Interpretation
Contrary to our hypothesis, we found no additional effect of having two
overweight or obese parents on infant birthweight outside what was seen
if one parent was overweight or obese. Evidence from our rodent model of
obesity also suggests that the effect on infant birthweight may unlikely
be additive, but an accumulation of both the negative maternal and
paternal phenotypes 20. This seems to be evident in
our human cohort where infant birthweight increased from 3.13kg
95%CI=[3.03, 3.23] to 3.44kg 95%CI=[3.31, 3.56] in normal
weight mothers compared with obese mothers when fathers were of a normal
weight. When fathers were obese, this increase was much smaller (3.33kg
95%CI=[3.20, 3.45] to 3.41kg [3.32, 3.51]). This is likely
because infants born to fathers who are obese already start out heavier
(~200 g) and therefore, only require a small additional
increase in size to match the effect of obese mothers. Whilst we saw no
additive effect of combined parental BMI on infant birthweight, the
effects maybe may be present as the infants grow. For instance, in
another rodent model, insulin resistance and liver steatosis were
greatest in offspring when both parents were fed a high fat diet prior
to and during gestation, compared to just one parent21. In humans, Rath et al.,22, found that parental obesity was the strongest
predictor of offspring adult BMI. These data suggest that the combined
effect of having two obese parents on infant programming may manifest
later in life.
There is a large body of literature demonstrating the impact of maternal
BMI on infant birthweight including LGA 23, and there
is some suggestion for paternal BMI also having an impact on infant
birthweight 9. Unfortunately, much of the literature
on paternal BMI included self-reported paternal height and weight from
the mother, or, collection during pregnancy, at birth, or when the child
was a toddler, rather than preconception 24, 25.
Furthermore, studies that have assessed preconception paternal BMI have
not always adequately controlled for maternal and other parental
cofactors, and therefore, the results are currently conflicting. For
example Chen et al., 26 found that paternal
overweight and obesity only influence male infant birthweight, with a 1
unit increase in paternal BMI associated with a 19.5 g increase in
infant birthweight, while Noor et al .,27 found
that fathers with a BMI greater than 25kg/m2 increased
infant birthweight in both sexes (z score, 0.38 [0.91] vs 0.11
[0.96]. In contrast, three other studies found no effect of paternal
BMI on infant birthweight 28-30. Interestingly, when
assessing the extreme ends of infant birthweight (SGA or LGA), McCownet al., 31 found that obese men were 1.5 times
more likely to father SGA infants, while Yang et al.,32 found that overweight and obese men were 1.3 times
and 1.9 times respectively more likely, to father an LGA infant.
Similarly, in an ART cohort following frozen embryo transfer Ma et
al., 19 found that men who were overweight or obese
had an increased odds of having a LGA infant (OR=1.43; 95%CI=[1.27,
1.63] and OR=1.36; 95%CI=[1.04, 1.79] respectively). In our
study, we found no evidence for an association between paternal
overweight and obesity and SGA or LGA infants
(<10th and
>90th percentiles), although the median
birthweight of infants were higher with increased paternal BMI (7.3 g
for every 1 unit increase in paternal BMI). The lack of consensus in the
reported effects of paternal overweight and obesity on infant
birthweight highlights the necessity for further adequately controlled
cohort studies. Nevertheless, animal models of male obesity support
findings for increased infant birthweight 33-35.
The mechanism for transmission of altered infant birthweight from
increasing paternal BMI is likely due to a combination of genetic and
epigenetic factors delivered by sperm to the egg at fertilisation36, 37. A number of genes are known to play a part in
the heritability of weight 38, 39, however these
genetic loci do not fully account for the transmission. A number of
studies in animal models and humans directly show a link between
paternal obesity at conception, sperm epigenetic changes (non-coding
RNAs and DNA and histone methylation) and altered fetal phenotypes27, 40-44, indicating that the paternal effect goes
beyond that of a shared living environment, with preconception factors
able to influence the health of subsequent offspring.
Our data shows that infants born from mothers or fathers of increasing
BMI start their growth trajectory heavier than those infants born to
normal weight mothers or fathers. This is of concern as birthweight has
been reported to play an important role in the establishment of
adolescent and early adulthood BMI 22, 45. For
instance, evidence from the Early Childhood Longitudinal Study in the
USA, found that LGA infants made up 1/3 (36%) of all children who were
obese by age 14 years 45 and data from the RAINE
cohort in Western Australia, Australia, found that both maternal and
paternal preconception BMI were strong predictors of childhood,
adolescent and adulthood obesity 22. If obesity
aggregates within families, then a focus on preconception planning for
family units is recommended. In Australia, there are no primary male
preconception health-care initiatives 46. While
Healthy Male (Andrology Australia) does provide education on the
reproductive health of men, focusing on fertility, sexuality and
fathering, and the Australian men’s health policy addresses various
issues related to sexual problems, neither of these primarily focus on
preconception health 46. Further, missing data for
paternal preconception BMI in our study was nearly double that of
missing maternal BMI (33% vs 18%). While some of this may be due to
the lack of males in preconception care appointments, it highlights the
dogma that mother’s preconception health is a key focus rather than
fathers. Therefore, it is recommended that preconception health messages
focus on ‘healthy couples’, emphasising the need to improve lifestyle
for the family unit prior to pregnancy.