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

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

INTRODUCTION: Fetal growth restriction (FGR) carries an increased risk of perinatal mortality and morbidity. A major cause of FGR is placental insufficiency. After in utero chemotherapy-exposure, an increased incidence of FGR has been reported. In a prospective cohort study we aimed to explore which pathways may contribute to chemotherapy-associated FGR. METHODS: Placental biopsies were collected from 25 cancer patients treated with chemotherapy during pregnancy, and from 66 control patients. Differentially expressed pathways between chemotherapy-exposed patients and controls were examined by whole transcriptome shotgun sequencing (WTSS) and Ingenuity Pathway Analysis (IPA). Immunohistochemical studies for 8-OHdG and eNOS (oxidative DNA damage), proliferation (PCNA) and apoptosis (Cleaved Caspase 3) were performed. The expression level of eNOS, PCNA and IGFBP6 was verified by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR). RESULTS: Most differential expressed genes between chemotherapy-exposed patients and controls were related to growth, developmental processes, and radical scavenging networks. The duration of chemotherapy exposure had an additional impact on the expression of genes related to the superoxide radicals degeneration network. Immunohistochemical analyses showed a significantly increased expression of 8-OHdG (P = 0.003) and a decreased expression of eNOS (P=0.015) in the syncytiotrophoblast of the placenta of cancer patients. A decreased expression of PCNA was detected by immunohistochemistry as RT-qPCR (NS). CONCLUSION: Chemotherapy exposure during pregnancy results in an increase of oxidative DNA damage and might impact the placental cellular growth and development, resulting in an increased incidence of FGR in this specific population. Further large prospective cohort studies and longitudinal statistical analyses are needed.

• MeSH
• antitumorózní látky škodlivé účinky   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové komplikace v těhotenství farmakoterapie   metabolismus   patologie   MeSH
• placenta metabolismus   patologie   MeSH
• prospektivní studie MeSH
• růstová retardace plodu chemicky indukované   metabolismus   patologie   MeSH
• sekvenování exomu MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Air pollution with increased concentrations of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs, represented by benzo[a]pyrene, B[a]P) affect fetal development, reduce birth weights (LBW) of newborns, and increases intrauterine growth retardation (IUGR). The Southern Bohemia Region is believed to be one of the least air polluted regions in the Czech Republic. Monitoring air pollution in the city of České Budějovice from 2011-2015, PM2.5 (particulate matter <2.5 µm) decreased from 20.3 ± 14.5 µg/m3 to 14.3 ± 8.6 µg/m3, but concentrations of B[a]P did not change between the years 2007-2015: 1.5 ± 0.6 ng/m3 vs. 1.4 ± 1.4 ng/m3. Higher B[a]P concentrations the winter induce genetic damage in newborns, increase frequency of micronuclei (chromosomal aberrations), deregulate genes for immunity in umbilical cord blood, and increase incidence of IUGR and LBW in newborns.

• MeSH
• benzopyren škodlivé účinky   MeSH
• chromozomální aberace chemicky indukované   MeSH
• dospělí MeSH
• látky znečišťující vzduch škodlivé účinky   MeSH
• lidé MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• nemoci novorozenců chemicky indukované   MeSH
• novorozenec s nízkou porodní hmotností MeSH
• novorozenec MeSH
• pevné částice škodlivé účinky   MeSH
• růstová retardace plodu chemicky indukované   MeSH
• těhotenství MeSH
• znečištění ovzduší škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Cigaretový kouř představuje nejrozšířenější reprodukční škodlivinu současnosti. Kouření cigaret je rizikem pro lidskou reprodukci ještě předtím, než žena zjistí, že je těhotná. Prevalence kouření v těhotenství se v České republice pohybuje mezi 6 a 24 % a předpokládá se, že i tato data jsou podhodnocená. Kouření se na patologickém průběhu těhotenství a vývoji plodu podílí mnoha mechanismy. U těhotných kouřících žen je udáván vyšší výskyt mimoděložních těhotenství, spontánních potratů, abrupce placenty, placenta previa, předčasného protržení plodových blan, předčasných porodů. Naopak nižší je u kouřících těhotných žen incidence preeklampsie. Kouření ženy-matky také nepříznivě ovlivňuje kojení. Kouření může negativně ovlivnit samotný intrauterinní vývoj plodu a má podstatné následky i pro následný vývoj dítěte. Na zvýšení rizika poškození plodu má podíl i kuřáctví otce. Kouření matky má vliv na vznik a vývoj f etálního tabákového syndromu, syndromu náhlého úmrtí, vrozených vývojových vad, nemocí dýchacího ústrojí, na zvýšené riziko zhoubných nádorů v dětství, kardiovaskulární rizika, neurální poškození a behaviorální poruchy. Také pasivní kouření těhotné ženy má značný negativní efekt na vyvíjející se plod.

Cigarette smoke is currently the most widespread harmful substance affecting reproduction. Smoking cigarettes is risky even before the woman finds out that she is pregnant. Nhile the prevalence of smoking during pregnancy in the Czech Republic ranges from 6 to 24%, it is assumed that even this data represents an underestimate. Smoking and its many mechanisms contribute to the development of pathological pregnancy. The rates of extra-uterine pregnancy, spontaneous miscarriage, placental abruption, placenta praevia, premature rupture of foetal membranes, and premature birth are stated to be higher among pregnant women who smoke. The incidence of pre-eclampsia is, on the other hand, lower in pregnant women who smoke. The incidence of pre-eclampsia is, on the other hand, lower in pregnant women who smoke. Smoking cigarettes can negatively influence the actual intrauterine development of the foetus, and has consequences of considerable importance even for the subsequent development of the child. Smoking on the part of the father adds to the increased risk of foetal damage. Smoking on the part of the mother influences the establishment and development of foetal tobacco syndrome, sudden infant death syndrome, inborn errors of development, disorders of the respiratory sysem, increased risk of having malignant tumours during childhood, cardiovascular risks, neural damage, and behavioural disorders. Smoking on the part of mothers also has adverse effects on breastfeeding. Passive smoking on the part of a pregnant woman has a considerable negative effeet on the development of the foetus.

• MeSH
• dítě MeSH
• komplikace těhotenství * epidemiologie   etiologie   prevence a kontrola   MeSH
• kouření * epidemiologie   psychologie   škodlivé účinky   MeSH
• lidé MeSH
• náhlá smrt kojenců epidemiologie   etiologie   MeSH
• nemoci novorozenců epidemiologie   chemicky indukované   prevence a kontrola   MeSH
• novorozenec MeSH
• růstová retardace plodu chemicky indukované   MeSH
• těhotenství MeSH
• vrozené vady epidemiologie   etiologie   MeSH
• znečištění tabákovým kouřem prevence a kontrola   škodlivé účinky   MeSH
• zpožděný efekt prenatální expozice epidemiologie   etiologie   prevence a kontrola   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• dítě MeSH
• kojenec MeSH
• komplikace těhotenství chemicky indukované   klasifikace   MeSH
• kouření tabáku * škodlivé účinky   MeSH
• lidé MeSH
• mutageny škodlivé účinky   MeSH
• nemoci plodu chemicky indukované   klasifikace   MeSH
• nikotin farmakologie   škodlivé účinky   MeSH
• odvykání kouření MeSH
• pití alkoholu * škodlivé účinky   MeSH
• růstová retardace plodu chemicky indukované   MeSH
• spektrum vrozených alkoholových poruch MeSH
• těhotenství * MeSH
• teratogeny MeSH
• zdraví dítěte MeSH
• zdraví kojenců MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• těhotenství * MeSH
• ženské pohlaví MeSH

BACKGROUND: Oxidative damage to placental DNA can result in negative pregnancy outcomes, including intrauterine growth restriction (IUGR) and low birth weight (LBW). OBJECTIVE: We investigated associations between the levels of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage, in placental DNA, exposure to air pollutants during pregnancy, genetic polymorphisms in 94 selected genes, and pregnancy outcomes. METHODS: We studied 891 newborns who were IUGR- or LBW-affected or normal weight and were born between 1994 and 1999 in the Czech Republic in two districts with different levels of air pollution. RESULTS: We found nonsignificantly elevated 8-oxodG levels in the IUGR-affected group compared with the non-IUGR group (p = 0.055). Similarly, slightly elevated 8-oxodG levels were found in the LBW-affected group compared with the non-LBW group (p < 0.050). In univariate analyses, we identified single nucleotide polymorphisms associated with 8-oxodG levels, IUGR, and LBW. Exposure to particulate matter < 2.5 µm was associated with increased 8-oxodG levels in placental DNA and LBW. However, multivariate-adjusted logistic regression revealed that above-median 8-oxodG levels were the only factor significantly associated with IUGR [OR = 1.56; 95% confidence interval (CI), 1.07-2.37; p = 0.022]. Above-median levels of 8-oxodG were associated with LBW (OR = 1.88; 95% CI, 1.15-3.06; p = 0.011). Other variables associated with LBW included sex and gestational age of the newborn, maternal smoking, and haplotypes in the promoter region of the gene encoding mannose-binding lectin 2 (MBL2). The role of air pollutants in the risk of adverse pregnancy outcomes seemed to be less important. CONCLUSIONS: Levels of 8-oxodG in placental DNA were associated with the risk of IUGR as well as LBW. Newborn's sex, gestational age, maternal smoking, and genetic polymorphisms in the promoter region of the MBL2 gene were associated with LBW incidence.

• MeSH
• deoxyguanosin analogy a deriváty   analýza   MeSH
• DNA chemie   MeSH
• lidé MeSH
• novorozenec s nízkou porodní hmotností metabolismus   MeSH
• novorozenec MeSH
• pevné částice toxicita   MeSH
• růstová retardace plodu chemicky indukované   metabolismus   MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: The aim of the study was to evaluate the effect of substitution therapy in heroin addicted pregnant women on the course of pregnancy, perinatal outcomes and course of the neonatal abstinence syndrome.

• MeSH
• buprenorfin škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• financování organizované MeSH
• heroin aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• methadon škodlivé účinky   terapeutické užití   MeSH
• narkotika škodlivé účinky   terapeutické užití   MeSH
• novorozenec MeSH
• novorozenecký abstinenční syndrom patofyziologie   prevence a kontrola   MeSH
• pacienti ambulantní MeSH
• poporodní období účinky léků   MeSH
• porodní hmotnost účinky léků   MeSH
• prospektivní studie MeSH
• růstová retardace plodu chemicky indukované   patofyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• závislost na heroinu rehabilitace   MeSH
• životní styl MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

The thalidomide tragedy stimulated an intense research in the etiology, prevention and treatment of congenital malformations. The Government requires that drugs and food additives be evaluated pre-clinically for toxicity, including developmental toxicity, before being marketed. The number of compounds which must be tested has increased dramatically with the continuous development of therapeutic, cosmetic and food additive chemicals. Such tests include: in vitro studies which can serve as efficient pre-screens to rank chemicals for further batteries of in vivo tests on pregnant animals. However, the safety of any drug would be determined only by a post-marketing epidemiological survey. Taking into account the altered susceptibility to different drugs in a pregnant individual, it could be said that administration of any drug during the first trimester is an experiment in human teratology.

• MeSH
• abnormality vyvolané léky prevence a kontrola   MeSH
• lidé MeSH
• odumření plodu chemicky indukované   MeSH
• preklinické hodnocení léčiv MeSH
• růstová retardace plodu chemicky indukované   MeSH
• těhotenství MeSH
• teratogeny toxicita   MeSH
• teratologie MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• agonisté beta-2-adrenergních receptorů * škodlivé účinky   terapeutické užití   MeSH
• antiastmatika škodlivé účinky   terapeutické užití   MeSH
• bronchiální astma * farmakoterapie   MeSH
• formoterol fumarát škodlivé účinky   terapeutické užití   MeSH
• komplikace těhotenství MeSH
• lidé MeSH
• růstová retardace plodu chemicky indukované   etiologie   MeSH
• těhotenství fyziologie   účinky léků   MeSH
• Check Tag
• lidé MeSH
• těhotenství fyziologie   účinky léků   MeSH
• ženské pohlaví MeSH