Hypertensive Retinopathy is Not Associated with Low or High Birth Weight – Results from the Population-Based German Gutenberg Health Study

Introduction

Individuals with low birth weight (BW) are more likely to develop high blood pressure later in life. Although the exact mechanisms underlying these findings remain unclear, many studies have shown that high blood pressure in adulthood is a major risk factor for developing hypertensive retinopathy (HR).¹ As previous findings in this cohort were able to show that extreme BW in both directions is linked to a higher prevalence of diabetic retinopathy,² this study aims to assess the frequency of HR and its correlation with fetal growth restriction indicated by self-reported birth weight in a large population-based cohort in Germany.

Materials and Methods

The Gutenberg Health Study (GHS) is an observational cohort study that aims to gather prospective data from a population-based sample. The study involves analyzing fundus photographs of individuals between the ages of 35 and 74. Various signs of HR were graded according to the Mitchell-Wong-Classification.³ The measurements were conducted by two examiners, showing a high inter-rater reliability of 0.90. For statistical analysis, HR was dichotomized into “HR present in at least one eye” and HR “not present in any eye”. Birth weight information was obtained via self-reported responses in a questionnaire. The distribution of low, normal, and high birth weights in our cohort was compared to reported birth weight data in the medical literature and to data of the German Federal Statistical Office. Furthermore, birth weight data reported by a subset of participants born at the University Medical Center Mainz (UMCM) was validated against data recorded in medical charts and birth registries at the UMCM. This comparison showed a strong intraclass correlation coefficient of 0.89 (confidence interval 0.83; 0.92), indicating that the self-reported birth weights are highly accurate.

Results

A GHS subsample of 6855 participants (3714 females, aged 51.23 ± 10.5 years) with self-reported BW and available grading for HR were assessed. Both univariable and multivariable logistic regression analyses were conducted for linear and categorical birth weight data. The multivariable analysis took into account potential confounding factors such as age, sex, and cardiovascular risk factors that have been previously associated with HR. Adjustments were made to account for these variables and evaluate their impact on the association between BW and HR.

Descriptively, HR-frequency did not differ between the low BW group (<2500g) (10.3%; 39/379) and the normal BW group (2500–4000g) (9.6%; 540/5609) and the high birth weight group (12%; 104/867). In univariable analysis, HR showed a significant association with high BW (>4000g) (model #1: OR = 1.28 [1.02, 1.6]; p = 0.03). However, when adjusted for age and sex [female], BW was not associated with hypertensive retinopathy (model #2: OR = 1.08 [0.85; 1.36]; p = 0.53) and also remained non-associated when we additionally adjusted for cardiovascular risk factors (diabetes [yes], BMI, family history of stroke [yes] or myocardial infarction [yes], dyslipidemia [yes], smoking [yes] (model #3: OR = 1.08 [0.86; 1.37]; p = 0.51) (Table 1)). No association was observed between low BW and HR neither in univariable nor in multivariable analyses. No association was observed for linear relationships.

Table 1 Associations of Hypertensive Retinopathy with Birth Weight in the Gutenberg Health Study (2007–2012)

Discussion

Our findings could not show an association of either low or high BW with HR. To our knowledge, up to this point there are no population-based studies, which have conducted research regarding this particular association. While Liew et al found an association of low BW and narrower retinal arteriolar caliber in adults,⁴ a previous study investigating the retinal vessel calibres in our adult GHS-cohort did not find an association between BW and retinal vessel equivalents.⁵ Our observations regarding the lack of association between HR and BW within the same cohort align with these considerations. The absence of a noticeable correlation could be attributed to the relatively younger age of the cohort and advancements in hypertension management strategies. Moreover, it is important to highlight that older participants, who typically have a greater susceptibility to arterial hypertension, may also face a higher likelihood of inaccuracies in self-reported birth weight. This could stem from less precise record-keeping practices in the past, potentially leading to misclassification in our data. In a subcohort of participants, self-reported birth weight showed high validity when compared to individual chart reports (ICC = 0.89; 95%-CI: 0.83–0.92).

Our results are limited because in only 56% of all participants birth weight data were available and gradable fundus images were not available in about 15%. Furthermore, the reliance on self-reported birth weight data, while a common practice in epidemiological studies due to the logistical challenges of collecting information from a large number of participants may introduce recall bias.

Conclusion

In conclusion, based on the outcomes of this large population-based study, there is no substantial evidence to support a significant association between birth weight and hypertensive retinopathy.