In this study investigating the association between the environment present around birth and cognition in old age, we found little evidence to support a substantial influence. We only found weak support for any anthropometric measures obtained at birth being predictive of cognitive function in old age. Specifically, only head circumference was associated with a better performance on COWAT and TMA in old age in the unadjusted model. This is contradictory to a previous paper which found no association between head circumference at birth and adult cognitive function, but a positive association between adult head circumference and adult cognitive function (Gale et al. 2003). Negative findings were present for birth complications and maternal health status. We did, however, find support for an association between higher parental SES (as measured by father’s occupation) and global cognitive function in old age in addition to specific associations with Digit Symbol and TMA test performance, both representing timed tests involving attention, speed and effortful mental processing. This highlights the importance of parental SES in relation to some specific domains of cognitive functioning in old age (Jefferis et al. 2002; Zhang et al. 2009), perhaps relatively independent of birth size (Zhang et al. 2009), a notion which was confirmed also in our study.
Important strengths of this study included access to birth records from the 1920s and the possibility to link this information to a population-based health survey in the late 1990s, enabling a 72–74 year follow-up. Data sources for both exposure and outcome status contained detailed information, and the gathering of information is unlikely to be biased in any particular direction. Considering the birth records, these were used at the time in the education of midwives under the supervision of the head physician with a high level of attention to quality, and included detailed anthropometric measures, as well as information about maternal health and circumstances, the birth process and the early post-natal period. Another strength, is that the cognitive examination part of the HUSK study included cognitive tests investigating several different cognitive domains ranging from episodic memory, executive function visuospatial and motor skills and verbal fluency.
A key limitation is that a relatively small proportion of the HUSK sample could be traced to their birth records. There are several potential reasons for this: the birth records were only available for a subgroup as not everyone who participated in HUSK was born in the Bergen area, and some were born at home or at other hospitals. Based on a conservative estimate, at least one-third of the HUSK sample would not be within the catchment area of the public maternity ward at the time of birth. The sample that was traced was representative of the participants in the HUSK cognitive examination. The results of the analysis are therefore likely to generalize to others of this generation and residence. However, it cannot be assumed that the traced participants were representative of people born in the location from which the early life records were taken. In particular, the representativeness of the birth cohort in HUSK might well have been influenced by intervening migration and survival effects because of the long follow-up. Healthy survivor effects (Baillargeon & Wilkinson 1999) or non-participation bias (Knudsen et al. 2010) are also possible. Negative findings could have resulted from inaccuracies in the measurement of either exposures or outcomes; for example, information on maternal health and family circumstances was derived from relatively crude measures. However, despite this, the similarly crude measure of parental SES included provided the most consistent significant associations identified with the outcomes. As previously described, three different social classes dominated Bergen during the time when the participants were born. Based on information from paternal occupational status, however, most of the participants in our study sample were from middle to lower socioeconomic strata with the occupation of the fathers varying from unskilled manual workers to teachers and general managers. This should be considered as a characteristic of the analysed sample when interpreting findings. Given the high number of associations tested, Type I errors cannot be ruled out, although we chose to focus on patterns of significant associations rather than significant associations per se. Differential bias arising from measurement is unlikely since reporting in HUSK is unlikely to be influenced by birth circumstances and recording of birth circumstances was carried out blind to all HUSK measures. The low traceability and small sample size constitute central limitations to our study, and warrants caution with regards to the precision of our estimates, and the interpretation and generalisability of the present study. Also of note, the limited size of the sample did not provide sufficient statistical power to specifically investigate low (<2.5 kg) or high (>4.5 kg) birth weight, or any influence of rare birth complications on cognitive function in old age, such as obstruction, foetal hypoxia or abnormally low birth weight.
Interpretation of our findings
We found little evidence to support a substantial association between intrauterine or birth environment and cognitive function in old age in general. The only anthropometric measure which to a certain degree predicted cognition in old age was head circumference, and parental SES was the only exposure which was associated with the composite cognitive score. Both a higher head circumference and SES seemed to predict a higher cognitive function in old age independently of each other. One potential explanation for this is that early SES and head circumference are predictors of two different aspects of later cognitive function (Stern 2002). The association between SES and later cognitive function may represent cognitive reserve, while the association between head circumference and later cognitive function may represent brain reserve, both of which are relevant concepts for understanding cognitive function and vulnerability to cognitive impairments in old age (Stern 2002). In this respect, it also interesting that adjusting for educational attainment substantially weakened the associations between paternal SES and cognitive function in old age, suggesting that these associations might be substantially mediated through education. On the other hand, self-rated health reported in later life did not appear to influence these associations meaningfully. Further specific causal pathway modeling was felt to be beyond the scope of this study and not warranted by the largely negative associations of interest.
The lack of a substantial association between intrauterine or birth environment and cognitive function in old age, may be also be a reflection of a diminished impact of these early factors as other influences comes into play across the lifespan (Zhang et al. 2009). Both birth weight and socioeconomic status have been found to be associated with cognitive function in childhood (Shenkin et al. 2001; Jefferis et al. 2002), although socioeconomic status and postnatal influences have been suggested to be more important than prenatal factors (Jefferis et al. 2002; Erickson et al. 2010), similar to our own finding of the importance of parental SES. Other studies have also found that social disadvantage and early life stressors are related to cognitive function in later life (Mak et al. 2006; Nguyen et al. 2008; Fors et al. 2009), and it is generally accepted that childhood SES is an important predictor for later cognitive function (Mak et al. 2006; Hackman & Farah 2009), and cognitive reserve (Stern 2002). Even though anthropometric measures obtained at birth did not predict cognitive function later in life, it is possible that other factors mitigated these initial differences and reduced or eliminated their influence in later adult life (Zhang et al. 2009). These may include later nutrition, education and occupational status (Stern 2002).