Inflammatory bowel disease: management issues during pregnancy

Introduction Inflammatory bowel disease often affects women during their reproductive years, causing management concerns for obstetricians caring for these patients during pregnancy. Treatment Apart from methotrexate, most drugs used regularly to treat ulcerative colitis and Crohn's disease can safely be used by pregnant women. No causal relationship has been established between exposure to sulfasalazine or other 5-aminosalicylic acid drugs and the development of congenital malformations and these drugs may be used with relative safety during pregnancy and lactation. Current evidence indicates that maternal use of azathioprine and mercaptopurine is not associated with an increased risk of congenital malformations, though impaired foetal immunity, intrauterine growth retardation and prematurity are occasionally observed. Cyclosporin is not teratogenic, but may be associated with growth retardation and prematurity. Conclusions Pregnancy should be avoided in women treated with methotrexate because of its known abortifacient effects and risk of causing typical malformations. There is no actual evidence of adverse effect in pregnant women receiving Infliximab but the amount of clinical information is small. The treatment with metronidazole or ciprofloxacin for short durations appear to be safe, but there is no data about the effects of increased length of treatment as required in Crohn's disease remains unknown. Control of disease activity before conception and during pregnancy is critical to optimise both maternal and foetal health. A multidisciplined approach involving both obstetrician and gastroenterologist and education about pregnancy are essential components of the treatment of any young women with IBD.     

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.     

Should we continue or stop insulin sensitizing drugs during pregnancy?

PURPOSE OF REVIEW: The use of insulin sensitizing drugs such as metformin in polycystic ovary syndrome has been increasingly popular and validated by systematic reviews. There has also been an interest in the use of metformin for gestational diabetes. However, administration of metformin to prevent miscarriage is controversial and widespread use of this drug in early pregnancy requires investigation. RECENT FINDINGS: There are claims that miscarriage and gestational diabetes are more common in polycystic ovary syndrome and that use of insulin sensitizers improves outcomes dramatically. This review suggests there is no evidence for increased risk of miscarriage solely due to polycystic ovary syndrome and that there are insufficient data for promoting therapy with metformin. There is some reason for use of metformin in mid-pregnancy for gestational diabetes but better evidence from randomized controlled trials is urgently needed. SUMMARY: The use of metformin in early pregnancy for reducing the risk of miscarriage should be avoided outside of the context of properly designed prospective randomized trials. Safety in early pregnancy appears to be reassuring but not completely proven. The use of metformin in mid-pregnancy for gestational diabetes appears more logical but also needs adequate trials before general use is advocated.     

Myasthenia gravis: management issues during pregnancy

Myasthenia gravis (MG) often affects women in the second and third decades of life, overlapping with the childbearing years. The course of the disease is unpredictable during pregnancy; however, worsening of symptoms occurs more likely during the first trimester and postpartum. MG can be well managed during pregnancy with relatively safe and effective therapies. Anticholinesterase drugs are the mainstay of treatment, when MG symptoms are not satisfactorily controlled, corticosteroids, azathioprine and in some cases cyclosporin A can be used. Until information is available regarding safety, mycophenolate mofetil should be discontinued before pregnancy. Pregnancy should be avoided in women treated with methotrexate because of the risk of causing typical malformations. Plasmapheresis and intravenous immunoglobulins have been successfully used in the treatment of MG crisis during pregnancy. Caesarean section is recommended only for obstetric reasons; forceps delivery and vacuum extraction are sometimes required. Epidural anesthesia is advised to reduce physical and emotional stress. MG during pregnancy can lead to serious life-threatening conditions, including respiratory insufficiency; therefore, intensive checkups by a gynaecologist and a neurologist are necessary. Women with myasthenia gravis should not be discouraged from conceiving; however, they should discuss their plan for pregnancy with their neurologist and their gynaecologist.     

Respiratory disease in pregnancy

Breathlessness in the absence of an underlying pathology is common in pregnancy. Asthma affects about 7% of women of childbearing age. Treatment is the same as for the non-pregnant population and most drugs are safe in pregnancy. Educating women to continue preventer inhaled corticosteroid therapy will reduce the risk of attacks. Respiratory infections are associated with a higher morbidity in pregnancy and should be treated aggressively. Most chronic pulmonary diseases do not alter fertility. Large reserves in respiratory function allow the fetus and mother to survive without compromise in most cases. The use of chest X-rays should not be avoided in pregnancy. Women with a chronic respiratory disease should receive pre-pregnancy counselling and education. Women should be managed in a multidisciplinary setting with the respiratory team. The presence of pulmonary hypertension and cor pulmonale is associated with a high risk of death in pregnancy.     

Respiratory disease in pregnancy

Breathlessness in the absence of an underlying pathology is common in pregnancy. Asthma affects about 7% of women of child-bearing age. Treatment is the same as for the non-pregnant population and most drugs are safe in pregnancy. Educating women to continue preventer inhaled corticosteroid therapy will reduce the risk of attacks. Respiratory infections are associated with a higher morbidity in pregnancy and should be treated aggressively. Most chronic pulmonary diseases do not alter fertility. Large reserves in respiratory function allow the fetus and mother to survive without compromise in most cases. The use of chest X-rays should not be avoided in pregnancy. Women with a chronic respiratory disease should receive pre-pregnancy counselling and education. Women should be managed in a multidisciplinary setting with the respiratory team. The presence of pulmonary hypertension and cor pulmonale is associated with a high risk of death in pregnancy.     

妊娠合并类风湿性关节炎对母胎的影响及诊治

类风湿性关节炎是一种自身免疫性疾病,在妊娠期,疾病症状有所缓解,而在产后加重,这种现象可能是多种机制作用的结果。妊娠期抗风湿药物的使用受到限制,其用药应依据病情活动性和避免对母儿的毒副反应进行,非甾体抗炎药、柳氮磺胺吡啶、羟氯喹和肿瘤坏死因子（TNF）抑制剂由于被证明在妊娠期使用较安全,可以用来治疗妊娠合并类风湿性关节炎。     

Respiratory disease in pregnancy

Breathlessness in the absence of an underlying pathology is common in pregnancy, but serious causes should be excluded depending on symptoms. The use of chest X-rays should not be avoided in pregnancy.Asthma affects about 7% of women of child-bearing age. Treatment is the same as for the non-pregnant population and most drugs are safe in pregnancy. It is important to educate women to continue inhaled corticosteroid preventer therapy to reduce the risk of attacks. Respiratory infections are associated with a higher morbidity in pregnancy and should be treated aggressively.Women with a chronic respiratory disease should receive pre-pregnancy counselling and education, and during pregnancy managed in a multidisciplinary setting with the respiratory team. Most chronic pulmonary diseases do not alter fertility, and in the majority of cases large reserves in respiratory function allow a good pregnancy outcome for fetus and mother. In contrast, the presence of pulmonary hypertension and cor pulmonale is associated with a high risk of death in pregnancy.     

Chronic hypertension in pregnancy

Pregnant women with chronic hypertension are at risk for maternal and perinatal morbidity. Careful assessment and management of these patients during pregnancy are the keys to reducing maternal and fetal complications. Antihypertensive treatment should be used in women with high-risk chronic hypertension, whereas drug therapy does not improve pregnancy outcome in women at low risk. Prophylactic low-dose aspirin started early in pregnancy in women with chronic hypertension is not effective in reducing the frequency of superimposed preeclampsia and should be avoided.     

Psychiatric and nervous disorders

There has recently been increased occasions to treat patients complicated with psychiatric and nervous disorders, in accordance with the rise of interest in human right and the improved social acceptance of these diseases. In the past, most cases were reluctantly terminated because of the prejudice against diseases and anxiety about the teratogenicity of the drugs. In this paper, the management of pregnancy and delivery including neonatal period are discussed. 1) Epilepsy Epilepsy is one of the most common medical complications of pregnancy with about 0.5%. Pregnancy has no obvious effect on epilepsy. Although the teratogenicity of the antiepileptic drugs has been repeatedly reported, anticonvulsant therapy should be continued during pregnancy. Because the risk of the fetal brain damage from hypoxia under the epileptic convulsion of the untreated patients is higher than that of the teratogenicity of drugs. Phenobarbital or phenytoin are commonly used. Trimethadione which has been used for the petit mal epilepsy should not be used because of the high potent of teratogenicity. The serum concentrations of these drugs tend to decrease in the third trimester. Therefore the frequent monitoring of the serum drug concentration is very important. The monitoring of the blood clotting factors after delivery is also very important to avoid the neonatal vitamin K deficiency bleeding. Vitamin K is administered if required. Breast feeding is not contraindicated. Withdrawal syndrome in the neonatal state should not be overlooked. 2) Schizophrenia Pregnancy has no effect on schizophrenia. The teratogenicity of chlorpromazine or haloperidol in human pregnancy is thought to be negative. The function of the fetal central nervous system is suppressed with antipsychotic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy

Depression is a common condition among women of reproductive age, and selective serotonin reuptake inhibitors (SSRIs) are frequently used for the treatment of depression. However, recent reports regarding SSRI use during pregnancy have raised concerns about fetal cardiac defects, newborn persistent pulmonary hypertension, and other negative effects. The potential risks associated with SSRI use throughout pregnancy must be considered in the context of the risk of relapse of depression if maintenance treatment is discontinued. The American College of Obstetricians and Gynecologists' Committee on Obstetric Practice recommends that treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible.     

Preterm delivery: an overview

Preterm delivery is the leading factor causing neonatal mortality and morbidity. We have conducted a PubMed literature search to obtain an update on the etiology, diagnostic problems and therapeutic considerations of preterm delivery. Approximately 5-10% of all births are premature. Preterm labor is associated with preterm rupture of membranes, cervical incompetence, polyhydramnion, fetal and uterine anomalies, infections, social factors, stress, smoking, heavy work and other risk factors. The diagnosis is made on the patients presenting symptoms, clinical findings and of progressive effacement and dilatation of the cervix. Biochemical markers of preterm delivery are of minor importance in daily clinical work. Measurement of the cervix, however, is a practical and valuable tool to predict preterm delivery. Cervical cerclage can be useful in selected cases. Antibiotics may help to prevent preterm labor in cases of known etiologic agents (e.g. preterm rupture of membranes and urinary infection). The use of tocolytic agents such as beta-sympathetic receptor stimulators can be advocated for a few days. There is evidence that their long-term use is not beneficial and could even be harmful to the fetus. Calcium channel blockers (nifedipine) and a new selective oxytocin receptor antagonist, atosiban, appear to be as effective as beta-sympathomimetic drugs on uterine contractions with fewer side-effects. Prostaglandin synthetase inhibitors such as indomethacin may prevent uterine contractions and can be used prior to the 32nd week of pregnancy. A single course of corticosteroid treatment in two doses of 12 mg betamethasone or 6 mg of dexamethasone is important for the prevention of respiratory distress between the 24th and 34th weeks of pregnancy. Multiple doses may be harmful and should be avoided. In these cases management should depend on gestation age (fetal maturity). Uterine contractions after 34 weeks' gestation are not an indication for tocolytic treatment.     

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.     

Chemotherapie in der Schwangerschaft

In the majority of women diagnosed with breast cancer in pregnancy adjuvant or neoadjuvant chemotherapy is indicated. Administration of chemotherapy should not start before 14 weeks of gestation when fertilization, implantation and organogenesis have been completed. An earlier start with cytotoxic drugs results in a higher rate of miscarriage, fetal death and major malformations. The use of anthracyclines and taxanes is possible in the second and third trimester. These substances seem to have a good safety profile but there is a need for more data about the long-term outcome in children with prenatal exposure to chemotherapy, particularly about a higher risk for malignancies, sterility and cardiotoxicity. Trastuzumab is currently not recommended in any trimester during pregnancy.     

Drugs in pregnancy. 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.     

Should multifetal pregnancy reduction be used for prevention of preterm deliveries in triplet or higher order multiple pregnancies?

This article reviews the arguments for the use of multifetal pregnancy reduction (MFPR) for the prevention of preterm deliveries in triplet and higher order multiple pregnancies and evaluates its effectiveness based on data from published studies. The arguments in favour of pregnancy reduction are based on the substantial mortality and morbidity associated with these pregnancies. Triplets and higher order multiples have increased rates of preterm delivery and intrauterine growth retardation, both of which are independent risk factors for death and handicap. Even controlling for gestational age, rates of mortality and handicap are higher for multiples than for singletons. Moreover, the family's risk of losing a child or having a handicapped child is greater because there are more infants at risk. MFPR effectively lowers these risk by reducing the frequency of preterm delivery. However, its effectiveness may be limited. In some studies, the proportion of preterm deliveries in reduced pregnancies remains above levels found in spontaneous twin or singleton pregnancies and MFPR does not appear to reduce the prevalence of low birth weight. Furthermore, the procedure itself has unwanted side effects: it increases the risk of miscarriage, premature rupture of the membranes and causes adverse psychological effects such as grief or depression for many patients. The authors note that a majority of the higher order multiple pregnancies result from a medical intervention in the first place, either through IVF techniques or the use of ovulation stimulation drugs. Although MFPR is an effective measure for reducing the substantial morbidity and mortality associated with higher order multiple pregnancies, preventive methods, such as limiting to 2 the number of embryos transferred for IVF and better control of the use of ovulation induction drugs, remain more effective and less intrusive.     

Interval delivery and aggressive tocolysis in high-order multiple gestation. A report of three cases

BACKGROUND: High-order multiple pregnancy (four and above) should be avoided if at all possible. The major fetal risk of high-order multiple gestation is that of extreme prematurity. Interval delivery has been used with twin and triplet pregnancies. CASES: An octuplet, sextuplet and quadruplet pregnancies were managed with interval delivery. The interval from delivery of the first infant to the remainder of pregnancy was 12 days for the octuplet pregnancy, 24 for the sextuplet pregnancy and 12 for the quadruplet pregnancy. CONCLUSION: In high-order multiple pregnancy, delayed interval delivery is strongly recommended, provided that there are no signs of chorioamnionitis, fetal distress or maternal compromise.