Seminars in Fetal & Neonatal Medicine - Articles in Press

Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: An observational study - Corrected Proof

Luc Cornette — 2012-05-21

Amant F, Van Calsteren K, Halaska M, et al. Lancet Oncol 2012;13:256–264. In this multicentre observational cohort study, the authors investigate whether prenatal exposure to chemotherapy, given after the first trimester of pregnancy, has deleterious effects on general health, cardiac function and neurodevelopmental outcome within the offspring.

Renal and hepatic tumors in the neonatal period - Corrected Proof

Patrick A. Thompson, Murali Chintagumpala — 2012-05-18

Summary: Renal and hepatic tumors in neonates are extremely rare. Nevertheless it is important for clinicians to be familiar with them. Both renal and hepatic neonatal tumors are heterogeneous collections of several tumor types. Some renal and hepatic tumors are benign and may require no interventions whereas others can be associated with significant morbidity and even mortality and may require multimodality treatment. Early diagnosis and initiation of the proper treatment plan is crucial for achieving the best outcomes for these rare tumors in this vulnerable population.

Leukaemia & cancer in neonates - Corrected Proof

Josef Vormoor, Murali Chintagumpala — 2012-05-10

In the UK between 1993 and 2007, 303 neonates were reported to the National Registry of Childhood Tumours with a diagnosis of a cancer (including non-malignant CNS tumours) in the first four weeks of life, corresponding to an incidence of 28 neonatal cancers per one million live births (data kindly provided by Charles Stiller, Childhood Cancer Research Group, University of Oxford). These included 70 children with extracranial germ cell tumours (mainly teratomas), 63 neuroblastomas, 51 leukaemias, 51 brain tumours, 29 retinoblastomas, 25 soft tissue sarcomas and a few other rare tumours. These statistics exclude “benign” disorders such as transient abnormal myelopoiesis and mesoblastic nephroma.

Diagnosis and management of neonatal leukaemia - Corrected Proof

Marieke H. van der Linden, Sara Creemers, Rob Pieters — 2012-04-17

Summary: Leukaemia in neonates (infants <1 month) is rare, whereby neonatal acute myeloid leukaemia (AML) is more frequent than neonatal acute lymphoblastic leukaemia (ALL). High mortality rates are observed, though AML has a better prognosis than ALL. Neonatal leukaemia is typically presented with hepatosplenomegaly, leukaemia cutis and/or hyperleucocytosis. Congenital infections should be ruled out before diagnosis. Rearrangement of the MLL gene is the most frequently occurring genetic aberration. Treatment includes intensive multi-agent chemotherapy, usually with age-related dose adjustments next to supportive care. Treatment intensification for ALL could be indicated in the future as the dismal prognosis is subject to high relapse rates in ALL.

Diagnosis and management of brain and spinal cord tumors in the neonate - Corrected Proof

Steven W. Hwang, Jack M. Su, Andrew Jea — 2012-04-05

Summary: Congenital central nervous system (CNS) tumors are rare, accounting for <5% of childhood CNS tumors. Although the definition remains arbitrary, ‘congenital’ is often defined as CNS tumors diagnosed at birth or within a few months after birth. Congenital CNS tumors are now increasingly detected on prenatal ultrasound, with polyhydramnios as the most frequent finding. After delivery, most congenital CNS tumors are associated with macrocrania and hydrocephalus. Teratomas are the most common congenital CNS tumors; other common tumors include astrocytomas, embryonal tumors such as medulloblastomas, and choroid plexus tumors. Choroid plexus tumors (predominantly papillomas) have the best outcome, as aggressive surgical resection can be curative. Other congenital CNS tumors have a collectively poor prognosis, although some subtypes may benefit from complete resections and chemotherapy. Given the rare incidences and diverse pathology of congenital CNS tumors, multicenter studies are required to accurately assess treatment efficacy and outcome measures.

Chemotherapy in newborns and preterm babies - Corrected Proof

Gareth J. Veal, Alan V. Boddy — 2012-03-30

Summary: The determination of appropriate dosing regimens for the treatment of infants and very young children with cancer represents a major challenge in paediatric oncology. Whereas dose reductions are commonplace for many chemotherapeutics in this patient group, the appropriateness of dose reductions for drugs is unclear when the limited number of published studies reporting on pharmacokinetics in infant patient populations are considered. Developmental physiological changes, potentially impacting significantly on drug disposition, occur throughout childhood, with a number of important changes observed within the first few weeks from birth. The current review focuses on the developmental physiology of preterm babies and infants and the potential impact of physiological changes on drug disposition, clinical response and toxicity. Dose reductions for a number of important anticancer drugs are compared between tumour types and clinical protocols. Where data exist, differences in pharmacokinetics between infants and older children are highlighted. In addition, the impact of confounding factors relating to the availability of appropriate drug formulations and ethical challenges concerning the conduct of clinical pharmacology studies in infant patient populations are addressed. As many currently used drugs are highly likely to be important in the treatment of cancer in infants and young children for the foreseeable future, it would seem advantageous for appropriately planned population pharmacokinetic studies to be carried out in this patient population.

Evaluation of the prenatally diagnosed mass - Corrected Proof

Timothy C. Lee, Oluyinka O. Olutoye — 2012-03-19

Summary: With the advent of advanced imaging technologies, the field of prenatal diagnosis and counseling has grown rapidly. The use of fetal ultrasound and ultrafast magnetic resonance imaging has allowed for prenatal identification of structural anomalies as well as neoplasm. The differential diagnosis of a fetal mass is dependent upon its location and the tissue characteristics of the mass on imaging. The use of amniocentesis for chromosomal analysis and genetic testing for known tumor-related genetic abnormalities may aid in further refining the diagnosis. Herein we describe a general diagnostic algorithm for fetal masses based upon their location within the body and how the appropriate diagnostic modalities may be applied in the clinical setting.

Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome - Corrected Proof

Anindita Roy, Irene Roberts, Paresh Vyas — 2012-03-15

Summary: Children with Down syndrome (DS) have an increased risk of Acute Myeloid Leukaemia (ML-DS), particularly megakaryoblastic leukaemia, which is clonally -related to the neonatal myeloproliferative syndrome, Transient Abnormal Myelopoiesis (TAM) unique to infants with DS. Molecular, biological, and clinical data indicate that TAM is initiated before birth when fetal liver haematopoietic cells trisomic for chromosome 21 acquire mutations in GATA1. TAM usually resolves spontaneously by 6 months; however 20–30% subsequently develop ML-DS harbouring the same GATA1 mutation(s). This review focuses on recent studies describing haematological, clinical and biological features of TAM and discusses approaches to diagnose, treat and monitor minimal residual disease in TAM. An important unanswered question is whether ML-DS is always preceded by TAM as it may be clinically and possibly haematologically ‘silent’. We have briefly discussed the role of population-based screening for TAM and development of treatment strategies to eliminate the preleukaemic TAM clone, thereby preventing ML-DS.