INTRODUCTION
Increasing evidence demonstrates an association between offspring size
at birth and maternal cardiovascular disease (CVD) risk. A meta-analysis
of six studies, published in 2007, showed an inverse relationship
between offspring weight at birth and maternal CVD mortality (pooled
adjusted hazard ratio (aHR) of 0.75 (95% confidence interval (CI): 0.67
to 0.84) for 1-standard deviation (SD) increase in offspring
birthweight)1. A subsequent study of 1,400,383 women
showed 1.8 times higher risk of mortality from CVD among women who gave
birth to low birth weight (LBW, birthweight <2500g) infants
compared to those who gave birth to normal birthweight (2500-3999g)
infants (aHR: 1.85; 95% CI 1.57 to 2.18)2. Recent
studies have shown similar associations for women who give birth to
infants diagnosed as small for gestational age (SGA) at birth compared
to women who give birth to average for gestational age (AGA)
infants3, 4. The terms “LBW” and “SGA” are both
used to define infants considered small at birth. Although many infants
classified as SGA or LBW have intrauterine growth restriction (IUGR) and
many growth restricted infants are born with LBW or are classified as
SGA, the three terms are not synonymous5. LBW simply
means birthweight < 2.5 kg and at present, the definition is
mostly used in developing countries where gestational age is often
uncertain, and reliable population centiles let alone customized
centiles are not available. SGA means birthweight <
10th centile for a given gestational age. Population
centiles use birthweight centiles on a whole population, irrespective of
maternal ethnicity, height and weight and customized centiles provide
birthweight centiles customized for maternal ethnicity, height, weight
and parity. Infants with IUGR are those that do not achieve fullin utero growth potential because of genetic or environmental
factors and are at increased risk for significant morbidity and
mortality compared to infants with normal in utero growth.
Infants born growth restricted are at increased risk of CVD and type 2
diabetes mellitus in adulthood and “programming in response to an
adverse intrauterine environment” as well as genetic and environmental
influences are proposed to contribute to the risk. However, associations
between offspring SGA/LBW and maternal CVD risk cannot be explained to a
large extent by programming. This, however, can be explained by the
presence of genetic polymorphisms that influence both fetal growth and
CVD as well as by adverse environmental influences that operate across
the parental life course and affect both offspring and adult health. To
our knowledge there is no systematic review and meta-analysis that has
assessed maternal risk for CVD using data from studies reporting on the
three common classifications of offspring size at birth. Therefore, the
aim of this study was to identify the relationship between offspring
size at birth and maternal CVD risk based on different classifications
of offspring size at birth.