BACKGROUND: Platina and taxanes are frequently used chemotherapeutic agents to treat cancer, also when diagnosed during pregnancy. This report presents an interim analysis of the largest series of children prenatally exposed to platinum and/or taxane agents and aims to determine their physical health and neurocognitive outcomes. METHODS: As part of a multicentre, prospective cohort study (ClinicalTrials.gov: NCT00330447), children born between 2000 and 2022 were assessed between 2005 and 2024 at ages 1.5-18 years (interim analysis; median length of follow-up, 3.2 years (IQR 3.0-6.4)) by a comprehensive neurocognitive test battery, parent-reported questionnaires, and a physical assessment. Mixed-effects regression and Type III Analysis of Variance models were used to investigate associations between these outcomes and platinum/taxane cumulative dose and agent type, with best-fit models corrected for age and covariates (gestational age at birth, chemotherapy timing, other chemotherapy, sex, parental education level, maternal death). FINDINGS: In total, 144 children were included (13% exposed to platinum, 62% to taxanes, 25% to both). Of these, 101 were assessed at age 1.5 years, 96 at age 3, 63 at age 6, 32 at age 9, 18 at age 12, 7 at age 15, and 2 at age 18 years. Neurocognitive outcomes were within normal ranges across all ages, compared with test-specific normative data. Eight children (6%) reported ototoxicity, seven (5%) reported chronic medical conditions, three (2%) had congenital malformations, and two (1%) were diagnosed with Attention-Deficit Hyperactivity Disorder. Thirty-three children (23%) needed extra neurocognitive support, of which 64% were born preterm. Children prenatally exposed to paclitaxel scored lower on visuospatial (β = 0.64 ± 0.21, p = 0.0052) and verbal memory (β = 0.68 ± 0.27, p = 0.015) than those exposed to docetaxel. INTERPRETATION: In this interim analysis, we found normal neurocognitive outcomes and no increase in congenital malformations nor medical conditions after prenatal exposure to platinum/taxane-based chemotherapy. However, owed to the limited number of older children, further investigation regarding their potential neurotoxicity and its long term effects is necessary in follow-up studies with larger samples. FUNDING: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Cooperatio program, Research Foundation Flanders.
- Publikační typ
- časopisecké články MeSH
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 <10th percentile). Limiting research to birth weights only might misjudge fetal growth restriction (FGR) in this high-risk population with multiple risk factors for impaired fetal growth. Moreover, the role of the duration of chemotherapy and gestational age at initiation of chemotherapy in fetal growth is yet poorly understood. OBJECTIVE: This retrospective cohort study evaluates fetal growth and neonatal birthweights in pregnant women receiving chemotherapy. STUDY DESIGN: All pregnant patients, registered by the International Network of Cancer, Infertility and Pregnancy (INCIP), treated with chemotherapy with at least two ultrasounds reporting on fetal growth, were eligible for this study. Duration and gestational age at initiation of chemotherapy were our major determinants, followed by cancer type and stage, maternal characteristics (parity, BMI, ethnicity hypertension, and diabetes) and individual cytotoxic agents (anthracycline, taxanes, and platinum). Fetal growth outcomes were described using the following mutually exclusive groups (1) FGR, based on a Delphi consensus (2016); (2) "low risk SGA" (birth weight below the 10th percentile), but an estimated growth above the 10th percentile; (3) "fetal growth disturbance", which did not meet all FGR criteria; (4) "non-FGR". Obstetric and oncological characteristics were compared between the growth impaired groups and non-FGR group. We calculated estimated fetal weight (EFW) according to Hadlock's formula (1991) and birth weight percentile according to Nicolaides (2018). We used univariable and multivariable regression, and linear mixed effect models to investigate the effect of duration and gestational age at initiation of chemotherapy on birth weight, and fetal growth, respectively. RESULTS: We included 201 patients, diagnosed with cancer between March 2000 and March 2020. Most patients were diagnosed with breast cancer (n = 132, 66%). Regimens included anthracyclines (n = 121, 60%), (anthracyclines and) taxanes (n = 45, 22%) and platinum (n = 35, 17%). Fetal growth abnormalities were detected in 75 pregnancies: 43 (21%) FGR, 10 (5%) low risk SGA and 22 (8.5%) fetal growth disturbance. Chemotherapy prior to 20 weeks of gestation (47% vs. 25%, p = .04) and poor maternal gestational weight gain (median percentile 15 (range 0-97) vs. 8 (0-84), p = .03) were more frequent in the FGR group compared to the non-FGR group, whereas no difference was seen for specific chemotherapy or cancer types. Univariable regression identified gestational weight gain, hypertension, systemic disease, parity, neonatal sex and maternal BMI as confounders for birth weight percentiles. Multivariable regression revealed that each additional week of chemotherapy was associated with lower birth weight percentiles (-1.06; 95%CI -2.01; -0.04; p = .04), and that later initiation of chemotherapy was associated with an increase in birth weight percentile (1.10 per week; 95%CI 0.26; 1.95; p = .01). Each additional week of chemotherapy was associated with lower EFW and abdominal circumference (AC) percentiles (-1.77; 95%CI -2.21; -1.34, p < .001; -1.64; 95%CI -1.96; -1.32, p < .001, respectively). CONCLUSIONS: This study demonstrates that FGR is common after chemotherapy in pregnancy, and that the duration of chemotherapy has a negative impact. Sonographic follow-up of fetal growth and well-being is recommended.
- MeSH
- gestační stáří MeSH
- hmotnost plodu MeSH
- hypotrofický novorozenec MeSH
- lidé MeSH
- novorozenec MeSH
- platina MeSH
- porod MeSH
- porodní hmotnost MeSH
- retrospektivní studie MeSH
- růstová retardace plodu chemicky indukované epidemiologie diagnóza MeSH
- těhotenství MeSH
- ultrasonografie prenatální MeSH
- vývoj plodu MeSH
- zvýšení váhy v těhotenství * MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- antitumorózní látky * MeSH
- dítě MeSH
- hematologické nádory * komplikace MeSH
- inteligence MeSH
- kojenec MeSH
- lidé MeSH
- matky MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- vývoj dítěte MeSH
- zpožděný efekt prenatální expozice * MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Gastric cancer during pregnancy is extremely rare and data on optimal treatment and possible chemotherapeutic regimens are scarce. The aim of this study is to describe the obstetric and maternal outcome of women with gastric cancer during pregnancy and review the literature on antenatal chemotherapy for gastric cancer. MATERIAL AND METHODS: Treatment and outcome of patients registered in the International Network on Cancer, Infertility and Pregnancy database with gastric cancer diagnosed during pregnancy were analyzed. RESULTS: In total, 13 women with gastric cancer during pregnancy were registered between 2002 and 2018. Median gestational age at diagnosis was 22 weeks (range 6-30 weeks). Twelve women were diagnosed with advanced disease and died within 2 years after pregnancy, most within 6 months. In total, eight out of 10 live births ended in a preterm delivery because of preeclampsia, maternal deterioration, or therapy planning. Two out of six women who initiated chemotherapy during pregnancy delivered at term. Two neonates prenatally exposed to chemotherapy were growth restricted and one of them developed a systemic infection with brain abscess after preterm delivery for preeclampsia 2 weeks after chemotherapy. No malformations were reported. CONCLUSIONS: The prognosis of gastric cancer during pregnancy is poor, mainly due to advanced disease at diagnosis, emphasizing the need for early diagnosis. Antenatal chemotherapy can be considered to reach fetal maturity, taking possible complications such as growth restriction, preterm delivery, and hematopoietic suppression at birth into account.
- MeSH
- antitumorózní látky škodlivé účinky MeSH
- dospělí MeSH
- lidé MeSH
- maternofetální výměna látek MeSH
- nádorové komplikace v těhotenství farmakoterapie MeSH
- nádory žaludku farmakoterapie MeSH
- novorozenec MeSH
- předčasný porod MeSH
- preeklampsie chemicky indukované MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- růstová retardace plodu chemicky indukované MeSH
- těhotenství MeSH
- výsledek těhotenství * MeSH
- zpožděný efekt prenatální expozice * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
PURPOSE OF REVIEW: Cancer diagnosis in young pregnant women challenges oncological decision-making. The International Network on Cancer, Infertility and Pregnancy (INCIP) aims to build on clinical recommendations based on worldwide collaborative research. RECENT FINDINGS: A pregnancy may complicate diagnostic and therapeutic oncological options, as the unborn child must be protected from potentially hazardous exposures. Pregnant patients should as much as possible be treated as non-pregnant patients, in order to preserve maternal prognosis. Some approaches need adaptations when compared with standard treatment for fetal reasons. Depending on the gestational age, surgery, radiotherapy, and chemotherapy are possible during pregnancy. A multidisciplinary approach is the best guarantee for experience-driven decisions. A setting with a high-risk obstetrical unit is strongly advised to safeguard fetal growth and health. Research wise, the INCIP invests in clinical follow-up of children, as cardiac function, neurodevelopment, cancer occurrence, and fertility theoretically may be affected. Furthermore, parental psychological coping strategies, (epi)genetic alterations, and pathophysiological placental changes secondary to cancer (treatment) are topics of ongoing research. Further international research is needed to provide patients diagnosed with cancer during pregnancy with the best individualized management plan to optimize obstetrical and oncological care.
- MeSH
- adaptace psychologická MeSH
- internacionalita MeSH
- lidé MeSH
- nádorové komplikace v těhotenství * diagnóza epidemiologie psychologie terapie MeSH
- nádory diagnóza epidemiologie psychologie terapie MeSH
- nemoci placenty diagnóza etiologie terapie MeSH
- novorozenec MeSH
- registrace statistika a číselné údaje MeSH
- těhotenství MeSH
- týmová péče o pacienty MeSH
- výsledek těhotenství epidemiologie MeSH
- ženská infertilita epidemiologie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH