[DGRh recommendations for the implementation of current security aspects in the NSAID treatment of musculoskeletal pain]. / DGRh-Empfehlungen zur Implementierung aktueller Sicherheitsaspekte in die NSAR-Therapie muskuloskelettaler Schmerzen.

NSAIDs exert their anti-inflammatory and analgesic effects by inhibition of COX­2, a key enzyme for proinflammatory prostanoid synthesis. Therapy with NSAIDs is limited by their typical gastrointestinal, cardiovascular and renal side effects, which are caused by inhibition of COX­1 (gastrointestinal toxicity), COX­2 (cardiovascular side effects) or both COX-isoenzymes (renal side effects). Appropriate prevention strategies should be employed in patients at risk. If gastrointestinal risk factors are present, co-administration of a proton pump inhibitor or misoprostol is recommended; in patients with cardiovascular risk, coxibs, diclofenac and high-dose ibuprofen should be avoided. Furthermore, drug interactions and contraindications should be considered. In patients with renal impairment (GFR < 30 ml/min) all NSAIDs must be avoided. Ulcer anamnesis is a contraindication for traditional NSAIDs. Preexisting cardio- or cerebrovascular diseases are contraindications for coxibs. Treatment decisions should be individually based with a continuous monitoring of the risk - benefit ratio and exploitation of non-pharmacological treatment options.

Short-term placebo response in trials of patients with symptomatic osteoarthritis: differences between hip and knee.

BACKGROUND: In placebo-controlled RCT of symptomatic treatment in osteoarthritis (OA) the extent of pain reduction is heterogeneous, the pooled effect size rather small. Pain reduction is typically higher in knee than in hip trials. The recommended trial duration is 3 months, but in knee OA the best treatment effect vs placebo is observed at 2 weeks. We hypothesized that the placebo response differs in knee vs hip OA. OBJECTIVE: We performed a meta-analysis to describe the time course of pain in placebo groups of trials in knee and hip OA over 3 months. METHODS: A systematic search of PubMed, MEDLINE and Google Scholar of placebo-controlled cox-2 inhibitor (coxib) RCT (from 1999 to 2007) of hip and knee OA was performed. Pain levels (visual analogue scale [VAS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the placebo groups at different measurement time points were extracted, expressed as weighted mean at weeks 2, 4, 6-8 and 12-13. RESULTS: Twenty-one studies included 3064 knee OA patients and 608 hip OA patients. For knee OA, pain (VAS) decreased from 15 mm at week 2, to 20 mm at week 6-8, and 21 mm at week 12-13. For hip OA patients, pain decreased by 12 mm, 14 mm and 14 mm, respectively. CONCLUSION: Pain decreased in both knee and hip OA patients treated with placebo at 2 weeks, but further decreases up to week 12 occurred only in knee OA, especially for pain VAS, resulting in a time dependent impact on the magnitude of treatment outcome. Primary endpoint pain should be assessed at 2-4 weeks.

Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement.

OBJECTIVE: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). DESIGN: Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. RESULTS: It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). CONCLUSIONS: This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA.

Republished: Value of biomarkers in osteoarthritis: current status and perspectives.

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.

Value of biomarkers in osteoarthritis: current status and perspectives.

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.

Evaluation of different protocols for gene transfer into non-obese diabetes/severe combined immunodeficiency disease mouse repopulating cells.

PURPOSE: Although gene transfer with retroviral vectors has shown distinct clinical success in defined settings, efficient genetic manipulation of hematopoietic progenitor cells remains a challenge. To address this issue we have evaluated different transduction protocols and retroviral constructs in the non-obese diabetes (NOD)/severe combined immunodeficiency disease (SCID) xenograft model. METHODS: An extended transduction protocol requiring 144 h of in vitro manipulation was compared to a more conventional protocol requiring 96 h only. RESULT: While pretransplantation analysis of cells transduced with a retroviral vector, expressing the enhanced green fluorescent protein (EGFP) marker gene, demonstrated significantly higher overall transduction rates for the extended protocol (33.6 +/- 2.3 vs. 22.1 +/- 3.8%), EGFP expression in CD34+ cells before transplantation (4.0 +/- 0.9 vs. 11.6 +/- 2.5%), engraftment of human cells in NOD/SCID bone marrow 4 weeks after transplantation (4.5 +/- 1.7 vs. 36.5 +/- 9.4%) and EGFP expression in these cells (0 +/- 0 vs. 11.3 +/- 2.8%) were significantly impaired. When the 96 h protocol was used in combination with the spleen focus forming virus (SFFV)/murine embryonic stem cell (MESV) hybrid vector SFbeta11-EGFP, high transduction rates for CD45+ (41.0 +/- 5.3%) and CD34+ (38.5 +/- 3.7%) cells prior to transplantation, as well as efficient human cell engraftment in NOD/SCID mice 4 weeks after transplantation (32.4 +/- 3.5%), was detected. Transgene expression was observed in B-lymphoid (15.9 +/- 2.0%), myeloid (36.5 +/- 3.5%) and CD34+ cells (10.1 +/- 1.5%). CONCLUSION: Our data show that CD34+ cells maintained in cytokines for multiple days may differentiate and loose their capacity to contribute to the haematological reconstitution of NOD/SCID mice. In addition, the SFFV/MESV hybrid vector SFbeta11-EGFP allows efficient transduction of and gene expression in haematopoietic progenitor cells.

Pregnancy in congenital cardiac disease: an increasing challenge for cardiologists and obstetricians -- a prospective multicenter study.

OBJECTIVES: Aim of this study was to assess the occurrence of pregnancy-related complications of mother and child during pregnancy, delivery and puerperium in women with CCD prospectively. STUDY DESIGN, POPULATION: This prospective multicenter study included 122 pregnancies in 106 women with CCD (72 with, 34 without previous cardiac surgery). Patient age was 17-44, median 26 years. Cardiac and non-cardiac complications, mode of delivery, abortion, and CCD of the newborn were assessed. RESULTS: Initially all women were in Functional Class I or II. Worsening during pregnancy occurred in 25.5% (n=27), mainly during the second and third trimester. Significant problems due to bleeding, hypertension, rhythm disturbances, endocarditis, liver congestion, increasing cyanosis or death, occurred in 11.3%. Twelve per cent of deliveries were premature. Five women had therapeutic abortion, nine spontaneous abortions, nine preterm births, and one intrauterine death. Seventy-nine per cent (n=85) delivered spontaneously; 21.3% (n=23) had caesarean section. Of the 111 live born children, 5.4% (n=6) had a CCD. CONCLUSIONS: Most women with CCD and a good functional class before pregnancy tolerate pregnancy without major problems. However, pregnancy may induce serious cardiac and obstetric complications. The specific risks require an individualized multidisciplinary patient-management by experienced physicians.

[The course of hypertension in pregnancy]. / Verlaufsform der Hypertonie in der Schwangerschaft.

Pregnancy-included hypertension (PIH) and chronic hypertension are the most common medical disorders during pregnancy. They are a major cause of maternal and neonatal morbidity and mortality. Therefore a correct diagnosis and the knowledge of the classification of hypertension are necessary to choose the best treatment for the mother and the child. This review presents the guidelines for the diagnosis and management of the different forms of PIH.

Outcome of 22 successful pregnancies after liver transplantation.

To evaluate course and outcome of pregnancies in liver transplanted patients and to provide a brief summary on the development of these children, 22 pregnancies and 23 children (1 month-99 months old) of 16 patients who had been liver transplanted at our institution (mean interval from transplantation to pregnancy 43.1 months) were reviewed. Standard immunosuppressive regimen during pregnancy consisted of cyclosporine A (CyA), tacrolimus (FK), azathioprine (Aza) and/or a low-dose steroid therapy. CyA and FK whole blood trough levels were monitored on a routinely basis to keep therapeutic range (CyA 80-150 ng/mL; FK 4-8 ng/mL). No patient had a graft loss and there were no lethal complications. Beside de novo hypertension (n = 3) and preeclampsia (n = 3) problems during pregnancy included one steroid-sensitive rejection at 36 wk gestation, one case of tacrolimus toxicity at 24 wk with complete reconstitution, and one case of de novo choledocholithiasis with recurrent cholangitis. Three cases of infections occurred. In total, 23 children, including one set of twins, were born. Terms of gestation (mean = 38.1 wk, +/- 2.2 SD), deliveries (spontaneous n = 13, cesarean section n = 7, forceps n = 1, vacuum extraction (VE) n = 1) and birth weights (2876 g, +/- 589.3 SD) were typical. Three pregnancies were preterm, one being a twin pregnancy. Neither congenital malformations nor unusual infections were seen in the children. Postnatal follow-up revealed appropriate physical growth to date. Psychological development seems to be adequate. Our data indicate that successful pregnancies after liver transplantation (LTX) under careful management by transplant specialists, obstetricians and perinatalogists have a good outcome. So far, neither pre- nor postnatal child development appear to be influenced by maternal immunosuppressive therapy during pregnancy.

[Wilson disease and pregnancy. Review of the literature and case report]. / Morbus Wilson und Schwangerschaft. Literaturübersicht und kasuistische Mitteilung.

Wilson's disease is an autosomal recessive disorder of copper metabolism. Since the introduction of penicillamine treatment successful pregnancies have been reported. However little is known about the risks of breast feeding in patients on this medication. We describe the case of a patient suffering from Wilson's disease, who had two uncomplicated pregnancies and breast fed both children for a period of three months each. In the 22 year old gravida I para I the diagnosis of Wilson's disease had been previously made by liver biopsy and penicillamine therapy had been begun. At the time of her first presentation at our department she was 8 week pregnant. Her renal and liver function were normal. Neurologic or psychiatric symptoms were not observed. At 18 weeks the dosage of penicillamine was reduced from 900 mg/d to 750 mg/d. The course of the pregnancy remained uneventful. At 38 + 1 weeks a healthy boy of 3100 gm was delivered. 19 months later the patient presented again in the 16th week of her second pregnancy. Concerning Wilson's disease no major changes were observed, especially liver and renal function were not impaired. The dosage of penicillamin was reduced from 900 mg/d to 750 mg/d during the 21st week. The pregnancy again was uncomplicated and at 38 + 2 weeks resulted in the spontaneous deliver of a healthy boy, weighting 3940 gm. Both children were breast fed over a period of three months and with the exception of an icterus prolongatus no adverse effects were noted.

[Prevalence of hepatitis B in pregnancy and selective screening]. / Prävalenz der Hepatitis B in der Schwangerschaft und selektives Screening.

Infants of mothers positive for HBsAg are at risk for peripartal transmission of hepatitis B infection. Active and passive immunisation administered immediately after birth can prevent neonatal hepatitis B. In a prospective study the prevalence of hepatitis B in pregnant women and the efficiency of selective antepartal screening of women with identifiable risk factors for hepatitis B were analysed. From November 1992 to May 1994, 912 women presenting at the department of obstetrics and gynaecology of the Medizinischen Hochschule Hannover were tested for HBsAg, HBeAg, anti HBs, anti Hbc, and HBV-DNA. Venous blood samples were taken during the third trimester of pregnancy or immediately post partum. 13 (1.4%) patients were found to be HBsAg positive. The prevalence of HBsAg in German females and women from countries with low endemia for hepatitis B was 0.38% versus 5.7% for women from endemic areas. HBeAg was detected in two patients. 10 patients with a positive serological result belonged to groups considered to be of increased risk for hepatitis B infection. Nevertheless, 6 of these women had not undergone antepartal screening. These findings support a need for routine screening of all pregnant women for HBsAg, as it has been recently introduced in Germany.

-Obstetric prognosis after pre-eclampsia, eclampsia or HELLP syndrome-. / Geburtshilfliche Prognose nach Präeklampsie, Eklampsie under HELLP-Syndrom.

Preeclampsia, eclampsia and the HELLP syndrome are serious pregnancy complications associated with increased maternal and perinatal mortality and morbidity. The question of subsequent pregnancy outcome in these patients is of great importance for the patient and the obstetrician. The risk of recurrence of hypertensive complications during subsequent pregnancy is related to the time of the onset and the clinical signs of hypertension during the first pregnancy. Patients having hypertensive pregnancies should be examined for chronic hypertension, kidney disease and other internal diseases. The recurrence risk is for preeclampsia between 19.5% and 25.9% and for eclampsia between 21.9% and 46.8%. Patients developing the disease early in pregnancy and with chronic hypertension are at higher risk. For the HELLP syndrome the risk of recurrence is between 3% and 5%. These patients should be considered to be at increased risk for obstetric complications in subsequent pregnancies and close perinatal care is indicated in subsequent pregnancies.

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

[Estriol and human placental lactogen as risk indicators in pregnancies of diabetic and hypertensive patients]. / Ostriol und Humanes Plazentares Laktogen als Risikoindikatoren in Schwangerschaften von Diabetikerinnen und Hypertonikerinnen.

The correlation between estriol (E3) and human placenta lactogen (HPL) and perinatal morbidity was investigated in 105 diabetic, 96 hypertensive and 96 pregnancies without diabetes and hypertension. The hormones were determined by radioimmunoassay. Only if two determinations were outside the normal range the values were accepted as pathological. In pregnancies with hypertension a decrease of E3- and HPL-concentrations was correlated to significant higher incidence of operative deliveries and pathological APGAR-Scores. In the diabetic group is the low E3-concentration of significant predictive value in respect of the pathological cardiotocography as the indication of the operative delivery, the same applies to low HPL-concentrations in the hypertension group, in the control group no significant differences could be determined relating thereto. Hypotrophic newborns in the hypertension and control group are significant more frequent, if the concentration of E3 is decreased. The same applies to decreased HPL-concentrations in every group, where the hypertension group shows the highest predictive values.

[Influence of non-diabetic pregnancy on fructosamine and HbA1c concentration]. / Der Einfluss der nichtdiabetischen Schwangerschaft auf die Fructosamin- und HbAIc-Konzentration.

HbAIc and fructosamine concentrations were measured in the course of 177 nondiabetic pregnancies and compared with the corresponding values of 24 nondiabetic nonpregnant women. In all three trimesters HbAIc and fructosamine were significantly lower than the corresponding values in the nonpregnant women; HbAIc: 1st trimester 4.77 +/- 0.62%, 2nd trimester 4.38 +/- 0.59%, 3rd trimester 4.33 +/- 0.49%, p < 0.01; fructosamine 1st trimester 2.13 +/- 0.17 mmol/l, 2nd trimester 2.02 +/- 0.15 mmol/l, 3rd trimester 1.90 +/- 0.15 mmol/l, p < 0.01; nonpregnant women: HbAIc 5.13 +/- 0.41%, fructosamine 2.53 +/- 0.17 mmol/l. However, if the fructosamine is correlated to the respective total protein concentration a constant value results for the course of pregnancy. The changes in the HbAIc and fructosamine concentrations in pregnancy should be taken into account when treating pregnant diabetics.

[Atrial natriuretic peptide in normotensive pregnancy: concentrations in physical stress, pre- and postpartal and in the umbilical cord]. / Das atriale natriuretische Peptid in der normotensiven Schwangerschaft: Konzentrationen unter körperlicher Belastung, prä- und postpartal und in der Nabelschnur.

The concentrations of the atrial natriuretic peptide (ANP) during the 3rd trimester of pregnancy (n = 54), the 1st, 2nd, and 3rd day post partum and in 10 non pregnant females were measured and compared. Moreover ANP was determined in the umbilical cord (artery n = 10, vein n = 48) and the influence of exercise on the concentration of ANP in pregnant (n = 10) and non pregnant women (n = 10) was analyzed. There was no significant difference of the ANP-values measured in non pregnant patients and during the third trimester (100 +/- 57 vs. 97 +/- 27 pg/ml). On the 3rd day post partum a significant rise of ANP was noted (1st day post partum 78 +/- 43, 3rd day post partum 102 +/- 46, 5th day post partum 84 +/- 40 pg/ml). During physical exercise the concentration of ANP increases significantly in pregnant (103 +/- 45 vs. 120 +/- 57 pg/ml, p < 0.05) as well as in non pregnant females (97 +/- 27 vs. 111 +/- 39 pg/ml, p < 0.05). In arterial blood samples from the umbilical cord the concentration of ANP was higher than in venous cord blood (62 +/- 34 vs. 51 +/- 28 pg/ml, p > 0.05).

-Glucose, insulin and C-peptide kinetics during tocolysis with oral fenoterol-. / Glukose-, Insulin- und C-Peptid-Kinetik unter Tokolyse mit oralem Fenoterol.

OBJECTIVE: The effect of oral fenoterol therapy (40 mg/day) on the kinetics of glucose, insulin and C-peptide during an oral glucose tolerance test (oGTT; 100 g glucose) was investigated in the third trimester. METHODS: 54 patients without tocolytic therapy (25 with a pathologic oGTT) were compared with 36 patients who received tocolytic therapy (18 patients with a pathologic oGTT). RESULTS: The patients with a normal or pathologic oGTT and with or without tocolytic therapy showed no significant differences in respect of the concentrations of glucose, insulin and C-peptide. During tocolytic therapy, an early increase in insulin was observed as well as slightly elevated C-peptide concentrations and a decreased C-peptide/insulin quotient.

Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions.

Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.

[Pregnancy and congenital heart failure]. / Schwangerschaft und angeborene Herzfehler.

While in the past, rheumatic heart disease accounted for the largest number of pregnant women with heart disease, the incidence has declined over the years. On the other hand, because of advances in medical treatment and surgical management, the ratio of adolescent females with congenital heart disease increased significantly during the last decade. Pregnancy is associated with many physiologic adjustments such as changes in blood volume, stroke volume, and cardiac output, and may result in deleterious clinical effects in patients with congenital heart disease. Although a good outcome for these women can often be expected, congenital heart disease still presents a high-risk pregnancy involving both mother and infant. The actual risk depends on the type of malformation and functional impairment of the mother. To bring these women safely through pregnancy, a strong cooperation between pediatric and adult cardiologists, obstetrician, and other physicians is necessary.