The purpose of this study was to assess major neurodevelopmental aspects of children conceived by assisted reproductive treatments compared to spontaneously conceived children during the early school years.
Material & Methods:
In this follow-up study, mothers of 358 children born following assisted reproductive treatments and 401 spontaneously-conceived children were interviewed by telephone regarding their children’s health and development, when the children were 7-8 years old. The main outcomes were maternal responses to 4 questionnaires: Developmental Coordination Disorder Questionnaire, Short Sensory Profile, Autism Spectrum Screening Questionnaire, and the Attention-deficit hyperactive disorder (ADHD) Child Symptom Inventory-4 subscale. Mothers reported diagnoses of ADHD and autism spectrum disorder.
Results:
No significant differences were found between the groups in Developmental Coordination Disorder Questionnaire or Short Sensory Profile scores upon univariate or multivariable analyses. There was a slightly higher but nonsignificant rate of diagnosed ADHD among children in the assisted reproductive treatment group (9.6% vs 5.5%; P = .18); on multivariable analysis, a nonsignificant increase in ADHD was also found for assisted reproductive treatment children (hazard ratio 1.45, 95% confidence interval 0.81-2.61). Regarding the Child Symptom Inventory-4 criteria for ADHD among the children who had never been diagnosed, there was also a slightly higher but nonsignificant rate among the assisted reproductive treatments compared to spontaneously-conceived children on univariate (2.4% vs 1.8%; P = .50) and multivariable analysis (odds ratio 0.88, 95% confidence interval 0.27-2.86). Autism spectrum disorder diagnosis or Autism Spectrum Screening Questionnaire scores were not significantly different; however, 5 of the 6 children with autism spectrum disorder diagnoses were in the assisted reproductive treatment group.
Conclusions:
Neurodevelopmental measures were similar in both groups, although nonconclusive regarding ADHD and autism spectrum disorder risk. These findings contribute to the knowledge regarding long-term assisted reproductive treatment outcomes.
QinJShengXWuD, et al.Adverse obstetric outcomes associated with in vitro fertilization in singleton pregnancies. Reprod Sci. 2017;24(4):595–608.
4.
HansenMKurinczukJJMilneEde KlerkNBowerC. Assisted reproductive technology and birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2013;19(4):330–353.
5.
HargreaveMJensenAToenderAAndersenKKKjaerSK. Fertility treatment and childhood cancer risk: a systematic meta-analysis. Fertil Steril. 2013;100(1):150–161.
6.
HartRNormanRJ. The longer-term health outcomes for children born as a result of IVF treatment. Part II—mental health and development outcomes. Hum Reprod Update. 2013;19(3):244–250.
7.
RumboldARMooreVMWhitrowMJ, et al.The impact of specific fertility treatments on cognitive development in childhood and adolescence: a systematic review. Hum Reprod. 2017;32(7):1489–1507.
8.
FarhiAReichmanBBoykoVHourvitzARon-ElRLerner-GevaL. Maternal and neonatal health outcomes following assisted reproduction. Reprod Biomed Online. 2013;26(5):454–461.
9.
FarhiAGlasserSFrankS, et al.When the ideal meets the feasible: constructing a protocol for developmental assessment at early school-age. Front Pediatr. 2018;6:256.
10.
WilsonBNKaplanBJCrawfordSGCampbellADeweyD. Reliability and validity of a parent questionnaire on childhood motor skills. Am J Occup Ther. 2000;54(5):484–493.
11.
WilsonBNCrawfordSGGreenDRobertsGAylottAKaplanBJ. Psychometric properties of the revised Developmental Coordination Disorder Questionnaire. Phys Occup Ther Pediatr. 2009;29(2):182–202.
12.
McIntoshDMillerLJShyuV. Development and validation of the Short Sensory Profile. In: DunnW, ed. Sensory profile manual. San Antonio, TX: Psychological Corporation; 1999:59–73.
SprafkinJGadowKDSalisburyHSchneiderJLoneyJ. Further evidence of reliability and validity of the Child Symptom Inventory–4: parent checklist in clinically referred boys. J Clin Child Adolesc Psychol. 2002;31(4):513–524.
15.
EhlersSGillbergCWingL. A screening questionnaire for Asperger syndrome and other high-functioning autism spectrum disorders in school age children. J Autism Dev Disord. 1999;29(2):129–141.
16.
LingamRHuntLGoldingJJongmansMEmondA. Prevalence of developmental coordination disorder using the DSM-IV at 7 years of age: a UK population-based study. Pediatrics. 2009;123(4):e693–e700.
17.
WrightHCSugdenDA. A two-step procedure for the identification of children with developmental co-ordination disorder in Singapore. Dev Med Child Neurol. 1996;38(12):1099–1105.
18.
PinborgALoftASchmidtLGreisenGRasmussenSAndersenAN. Neurological sequelae in twins born after assisted conception: controlled national cohort study. BMJ. 2004;329(7461):311.
19.
LudwigAKatalinicAThyenUSutcliffeAGDiedrichKLudwigM. 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. Fertil Steril. 2009;91(1):125–132.
20.
LeunensLCelestin-WestreichSBonduelleMLiebaersIPonjaert-KristoffersenI. Cognitive and motor development of 8-year-old children born after ICSI compared to spontaneously conceived children. Hum Reprod. 2006;21(11):2922–2929.
21.
BayBMortensenELKesmodelUS. Assisted reproduction and child neurodevelopmental outcomes: a systematic review. Fertil Steril. 2013;100(3):844–853.
22.
ZhuJLObelCBassoOOlsenJ. Parental infertility and developmental coordination disorder in children. Hum Reprod. 2010;25(4):908–913.
23.
KallenAJFinnstromOOLindamAPNilssonEMNygrenKGOtterblad OlaussonPM. Is there an increased risk for drug treated attention deficit/hyperactivity disorder in children born after in vitro fertilization?Eur J Paediatr Neurol. 2011;15(3):247–253.
24.
BayB. Fertility treatment: long-term growth and mental development of the children. Dan Med J. 2014;61(10):B4947.
25.
KnoesterMHelmerhorstFMvan der WesterlakenLAWaltherFJVeenSLeiden Artificial Reproductive Techniques Follow-up Project (L-art-FUP). 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.
26.
WagenaarKvan WeissenbruchMMKnolDLCohen-KettenisPTDelemarre-van de Waal HA, Huisman J. Behavior and socioemotional functioning in 9-18-year-old children born after in vitro fertilization. Fertil Steril. 2009;92(6):1907–1914.
27.
BelvaFHenrietSLiebaersIVan SteirteghemACelestin-WestreichSBonduelleM. 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.
28.
BarnesJSutcliffeAGKristoffersenI, 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.
29.
TullyLAMoffittTBCaspiA. Maternal adjustment, parenting and child behaviour in families of school-aged twins conceived after IVF and ovulation induction. J Child Psychol Psychiatry. 2003;44(3):316–325.
30.
BayBMortensenELHvidtjornDKesmodelUS. Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study. BMJ. 2013;347:f3978.
31.
WagenaarKvan WeissenbruchMMKnolDLCohen-KettenisPT, Delemarre-van de Waal HA, Huisman J. Information processing, attention and visual-motor function of adolescents born after in vitro fertilization compared with spontaneous conception. Hum Reprod. 2009;24(4):913–921.
32.
PitcherTMPiekJPHayDA. Fine and gross motor ability in males with ADHD. Dev Med Child Neurol. 2003;45(8):525–535.
33.
NodaWItoHFujitaC, et al.Examining the relationships between attention deficit/hyperactivity disorder and developmental coordination disorder symptoms, and writing performance in Japanese second grade students. Res Dev Disabil. 2013;34(9):2909–2916.
34.
Mimouni-BlochAOffekHRosenblumSPosenerISilmanZEngel-YegerB. Association between sensory modulation and daily activity function of children with attention deficit/hyperactivity disorder and children with typical development. Res Dev Disabil. 2018;83:69–76.
35.
Engel-YegerBZiv-OnD. The relationship between sensory processing difficulties and leisure activity preference of children with different types of ADHD. Res Dev Disabil. 2011;32(3):1154–1162.
36.
SandinSSchendelDMagnussonP, et al.Autism risk associated with parental age and with increasing difference in age between the parents. Mol Psychiatry. 2016;21(5):693–700.
37.
ZachorDABen ItzchakE. Assisted reproductive technology and risk for autism spectrum disorder. Res Dev Disabil. 2011;32(6):2950–2956.
38.
DavidovitchMChodickGShalevV, et al.Infertility treatments during pregnancy and the risk of autism spectrum disorder in the offspring. Prog Neuropsychopharmacol Biol Psychiatry. 2018;86:175–179.
39.
MaimburgRDVaethM. Do children born after assisted conception have less risk of developing infantile autism?Hum Reprod. 2007;22(7):1841–1843.
40.
LehtiVBrownASGisslerMRihkoMSuominenASouranderA. Autism spectrum disorders in IVF children: a national case-control study in Finland. Hum Reprod. 2013;28(3):812–818.
41.
HvidtjornDGroveJSchendelD, et al.Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study. J Epidemiol Community Health. 2011;65(6):497–502.
42.
FountainCZhangYKissinDM, et al.Association between assisted reproductive technology conception and autism in California, 1997-2007. Am J Public Health. 2015;105(5):963–971.
43.
SandinSNygrenKGIliadouAHultmanCMReichenbergA. Autism and mental retardation among offspring born after in vitro fertilization. JAMA. 2013;310(1):75–84.
44.
HvidtjornDSchieveLSchendelDJacobssonBSvaerkeCThorsenP. Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2009;163(1):72–83.
45.
Bar LevLKeren-AbrahamYHaberYAdmon-RickG, eds. People With Disabilities in Israel 2015. Jerusalem, Israel: Myers-JDC-Brookdale Center for Research on Disabilities; 2015.
46.
OrnoyAOvadiaMRivkinDMilshteinEBarlevL.Prevalence of ADHD among 7-9-year-old children in Israel. A comparison between Jewish and Arab populations. Isr J Psychiatry Relat Sci. 2016;53(2):3–8.
47.
RazRWeisskopfMGDavidovitchMPintoOLevineH. Differences in autism spectrum disorders incidence by sub-populations in Israel 1992-2009: a total population study. J Autism Dev Disord. 2015;45(4):1062–1069.
48.
McCormickMCBrooks-GunnJ. Concurrent child health status and maternal recall of events in infancy. Pediatrics. 1999;104(5, pt 2):1176–1181.
49.
RobertsonHSchluterPJSundbornG. Reliability and validity of maternal recall of injuries in Pacific children: findings from the Pacific Islands Families Study. Pac Health Dialog. 2011;17(2):164–174.
50.
MajewskaRMrozek-BudzynDKieltykaAAugustyniakM. Usefulness of maternal assessment of children development based on reported age of achieved milestones. Przegl Epidemiol. 2013;67(3):487–490, 585-587.
51.
RiceFLewisAHaroldG, et al.Agreement between maternal report and antenatal records for a range of pre and peri-natal factors: the influence of maternal and child characteristics. Early Hum Dev. 2007;83(8):497–504.
52.
WillcuttEGBoadaRRiddleMWChhabildasNDeFriesJCPenningtonBF. Colorado learning difficulties questionnaire: validation of a parent-report screening measure. Psychol Assess. 2011;23(3):778–791.
53.
LaiWWO’MahonyMMulliganA. A telephone interview version of the middle childhood HOME observation measurement of the environment. Child Care Health Dev. 2015;41(6):1152–1160.
54.
NosakaNFujiwaraTKnaupEOkadaATsukaharaH. Validity of mothers’ reports of children’s weight in Japan. Acta Med Okayama. 2016;70(4):255–259.
55.
MiddelburgKJHeinemanMJBosAFHadders-AlgraM. Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI—a systematic review. Hum Reprod Update. 2008;14(3):219–231.
