Cancer in pregnancy - The obstetrical management.

Cancer in pregnancy, defined as a cancer diagnosed during pregnancy, is a rare but severe condition presenting both clinical and ethical challenges. During the last two decades a paradigm shift has occurred towards recommending similar staging and treatment regimens of pregnant and non-pregnant cancer patients. This strategy is a result of an increasing number of reassuring reports on chemotherapy treatment in pregnancy after the first trimester. The management of cancer in pregnancy should be managed in a multidisciplinary team where staging, oncological treatment, social and mental care, timing of delivery, and follow-up of the infant should be planned. Due to the rarity, centralization is recommended to allow experience accumulation. Furthermore, national and international advisory boards are supportive when there is a lack of expertise.

Cancer in pregnancy and the risk of adverse pregnancy and neonatal outcomes: A nationwide cohort study.

OBJECTIVES: To investigate the obstetrical management of cancer in pregnancy and to determine adverse pregnancy and neonatal outcomes. DESIGN: A nationwide cohort study. SETTING AND POPULATION: We included all pregnancies (n = 4 071 848) in Denmark from 1 January 1973 to 31 December 2018. METHODS: Exposure was defined as pregnancies exposed to maternal cancer (n = 1068). The control group comprised pregnancies without cancer. The groups were compared using logistic regression analysis and adjusted for potential confounders. MAIN OUTCOME MEASURES: The outcomes were induced abortion, preterm birth and adverse neonatal outcomes. RESULTS: More women with cancer in pregnancy, as compared with the control group, experienced induced abortion (24.8% vs. 20.0%); first-trimester induced abortion adjusted odds ratio (aOR) 3.5 (95% confidence interval [CI] 2.7-4.5), second-trimester induced abortion; aOR 8.8 (95% CI 6.3-12.3), planned preterm birth (11.8% vs. 1.3%); aOR 10.8 (95% CI 8.0-14.6) and planned preterm birth at <32 gestational weeks; aOR 16.3 (95% CI 8.3-31.7). Neonates born to mothers with cancer in pregnancy had a higher risk of respiratory distress syndrome; aOR 3.5 (95% CI 2.8-4.4), low birthweight; aOR 3.8 (95% CI 3.1-4.8), admission to neonatal intensive care unit for >7 days; aOR 5.1 (95% CI 3.9-6.6), neonatal infection; aOR 1.8 (95% CI1.1-3.1) and neonatal mortality; aOR 4.7 (95% CI 2.7-8.2), but not of SGA; aOR 1.0 (95% CI 0.6-1.5) and malformations; 1.2 (95% CI 0.9-1.7). CONCLUSION: Cancer in pregnancy increases the risk of induced abortion and planned premature birth. Neonates born to mothers with cancer in pregnancy had an increased risk of neonatal morbidity and mortality, presumably due to prematurity. TWEETABLE ABSTRACT: Cancer in pregnancy is associated with an increased risk of premature birth leading to adverse neonatal outcomes.

Potentially modifiable risk factors of preterm delivery in women with type 1 and type 2 diabetes.

AIMS/HYPOTHESIS: We aimed to identify potentially modifiable risk factors and causes for preterm delivery in women with type 1 or type 2 (pre-existing) diabetes. METHODS: A secondary analysis of a prospective cohort study of 203 women with pre-existing diabetes (117 type 1 and 86 type 2 diabetes) was performed. Consecutive singleton pregnancies were included at the first antenatal visit between September 2015 and February 2018. RESULTS: In total, 27% (n = 55) of the 203 women delivered preterm at median 36 + 0 weeks. When stratified by diabetes type, 33% of women with type 1 diabetes delivered preterm compared with 20% in women with type 2 diabetes (p = 0.04). Women delivering preterm were characterised by a higher prevalence of pre-existing kidney involvement (microalbuminuria or diabetic nephropathy) (16% vs 3%, p = 0.002), preeclampsia (26% vs 5%, p < 0.001), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (2.7% vs -1.6% from the mean, p = 0.008), higher gestational weight gain (399 g/week vs 329 g/week, p = 0.01) and similar HbA1c levels in early pregnancy (51 mmol/mol [6.8%] vs 49 [6.6%], p = 0.22) when compared with women delivering at term. Independent risk factors for preterm delivery were pre-existing kidney involvement (OR 12.71 [95% CI 3.0, 53.79]), higher gestational weight gain (per 100 g/week, OR 1.25 [1.02, 1.54]), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (% from the mean, OR 1.07 [1.03, 1.12]) and preeclampsia (OR 7.04 [2.34, 21.19]). Two-thirds of preterm deliveries were indicated and one-third were spontaneous. Several contributing factors to indicated preterm delivery were often present in each woman. The main indications were suspected fetal asphyxia (45%), hypertensive disorders (34%), fetal overgrowth (13%) and maternal indications (8%). Suspected fetal asphyxia mainly included falling insulin requirement and abnormal fetal haemodynamics. CONCLUSIONS/INTERPRETATIONS: Presence of preeclampsia, higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks and higher gestational weight gain were independent potentially modifiable risk factors for preterm delivery in this cohort of women with pre-existing diabetes. Indicated preterm delivery was common with suspected fetal asphyxia or preeclampsia as the most prevalent causes. Prospective studies evaluating whether modifying these predictors will reduce the prevalence of preterm delivery are warranted.

Prophylactic progesterone and preterm birth.

This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.

School performance and educational achievement in children exposed to maternal cancer in utero.

BACKGROUND: In utero exposure to maternal cancer and cancer treatment might influence the child's cognitive development. This study investigated if exposure to maternal cancer during fetal life impacted school performance and educational achievement as adults. METHODS: This nationwide retrospective cohort study identified all live-born children in Denmark between January 1978 and December 2013. Exposure was defined as maternal cancer diagnosis during pregnancy. Four partly overlapping birth cohorts were constructed depending on the outcome of interest: (1) receiving special educational support for birth years 2001-2013; (2) grade point average (GPA) at the final exams after 10th grade for 1986-2003; (3) educational achievement at 20 years for 1978-1998; and (4) education at 30 years for 1978-1988. Logistic and linear models were adjusted for birth year, maternal age, maternal education and maternal death. RESULTS: The estimated probability of receiving special educational support was similar in the exposed group and the reference (adjusted OR 0.96; 95% CI 0.46 to 1.77, non-significant). The GPA did not statistically differ (0.13 grade points; 95% CI -0.18 to 0.45, non-significant). The achieved educational levels were similar for the exposed group and the reference at 20 years, with an adjusted OR of 1.07 (95% CI 0.82 to 1.40) for low versus medium educational level, and at 30 years with an adjusted OR of 0.73 (95% CI 0.35 to 1.50) for low versus high educational level and of 1.07 (95% CI 0.66 to 1.72) for medium versus high educational level. CONCLUSION: Our findings did not indicate poorer performance in compulsory school nor impairment of adult educational achievement after exposure to maternal cancer in utero.

New expert advice on cancer in pregnancy.

Cancer in pregnancy is rare, and most physicians lack knowledge in handling pregnant cancer patients. This review summarises the present knowledge on this condition. In the Netherlands, an Advisory Board on Cancer in Pregnancy was established in 2012. The board supports Dutch physicians' decisions in the management of pregnant patients with cancer. In 2021 the International Advisory Board on Cancer in Pregnancy was established, and in continuation, the Danish Advisory Board on Cancer in Pregnancy (DABCIP) has now been founded. DABCIP consists of 22 members from 13 different medical disciplines.

Toxoplasma gondii-associated Placentitis in the absence of maternal seroconversion.

Severe granulomatous chronic villitis with focal remnants of Toxoplasma was confirmed by immunohistochemistry and DNA-based methods in the placenta from a child that died four days after birth. The immunocompetent mother was seronegative for Toxoplasma at delivery and 10 months later. Placental infection may happen without maternal systemic infection.

Long-Term Morbidity and Mortality in Children After In Utero Exposure to Maternal Cancer.

PURPOSE: In utero exposure to maternal cancer and cancer treatment might influence the child's short- and long-term health and development. The objective of the study was to investigate short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero. METHODS: This nationwide cohort study identified all liveborn children in Denmark between January 1978 and December 2018. Exposure was defined as maternal cancer diagnosis during pregnancy, and in a subgroup analysis, exposure to chemotherapy in utero. The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Follow-up started at birth and ended at an event, death, emigration, or end of 2018. Hazard ratios of end points adjusted for potential confounders were estimated using Cox regression analysis. RESULTS: Of 2,526,163 included liveborn children, 690 (0.03%) were exposed to maternal cancer in utero. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality, adjusted hazard ratio 0.8 (95% CI, 0.4 to 1.5), nor increased risk of congenital malformations, overall somatic or psychiatric disease. During the period 2002-2018, of 378 (0.03%) children exposed to cancer in utero, 42 (12.5%) were exposed to chemotherapy. Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases nor to congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy. CONCLUSION: Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.

Survival in Women Diagnosed With Breast Cancer During Pregnancy.

INTRODUCTION: Pregnancy rarely coincides with breast cancer, but when it does, uncertainties remain about how survival is affected. In a nation-wide study, we investigated survival in women diagnosed with breast cancer during pregnancy. MATERIALS AND METHODS: Through health registries, we identified women with breast cancer at ages 15-44 years from 1973-2016 in Denmark and included 156 who were pregnant at diagnosis and 11,110 who were not. We compared overall mortality in pregnant and non-pregnant women using multivariate Cox regression stratified by time since cancer: <2 and ≥2 years. RESULTS: During the first 2 years after diagnosis, the hazard ratio of overall death was 2.28 (95% CI: 1.48-3.52) for pregnant versus non-pregnant breast cancer patients after adjustment for age and calendar period and 1.62 (95% CI: 1.05-2.50) after further adjustment for extent of disease. Adjusting for additional tumor characteristics, the hazard ratio was still significantly increased. Beyond the first 2 years, there was no excess mortality. CONCLUSION: Our study identifies the early period after breast cancer as a period of particular interest in future studies on survival after breast cancer in pregnancy. We found no evidence that survival is affected by pregnancy when 2 or more years have passed since diagnosis.

Falling Insulin Requirement in Pregnant Women With Diabetes Delivering Preterm: Prevalence, Predictors, and Consequences.

CONTEXT: Falling insulin requirements often lead to considerations of whether a pregnancy can continue safely or if delivery is indicated. OBJECTIVE: To evaluate prevalence and predictors of falling insulin requirements in pregnant women with preexisting diabetes delivering preterm and to explore the relationship to fetal asphyxia and neonatal morbidity. METHODS: A prospective cohort study of 101 consecutive singleton pregnant women with preexisting diabetes delivering preterm < 37 weeks (68 type 1 and 33 type 2 diabetes) where the prevalence of falling insulin requirements (≥20%) before delivery was recorded. RESULTS: In total, 27% (27/101) experienced falling insulin requirements of median 30% (interquartile range 24-40) before delivery. In all women with type 1 diabetes, the prevalence was 37% (25/68), whereas it was 43% (24/56) in those with indicated preterm delivery and 6% (2/33) among women with type 2 diabetes. In women with type 1 diabetes and indicated preterm delivery, falling insulin requirements were first identified at 34 + 5 (33 + 6-35 + 4) weeks + days and delivery occurred 3 (1-9) days later. Gestational age at delivery, prevalence of suspected fetal asphyxia, and neonatal morbidity were similar in women with and without falling insulin requirements. Neither glycemic control, nausea, or preeclampsia was associated with falling insulin requirement. CONCLUSION: Falling insulin requirements often preceded preterm delivery in women with type 1 diabetes, foremost when preterm delivery was indicated, but was not related to fetal asphyxia or neonatal morbidity. Whether falling insulin requirements in late pregnancy are a warning sign of placental insufficiency or mainly reflects variations in normal physiology needs further investigation.

[Biological disease-modifying anti-rheumatic drugs for pregnant and lactating women or male partners].

Effective medical treatment of rheumatic diseases during pregnancy and lactation is important, but the evidence for use of biological disease-modifying anti-rheumatic drugs (bDMARDs) is sparse and recommendations conflicting, which we discuss in this review. While some tumour necrosis factor (TNF)-α inhibitors appear safe during pregnancy and lactation, the evidence for use of non-TNF-α inhibitors is still too sparse to exclude adverse pregnancy outcomes and harm to the lactating child. The limited evidence on paternal exposure indicates, that TNF-α inhibitors do not affect male fertility or harm offspring. For non-TNF-α inhibitors, the evidence is still insufficient to draw any conclusion.

Male reproductive disorders in humans and prenatal indicators of estrogen exposure. A review of published epidemiological studies.

Male reproductive disorders in humans and prenatal indicators of estrogen exposure. A review of published epidemiological studies. Reports of an increase in male reproductive disorders in several countries led to the hypothesis that estrogens during fetal life may cause reduced sperm counts, cryptorchidism, hypospadias and testicular cancer. So far the hypothesis is based on animal studies and reports from the wild life. We systematically searched the epidemiological literature for evidence linking indicators of prenatal serum levels of maternal estrogens with sperm density, hypospadias, cryptorchidism and testicular cancer in humans. Indicators of fetal estrogen exposure included direct measurements, recorded intake of hormones (diethylstilbestrol (DES), oral contraceptives (OCs) and estrogens), pregnancy conditions with known deviant estrogen level as for instance twin pregnancies and some environmental exposures. Among 425 papers we reviewed 81 publications with appropriate information. With the possible exception of testicular cancer there is no strong epidemiological evidence to indicate that prenatal exposure to estrogen are linked to disturbed development of the male reproductive organs.

[Cancer in pregnancy]. / Cancer under graviditeten.

Cancer in pregnancy occurs in about one in 1,000 pregnancies. Recent reports have shown that most treatment regimes in second and third trimester are safe for the mother and the child. This has led to a paradigm shift in treating pregnant women with cancer. The management of the pregnant woman should be in a multidisciplinary setting, and delivery should be postponed to avoid very preterm delivery and planned 2-3 weeks after the last chemotherapeutic treatment allowing both maternal and foetal bone marrow to recover.

[Chemotherapy in the second and third trimester of pregnancy is compatible with the delivery of a healthy infant]. / Kemoterapi i andet og tredje trimester er foreneligt medforløsning af et raskt barn

This case report describes the delay in diagnosis and treatment of a diffuse large B-cell lymphoma in pregnancy of a 27-year-old woman. Chemotherapy was initiated in week 21 of pregnancy - the tumour regressed and the foetus had linear growth. The patient had caesarean section in week 34, and after delivery she received high doses of methotrexate and obtained complete remission. The two-year-old infant had a normal development.

The relation between daily activities and scrotal temperature.

Normal sperm production depends on a testicular temperature below body temperature, but the thermogenic effects of daily life activities are not well known. We described the association between scrotal temperature and daily activities in 101 males using a non-invasive method for measuring scrotal temperature. A thermistor was attached to the underwear and the temperature of the scrotal skin was logged by a portable device every 5 min for 24h. Participants reported sedentary position and activities at work and during spare time in a questionnaire. Scrotal temperature was strongly correlated with sedentary work position with a dose-effect association (<1 h sedentary: 33.1 degrees C, >6 h sedentary: 34.7 degrees C, median values). The variation in sedentary work accounted for 31.5% of the variation in median temperature during the entire 24h. Sedentary position during spare time did not correlate with scrotal temperature. Median temperature at night was 1.2 degrees C higher than during the daytime. No effect was found for size or reported tightness of the underwear. In a model experiment, the deviance between testicular and scrotal temperature was estimated as maximally 0.1-0.6 degrees C, depending on the type of activity. Measuring scrotal temperature provides a valid estimate of testicular temperature and is feasible in large cohorts. We conclude that work position is an important determinant of testicular temperature.

Impact of diurnal scrotal temperature on semen quality.

A high scrotal temperature is a common finding in infertile patients and experimental studies indicate that specific types of heat exposure reduce semen quality. More and more men have a sedentary work position, which increases scrotal temperature. Semen and blood samples from 99 healthy men were analysed in relation to scrotal skin temperature obtained by a 24-h continuous monitoring protocol. Information on sedentary position at work and during spare time was collected by questionnaires. A negative correlation was found between high scrotal temperature and sperm output. Sperm concentration decreased 40% per 1 degrees C increment of median daytime scrotal temperature (95% CI: 8-71%). Similar results were found for total sperm count, FSH, and inhibin B. Motility, morphology, pH, and testosterone were not significantly associated with temperature. Only weak and inconsistent associations were found between sedentary position and semen quality. We conclude that scrotal temperature and semen quality are closely associated. Sedentary work position encountered in ordinary jobs, although a strong determinant of scrotal temperature, does not seem to have any effect on semen quality.

[Is change of general practitioners more frequent among patients diagnosed with cancer or other serious diseases?]. / Skifter patienter hyppigere laege efter diagnostik af cancersygdom og andre alvorlige sygdomme?

INTRODUCTION: Change of GP may imply that the patient is dissatisfied with the health service provided. The aim of this study was to investigate whether newly diagnosed cancer patients change their GP more often than other patient groups and the background population. MATERIAL AND METHODS: The investigation was conducted using data on inhabitants from the counties of Aarhus, Vejle and South Jutland. We included 900 Group 1 insured patients, aged 18-75 years, distributed into three groups: 1) frequent cancers, 2) rare cancers and 3) benign, but chronic or severe new diseases. The diagnoses included occurred for the first time at the time of inclusion. Three hundred controls were randomly selected from the regional health care registry in Aarhus. The study period was from March 1 to August 30 1994. A change of GP was defined as a change not caused by the patient's change of residence or the GP's change of practice registration number due to expansion, takeover or split up of practice. RESULTS: In the three disease groups, 28 cases of change of GP were registered with a frequency of 5% (frequent cancers), 2.7% (rare cancers) and 1.7% (benign, but chronic or severe new diseases). The frequency in the background population was 2.7%. None of the differences were statistically significant. DISCUSSION: During the first year following a cancer or chronic disease diagnosis, change of GP is rare, particularly among patients with rare cancers. We reject the hypothesis that change of GP is frequent among newly diagnosed cancer patients.

[The use of amniotomy to shorten spontaneous labour. A survey of a Cohrane review]. / Brug af amniotomi til afkortning af den spontane fødsel. Gennemgang af et Cochrane-review.

The main results from the Cohrane review "Amniotomy for shortening spontaneous labour" from 2007 was evaluated and compared to Danish obstetrics practice. Routine use of amniotomy was not recommended, since there was no difference in the duration of first stage of labour in five randomised, controlled studies (n = 1,127 women), and a tendency towards a higher risk of caesarean section in the amniotomy group, although this was not statistically significant (nine randomized controlled trials, n = 4,370). The results were in accordance with Danish practice.