Euthyroid Collaboration


The Millennium Cohort: neurodevelopmental follow up of preterm and term infants at 5.5 years.

Information for Parents and Carers


This is a Scottish, multi-centre, follow-up study involving a group of preterm and term infants, The Millennium Cohort. The infants took part in a cohort study which measured thyroid hormone levels in the first month of life. The first follow up study assessed their neurodevelopmental status at a corrected age of 5.5 years to determine if there was an association between newborn thyroid hormone levels and later outcome.

These infants were first recruited in 1998 in various hospitals around Scotland: Aberdeen Maternity Hospital; Ayrshire Central Hospital; Ninewells Hospital and Medical School, Dundee; Simpson Memorial Maternity Pavilion, Edinburgh; Glasgow Royal Maternity Hospital, Glasgow; Queen Mother’s Maternity Hospital, Glasgow; Southern General Hospital, Glasgow; Forth Park Hospital, Kirkcaldy; Royal Alexandra Hospital, Paisley; Stirling and Falkirk Forth Valley; and Bellshill Maternity Hospital, Lanarkshire. The thyroid hormone levels of over 800 infants are recorded.

Low thyroid hormones, specifically T4, can give rise to a condition known as transient hypothyroxinaemia. Transient hypothyroxinaemia is the commonest thyroid dysfunction of premature infants.  Previously it was not thought to be associated with long-term detriment but some studies have found adverse association with neurodevelopment. The validity of the association is unclear, as the studies adjusted for a differing range of factors likely to influence neurodevelopment, and there is no consensus about the level used to define ‘hypothyroxinaemia’, which thyroid hormone to use in the classification, nor when the measurements should be made. 

During the follow up study infants were assessed using the McCarthy Scale and in the analysis we were able to adjusted for 26 influences of neurodevelopment including a measure of parental intellect, transient hypothyroxinaemia, postnatal illnesses, home environment, whether the child was breast or formula fed, multiple birth, growth retardation, and use of postnatal drugs.

We had neonatal serum measurements of T4 and assessment data at 5.5 years for 442 infants born under 35 weeks gestation and 100 term infants. Infants with hypothyroxinaemia (defined as a T4 level ?10th percentile on day 7, 14 or 28 corrected for gestational age) scored significantly lower than euthyroid infants (defined as a T4 level between >10th percentile and <90th percentile on all days) on all aspects of the McCarthy scales.  Following adjustment for confounders of neurodevelopment, hypothyroxinaemia contributed significant variation to the General Cognitive scale (-7 points) and one of its three sub- scales, the Verbal scale (-5 points). 

This is the first follow up and at the moment our findings do not support the view that the hypothyroxinaemic state, in the context of this analysis, is harmless in preterm infants.

You can find more detailed information regarding our research by exploring this web site.


Key References

  1. Dunn LM, Dunn L, Whetton C, Pintilie D. British Picture Vocabularly Scale: adapted from the Peabody Picture Vocabularly Test – revised edition. Windsor: NFER – Nelson., 1982.
  2. McCarthy D. Manual for the McCarthy Scales of children’s abilities. New York. Psychological Corporation, Harcourt Brace Jovanovich. 1972.


Where to next?

The associations that we found are interesting (and have been submitted for publication in a peer reviewed medical journal), but it is important that we understand more. For example, do the associations persist as the children get older? We should like to invite the children for assessment again when they reach young adulthood.  We hope you and your child(ren) will agree to help us when we next invite you. In the meantime if you have any queries or if you move house, please will you let us know?

You can write to us:

The Millennium Cohort
Human Brain Development Group
Mackenzie Building
University of Dundee
Ninewells Hospital and Medical School Campus
Dundee DD2 4BF

or email:

On behalf of the research team, very many thanks for your continued support.