患癌孕妇化疗不影响胎儿心脏和神经系统

在过去10年时间里患有癌症的孕妇在妊娠期间接受化学药物治疗的例子越来越多，然而医学界关于孕妇接受化疗是否会影响胎儿心脏和神经系统的发育仍然没有定论。近日，发表在The Lancet Oncology杂志上一项研究证实：怀孕妇女在妊娠期间接受化疗并不会影响胎儿心脏和神经系统的发育。

该研究的主要领导者--新泽西州罗文大学Elyce Cardonick教授表示：这项研究对罹患癌症的孕妇具有很大的临床指导意义，一方面孕妇并不需要担心化疗会对胎儿造成影响，完全可以继续接受癌症化疗，另一方面也不必因担心化疗对胎儿有影响而终止妊娠。

研究人员将不同年龄段的70名婴儿纳入研究（婴儿包括刚出生的、18个月大的、5至6岁、8至9岁、11至12岁、14至15岁、18岁），对妊娠期期间接受化疗的罹患癌症孕妇所生婴儿的做了一项多中心队列观察研究。同时收集了孕妇平均妊娠期为35.7周，接受236轮化疗，平均随访时间为22.3月等相关数据。

为了分析婴儿心脏和神经系统发育情况，工作人员运用了临床常规神经功能检查、整体认知功能测试（语言测试或IQ测试）、心电图、心回波描记以及与健康和发育相关的问卷调查等形式。对于年龄在5岁以上的孩子还做了听力测试、记忆能力测试和注意力测试等。

结果发现那些接受化疗的罹患癌症孕妇所生的婴儿的神经认知功能、机体行为、整体健康状况、听力、生长发育情况、心脏容积、心脏功能等指标都处在正常值范围内。

研究人员表示：肚中胎儿暴露于化疗环境下并不会影响中枢神经系统的发育、心脏功能以及听力等功能。拿这些婴儿与正常婴儿相比，结果在整体健康状况、生长发育情况上也未出现差异。(生物谷 Bioon.com)

doi:10.1016/S1470-2045(11)70363-1
PMC:
PMID:

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

Dr Frédéric Amant PhD a , Kristel Van Calsteren PhD b, Michael J Halaska PhD e, Mina Mhallem Gziri MD b, Wei Hui MD k, Lieven Lagae PhD c, Michèl A Willemsen PhD f, Livia Kapusta PhD g i, Ben Van Calster PhD a b, Heidi Wouters MSc c, Liesbeth Heyns MSc a, Sileny N Han MD a, Viktor Tomek MD j, Luc Mertens PhD d k, Petronella B Ottevanger PhD h

Background

Chemotherapy for the treatment of maternal cancers during pregnancy has become more acceptable in the past decade; however, the effect of prenatal exposure to chemotherapy on cardiac and neurodevelopmental outcomes of the offspring is still uncertain. We aimed to record the general health, cardiac function, and neurodevelopmental outcomes of children who were prenatally exposed to chemotherapy.

Methods

We did an interim analysis of a multicentre observational cohort study assessing children who were prenatally exposed to maternal cancer staging and treatment, including chemotherapy. We assessed children at birth, at age 18 months, and at age 5—6, 8—9, 11—12, 14—15, or 18 years. We did clinical neurological examinations, tests of the general level of cognitive functioning (Bayley or intelligence quotient [IQ] test), electrocardiography and echocardiography, and administered a questionnaire on general health and development. From age 5 years, we also did audiometry, the Auditory Verbal Learning Test, and subtasks of the Children's Memory Scale, and the Test of Everyday Attention for Children, and we also completed the Child Behavior Checklist. This study is registered with ClinicalTrials.gov, number NCT00330447.

Findings

236 cycles of chemotherapy were administered in 68 pregnancies. We assessed 70 children, born at a median gestational age of 35·7 weeks (range 28·3—41·0; IQR 3·3; 47 women at <37 weeks), with a median follow-up period of 22·3 months (range 16·8—211·6; IQR 54·9). Although neurocognitive outcomes were within normal ranges, cognitive development scores were lower for children who were born preterm than for those born at full term. When controlling for age, sex, and country, the score for IQ increased by an average 11·6 points (95% CI 6·0—17·1) for each additional month of gestation (p<0·0001). Our measurements of the children's behaviour, general health, hearing, and growth corresponded with those of the general population. Cardiac dimensions and functions were within normal ranges. We identified a severe neurodevelopmental delay in both members of one twin pregnancy.

Interpretation

Fetal exposure to chemotherapy was not associated with increased CNS, cardiac or auditory morbidity, or with impairments to general health and growth compared with the general population. However, subtle changes in cardiac and neurocognitive measurements emphasise the need for longer follow-up. Prematurity was common and was associated with impaired cognitive development. Therefore, iatrogenic preterm delivery should be avoided when possible.