Subfertility factors rather than assisted conception factors affect cognitive and behavioural development of 4-year-old singletons.
Research on cognitive and behavioural development of children born after assisted conception is inconsistent. This prospective study aimed to explore underlying causal relationships between ovarian stimulation, in-vitro procedures, subfertility components and child cognition and behaviour. Participants were singletons born to subfertile couples after ovarian stimulation IVF (n = 63), modified natural cycle IVF (n = 53), natural conception (n = 79) and singletons born to fertile couples (reference group) (n = 98). At 4 years, cognition (Kaufmann-ABC-II; total IQ) and behaviour (Child Behavior Checklist; total problem T-score) were assessed. Causal inference search algorithms and structural equation modelling was applied to unravel causal mechanisms. Most children had typical cognitive and behavioural scores. No underlying causal effect was found between ovarian stimulation and the in-vitro procedure and outcome. Direct negative causal effects were found between severity of subfertility (time to pregnancy) and cognition and presence of subfertility and behaviour. Maternal age and maternal education acted as confounders. The study concludes that no causal effects were found between ovarian stimulation or in-vitro procedures and cognition and behaviour in childrenaged 4 years born to subfertile couples. Subfertility, especially severe subfertility, however, was associated with worse cognition and behaviour.
University Medical Center Groningen, Department of Paediatrics, Division of Developmental Neurology, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Pamela
P
Schendelaar
University Medical Center Groningen, Department of Epidemiology, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Sacha
S
La Bastide-Van Gemert
Department of Obstetrics and Gynaecology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Maas Jan
MJ
Heineman
Department of Department of Mathematics and Computer Science, Division of Stochastics W&I, Eindhoven University of Technology, De Rondom 70, 5612 AP Eindhoven, The Netherlands.
Karin J
KJ
Middelburg
University Medical Center Groningen, Department of Paediatrics, Division of Developmental Neurology, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Jorien
J
Seggers
Department of Department of Mathematics and Computer Science, Division of Stochastics W&I, Eindhoven University of Technology, De Rondom 70, 5612 AP Eindhoven, The Netherlands.
Edwin R
ER
Van den Heuvel
University Medical Center Groningen, Department of Paediatrics, Division of Developmental Neurology, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: m.hadders-algra@umcg.nl.
Mijna
M
Hadders-Algra
D000328:Adult; D000465:Algorithms; D002653:Child Behavior Disorders / Q000209:etiology*; D002657:Child Development; D002675:Child, Preschool; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology*; D004522:Educational Status; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D007247:Infertility, Female / Q000503:physiopathology*; D008297:Male; D008423:Maternal Age; D010062:Ovulation Induction / Q000009:adverse effects*; D011446:Prospective Studies; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods; D055815:Young Adult
assisted reproduction techniques; causal inference search algorithm; cognitive and behavioural outcome; ovarian stimulation; subfertility