Pregnancy and inborn errors of metabolism

Increasing number of patients with inborn errors of metabolism (IEM) are now reaching adulthood and are in position to reproduce. Because of the rarity of individual disorders our knowledge of risks factors associated with pregnancy is limited. Obstetrics problems in IEM can be divided into two categories: pregnancy effects on maternal metabolic disorders and relation between mother and fetus related to who of them is affected. Detrimental effects upon the fetus may be directly caused by maternal disease, as it occurs in PKU, or indirectly by maternal supplementation with harmful substrate, as occurs in galactosemia. Less commonly, fetal inborn error of metabolism may affect the mother's health. Pregnancies in which the fetus had long-chain hydroxyacyl-CoA dehydrogenase deficiency have been complicated by life-threatening HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) or AFL (acute fatty liver of pregnancy) during third trimester. The management of labor and the postpartum period (for women and newborns) has to be carefully planned to avoid significant metabolic decompensation.     

Pituitary and adrenal disorders complicating pregnancy

PURPOSE OF REVIEW: Confidential enquiries of maternal deaths in the UK for 1997-1999 revealed that the number of indirect deaths from medical conditions exacerbated by pregnancy was greater than deaths from conditions directly caused by pregnancy. Indirect maternal deaths accounted for 36% of all deaths. Although neoplastic disorders of the pituitary and adrenal glands are very rare during pregnancy, they can be potentially fatal. The rarity of these disorders may pose difficulty in formulating an optimum plan of management. Biochemical tests that can be performed in the non-pregnant state may be of little value during pregnancy. The presence of a fetus may also influence the type and timing of intervention. RECENT FINDINGS: A few case reports have been reported in the literature, but unfortunately no large series to develop guidelines or protocols. However, endoscopic surgical procedures have recently been used in their management with good outcomes. New drugs such as octreotide and lanreotide are increasingly being used during pregnancy. Although too soon to assess the safety of these new treatments, results so far have been very encouraging. SUMMARY: Awareness of these potentially fatal neoplastic disorders of the pituitary and adrenal glands, coupled with early diagnosis and appropriate treatment, may help improve maternal and fetal outcomes. Advances in imaging techniques and endoscopic procedures are also likely to change clinical practice. Various new treatment options are being reported in the literature, but they are not supported by randomized, controlled trials. Further research is needed to determine their safety and efficacy during pregnancy.     

Connective tissue and skin disorders in pregnancy

Connective tissue disorders are multisystem diseases which most frequently present in young women. They are therefore relatively common in pregnancy and are a challenge to the treating physician. These disorders may affect both mother and baby. Women should be cared for in specialized clinics with the appropriate expertise.Skin disorders are either preexisting, co-incidental or specific to pregnancy. Some of these disorders may have harmful effects on the fetus and therefore appropriate diagnosis is mandatory.In this article, we aim to review current knowledge and the practical management of connective tissue and skin disorders in pregnant women. The possible adverse fetal and neonatal effects of the diseases and the drugs used during pregnancy and breast-feeding are also considered.     

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.     

Pregnancy and bronchial asthma

Asthma is one of the most common potentially serious medical problems to complicate pregnancy. Issues commonly raised by the clinician caring for the pregnant asthmatic patient include: 1) effects of pregnancy on asthma; 2) effects of asthma on pregnancy, and 3) management of asthma in pregnancy. Recent asthma medication carries less risk to the fetus than a severe asthma attack. Inadequately treated asthma can cause maternal and fetal hypoxaemia, which leads to complications during pregnancy and poorer birth outcomes.     

Hormone therapies in pregnancy

Maternal endocrine disorders can have detrimental effects on the fetus and the pregnancy can affect the course of a pre-exisiting endocrinopathy or induce the onset of one of these disorders. Therapies for endocrine disorders are not always safe to administer during pregnancy. Before administering any therapy to the mother, the effects on the fetus, the degree of placental trespassing as well as the potential damaging effects must be assessed. An accurate evaluation of the risks/benefits of any drug to be used on the mother is needed, assessing above all a potential theratogenic effect. In this review, the incidence of the main endocrine disorders, their evolution during pregnancy, their effects on mothers and fetuses and new acquisition on the treatment during pregnancy are discussed.     

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.     

Anxiety disorders during pregnancy and postpartum

Approximately 30% of women experience some type of anxiety disorder during their lifetime. Women with these disorders may experience profound changes in their symptoms during pregnancy and the postpartum period. In addition, some evidence exists that anxiety disorders can affect pregnancy outcomes. It is important that physicians understand the course of these disorders during pregnancy and available treatments so they can appropriately counsel women who are or intend to become pregnant. This article reviews the literature on the course of anxiety disorders during pregnancy and the postpartum period and presents guidelines for management.     

Review: Placental derived biomarkers of pregnancy disorders

Pregnancy is one of the greatest physiological challenges that a women can experience. The physiological adaptations that accompany pregnancy may increase the risk of developing a number of disorders that can lead to both acute and chronic physiological outcomes. In addition, fetal development may be impaired and, if the fetus survives, the child may be at an increased risk of disease throughout life. Pregnancy disorders are poorly predicted by traditional risk factors and maternal history alone. The identification of biomarkers that can predict incidence and severity of disease would allow for improved and targeted prophylactic therapies to prevent adverse maternal and fetal outcomes. Many of these pregnancy disorders, including preeclampsia, intrauterine growth restriction, gestational diabetes mellitus and preterm birth are known to be regulated at least in part by poor trophoblast invasion and/or dysregulated placental function. Cellular stress within the placenta increases the release of a number of factors into the maternal circulation. While many of these factors minimally impact maternal biology, others affect key physiological systems and contribute to disease. Importantly, these factors may be detected in physiological fluids and have predictive capacity making them ideal candidates as biomarkers of pregnancy disorders. This review will discuss what is known about these placental derived biomarkers of pregnancy disorders and highlight potential clinical opportunities for disease prediction and diagnosis.     

Placenta, umbilical cord and amniotic fluid: the not-less-important accessories

The placenta and umbilical cord are crucial to the survival and well-being of the fetus. In fact, disorders of either of these may lead to fetal death or severe morbidity. Yet, they are often not accorded appropriate attention in the prenatal sonographic examination. Similarly, the amniotic fluid often reflects the state of fetal health. Frequently, disorders of the placenta, umbilical cord, and amniotic fluid are picked up during routine ultrasound examination. Without ultrasound, these problems would not be detected and might jeopardize the pregnancy. Detection allows interventions that may improve perinatal and maternal outcomes. However, not infrequently, controversial findings, of uncertain significance, demonstrated on routine sonography lead to anxiety and worry. The goal of this chapter is to address the normal appearances of the placenta, cord, and fluid and to describe several of the more common conditions affecting these structures that the clinician may have to deal within pregnancy.     

Parasitic infections in pregnancy

Parasitic infections affect tens of millions of pregnant women worldwide. These infections lead directly and indirectly to a spectrum of adverse maternal and fetal/placental effects. With the increase in global travel, healthcare providers will care for women who have recently moved from or traveled to areas where these infections are endemic. We reviewed the literature, assessing case reports, case series, and prospective and retrospective trials, to provide guidelines for management of common parasitic infections in pregnancy. Parasitic infections tend to preferentially affect 1 part of the maternal-fetal unit. Thus, we categorize parasitic infections into those that preferentially cause harm to the mother, preferentially affect the fetus, and preferentially affect the placenta. TARGET AUDIENCE: Obstetricians and Gynecologists, Family Physicians, and Nurse Midwives. LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to differentiate immune modulators associated with parasitic infection and their relationship to adverse pregnancy outcomes; assess the specific effects of certain parasitic infections on the gravid female, her placenta, and her fetus; and in addition, design a treatment regimen for pregnant women presenting with a parasitic infection.     

Maternal experience of musculoskeletal pain during pregnancy and birth outcomes: Significance of lower back and pelvic pain

Aimto examine the association between back and pelvic pain during pregnancy and birth outcomes.Backgroundback and pelvic pain during pregnancy is a common occurrence. It is known to affect maternal functioning and well-being during pregnancy and can persist postnatally and beyond. However, there has been little examination of the impact upon birth outcomes such as birth mode, duration of labour and pain experience.Methodfive hundred and eighty mothers with an infant aged zero to six months completed a retrospective questionnaire documenting their pain during pregnancy and birth outcomes (e.g. mode, duration, interventions, perception of pain). Participants also rated overall pain and pain in specific body regions for each of the three trimesters. Estimations of fetal position before birth were given.Findingshigher pain ratings during the third trimester of pregnancy were associated with increased incidence of caesarean section, assisted delivery and a longer duration of labour. Specifically, lower back and pelvic pain were associated with an increase in complications, potentially due to occurrence of malpositioning of the fetus during pregnancy.Conclusionmothers who experience high levels of pain during pregnancy may be at increased risk of complications during labour. Explanations for this may be physiological, mechanical or psychological but greater awareness should be given to the potential impact of maternal pain ratings during pregnancy upon birth outcomes.     

Trastornos respiratorios del sueño en la gestación y sus implicaciones maternofetales

The association between sleep disorders during pregnancy and perinatal outcomes is essential for good maternal childcare. Adverse changes in the course of pregnancy due to sleep disorder can be permanent and structural in infants. Sleep disorders are rare in women of childbearing age, but several factors can contribute to making it more common during pregnancy. The lack of information and training for pregnant women, means that they do not give significant importance to this disorder.     

Psychiatric disorders in pregnancy

Psychiatric disorders are common in pregnancy and can be associated with a range of adverse outcomes, including maternal death. Early identification and, where appropriate, referral to a specialist mental health service, is the key to successful management. Women with more severe psychiatric disorders, such as bipolar affective disorder, schizophrenia and moderate to severe depression, benefit from a shared management approach involving obstetric, primary care and specialist mental health services, formalized within a written perinatal care plan. Large numbers of women take psychotropic medication during pregnancy, but when it represents an appropriate alternative to medication, timely psychological treatment is the preferred approach for a range of psychiatric disorders. When medication is used, it should be based on a risk/benefit analysis that takes appropriate notice of the dangers of stopping or avoiding medication as well as any risk to the exposed fetus. All decisions about the management of a psychiatric disorder should involve the pregnant women as a fully informed partner in a shared decision-making approach. This review summarizes general guidance on management for the obstetrician and issues arising in relation to a number of specific psychiatric disorders and specific psychiatric treatments.     

Management of stage I cervical cancer in pregnancy

Although cervical carcinoma is the most common gynecologic malignancy associated with pregnancy, its occurrence is rare with an incidence of approximately 1 per 1,200 to 10,000 pregnancies. There are inadequate data addressing both the obstetric implications of the diagnostic evaluation and the impact of intervention on maternal and infant outcomes. Certain conclusions and recommendations, however, can be drawn from the available data. Diagnostic evaluation includes cytological screening, colposcopy and if necessary, biopsy, and selective conization. Staging of the pregnant patient is modified to minimize radiation exposure to the developing fetus. The treatment schema for patients with stage I cervical cancer in pregnancy varies with the stage of disease and gestational age at diagnosis. With close surveillance, deliberate delay of therapy to achieve fetal maturity is a reasonable option for patients with microinvasive and early stage IB cervical cancer. Tumor characteristics and maternal survival are not adversely affected by pregnancy. Conversely, cervical cancer does not seem adversely to affect pregnancy. However, timing and type of therapy may have a significant influence on the fate of the fetus. In counseling patients with cervical cancer during pregnancy, many factors must be considered, including the patient's desire for the pregnancy, stage of disease, and gestational age at diagnosis. Pregnant patients with stage I cervical cancer should be fully informed of all possible treatment options and consequences. The care of these patients should be closely coordinated by experts in perinatology and gynecologic oncology. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the signs and symptoms of cervical cancer during pregnancy and the indications for conization during pregnancy, as well as being able to outline management strategies for the various stages of cervical cancer during pregnancy.     

Origins of fetal growth restriction

Regulation of growth of the fetus and its placenta begins before pregnancy. Early in pregnancy the mother sets the rate of growth of the fetus on a trajectory, which may be modified by events later in pregnancy.Low maternal weight for height, history of previous small babies, maternal undernutrition, pregnancy disorders, e.g. pre-eclampsia, are associated with low birthweight. Maternal smoking is a major factor in developed countries; infections and undernutrition in developing countries.Recently, there has been emphasis on adverse long-term outcomes including ischaemic heart disease, hypertension and diabetes associated with poor fetal growth. Experimental studies in animals show that some of these outcomes can readily be induced by restriction of fetal growth.Progress in determining successful treatments to improve the growth of the fetus has lagged behind these epidemiological and experimental findings. However, nutrient supplements improve growth in undernourished women and smoking cessation also improves fetal size and outcome.     

Exercise during pregnancy: a critical appraisal of the literature

To review the effects of exercise during pregnancy on fetal and maternal outcomes, a selective literature search was performed using MEDLINE, the Cochrane Database and bibliographies from relevant articles to identify additional references. The data on exercise during pregnancy are limited but suggest that moderate exercise during a low-risk pregnancy does not lead to adverse outcomes for the fetus or mother and improves overall maternal fitness and well-being. The data examining the impact of exercise on labor outcomes, maternal weight gain and fetal weight are conflicting. Moderate exercise in the low-risk pregnancy improves maternal well-being and does not seem to have adverse effects on the fetal or maternal outcome. However, further studies are needed.     

Impact of pregnancy on complications of insulin-dependent diabetes mellitus

The effects of pregnancy on acute metabolic complications of diabetes may have important consequences for both mother and fetus. The consequences of pregnancy for chronic complications of diabetes, including retinopathy, nephropathy, neuropathy, and hypertension, are not clear. Recent data are reviewed so that health care providers will be able to provide reasonable advice to insulin-dependent diabetic women contemplating pregnancy both for problems that may potentially arise during gestation and those that may affect long-term health and survival. Diabetic ketoacidosis is an uncommon problem that arises during gestation. Acute alterations in pH and electrolyte concentrations as well as hyperglycemia, however, may have important consequences for mother and fetus, including perinatal asphyxia and reduced fetal oxygen delivery. Hypoglycemia, on the other hand, may result in maternal coma or seizures and, when frequent, has been associated with infant respiratory distress syndrome. Background retinopathy often worsens during gestation, with regression common postpartum. Data suggest that progression of background disease is related to both glycemic control and the acute institution of intensive insulin therapy with those patients with poor control requiring more aggressive therapeutic intervention most adversely affected. The course of proliferative retinopathy is more variable, with both progression and regression reported. Preconception photocoagulation may prevent progression. Preconceptional ophthalmologic evaluation with frequent assessments during pregnancy is advised. Increases in 24-hour protein excretion are common during gestation in patients with preexisting renal disease and resolve in many patients postpartum. Serum creatinine and creatinine clearance increase during the first trimester and generally do not change during the remainder of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anticoagulants

Pregnancy is a period of heightened coagulability and enhanced risk for thrombotic complications. Thromboembolism is the leading cause of maternal mortality. Anticoagulants are very useful during pregnancy for the acute treatment of venous thromboembolism and for the prevention of recurrent venous thromboembolism. They may also be beneficial in patients with thrombophilias, particularly among women who have experienced adverse pregnancy outcomes such as recurrent pregnancy loss. Anticoagulation is essential but problematic in the management of pregnant women with mechanical heart valve prostheses. When utilizing these medications among pregnant women the potential benefits must be balanced against the possibility of maternal haemorrhagic complications, adverse effects on the pregnancy or toxic effects on the fetus. This chapter summarizes current knowledge about the anticoagulant agents, their potential toxicities and their therapeutic role in pregnant women with various indications for anticoagulant therapy.     

妊娠期高浓度血红蛋白对妊娠结局的影响

妊娠期母体血液系统发生一系列生理变化以适应胎儿生长发育,血液总容量增加并有一定程度的血液稀释。如果妊娠期血液不能有效稀释,血红蛋白浓度过高,会引起血液黏度增加,全身血液循环不能适应子宫-胎盘血流的需要。其结果可能导致子宫-胎盘血流量减少、减慢,而引起子宫胎盘缺血缺氧、血管痉挛、血压升高等,而发生妊娠期高血压疾病、小于胎龄儿、早产、低出生体质量、妊娠期糖尿病、死产等。综述妊娠期高浓度血红蛋白对不良妊娠结局的影响, 以引起对妊娠期高浓度血红蛋白的重视。