Middelburg K J, Heineman M J, Bos A F, Hadders-Algra M
Department of Paediatrics, Division of Developmental Neurology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Hum Reprod Update. 2008 May-Jun;14(3):219-31. doi: 10.1093/humupd/dmn005. Epub 2008 Mar 26.
The effect of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) on the developing human brain is unclear. The objective of this study is to evaluate neurodevelopmental (ND) outcome of children born following these techniques.
This systematic review includes studies which compare a group of children born following IVF/ICSI to children born after natural conception by assessing outcome in terms of neuromotor development, cognition, speech/language and behaviour. Specific attention is paid to the studies' methodological quality based on study design, attrition, blinding of the assessor, validity of ND tests used, confounders included and group size or power analysis.
Twenty-three out of 59 studies had a good methodological quality including 9 register-based (RB) and 14 controlled studies. RB studies suggested that IVF/ICSI per se does not increase the risk for severe cognitive impairment (i.e. mental retardation) or neuromotor handicaps such as cerebral palsy (CP), the association of IVF/ICSI and CP being brought about by the association of assisted conception with risk factors, like preterm birth. In general, controlled studies of good quality did not report an excess of ND disorders in IVF/ICSI-children. However, the majority of studies followed the children during infancy only, thereby precluding pertinent conclusions on the risk of ND disorders that come to the expression at older ages, such as fine manipulative disability or dyslexia.
A negative effect of assisted conception on the developing human brain is not identified; however, further research of high methodological quality in children beyond pre-school age is needed.
体外受精(IVF)或胞浆内单精子注射(ICSI)对人类大脑发育的影响尚不清楚。本研究的目的是评估通过这些技术出生的儿童的神经发育(ND)结局。
本系统评价纳入了一些研究,这些研究通过评估神经运动发育、认知、言语/语言和行为方面的结局,将一组通过IVF/ICSI出生的儿童与自然受孕出生的儿童进行比较。基于研究设计、损耗、评估者的盲法、所用ND测试的有效性、纳入的混杂因素以及样本量或功效分析,特别关注研究的方法学质量。
59项研究中有23项具有良好的方法学质量,包括9项基于登记的(RB)研究和14项对照研究。RB研究表明,IVF/ICSI本身不会增加严重认知障碍(即智力迟钝)或神经运动障碍如脑瘫(CP)的风险,IVF/ICSI与CP之间的关联是由辅助受孕与早产等危险因素的关联所致。一般来说,高质量的对照研究并未报告IVF/ICSI儿童中ND障碍过多。然而,大多数研究仅在婴儿期对儿童进行随访,因此无法就ND障碍在较大年龄出现的风险得出相关结论,如精细操作障碍或诵读困难。
未发现辅助受孕对人类大脑发育有负面影响;然而,需要对学龄前以上儿童进行更高方法学质量的进一步研究。