O-270 Neurodevelopment at 5 years of age for preterm-born children according to mode of conception: a cohort study
Authors: Verhaeghe C , Laetitia M.M , Monique K , Géraldine G , Laurence F.L , Pierre-Yves A , Pierre-Emmanuel B , Andrei M 
Published: June 2022

Study question

Do neurodevelopmental outcome at 5 ½ years of age of children born preterm differ according to the mode of conception (spontaneous versus Medically-Assisted Reproduction (MAR)) ?

Summary answer

There was no evidence of an impact of the mode of conception on neurodevelopmental outcomes at 5 ½ years of age.

What is known already

Preterm delivery is a risk factor for sub-optimal neurological development. Pregnancies conceived after Medically-Assisted Reproduction – which includes in vitro fertalisation (IVF), IVF with intracytoplasmic insemination (IVF-ICSI), as well as intra-uterine insemination (IUI) following induction of ovulation (IO) or timed intercourse (TIC) following IO – have a higher risk of preterm delivery. Few studies have evaluated the outcome at more than 2 years of age of such preterm-born children.

Study design, size, duration

The French prospective, national cohort study “EPIPAGE-2” collected information about all births below 35 weeks GA in 546 maternity hospitals in France in 2011.Children born below 27 weeks’ GA were recruited over 8 months, those born between 27 and 31 completed weeks GA over 6 months, and those between 32 and 34 weeks GA over five weeks.

Participants/materials, setting, methods

Only children born between 24 and 34 weeks’ GA were included.

At birth, maternal, obstetric and neonatal data were obtained from medical records and mothers were interviewed to obtain information on their social characteristics and pregnancy.

Surviving children were seen by trained investigators at 5 ½ years of age: this included medical and neurodevelopmental examinations, and parents completed a questionnaire.

Birth following MAR was compared to that following natural conception.

Main results and the role of chance

4349 children who survived to 5 ½ years of age were included: 814 in the ART group and 3535 in the spontaneously conceived group.

No difference in cerebral palsy (aOR=1.00, 95% CI 0.67-1.49), neurodevelopmental disabilities (aOR=1.09; 95% CI 0.82-1.45) and developmental coordination disorders (aOR=0.75; 95% CI 0.50-1.12) were found between children born following MAR and children born following spontaneous conception after adjustment for sociodemographic factors.

For proportions of IQ &lt; 1 SD and &lt;2 SD, there were no significant differences between the ART group and the spontaneous pregnancy group (respectively, aOR= 0.99 95% CI 0.80-1.23, and aOR=1.14; 95% CI 0.83-1.56).

In subgroup analyses, no differences were seen between children born following IO or IUI nor among those conceived through IVF or IVF-ICSI when compared to children conceived spontaneously.

Limitations, reasons for caution

The main difficulty in prospective cohort studies is loss to follow-up. We are further reassured because analyses using complete cases found very similar results.

We were limited in the extent of our analyses by the infertility treatment information available.

Furthermore, we could not study outcomes for children born from donated gametes.

Wider implications of the findings

To our knowledge, this is the first published study evaluating multiple dimensions of longer term neurodevelopment among children born preterm according to the mode of conception. The large, prospectively-collected national cohort meant we could study several neurodevelopmental outcomes taking into consideration important confounding factors with sufficient power.

Trial registration number

CPP-2873