Aim of the project

The aim of the project is to investigate the relationship between the infants born "near term" (32 to 36 weeks gestation) and IQ.

Background

The long term effects of prematurity are well recorded in infants born before 32 weeks corrected gestation. Extreme prematurity is associated with increased risks of cerebral palsy, speech[1], educational[1], and executive functioning[2] deficits as well as reduction in more global measures of cognition. The long term outcome of infants born at only moderately premature gestations however is less clear. Previous studies have suggested increased rates of educational concerns in infants born before 37 weeks gestation[3, 4] but little evidence exists on specific measures of cognition, particularly IQ, and other measures of neuro-development. At present these infants little specific educational input, and indeed recent recommendations have suggested that that only infants below 32 weeks of gestational age should be offered formal neuro-developmental follow-up.

Experimental design and methods to be used in investigating this problem

Infants born above 31 weeks gestational age will be identified from the ALSPAC cohort. The exposure of interest will be gestational age, categorized as near term (less than 37 weeks corrected gestation) or term (37 weeks or more). The primary outcome will be IQ (as measured by the WISC-II at 8 years). In addition measures of school performance, manual dexterity, attention, memory and language skills will also be assessed.

Covariates

Measures of neonatal wellbeing will be obtained from the STORK dataset (available for all infants born in St Michaels orSouthmeadHospital). Measures used in the analysis will be:

• Antenatal factors: Gender, maternal parity and maternal hypertension.
• Intrapartum factors: Birth weight, length and head circumference (corrected for gestation), mode of birth (i.e. spontaneous cephalic, emergency or elective caesarian section, instrumental or breech) and maternal pyrexia.
• Social factors: Maternal age, socioeconomic group and educational achievements, car ownership, housing tenure, crowding and ethnicity.

Any infants who are admitted to the neonatal unit will have further data on presence or not of neurological signs recorded from the Neonatal Data. Covariates will be added to the model in the blocks above.

Analysis Strategy

Exposure groups will be defined by completed gestational age (32-36 weeks). A reference groups will be defined of infants born at term (37 weeks or more completed weeks) who did not require admission to a neonatal unit.

Outcomes will be both the difference in mean value in the outcome variable (if normally distributed) and the proportion of infants in the lowest 10%. An IQ of less than 80 will be considered 'low'. Linear and logistic regression models will be used to assess the association between the exposure and the outcomes as appropriate.

A secondary analysis will be performed with the results stratified by the completed week of gestation and including all infants born at term (including those admitted to the neonatal units).

Chained Equations may be used to impute the value of any missing covariate data. All analysis will be performed using STATA 10 software (Stata Corp, TX,USA).

Study power

Assuming that around 5% of infants will be born moderately preterm and that there is IQ data available on 6000 infants within the cohort, we would have a power of greater than 99% to find a clinically important difference of 3.25 IQ points (a quarter of one standard deviation) with an alpha of 5%.

References

1. Wolke D, Samara M, Bracewell M, Marlow N, Group EPS: Specific language difficulties and school achievement in children born at 25 weeks of gestation or less.[see comment]. Journal of Pediatrics 2008;152:256-262.

2. Marlow N, Hennessy EM, Bracewell MA, Wolke D, Group EPS: Motor and executive function at 6 years of age after extremely preterm birth. Pediatrics 2007;120:793-804.

3. Chyi LJ, Lee HC, Hintz SR, Gould JB, Sutcliffe TL: School outcomes of late preterm infants: special needs and challenges for infants born at 32 to 36 weeks gestation. J Pediatr 2008;153:25-31.