title: Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children. Mental health and developmental outcomes for children born after ART: a comparative prospective study on child gender and treatment type. US National Longitudinal Lesbian Family Study: Psychological Adjustment of 17-Year-Old Adolescents Visual memory and learning in extremely low-birth-weight/extremely preterm adolescents compared with controls: a geographic study. Effect of pregnancy planning and fertility treatment on cognitive outcomes in children at ages 3 and 5: longitudinal cohort study Families with children conceived by donor insemination: a follow-up at age twelve. Language assessment of non-handicapped twins at 5 years of age. Cognitive and psychomotor development of 5- to 6-year-old singletons born after PGD: a prospective case-controlled matched study. Neuromotor development and mental health at 5.5 years of age of singletons born at term after intracytoplasmatic sperm injection ICSI: results of a prospective controlled single-blinded study in Germany. 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. Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study
abstract: BACKGROUND As a continuation of two large-scale , multicentre studies on the development of 5-year-old ICSI children , we present results of the follow-up study undertaken on the cognitive and motor development of 8-year-old ICSI children . METHODS Developmental outcomes of 151 8-year-old singletons born through ICSI after 32 weeks of gestation were compared with those of 153 singletons of the same age born after spontaneous conception ( SC ) . Part of this population was seen in a cohort at the age 5 years . Outcome measures include Wechsler Intelligence Scale for Children-Revised ( WISC-R ) and Movement Assessment Battery for Children ( ABC ) . RESULTS Regarding intellectual functioning , ICSI children tend to obtain significantly higher total ( P < 0.01 ) , verbal ( P < 0.01 ) and performance ( P < 0.05 ) intelligence scores than SC children , nevertheless remaining in similar ranges . These effects are small ( Cohen 's d < 0.50 ) . High maternal educational level stayed in the regression as a factor accounting for some of the variance in total IQ between the groups . In terms of motor development , no significant differences were found between ICSI and SC children regarding overall motor skills , manual , balance and ball skills . CONCLUSION In this follow-up study , ICSI and SC children show a comparable cognitive and motor development until the age of 8 years STUDY QUESTION Do children born after assisted reproductive techniques ( ART ; IVF/ICSI )  display more mental health issues or social and cognitive developmental problems at 7 - 8 years than naturally conceived ( NC ) controls , and does child gender play a role ? SUMMARY ANSWER ART children do not differ with regard to mental health or social and cognitive developmental problems when compared with controls , but some gender-specific differences do exist . WHAT IS KNOWN ALREADY Systematic review s have not found any evidence of delays in neurocognitive or sensorimotor development in ART children . However findings on the effect of the type of ART treatment ( IVF versus ICSI ) on the offspring 's physical and mental development have not been uniform . Knowledge of the role of child gender in ART research is scarce . STUDY DESIGN , SIZE , DURATION This prospect i ve follow-up study compares mental health and social and cognitive developmental problems between 7 - 8-year-old ART and NC children , controlling for the father 's age , length of the parents ' partnership , mother 's parity , child 's gestational age , and the need of neonatal intensive care unit ( NICU ) . Further , within the ART group , we analysed whether the treatment type ( IVF versus ICSI ) and the child 's gender are associated with the mental health and developmental outcomes . PARTICIPANTS / MATERIAL S , SETTING , METHODS In this study , 255 singleton ART children ( IVF and ICSI ) were compared with 278 NC children on parent-reported internalizing and externalizing symptoms , and social ( social skills and peer relations ) and cognitive development ( executive functioning , perception , memory , and language ) . Within the ART group , 164 IVF and 76 ICSI children were compared on the same outcomes . Statistics included analyses of covariates ( ANCOVA ) with group main effects , group and gender interaction effects , and Bonferroni post hoc tests . MAIN RESULTS AND THE ROLE OF CHANCE ART and NC children did not differ generally in terms of their internalizing and externalizing symptoms or in the number of social and cognitive developmental problems ( Group main effects , P > 0.05 ) , but gender-specific group differences existed . The ART boys showed lower levels of cognitive problems than the NC boys , whereas ART girls showed higher levels of cognitive problems than the NC girls ( Group × Gender-interaction effects with Bonferroni post hoc tests on mother-reports , P < 0.01 ) . Further , unlike in the NC group , where boys showed more externalizing symptoms and social and cognitive developmental problems than girls ( Group × Gender-interaction effects with Bonferroni post hoc tests for both parents ' reports , P < 0.05 ) , gender differences were not found in the ART group . Within the ART group , IVF and ICSI children did not differ in terms of mental health or developmental outcomes , and no significant gender differences emerged . LIMITATIONS , REASONS FOR CAUTION The information on children 's mental health and development was based on parental reports only . The dropout rate between the child 's first year and the school age assessment s was very high for fathers ( 57.4 % ) and substantial for mothers ( 30.1 % ) , and the participating group was biased for older age of both parents and for better education of the fathers . WIDER IMPLICATION S OF THE FINDINGS The findings indicate the importance of considering child gender in learning about multiple developmental outcomes among children born after ART . STUDY FUNDING /COMPETING INTERESTS This study was supported by the Academy of Finl and ( # 11232276 ) , the Emil Aaltonen Foundation , The Family Federation of Finl and , Helsinki University Central Hospital Research Funds , and the National Graduate School of Psychology . None of authors has any competing interests to declare OBJECTIVES : The objective of this study was to document the psychological adjustment of adolescents who were conceived through donor insemination by lesbian mothers who enrolled before these offspring were born in the largest , longest running , prospect i ve , longitudinal study of same-sex – parented families . METHODS : Between 1986 and 1992 , 154 prospect i ve lesbian mothers volunteered for a study that was design ed to follow planned lesbian families from the index children 's conception until they reached adulthood . Data for the current report were gathered through interviews and question naires that were completed by 78 index offspring when they were 10 and 17 years old and through interviews and Child Behavior Checklists that were completed by their mothers at corresponding times . The study is ongoing , with a 93 % retention rate to date . RESULTS : According to their mothers ' reports , the 17-year-old daughters and sons of lesbian mothers were rated significantly higher in social , school/academic , and total competence and significantly lower in social problems , rule-breaking , aggressive , and externalizing problem behavior than their age-matched counterparts in Achenbach 's normative sample of American youth . Within the lesbian family sample , no Child Behavior Checklist differences were found among adolescent offspring who were conceived by known , as-yet-unknown , and permanently unknown donors or between offspring whose mothers were still together and offspring whose mothers had separated . CONCLUSIONS : Adolescents who have been reared in lesbian-mother families since birth demonstrate healthy psychological adjustment . These findings have implication s for the clinical care of adolescents and for pediatricians who are consulted on matters that pertain to same-sex parenting BACKGROUND Contemporary data on visual memory and learning in survivors born extremely preterm ( EP ; < 28 weeks gestation ) or with extremely low birth weight ( ELBW ; < 1,000 g ) are lacking . METHODS Geographically determined cohort study of 298 consecutive EP/ELBW survivors born in 1991 and 1992 , and 262 r and omly selected normal-birth-weight controls . RESULTS Visual learning and memory data were available for 221 ( 74.2 % ) EP/ELBW subjects and 159 ( 60.7 % ) controls . EP/ELBW adolescents exhibited significantly poorer performance across visual memory and learning variables compared with controls . Visual learning and delayed visual memory were particularly problematic and remained so after controlling for visual-motor integration and visual perception and excluding adolescents with neurosensory disability , and /or IQ < 70 . Male EP/ELBW adolescents or those treated with corticosteroids had poorer outcomes . CONCLUSION EP/ELBW adolescents have poorer visual memory and learning outcomes compared with controls , which can not be entirely explained by poor visual perceptual or visual constructional skills or intellectual impairment Objective To investigate how pregnancy planning , time to conception , and infertility treatment influence cognitive development at ages 3 and 5 . Design Prospect i ve population based cohort study . Setting Millennium Cohort Study in the United Kingdom . Participants 18 818 children recruited at 9 months and followed up at 3 and 5 years . 11 790 singletons with available data on pregnancy , cognitive outcomes , and confounders were included in analyses at age 3 and 12 136 at age 5 . Exposure measures Mothers reported whether the pregnancy was planned , and their feelings when first pregnant ; those in whom the pregnancy was planned provided time to conception , and details of any assisted reproductive technologies . The population was divided into “ unplanned ” ( unplanned and unhappy ) , “ mistimed ” ( unplanned but happy ) , “ planned ” ( planned , time to conception < 12 months ) , “ subfertile ” ( planned , time to conception ≥12 months ) , “ induced ovulation ” ( received clomiphene citrate ) , and “ assisted reproduction ” ( in vitro fertilisation or intracytoplasmic sperm injection ) . The “ planned ” group was the comparison group in all analyses . Outcome measures Three components of the British Ability Scales ( BAS II ) . Naming vocabulary assessed verbal ability at age 3 ; this test was repeated at age 5 with the picture similarities and pattern construction subscales , which measure non-verbal and spatial abilities . Results In unadjusted analyses , the scores on all scales in children from unplanned pregnancies were significantly lower than in those from planned pregnancies — for example , the difference in mean verbal ability score at age 3 was −4.8 ( 95 % confidence interval −6.0 to −3.7 ; P<0.05 ) , equivalent to an average delay of four months . After adjustment for sociodemographic factors these differences were attenuated : −0.3 ( −1.3 to 0.7 ) , equivalent to no delay . Children born after assisted reproduction performed consistently better in verbal ability tests ( 3.8 ( −0.2 to 7.9 ) at age 3 and 3.5 ( 0.2 to 6.8 ) at age 5 ) , which suggests that on average these children are three to four months ahead ; this difference did not completely disappear with adjustment for confounders . Children born after infertility treatment had lower mean scores in non-verbal tests ( −1.2 ( −4.1 to 1.6 ) after assisted reproduction and −1.5 ( −3.5 to 0.4 ) after induced ovulation ) and in spatial ability tests ( −2.7 ( −6.9 to 1.6 ) after assisted reproduction ) , though the differences were not significant . Conclusions Pregnancy planning , subfertility , or assisted reproduction do not adversely affect children ’s cognitive development at age 3 or 5 . The differences observed in the unadjusted analyses are almost entirely explained by marked inequalities in socioeconomic circumstances between the groups Growing public awareness of the use of donor insemination ( DI ) to enable infertile couples to become parents has been accompanied by increasing concern regarding the potentially negative consequences for family relationships and child development . Findings are presented from a prospect i ve study of the quality of parenting and psychological adjustment of DI children at age 12 . Thirty-seven DI families , 49 adoptive families , and 91 families with a naturally conceived child were compared on st and ardized interview and question naire measures administered to mothers , fathers , children , and teachers . The differences between DI families and the other family types reflected greater expressive warmth of DI mothers toward their children and less involvement in the discipline of their children by DI fathers . The DI children were well adjusted in terms of their social and emotional development . The findings are discussed with respect to the secrecy surrounding DI and the imbalance in genetic relatedness between the parents and the child BACKGROUND The aim of the present study was to determine language levels in twins and singletons born after at least 34 weeks gestation and without identifiable neurological abnormality and to evaluate whether in vitro fertilization ( IVF ) affects language development in twin pregnancies . METHODS A prospect i ve study of a large cohort of all children born between 1 January 2001 and 31 December 2003 was carried out at Gazi University Hospital . All live-born twin pairs in which both twins survived were identified , and a comparable sample of families with pairs of singletons were chosen . The  Stanford-Binet Intelligence Scale Form and the translated Turkish form of the Peabody Picture Vocabulary Test  were completed at 60 months . RESULTS Even after excluding the most premature twins and those with diagnosable neurological damage , twins performed worse than singletons on language development tests . Twin girls had better scores than twin boys . A statistically significant difference was found between the scores of term and preterm twins . No significant difference was noted when compared according to birth order . Appropriate for gestational age ( AGA ) twins did better than small for gestational age ( SGA ) twins in the test scores . All twin girls did not differ from singleton girls , but all twin boys performed worse than singleton boys . Term twins had similar results with term singletons , but preterm twins had lower scores than preterm singletons . SGA singletons had better scores than SGA twins , while AGA twins and singletons did not differ . When the children were compared with regard to method of conception , IVF children had significantly lower scores on the tests than those in the spontaneous conception group . CONCLUSION It is hoped that the present findings could lead to a more precise assessment of children for speech impairment and , above all , to more efficient preventive intervention . Whatever mechanisms are involved , the present results indicate that twins born as a result of IVF , are at a disadvantage in terms of language development in comparison with spontaneously conceived twins STUDY QUESTION Do preschool preimplantation genetic diagnosis ( PGD ) children differ in their cognitive and psychomotor development from children born after ICSI and spontaneous conception ( SC ) ? SUMMARY ANSWER The cognitive development of PGD pre-schoolers was comparable to children born after ICSI and SC but motor development differed between ICSI and SC groups . STUDY DESIGN , SIZE DURATION The cognitive abilities and motor skills of 5- to 6-year-old singletons born after PGD ( n = 47 ) were assessed in comparison with 49 ICSI and 48 SC children in a prospect i ve , case-controlled , matched follow-up study between April 2011 and May 2013 . PARTICIPANTS / MATERIAL S , SETTING , METHODS PGD singletons , ICSI and SC children of preschool age were examined with the Wechsler Preschool and Primary Scale of Intelligence ( WPSSI-III-NL ) and the Movement ABC ( M ABC ) . The WPSSI-III-NL revealed scores for Full IQ , Verbal IQ and Performance IQ . The M ABC yields a total score and comprising scores for measurements of balance , dexterity and ball skills . Since embryo biopsy is the only technical difference between the PGD and ICSI procedures , ICSI children were included as controls . These children were part of a Dutch-speaking cohort of children conceived after assisted reproduction technology ( ART ) at the Universitair Ziekenhuis Brussel ( UZ Brussel ) who received longitudinal follow-up . The SC children acted as a second control group similar to the fertile PGD sample and in contrast to the ICSI group . The SC group was recruited through announcements in a variety of media . The children were matched for age , gender , birth order and educational level of the mother . The assessment s carried out for the ART groups were blinded whenever possible . The data were analysed using analysis of covariance ( ANCOVA ) and partial eta squared ( η(2 ) ) , which was used as a measurement of effect size . MAIN RESULTS AND THE ROLE OF CHANCE The overall cognitive development of PGD singletons did not differ from controls [ P = 0.647 , η(2 ) = 0.006 ; 95 % confidence interval ( CI ) ( 0 , 0.043 ) ] . The partial IQ scores for Verbal and Performance intelligence revealed similar results . Analysis of motor development based on the total score as well as subscales did indicate a significant difference between the three conception groups [ P = 0.033 , η(2 ) = 0.050 , 95 % CI ( 0 , 0.124 ) ] . Post hoc analysis indicated that the significant difference was situated between performances of ICSI and SC children . Balance capacities [ P = 0.004 , η(2 ) = 0.079 , 95 % CI ( 0.025 , 0.163 ) ] and its post hoc analysis yielded equivalent results . Motor capacities of PGD singletons , however , did not differ from any of the two other conception groups . LIMITATIONS , REASONS FOR CAUTION Given that we only assessed Caucasian singletons born after PGD , caution is required when drawing more general inferences from our results . The small sample size may be a limitation . A priori power analysis , however , revealed that at least 52 children per group were needed to detect a medium effect and 80 % power using ANCOVA . Originally our sample met this threshold but we had to exclude six cases in order to remove outliers and due to missing data . WIDER IMPLICATION S OF THE FINDINGS Long-term follow-up of children born after embryo biopsy , in this case for PGD , is needed to confirm that the development of these children remains comparable to ICSI and SC children . Our findings do support the safety of the PGD technique and will reassure patients with hereditary genetic diseases regarding the health of their future offspring conceived with PGD . STUDY FUNDING /COMPETING INTERESTS Funding for this study was obtained from the OZR ( Research group of the Vrije Universiteit Brussel ) , the FWO ( Fonds Wetenschappelijk Onderzoek ) and the Wetenschappelijk Fonds Willy Gepts . The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection . UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection , from IBSA , Ferring , Organon , Shering-Plough , Merck and Merck Belgium . M.B. has received consultancy and speaker 's fees from Organon , Serono Symposia and Merck OBJECTIVE To assess the neurodevelopmental health of children born after intracytoplasmatic sperm injection ( ICSI ) .  DESIGN Prospect i ve controlled blinded study . SETTING Tertiary care center . PATIENT(S ) A total of 276 term-born singletons conceived by ICSI and 273 matched spontaneously conceived ( SC ) singletons at the age of 5.5 years . MAIN OUTCOME MEASURE(S ) Neuromotor development assessed by a detailed neurologic examination , including the st and ardized motor test MOT 4 - 6 , and emotional/behavioral development and intelligence assessed with the Kaufman- Assessment Battery for Children . RESULT ( S ) There were no significant differences between ICSI children and control children regarding the neurologic examination , motor skills , emotional/behavioral development , and intelligence . CONCLUSION ( S ) The ICSI children born at term develop normally , similar to SC children OBJECTIVE To assess the somatic , psychomotor , and intellectual development of children conceived through intracytoplasmic single sperm injection ( ICSI )  over the whole preschool period . DESIGN Prospect i ve , controlled , cohort study . SETTING Fertility clinic in Brussels , Belgium . PATIENT(S ) Sixty-six ICSI-conceived children prospect ively compared with 52 IVF-conceived and 59 spontaneously conceived children . All children were full-term singletons . INTERVENTION(S ) Home visits by a trained psychologist . St and ardized interviews . Assessment s using the revised Brunet-Lézine scale and the revised Wechsler preschool and primary scale of intelligence . MAIN OUTCOME MEASURE(S ) Physical growth and general health . Formal developmental and intellectual assessment s. RESULT ( S ) Children conceived by ICSI were healthy : no significant differences appeared in the incidence of combined congenital malformations ( 11.3 % ) , health problems ( 44.1 % ) , surgical interventions ( 18.6 % ) , and hospitalizations ( 6.8 % ) , nor for the developmental assessment s ( mean developmental quotient at 9 months : 93.9 ; at 18 months : 102.0 ) . For the intellectual assessment s , the between-group differences disappeared when adjusted for levels of parental education ( mean intelligence quotient at 3 years : 97.0 ; at 5 years : 103.3 ) . CONCLUSION ( S ) This pilot study shows that throughout the preschool period , ICSI-conceived children have psychomotor and intellectual development similar to that of IVF-conceived and spontaneously conceived children . These conclusions need to be confirmed by multicenter studies Objective To assess the mental health of children born after fertility treatment  by comparing their risk of mental disorders with that of spontaneously conceived children . Design Prospect i ve register based cohort study . Setting Nationwide register based information from Danish National Health Registers cross linked by a unique personal identification number assigned to all citizens in Denmark . Participants All children born in Denmark in 1995 - 2003 with follow-up in 2012 when the children were aged 8 - 17 ; 33 139 children were conceived after fertility treatment and 555 828 children were born after spontaneous conception .  Main outcome measures Absolute risks and hazard ratios for overall and specific mental disorders estimated with adjustment for potential confounding variables . Estimated association between the risk of mental disorders and subtypes of procedures , hormone treatments , gamete types , and cause of infertility . Results The risk of mental disorders in children born after in vitro fertilisation or intracytoplasmic sperm injection was low , and was no higher than in spontaneously conceived children , except for a borderline significant increased risk of tic disorders ( hazard ratio 1.40 , 95 % confidence interval 1.01 to 1.95 ; absolute risk 0.3 % ) . In contrast , children born after ovulation induction with or without insemination had low but significantly increased risks of any mental disorder ( 1.20 , 1.11 to 1.31 ; absolute risk 4.1 % ) , autism spectrum disorders ( 1.20 , 1.05 to 1.37 ; 1.5 % ) , hyperkinetic disorders ( 1.23 , 1.08 to 1.40 ; 1.7 % ) , conduct , emotional , or social disorder ( 1.21 , 1.02 to 1.45 ; 0.8 % ) , and tic disorders ( 1.51 , 1.16 to 1.96 ; 0.4 % ) . There was no risk systematic ally related to any specific type of hormone drug treatment . Conclusions There was a small increase in the incidence of mental disorders in children born after ovulation induction/intrauterine insemination . Children born after in vitro fertilisation/intracytoplasmic sperm injection were found to have overall risk comparable with children conceived spontaneously
target: SUMMARY ANSWER The available high- quality evidence indicates that specific treatments may give rise to different effects on cognitive development , with certain treatments , including ICSI , associated with cognitive impairment .
background: STUDY QUESTION Does  fertility treatment  influence cognitive ability in school aged children , and does the impact vary with the type of treatment ?
  WHAT IS KNOWN ALREADY Previous review s of the literature concerning cognitive outcomes among children conceived with medical assistance have concluded that study findings are generally ' reassuring ' , but limited attention has been paid to the quality of this research .
  In addition , no review has separately assessed the range of treatment modalities available , which vary in invasiveness , and thus , potentially , in their effects on developmental outcomes .