregnancy outcome. Moreover, improving glycemic control in the pregnant woman with diabetes may mitigate the additive adverse effects of diabetes and obesity on pregnancy outcome.     

Anticoagulants in pregnancy

Pregnancy is a hypercoagulable state that increases the risk of thromboembolic events. These risks may be further increased in the presence of an acquired or inherited thrombophilia. Thrombophilias have been associated with both maternal and fetal complications. The use of anticoagulants during pregnancy may reduce the risk of maternal thromboses as well as the risk of adverse pregnancy outcomes. The choice of an anticoagulant requires consideration of maternal risks, potential for teratogenicity, the underlying condition necessitating the treatment, and cost. This review examines the options for anticoagulation, the clinical situations that may warrant such treatment, and factors to be considered at delivery and during the postpartum period. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the roles of acquired and inherited thrombophilia in furthering the hypercoagulable state of pregnancy, identify the potential consequences of using anticoagulants during pregnancy, and summarize the treatment options when anticoagulation is required during pregnancy.     

Management of the Eclamptic Patient

Eclampsia is defined as the development of convulsions and/or coma unrelated to other cerebral pathology during pregnancy or in the postpartum period in patients with signs and symptoms of preeclampsia. It is a life-threatening obstetrical emergency that is not limited to occurrence in tertiary care centers. Obstetricians and perinatal nurses in every facility therefore must be familiar with the diagnosis and management of this complication of pregnancy. Astute care by the obstetrical team is of paramount importance in eclampsia management because of increased risks of maternal trauma, volume overload, gastric aspiration, and fetal distress. Basic principles in the management of eclampsia are maternal support of vital functions, protection of mother from injury, prevention of recurrent convulsions, correction of maternal hypoxemia or acidemia, control of severe hypertension, and initiation of the delivery process. Parenteral magnesium sulfate remains the anticonvulsant agent of choice in eclamptic patients. Administration of magnesium sulfate requires personnel to be familiar with its pharmacology, side effects, and appropriate antidote in the event of overdosage. With a well-formulated management plan, improved maternal and fetal outcome is achievable in this infrequent but severe complication of pregnancy.     

Corticosteroids, pregnancy, and HELLP syndrome: a review

Corticosteroids are potent antiinflammatory and immunosuppressive drugs, which are used in the treatment of a wide range of medical disorders. During pregnancy, several corticosteroids are administered for maternal as well as fetal reasons. Prednisone and prednisolone show limited transplacental passage and are thus used for treatment of maternal disease. Dexamethasone and betamethasone, drugs that can easily cross the placenta, are more suitable for fetal indications. During the last decade, administration of corticosteroids was introduced in the treatment of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), a severe form of preeclampsia unique to human pregnancy. Several randomized, controlled trials as well as other prospective and retrospective studies have been performed to investigate this beneficial effect of corticosteroids on biochemical measures and clinical signs. This review discusses the characteristics of corticosteroids in humans and details the use of corticosteroids during pregnancy. A review of literature on the effect of corticosteroids on HELLP syndrome is given and possible mechanisms of action are discussed.     

Type 2 diabetes in pregnancy: exposing deceptive appearances.

Now that we have been forewarned of the growing pandemic of type 2 diabetes and obesity in pregnancy, we need to become forearmed. Over the past few decades there has been no significant improvement in perinatal outcome complicated by diabetes mellitus (type 1 and type 2). The recognition of modifiable risk factors such as maternal glycemic control using self-monitoring blood glucose in combination with pharmacological therapy (intensified therapy) and weight gain in pregnancy should enhance pregnancy outcome. The overemphasis and concentration on the non-modifiable risk factors in pregnancy is a futile pursuit that may generate lively discussion but paucity of results. The focus needs to be in education for the care provider, i.e., enhanced recognition of this growing entity and a heightened awareness of the need for pre-pregnancy counseling about preconception glycemic control. Another center of attention should be the dissemination of information to patients of the impending maternal and fetal risks of type 2 diabetes in pregnancy. This care would include antenatal care for surveillance of maternal diabetes complications as well as careful obstetric surveillance to improve maternal and fetal outcomes.     

Prolonged pregnancy

Prolonged pregnancy is defined by duration greater than 294 days from the last menstrual period, or equivalent gestational age calculated by ultrasonic fetal biometry. The latter is a more accurate method for establishing the diagnosis. The specific causes of prolonged pregnancy are unknown, but identified risk factors are nulliparity, increased maternal weight, and previous history of prolonged pregnancy. Prolonged pregnancy is associated with obstetrical and neonatal adverse outcomes, and the risks appear to increase along a spectrum with the degree of prolongation. Prolonged pregnancy may be avoided by interventions to cause delivery prior to 294 days gestation, including complementary therapies, labour induction, or caesarean section.The risks of these interventions must be considered in the context of the low absolute risks of prolonged pregnancy. There remains no clear evidence of benefit in these strategies from well-designed prospective studies. However, retrospective studies have shown reduced perinatal problems when methods to avoid prolonged pregnancy have been utilized. In addition to consideration of risks, decision-making in cases of prolonged pregnancy must also take into account healthcare resources and maternal wishes.     

A successful pregnancy in a Turner syndrome with oocyte donation

Advances in reproductive medicine using oocyte donation have made it possible for women with Turner syndrome (TS) to achieve successful pregnancies. These pregnancies carry substantial fetal and maternal risks, with hypertensive disorders or pregnancy and fetal growth restriction common, and an increased risk of aortic dissection, sometimes fatal, for the woman. Careful prepregnancy assessment and fetal and maternal vigilance during pregnancy is a necessary prerequisite for a successful outcome. We present a case of a woman with Turner syndrome achieving a successful pregnancy from donor oocyte and review the relevant literature.     

Glycemic control in the diabetic pregnancy: is tighter always better?

Glucose is the principal nutrient that the mother supplies to the fetus through the placenta by way of concentration-dependent mechanisms. In the presence of maternal hypoglycemia, with limited glucose supply, fetal hypoglycemia and hypoinsulinism ensue. This may be viewed as an adaptive mechanism to increase the chances of fetal survival in the face of limited maternal supply, albeit of a growth-restricted fetus. Fetal nutrient deprivation and the resulting hypoinsulinism may have both short- and long-term consequences. Intrauterine growth failure is associated with higher rates of gestational age-specific neonatal mortality and with long-term cognitive deficits. Furthermore, epidemiologic data suggest that diabetes, coronary artery disease, and hypertension are more common among adults who were small for gestational age at birth. Thus, pancreatic failure in adulthood may be either a response to excessive exposure to glucose as a result of maternal hyperglycemia, or as a result of hypoglycemia where nutrient deprivation leads to fetal growth restriction and reduced islet cell proliferation. Because low mean concentrations of maternal glucose in gestational diabetes are associated with an increased risk of fetal growth restriction, overzealous glycemic control during pregnancy may raise concerns regarding the possible effects on the infant. In the mother with Type 1 diabetes, strict glycemic control is often associated with an increased incidence of severe hypoglycemia. Up to 40% of women report at least one episode of severe hypoglycemia during pregnancy, requiring assistance by another person or professional intervention. It is quite possible that in some patients striving to optimize pregnancy outcome by maintaining the best possible glycemic control jeopardizes the well-being of the mother and the fetus. Thus, with respect to tight glycemic control of pregnant women with diabetes, the question arises: How tight is too tight? Is there a threshold below which the trade-off in terms of maternal morbidity as well as fetal growth restriction and its consequences outweighs the benefits of preventing the effects of maternal hyperglycemia?     

Prescribing in pregnancy. Thyroid disease

When treating thyroid disease, as with other conditions in pregnancy, one is concerned with the welfare of both mother and developing child. Thyroid disease causes few maternal problems; thyrotoxicosis in fact tends to improve in pregnancy, allowing medical management with lower drug doses than usual. Relapse of thyroid disease may occur postpartum, when transient hypo- and hyperthyroidism are relatively common. In contrast, the fetus and neonate are threatened in a number of ways by drugs given to the mother and by transplacental passage of maternal antibodies capable of inducing thyroid disease. Antithyroid drugs may cause fetal goitre with airway obstruction, and are associated with mild neonatal hypothyroidism. Thyroid antibodies in primary myxoedema and Hashimoto's thyroiditis are occasionally implicated in neonatal hypothyroidism and may even cause thyroid dysgenesis. Neonatal hyperthyroidism has a high morbidity and mortality and may have long-term skeletal effects such as craniosynostosis. Fetal problems may not be apparent at birth but may emerge in the next eight to ten days, especially in hyperthyroidism when the mother has been on treatment. Close monitoring throughout pregnancy and for the first ten days postpartum is required to minimize risks to the fetus and neonate. Most pregnancies associated with thyroid disease will have a successful outcome. If the occasional at-risk fetus is to be identified and treated successfully there should ideally be close cooperation between obstetrician, endocrinologist and paediatrician.     

Diagnosis and management of gestational hypertension and preeclampsia

Gestational hypertension and preeclampsia are common disorders during pregnancy, with the majority of cases developing at or near term. The development of mild hypertension or preeclampsia at or near term is associated with minimal maternal and neonatal morbidities. In contrast, the onset of severe gestational hypertension and/or severe preeclampsia before 35 weeks' gestation is associated with significant maternal and perinatal complications. Women with diagnosed gestational hypertension-preeclampsia require close evaluation of maternal and fetal conditions for the duration of pregnancy, and those with severe disease should be managed in-hospital. The decision between delivery and expectant management depends on fetal gestational age, fetal status, and severity of maternal condition at time of evaluation. Expectant management is possible in a select group of women with severe preeclampsia before 32 weeks' gestation. Steroids are effective in reducing neonatal mortality and morbidity when administered to those with severe disease between 24 and 34 weeks' gestation. Magnesium sulfate should be used during labor and for at least 24 hours postpartum to prevent seizures in all women with severe disease. There is an urgent need to conduct randomized trials to determine the efficacy and safety of antihypertensive drugs in women with mild hypertension-preeclampsia. There is also a need to conduct a randomized trial to determine the benefits and risks of magnesium sulfate during labor and postpartum in women with mild preeclampsia.     

Connective tissue disorders and dermatological disorders in pregnancy

Connective tissue disorders, particularly those that are autoimmune, are being seen with increasing frequency in the pregnant population. The care of these patients in pregnancy ranges from the routine to the complicated, with some of the conditions posing significant risks both to the mother and the fetus.Dermatological conditions are often encountered in pregnancy, and again range from the benign to those resulting in serious fetal and maternal morbidity, with a number being specific to pregnancy.An important issue for both groups of disorders is the use of particular medications during pregnancy. Those with pre-existing disease should ideally be counselled pre-pregnancy to optimize treatment and adjust medication as appropriate. During pregnancy, frequency of review and degree of treatment will depend on the severity of the condition, and may require multidisciplinary team involvement to optimize both maternal and fetal outcomes.     

Making Sense Out of the Controversy: Use of SSRIs in Pregnancy

Perinatal depression complicates up to 20 % of all pregnancies. Selective serotonin reuptake inhibitor (SSRI) drugs have become the first-line treatment of depressive symptoms during pregnancy. About 7.5 % of all pregnancies are currently exposed to psychotropic medications. Recent studies suggest the SSRI medications may have some detrimental effects in pregnancy, including a possible increased risk of miscarriage, preterm delivery, clubfoot, heart defects, brain and craniofacial abnormalities, persistent pulmonary hypertension of the newborn, neonatal seizures, low neonatal Apgar score, as well as neurodevelopmental and behavioral changes. Patients and healthcare providers should take into consideration all the possible known negative effects of untreated depression during pregnancy, but also the possible fetal risks associated with the use of SSRIs.     

Connective tissue and dermatological disorders in pregnancy

Connective tissue disorders, particularly those that are autoimmune, are being seen with increasing frequency in the pregnant population. The care of these patients in pregnancy ranges from the routine to the complicated, with some of the conditions posing significant risks both to the mother and the fetus. Dermatological conditions are often encountered in pregnancy, and again range from the benign to those resulting in serious fetal and maternal morbidity, with a number being specific to pregnancy. An important issue for both groups of disorders is the use of particular medications during pregnancy. Those with pre-existing disease should ideally be counselled pre-pregnancy to optimize treatment and adjust medication as appropriate. During pregnancy, frequency of review and degree of treatment will depend on the severity of the condition, and may require multidisciplinary team involvement to optimize both maternal and fetal outcome, including obstetric physicians, obstetricians, anaesthetists, neonatologists, and geneticists.     

Common Sleep Disorders: Management Strategies and Pregnancy Outcomes

Sleep disorders, prevalent in industrialized countries, are associated with adverse health outcomes such as hypertension, diabetes, and obesity. Disturbed sleep during pregnancy is frequently overlooked by health care providers, yet recent studies suggest there is an association between sleep disorders and adverse pregnancy outcomes, including preeclampsia, elevated serum glucose, depression, prolonged labor, and cesarean birth. Growing evidence indicates that the recognition and management of prenatal sleep disorders may minimize adverse pregnancy outcomes and improve maternal and fetal well‐being. This focused review of prenatal sleep disturbance literature suggests there are 3 main sleep disorders of interest: breathing‐related sleep disorders (ie, habitual snoring and obstructive sleep apnea), restless legs syndrome, and insomnia. These sleep disorders are common in pregnancy and have maternal and fetal consequences if left untreated. This article describes sleep disorders of pregnancy, elucidates their relationship with maternal and neonatal outcomes, and presents current evidence regarding diagnostic and management strategies.