Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI - A systematic review

Department of Paediatrics, Division of Developmental Neurology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Human Reproduction Update (Impact Factor: 10.17). 02/2008; 14(3):219-31. DOI: 10.1093/humupd/dmn005
Source: PubMed


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.

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    • "Basatemur et al. (2010) compared children conceived by IVF or ICSI with age matched naturally conceived children and found no significant difference regarding developmental parameters (28). Nevertheless, in study by Basatemur (2010) and other similar studies have stated that further researches are needed for certain judgment (28, 29). It seems that more precise conclusion regarding refractive status of Iranian ART infants is required in order to gather sufficient information about normal infants (ART and naturally conceived infants) less than one year of age. "
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    ABSTRACT: Objective Nowadays, many infertile couples can have child by assistant reproductive technology (ART). Always the undesirable effects of these methods on newborn are considered and are evaluated. The aim of this study is to describe the impact of ART on ocular and visual performances of infants born by these methods. Materials and methods In a cross-sectional descriptive study, 479 infants aged three-nine months presented to an optometry clinic of Child Health and Development Research Department (CHDRD), Tehran, Iran. Static retinoscopy, qualitative fixation evaluation, Hirschberg test, red reflex assessment and external eye examination were carried out. Other information such as birth weight and maturity of the infants was recorded. Results It was possible to assess only 320 out of 479 infants due to general condition of some participants. Comparison of mean refractive error in infants’ right and left eyes did not show any significant difference. Our findings confirmed that 20.3% had poor fixation, while 2.9% revealed manifest strabismus. The results also revealed the prevalences of myopia, hyperopia and emmetropia are 2.9%, 87%, and 10.1%, respectively. Red reflex abnormalities were significantly found in boys and in preterm infants (p < 0.05). Failure of fixation control was seen more frequently with increasing refractive error, which significantly developed in preterm infants (p < 0.001). Conclusion These results reflect the necessity of more comprehensive assessments and further follow-up of infants born by ART, especially for premature male ART infants. These results also suggest the probability of fixation condition and visual deficiencies in these infants. It is recommended to pay close attention to this preliminary report about the refractive and fixation condition of the infants born after ART.
    12/2013; 7(4):181-6.
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    • "Quantitative studies over two decades have consistently shown that compared with those conceiving spontaneously, women conceiving through ART report comparable symptoms of depression, state and trait anxiety, but higher anxiety focused on the outcome of the pregnancy (Hammarberg et al., 2008). Reviews indicate, however, that children conceived through ART, show comparable neurodevelopmental (Middelburg et al., 2008) and behavioural outcomes (Golombok, 2003) compared with spontaneously conceived children. "
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    ABSTRACT: STUDY QUESTION: Is anxiety focused on the pregnancy outcome, known to be particularly salient in women conceiving through assisted reproductive technology (ART), related to difficult infant temperament?SUMMARY ANSWERWhile trait anxiety predicts infant temperament, pregnancy-focused anxiety is not associated with more difficult infant temperament.WHAT IS KNOWN ALREADYA large body of research has provided convincing evidence that fetal exposure to maternal anxiety and stress in pregnancy has adverse consequences for child neurodevelopmental, behavioural and cognitive development, and that pregnancy-specific anxiety (concerns related to the pregnancy outcome and birth) may be of particular significance. Women conceiving through ART are of particular interest in this regard. Research over more than 20 years has consistently demonstrated that while they do not differ from spontaneously conceiving (SC) women with respect to general (state and trait) anxiety, they typically report higher pregnancy-specific anxiety. While research suggests normal behavioural and developmental outcomes for children conceived through ART, there is some evidence of more unsettled infant behaviour during the first post-natal year.STUDY DESIGN, SIZE, DURATIONThe longitudinal cohort design followed 562 nulliparous women over a 7-month period, during the third trimester of pregnancy and at 4 months after birth.PARTICIPANTS/MATERIALS, SETTING, METHODS Approximately equal numbers of nulliparous women conceiving through ART (n = 250) and spontaneously (SC: n = 262) were recruited through ART clinics and nearby hospitals in Melbourne and Sydney, Australia. Participants completed three anxiety measures (state, trait, pregnancy specific) at time 1 in the third trimester of pregnancy and a measure of infant temperament at time 2, 4 months after birth. At time 1, relevant socio-demographic, pregnancy (maternal age, smoking, alcohol, medications, medical complications) information was recorded and at time 2, information regarding childbirth (gestation, infant birthweight, mode of delivery) and post-natal (concurrent mood) variables was recorded and controlled for in analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the third trimester of pregnancy, women conceiving through ART reported lower state and trait anxiety, but higher pregnancy-focused anxiety than their SC counterparts (all Ps < 0.05). Hierarchical regression analyses including mode of conception, all anxiety variables and relevant covariates indicated that while trait anxiety in pregnancy predicted more difficult infant temperament (P < 0.001), pregnancy specific and state anxiety did not. Mode of conception predicted infant temperament; with ART women reporting less difficult infant temperament (P < 0.001) than their SC counterparts. LIMITATIONS, REASONS FOR CAUTION: The major limitations in the study are the reliance on a self-report measure of infant temperament and the fact that the study did not assess quality of caregiving which may moderate the effect of pregnancy anxiety on infant temperament. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to our knowledge to prospectively examine the impact of gestational stress (pregnancy anxiety) on infant temperament in women conceiving through ART. Findings confirm existing research indicating that trait anxiety in pregnancy is associated with difficult infant temperament and suggest that pregnancy-specific anxiety (measured in the third trimester) is not implicated. These findings are reassuring for women conceiving through ART whose pregnancies may be characterized by particularly intense concerns about the wellbeing of a long sought after baby. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by a grant from the Australian Research Council (ARC) and in kind and financial contributions from IVF Australia and Melbourne.TRIAL REGISTRATION NUMBERN/A.
    Human Reproduction 02/2013; 28(4). DOI:10.1093/humrep/det029 · 4.57 Impact Factor
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    • "Discrepant data are available on this topic and have underlined that neurological abnormalities and cerebral palsy may be more frequent or not in ARTchildren. A recent systematic review taking account of methodological bias concluded that children conceived after IVF/ICSI do not have impaired neuromotor, cognitive, language, and behavioural development compared to naturally conceived children [35]. In this study, the observed neurological effects may be consequences of prematurity and low birth weight observed in ART children especially in case of multiple births. "
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    ABSTRACT: Assisted reproductive technologies (ARTS) are used for more than 30 years to help infertile couples. Concerns about long-term health of children conceived following ART have led to start follow-up studies. Despite methodological limitations and discrepant results, many of the studies and meta-analyses have reported an increased risk of birth defects after ART. Etiologies may be multiple births, a major drawback of ART, parents' subfertility, or technologies themselves. Prematurity and intrauterine growth retardation (IUGR) seem to cause most of the pathologies reported in ART children. Nevertheless, epigenetic disorders need to be followed up since increases of imprinting diseases were reported. Consequently, alteration of gametes and early embryo development with ART may have consequences on children health since periconceptional period is critical for long-term development. Yet general condition of most of children conceived with ART is reassuring, but long-term followup is still strongly needed.
    ISRN obstetrics and gynecology 06/2012; 2012(4):405382. DOI:10.5402/2012/405382
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