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Contains fulltext : 252036.pdf (Publisher’s version ) (Closed access) BACKGROUND: Most physicians encounter pregnant women with cancer incidentally, leading to a lack of expertise or confidence to inform and treat these patients based on the most recent guidelines and expert opinions. In the Netherlands, a national multidisciplinary tumour board for cancer, infertility and pregnancy (CIP-MDT) was founded in December 2012, including 35 specialists from a variety of disciplines. This study evaluates the frequency of consultation of the CIP-MDT, the types of questions asked and the satisfaction of consulting physicians with its existence. METHODOLOGY: Of all requests to the CIP-MDT between December 2012 and June 2021, tumour type, stage, gestational age at diagnosis and recommendations were collected and analysed. For evaluating the methods of the CIP-MDT, a survey with questions regarding experiences with the CIP-MDT and its impact on treatment decisions was sent out to physicians that consulted the CIP-MDT. RESULTS: Recommendations (n = 213) concerned preferred and safest options for imaging, treatment options during pregnancy, possible effects on the child and fertility preserving options. Most frequently discussed malignancies were breast cancer (n = 66), cervical cancer (n = 34), haematological malignancies (n = 32) and melanoma (n = 21). The questionnaire was completed by 54% of the physicians (n = 50). Satisfaction with the recommendations of the CIP-MDT was high, and 94% of the physicians informed their patients about consulting the CIP-MDT and felt supported by the received recommendations. DISCUSSION: The national Dutch CIP-MDT contributes to a high level of satisfaction among physicians requesting advice. Further research should be executed to confirm that a CIP-MDT improves the outcomes for pregnant women and their children.

Although medication use during pregnancy is common, most available products lack sufficient safety information. As prospective data collection and perinatal pharmacoepidemiologic research on medication safety in pregnancy did not exist in Belgium yet, the BELpREG data registration system was developed. BELpREG enables comprehensive ‘real-world’ data collection on perinatal medication use and mother-infant outcomes via online questionnaires that are completed by pregnant women every four weeks during pregnancy and in the first eight weeks after childbirth. This paper describes the development and current design of the BELpREG system, including the list of BELpREG variables. To compile this list of variables, relevant documents were explored, followed by consultation of an interdisciplinary expert panel. The included variables were structured in seven categories: 1) Sociodemographic characteristics; 2) Information on the current pregnancy and health status; 3) Maternal-obstetric history; 4) Use of medicines, folic acid / pregnancy vitamins and other health products; 5) Substance use; 6) Pregnancy outcomes; and 7) Neonatal outcomes. An electronic informed consent and linkage to medication databases, with images of drug packages and underlying structured data fields, are built into the system. Data collection has officially started in November 2022. Based on its rigorous design, BELpREG holds the potential to be a successful and sustainable research tool, enabling perinatal pharmacoepidemiologic research in Belgium and beyond.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education. ispartof: JOURNAL OF CLINICAL ONCOLOGY vol:41 issue:8 pages:1527-+ ispartof: location:United States status: published

BACKGROUND: The Netherlands and Belgium have been among the first countries to offer non-invasive prenatal testing (NIPT) as a first-tier screening test. Despite similarities, differences exist in counseling modalities and test uptake. This study explored decision-making and perspectives of pregnant women who opted for NIPT in both countries. METHODS: A questionnaire study was performed among pregnant women in the Netherlands (NL) (n = 587) and Belgium (BE) (n = 444) opting for NIPT, including measures on informed choice, personal and societal perspectives on trisomy 21, 18 and 13 and pregnancy termination. RESULTS: Differences between Dutch and Belgian women were shown in the level of informed choice (NL: 83% vs. BE: 59%, p

Cancer is diagnosed in one in 1000 to 1500 pregnancies. Most frequently encountered malignancies during pregnancy are breast cancer, hematological cancer, cervical cancer and malignant melanoma. Maternal cancer is associated with an increased risk of IUGR and preterm labor, especially in patients with systemic disease or those receiving chemotherapy during pregnancy, requiring a high-risk obstetrical follow-up. Fetal aneuploidy screening by non-invasive prenatal testing (NIPT) can lead to the incidental identification of copy number alterations derived from non-fetal cell-free DNA (cfDNA), as seen in certain cases of maternal malignancy. The identification of tumor-derived cfDNA requires further clinical, biochemical, radiographic and histological investigations to confirm the diagnosis. In such cases, reliable risk estimation for fetal trisomy 21, 18 and 13 is impossible. Therefore, invasive testing should be offered when ultrasonographic screening reveals an increased risk for chromosomal anomalies, or when a more accurate test is desired. When the fetal karyotype is normal, long term implications for the fetus refer to the consequences of the maternal disease and treatment during pregnancy. This manuscript addresses parental questions when NIPT suggests a maternal malignancy. Based on current evidence and our own experience, a clinical management scheme in a multidisciplinary setting is proposed.

BACKGROUND: Community pharmacists acknowledge to have an important role in providing pharmaceutical care during preconception, pregnancy and lactation. However, pharmacists' knowledge and counseling regarding this topic is still insufficient. Hence, educational initiatives are urgently needed. OBJECTIVES: To assess the impact of a blended learning program ('intervention') on community pharmacists' barriers, knowledge, and counseling practice with regard to preconception, pregnancy and lactation. METHODS: A pre-post study was performed in collaboration with 40 randomly selected pharmacies belonging to a large pharmacy chain in Belgium. All pharmacists employed in these pharmacies were eligible to participate in a blended learning program consisting of an e-learning and an on-site training day. Data were collected using online surveys, mystery shopping visits and pharmacy records. Pharmacy conversations were assessed on information gathering, dispensed product, and case-specific information. A retention knowledge test was completed 3-6 months after the intervention. RESULTS: In total, 60 pharmacists completed the post-intervention surveys (response rate: 95%). The total number of barriers decreased after the intervention, while organizational barriers such as lack of privacy (73%) and lack of time (67%) became more prevalent. Pharmacists' short and long-term knowledge improved after the intervention (p ≤ 0.001), although knowledge declined again over time (p ≤ 0.001). During counseling, pharmacists more often spontaneously provided information about folic acid when dispensing a pregnancy test, and more often suggested the correct dose/dosage for the dispensed OTC-product against pregnancy-related nausea. However, poor information gathering, dosing errors and incomplete information were still observed. CONCLUSION: The blended learning decreased pharmacists' barriers and improved their short- and long-term knowledge, while counseling practice only partially improved. Hence, the blended learning was insufficient to enhance pharmacists' information gathering competences and to fully implement pharmaceutical care services with regard to preconception, pregnancy and lactation. ispartof: Research in Social and Administrative Pharmacy vol:17 issue:7 pages:1242-1249 ispartof: location:United States status: published

Cancer during pregnancy threatens the lives of mother and foetus and its incidence is rising, making it an emerging medical challenge. Evidence on the direct impact of cancer therapies on neonatal outcomes resulted in general guidelines for maternal treatment that safeguards foetal development. Less focus has been placed on indirect factors, in pre- and postnatal periods, that may exert long-term impacts specifically on child neurocognition. Foetal development, in the context of maternal cancer during pregnancy, may be influenced directly by exposure to cancer diagnostics and (co-)treatment, or indirectly through maternal inflammation, malnutrition, hormonal fluctuations, prematurity, and psycho-biological stress. Maternal stress and insecure mother-infant bonding related to postpartum cancer treatment may further impact child cognitive-behavioural development. Understanding the independent and synergistic effects of the factors impacting neurocognitive development creates the opportunity to intervene during the oncological treatment to improve the child's long-term outcome, both by medical and psychosocial care and support. ispartof: CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY vol:179 ispartof: location:Netherlands status: published

Data on the long-term neurodevelopmental outcomes of children exposed to hematological maternal cancer with or without treatment during pregnancy are lacking. A total of 57 children, of whom 33 males and 24 females, prenatally exposed to hematological malignancies and its treatment, were invited for neuropsychological and physical examinations at 18 months, 36 months, 6, 9, 12, 15 and 18 years of age. Oncological, obstetrical, neonatal and follow-up data of these children were collected. Parents were asked to complete questionnaires on their child's general health, school performances, social situation, behavioral development, executive functioning, and if their child receives supportive care. Non-Hodgkin lymphoma was diagnosed in 35.1%, Hodgkin lymphoma in 28.1%, acute myeloid leukemia in 15.8%, chronic myeloid leukemia in 12.3%, and acute lymphoblastic leukemia in 8.8%. Cognitive development at a median age of 10.7 years was within the normal range. In subgroup analyses of children in early childhood, the gestational age at birth was correlated with the cognitive outcome at a median age of 1.7 years. Scores for language development, intelligence, attention, memory and behavior, as well as clinical neurological and general pediatric examinations were within normal ranges. In subgroup analyses, the need for supportive care in the child was associated with the loss of the mother. Prenatal exposure to hematological maternal malignancies with or without treatment did not affect the neurodevelopment of the child in the long term. Yet, caution is indicated and surveillance of the emotional development of the child is needed, especially when the mother is deceased to cancer. ispartof: CHILD NEUROPSYCHOLOGY vol:27 issue:6 pages:822-833 ispartof: location:England status: published

Non-invasive prenatal testing has been introduced for the detection of Trisomy 13, 18, and 21. Using genome-wide screening also other "rare" autosomal trisomies (RATs) can be detected with a frequency about half the frequency of the common trisomies in the large population-based studies. Large prospective studies and clear clinical guidelines are lacking to provide adequate counseling and management to those who are confronted with a RAT as a healthcare professional or patient. In this review we reviewed the current knowledge of the most common RATs. We compiled clinical relevant parameters such as incidence, meiotic or mitotic origin, the risk of fetal (mosaic) aneuploidy, clinical manifestations of fetal mosaicism for a RAT, the effect of confined placental mosaicism on placental function and the risk of uniparental disomy (UPD). Finally, we identified gaps in the knowledge on RATs and highlight areas of future research. This overview may serve as a first guide for prenatal management for each of these RATs.

There is almost no experience with concentrated ginger extracts during pregnancy. The purpose of this trial was to include 50 pregnant women in a clinical feasibility study with EXT.GR10, a 10 × concentrated ethanolic extract of ginger root. The primary objective was to detect complications in the mother during pregnancy and malformations or complications in the newborn at delivery. The secondary purpose was to evaluate the satisfaction of the patients. In total, 51 pregnant women were included in this observational study. They could freely use ginger tablets with a maximum of 2 tablets of 50 mg EXT.GR10 a day in case of gastrointestinal discomfort. Tablets were taken by 44 patients. Stillbirth, prematurity, hypertension, and gestational diabetes occurred. There were no serious complications at birth. In the newborn, 4 cases of dysplasia of the hip were seen and 2 minor malformations. There was no relation between events affecting mother and child and the number of EXT.GR10 tablets taken. About ⅔ of patients appreciated the effects of ginger. This is the first clinical study with the EXT.GR10 extract. Based on this feasibility study, a follow-up clinical trial is planned with a fixed minimum of exposure to EXT.GR10 during the first trimester of pregnancy.

Cancer during pregnancy is increasingly diagnosed due to the trend of delaying pregnancy to a later age and probably also because of increased use of non-invasive prenatal testing for fetal aneuploidy screening with incidental finding of maternal cancer. Pregnant women pose higher challenges in imaging, diagnosis, and staging of cancer. Physiological tissue changes related to pregnancy makes image interpretation more difficult. Moreover, uncertainty about the safety of imaging modalities, fear of (unnecessary) fetal radiation, and lack of standardized imaging protocols may result in underutilization of the necessary imaging tests resulting in suboptimal staging. Due to the absence of radiation exposure, ultrasound and MRI are obvious first-line imaging modalities for detailed locoregional disease assessment. MRI has the added advantage of a more reproducible comprehensive organ or body region assessment, the ability of distant staging through whole-body evaluation, and the combination of anatomical and functional information by diffusion-weighted imaging which obviates the need for a gadolinium-based contrast-agent. Imaging modalities with inherent radiation exposure such as CT and nuclear imaging should only be performed when the maternal benefit outweighs fetal risk. The cumulative radiation exposure should not exceed the fetal radiation threshold of 100 mGy. Imaging should only be performed when necessary for diagnosis and likely to guide or change management. Radiologists play an important role in the multidisciplinary team in order to select the most optimal imaging strategies that balance maternal benefit with fetal risk and that are most likely to guide treatment decisions. Our aim is to provide an overview of possibilities and concerns in current clinical applications and developments in the imaging of patients with cancer during pregnancy. ispartof: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER vol:31 issue:3 pages:423-431 ispartof: location:England status: published

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients. ispartof: BRITISH JOURNAL OF HAEMATOLOGY vol:193 issue:1 pages:52-62 ispartof: location:England status: published

Background Aortic dilatation and pregnancy are major concerns in women with aortopathy (AOP). This single-centre retrospective analysis focuses on the evolution of aortic diameters during and after pregnancy in women with Marfan syndrome (MS), Turner syndrome (TS) and bicuspid aortic valve (BAV) aortopathy. Methods and results Thirty-eight women who had one or more single pregnancies were included. The ascending aorta was measured during pregnancy and postpartum. During pregnancy, a significant increase of diameters of the sinus aortae (median 1.4 mm; [−1.3; 3.8]) and ascending aorta (median 2.1 mm; [0.0; 4.0]) was noted. Systemic hypertension gives dilation of the aorta, but it did not influence the overall trajectory during pregnancy. Conclusion Significant aortic dilatation is noted during pregnancy in women with underlying AOP, even persisting in the long term. Pre-existing systemic hypertension is associated with larger aortic diameters prior to pregnancy. More research on a larger study population however is needed.

In the UK, mortality rate during pregnancy/in the peripartal period is 14.1 per 100,000 maternities with heart disease being the leading cause of non-obstetric maternal mortality (10% to 15% of all maternal deaths). Owing to the advances in the treatment of congenital heart disease (CHD), an increasing percentage of women has reached childbearing age, making CHD nowadays the most frequent cardiovascular disease during pregnancy in the Western world. In the pregnant woman, several adaptive changes occur in the cardiovascular and pulmonary system that in the worst case can lead to cardiovascular collapse in women with pre-existing heart disease. If medical management is not sufficient, cardiac interventions have to be considered, including percutaneous endovascular interventions, cardiac surgery, the use of extracorporeal membrane oxygenation or the placement of assist devices. While all these interventions seem to be relatively safe for the mother, fetal mortality remains considerably high. A thorough understanding of maternal physiology during pregnancy and of the perfusion of the feto-maternal unit is mandatory for the successful management of pregnant patients in need of cardiac (surgical) interventions.

515 Background: Overall a diagnosis of breast cancer during pregnancy (BCP) appears not to impact maternal prognosis if standard treatment is offered. However, caution is warranted as gestational changes in pharmacokinetics with respect to the distribution, metabolism and excretion of drugs may lead to reduced chemotherapy concentration in pregnant patients. This cohort study was designed to focus on the maternal prognosis of BCP patients that receive chemotherapy during pregnancy. Methods: The outcome of BCP patients treated with chemotherapy during pregnancy was compared to non-pregnant breast cancer patients treated with chemotherapy, diagnosed after 2000, excluding postpartum diagnosis and with an age limit of 45 years. The data was registered by two multicentric registries (the International Network of Cancer, Infertility and Pregnancy and the German Breast Cancer Group) that collect both retro-and prospectively breast cancer data. Cox proportional hazards regression was used to compare disease-free (DFS) and overall survival (OS) between both groups, adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status and histology, weighted by propensity scoring in order to account for the differences in baseline characteristics between pregnant patients and controls. Results: In total, 662 pregnant and 2081 non-pregnant patients, were eligible for analysis. Median age at diagnosis was 34 (range 22-47) years for pregnant and 38 (range 19-45) years for non-pregnant patients. Pregnant patients were more likely to have stage II breast cancer (60.1% vs 56.1%, p = 0.035), grade 3 tumors (74.0% vs 62.2%, p < 0.001), hormone receptor-negative tumors (48.4% vs 34.0%, p < 0.001) or triple-negative breast cancer (38.9% vs 26.9%, p < 0.001). Median follow-up was 66 months. DFS and OS were comparable for pregnant and non-pregnant patients (DFS: HR 1.02, 95%CI 0.82-1.27, p = 0.83; OS: HR 1.08, 95% CI 0.81-1.45, p = 0.59). A subgroup analysis of 339 women that received more than 60% of chemotherapy during pregnancy (cut-off at median) revealed a comparable survival compared to non-pregnant women (DFS: HR 0.81, 95%CI 0.62-1.06, p = 0.13; OS: HR 0.85 95% CI 0.58-1.23, p = 0.39). Conclusions: Pregnancy-induced alternations in chemotherapy concentration do not seem to affect maternal prognosis in breast cancer patients. These results support initiation of chemotherapy for BCP where indicated for oncological reasons.

BACKGROUND: Chemotherapy crosses the placenta, however, it remains unclear to what extent it affects fetal growth. The current literature suggests up to 21% of the offspring of women receiving chemotherapy are small for gestational age (SGA, birth weight

Background Breast cancer and hematological cancers are the most commonly diagnosed malignancies during pregnancy. This case report is the first to describe the ultimate challenge to preserve a pregnancy while the expectant mother is diagnosed and treated simultaneously for two concurrent primary malignancies, a stage IIA Hodgkin lymphoma and pT2N0(Sn) breast cancer. Clinical case A 36-year-old pregnant primigravida underwent a routine non-invasive prenatal test at 14 weeks and 4 days of gestation. Genome-wide sequencing was used and revealed an aberrant DNA/chromosome copy number profile among which a strong 2p-gain, possibly related to a maternal malignancy. Physical examination showed an enlarged cervical lymph node and ultrasound guided biopsy confirmed the diagnosis of a nodular sclerosing classical Hodgkin lymphoma subsequently staged as an early stage, unfavorable (IIA) Hodgkin lymphoma. Whole body magnetic resonance imaging for further staging also indicated a suspicious nodule in the right breast. Further investigation resulted in the concurrent diagnosis of a pT2N0(Sn) invasive ductal adenocarcinoma. Patient underwent a mastectomy with sentinel lymph node biopsy at 15 weeks and 5 days of gestation, followed by 4-weekly chemotherapy administration, consisting of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). Pregnancy went further relatively uncomplicated and fetal assessment was reassuring during pregnancy. Due to fever of unknown origin and preterm labor, a cesarean section was performed on a gestational age of 35 weeks and 4 days. Oncological treatment was completed after delivery with involved-field radiation therapy for the Hodgkin lymphoma. Completion of systemic treatment for breast cancer consisted of docetaxel/cyclophosphamide chemotherapy, and anti-hormonal treatment in the form of ovarian function suppression and letrozole. Conclusion Here we show for the first time that two concurrent primary malignancies can be treated successfully during pregnancy with respect to maternal and fetal chances. Motivated modifications of breast cancer treatment (mastectomy instead of lumpectomy, AVBD instead of epirubicin-cyclophosphamide chemotherapy), allowed treatment of both cancers during pregnancy. Final treatment was administered after delivery. ispartof: Gynecologic Oncology Reports vol:39 ispartof: location:Netherlands status: Published online

Background and Objective Although acetaminophen is frequently used during pregnancy, little is known about fetal acetaminophen pharmacokinetics. Acetaminophen safety evaluation has typically focused on hepatotoxicity, while other events (fetal ductal closure/constriction) are also relevant. We aimed to develop a fetal–maternal physiologically based pharmacokinetic (PBPK) model (f-m PBPK) to quantitatively predict placental acetaminophen transfer, characterize fetal acetaminophen exposure, and quantify the contributions of specific clearance pathways in the term fetus. Methods An acetaminophen pregnancy PBPK model was extended with a compartment representing the fetal liver, which included maturation of relevant enzymes. Different approaches to describe placental transfer were evaluated (ex vivo cotyledon perfusion experiments, placental transfer prediction based on Caco-2 cell permeability or physicochemical properties [MoBi®]). Predicted maternal and fetal acetaminophen profiles were compared with in vivo observations. Results Tested approaches to predict placental transfer showed comparable performance, although the ex vivo approach showed highest prediction accuracy. Acetaminophen exposure in maternal venous blood was similar to fetal venous umbilical cord blood. Prediction of fetal acetaminophen clearance indicated that the median molar dose fraction converted to acetaminophen-sulphate and N-acetyl-p-benzoquinone imine was 0.8% and 0.06%, respectively. The predicted mean acetaminophen concentration in the arterial umbilical cord blood was 3.6 mg/L. Conclusion The median dose fraction of acetaminophen converted to its metabolites in the term fetus was predicted. The various placental transfer approaches supported the development of a generic f-m PBPK model incorporating in vivo placental drug transfer. The predicted arterial umbilical cord acetaminophen concentration was far below the suggested postnatal threshold (24.47 mg/L) for ductal closure. Electronic supplementary material The online version of this article (10.1007/s40262-020-00861-7) contains supplementary material, which is available to authorized users.

BACKGROUND: Although preferably avoided, pregnant and lactating women often use medicines, including potentially inappropriate products. Pregnant women also commonly search for online information on medication. This underscores the need for appropriate counseling by healthcare professionals, including community pharmacists. However, little is known about pharmacists' perceptions and barriers towards this role, nor about their knowledge and counseling practice. OBJECTIVES: To explore licensed pharmacists' attitudes, barriers, knowledge and counseling practice regarding pharmaceutical care during preconception, pregnancy and lactation. METHODS: All pharmacists employed in 40 randomly selected pharmacies of a Belgian pharmacy chain ('Surplus Network') were asked to complete an online survey between September 2018-February 2019. The survey assessed pharmacists' attitudes and current practice regarding their role, as well as barriers and knowledge. Additionally, the 40 pharmacies were visited twice in December 2017 by simulated patients. The scenarios included a request for a pregnancy test and for an over-the-counter (OTC) product to treat pregnancy-related nausea. RESULTS: All 63 invited pharmacists completed the survey. For all attitude-related statements, at least 80% agreed that pharmacists should take up the presented roles. However, for only 1 in 5 statements did at least 80% report currently taking up these roles for all or most patients. Most commonly reported barriers related to difficulties identifying the woman's status (71%) and lack of education (67%). The median score for the knowledge test was 23/45 (range: 6-36). The mystery shopping showed inadequate questioning and insufficient counseling. Only in 10% of cases was folic acid intake spontaneously discussed; in 39% of cases, incorrect advice about the dispensed OTC-product was given. CONCLUSION: Pharmacists acknowledged having an important role during preconception, pregnancy and lactation, but currently do not provide pharmaceutical care in this area to most patients. Educational programs are urgently needed to improve licensed pharmacists' knowledge and counseling regarding this topic. ispartof: Research in Social and Administrative Pharmacy vol:16 issue:9 pages:1192-1200 ispartof: location:United States status: published

Background and Objective Little is known about acetaminophen (paracetamol) pharmacokinetics during pregnancy. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict acetaminophen pharmacokinetics throughout pregnancy. Methods PBPK models for acetaminophen and its metabolites were developed in non-pregnant and pregnant women. Physiological and enzymatic changes in pregnant women expected to impact acetaminophen pharmacokinetics were considered. Models were evaluated using goodness-of-fit plots and by comparing predicted pharmacokinetic profiles with in vivo pharmacokinetic data. Predictions were performed to illustrate the average concentration at steady state (Css,avg) values, used as an indicator for efficacy, of acetaminophen achieved following administration of 1000 mg every 6 h. Furthermore, as a measurement of potential hepatotoxicity, the molar dose fraction of acetaminophen converted to N-acetyl-p-benzoquinone imine (NAPQI) was estimated. Results PBPK models successfully predicted the pharmacokinetics of acetaminophen and its metabolites in non-pregnant and pregnant women. Predictions resulted in the lowest Css,avg in the third trimester (median [interquartile range]: 4.5 [3.8–5.1] mg/L), while Css,avg was 6.7 [5.9–7.4], 5.6 [4.7–6.3], and 4.9 [4.1–5.5] mg/L in non-pregnant, first trimester, and second trimester populations, respectively. Assuming a constant raised cytochrome P450 2E1 activity throughout pregnancy, the molar dose fraction of acetaminophen converted to NAPQI was highest during the first trimester (median [interquartile range]: 11.0% [9.1–13.4%]), followed by the second (9.0% [7.5–11.0%]) and third trimester (8.2% [6.8–10.1%]), compared with non-pregnant women (7.7% [6.4–9.4%]). Conclusion Acetaminophen exposure is lower in pregnant than in non-pregnant women, and is related to pregnancy duration. Despite these findings, higher dose adjustments cannot be advised yet as it is unknown whether pregnancy affects the toxicodynamics of NAPQI. Information on glutathione abundance during pregnancy and NAPQI in vivo data are required to further refine the presented model. Electronic supplementary material The online version of this article (10.1007/s40262-019-00799-5) contains supplementary material, which is available to authorized users.

What's already known about this topic? Incidental diagnoses of an occult maternal malignancy have been reported upon aberrant routine noninvasive prenatal testing (NIPT). The presence of tumor‐derived cell‐free DNA in the maternal circulation can skew the NIPT profile. What does this study add? Pregnant women with a confirmed neoplastic disease should not have NIPT testing for fetal aneuploidy screening since NIPT results cannot accurately be applied to assess the fetal chromosomal constitution in this condition. ispartof: PRENATAL DIAGNOSIS vol:39 issue:12 pages:1162-1165 ispartof: location:England status: published

BACKGROUND: Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. METHODS: We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995-2004, and 2005-18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997. FINDINGS: Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4-91·1) for 62 pregnant patients and 88·3% (81·6-92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84-3·87; p=0·130; 5-year overall survival was 97·3% (82·3-99·6) and 98·4% (93·6-99·6; HR 1·63, 0·35-7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8-98·7) versus 74·0% (60·9-83·3); HR 0·36, 95% CI 0·04-2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5-99·1; HR cannot be estimated; p=0·146). INTERPRETATION: Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth. FUNDING: European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic. ispartof: LANCET HAEMATOLOGY vol:6 issue:11 pages:E551-E561 ispartof: location:England status: published

Knowledge of the impact of in utero exposure to lithium during the postnatal period is limited. Besides a possible teratogenic effect during the first trimester, exposure during the second and third trimesters might lead to neonatal effects. Uniform guidelines for postnatal management of these neonates are lacking. The aim was to retrospectively describe all neonates admitted to the University Hospitals Leuven after in utero exposure to lithium (January 2010 to April 2020), and to propose a postnatal care protocol. Descriptive statistics were performed. For continuous parameters with serial measurements, median population values were calculated. In total, 10 mother-neonate pairs were included. The median gestational age was 37 (interquartile range, IQR, 36-39) weeks. Neonatal plasma lithium concentration at birth was 0.65 (IQR 0.56-0.83) mmol/L with a median neonate/mother ratio of 1.02 (IQR 0.87-1.08). Three neonates needed respiratory support, 7/10 started full enteral (formula) feeding on day 1. The median length of neonatal stay was 8.5 (IQR 8-12) days. One neonate developed nephrogenic diabetes insipidus. This study reported in detail the postnatal characteristics and short-term neonatal outcomes. A postnatal care protocol was proposed, to enhance the quality of care for future neonates, and to guide parental counselling. Future prospective protocol evaluation is needed. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:19 issue:16 ispartof: location:Switzerland status: published

Data on the long-term neurodevelopmental outcomes of children exposed to hematological maternal cancer with or without treatment during pregnancy are lacking. A total of 57 children, of whom 33 males and 24 females, prenatally exposed to hematological malignancies and its treatment, were invited for neuropsychological and physical examinations at 18 months, 36 months, 6, 9, 12, 15 and 18 years of age. Oncological, obstetrical, neonatal and follow-up data of these children were collected. Parents were asked to complete questionnaires on their child's general health, school performances, social situation, behavioral development, executive functioning, and if their child receives supportive care. Non-Hodgkin lymphoma was diagnosed in 35.1%, Hodgkin lymphoma in 28.1%, acute myeloid leukemia in 15.8%, chronic myeloid leukemia in 12.3%, and acute lymphoblastic leukemia in 8.8%. Cognitive development at a median age of 10.7 years was within the normal range. In subgroup analyses of children in early childhood, the gestational age at birth was correlated with the cognitive outcome at a median age of 1.7 years. Scores for language development, intelligence, attention, memory and behavior, as well as clinical neurological and general pediatric examinations were within normal ranges. In subgroup analyses, the need for supportive care in the child was associated with the loss of the mother. Prenatal exposure to hematological maternal malignancies with or without treatment did not affect the neurodevelopment of the child in the long term. Yet, caution is indicated and surveillance of the emotional development of the child is needed, especially when the mother is deceased to cancer.

The diagnosis of cancer during pregnancy imposes a medical-ethical dilemma in weighing the risks of both mother and child. Increasing awareness of the feasibility of chemotherapy during pregnancy results in more pregnant patients receiving treatment for cancer. Information on obstetric and pediatric outcome of these high-risk pregnancies is greatly needed to guide physicians in patient counseling. In this review we present reported evidence for the incidence, diagnostic options, therapeutic management, obstetric risks, and neonatal outcome when cancer treatment is initiated during pregnancy. Decision-making when a cancer is diagnosed in a pregnant patient should be multidisciplinary, always taking the patient's perspective into account. Cancer treatment during pregnancy is associated with low birth weight and preterm delivery, therefore frequent obstetric follow-up during oncological treatment in a specialized center is mandatory. Short-term clinical, cardiac, and cognitive outcome of children pre-natally exposed to cancer treatment is overall reassuring. Long-term follow-up of children is warranted to define the possible effect of pre-natal cancer treatment on general health, fertility outcome, and the risk of secondary cancers. ispartof: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER vol:29 issue:2 pages:404-416 ispartof: location:England status: published

PURPOSE: To explore beliefs about medicines and information needs among pregnant women visiting a tertiary hospital in Belgium and to identify patient characteristics associated with beliefs about medicines. METHODS: A cross-sectional study was performed at the outpatient obstetrics clinic of the University Hospital Leuven, Belgium, between December 2016 and March 2017. All pregnant women ≥ 18 years were invited to complete a web survey. The survey consisted of general and pregnancy-specific statements of the "Beliefs about Medicines" questionnaire and questions about information needs. Descriptive statistics, chi-square tests, Fisher's exact tests, and multinomial logistic regression were used to analyze the findings. RESULTS: In total, 372 pregnant women participated. Most women showed positive attitudes towards medicines in general. However, almost 90% of women agreed to have a higher threshold to use medicines during pregnancy compared with non-pregnant situations. Likewise, 40% preferred natural remedies during pregnancy. Education in healthcare and education level were the main determinants associated with beliefs, with highly educated women showing a higher threshold to use medicines during pregnancy (p = 0.005). Most women searched online for pregnancy-related information (85%) and for information about medicines (74%). However, less than one-third discussed online-retrieved information with healthcare professionals (HCPs). CONCLUSIONS: Pregnant women visiting a tertiary hospital in Belgium showed a higher threshold to use medicines during pregnancy compared with non-pregnant situations and had high information needs, including for information about medicines during pregnancy. HCPs should be aware of women's individual beliefs, guide them towards reliable websites, and discuss online-retrieved information during counseling. ispartof: European Journal Of Clinical Pharmacology vol:75 issue:7 pages:995-1003 ispartof: location:Germany status: published

Data on the use of Granulocyte colony-stimulating factor (G-CSF) in pregnant cancer patients are scarce. The International Network of Cancer, Infertility and Pregnancy (INCIP) reviewed data of pregnant patients treated with chemotherapy and G-CSF, and their offspring. Among 2083 registered patients, 42 pregnant patients received G-CSF for the following indications: recent chemotherapy induced febrile neutropenia (5, 12%), dose dense chemotherapy (28, 67%), poly chemotherapy (7, 17%), or prevention of neutropenia at delivery (2, 5%). Among 24 women receiving dose dense chemotherapy, three (13%) patients recovered from asymptomatic neutropenia within 5 days. One patient developed pancytopenia following polychemotherapy after which the pregnancy was complicated by chorioamnionitis and intrauterine death. Nineteen singleton livebirths (49%) were born preterm. Sixteen neonates (41%) were admitted to the Neonatal Intensive care Unit (NICU). No neonatal neutropenia occurred. Two neonates had congenital malformations. Out of 21 children in follow-up, there were four children with a motor development delay and two premature infants had a delay in cognitive development. In conclusion, the rate of maternal and neonatal complications are similar to those described in (pregnant) women treated with chemotherapy. Due to small numbers and limited follow-up, rare or delayed effects among offspring exposed to G-CSF in utero cannot be ruled out yet.

OBJECTIVE: To evaluate the economic impact of introducing the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test into clinical practice in Belgium for the prediction of preeclampsia (PE). STUDY DESIGN: We developed a one-year time-horizon decision tree model to evaluate the short-term costs associated with the introduction of the sFlt-1/PlGF test for guiding the management of women with suspected PE from the Belgian public healthcare payers' perspective. The model estimated the costs associated with the diagnosis and management of PE in pregnant women managed in either a test scenario, in which the sFlt-1/PlGF test is used in addition to current clinical practice, or a no test scenario, in which clinical decisions are based on current practice alone. Test characteristics were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of PE. Unit costs were obtained from Belgian-specific sources. The main model outcome was the total cost per patient. RESULTS: Introduction of the sFlt-1/PlGF ratio test is expected to result in a cost saving of €712 per patient compared with the no test scenario. These savings are generated mainly due to a reduction in unnecessary hospitalizations. CONCLUSIONS: The sFlt-1/PlGF test is projected to result in substantial cost savings for the Belgian public healthcare payers through reduction of unnecessary hospitalization of women with clinical suspicion of PE that ultimately do not develop the condition. The test also has the potential to ensure that women at high risk of developing PE are identified and appropriately managed. ispartof: PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH vol:26 pages:31-37 ispartof: location:Netherlands status: published

BACKGROUND: Based on reassuring short-term foetal and maternal safety data, there is an increasing trend to administer chemotherapy during the second and third trimesters of pregnancy. The pharmacokinetics (PK) of drugs might change as a result of several physiological changes that occur during pregnancy, potentially affecting the efficacy and safety of chemotherapy. OBJECTIVE: With this analysis, we aimed to quantitatively describe the changes in the PK of docetaxel, paclitaxel, doxorubicin and epirubicin in pregnant women compared with non-pregnant women. METHODS: PK data from 9, 20, 22 and 16 pregnant cancer patients from the International Network of Cancer, Infertility and Pregnancy (INCIP) were available for docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. These samples were combined with available PK data from non-pregnant patients. Empirical non-linear mixed-effects models were developed, evaluating fixed pregnancy effects and gestational age as covariates. RESULTS: Overall, 82, 189, 271, and 227 plasma samples were collected from pregnant patients treated with docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. The plasma PK data were adequately described by the respective models for all cytotoxic drugs. Typical increases in central and peripheral volumes of distribution of pregnant women were identified for docetaxel, paclitaxel, doxorubicin and epirubicin. Additionally, docetaxel, doxorubicin and paclitaxel clearance were increased in pregnant patients, resulting in lower exposure in pregnant women compared with non-pregnant patients. CONCLUSION: Given the interpatient variability, the identified pregnancy-induced changes in PK do not directly warrant dose adjustments for the studied drugs. Nevertheless, these results underscore the need to investigate the efficacy of chemotherapy, when administered during pregnancy. ispartof: CLINICAL PHARMACOKINETICS vol:60 issue:6 pages:775-784 ispartof: location:Switzerland status: published

Background Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q, Highlights • Cancer treatment including chemotherapy is possible during pregnancy. • Children are at risk for lower verbal IQ and visuospatial long-term memory scores. • Other cognitive functions and cardiac outcomes were normal at the age of 6 years. • We documented ototoxicity in three children exposed to cisplatin. • Follow-up until adulthood is recommended.

COVID-19 also affects pregnant and breastfeeding women. Hence, clinicians and policymakers require reliable evidence on COVID-19 epidemiology and consequences in this population. We aimed to assess the susceptibility of pregnant women to SARS-CoV-2 and women&rsquo, s perceived impact of the pandemic on their breastfeeding practices, medical counseling and social support. We performed a cross-sectional study using an online survey in primary care in Belgium. Pregnant and breastfeeding women and women who breastfed in the preceding four weeks were eligible to participate. The survey was distributed through social media in April 2020. In total, 6470 women participated (i.e., 2647 pregnant and 3823 breastfeeding women). Overall, 0.3% of all respondents reported to have tested positive for SARS-CoV-2, not indicating a higher susceptibility of pregnant women to contracting COVID-19. More than 90% refuted that the pandemic affected their breastfeeding practices, nor indicated that the coronavirus was responsible for breastfeeding cessation. Half of the women even considered giving longer breastmilk because of the coronavirus. In contrast, women&rsquo, s medical counseling and social support were negatively affected by the lockdown. Women without previous breastfeeding experience and in the early postpartum period experienced a higher burden in terms of reduced medical counseling and support. In the future, more consideration and alternative supportive measures such as tele-visits by midwives or perinatal organizations are required for these women.

BACKGROUND: Cancer treatment during pregnancy imposes a dilemma. Maternal advantage should be weighed against the potential impact of chemotherapy on child development. Recent studies in cancer survivors have shown that exposure to chemotherapeutic agents can have late adverse effects on cognitive functioning and executive functioning (EF). It is still unclear whether these late adverse effects also arise if a child is exposed to chemotherapy in utero. AIM: To compare the development of executive functioning in 6 year old children prenatally exposed to chemotherapy (study group) and children born to healthy women after an uncomplicated pregnancy (control group). METHODS AND STUDY DESIGN: In a multicenter cohort study, the outcome on a measure of EF was compared. Study and control children were prospectively examined by means of the Behavior Rating Inventory of Executive Function (BRIEF), a health questionnaire and an intelligence test. RESULTS: In total 37 study children and 37 matched controls were included. In the study group, 11 children (29.7%) were exposed to chemotherapy alone, 22 children (59.5%) were exposed to chemotherapy and surgery and 4 children (10.8%) were exposed to chemotherapy, surgery and radiotherapy during pregnancy. All outcome scales of the BRIEF were within normal ranges. However, a significant between-group difference in emotional control was found. CONCLUSION: Overall outcomes of EF were reassuring. However, children prenatally exposed to chemotherapy have weaker emotion regulation skills compared to their matched controls. The results underscore the need for long-term follow-up of these children. ispartof: EARLY HUMAN DEVELOPMENT vol:151 ispartof: location:Ireland status: published