This study examined the relationship between birth weight and risk factors for renal disease in 1160 Canadians from rural and Aboriginal communities. The results showed: 1) Low birth weight (LBW) and high birth weight (HBW) were both associated with hypertension in the overall cohort. 2) LBW, but not HBW, was significantly associated with later life diabetes, particularly in the Aboriginal subgroup. 3) As expected, diabetes, hypertension and metabolic syndrome were interrelated and likely confounded the relationships with birth weight, though each may be independently programmed during fetal development. The results were consistent with prior research linking LBW and HBW to increased risk of cardiovascular and renal diseases later in life.

1. Association of birth weight and risk factors for renal
disease in a rural Canadian cohort of mixed ethnicity
Valerie A. Luyckx MBBCh1, Samantha L. Bowker PhD2, Alison Miekle3, Ellen L. Toth, MD3.
1Division ofNephrology, 2 School of Public Health and 3Division of Endocrinology,University of Alberta,
Edmonton, Alberta, Canada
Introduction
1160 Canadians (ages 6 – 90 years) from off reserve Aboriginal communities or rural
towns participated in 2 voluntary programs screening for diabetes risk factors and
diabetes and its complications. Individuals gave consent for aggregate analysis of their
data. Participants underwent a 2 hour visit with a trained heath care worker. Data was
recorded for demographic factors, measured anthropomorphic factors, blood pressure,
blood glucose, hemoglobin A1c, lipid panel, urine protein and medication usage. Birth
weights were recalled by the subject or their parent. Recalled birth weights have been
validated in several populations (Curhan et al., 1996). Subject ethnicity was self‐defined.
The status/non‐status group contains individuals from remote communities. Metis and
non‐aboriginal groups were still rural but lived closer to larger towns. High blood
pressure was defined as a value above the normal for age, in adults a systolic or a
diastolic blood pressure ≥ 140/90 and or the use of antihypertensive medication.
Diabetes was defined as a positive history of diabetes and or use of insulin or
hypoglycaemic medication.
Statistical Analysis: Descriptive analyses were stratified by Aboriginal Status. Subjects
were grouped as Non‐Aboriginals, Status/Non‐Status, or Métis. Comparisons between
the three groups were evaluated using univariate analysis of variance (ANOVA) for
continuous variables and Chi square tests for categorical variables; all tests of statistical
significance were two‐sided. Logistic Regression was then used to evaluate the
relationship between: 1) Birth weight and Diabetes (Yes vs. No) and 2) Birth weight and
Blood Pressure (Hypertensive vs. Normal). Birth weight was collapsed into: low (<2500
grams), reference group (2500‐4499 grams), and high (4500 grams). In multivariate
Logistic regression models, the following potential confounding variables were
included: age, sex, Aboriginal status, Metabolic Syndrome (Yes vs. No), blood pressure
(in the diabetes model) (hypertensive vs. normal), waist circumference (high vs.
normal), and diabetes status (in the blood pressure model) (Yes vs. No). Interaction
terms between birth weight and each variable in the model were also examined. None of
these interaction terms were statistically significant (at the p <0.10 level), however, so
no interaction terms were included in the final model. All statistics were performed
using Predictive Analytics Software (PASWStatistics; v18.0, Chicago, IL).
Individuals who are identified as Indian (First Nations), Métis and Inuit are recognized in
the Canadian Constitution. North American Indian is the term used for those persons who
self‐identity as such, and generally refers to persons who consider themselves as part of
the First Nations in Canada, whether or not they have legal Indian Status (“Registered
Indians”) according to the Indian Act of Canada. Inuit is the term for Aboriginal people
who originally lived north of the tree line in Canada and who self‐identify as such.
Status Indians ‐ Status Indians are people who are entitled to have their names included
on the Indian Register, an official list maintained by the federal government. Certain
criteria determine who can be registered as a Status Indian. Only Status Indians are
recognized as Indians under the Indian Act and are entitled to certain rights and benefits
under the law.
Non­Status Indians ‐ Non‐Status Indians are people who consider themselves Indians or
members of a First Nation but whom the Government of Canada does not recognize as
Indians under the Indian Act, either because they are unable to prove their Indian status
or have lost their status rights. Non‐Status Indians are not entitled to the same rights and
benefits available to Status Indians.
Métis ‐ The word Métis is French for "mixed blood." The Constitution Act of 1982
recognizes Métis as one of the three Aboriginal Peoples. Today, the term is used broadly to
describe people with mixed First Nations and European ancestry who identify themselves
as Métis.
Non­Aboriginal subjects in this cohort were Caucasian, largely from Mennonite
communities.
Low (LBW) and high (HBW) birth weight are emerging as consistent risk factors for adult
cardiovascular and renal disease. Since the 1980’s, when the inverse correlation between
LBW and hypertension was reported, numerous studies in humans and animal models
have supported this observation. It is important to note that in LBW children, blood
pressures tend to be higher than those of normal birth weight (NBW) children, but are
not in the hypertensive range, although with time, blood pressures increase and LBW
individuals become overtly hypertensive with age. A recent systematic review found a
significantly increased risk of chronic kidney disease with LBW in various populations
(White et al., 2009). Among Pima Indians and subjects from the Southern United States, a
U‐ shaped association, i.e. both LBW and HBW were associated with increased albumin
excretion and end‐stage renal disease, especially among diabetic subjects (Nelson et al,
1998, Lackland et al, 2000). A similar association has been found between birth weight
and type 2 diabetes in a systematic review incorporating 31 studies(Whincup et al.,
2008). The relationship between birth weight, hypertension, diabetes and renal disease
has not been well studied among Canadian populations thus far, although high birth
weights are associated with increased prevalence of Type 2 diabetes in Native North
Americans (Dyck et al., 2001). We investigated the relationship between birth weight and
risk factors for renal disease among a cohort of rural Canadians of varied ethnicity.
Results
In univariate analysis, stratified by ethnicity, Diabetes was significantly associated with
birth weight among Aboriginal subjects (12.2% of LBW, 5.3 % of NBW, 7.9% of HBW, p =
0.035). Hypertension was associated with birth weight among Non‐Aboriginal subjects
(37% of LBW, 20.8% of NBW, 29% of HBW, p = 0.028). Proteinuria data was missing in
80% of the cohort. In those where it was measured, proteinuria the prevalence was 32.6%
of LBW, 19.9% of NBW and 7% of HBW subjects.
LBW and HBW are both associated with hypertension in this rural Canadian cohort
comprised of subjects of various ethnicities
LBW, but not HBW, is significantly associated with later life Diabetes in the cohort as a
whole, including the Aboriginal subgroup. The latter finding is in contrast to prior
published data (Dyck et al., 2001) and may reflect the fact that the status/non‐status
group contains an over‐representation of individuals from remote communities.
As expected, diabetes, hypertension and metabolic syndrome are all associated with
each other and therefore may confound the relationship with birth weight, however each
may be independently programmed during fetal development and may compound each
other’s impact on subsequent cardiovascular risk.
These data are in general agreement with reports from other populations around the
world supporting the role of developmental programming in adult disease
Table 1. Descriptive Analyses by Aboriginal Status
*Denominators different for these two variables (i.e. missing data)
Table 2. Logistic regression with Diabetes as dependent variable
Table 3. Logistic regression with Blood Pressure as dependent variable
Methods
Subject ethnicity
Results
Results
Conclusions