Pregnancy In Female Patients Research Articles

Pregnancy-Related Outcomes in Patients with Congenital Thrombotic Thrombocytopenic Purpura: Post Hoc Analysis of a Retrospective Chart Review Study

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening inherited deficiency of the von Willebrand factor-cleaving metalloprotease, ADAMTS13, leading to consumptive thrombocytopenia due to microvascular thrombosis. Symptoms typically present either in early infancy, in adulthood during pregnancy, or in association with systemic infections, periods and conditions in life that are associated with an increased risk of acute cTTP episodes. Prophylaxis with plasma or plasma-derived therapies to replenish ADAMTS13 are commonly used. Limited evidence is available about the clinical burden of cTTP among female patients during pregnancy. Aims: A chart review was undertaken to gain insight into the natural history of cTTP, short- and long-term clinical outcomes, burden of disease, and treatment patterns. A post hoc analysis aimed to assess the clinical characteristics, treatment patterns and outcomes of patients with cTTP during pregnancy. Methods: An international, multi-center, retrospective chart review collected data from January 01, 2009 to December 31, 2020. Patients with cTTP were included if they were diagnosed with cTTP, received therapeutic intervention for cTTP, or had a cTTP-related clinical event recorded between January 01, 2009 and December 31, 2017 (index identification period). Patients were followed from their study index date until loss to follow-up, enrollment in a clinical trial, death, or the end of the study period. Ethics approval and informed consent were obtained where applicable. Data presented are from a post hoc analysis which assessed clinical characteristics and outcomes during pregnancy in female patients who were >14 years of age at study index. Results:A total of 78 patients with cTTP were identified during the index identification period and included in the analysis, 61 (78%) were female and the median (IQR) age at diagnosis was 26.5 (14.5-37.0) years. Overall, 92 acute episodes were reported by 55 of the 78 patients included in the analysis. Triggers for acute episodes were recorded in 46 of the 92 episodes, with infection (n=21/46) and pregnancy (n=17/46) being the most common. Prophylaxis was administered in 47/78 patients, with pregnancy (n=13/47) and clinical symptomatology (n=13/47) being the most common reasons to initiate prophylaxis. Information regarding pregnancy was collected from 55 female patients who were aged >14 years at study index. Of these 55 patients, 45 reported ≥1 pregnancy and 30 were diagnosed with cTTP during or immediately after pregnancy. One or more pregnancy-related complications were reported by 26/45 patients who were ever pregnant. The most common complication was fetal death or pregnancy loss which was reported in 16/45 patients (Table 1). Of the 55 female patients >14 years of age at study index, 41 had documented acute episodes during the study period, of whom 22 were pregnant at the time an episode occurred. Each of these 22 patients experienced 1 acute episode while pregnant during the study. Twenty-six pregnancy-related complications were reported during 18 of these 22 acute episodes (Table 2). The most frequently reported were fetal death or pregnancy loss (n=8), hemolysis, elevated liver enzymes and low platelet count (n=7; HELLP syndrome), and pre-eclampsia (n=6). A total of 54 treatments (plasma exchange [PEX], fresh frozen plasma [FFP], steroids, red blood cell transfusion, platelet transfusion, caesarean section, intravenous immunoglobulins, rituximab, and hemodialysis) were received by the 22 pregnant patients who experienced an acute episode while pregnant during the study period. Forty-four treatments were administered for acute episodes associated with pregnancy-related complications. Of the 54 treatments administered, PEX (n=15/54) and FFP (n=11/54) were the most common. Conclusions: Data from this chart review show that a high proportion of pregnant patients with cTTP experience pregnancy-related complications which could result in poor fetal and maternal outcomes. Pregnancy is a common trigger for acute cTTP episodes and initiation of prophylaxis. Despite current therapeutic interventions, pregnancy-related complications represent a high clinical burden for cTTP patients. Novel therapies with demonstrated efficacy and safety profiles are needed to address the poor clinical outcomes experienced by pregnant patients with cTTP.

Fertility Trends and Adverse Pregnancy Outcomes in Female Patients With Psoriasis in the UK

Evidence regarding fertility trends and obstetric outcomes among patients with psoriasis is limited by studies of small sample sizes, noninclusion of comparators, and the lack of accurate pregnancy records. To investigate fertility rates and obstetric outcomes of pregnancies in female patients with psoriasis compared with age- and general practice-matched comparators without psoriasis. This population-based cohort study used data from 887 primary care practices that contributed to the UK Clinical Practice Research Datalink GOLD database between 1998 and 2019, linked to a pregnancy register and Hospital Episode Statistics. There were 6 223 298 patients of common childbearing ages (15-44 years), and 63 681 patients with psoriasis had at least 1 year of follow-up data prior to the diagnosis of psoriasis. For each patient with psoriasis, 5 patients were matched by age from the same general practice. The median follow-up duration was 4.1 years. Data analysis was performed in 2021. Patients with psoriasis were identified using clinical diagnostic codes from consultations. Fertility rates were calculated as the number of pregnancies per 100 patient-years. The outcomes of each pregnancy recorded in the pregnancy register or Hospital Episode Statistics were screened to identify obstetric outcomes. A negative binomial model was used to examine the association between psoriasis and the fertility rate. Logistic regression was applied to compare the association between psoriasis and obstetric outcomes. A total of 63 681 patients with psoriasis and 318 405 matched comparators were included in the analysis (median [IQR] age, 30 [22-37] years). Lower fertility rates (rate ratio, 0.75; 95% CI, 0.69-0.83) were found in patients with moderate to severe psoriasis. Compared with matched comparators without psoriasis, pregnancies in patients with psoriasis had a higher risk of loss (odds ratio, 1.06; 95% CI, 1.03-1.10); however, there was no increase in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes. In this cohort study, patients with moderate to severe psoriasis had a lower fertility rate, and the risk of pregnancy loss was higher than in matched comparators without psoriasis. Future research should identify the mechanism of increased risk of pregnancy loss among patients with psoriasis.

Возможности сохранения репродуктивной функции у пациенток с атипической гиперплазией и начальным раком эндометрия

Due to the childbearing shift to the fourth decade of life, the probability of detecting endometrial cancer (EС) in female patients who did not have time to realize their reproductive life plan increases. If cancer is detected in female patients of reproductive age and they want to realize their fertility in the future, this option should be considered at the stage of treatment planning. Discussion concerning the admissibility and safety of conservative EC treatment is extremely relevant in the current demographic conditions. The article considers the decision-making algorithm on the conservative therapy indication in the cancer manifestation in a female patient of reproductive age with unrealized fertility, as well as the protocol when making such a decision. Data on the frequency of pregnancy in female patients after conservative treatment of EC are given. The accumulated experience showed that drug treatment of atypical hyperplasia and initial EC is effective, and upon condition of subsequent pregnancy does not aggravate the oncological prognosis. KEYWORDS: endometrial cancer, uterine cancer, atypical hyperplasia, pregnancy, assisted reproductive technologies, conservative therapy. FOR CITATION: Serova O.F., Dobrokhotova Yu.E., Borovkova E.I., Charkhifalakyan A.V. Possibilities of preserving reproductive function in female patients with atypical hyperplasia and endometrial cancer at an early stage. Russian Journal of Woman and Child Health. 2023;6(4):352–361 (in Russ.). DOI: 10.32364/2618-8430-2023-6-4-5.

Post-authorisation safety study of burosumab use in paediatric, adolescent and adult patients with X-linked hypophosphataemia: rationale and description.

Background:X-linked hypophosphataemia (XLH) is a rare, inherited, phosphate-wasting disorder that elevates fibroblast growth factor 23 (FGF23), causing renal phosphate-wasting and impaired active vitamin D (1,25(OH)2D) synthesis. Disease characteristics include rickets, osteomalacia, odontomalacia, and short stature. Historically, treatment has been oral phosphate and 1,25(OH)2D supplements. However, these treatments do not correct the primary pathogenic mechanism or treat all symptoms and can be associated with adverse effects. Burosumab is a recombinant human immunoglobulin G1 monoclonal antibody against FGF23, approved for treating XLH in several geographical regions, including Europe and Israel. Burosumab restores normal serum phosphate levels, minimising the clinical consequences of XLH. Safety data on long-term treatment with burosumab are lacking owing to the rarity of XLH. This post-authorisation safety study (PASS) aims to evaluate the safety outcomes in patients aged >1 year.Methods:The PASS is a 10-year retrospective and prospective cohort study utilising data from the International XLH Registry (NCT03193476), which includes standard diagnostic and monitoring practice data at participating centres. The PASS aims to evaluate frequency and severity of safety outcomes, frequency and outcomes of pregnancies in female patients, and safety outcomes in patients with mild to moderate kidney disease at baseline, in children, adolescents and adults treated with burosumab for XLH. It is expected that there will be at least 400 patients who will be administered burosumab.Results:Data collection started on 24 April 2019. The expected date of the final study report is 31 December 2028, with two interim reports.Conclusion:This PASS will provide data on the long-term safety of burosumab treatment for XLH patients and describe safety outcomes for patients receiving burosumab contrasted with those patients receiving other XLH treatments, to help inform the future management of XLH patients. The PASS will be the largest real-world safety study of burosumab.Registry identification:The International XLH Registry is registered with clinicaltrials.gov as NCT03193476 (https://clinicaltrials.gov/ct2/show/NCT03193476), and the PASS is registered with the European Union electronic Register of Post-Authorisation Studies as EUPAS32190 (http://www.encepp.eu/encepp/viewResource.htm?id=32191).

MO959KIDNEY TRANSPLANT TRANSITION FROM PEDIATRIC TO ADULT FACILITY CARE: DIFFICULTIES AND RISK FACTORS

Abstract Background and Aims Kidney transplantation (KTx) in pediatric ages is successful, leading to optimal patients and graft survival with indication, in adolescent age, to transition toward an adult transplant facility. To date, the transition process of adolescents and young adults with KTx is not well defined. Transfer to a different medical facility marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Some studies report unexpected loss rates in kidney grafts as high as 24%–42% within 3 years after transfer. In addition, some studies show that the age ranging from 18 to 26 years is the age in which graft losses are most concentrated, an age that coincides with the transition. Several makers have been shown to influence non-adherence rate in kidney transplanted patients during transition: a bad doctor-patient relationship, the absence of specialized centers capable to face these particular needs and care requests, the lack of psychological support, and a low availability of specialized nurses. Moreover, many patients are lost to follow-up as the result of breakdowns in the transition and transfer to adult medical care. Method In this study we enrolled patients transited from the pediatric transplant Centre to the adult transplant nephrological facility between 2017 and 2020. Data of KTx, baseline renal disease, post-transplant medications and post-transplant complications were recorded. Follow-up of renal function were performed and analyzed during the transition process and forward during the adult follow-up. Results Data of 19 patients (pts) were analysed. Six were male (31.6%) and 13 female (68.4%). The cause of renal dysfunction was malformations in 10 patients (52.6%), glomerulonephritis (GN) in 5 pts (26.3%) and genetic syndromes in 4 pts (21.1%). They received the kidney transplantation at a median age of 12 years [IQR 10-18]. Median age at transition resulted 31 years [interquartile range (IQR) 30-33]. Seven pts (36.8%) had a history of post-transplant lymphoproliferative disease (PTLD). All patients were receiving steroids, 11 pts (57.9%) cyclosporine A and 8 pts (42.2%) tacrolimus; only 9 pts (47.4%) were receiving mycophenolate or azathioprine. The median follow-up at the adult Transplant Centre was 1 year [IQR 1-2]. After transition, five patients experienced complications: 2 pts developed PTLD de novo, 2 pts had a recurrence of native GN after reduction of immunosuppression for PTLD and pregnancies (one pt underwent re-tx), 1 pt experienced an acute cellular rejection after transition to another Centre and is developing ESRD. The median eGFR slightly decreased from baseline at transition to the last follow-up (80 ml/min/1.73 m2 at baseline [55-112]; 74 ml/min/1.73m2 at last follow-up [35-98]) but this was not significant (p=0.127). Conclusion Our results confirm that the transition from pediatric to adult transplant Centre is not a simple process. Several factors linked to the patient and to the kidney have to be considered in the development of post-transplant complications: the age of transplantation with long term immunosuppression; infections typical of pediatric ages that may develop in adulthood, such as EBV, that force to modulate immunosuppression exposing the patient to increased risk of rejection or recurrence of native disease; the exposure to different immunological stimuli and physiological events such as pregnancies in female patients. These patients may develop complications linked to non-adherence and low compliance to immunosuppressive medications, but also complications typical of adult age, like arterial hypertension, obesity, diabetes, and dyslipidemias. Therefore, defining effective practices for recipient transition and transfer from pediatric to adult medical care are essential to optimize the KTx patients follow-up and outcome.

Pregnancy in Pateints With Exstrophy-Epispadias Complex: Are Higher Rates of Complications and Spontaneous Abortion Inevitable?

ObjectiveTo report on the characteristics of pregnancy in female patients with EEC (exstrophy-epispadias complex), determining in particular whether they are at higher risk of spontaneous abortion or complications. Materials and methodFifty patients diagnosed with EEC and treated in a reference center for this pathology were reviewed. Those with an incomplete medical history were excluded, leaving a total of 37 women with a median follow-up of 26 years (1-48 years). The outcome measurements were successful pregnancies, miscarriages, urological, gynecological and obstetric complications, impaired renal function, newborn characteristics, and postpartum urogynecological complications. Descriptive statistics was used. ResultsEight patients achieved 17 pregnancies (88.2% spontaneous). Of these pregnancies, 10 (58.8%) were successful, while 7 (41.2%) terminated in miscarriages. Urinary tract infection (UTI) was the most frequent complication (41.6%) and intestinal occlusion was the most severe. A total of 62.5% of the patients presented genital prolapses after pregnancies. A total of 85.7% of patients were dry during the follow-up after their pregnancies. No newborn presented EEC or any other type of malformation. Our study has the limitation of being a retrospective review of a very heterogeneous and small group of patients. ConclusionEEC patients can achieve spontaneous pregnancies but have an increased risk of miscarriage. For this reason, monitoring and control by a specialized and integrated multidisciplinary team is required to minimize complications.

Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association.

It has been 50 years since Francis Fontan pioneered the operation that today bears his name. Initially designed for patients with tricuspid atresia, this procedure is now offered for a vast array of congenital cardiac lesions when a circulation with 2 ventricles cannot be achieved. As a result of technical advances and improvements in patient selection and perioperative management, survival has steadily increased, and it is estimated that patients operated on today may hope for a 30-year survival of >80%. Up to 70 000 patients may be alive worldwide today with Fontan circulation, and this population is expected to double in the next 20 years. In the absence of a subpulmonary ventricle, Fontan circulation is characterized by chronically elevated systemic venous pressures and decreased cardiac output. The addition of this acquired abnormal circulation to innate abnormalities associated with single-ventricle congenital heart disease exposes these patients to a variety of complications. Circulatory failure, ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, protein-losing enteropathy, and plastic bronchitis are potential complications of the Fontan circulation. Abnormalities in body composition, bone structure, and growth have been detected. Liver fibrosis and renal dysfunction are common and may progress over time. Cognitive, neuropsychological, and behavioral deficits are highly prevalent. As a testimony to the success of the current strategy of care, the proportion of adults with Fontan circulation is increasing. Healthcare providers are ill-prepared to tackle these challenges, as well as specific needs such as contraception and pregnancy in female patients. The role of therapies such as cardiovascular drugs to prevent and treat complications, heart transplantation, and mechanical circulatory support remains undetermined. There is a clear need for consensus on how best to follow up patients with Fontan circulation and to treat their complications. This American Heart Association statement summarizes the current state of knowledge on the Fontan circulation and its consequences. A proposed surveillance testing toolkit provides recommendations for a range of acceptable approaches to follow-up care for the patient with Fontan circulation. Gaps in knowledge and areas for future focus of investigation are highlighted, with the objective of laying the groundwork for creating a normal quality and duration of life for these unique individuals.

Planned Pregnancy in Female Patients with Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitor Therapy.

The aim of this study was to explore outcomes of planned pregnancy in female patients with chronic myeloid leukemia (CML) on tyrosine kinase inhibitors (TKIs). Data of female patients proceeding with a planned pregnancy were retrospectively reviewed. A total of 17 patients with CML who achieved at least a major molecular response (MMR) during imatinib (n = 13) or nilotinib (n = 4) therapy prior to a planned pregnancy were enrolled. At the time of TKI interruption, six were in MMR, two in molecular response 4 (MR4), and nine in molecular response 4.5 (MR4.5). TKI therapy was discontinued 6 weeks (range, 2-15 weeks) before conception in 4 patients and at gestational age of 4 weeks (range, 2-5 weeks) after determination of pregnancy in 13 patients. Apart from 1 patient who suffered a spontaneous abortion, 16 patients delivered uneventfully. A total of 10 patients lost MMR after stopping TKIs; 8 lost molecular response 2, and 3 lost complete hematological response. Log-rank analyses showed achieving MR4 (p = .030) or MR4.5 (p = .031), complete cytogenetic response duration ≥3.5 years (p = .049), and MMR duration ≥3.5 years (p = .040) were significantly associated with longer MMR-failure-free survival during TKI interruption. Planned pregnancy might be pragmatic in female patients with CML on TKIs. Achieving deep molecular response and, importantly, MMR duration ≥3.5 years were significantly associated with maintaining MMR during pregnancy. Female patients with chronic myeloid leukemia on tyrosine kinase inhibitors (TKIs) wishing to conceive are currently advised to discontinue TKIs before conception. However, the ideal degree and duration of response before stopping TKI, in addition to whether there will be any adverse effect caused by a short exposure of TKI, is unknown. Data of 17 female patients, who achieved at least a major molecular response (MMR) before TKI interruption, was revised, and it was found that achieving deep molecular response and MMR duration ≥3.5 years was significantly associated with maintaining MMR during pregnancy. This provides direct evidence for a planned pregnancy strategy, and stopping TKI immediately after determination of pregnancy in female patients might be pragmatic.

PF421 PLANNED PREGNANCY IN FEMALE PATIENTS WITH CHRONIC MYELOID LEUKEMIA RECEIVING TYROSINE KINASE INHIBITOR THERAPY

Background:Pregnancy has become an important issue in female patients with chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI). Female patients with CML who wish to conceive are currently advised to discontinue TKI before conception due to the recognized teratogenic effects of TKI. However, it is not known what the ideal degree and duration of response a female patient should achieve before stopping TKI‐therapy for pregnancy. Concrete infant outcomes for female patients who discontinued TKI‐therapy immediately once pregnancy was confirmed are also lacking.Aims:To explore disease and fetal outcomes of planned pregnancy in female patients with CML on tyrosine TKI therapy.Methods:Data of female patients with CML proceeding with a planned pregnancy were retrospectively reviewed.Results:A total of 17 female CML patients who achieved at least a major molecular response (MMR) during imatinib (n = 13) or nilotinib (n = 4) therapy prior to a planned pregnancy were enrolled. At the time of TKI interruption, patients had received TKI‐therapy for a median of 49 months (range, 6–102 months), 6 were in MMR, 2 in MR4, and 9 in MR4.5. TKI‐therapy was discontinued at a median of 6 weeks (range, 2–15 weeks) before conception in 4 patients and at a median gestational age of 4 weeks (range, 2–5 weeks) after determination of pregnancy in 13 patients. Apart from one patient who suffered a spontaneous abortion, 16 patients delivered uneventfully at full term. A total of 10 patients lost MMR at a median of 3 months (range, 1–9 months) after stopping TKI; 8 patients lost MR2 at 4 months (range, 2–7 months) and 3 lost complete hematological response (CHR) at 3 months (range, 3–4 months) after TKI cessation. None of the patients progressed to an advanced phase. Log‐rank analyses showed achievement of MR4 (p = 0.030), MR4.5 (p = 0.031), CCyR (p = 0.049) or MMR duration (p = 0.040) ≥3.5 years were significantly associated with longer MMR‐failure free survival. Each of the 10 patients losing MMR during pregnancy regained MMR at a median of 4 months (range, 2–7 months) after resuming TKI‐therapy, and 1 patient who maintained MR4.5 during pregnancy remained off treatment at 6 months after delivery. All 16 babies that were successfully delivered have continued normal growth and development during a median follow‐up of 19 months (range, 7–78 months).Summary/Conclusion:Planned pregnancy might be safe and practicable in female patients with CML on TKI‐therapy. Achieving deep molecular response and importantly MMR duration ≥3.5 years before conception were significantly associated with maintaining MMR during pregnancy.image

Gimema Registry of Conception/Pregnancy in Adult Italian Patients Diagnosed with Chronic Myeloid Leukemia (CML): Report on 166 Outcomes

Background. The availability of multiple tyrosine kinase inhibitors (TKIs) and precise molecular monitoring has dramatically changed the prognosis in CML patients. With proper medical management, the planning of a pregnancy in both male (M) and female (F) patients is now possible. Towards this goal, the GIMEMA CML working party initiated a retrospective and prospective study to describe all male conceptions/female pregnancy outcomes in the CML Italian population from January 2013.Aims. The specific aims of this study were to analyze conceptions and pregnancies in male and female patients with regard to 3 general issues: 1) Illness issues, including CML treatment prior to conception/during/after pregnancy, transcript kinetics, the recovery of a lost response after therapy cessation, and the effects of treatment modifications (e.g., resistance, switching); 2) Conception/pregnancy issues, including planned, unplanned, spontaneous and medically assisted pregnancies (MAP), spontaneous/elective abortions, pregnancy progression, delivery, and breast feeding; and , 3) Post-natal health issues from birth to walking including speaking and academic performance.Patients and methods. Patients included in the study had to meet the following criteria A) Age >18 yrs; B) Confirmed CML diagnosis; C) Conception or pregnancy; D) TKI treatment before, during and/or after pregnancy; and E) Signed, IRB-approved written informed consent form. Of the 143 enrollees, data were obtained from 135 patients (83M and 52F). A total number of 166 cases were analyzable. Male conceptions were 106, and female pregnancies 60.Results 1) At time of conception 34 patients had no treatment (TF), 8 received interferon-a (IFN), and the remaining were treated with a TKI (Table 1). Considering only female patients, all stopped TKI treatment when pregnancy was discovered at 3-6 weeks (w). After placental maturation (>20w) 13 patients were treated with IFN (10), 2 with Imatinib, and 1 with Nilotinib (N). In this latter patient N concentration was tested in maternal plasma and cord blood at delivery and showed no transfer to the baby. Kinetics of rise was calculated in a subgroup of 17 patients. Doubling time [DT = duration x log(2) /log (final ratio)-log (initial ratio)] exhibits a bimodal trend, very short for some patients (5.8 days mean, range 4.5-8.2) and much longer for others (182 days mean, range 59.2-328.4), This result does not correlate with molecular status pre TF. Furthermore 76.5% of patients will not lose Major Molecular Response during pregnancy, while in TF, that is more than expected when compared to non pregnant controls (TFR). No cases of CML progression or resistance to re-treatment were observed. CML transcript ratios during pregnancy are shown in Fig.1.2) The majority of pregnancies were planned. MAPs were reported in 5M and 3F. Two spontaneous conceptions occurred in 2M after allogeneic transplant. Eleven abortions before 12 w (2 M ,induced; 9F, 5 induced) were reported (not included in the 166 cases). Pregnancies in all cases progressed normally. In F there were 2 pre-eclampsia, 2 oligohydramnios, 1 abruption placenta. In 8M and 8 F babies were born pre term and 1M and 2F were small at birth with no further consequences. Forty-two F (70%) delivered spontaneously. Babies were born at a mean 40 w (34-44) in M, 39 w (33-42) in F. Breast feeding information was collected for 45F of which18 (29%) breast feed for at least one month (range 1-28 mo).3) Post-natal information showed normal child development and growth. One respiratory arrest was noted at birth with rapid recovery and 1 macrocephaly was described with no further consequences. Of the 56 children >3 yrs old attending school (44M,12F), 2M presented with language problems and in one case autism was diagnosed. Other reported outcomes include 1 child diagnosed as having rheumatoid arthritis at 2 yr (F), and 1 diagnosed with celiac disease (M).Conclusions TKI therapy has allowed CML patients to pursue a normal life including planning/managing a family. Males do not need to stop therapy to conceive due to the therapy's non-genotoxic nature, in contrast to females who must cease therapy due to the teratogenic nature of TKIs. Kinetics of regrowth of the CML residual disease during pregnancy in female patients is different than in TFR patients. To our knowledge this is the largest multicentric study regarding CML and reproduction. Results and practical management will be presented. [Display omitted] DisclosuresAbruzzese:Novartis: Research Funding; Pfizer: Consultancy; Ariad: Consultancy; BMS: Consultancy. Castagnetti:Incyte: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Gambacorti-Passerini:Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Rambaldi:Pfizer: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Omeros: Consultancy; Roche: Consultancy; Celgene: Consultancy; Amgen Inc.: Consultancy. Gaidano:Roche: Consultancy, Honoraria; Morphosys: Honoraria; AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.

Outcome of Pregnancies in Female Patients With Inflammatory Bowel Diseases Treated With Vedolizumab.

Vedolizumab is an IgG1 anti-α4β7 integrin antibody approved for the treatment of inflammatory bowel diseases [IBD], but without clear safety data during conception, pregnancy and nursing. Animal studies showed that mucosal vascular addressin cell adhesion molecule 1 [MAdCAM-1] is expressed by maternal vessels in the placenta and recruits α4β7-expressing cells that are considered important for maternal/fetal tolerance. Blocking this interaction by vedolizumab might affect this process. We aimed to evaluate pregnancy outcomes in vedolizumab-treated female IBD patients. We conducted a retrospective, multicentre Belgian observational study. Details on disease activity, prenatal complications, delivery and neonatal outcome were collected through a case report form. Twenty-four pregnancies were reported. Five women had active disease at conception and one patient flared during pregnancy. There were 23 live births. Complications were observed in 25% of pregnancies [premature rupture of membranes, pre-eclampsia, miscarriage, elective termination and stillbirth] and in 35% of infants [prematurity, intra-uterine growth retardation, small for gestational age and congenital malformations including hip dysplasia, pulmonary valve stenosis and Hirschprung's disease]. Vedolizumab was continued throughout pregnancy in two females and stopped in the 1st and 2nd trimester in five and 16 patients, respectively. For live born children, the median [interquartile range] gestational age, weight and Apgar score 5 min after birth were 39 [37-39.6] weeks, 3270 [3080-3585] grams and 10 [9-10], respectively. Although several complications were observed, both in mothers and in newborns, no firm conclusions can be drawn. Awaiting prospective and controlled registries, vigilance and strict follow-up of pregnant patients treated with vedolizumab seems mandatory.

Decision making and outcome of pregnancies in female patients with inflammatory bowel disease: findings from a community-based practice.

The aim of this study was to evaluate information provided on pregnancy, personal decision making, disease course, and outcome of pregnancy from a patient's perspective in a population of patients with inflammatory bowel disease (IBD) attending two general hospitals. A questionnaire was sent to all female patients with IBD in two general hospitals in the Netherlands. The questionnaire comprised four sections: (i) demographic data and medication use (ii) details on previous pregnancies and reasons for not becoming pregnant, (iii) outcome of pregnancies before IBD diagnosis, and (iv) outcome of pregnancies after IBD diagnosis. If necessary, medical records were reviewed to verify responses or for further medical details. In total, 385 women returned the questionnaire, 501 completed pregnancies were reported, and 113 women had never been pregnant. In 272 women with at least one pregnancy, 334 pregnancies occurred before IBD diagnosis, 157 after IBD diagnosis, and in 10 cases, IBD was diagnosed during pregnancy. Medication for IBD was used in 67% of pregnancies after IBD diagnosis, mainly 5-ASA preparations (54%). Women with ulcerative colitis experienced more IBD-related complaints during pregnancy compared with women with Crohn's disease (25 vs. 14%, P=0.016). Additional medication (n=21) or surgery (n=2) for IBD during pregnancy was indicated in 14% of cases. Most women reported an uneventful pregnancy course (79%). Preterm birth occurred in 13% of pregnancies. Pregnancy in women with IBD seen in a general hospital can be managed with a good outcome. Step-up therapy is needed in a minority of cases, and severe complications are rare.

P043 - Pregnancy outcomes in female patients and partners of male patients in the teriflunomide clinical development program

Background/objectives Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis. Consistent efficacy and safety of teriflunomide were demonstrated in a large clinical trial program. Animal data suggest that teriflunomide may be associated with a risk of teratogenicity. Teriflunomide plasma concentrations Design and methods Despite the requirement for reliable contraception, pregnancies were reported across the teriflunomide clinical trial program. Upon discovery of pregnancy, patients were instructed to discontinue treatment and undergo an accelerated elimination procedure. Pregnancy outcomes were collected across phase 2 and 3 clinical studies in the teriflunomide clinical development program and available data through October 2013 are reported. Results Eighty-three pregnancies were reported in female patients and 22 in partners of male patients; 26 live births occurred in female patients and 16 in partners of male patients receiving teriflunomide. Twenty-nine pregnancies in female patients and two in partners of male patients were terminated electively. Newborns whose parents were exposed to teriflunomide were healthy and had no structural defects or functional deficits at birth. Spontaneous abortion rate (18.6%) was within the range for general population. Median birth weight for 18 newborns was 3.3 kg, and mean gestational age at birth among 23 cases was 39 weeks, all within typical ranges for general population. Conclusions Data from the clinical program have shown no teratogenic signals for teriflunomide in humans, consistent with findings of the Organization of Teratology Information Specialists registry and over 2.5 million patient-years of postmarketing data for leflunomide. Further prospective data in the postmarketing setting are being collected in global teriflunomide pregnancy registries.

Pharmacological management of pulmonary arterial hypertension.

Pharmacological management of pulmonary arterial hypertension.

Effect of Pre and Post Nursing Intervention on the Occurrence of Tension Headache among Surgical Patients Undergoing Spinal Anesthesia

Spinal anesthesia is a frequently performed procedure in medical emergencies and anesthesia. Tension headache after lumbar puncture is a common occurrence (32%) and carries a considerable morbidity, with symptoms lasting for several days, at times severe enough to immobilize. The aim of this study is to assess the effect of pre and post nursing intervention on the occurrence of tension headache among surgical patients undergoing spinal anesthesia. This quasi-experimental study was conducted in El-Naser Health Insurance Hospital; in Helwan city in Egypt, 60 adult patients admitted for lower abdominal surgery using spinal anesthesia were recruited. The only exclusion criterion was pregnancy in female patients. Participants were alternatively assigned to either the intervention or control groups, ending with 30 patients in each group. The data collection tools consisted of two tools. Tool 1 was concerned with characterization of the pain and patient’s personal data. The second tool was a visual analog scale (VAS). The researchers designed a structured pre-spinal anesthetic nursing intervention to be applied to the study group. Control group received the routine nursing intervention only. The results revealed that the incidence of tensions headache became significantly lower in the study group, reaching its lowest rate (3.3%) by the end of the third day, compared to 76.7% in the control group (p<0.001) the mean duration of tension headache was shorter in the study (22.1 ± 34.0 hours) than in the control (111.2 ± 55.9 hours) group, p<0.001 as well patients in the study and control groups also demonstrated statistically significant differences in the experience of symptoms associated with tension headache (p < 0.001). In conclusion, the structured nursing measures before and after the procedure was successful in decreasing the incidence and duration of this tension headache and its associated symptoms. Therefore, it is recommended to generalize these structured nursing measures in hospitals to be included in the routine pre-operative and post-operative nursing care for patients undergoing lower abdominal surgery with spinal anesthesia.

The impact of the iPLEDGE program on isotretinoin fetal exposure in an integrated health care system

Preventing fetal exposure to isotretinoin is widely acknowledged as an important safety issue. The iPLEDGE program is the latest in a series of Food and Drug Administration-mandated risk management programs designed to prevent pregnancies in female patients of childbearing potential (FCBP) taking isotretinoin. We sought to evaluate the effect of iPLEDGE relative to the prior risk management program (system to manage Accutane-related teratogenicity [SMART]) on the risk of isotretinoin fetal exposure in FCBP in a managed care setting. All FCBP at Kaiser Permanente Southern and Northern California who filled at least one prescription for isotretinoin during a 4-year period (March 1, 2004, to February 29, 2008) were included in this retrospective cohort study (n= 8344). Chart review was performed to confirm fetal exposures and outcomes. ACox proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals. There were a total of 29 fetal exposures and 9912 isotretinoin treatment courses. After iPLEDGE was implemented, the unadjusted rate of fetal exposure decreased from 3.11 to 2.67 per 1000 treatment courses (P= .69). The hazard ratio= 0.76 (95% confidence interval 0.36-1.61) for fetal exposures to isotretinoin during treatment courses filled after iPLEDGE implementation compared with SMART. Limitations include limited generalizability of results, small sample size (n= 29 total documented fetal exposures), and potential uncontrolled confounders. Evaluating the impact of iPLEDGE on isotretinoin fetal exposures is important in understanding the full risks and benefits of isotretinoin treatment. We found no evidence that iPLEDGE significantly decreased the risk of fetal exposure in FCBP compared to the SMART program.

RevAssist®

Lenalidomide (Revlimid) is an immunomodulatory drug and an analogue of thalidomide, a known teratogen. To prevent fetal exposure, in the US lenalidomide is available only under a special restricted distribution programme called RevAssist. Under this risk minimization programme, only prescribers and contract pharmacies registered with the programme are able to prescribe and dispense the product. Patients must be advised of, agree to and comply with the requirements of the RevAssist programme in order to receive lenalidomide through a registered prescriber. A total of 15 584 patients were registered in the RevAssist programme during the first year lenalidomide was on the market. There were four reports of false-positive beta-human chorionic gonadotrophin measurements in patients aged 43-57 years. Mandatory patient and prescriber surveys have shown discrepant responses that were resolved by risk management intervention specialists 99% of the time. The voluntary patient surveys have shown understanding of the risks of lenalidomide use and of behaviours necessary to minimize risks in >95% of females of childbearing potential and adult males. To date, there have been no reports of pregnancy in female patients or female partners of male patients. The pharmacy audit findings showed compliance with RevAssist was high. Although RevAssist is labour-intensive, time-consuming and costly, it continues to be effective in preventing fetal exposure to lenalidomide.

Puberty, Gonadal Function and Pregnancy in Female Patients Following Hematopoietic Cell Transplantation (HCT).

With increasing success of myeloablative HCT for patients with hematologic disorders, development of pre-pubertal children through puberty, return of gonadal function and the ability to become pregnant are of concern. To determine the impact of the preparative regimen on these issues, long-term follow-up records of more than 2,000 patients have been evaluated. Preparative regimens include cyclophosphamide (CY) 200 mg/kg, busulfan (BU) 16 mg/kg plus 120 or 200 mg/kg CY, or CY 120 mg/kg and 12–15.75 Gy total body irradiation (TBI). Among girls who were pre-pubertal at HCT and are now >12 years of age, 24/26 (92%) CY recipients, 11/23 (52%) BUCY recipients, and 46/96 (51%) CY + TBI recipients have developed normally through puberty. Among 148 post-pubertal women transplanted with CY only, 75 (50%) recovered gonadal function at a median of 6 months after HCT and 45 (30%) have become pregnant. This is in contrast to 2 (1%) of the 207 women who received BUCY who have shown gonadal function recovery and 1 has become pregnant. Among the fractionated TBI recipients, 39 (8%) of 460 women who received CY + 12 Gy TBI recovered ovarian function and 17 (3%) have become pregnant whereas among the 366 women who received 14.0–15.75 Gy TBI, 14 (4%) have recovered ovarian function and 4 (1%) have become pregnant. All women who recovered ovarian function after BUCY or TBI regimens were <25 years of age at HCT. The primary pregnancy complication was preterm labor and delivery, but all babies born were normal. For those women who do not recovery ovarian function, in vitro fertilization may be an option, and 14 women in this category have had successful pregnancies with 21 babies born using donated oocytes or pre-HCT stored gametes. These data demonstrate that pre-pubertal girls have more than 50% rate of developing normally through puberty and among women <25 years of age at HCT, recovery of ovarian function varies between 1%-50% depending on preparative regimen and some have become pregnant. For those who do not recover ovarian function, in vitro fertilization may be an option.

Problems during and after pregnancy in female patients with biliary atresia

Background/Purpose Advances in the management for biliary atresia (BA) have improved the prognosis and has greatly increased the number of long-term survivors. Even the long-term survivors, however, still face some problems. This retrospective review was performed to assess pregnancy-associated issues in long-term survivors after surgery for BA. Materials and Methods Of 55 patients with BA surviving for 16 years or more without liver transplantation, 9 patients have experienced pregnancy and delivery. Clinical courses, the outcome of pregnancy and delivery, and current statuses were retrospectively evaluated from their clinical records. Results The study revealed 14 pregnancies and 11 deliveries. Before pregnancy, no patient showed visible jaundice, but 6 patients had some complications such as episodes of cholangitis and portal hypertension. Two of the patients had both conditions and 2 others developed visible jaundice after pregnancy. One intrauterine fetal death occurred. Conclusions Our retrospective review suggests that the previously mentioned conditions can be risk factor for cholangitis and gastrointestinal bleeding during or after pregnancy but are not considered to be contraindications for pregnancy and delivery. Complications can occur with pregnancy even during the normal course. Thus, careful observation is recommended.

Can we consider thymectomy before pregnancy in female patients with myasthenia gravis?

I read with interest a recent article by Thubrikar et al.[1] where they suggest that in dilated aortic roots theanatomically normal leaflets, however, were not geome-trically normal. Thus they conclude that during valve-sparing surgery, it may be necessary in some cases tocorrect not only the dilatation of the aortic root but alsothe leaflet free-edge length in order to achieve a competentvalve.We studied the nervous fibers distributions with glycosa-minolglycans’ (GAG’s) leaflet distribution in 15 aortic valveleafletsinaorticrootdilatedandjudgedanatomicallynormaland 15 leaflets in normal aortic valve (homograft). We founda significant decrease in the fibers innervation — acetylcho-linesterase positive fibers — and also in GAG’s total quantityand distribution [2,3].The simple, anatomical, analysis of aortic leaflet beforethe surgery cannot be sufficient. As a matter of fact, thisquestion is particularly relevant in case of plastic of aorticvalve leaflets or valve-sparing procedures.