Tineke Vandenbroucke

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.).

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.

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 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.

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.

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.

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.

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

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.

Development of children born to mothers with cancer during pregnancy: comparing in utero chemotherapy-exposed children with nonexposed controls

both surgical procedures are important factors that could lead to impaired healing of uterine scar, uterine rupture, and impaired placentation (placenta accreta) in the next pregnancies. While there is no evidence that locking the second layer is related to impaired healing of the uterine scar, it is, to our knowledge, an unusual procedure that has not been reported in literature. With all our respect, we are skeptical that this could be a common practice, as we do not understand why a surgeon would do this. To our opinion, beside good surgical principles, there are 3 modifiable factors that have been interrelated and that can be implicated in long-term impaired healing of the uterine scar: a single-layer; the inclusion of endometrium (decidual layer of the uterine wall); and the locking of the first layer. The actual literature suggests that a combination of the 3 (a locked single-closure of the uterus including the full thickness of the myometrium with the endometrium into the scar) is detrimental for future pregnancies’ outcomes when compared to the unlocked double-layer closure aiming at good approximation of the individual layers (endometrium-endometrium; myometrium-myometrium) of the uterine wall. Future randomized controlled trials with adequate power should be designed to evaluate this specific hypothesis using shortterm surrogate outcomes, such as scar defect and remaining

Neonatal and Long-Term Consequences of In Utero Exposure to Systemic Anticancer Therapy

Many physicians remain reluctant to administer chemotherapy during pregnancy. Chemotherapy is cytotoxic and interferes with cell growth. When chemotherapy is given during the first trimester of pregnancy, the period of organogenesis, there is an increased risk of structural anomalies. When given beyond the first trimester, chemotherapy does not cause other or more congenital malformations. Several studies have reported on the short- and long-term outcome of children exposed to chemotherapy during the second and third trimester of pregnancy with reassuring results for neurocognitive development and cardiac functions. A single case of secondary malignancy in the child was reported. Chemotherapy administration during pregnancy may lead to lower birth weights, but biometry curves seem to normalize during the first months of childhood. Prenatal exposure to platinum-based antineoplastics may induce hearing loss, especially when high dosages are used. Since prematurity has been related to decreased cognitive functioning, postponement of delivery can be achieved by maternal cancer treatment during pregnancy. Overall, the use of several chemotherapeutic agents during pregnancy is considered safe and could help optimizing patient management without compromising fetal outcome.