Opioid dependence and pregnancy: minimizing stress on the fetal brain.

Increase in the number of opioid-dependent pregnant women delivering babies at risk for neonatal abstinence syndrome prompted a US Government Accountability Office report documenting deficits in research and provider knowledge about care of the maternal/fetal unit and the neonate. There are 3 general sources of dependence: untreated opioid use disorder, pain management, and medication-assisted treatment with methadone or buprenorphine. A survey of methadone patients' experiences when telling a physician of their pregnancy and opioid dependence demonstrated physician confusion about proper care, frequent negative interactions with the mother, and failures to provide appropriate referral. Patients in pain management were discharged without referral when the physician was told of the pregnancy. Methadone and buprenorphine were frequently seen negatively because they "caused" neonatal abstinence syndrome. Most mothers surveyed had to find opioid treatment on their own. How dependence is managed medically is a critical determinant of the level of stress on both mother and fetus, and therefore another determinant of neonatal health. The effects of both opioid withdrawal stress and maternal emotional stress on neonatal and developmental outcomes are reviewed. Currently, there have been efforts to criminalize maternal opioid dependence and to encourage or coerce pregnant women to undergo withdrawal. This practice poses both acute risks of fetal hypoxia and long-term risks of adverse epigenetic programming related to catecholamine and corticosteroid surges during withdrawal. Contemporary studies of the effects of withdrawal stress on the developing fetal brain are urgently needed to elucidate and quantify the risks of such practices. At birth, inconsistencies in the hospital management of neonates at risk for neonatal abstinence syndrome have been observed. Neglect of the critical role of maternal comforting in neonatal abstinence syndrome management is an iatrogenic and preventable cause of poor outcomes and long hospitalizations. Rooming-in allows for continuous care of the baby and maternal/neonatal attachment, often unwittingly disrupted by the neonatal intensive care unit environment. Recommendations are made for further research into physician/patient interactions and into optimal dosing of methadone and buprenorphine to minimize maternal/fetal withdrawal.

Sex Matters in Neuroinfectious Diseases.

Although sex and gender have a major impact on the susceptibility and immunologic response to infectious diseases, these factors are often neglected. Identifying the mechanisms underlying sex-based differences in infectious diseases will facilitate the rational design and implementation of preventive and therapeutic strategies that reduce risk and improve outcomes for women and men. In this article, we discuss two examples in neuroinfectious diseases of how sex matters: (1) the heightened risk of cerebrovascular disease in women living with HIV infection and (2) the implications of Zika virus infection on sexual and reproductive health and vaccine development for women.

Geburtshilfe: kombinierte Spinal-Epidural-Analgesie (CSE).

Due to intrathecal application, CSE combines rapid response with adequate analgesia with the possibility of providing unlimited neuraxial obstetrical pain relief via the indwelling epidural catheter. The superiority of CSE over EDA lies above all in its rapid action, excellent analgesia, lack of motor blockade after a single intrathecal opioid administration, lower rate of unilateral blockages and less need for subsequent epidural injections. The most common side effect is pruritus, which is harmless and usually does not require any therapeutic intervention. Even if no effect on rate of C-sections and APGAR values have been observed, the increased rate of fetal bradycardia after CSE must be kept in mind. A reduction of these fetal bradycardias and after intrathecal administration, prolongation of analgesia by means of appropriate drug combinations or additives should be the subject of future research.

Procreation in families with inborn error of metabolism--new challenges for medical care.

Several years ago genetic counseling with the estimation of the risk of the disease in the next pregnancies of the same parents was the only offer for the family with a child with an inborn error of metabolism (IEM). Nowadays diagnostics and treatment of IEM improve. So there are more and more adult patients thinking about having their own offspring. Each woman with IEM who wants to have own child needs special medical care from preconception time up to postpartum period. Depending on the type of disease, such elements as the mother's diet and medicines used for her treatment may influence the foetus and child health and development. In the opposite the growing foetus may have an influence on mother's metabolic status and on her health complications. Therefore interdisciplinary team of specialists should be involved in the health care of women with inborn errors of metabolism.

Nutrition in early life, immune-programming and allergies: the role of epigenetics.

Early life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. The associated parallel rise in metabolic diseases including obesity, childhood type 2-diabetes and non-alcoholic fatty liver disease highlights the interplay between modern dietary patterns and increasing abnormalities of both immune and metabolic health. The low-grade inflammation that characterize these non-communicable diseases (NCDs) suggests a central role of the immune system in the pathogenesis of these conditions. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programing is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While epigenetic mechanism provides a strong explanation of how nutritional exposures can affect the fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients such as folic acid levels, which have clear epigenetic effects on programming. Here we examine the current knowledge of the nutritional-programming of immune health and how research into nutritional-epigenetics in the context of allergic disease as one of the earliest onset NCDs can expand our knowledge to discover the biological processes sensitive to nutritional exposures in early life to prevent later disease risk.

[Dermatoses of pregnancy]. / Terhességi dermatosisok.

Pregnancy is associated with hormonal, metabolic, immunologic, haemodynamic and vascular changes which produce physiological and pathological cutaneous manifestations. Most skin disorders during pregnancy represent physiological changes. The specific dermatoses of pregnancy are disease entities almost exclusively related to the pregnancy or the postpartum period. Some dermatoses characteristically improve or exacerbate during pregnancy. Dermatoses of pregnancy can potentially be a serious risk to the foetus. Although the foetal outcome is almost always favourable, early diagnosis and prompt treatment are essential. Use of any medication during pregnancy should be carefully considered, and as few medications as possible should be administered. In this review, the authors discuss the various dermatoses of pregnancy in detail, based on novel classification, aetiology and pathogenesis, diagnostic approach, disease course, prognosis, foetal risk and therapy.

Long-term outcome after intrauterine laser treatment for twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) is a severe complication occurring in about 10% of monochorionic twin pregnancies. The chronic unbalanced transfusion of blood across placental vascular communications from the donor to the recipient twin may lead to impairment of various organ systems in the affected twins. In Hamburg, Germany, since 1995 patients with TTTS were treated with fetoscopic laser coagulation as the first causal therapeutic strategy. All survivors after laser surgery were followed up in the University Children's Hospital in Bonn, Germany. In this article, we summarize long-term follow-up studies from our German study population and compare our results with data from the literature.

Melatonin for the prevention of fetal injury associated with intrauterine inflammation.

Intrauterine inflammation is shown to be associated with preterm birth, fetal inflammatory response syndrome, and other pregnancy-related comorbidities such as central nervous system diseases including cerebral palsy and periventricular leukomalacia, pulmonary diseases such as bronchopulmonary dysplasia and respiratory distress syndrome, and necrotizing enterocolitis, to name a few. Many animal studies on intrauterine inflammation demonstrate that ascending infection of reproductive organs or the production of proinflammatory cytokines by some stimuli in utero results in such manifestations. Melatonin, known for its primary function in maintaining circadian rhythm, is now recognized as one of the most potent antioxidant and anti-inflammatory drugs. In some studies, melatonin injection in pregnant animals with intrauterine inflammation significantly reduced the number of preterm births, the severity of structural disintegration of the fetal lungs observed in bronchopulmonary dysplasia, and perinatal brain injuries with improvement in neuromotor function. These implicated benefits of melatonin in pregnant women with intrauterine inflammation seem promising in many research studies, strongly supporting the hypothesis that melatonin has antioxidative and anti-inflammatory properties that can potentially be taken by pregnant women who are at risk of having intrauterine inflammation. In this review, the potential of melatonin for improving outcomes of the pregnancies with intrauterine inflammation will be discussed.

The benefits of transplacental treatment of isolated congenital complete heart block associated with maternal anti-Ro/SSA antibodies: a review.

Isolated congenital complete atrio-ventricular block (CAVB) is associated with the transplacental passage of maternal autoantibodies directed to foetal Ro/SSA ribonucleoproteins. Their interactions most likely trigger the inflammation of the atrio-ventricular node and the myocardium in susceptible foetuses. The inflamed tissues may then heal with fibrosis that may cause heart block, endocardial fibroelastosis, and dilated cardiomyopathy. CAVB, the most common cardiac complication, typically develops between 18 and 24 gestational weeks. Untreated, the condition carries a significant mortality risk as the foetus needs to overcome the sudden drop in ventricular rate, the loss of normal atrial systolic contribution to ventricular filling, and perhaps concomitant myocardial inflammation and fibrosis. The rationale to treat a foetus at the stage of CAVB is primarily to mitigate myocardial inflammation and to augment foetal cardiac output. Maternal dexamethasone administration has been shown to improve incomplete foetal AV block, myocardial dysfunction, and cavity effusions. Beta-sympathomimetics may be useful to increase the foetal heart rate and myocardial contractility. Published data from our institution suggest an improved survival >90% if maternal high-dose dexamethasone was initiated at the time of CAVB detection and maintained during the pregnancy and if a beta-adrenergic drug was added at foetal heart rates below 55 beats/min. Despite the improvement in outcome, there is an ongoing debate about treatment-related risks. In this review, we will appraise the natural history of untreated CAVB, discuss currently available management options, and examine the results and risks of in-utero treatment of antibody-mediated CAVB.

Third trimester fetal intracranial hemorrhage owing to vitamin K deficiency associated with hyperemesis gravidarum.

In rare cases, severe fetal vitamin K deficiency bleeding may occur in utero as a result of insufficient vitamin K placental transfer. We present a case of a 32-week-preterm infant born with severe intracranial hemorrhage to a pregnant woman who suffered from hyperemesis gravidarum. Neonatal hematologic status was compatible with vitamin K deficiency whereas the maternal coagulation function was normal. This case emphasizes the potential risk of fetal bleeding owing to vitamin K deficiency in pregnancies complicated with hyperemesis gravidarum. These women should be closely monitored and vitamin K prophylaxis might be considered.

Hyperthyroidism during pregnancy.

QUESTION: I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 times daily. She was initially treated with propylthiouracil but was switched to methimazole owing to urticaria. I have heard about birth defects in infants whose mothers used methimazole during pregnancy. How safe is it? ANSWER: In North America, propylthiouracil has been the drug of choice for hyperthyroidism during pregnancy. Methimazole is widely used in Europe, South America, and Asia, and is an alternative for patients who cannot tolerate propylthiouracil. Some case reports raised concern about fetal toxicity from methimazole, which is reportedly characterized by aplasia cutis, esophageal atresia, choanal atresia, facial abnormalities, and mental retardation. However, causality is unclear and the overall risk of congenital abnormalities in infants exposed to methimazole in utero was not higher than in those exposed to nonteratogenic drugs in cohort studies. It is important for a pregnant woman to continue methimazole, if necessary, because uncontrolled hyperthyroidism increases the risk of complications such as preterm labour and low birth weight.

[Successful outcome of a pregnancy with an extremely low fetal heart rate (34 bpm) due to isolated complete heart block--case report]. / Pomyslne zakonczenie ciazy u plodu ze skrajnie wolna czynnoscia komór (34/min.) w przebiegu izolowanego calkowitego bloku przedsionkowo-komorowego--opis przypadku.

Isolated complete congenital heart block (CHB) in the majority of cases is associated with the presence of autoantibodies to SSA (Ro) and SSB (La) antigens in the maternal serum. The prognosis is less favorable in fetuses with a ventricular rate < 55bpm. We have reported a case of a fetus with an isolated non-autoimmune CHB with an extremely low ventricular rate (34bpm) in which the outcome was favorable. In the neonate the non-compaction of the myocardium was diagnosed.

[Clinical guideline for the diagnosis and treatment of subclinical thyroid dysfunction in pregnancy. Working Group on Subclinical Thyroid Dysfunction of the Spanish Endocrinology Society]. / Guía clínica para el diagnóstico y el tratamiento de la disfunción tiroidea subclínica en la gestación. Grupo de Trabajo sobre la Disfunción Tiroidea Subclínica de la Sociedad Española de Endocrinología.

Subclinical thyroid disease is a biochemical diagnosis and is common during pregnancy. Because of the physiological hormonal changes that take place during pregnancy and the absence of normal ranges for thyroid hormones during this period, subclinical thyroid disease is difficult to interpret during pregnancy. Subclinical hyperthyroidism during pregnancy has few clinical consequences and no treatment is required. In contrast, subclinical hypothyroidism seems to improve with thyroxine treatment. Iodine supplements during pregnancy and lactation, even in iodine-sufficient areas, are also indicated.

Perinatal stroke: mechanisms, management, and outcomes of early cerebrovascular brain injury.

Perinatal stroke encompasses a heterogeneous group of focal neurological injuries early in brain development that probably affects more than 5 million people worldwide. Many such injuries are symptomatic in the first days of life, including neonatal arterial ischaemic stroke, cerebral sinovenous thrombosis, and neonatal haemorrhagic stroke. The remaining focal neurological injuries usually present later in the first year with motor asymmetry, such as arterial presumed perinatal ischaemic stroke, periventricular venous infarction, and presumed perinatal haemorrhagic stroke. The numerous sequelae of these injuries include hemiparesis (cerebral palsy), epilepsy, and cognitive, language, and behavioural challenges. In this Review we summarise each perinatal stroke disease, examining the epidemiology, pathophysiology, acute management, and outcomes, including the effect on parents and families, and emerging therapies to mitigate these lifelong morbidities.

RETIRED: Teratogenicity associated with pre-existing and gestational diabetes.

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Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn - review on current management and outcome.

INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) remains a serious pregnancy complication which can lead to severe fetal anemia, hydrops and perinatal death. Areas covered: This review focusses on the current prenatal management, treatment with intrauterine transfusion (IUT) and promising non-invasive treatment options for HDFN. Expert commentary: IUTs are the cornerstone in prenatal management of HDFN and have significantly improved perinatal outcome in the past decades. IUT is now a relatively safe procedure, however the risk of complications is still high when performed early in the second trimester. Non-invasive management using intravenous immunoglobulin may be a safe alternative and requires further investigation.

Rapid growth of a fetal sacrococcygeal teratoma in an HIV-infected woman: a case report.

BACKGROUND: Sacrococcygeal teratoma, the most common congenital neoplasm of the newborn, associated with fetal hydrops and high morbidity and mortality related to the secondary effects of the tumor mass, is of unknown etiology. Prompt diagnosis and early treatment have proven to be effective. CASE: A 24-year-old woman, gravida 3, para 2, at 385/7 weeks' gestation, with a pregnancy complicated by HIV diagnosed during pregnancy, seizure disorder and tobacco use, presented with premature rupture of membranes. Ultrasound examination at 17 weeks' gestation showed normal fetal anatomy. Cesarean delivery was complicated by difficulty delivering a live infant with a large sacral mass. Successful surgical excision of a 650-g mass and stabilization of the infant occurred in the neonatal period. CONCLUSION: This is the first case report to describe a rapidly growing sacrococcygeal teratoma in a neonate from a pregnancy complicated by HIV. Ultrasound in the first and second trimesters identified no fetal abnormalities of the spine. Further research concerning sacrococcygeal teratoma and HIV in pregnancy is necessary for prompt and early diagnosis and treatment of antepartum and peripartum complications.

[Current problems in the treatment of Graves' disease in pregnancy and in lactation].

In Graves' patients complicated by pregnancy, both maternal and fetal problems related to the disease can be reduced or avoided by controlling hyperthyroidism. However, optimal treatment for mothers may exert detrimental effects on fetuses. Methimazole may cause "methimazole embryopathy". Antithyroid drug doses that maintain mothers in euthyroid status are sometimes excessive fetuses. Furthermore, successful treatment with surgery or radioiodine occasionally may result in fetal hyperthyroidism due to TSH receptor antibody(TRAb). There are approaches to manage these problems. Propylthiouracil is chosen in treating Graves' disease in early pregnancy. In later pregnancy, maternal free thyroxine is maintained near or somewhat above normal. Ablative therapy is not recommended in women whose TRAb levels are extremely high from the standpoint of fetal thyroid state.