Management of cancer during pregnancy and current evidence of obstetric, neonatal and pediatric outcome: a review article.

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.

Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy.

BACKGROUND: Data on the long-term outcome of children who are exposed to maternal cancer with or without treatment during pregnancy are lacking. METHODS: In this multicenter case-control study, we compared children whose mothers received a diagnosis of cancer during the pregnancy with matched children of women without a cancer diagnosis. We used a health questionnaire and medical files to collect data regarding neonatal and general health. All children were prospectively assessed (by means of a neurologic examination and the Bayley Scales of Infant Development) at 18 months, 36 months, or both. A cardiac assessment was performed at 36 months. RESULTS: A total of 129 children (median age, 22 months; range, 12 to 42) were included in the group whose mother had cancer (prenatal-exposure group) with a matching number in the control group. During pregnancy, 96 children (74.4%) were exposed to chemotherapy (alone or in combination with other treatments), 11 (8.5%) to radiotherapy (alone or in combination), 13 (10.1%) to surgery alone, 2 (1.6%) to other drug treatments, and 14 (10.9%) to no treatment. Birth weight was below the 10th percentile in 28 of 127 children (22.0%) in the prenatal-exposure group and in 19 of 125 children (15.2%) in the control group (P=0.16). There was no significant between-group difference in cognitive development on the basis of the Bayley score (P=0.08) or in subgroup analyses. The gestational age at birth was correlated with the cognitive outcome in the two study groups. Cardiologic evaluation among 47 children at 36 months of age showed normal cardiac findings. CONCLUSIONS: Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. Prematurity was correlated with a worse cognitive outcome, but this effect was independent of cancer treatment. (Funded by Research Foundation-Flanders and others; ClinicalTrials.gov number, NCT00330447.).

Cancer in pregnancy: safety and efficacy of systemic therapies.

PURPOSE OF REVIEW: Cancer in pregnancy has become increasingly frequent. It has become clear that for specific cancers under well defined circumstances, oncological treatment in pregnancy can be well tolerated and feasible for both mother and fetus. Continued critical assessment of the available literature and registration of cancer in pregnancy cases and outcomes for mother and child are necessary to work toward implementing optimal cancer treatment during pregnancy. RECENT FINDINGS: Physiologic changes in pregnancy may alter distribution and efficacy of systemic therapy. Data on systemic therapy including, chemotherapy, hormonal therapy, and targeted therapy during pregnancy are available but incomplete. Outcomes of fetuses exposed to chemotherapy in utero are generally reassuring, but new targeted therapies are mostly discouraged in pregnancy. SUMMARY: Cancer treatment during pregnancy is possible, depending on type and timing of systemic therapy and treatment modality. Available data are reassuring with a modest increase in complications such as growth restriction and preterm birth. The effect of new targeted therapies is often still unclear and therefore discouraged.

Psychological distress and cognitive coping in pregnant women diagnosed with cancer and their partners.

OBJECTIVE: A cancer diagnosis during pregnancy may be considered as an emotional challenge for pregnant women and their partners. We aimed to identify women and partners at risk for high levels of distress based on their coping profile. METHODS: Sixty-one pregnant women diagnosed with cancer and their partners filled out the Cognitive Emotion Regulation Questionnaire (CERQ) and the newly constructed Cancer and Pregnancy Questionnaire (CPQ). K-means cluster analysis was performed on the CERQ scales. Scores on the CPQ were compared between the women and their partners and between the CERQ-clusters. RESULTS: Comparison of women and partners on the CPQ did not reveal significant differences on distress about the child's health, the cancer disease, and the pregnancy or on information satisfaction (P = .16, P = .44, P = .50, and P = .47, respectively). However, women were more inclined to maintain the pregnancy than their partners (P = .011). Three clusters were retrieved based on the CERQ scales, characterized by positive coping, internalizing coping, and blaming. Women and partners using internalizing strategies had significantly higher scores on concerns about the child's health (P = .039), the disease and treatment (P < .001), and the pregnancy and delivery (P = .009) compared with positive and blaming strategies. No cluster differences were found for information satisfaction (P = .71) and tendency to maintain the pregnancy (P = .35). CONCLUSION: Women and partners using internalizing coping strategies deal with the highest levels of distress and may benefit from additional psychosocial support.

Management of gynecological cancers during pregnancy.

The diagnosis of a gynecological malignancy during pregnancy is rare but not uncommon. Cancer treatment during pregnancy is possible, but both maternal and fetal interests need to be respected. Different treatment plans may be justifiable and multidisciplinary treatment is advised. Clinical trials are virtually impossible, and current evidence is mainly based on small case series and expert opinion. Individualization of treatment is necessary and based on tumor type, stage, and gestational age at time of diagnosis. Termination of pregnancy is not necessary in most cases. Surgery and chemotherapy (second trimester and onwards) are possible types of treatment during pregnancy. Radiotherapy of the pelvic area is not compatible with an ongoing pregnancy. This article discusses the current recommendations for the management of gynecological malignancies (cervical, ovarian, and vulvar cancers) during pregnancy.

Quality of information and decision regrets during fertility-sparing management for atypical hyperplasia and endometrial cancer in a prospective cohort study.

OBJECTIVE: To evaluate satisfaction with information, treatment, and decision regret during management to preserve fertility for atypical hyperplasia (AH) or endometrial cancer (EC). METHODS: A cohort study with standardized management using chlormadinone acetate was established through a national referral centre between January 2013 and November 2019. During this period, a questionnaire was given to 136 patients aged 19 to 43 years who were followed for fertility preservation for AH or EC. The questionnaire included the validated EORTC-QLQ-INFO25, as well as questions from the validated EVAPIL questionnaire, the Treatment Satisfaction with Medicines Questionnaire, and the Decision Regret Scales concerning treatment tolerability and general satisfaction. The main outcomes measured were the quality and satisfaction with the information and treatment received and the decision regret. RESULTS: 75 patients (55.1 %) responded to the questionnaire. Overall, patients were satisfied with the information received (median 75.0, range: 25-100) and thought it was helpful (median 100.0, range: 25-100). However, 54.7 % wished for more information. Most women (52.0 %) indicated that psychological support should be available. Patients who were less satisfied with the information received or wished to receive more information thought about stopping treatment more frequently. Decision regret was not related to treatment outcome (remission, hysterectomy, live birth), and 47 of the 56 patients who did not obtain a live birth did not regret fertility preservation. None of the nine patients who regretted fertility preservation obtained a live birth. Almost all the patients reported side effects. CONCLUSIONS: Dedicated information tools that detail conservative treatment for AH and EC as well as its secondary effects should be provided to improve adherence to treatment and follow-up. Furthermore, psychological support should be systematically proposed.

Executive functioning in 6 year old children exposed to chemotherapy in utero.

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.

Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy.

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 < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6-4.3, versus 4.5, 95% CI: 4.1-4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). CONCLUSIONS: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, NCT00330447.

Data describing child development at 6 years after maternal cancer diagnosis and treatment during pregnancy.

This manuscript is an accompanying resource of the original research article entitled "Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy" and present data that compare the outcome of 6-year-old-children born to women diagnosed with cancer during pregnancy (with or without treatment during pregnancy) (study group) with children born after an uncomplicated pregnancy (control group). Oncological, obstetrical and neonatal data were collected. Neurodevelopment was examined by clinical evaluation and neuropsychological testing (including intelligence, attention and memory tests) and by general health and behavior questionnaires. Cardiac evaluation included electro- and echocardiography. Univariate analyses of covariance were used to investigate between-group differences. A subgroup analysis was performed in chemotherapy-exposed children versus controls and anthracycline-exposed versus controls. Additionally, the incidence of behaviour problems was compared to matched controls for children whose mothers died and for those with surviving mothers.

Long-term impact of prenatal exposure to chemotherapy on executive functioning: An ERP study.

OBJECTIVE: This study examines the long-term impact of prenatal exposure to chemotherapy on executive functioning and the contribution of late-prematurity to this effect, using event-related potentials. METHODS: Mothers of the prenatal-exposed children (n = 20) were diagnosed with cancer and received chemotherapeutic treatment during pregnancy. We recruited healthy controls (n = 20) who were matched on a 1:1 ratio regarding prematurity, age and sex. We assessed executive functioning at the age of nine, using two event-related potential paradigms: a Go/Nogo paradigm to investigate processes of response inhibition and conflict monitoring, as well as a Posner paradigm to investigate spatial attention. RESULTS: Lower potentials were found in prenatal-exposed children compared to controls in the Go/Nogo P3 and Posner positive slow wave. Moreover, prenatal-exposed children responded slower on the Posner paradigm compared to controls (p < .033), with more incorrect responses (p = .023). In the control group, the N2 Go/Nogo wave was more pronounced in children born after a longer gestation. CONCLUSIONS: This is the first study that demonstrates an effect of prenatal exposure to chemotherapy on the development of executive functioning, not limited to the effect of late-prematurity. SIGNIFICANCE: This study emphasizes the necessity of a long-term follow-up of prenatal-exposed children to re-inform clinical practice on the costs and benefits of late-premature induction over treatment during pregnancy.

Effects of cancer treatment during pregnancy on fetal and child development.

It has become clear that, for specific cancers and under well defined circumstances, oncological treatment in pregnancy is possible. In this Review, we summarise the evidence on fetal, neonatal, short-term, and long-term effects of prenatal exposure to cancer treatment on the child. So far, outcomes of children are generally reassuring, but long-term follow-up is insufficient. The most important risks of chemotherapy during pregnancy are preterm birth and babies being small for gestational age. Chemotherapy in the first trimester is contraindicated because of an increased risk of congenital malformations. Studies on outcomes of children exposed to radiotherapy, targeted therapy, or hormonal therapy in pregnancy are scarce. Careful registration of women undergoing cancer treatment in pregnancy and long-term follow-up of their children are important. Comprehensive documentation of the mental and physical status of children exposed to cancer treatment in utero will allow physicians and parents to best decide whether to treat cancer during pregnancy.

Hematologic Malignancies in Pregnancy: Management Guidelines From an International Consensus Meeting.

PURPOSE: The incidence of hematologic malignancies during pregnancy is 0.02%. However, this figure is increasing, as women delay conception until a later age. Systemic symptoms attributed to the development of a hematologic cancer may overlap with physiologic changes of pregnancy. A favorable prognosis is contingent upon early diagnosis and treatment. Therefore, a high index of suspicion is required by health care providers. Although timely, accurate diagnosis followed by appropriate staging is essential and should not be delayed due to pregnancy, management guidelines are lacking due to insufficient evidence-based research. Consequently, treatment is delayed, posing significant risks to maternal and fetal health, and potential pregnancy termination. This report provides guidelines for clinical management of hematologic cancers during the perinatal period, which were developed by a multidisciplinary team including an experienced hematologist/oncologist, a high-risk obstetrics specialist, a neonatologist, and experienced nurses, social workers, and psychologists. METHODS: These guidelines were developed by experts in the field during the first International Consensus Meeting of Prenatal Hematologic Malignancies, which took place in Leuven, Belgium, on May 23, 2014. RESULTS AND CONCLUSION: This consensus summary equips health care professionals with novel diagnostic and treatment methodologies that aim for optimal treatment of the mother, while protecting fetal and pediatric health.

Management of cancer in pregnancy.

A multidisciplinary discussion is necessary to tackle a complex and infrequent medical problem such as cancer occurring during pregnancy. Pregnancy does not predispose to cancer, but cancers occurring in women of reproductive age are encountered during pregnancy. Ultrasonography and magnetic resonance imaging are the preferred staging examinations, but also a sentinel node staging procedure is possible during pregnancy. Standard cancer treatment is aimed for. Operations can safely be performed during pregnancy, but surgery of genital cancers can be challenging. The observation that chemotherapy administered during the second or third trimester of pregnancy, that is, after the period of organogenesis, has little effect on the long-term outcome of children adds to the therapeutic armamentarium during pregnancy. Cancer treatment during pregnancy adds in the continuation of the pregnancy and the prevention of prematurity.

Fetal outcome after prenatal exposure to chemotherapy and mechanisms of teratogenicity compared to alcohol and smoking.

INTRODUCTION: The treatment of cancer during pregnancy is challenging because of the involvement of two individuals and the necessity of a multidisciplinary approach. An important concern is the potential impact of chemotherapy on the developing fetus. AREAS COVERED: The authors review the available literature on neonatal and long-term outcome of children prenatally exposed to chemotherapy. Chemotherapy administered during first trimester of pregnancy results in increased congenital malformations (7.5 - 17% compared to 4.1 - 6.9% background risk), whereas normal rates are found during second or third trimester. Intrauterine growth restriction is seen in 7 - 21% (compared to 10%), but children develop normal weight and height on the long term. Children are born preterm in 67.1%, compared to 4% in general population. Normal intelligence, attention, memory and behavior are reported, although intelligence tends to decrease with prematurity. Global heart function remains normal, although small differences are seen in ejection fraction, fractional shortening and some diastolic parameters. No secondary cancers or fertility problems are encountered, but follow up periods are limited. EXPERT OPINION: Most evidence is based on retrospective studies with small samples and limited follow up periods, methodology and lack of control groups. A large prospective case-control study with long-term follow up is needed in which confounding factors are well considered.