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Review Article |

Cerebral Palsy, Autism Spectrum Disorders, and Developmental Delay in Children Born After Assisted Conception:  A Systematic Review and Meta-analysis FREE

Dorte Hvidtjørn, MPH; Laura Schieve, PhD; Diana Schendel, PhD; Bo Jacobsson, PhD; Claus Sværke, MSc; Poul Thorsen, PhD
[+] Author Affiliations

Author Affiliations: North Atlantic Nuro Epidemiolgy Alliances, Institute of Public Health, Department of Epidemiology, University of Aarhus, Århus, Denmark (Ms Hvidtjørn, Drs Jacobsson and Thorsen, and Mr Sværke); Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, Georgia (Drs Schieve and Schendel); Perinatal Center, Department of Obstetrics and Gynecology, Institute for the Health of Women and Children, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden (Dr Jacobsson); Department of Obstetrics and Gynecology, Rikshospitalet, Oslo, Norway (Dr Jacobsson); Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia (Dr Thorsen).


Arch Pediatr Adolesc Med. 2009;163(1):72-83. doi:10.1001/archpediatrics.2008.507.
Text Size: A A A
Published online

Objective  To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay.

Data Sources  Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008.

Study Selection  Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more.

Main Exposures  In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination.

Main Outcome Measures  Cerebral palsy, ASD, and developmental delay.

Results  Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively.

Conclusions  Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.

Figures in this Article

In this review, we examined studies on the long-term outcomes of assisted conception, defined as in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) or ovulation induction (OI) with or without subsequent intrauterine insemination (IUI).

In vitro fertilization treatment alone now accounts for an estimated 1% to 4% of births in European countries1 and 1% of US births.2 There is a particular obligation to evaluate treatments offered in health care systems to guarantee their safety.

In vitro fertilization is associated with adverse perinatal outcomes such as preterm delivery (PTD, <37 weeks of gestation) and low birth weight (LBW, <2500 g) because of the strong association between IVF and multiple pregnancies and because even IVF singletons have an increased risk of PTD and LBW compared with naturally conceived (NC) singletons.3 Likewise, OI leads to more multiple pregnancies than natural conception,1,4 and children born after OI also have an increased risk of PTD and LBW, as reported in most studies48 but not all.9,10 Pregnancy with multiples, PTD, and LBW are strongly associated with a range of long-term child health problems3,11,12 including admission to neonatal intensive care units and prolonged hospitalization,13 vision impairment,14 and cerebral palsy (CP).15 Moderate associations between delivery of multiples, PTD, LBW, advanced parental age, and developmental disabilities such as autism spectrum disorders (ASD) have also been reported.1623 Advanced parental age is strongly associated with assisted conception. Additionally, possible prenatal hormonal disturbances in autism, eg, elevated levels of prenatal testosterone24 and lower levels of oxytocin,25 have been reported and may be linked to reproductive problems.

We conducted a systematic review of the current evidence regarding associations between assisted conception and severe long-term outcomes, specifically CP and ASD. We also reviewed general developmental delay outcomes, as these are often the initiating diagnoses or symptoms.

LITERATURE SEARCH

We searched PubMed using the Medical Subject Headings of the National Library of Medicine terms presented in Table 1. We limited our search to studies reporting human outcomes of assisted conception published from January 1, 1996, through March 31, 2008 in English and including children exposed to assisted conception (IVF, ICSI, IUI, or OI). We performed our search on April 10, 2008. The main outcome measures of interest were CP, ASD, and developmental delay.

Table Graphic Jump LocationTable 1. MeSH Terms and Hits in Literature Searcha
STUDY SELECTION

A total of 130 articles met our initial search criteria. All abstracts were reviewed and 41 articles met the additional inclusion criteria of original data, follow-up time of 1 year or more, and a comparison group of unexposed NC children. Excluded articles are shown in an online appendix (http://www.nanea.dk/articles/hvidtjorn-2008-review). We examined the reference lists of all 41 articles eligible for full review, but did not identify any additional articles. We searched EMBASE using the search terms in Table 1 for CP and ASD, but did not identify any additional articles with original data. The initial screening of abstracts was conducted by an author (D.H.). Each of the articles meeting the final inclusion criteria were reviewed in full by 2 authors (D.H. and 1 coauthor; L.S., D.S., P.T., or B.J.).

Here, we present findings from the reviewed studies on CP, ASD, and developmental delay. For each outcome we discuss the main methodological strengths and limitations of the studies. Because of the elevated risk of multiple births in assisted conception, whenever possible we present the articles' findings for singletons and multiples separately, as well as all births combined, with or without adjusting for PTD.

META-ANALYSIS

We performed meta-analyses with fixed-effect models using the Mantel-Haenzel method and calculated nonadjusted summary estimates for the CP studies. Several studies included overlapping cohorts; for these we selected the study presenting the most detailed data (the necessary numbers to calculate a weighted summary). Stata software version 10.0 (Stata, College Station, Texas) was used.

We did not perform meta-analyses for the ASD studies reviewed because of the small number of studies within the specific study design types and potential methodological problems in the few studies similarly designed (see below). We did not perform meta-analyses with the developmental delay studies because a wide range of different measurements were used to assess cognitive, motor, and behavioral development. Moreover, even when 2 studies used the same instrument, child age at assessment was often variable, as were sample inclusion and/or exclusion criteria.

Of the 41 included studies, only 2 were case-control studies; the remainder were cohort studies. Nine studies assessed the risk of CP (Table 2) and 8 the risk of ASD (Table 3). Thirty studies assessed developmental delay based on various standardized scales (Table 4). Within all 3 outcomes there were overlapping study populations.

Table Graphic Jump LocationTable 2. Assisted Conception and Cerebral Palsy Associations by Reference
Table Graphic Jump LocationTable 3. Assisted Conception and Autism Spectrum Disorders Associations by Reference
Table Graphic Jump LocationTable 4. Assisted Conception and Developmental Delay Associations by Reference
CEREBRAL PALSY
Generalizability

Results for CP are shown in Table 3. Of the 9 studies assessing the risk of CP in children born after IVF, only 1 was conducted outside of Scandinavia (a Croatian study of triplets).26 The Scandinavian studies were population-based, diminishing any selection bias. However, the Scandinavian countries are very similar in demographic factors, socioeconomic status, ethnicity (mainly white), and free access to health care (including fertility treatment), and this uniformity might limit extrapolation of the findings to populations of different ethnic profiles, demography, and health care systems.

Methodological Quality of Included Studies

Sample Size and Precision. The Scandinavian studies were based on data from registers comprising health status on the whole population and information on IVF treatments from all fertility clinics retrieved via the unique identification number given to each citizen, resulting in large cohorts reporting fairly precise risk estimates. Risk estimates were less precise in the strata of multiplicity because of reduced sample sizes and lower expected prevalence within the group of singletons only.

Exposure Data. One study assessed the risk of CP in triplets born after all types of assisted conception, identified through a single hospital.26 The remaining 8 studies evaluated children born after IVF using specific population-based data on exposure and identified either through an IVF register (in Denmark) or through all fertility clinics in the specific country (Sweden or Finland); they likely included practically all children born after IVF. However, no study specifically examined OI and only 1 study specified that pregnancies resulting from OI (OI children) were excluded from the comparison group of children born after natural conception.27 Thus for most studies, some misclassification of the unexposed group likely occurred, as OI children were counted as NC children. This would presumably lead to bias toward the null hypothesis, as OI is strongly associated with multiple pregnancies.28,29 In the studies of twins, Pinborg et al30,31 reported that 17.3% of pregnancies in the unexposed groups were the result of OI.

Outcome Data. Cerebral palsy was defined as a diagnosis of International Statistical Classification of Diseases, 10thRevision (ICD-10) code G80.0-G83.9, stated as “ICD-10 diagnosis CP,” or described in 1 study as “children diagnosed with CP by a pediatric neurologist.”26 Six studies obtained information about CP diagnoses from hospital discharge registers27,3135; the remaining 3 used records from rehabilitation centers26,36 or questionnaires confirmed by discharge registers.30 However, the validity and completeness of the CP diagnoses in hospital discharge registers have been questioned.37 Klemetti et al27 supplemented their information on CP diagnosis using registers reporting child care support. Only Strömberg et al36 obtained the CP diagnoses from the medical records of all disability centers in Sweden.

All Birth Findings

All studies of singletons and multiples combined found a statistically significant increase in the risk of CP in children born as the result of IVF (IVF children) compared with NC children.27,3234,36 However, a disproportionate number of the IVF children were multiples. Odds ratios (OR) ranged from 1.6 to 3.7 in analyses adjusting for various factors other than PTD. The strongest association between IVF and CP (OR, 3.7; 95% confidence interval [CI], 2.0-6.6) was reported by Strömberg et al.36 A meta-analysis (without overlapping study cohorts) included 19 462 IVF children and demonstrated an increased risk of CP in IVF children (OR, 2.18; 95% CI, 1.71-2.77) (Figure).

Place holder to copy figure label and caption
Figure.

Meta-analyses of studies assessing the risk of cerebral palsy (CP) in children born as a result of in vitro fertilization (IVF). OR indicates odds ratio; CI, confidence interval; NC, naturally conceived.

Graphic Jump Location

Some studies also presented results from analysis including PTD. Although Strömberg et al found a decrease in the magnitude of the association after adjusting for PTD, it remained strong and statistically significant (OR, 2.9; 95% CI, 1.4-6.0). Hvidtjørn et al32 found no association between IVF and CP after adjusting for PTD. In the study by Källen et al,33 the OR in a stratum of children carried to term was 0.88 (95% CI, 0.46-1.70), and Klemetti et al27 found that 88% of IVF children with CP were born preterm. Dissimilarities in analytic approach complicate an immediate comparison of these findings; however, it seems clear that the risk of CP in IVF children at least partially operates through PTD.

Only Källen et al33 had information on time to pregnancy (TTP) and reported no association between IVF and CP after adjusting for TTP.

Singleton Findings

There was a tendency toward an increased risk for CP in singletons born as a result of IVF (IVF singletons) compared with non-IVF singletons,27,32,35,36 but not all studies reached statistical significance.27,32 The 2 Danish studies used overlapping cohorts but had different analytical approaches; Lidegaard et al35 reported a crude rate ratio of 1.8 (P < .01) in contrast to the non–statistically significant finding by Hvidtjørn et al32 who found a hazard rate ratio of 1.28 (95% CI, 0.80-2.03) in an analysis adjusting for sex, parity, maternal age, and educational level. Strömberg et al36 reported an OR of 2.8 (95% CI, 1.3-5.8) after adjusting for sex, year of birth, and birth hospital. A meta-analysis (without overlapping study cohorts) comprised 12 191 IVF singletons and showed an increased risk of CP in IVF singletons (OR, 1.82; 95% CI, 1.31-2.52) (Figure).

Multiples Findings

While the effect estimates varied (OR range, 0.6-1.5) of the 5 studies examining CP in twins born as a result of IVF (IVF twins) vs non-IVF twins, confidence limits were wide and overlapping (1.0) in all studies.27,3032,36 In contrast, in the study on the risk of CP in triplets, assisted conception had a statistically significant protective effect.26

AUTISM SPECTRUM DISORDERS
Generalizability

Data regarding ASD can be found in Table 4. All but 1 of the ASD studies (an Israeli case-control study)26 originated in Scandinavian countries; consequently, they have the same limitations regarding external validity as the CP studies.

Methodological Quality of Included Studies

Sample Size and Precision. The identified ASD studies covered the period from 1970 to 2001. During this period the prevalence of ASD apparently changed considerably from 4 to 5 per 10 000 children to 6 to 7 per 1000 children.38 It has been questioned whether this increase reflects a true rise in the prevalence of ASD or at least partly reflects changes in diagnostic criteria and increased medical and/or public awareness of these disabilities.39,40 Given that active monitoring of ASD was not in operation in most areas, the expected prevalence at a particular time and area is not known. If we apply a conservative estimate of about 3/1000 children for the time period of these ASD studies, it would require sample sizes of 5268 exposed and 15 804 unexposed to detect a risk of 2.0 in cohort studies with 80% power and 95% CI (estimations in Calculations in Epi Info; Centers for Disease Control, Atlanta, Georgia). Only 2 studies on multiples and singletons combined and 1 on singletons alone achieved this size.34,35

Exposure Data. For the cohort studies from Scandinavia, nondifferential misclassification of OI in the unexposed group was likely, as described above for the CP studies.

In the 1 case-control study, information on exposure was retrieved differently, namely from birth records. However, a validation study on information about infertility treatment in birth records indicated low sensitivity overall for fertility treatment reporting and potentially differential reporting. Higher-risk infants such as multiples were more likely than singletons to be correctly reported as conceived after infertility treatment (personal communication, L.S.; February 1, 2008).

Outcome Data. Most studies obtained information on outcome from hospital discharge registers27,31,34,35,41 and others used records from rehabilitation centers36,42 or questionnaires confirmed by discharge registers.30 Autism spectrum disorder was defined as a diagnosis of ICD-10 code F84.0, F84.1, F84.5, or F84.9 or ICD-8 and Diagnostic and Statistical Manual of MentalDisorders(Third or Fourth Edition) (DSM III-IV). Three of the studies used only infantile autism as the study outcome, 3 used ASD, and 2 used an even broader range of psychiatric diagnoses including ASD, complicating the comparison between the studies. Diagnosis was retrieved from Hospital Discharge Registers, from The Danish Psychiatric Central Research Register, and in 1 case from an autism treatment organization.42

Findings. Two studies evaluated children born after assisted conception in general,41,42 while the remaining 6 evaluated IVF using information from all of the fertility clinics in each country. Findings were inconsistent overall and when considering singletons and multiples separately. Only the study by Klemetti et al27 reported a statistically significant increased risk for a broad range of psychiatric disorders (F80-F98) including ASD in children born after IVF (OR, 1.68; 95% CI, 1.11-2.58); however, they did not provide results for ASD alone.

In contrast, Maimburg and Væth41 reported a protective effect between assisted conception and infantile autism in their case-control study, including 473 children with infantile autism and 473 matched control children (OR, 0.37; 95% CI, 0.14-0.98) adjusting for several factors including gestational age.

DEVELOPMENTAL DELAY
Generalizability

Developmental delay associations can be seen in Table 4. Most studies on developmental delay limited their study participants to children exposed to assisted conception at 1 or 2 fertility clinics, introducing the possibility of selection bias if these clinics were not representative of the entire population. Furthermore, bias might have resulted from differential participation because of substantial nonparticipation in some studies requiring individual examination of the included children. For example, in one of the largest international studies,43 participation rates varied across countries, with rates from 25% to 96% and differences of participation rates of exposed and nonexposed children up to 50%.

Perhaps the foremost problem with these studies was that 21 of them excluded children with risk factors such as multiplicity, PTD, and neonatal complications a priori to test the possible influence of IVF or ICSI on development apart from these complications. While this was certainly a reasonable method for the stated objective, it severely compromised the value of the studies to inform an increase in general developmental delay in the total population of children born after assisted conception, as one could argue that delivery of multiples and PTD are key factors in the causal pathway.

However, studies on developmental delay were conducted on several continents, ensuring representation of diverse populations.

Methodological Quality of Included Studies

Sample Size and Precision. Except for 1 population-based register study,33 the studies on developmental delay individually included between 43 and 999 children, with each study sample of insufficient size to identify relatively rare events such as CP or ASD. Many sample sizes were also insufficient to detect moderate differences in the broader child development measures.

Exposure and Outcome Data. Exposed children were identified at fertility clinics. Nearly all studies used parental questionnaires and/or some type of individual standardized examination of the child to assess development, but they used different measurement scales. The population-based study used hospital discharge registers and ICD codes.33 While ascertainment of both exposure and outcome were based on reliable sources and standardized measures, these strengths did not overcome the limitations of possible selection bias due to low participation rates in some studies and selection of specific low-risk children only.

Findings. We identified 30 studies assessing developmental delay in children born after assisted conception. Seventeen studies evaluated children born after ICSI solely, 13 also evaluated IVF, and 2 evaluated children born after assisted conception in general. Eight studies reported the number of children with CP in their cohorts and 2 stated the number of children with ASD. The numbers were too small for statistical estimation regarding these conditions, as would be expected in cohorts of fewer than 1000 children. In one study the children identified with CP or other adverse outcomes were excluded before further examination.44

Fourteen studies assessed motor development,4356 and 2 reported that children born as a result of ICSI (ICSI children) had a statistically significant higher risk of delayed motor development at 1 to 2 or 5 years of age, respectively.44,57 Eleven studies assessed behavioral development33,44,46,56,5864; 2 reported a statistically significant higher risk of delayed behavioral development in ICSI children aged 1 to 2 years44 and IVF children aged 9 to 10 years,58 respectively. The large population-based register study found an increased risk of behavioral problems in children born after IVF (OR, 1.74; 95% CI, 1.11-2.74).33 Nine studies assessed delay in cognitive development43,45,51,54,5658,65,66 and 1 study reported that ICSI children had a statistically significant lower risk of delayed cognitive development at 8 years of age, while another study reported that ICSI children had a statistically significant higher risk of delayed cognitive development at 5 to 8 years of age.65 Eleven studies assessed delay in mental development,44,4650,52,6771 and 1 found less adverse outcomes in twins born as a result of assisted conception71 while all other studies on developmental delay described non–statistically significant findings.

This systematic review included studies assessing the risks of CP, ASD, and developmental delay in children born after assisted conception. Owing to the size of the study cohorts and the concordant results, the CP studies offer persuasive evidence of an increased risk of CP in children born after IVF that is explained in part by an increased risk of PTD. Cerebral palsy is a lifelong condition and a heavy burden on the child, family, and health care system in terms of both personal and economic costs.72

In contrast, studies assessing the risk of ASD were inconsistent. This might have been owing to the aforementioned methodological problems in these studies or simply might have reflected a lack of association between assisted conception and ASD. As ASD seems to have a heterogenic etiology, the effect of weak associations will only be apparent in larger samples.40 Moreover, a possible association between assisted conception and ASD needs examination in studies covering recent time periods with more complete ASD reporting.

Studies on developmental delay following assisted conception mainly included small select groups of low-risk children, and they presented generally non–statistically significant results. Thus, data on larger samples of the full range of children conceived via assisted conception are needed.

We did not identify any studies assessing the risk of CP, ASD, or developmental delay in children born after OI specifically. The lack of evidence on the long-term risks of OI is of concern given associations shown in previous studies between OI and PTD, LBW, and delivery of multiples.1,48

While the studies offer persuasive evidence of an association between IVF and CP, gaps remain in understanding this relationship. Because the increased risk of CP in children born after IVF seems to operate partly through the causal pathway of IVF, delivery of multiples, and PTD, the extent of the CP risk associated with IVF in a population will likely depend on the rate of IVF multiples. This rate is lower in Scandinavian countries that regulate the number of embryos transferred; eg, in Denmark in 2005 only 1.5% of IVF children were triplets and 32.6% were twins.73 In contrast, the rate of multiples born after IVF in the United States in 2004 was 50%, with a larger proportion of triplets and longer gestations.2

The etiology behind the risk of CP in IVF singletons remains unclear, but 2 Danish studies suggest that the phenomenon of vanishing embryos in early pregnancy might be part of the etiology. Hvidtjørn et al74 found that 3.9 of 1000 (95% CI, 2.2-5.5/1000) singletons born after transfer of more than 1 embryo had CP, similar to the proportion among twins born after the transfer of 2 embryos (4.4 of 1000 children; 95% CI, 1.9-6.9). Pinborg et al75 showed that the group of IVF singletons in which a coembryo had vanished before 22 weeks of gestational age had nearly twice the risk of CP (OR, 1.9; 95% CI, 0.7-5.2) compared with IVF singletons originating from pregnancies with only 1 fetus at 8 weeks of gestational age. These findings need further exploration.

We also still need to determine whether the increased risk of CP after IVF is associated with subfertility, type of subfertility, or any specific subtype of IVF. Subfertility has been associated with adverse pregnancy outcomes such as PTD and neonatal death,76,77 though not by Kapitejn et al.9 Ericson et al34 found an increased risk of hospitalization with increasing time to pregnancy. We found only 1 study that adjusted for time to pregnancy33 and, in doing so, the risk of CP disappeared. The type of subfertility was taken into account in 1 study only, revealing similar risks of CP within the different types, though this was based on small numbers.32

While animal studies report long-term adverse effects of urinary gonadotrophins compared with other treatment regimens used in controlled ovarian stimulation,78,79 only a few studies in this review compared different treatment types. Three studies evaluated possible differences between conventional IVF and ICSI3133 and found comparable risks in the 2 groups. One study compared the risk of CP in children born after use of fresh vs frozen embryos and reported a hazard rate ratio of 2.32 (95% CI, 0.80-6.76) in the latter group,32 but this was based on small numbers.

A comprehensive search in PubMed and EMBASE revealed 130 articles, of which 41 were eligible for review. The main reasons for exclusion of articles were (1) commentary and/or review, (2) different exposure or outcome, and (3) no NC comparison group. Excluded articles are shown in an online appendix. We consider the possible selection bias minimal, as none of the studies excluded fulfilled the a priori criteria.

In summary, this systematic review revealed important gaps in the evidence of long-term outcomes in children born after assisted conception. Possible associations between assisted conception and ASD need assessment in larger studies with well-defined outcomes. Studies on assisted conception and CP from countries outside of Scandinavia are needed as well as studies with detailed information on TTP, underlying causes of infertility, and types of IVF treatment. The long-term outcomes of OI must be addressed. Given the continually increased use of fertility treatments worldwide, studies addressing these very large gaps in the knowledge of the long-term health and development of children born after assisted conception are an important public health objective.

Correspondence: Dorte Hvidtjørn, MPH, NANEA, Institute of Public Health, Department of Epidemiology, University of Aarhus, Paludan-Müllers vej 17, 8000 Aarhus C, Denmark (dh@soci.au.dk).

Accepted for Publication: May 29, 2008.

Author Contributions:Study concept and design: Hvidtjørn, Schieve, Schendel, and Jacobsson. Acquisition of data: Hvidtjørn, Schieve, and Jacobsson. Analysis and interpretation of data: Hvidtjørn, Schieve, Schendel, Jacobsson, Sværke, and Thorsen. Drafting of the manuscript: Hvidtjørn. Critical revision of the manuscript for important intellectual content: Hvidtjørn, Schieve, Schendel, Jacobsson, Sværke, and Thorsen. Statistical analysis: Schieve and Sværke. Obtained funding: Hvidtjørn. Administrative, technical, and material support: Hvidtjørn, Schendel, and Thorsen. Study supervision: Schieve, Schendel, Jacobsson, and Thorsen.

Financial Disclosure: None reported.

Funding/Support: The study was funded by the Danish Agency for Science, Technology, and Innovation; the University of Aarhus; the Elsass Foundation; the Health Insurance Foundation; the Augustinus Foundation; the Julie von Müllens Foundation; Direktør Jacob Madsen & Hustru Olga Madsens Fond; and the Aase and Ejnar Danielsen Foundation.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

This article was corrected online for typographical errors on 1/26/2009.

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Lauritsen  MBPedersen  CBMortensen  PB Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J Child Psychol Psychiatry 2005;46 (9) 963- 971
PubMed Link to Article
Knickmeyer  RCBaron-Cohen  S Fetal testosterone and sex differences in typical social development and in autism. J Child Neurol 2006;21 (10) 825- 845
PubMed Link to Article
Jacob  SBrune  CWCarter  CSLeventhal  BLLord  CCook  EH  Jr Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 2007;417 (1) 6- 9
PubMed Link to Article
Skrablin  SKuvacic  ISimunic  VBosnjak-Nadj  KKalafatic  DBanovic  V Long-term neurodevelopmental outcome of triplets. Eur J Obstet Gynecol Reprod Biol 2007;132 (1) 76- 82
PubMed Link to Article
Klemetti  RSevon  TGissler  MHemminki  E Health of children born as a result of in vitro fertilization. Pediatrics 2006;118 (5) 1819- 1827
PubMed Link to Article
 Multiple gestation pregnancy: the ESHRE Capri Workshop Group. Hum Reprod 2000;15 (8) 1856- 1864
PubMed Link to Article
Andersen  ANGianaroli  LFelberbaum  Rde Mouzon  JNygren  KGthe European IVF-monitoring programme (EIM), European Society of Human Reproduction and Embryology (ESHRE),  Assisted reproductive technology in Europe, 2001: results generated from European registers by ESHRE. Hum Reprod 2005;20 (5) 1158- 1176
PubMed Link to Article
Pinborg  ALoft  ASchmidt  LAndersen  AN Morbidity in a Danish national cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families. Hum Reprod 2003;18 (6) 1234- 1243
PubMed Link to Article
Pinborg  ALoft  ASchmidt  LGreisen  GRasmussen  SAndersen  AN Neurological sequelae in twins born after assisted conception: controlled national cohort study. BMJ 2004;329 (7461) 311
PubMed Link to Article
Hvidtjørn  DGrove  JSchendel  DE  et al.  Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery: a population-based, cohort study. Pediatrics 2006;118 (2) 475- 482
PubMed Link to Article
Källén  BFinnström  ONygren  KGOlausson  PO In vitro fertilization in Sweden: child morbidity including cancer risk. Fertil Steril 2005;84 (3) 605- 610
PubMed Link to Article
Ericson  ANygren  KGOlausson  POKallen  B Hospital care utilization of infants born after IVF. Hum Reprod 2002;17 (4) 929- 932
PubMed Link to Article
Lidegaard  OPinborg  AAndersen  AN Imprinting diseases and IVF: Danish national IVF cohort study. Hum Reprod 2005;20 (4) 950- 954
PubMed Link to Article
Strömberg  BDahlquist  GEricson  AFinnström  OKöster  MStjernqvist  K Neurological sequelae in children born after in-vitro fertilisation: a population-based study. Lancet 2002;359 (9305) 461- 465
PubMed Link to Article
Topp  MLanghoff-Roos  JUldall  P Validation of a cerebral palsy register. J Clin Epidemiol 1997;50 (9) 1017- 1023
PubMed Link to Article
Centers of Disease Control and Prevention, Prevalence of autism spectrum disorders. MMWR CDC Surveill Summ 2007;56 ((SS-011)) 12- 28
Atladóttir  HOParner  ETSchendel  DDalsgaard  SThomsen  PHThorsen  P Time trends in reported diagnoses of childhood neuropsychiatric disorders: a Danish cohort study. Arch Pediatr Adolesc Med 2007;161 (2) 193- 198
PubMed Link to Article
Coo  HOuellette-Kuntz  HLloyd  JEKasmara  LHolden  JJLewis  ME Trends in autism prevalence: diagnostic substitution revisited. J Autism Dev Disord 2008;38 (6) 1036- 1046
PubMed Link to Article
Maimburg  RDVaeth  M Do children born after assisted conception have less risk of developing infantile autism? Hum Reprod 2007;22 (7) 1841- 1843
PubMed Link to Article
Stein  DWeizman  ARing  ABarak  Y Obstetric complications in individuals diagnosed with autism and in healthy controls. Compr Psychiatry 2006;47 (1) 69- 75
PubMed Link to Article
Ponjaert-Kristoffersen  IBonduelle  MBarnes  J  et al.  International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization-conceived, and naturally conceived 5-year-old child outcomes: cognitive and motor assessments. Pediatrics 2005;115 (3) e283- e289
PubMed Link to Article
La Sala  GBGallinelli  AFagandini  P  et al.  Developmental outcomes at one and two years of children conceived by intracytoplasmic sperm injection. Int J Fertil Womens Med 2004;49 (3) 113- 119
PubMed
Leunens  LCelestin-Westreich  SBonduelle  MLiebaers  IPonjaert-Kristoffersen  I Follow-up of cognitive and motor development of 10-year-old singleton children born after ICSI compared with spontaneously conceived children. Hum Reprod 2008;23 (1) 105- 111
PubMed Link to Article
Agarwal  PLoh  SKLim  SB  et al.  Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study. BJOG 2005;112 (10) 1376- 1383
PubMed Link to Article
Papaligoura  ZPanopoulou-Maratou  OSolman  MArvaniti  KSarafidou  J Cognitive development of 12 month old Greek infants conceived after ICSI and the effects of the method on their parents. Hum Reprod 2004;19 (6) 1488- 1493
PubMed Link to Article
Koivurova  SHartikainen  ALSovio  UGissler  MHemminki  EJarvelin  MR Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF. Hum Reprod 2003;18 (11) 2328- 2336
PubMed Link to Article
Bowen  JRGibson  FLLeslie  GISaunders  DM Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection. Lancet 1998;351 (9115) 1529- 1534
PubMed Link to Article
Wennerholm  UBBertsson-Wikland  KBergh  C  et al.  Postnatal growth and health in children born after cryopreservation as embryos. Lancet 1998;351 (9109) 1085- 1090
PubMed Link to Article
Ito  AHonma  YInamori  EYada  YMomoi  MYNakamura  Y Developmental outcome of very low birth weight twins conceived by assisted reproduction techniques. J Perinatol 2006;26 (2) 130- 133
PubMed Link to Article
Sanchez-Albisua  IBorell-Kost  SMau-Holzmann  UALicht  PKrageloh-Mann  I Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection. Dev Med Child Neurol 2007;49 (2) 129- 134
PubMed Link to Article
Belva  FHenriet  SLiebaers  IVan  SACelestin-Westreich  SBonduelle  M Medical outcome of 8-year-old singleton ICSI children (born > or =32 weeks' gestation) and a spontaneously conceived comparison group. Hum Reprod 2007;22 (2) 506- 515
PubMed Link to Article
Leunens  LCelestin-Westreich  SBonduelle  MLiebaers  IPonjaert-Kristoffersen  I Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children. Hum Reprod 2006;21 (11) 2922- 2929
PubMed Link to Article
Bonduelle  MBergh  CNiklasson  APalermo  GDWennerholm  UB Medical follow-up study of 5-year-old ICSI children. Reprod Biomed Online 2004;9 (1) 91- 101
PubMed Link to Article
Place  IEnglert  Y A prospective longitudinal study of the physical, psychomotor, and intellectual development of singleton children up to 5 years who were conceived by intracytoplasmic sperm injection compared with children conceived spontaneously and by in vitro fertilization. Fertil Steril 2003;80 (6) 1388- 1397
PubMed Link to Article
Ponjaert-Kristoffersen  ITjus  TNekkebroeck  J  et al.  Psychological follow-up study of 5-year-old ICSI children. Hum Reprod 2004;19 (12) 2791- 2797
PubMed Link to Article
Levy-Shiff  RVakil  EDimitrovsky  L  et al.  Medical, cognitive, emotional, and behavioral outcomes in school-age children conceived by in-vitro fertilization. J Clin Child Psychol 1998;27 (3) 320- 329
PubMed Link to Article
Barnes  JSutcliffe  AGKristoffersen  I  et al.  The influence of assisted reproduction on family functioning and children's socio-emotional development: results from a European study. Hum Reprod 2004;19 (6) 1480- 1487
PubMed Link to Article
Colpin  HSoenen  S Parenting and psychosocial development of IVF children: a follow-up study. Hum Reprod 2002;17 (4) 1116- 1123
PubMed Link to Article
Golombok  SBrewaeys  ACook  R  et al.  The European study of assisted reproduction families: family functioning and child development. Hum Reprod 1996;11 (10) 2324- 2331
PubMed Link to Article
Golombok  SBrewaeys  AGiavazzi  MTGuerra  DMacCallum  FRust  J The European study of assisted reproduction families: the transition to adolescence. Hum Reprod 2002;17 (3) 830- 840
PubMed Link to Article
Golombok  SMacCallum  FGoodman  E The “test-tube” generation: parent-child relationships and the psychological well-being of in vitro fertilization children at adolescence. Child Dev 2001;72 (2) 599- 608
PubMed Link to Article
Knoester  MHelmerhorst  FMvan der Westerlaken  LAWalther  FJVeen  S Matched follow-up study of 5 8-year-old ICSI singletons: child behaviour, parenting stress and child (health-related) quality of life. Hum Reprod 2007;22 (12) 3098- 3107
PubMed Link to Article
Knoester  MHelmerhorst  FMVandenbroucke  JPvan der Westerlaken  LAWalther  FJVeen  S Cognitive development of singletons born after intracytoplasmic sperm injection compared with in vitro fertilization and natural conception. Fertil Steril 2008;90 (2) 289- 296
PubMed Link to Article
Leslie  GIGibson  FL McMahon  CCohen  JSaunders  DMTennant  C Children conceived using ICSI do not have an increased risk of delayed mental development at 5 years of age. Hum Reprod 2003;18 (10) 2067- 2072
PubMed Link to Article
D'Souza  SWRivlin  ECadman  JRichards  BBuck  PLieberman  BA Children conceived by in vitro fertilisation after fresh embryo transfer. Arch Dis Child Fetal Neonatal Ed 1997;76 (2) F70- F74
PubMed Link to Article
Sutcliffe  AGSaunders  K McLachlan  R  et al.  A retrospective case-control study of developmental and other outcomes in a cohort of Australian children conceived by intracytoplasmic sperm injection compared with a similar group in the United Kingdom. Fertil Steril 2003;79 (3) 512- 516
PubMed Link to Article
Sutcliffe  AGTaylor  BLi  JThornton  SGrudzinskas  JGLieberman  BA Children born after intracytoplasmic sperm injection: population control study. BMJ 1999;318 (7185) 704- 705
PubMed Link to Article
Sutcliffe  AGTaylor  BSaunders  KThornton  SLieberman  BAGrudzinskas  JG Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case-control study. Lancet 2001;357 (9274) 2080- 2084
PubMed Link to Article
Minakami  HSayama  MHonma  Y  et al.  Lower risks of adverse outcome in twins conceived by artificial reproductive techniques compared with spontaneously conceived twins. Hum Reprod 1998;13 (7) 2005- 2008
PubMed Link to Article
Michelsen  SIUldall  PKejs  AMMadsen  M Education and employment prospects in cerebral palsy. Dev Med Child Neurol 2005;47 (8) 511- 517
PubMed Link to Article
 Nye tal fra Sundhedsstyrelsen.  København, Denmark National Board of Health, Denmark2007;Årgang 11, No. 14
Hvidtjørn  DGrove  JSchendel  D  et al.  'Vanishing embryo syndrome' in IVF/ICSI. Hum Reprod 2005;20 (9) 2550- 2551
PubMed Link to Article
Pinborg  ALidegaard  Ola Cour  FNNyboe  AA Consequences of vanishing twins in IVF/ICSI pregnancies. Hum Reprod 2005;20 (10) 2821- 2829
PubMed Link to Article
Henriksen  TBBaird  DDOlsen  JHedegaard  MSecher  NJWilcox  AJ Time to pregnancy and preterm delivery. Obstet Gynecol 1997;89 (4) 594- 599
PubMed Link to Article
Basso  OOlsen  J Subfecundity and neonatal mortality: longitudinal study within the Danish national birth cohort. BMJ 2005;330 (7488) 393- 394
PubMed Link to Article
Sibug  RMDatson  NTijssen  AM  et al.  Effects of urinary and recombinant gonadotrophins on gene expression profiles during the murine peri-implantation period. Hum Reprod 2007;22 (1) 75- 82
PubMed Link to Article
de Kloet  ERSibug  RMHelmerhorst  FMSchmidt  Mathias V Stress, genes and the mechanism of programming the brain for later life [correction appears in Neurosci Biobehav Rev. 2005;29(2):271-81]. Neurosci Biobehav Rev 2005;29 (2) 271- 281
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Meta-analyses of studies assessing the risk of cerebral palsy (CP) in children born as a result of in vitro fertilization (IVF). OR indicates odds ratio; CI, confidence interval; NC, naturally conceived.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. MeSH Terms and Hits in Literature Searcha
Table Graphic Jump LocationTable 2. Assisted Conception and Cerebral Palsy Associations by Reference
Table Graphic Jump LocationTable 3. Assisted Conception and Autism Spectrum Disorders Associations by Reference
Table Graphic Jump LocationTable 4. Assisted Conception and Developmental Delay Associations by Reference

References

Andersen  ANGoossens  VGianaroli  LFelberbaum  Rde Mouzon  JNygren  KG Assisted reproductive technology in Europe, 2003: results generated from European registers by ESHRE. Hum Reprod 2007;22 (6) 1513- 1525
PubMed Link to Article
Wright  VCChang  JJeng  GChen  MMacaluso  MCenters for Disease Control and Prevention, Assisted reproductive technology surveillance: United States, 2004 [published erratum appears in MMWR Morb Mortal Wkly Rep. 2007;56(26):658]. MMWR Surveill Summ 2007;56 (6) 1- 22
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Helmerhorst  FMPerquin  DADonker  DKeirse  MJ Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ 2004;328 (7434) 261
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Källén  BOlausson  PONygren  KG Neonatal outcome in pregnancies from ovarian stimulation. Obstet Gynecol 2002;100 (3) 414- 419
PubMed Link to Article
Wang  JXNorman  RJKristiansson  P The effect of various infertility treatments on the risk of preterm birth. Hum Reprod 2002;17 (4) 945- 949
PubMed Link to Article
Olivennes  FRufat  PAndre  BPourade  AQuiros  MCFrydman  R The increased risk of complication observed in singleton pregnancies resulting from in-vitro fertilization (IVF) does not seem to be related to the IVF method itself. Hum Reprod 1993;8 (8) 1297- 1300
PubMed
Gaudoin  MDobbie  RFinlayson  AChalmers  JCameron  ITFleming  R Ovulation induction/intrauterine insemination in infertile couples is associated with low-birth-weight infants. Am J Obstet Gynecol 2003;188 (3) 611- 616
PubMed Link to Article
Ombelet  WMartens  GDe  SP  et al.  Perinatal outcome of 12,021 singleton and 3108 twin births after non-IVF-assisted reproduction: a cohort study. Hum Reprod 2006;21 (4) 1025- 1032
PubMed Link to Article
Kapiteijn  Kde Bruijn  CSde Boer  E  et al.  Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation? Hum Reprod 2006;21 (12) 3228- 3234
PubMed Link to Article
Shevell  TMalone  FDVidaver  J  et al.  Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 2005;106 (5 pt 1) 1039- 1045
PubMed Link to Article
Ludwig  AKSutcliffe  AGDiedrich  KLudwig  M Post-neonatal health and development of children born after assisted reproduction: a systematic review of controlled studies. Eur J Obstet Gynecol Reprod Biol 2006;127 (1) 3- 25
PubMed Link to Article
Schieve  LARasmussen  SABuck  GMSchendel  DEReynolds  MAWright  VC Are children born after assisted reproductive technology at increased risk for adverse health outcomes? Obstet Gynecol 2004;103 (6) 1154- 1163
PubMed Link to Article
Stoelhorst  GMRijken  MMartens  SE  et al.  Changes in neonatology: comparison of two cohorts of very preterm infants (gestational age <32 weeks): the Project On Preterm and Small for Gestational Age Infants 1983 and the Leiden Follow-Up Project on Prematurity 1996-1997. Pediatrics 2005;115 (2) 396- 405
PubMed Link to Article
Haines  LFielder  ARBaker  HWilkinson  AR UK population based study of severe retinopathy of prematurity: screening, treatment, and outcome. Arch Dis Child Fetal Neonatal Ed 2005;90 (3) F240- F244
PubMed Link to Article
Keogh  JMBadawi  N The origins of cerebral palsy. Curr Opin Neurol 2006;19 (2) 129- 134
PubMed Link to Article
Croen  LAGrether  JKSelvin  S Descriptive epidemiology of autism in a California population: who is at risk? J Autism Dev Disord 2002;32 (3) 217- 224
PubMed Link to Article
Eaton  WWMortensen  PBThomsen  PHFrydenberg  M Obstetric complications and risk for severe psychopathology in childhood. J Autism Dev Disord 2001;31 (3) 279- 285
PubMed Link to Article
Hultman  CMSparen  PCnattingius  S Perinatal risk factors for infantile autism. Epidemiology 2002;13 (4) 417- 423
PubMed Link to Article
Reichenberg  AGross  RWeiser  M  et al.  Advancing paternal age and autism. Arch Gen Psychiatry 2006;63 (9) 1026- 1032
PubMed Link to Article
Larsson  HJEaton  WWMadsen  KM  et al.  Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol 2005;161 (10) 916- 925
PubMed Link to Article
Glasson  EJBower  CPetterson  Bde Klerk  NChaney  GHallmayer  JF  Perinatal factors and the development of autism: a population study. Arch Gen Psychiatry 2004;61 (6) 618- 627
PubMed Link to Article
Kolevzon  AGross  RReichenberg  A Prenatal and perinatal risk factors for autism: a review and integration of findings. Arch Pediatr Adolesc Med 2007;161 (4) 326- 333
PubMed Link to Article
Lauritsen  MBPedersen  CBMortensen  PB Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J Child Psychol Psychiatry 2005;46 (9) 963- 971
PubMed Link to Article
Knickmeyer  RCBaron-Cohen  S Fetal testosterone and sex differences in typical social development and in autism. J Child Neurol 2006;21 (10) 825- 845
PubMed Link to Article
Jacob  SBrune  CWCarter  CSLeventhal  BLLord  CCook  EH  Jr Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 2007;417 (1) 6- 9
PubMed Link to Article
Skrablin  SKuvacic  ISimunic  VBosnjak-Nadj  KKalafatic  DBanovic  V Long-term neurodevelopmental outcome of triplets. Eur J Obstet Gynecol Reprod Biol 2007;132 (1) 76- 82
PubMed Link to Article
Klemetti  RSevon  TGissler  MHemminki  E Health of children born as a result of in vitro fertilization. Pediatrics 2006;118 (5) 1819- 1827
PubMed Link to Article
 Multiple gestation pregnancy: the ESHRE Capri Workshop Group. Hum Reprod 2000;15 (8) 1856- 1864
PubMed Link to Article
Andersen  ANGianaroli  LFelberbaum  Rde Mouzon  JNygren  KGthe European IVF-monitoring programme (EIM), European Society of Human Reproduction and Embryology (ESHRE),  Assisted reproductive technology in Europe, 2001: results generated from European registers by ESHRE. Hum Reprod 2005;20 (5) 1158- 1176
PubMed Link to Article
Pinborg  ALoft  ASchmidt  LAndersen  AN Morbidity in a Danish national cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families. Hum Reprod 2003;18 (6) 1234- 1243
PubMed Link to Article
Pinborg  ALoft  ASchmidt  LGreisen  GRasmussen  SAndersen  AN Neurological sequelae in twins born after assisted conception: controlled national cohort study. BMJ 2004;329 (7461) 311
PubMed Link to Article
Hvidtjørn  DGrove  JSchendel  DE  et al.  Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery: a population-based, cohort study. Pediatrics 2006;118 (2) 475- 482
PubMed Link to Article
Källén  BFinnström  ONygren  KGOlausson  PO In vitro fertilization in Sweden: child morbidity including cancer risk. Fertil Steril 2005;84 (3) 605- 610
PubMed Link to Article
Ericson  ANygren  KGOlausson  POKallen  B Hospital care utilization of infants born after IVF. Hum Reprod 2002;17 (4) 929- 932
PubMed Link to Article
Lidegaard  OPinborg  AAndersen  AN Imprinting diseases and IVF: Danish national IVF cohort study. Hum Reprod 2005;20 (4) 950- 954
PubMed Link to Article
Strömberg  BDahlquist  GEricson  AFinnström  OKöster  MStjernqvist  K Neurological sequelae in children born after in-vitro fertilisation: a population-based study. Lancet 2002;359 (9305) 461- 465
PubMed Link to Article
Topp  MLanghoff-Roos  JUldall  P Validation of a cerebral palsy register. J Clin Epidemiol 1997;50 (9) 1017- 1023
PubMed Link to Article
Centers of Disease Control and Prevention, Prevalence of autism spectrum disorders. MMWR CDC Surveill Summ 2007;56 ((SS-011)) 12- 28
Atladóttir  HOParner  ETSchendel  DDalsgaard  SThomsen  PHThorsen  P Time trends in reported diagnoses of childhood neuropsychiatric disorders: a Danish cohort study. Arch Pediatr Adolesc Med 2007;161 (2) 193- 198
PubMed Link to Article
Coo  HOuellette-Kuntz  HLloyd  JEKasmara  LHolden  JJLewis  ME Trends in autism prevalence: diagnostic substitution revisited. J Autism Dev Disord 2008;38 (6) 1036- 1046
PubMed Link to Article
Maimburg  RDVaeth  M Do children born after assisted conception have less risk of developing infantile autism? Hum Reprod 2007;22 (7) 1841- 1843
PubMed Link to Article
Stein  DWeizman  ARing  ABarak  Y Obstetric complications in individuals diagnosed with autism and in healthy controls. Compr Psychiatry 2006;47 (1) 69- 75
PubMed Link to Article
Ponjaert-Kristoffersen  IBonduelle  MBarnes  J  et al.  International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization-conceived, and naturally conceived 5-year-old child outcomes: cognitive and motor assessments. Pediatrics 2005;115 (3) e283- e289
PubMed Link to Article
La Sala  GBGallinelli  AFagandini  P  et al.  Developmental outcomes at one and two years of children conceived by intracytoplasmic sperm injection. Int J Fertil Womens Med 2004;49 (3) 113- 119
PubMed
Leunens  LCelestin-Westreich  SBonduelle  MLiebaers  IPonjaert-Kristoffersen  I Follow-up of cognitive and motor development of 10-year-old singleton children born after ICSI compared with spontaneously conceived children. Hum Reprod 2008;23 (1) 105- 111
PubMed Link to Article
Agarwal  PLoh  SKLim  SB  et al.  Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study. BJOG 2005;112 (10) 1376- 1383
PubMed Link to Article
Papaligoura  ZPanopoulou-Maratou  OSolman  MArvaniti  KSarafidou  J Cognitive development of 12 month old Greek infants conceived after ICSI and the effects of the method on their parents. Hum Reprod 2004;19 (6) 1488- 1493
PubMed Link to Article
Koivurova  SHartikainen  ALSovio  UGissler  MHemminki  EJarvelin  MR Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF. Hum Reprod 2003;18 (11) 2328- 2336
PubMed Link to Article
Bowen  JRGibson  FLLeslie  GISaunders  DM Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection. Lancet 1998;351 (9115) 1529- 1534
PubMed Link to Article
Wennerholm  UBBertsson-Wikland  KBergh  C  et al.  Postnatal growth and health in children born after cryopreservation as embryos. Lancet 1998;351 (9109) 1085- 1090
PubMed Link to Article
Ito  AHonma  YInamori  EYada  YMomoi  MYNakamura  Y Developmental outcome of very low birth weight twins conceived by assisted reproduction techniques. J Perinatol 2006;26 (2) 130- 133
PubMed Link to Article
Sanchez-Albisua  IBorell-Kost  SMau-Holzmann  UALicht  PKrageloh-Mann  I Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection. Dev Med Child Neurol 2007;49 (2) 129- 134
PubMed Link to Article
Belva  FHenriet  SLiebaers  IVan  SACelestin-Westreich  SBonduelle  M Medical outcome of 8-year-old singleton ICSI children (born > or =32 weeks' gestation) and a spontaneously conceived comparison group. Hum Reprod 2007;22 (2) 506- 515
PubMed Link to Article
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