2015 Public Health Grand Rounds 12/04

PUBLIC HEALTH GRAND ROUNDS Linking Research to Community Health Improvement

- [Emcee] women in the Department of Public Health Sciences.
Her goal is to improve the health
of individuals particularly as it relates to obesity.
Her research is focused on behavioral, genetic,
and environmental factors that contribute to obesity.
The majority of her work has been in women
during the child-bearing years.
She has had funding through the CSI and the NIH
for career development
and other agencies, such as the March of Dimes
and the Association of Women's Health, Obstetrics,
and Neonatal Nurses.
She worked with Dr. Diana Fernandez
as a co-investigator
on the NIH-funded (mumbles) study
which was an innovation to provide insights
into gestational weight gain.
Dr. Groth heads the behavioral lab in the school of nursing
that specializes in the analysis of dried blood spots
(mumbles) markers in research.
Dr. Groth has focused her research
on the components of physical activity, diet,
and other health behaviors,
along with the biological data
to inform the complexities of obesity.
Please join us to welcome Dr. Groth.
- Thank you, and welcome to Public Health Grand Rounds.
As you can see,
my topic is the complexities of gestational weight gain,
and the downstream effects.
And I wanna start
with just reminding us of the obesity epidemic,
and the background for discussing gestational weight gain,
in my mind, is to be thinking about this.
So I wanted to remind everybody
of the obesity challenges that we have in the United States
and globally.
Almost 35% of all adults are obese.
69% are overweight or obese,
and then when we look at the children, 17% are obese,
and 32% are overweight or obese.
And when we look at those percentages,
we do have to remember that those results
are generally higher for the ethnic minorities,
for those who are low-income or less educated,
and also the rural population.
I also want to mention, that from a cost perspective,
findings from a recent study presented at Obesity Week
indicated that the obese patients
incur a 46% increase in inpatient costs,
27% more doctors visits and outpatient visits,
and 80% more prescription costs.
Ultimately, obesity costs the American health care system
over 200 billion dollars annually,
and per-person health care spending is 56% higher
for patients with obesity compared to normal-weight adults.
So then when we think of obesity,
we know that overweight and obesity is not an easy fix.
There are a multitude of genetic, biochemical,
and environmental factors that do affect obesity.
And a lot of these factors are the same ones
that cause diseases such as depression and heart disease.
This graph is from a recent publication with NHANES data
and as you can see,
it depicts the age-adjusted prevalence of obesity
by sex and by age group.
And here we can see that nearly 32% of women ages 20-39,
which is our bulk of child-bearing age,
are obese in this data.
For this presentation,
I'm really gonna focus on excessive gestational weight gain.
Although there are some definite downstream effects
of low gestational weight gain as well.
Briefly, for people who under-gain
there's an increase of infant mortality,
increased risk of pre-term birth,
small-for-gestational-age infants,
intrauterine growth retardation.
And those things are more in the short term.
And then in the long term, for people with an under-gain,
there's poor immune development,
cognitive impairments, chronic disease,
and metabolic risk and obesity later on.
So then, the Institute of Medicine guidelines,
I just wanna mention
what are the appropriate gestational weight gain parameters.
The Institution of Medicine revised recommendations in 2009,
and these are the guidelines that we currently practice by,
and they are based on pre-pregnancy BMI,
with the goal of achieving the best outcomes
for both the mother and the infant.
And what these recommendations indicate
is that women who are normal weight
should gain more than women who are obese.
So, for instance, normal-weight women
should gain 25-35 pounds,
and obese women should gain somewhere between 11 and 20.
So the less you weigh the more you are allowed to gain
while you're pregnant.
Here's one more graph that I wanted to show you
because we do know that gestational weight gain
definitely contributes to obesity
and long-term disease risk in women.
This graph points out how this has escalated for women,
and some of that is due to
excessive gestational weight gain.
It also points out the gap based on race and ethnicity.
Here again, if you look here, nearly 59%
of our non-Hispanic black women,
are obese compared to our white women
or our Mexican-American women.
So we see that that is a population
where obesity is a bigger challenge.
So I consider this a high-risk population,
it's a population that I worked with
when I was in practice,
and I became very invested in them in terms of my research,
because they are high-risk,
and these are the women who I used to see for care
who are now suffering the results
of having gained excessively with their pregnancy.
82% of African-American women are overweight or obese.
33% of low-income African-American women
are obese prior to pregnancy.
And then, of all women, over 52% over-gain during pregnancy.
So why do we care about excessive gestational weight gain?
I've already mentioned that it ties into
post-partum weight retention,
and it also then affects long-term body weight increase,
and this effect has actually been seen out to 15-21 years
post-delivery for women in studies that have looked at this.
And also in adolescent women.
So whether someone was an adult or an adolescent
when they were pregnant,
we do see the effects out that much later.
In addition, excessive gestational weight gain
contributes to gestational diabetes,
pregnancy-induced hypertension,
c-sections, and childhood obesity.
For example, in childhood obesity,
there's a study that reported
the odds of the child's BMI
being greater than or equal to the 95th percentile,
which is obesity,
increased by 3% for every kilogram
of maternal pregnancy weight gain.
So the gestational weight gain,
every kilogram increased the child's risk of obesity by 3%.
In addition to weight consequences for the child,
we do see other effects.
We see cardiometabolic risk later in life.
We see an increased risk for asthma,
and we see a potential risk for autism.
When you think about gestational weight gain and its effects
it's really hard to sort out
what affects gestational weight gain,
and also the impact of the gestational weight gain
down the road.
Especially those long-term effects,
because we all know there's a lot of other things
that affect weight and obesity
besides a mother's weight gain
way back when she was pregnant.
There's a lot of things that happen along the way
that could be influencing it as well.
And the impact can differ,
depending on a constellation of genetics, behaviors,
and environment that happen at the time of the pregnancy.
So it isn't anywhere near as simple
as we might like it to be
or we would like to say,
"It's just diet and exercise,"
but it's nowhere near that simple.
On this slide, at the top,
are some of the factors that I have looked at
or other people have looked at
in terms of gestational weight gain
and things that we have considered important.
And then the results of gestational weight gain
are at the bottom part of the screen.
Especially if the gestational weight gain is excessive.
I realize this isn't an exhaustive list,
and that there's overlap among some of these,
but that just points out the complexity
of looking at gestational weight gain
and its consequences as well and what is causing it.
Especially when we think in terms of intervention.
What things do you key in on?
Because so many different things could affect
the gestational weight gain.
The Institute of Medicine report in 2009
gave a list of what they were suggesting
were some of the causative factors,
and among those are things like cultural norms,
behavioral factors, calories, dietary intake,
environment, food accessibility,
food and security, psychological factors,
and developmental programming.
So that was the list, that's also not exhaustive,
that comes out of the Institute of Medicine's report.
And again, as I said, if gestational weight gain
is appropriate, that amount is believed
to give you the best outcome for both infants and mothers.
And then when it's excessive,
there are short and long-term detrimental effects.
First I wanna focus on some of the factors
that contribute to gestational weight gain,
and influence gestational weight gain.
The first one I'd like to talk about just for a minute
is diet.
Eating for two is not necessarily
the best way for us to think about how a mother
should approach her diet in pregnancy.
She really only needs about 300 calories more per day,
but only in the second and third trimester,
which really isn't all that much.
This is about 300 calories.
And, since I don't have a dietitian here
to tell me otherwise,
no one's gonna argue with me on that.
But that's about how much more she needs per day,
but I would say in reality,
most women don't necessarily think it's that small amount.
And our tendency is to eat more than maybe we should.
Dietary intake has been associated with
excessive gestational weight gain
in a lot of different ways.
In particular, one of the ways is fast food intake.
An increase of fast food intake,
of fast food, which is nutrient-poor, calorie-dense,
increases the risk
of excessive gestational weight gain in women.
Another thing that's very interesting
is the cravings that women have.
Cravings seem to influence women and what they eat.
We conducted focus groups
and in-depth interviews with African-American women,
and it was very interesting to me
actually how much they indicated
that cravings influenced how they ate.
So these are the themes that came from that study.
We did three focus groups, a total of 26 women.
And the three main themes that we derived from it
were these that are on the slide.
So despite best intentions,
appetite, tastes, and cravings drive eating behavior.
It wasn't based on "what I think is healthy,
"what I intend to eat."
It was really these other things.
Secondly, "I'll decide for myself what to eat."
Didn't matter, really, what the care providers told them.
Didn't matter what their partner told them,
what their mother told them.
We tend to think sometimes, in this population,
that the mothers have a major role.
In this particular group of women, it did not.
They said, "I'm gonna eat what I wanna eat."
And then the third theme was
that eating out is a way of life.
And eating out, with these women, in general,
they did eat other places, but in general
tended to be your fast food restaurants.
McDonald's, Burger King, Wendy's, Taco Bell,
over and over those are the names that we heard.
So then we went a step further beyond the focus groups,
and held semi-structured interviews
with a different set of 25 low-income, pregnant,
African-American women
to try and get more at
what was really driving their behavior around these things.
And the findings were consistent with the focus groups,
and the interviews did give us more detail
in terms of how the women were thinking, or were acting.
So I just wanna give you a flavor of that,
so here's a couple of quotes from the women
from the interviews,
and this first woman says,
"My cravings, that's why I think.
"That's why I don't eat as much as I would any other time,
"Cuz if it's not what I'm craving,
"Then I don't wanna eat it."
So the craving is what drove what she chose to eat,
and she didn't eat anything other than that.
The second woman,
we referred to her quite a bit, actually,
when we were analyzing the data,
"Because I've been pregnant,
"I just really love the taco shells and sauce.
"I love tacos.
"I always liked tacos, but not to eat them every day.
"Now I could eat like 15 tacos in one day."
And she kinda told us that that's what she did.
So that's just a little bit of what the women were saying.
And then here's a final one, because I think this one
she nicely summarized the challenges
that some of these women were facing
when they thought about what they ate.
She said, "I'm not just fending for myself anymore.
"I've got a baby inside of me.
"I got to make sure she stays healthy,
"because I don't eat fast food,
"but I want to eat fast food all day.
"Fast food is awesome.
"Even though you're not supposed to eat it,
"it's awesome."
So the cravings, obviously, and what tasted good,
did interfere with women choosing to eat in a healthier way.
In these interviews, we also attempted
to identify what these women perceived
as barriers to eating healthy while pregnant.
And surprisingly,
or not surprisingly,
they reported the barriers included the cravings,
which we just talked about,
time and finances,
which are things we would expect to be.
Busy schedules, crazy lifestyles,
limited funds would be a factor.
The part that surprised us a bit
was that they didn't seem to really know
what a healthy diet was.
We kind of pushed them a little bit
to tell us what would be a healthy diet,
and they would say things like,
"Well I should avoid greasy foods."
Or, "I should avoid fried foods or sugar.
"I need to eat more protein."
Or maybe, "Don't use seasoning or salt."
Think what you food would taste like
if you don't use any seasoning or any salt.
They thought they shouldn't do that.
And, "I should drink more water."
When you think about those statements,
a lot of them were negatives, not positives.
It wasn't "I should do this."
It was like, "I shouldn't do this."
Which kind of, I'm not sure what that reflects,
but it was kind of an interesting way
that I didn't even think about
until I was putting this together for you.
They generally new to eat fresh fruits and vegetables,
but a lot of them said, "I don't really do it,
"even though I know it's what I'm supposed to do."
Let's move on from diet to physical activity.
That's another factor that can influence
gestational weight gain.
Just like it has an effect on weight outside of pregnancy.
When we did the focus groups
we were also looking to understand about physical activity
during pregnancy.
However, those women made it pretty clear,
right up front, that they were not all that interested
in physical activity,
and they were not really interested in talking about it.
Yet, there are benefits to physical activity
and being physically active during pregnancy.
It can reduce excessive gestational weight gain,
and it also can decrease complications
like gestational diabetes and pre-eclampsia.
It also can improve mood and mental health.
In reality, only about 15% of pregnant women
actually meet the recommendations of 150 minutes per week
of moderate-intensity physical activity
compared to around 26% of non-pregnant women.
Now, 26% for the non-pregnant women
is not a good number either,
but the pregnant women is even less.
Furthermore, pregnant women tend to decrease their activity
as their pregnancy progresses.
The women in our focus groups
indicated that they were not motivated to exercise.
Some were concerned that it was risky to do so.
So there their held beliefs were
beginning to come into the picture.
It wasn't just that they didn't wanna do it.
They just, they thought it was risky to do.
And then some indicated they were active enough at work
that they didn't need any more activity.
Studies have shown that beliefs
about safety of activity in pregnancy
predicts the amount,
beliefs about safety in pregnancy
predict the amount and duration of exercise.
Women who believe that being active during pregnancy is good
and will lead to a better labor and delivery experience
are motivated to be active.
Conversely, some women believe that relaxation and rest
are more important than being active,
and others consider eating healthy
as more crucial than activity.
And then there are barriers.
You think about activity,
and when we think about this low-income,
high-risk population, you think in terms of
unsafe neighborhoods, lack of time,
feeling tired or fatigued,
which crosses any type of socio-economic group,
as does the time issue.
But women in our focus groups
resonated with those thoughts.
Inheritance is another factor that we can't ignore
when we look at gestational weight gain
and when we look at obesity.
We collected saliva samples for DNA from 97 women.
Low-income, pregnant, African-American women together,
it was the same group of women,
to look at several things, including diet,
physical activity, gene snips that are related to obesity
and gestational weight gain.
These women were all low-income,
and we followed them from before 20 weeks
until six months post-delivery.
To be in the study
they had to be less than 20 weeks gestation,
they had to have a singleton pregnancy,
and their BMI had to be at least normal weight,
we didn't want them underweight,
up to 40 kilograms per meter squared, so,
obese Class 2.
The FTO gene is one of the ones that we looked at,
and that is one of the most commonly studied
obesity genes out there.
It has been associated with obesity in numerous studies.
It also is know to affect insulin resistance
associated with Type 2 diabetes,
it increases the risk for gestational diabetes,
and interacts with physical activity.
In addition, in pregnancy it's been associated
with gestational weight gain
in thin and obese Caucasian women
who are homozygous for the high-risk allele,
so they have two copies of the high-risk allele,
and in pregnant women from the United Kingdom,
it's been associated with pre-pregnancy weight and BMI.
In this case, we were looking at African-American women.
Here's what we had.
The a-allele is the risk allele.
We had 27% women who had two copies of the risk allele.
We had 31 women with one copy,
and 16 with no copies.
And one of the things we're looking
was to see if pre-pregnancy BMI would be different
depending on the gene, and as you can look at these numbers,
there's really not much difference in those numbers at all.
We're also looking at the gestational weight gain,
and here we had 36.3,
31, and 27.
So you can see there's a difference here
between this group and this group.
Which are your two homozygous groups.
And this result was a P was .051.
So if technically I were to say,
we had a trend.
It was technically not significant,
but we did have a trend there.
Infant birth weight wasn't different,
and their weight later on wasn't different.
So because we had that trend,
and in addition,
we know that in other reports
that this gene has been associated with pre-pregnancy BMI,
we decided that it would be important
to test for an interaction between the pre-pregnancy BMI
because previous reports suggest the relationship,
and also cuz the r-mean weight gains differed
depending on the BMI category.
Our normal-weight and overweight women
gained about 35 pounds,
and the obese gained 27 pounds.
So we did find an interaction between the gene
and the pre-pregnant BMI,
and discovered by sub-group analysis,
that it was the obese women who were different.
And as you can see on the screen,
the obese,
high-risk, because they had two risk alleles,
had a significantly higher gestational weight gain
than the women without the risk alleles.
And the difference was 41.5 pounds
compared to 19 pounds.
This suggests that
for the obese women homozygous for the risk-allele,
there was a greater risk
of excessive gestational weight gain
than in other women.
This is a small sample, though, for a gene study.
But it does give an example,
and this is why I put it up there,
as an example of how genetic make-up
might make a difference in what happens
with gestational weight gain.
Heritable factors certainly go beyond gene snips
and I'll talk about that more in a minute.
But first, I did wanna mention the pre-pregnancy BMI
cuz as I've said, what is recommended
is that the more you weigh, the less you should gain.
And there's a couple of intriguing questions
that come to my mind when I think about that,
when you think about pre-pregnancy BMI
and you think about the fact
that we have women who are obese,
and we tell 'em, "You can only gain 20 pounds,"
we say, "Okay, you need to restrict your eating," basically.
Now, women who are obese to begin with,
part of the reason why they're obese
has to do with their lifestyle,
most likely their dietary and behavioral factors,
so now when she's pregnant, dealing with cravings,
struggling with nausea
and all those different things we have in pregnancy,
we're saying, "You need to limit what you eat."
And does that even make sense?
When we think of our behavioral interventions,
what is our chance of being successful?
Another question that comes to my mind
that I find intriguing,
although I don't know an explanation for it,
is that there seems to be a natural weight
that women tend to gain.
And whether that's physiologically-based or otherwise,
I don't know, or behavioral-based,
or based, really, because women follow our recommendations.
I've looked at gestational weight gain data,
and data collected from pregnant women,
for instance, from Memphis,
some women I will be talking about more in a minute,
there average weight gain was 30 pounds.
It didn't matter what their pre-pregnancy BMI was,
it was 30 pounds.
And those were adolescents and those were adults.
In the eMoms data of 1789 women in Rochester,
the normal and overweight women gained about 30 pounds.
The obese women gained less,
they gained an average of 23,
so they were closer to that recommendation
of no more than 20.
And then, data from the
Pregnancy Risk Assessment Monitoring System,
which is CDC and state health department data,
supports this idea as well.
A recent presentation on data from 14 different states
that was collected from 2000-2009,
indicated that the average gestational weight gain
was 31 pounds in that large sample.
Alright, so now I want to shift gears
and look at the other side of the gestational weight gain.
I think about the outcomes of the pregnancies,
especially when there is excessive gestational weight gain,
so I have added a word in here for now just to say
specifically I am focusing on that piece.
There are short-term effects that are detrimental
in terms of pregnancy complications and birth outcomes,
and there are longer-term effects,
factors that go for years beyond that delivery.
And so, first let's talk about
the negative health outcomes for the mother.
In the short-term, there's the things I've mentioned:
increased risk for gestational diabetes,
hypertension, pre-eclampsia,
failure to initiate breastfeeding is another one.
In the long term, some of what we know
is that there's the risk of obesity,
post-partum weight retention,
and there's a risk of hypertension.
So what we did, is we looked at a sub-group
of 290 black women from the new mother's study,
which is a randomized, controlled trial
that was conducted in Memphis, Tennessee.
Harriet is sitting here,
she was part of the initiation of that study,
and has been involved with it for all these years.
And it is testing the effectiveness
of a nurse home visitation
on improving the health and well-being
of women and their children.
Data collection started in 1990,
and has continued until 18 years post-delivery
of that first child.
The sub-group we used for these analysis
were all low-income black women who were adolescents.
So they were less than or equal to 19 years old
when they enrolled in the randomized controlled trial.
To be included in the original study,
they had to have no previous live births,
no known chronic illness that could affect pregnancy,
and two of the three risk factors,
which are unmarried, less than 12 years of education,
or unemployed.
For this analysis,
we did combine the treatment in the control groups
after determining that there were no significant differences
between pre-pregnancy BMI, current BMI,
or gestational weight gain.
Women who reported a current pregnancy
or a pregnancy within the six months
of that 18-year measurement
were excluded from the analysis.
The sample at this point, then, at 18 years the women,
59% were obese, and 85% were overweight or obese.
As I've already mentioned,
their average gestational weight gain
was around 30 pounds.
And they ranged in age from 12 to 19 years
with a mean age of 16.3 at the time of conception.
At 18 years, 43% of the variance of BMI
was explained by our regression model.
The variables we included in the model were:
gestational weight gain, pre-pregnancy BMI,
parity, smoking, and age of conception.
Pre-pregnancy BMI, gestational weight gain, and smoking
were all significant predictors of the later BMI.
Pre-pregnancy BMI and gestational weight gain
had a positive effect, and smoking had a negative effect.
So if they smoked, then at 18 years
the BMI was actually lower.
We also put the gestational weight gain into categories
to assess, based on the Institute of Medicine recommendation
and the ones who over-gained weighed more later.
What we had is that, when you think about it,
for every pound gained during pregnancy,
there was a .148 BMI increase 18 years later.
If you do the math,
a 30-pound gestational weight gain,
which is what that average was,
translates to a 4.4 BMI increase,
which is around 25 pounds
if you consider an average-height woman.
So it definitely had an effect that was substantial.
So 31% of these normal-weight women over-gained,
and 59% of the overweight obese women over-gained.
And interestingly, our weight retention was higher
than that reported in adult women.
But remember, this was an adolescent population.
We also went on looking at women out of the same study.
We looked at the association
between gestational weight gain and health outcomes,
or health conditions at 18 years.
We're saying, "Okay, we have obesity, we have more obesity.
"That's an effect.
"Did we have other health problems
"that occurred as a result?"
For this sample we used 467 women,
including all of the black women
that were enrolled in this study, irrespective of age.
So now it's no longer just the adolescents,
we've added the adults to the sample.
Hypertension, diabetes, obesity, and self-reported health
were assessed with a combination
of self-reported measurements of blood pressure,
height, and weight at around 18 years post-childbirth.
The mean age of these women was 36 years old
at the time of this 18-year measurement.
And at this point, 59% had hypertension,
almost 10% had diabetes, 25% reported poor health,
and 60% were obese.
Higher pre-pregnancy BMI was associated
with increased probability of each health condition.
The hypertension, the diabetes, the poor health,
all of those.
I'm just showing you a slide for the hypertension
just so you can see an idea.
Now this is pre-pregnancy BMI, not gestational weight gain.
But if you look at this, you can see that
51% of our normal-weight women
developed hypertension by 18 years later,
where 89% of the obese women did.
And we had similar trends for the diabetes
where we had just under 6% developed diabetes
of our normal-weight women,
and 23% developed diabetes.
And these were all significant relationships.
Poor health, 25% in the normal
compared to 40% in the obese.
And then 57% of the normal-weight women became obese,
and 93% of the obese were obese.
So basically most of them stayed obese.
In terms of gestational weight gain,
gestational weight gain was directly associated
with obesity.
The odds ratio was 1.04.
But none of the other health outcomes.
So it was not associated with diabetes or poor health.
And actually, in the main model
it wasn't associated with hypertension.
However, once we put an interaction in
between the gestational weight gain and pre-pregnancy BMI,
in the model, an average marginal effect
of gestational weight gain on hypertension was significant
for certain pre-pregnancy BMI ranges.
Higher gestational weight gain was significantly associated
with hypertension, if the mother's BMI was under 21.3.
Alright, how did I...
If we look at this portion here, there's your 20,
so if you look at this portion of the women,
these are the women who later on went on to develop,
had a higher risk of hypertension.
Not these women, who were obese.
That was an interesting finding to have.
And then the same thing for women who,
in terms of gestational weight gain,
pre-pregnancy BMI and obesity, we also see interaction here.
Women who over-gained during pregnancy
had an increased risk of obesity
compared to those who gained appropriately or under-gained.
And here the effect, again,
was on women at a different point though.
It's at 25, it's right in here
is where we see the difference.
So the women in here are the ones
that had the much greater risk for obesity later.
Compared to our other women.
Diabetes and poor health
were not associated with gestational weight gain.
And then when gestational weight gain
was used as a categorical variable,
pre-pregnancy BMI remained
a significant predictor of the health,
but gestational weight gain, only the obesity.
So our women with a BMI less than 25.9
were actually at greater risk of having obesity later
than our obese women.
Let's switch to the children now.
Long-term health outcomes for children.
From the literature,
we know that these outcomes for offspring include,
as I've already mentioned,
overweight, obesity, chronic disease such as asthma.
In 2015, Mannan completed a meta-analysis of 12 studies
looking at the risk of offspring obesity.
And all these studies included,
they had to include maternal gestational weight gain
as a measurement or as a self-report.
The relative risk of obesity for offspring
with excessive gestational weight gain
out of this compilation of 12 studies, was 1.4
compared to women who had an appropriate
or adequate weight gain.
The study varied in terms of the age of the children.
But three of them were specific to teens,
so 18-20 years old.
Other studies have keyed in on younger children
have reported that when mothers gained excessively,
there's an increased waist size, fat mass,
leptin, systolic blood pressure, C-reactive protein,
IL-6 levels, lower HDL,
and then several studies
have also reported the risk of childhood asthma.
So again, we went back to the Memphis women one more time.
And using the women from that study,
we looked at 328 mother-child pairs
in terms of their BMI percentiles.
Now, we stayed with the teens,
so we were using the mom's BMI percentiles this time
instead of just the straight BMI.
The mean maternal pre-pregnancy BMI percentile was 58,
so they were in a normal weight range,
and the child was 69.6.
We excluded women with pre-term births,
a pre-pregnancy BMI of over 45,
there was one of those,
and then if the mother was over 19 we did not include her.
We included in our analysis birth weight, gender, SES,
breastfeeding, smoking or using of alcohol during pregnancy,
parity, number of pregnancies, the intervention itself,
because this was a randomized controlled trial
so we put that piece in there,
and then interactions of the interaction
with gestational weight gain
and also gender, with the intervention.
The outcomes we looked at were child BMI,
hypertension or pre-hypertension, asthma,
and breathing problems.
What we found is that
the mother's pre-pregnancy BMI percentile
was consistently associated with the child's weight
whether we looked at it as a BMI percentile,
as overweight, or as obese, at 18 years.
The mother's gestational weight gain
was also associated with the child's weight,
BMI percentile, overweight and obese at 18 years,
but only at certain maternal ranges.
So again, we're having an interaction effect happening,
just like we did with the mothers
that we see with the children.
Here, if we look at overweight at 18,
we see that it is significant,
the impact of the BMI percentile in gestational weight gain,
if we're less than 78%.
So it's the women down here,
again, they're in a normal weight range,
is where we see the effect then on their child's overweight.
Here's another one looking at child obesity.
Same type of thing,
a little lower mom's BMI percentile needed to be
to have us see that impact.
And this one, just to get back
to the Institute of Medicine recommendations,
this was over-gaining as opposed to gaining appropriately.
And again we see an effect here.
But it doesn't go down to your low level of underweight
or your overweight obese women.
It was in the middle again.
So those are the kind of findings that we're finding.
Gestational weight gain is having an impact on the child,
not just the mother.
The mother, yes, but also on the child.
And there's other studies that are showing
that there are findings
where the mother's gestational weight gain
does affect the child outcomes.
Which then leads me to say,
"Okay, what's behind these findings?
"What is going on that we're seeing this?"
Why do we see such a long-term effect
of gestational weight gain,
and also the mom's pre-pregnancy BMI
having an effect on her child.
There's a lot of other factors,
as I mentioned earlier.
Lot of other factors could be feeding into
what a child's weight is by the time they're 18 years old.
But we are seeing that, and these things did have an effect,
an independent effect.
And there's also the interesting interaction
between pre-pregnant BMI and gestational weight gain.
Now, the same author
who did that 12 study meta-analysis, Mammon,
also had four plausible suggestions
as to what they were thinking could be behind some of this.
And one of them is,
these babies are bigger to begin with, so they stay bigger.
So what's the big deal?
But if you looked at it
and included our analysis,
we did include the infant birth weight in the analysis.
So we did control for that,
and most of the studies have done that.
The association could be
through a pre-disposition of maternal genetics.
Offspring may inherit their mother's genetic potential
to gain weight or not gain weight,
which might explain a link between gestational weight gain
and offspring BMI later in life.
But in my mind, it more likely would explain
mom's pre-pregnancy BMI with her child's BMI later
as opposed to her gestational weight gain.
Third, it could be programming.
Greater gestational weight gain
might program greater adiposity in the offspring
as a result of a greater delivery of glucose,
amino acids, and free fatty acids
to the developing fetus in utero.
This phenomenon,
called the "developmental overnutrition hypothesis,"
has both biological support
and some support from epidemiological studies.
And then fourthly, is lifestyle.
Women who gain excess weight during pregnancy
may just have an unhealthy lifestyle,
that includes eating a lot of calorie-dense foods
and not being active,
that promotes weight gain.
And this could continue after the child's born
and they actually pass it on behaviorally
down to their children.
In all likelihood, it's a combination of these three,
of these four things,
and so I wanna spend a few minutes kind of teasing that out,
looking a little bit more closely at these.
However, in a simple, basic level,
as food for thought more than anything else,
I'm not a basic scientist, so I just wanna clarify
that this is pulling from the literature
and just, where we could think about these things.
So let's look at it a little bit more closely.
It's pretty obvious from a phenotype,
or what-we-see perspective,
that obesity has a heritable piece.
At least a pre-disposition.
The risk of being obese is higher
in children whose parents are obese.
I gave an example of the genes, for instance,
with the FTO gene contributing to obesity,
but the contributions of single genes like that
are pretty much small and inconsequential.
Adding an environment of an abundance of calorie-dense foods
certainly contributes to obesity,
as does lack of activity and sedentary behavior.
But it's not that simple, as I said before.
We have to consider that genes, heritability,
lifestyle, and developmental plasticity,
or nature's capacity to generate phenotypes
depending on the environmental situation,
suggests that things are much more complex
in the contribution to obesity.
And we need to recognize that those experiences
do begin in utero, or even before.
Programming in utero
is something we should specifically think about
when we think about gestational weight gain effects.
Because in the offspring outcomes for sure,
and maybe the maternal as well,
there are studies that have shown
that under-nutrition in utero, and later, adequate nutrition
results in low birth weight initially, but then later on
the constellation of abdominal obesity, dyslipidemia,
hypertension, insulin resistance, metabolic disease
in adulthood happens.
More recently, people have began looking at
the outcomes when there is over-nutrition.
Which can be in two forms.
Over-nutrition can be a result of a mother being obese,
or it can also be a result
of the type of diet of overeating.
And we found that they're beginning to find
that the same thing happens,
that when the child is over-nutriented,
that's not a word,
has over-nutrients in pregnancy,
that later on, they develop metabolic disease in adulthood.
And this could be part
of what's behind gestational weight gain,
or relationships that I've just been showing you,
linking gestational weight gain and pre-pregnancy obesity
to child obesity and disease.
One of the mechanisms that has surfaced
as an important determinate of obesity,
is epigenetics because it links pregnancy,
nutrition, and outcomes consistently.
Researchers are looking more closely
at the causal mechanisms and processes
behind these associations.
So I just put a quick slide up
for those of you who are not familiar with epigenetics.
It is a variety of mechanisms that affect DNA expression,
or turning on and off of genes.
Methylation is one of those mechanisms,
and involves methyl groups attaching to DNA
and regulating gene activity without a changing sequence.
So when you look at this diagram, this is a methyl group.
When a lot of methyl groups are attached to the DNA
it's also tightly bound together and nothing,
and it doesn't get expressed.
Where when it's open like this
without all the methyl groups attached to it,
there's more gene expression
and so it affects what happens
in terms of proteins that are produced.
Epigenetics can be plastic, or changeable.
Or they can be stable and have the potential
of passing from one generation to the next.
Thus, some of what we see in terms of obesity
could be inter-generational, epigenetic effects
from prior generations
and be going on to the next generations.
There are two components that I already mentioned
by which over-nutrition can occur and influence obesity.
One is the dietary intake,
and the other is maternal obesity.
When we look at nutrition,
animal models have shown methylation changes
in relation to under and over-nutrition
and developmental programming.
For instance, in animal models,
if a mother rat is fed a high-fat diet,
there's an increase of obesity in her offspring.
And then an interesting question that comes up
is one that we've been struggling with a little bit,
is when we consider methylation,
there have to be methyl donors
to attach to that DNA that I just showed you the picture of.
Methyl donors, one source is your diet.
Folate, choline, and vitamin B12
are sources of methyl donors.
So what does that affect?
If a mother has a poor intake of methyl donors,
does that change the methylation patterns,
or is there enough manufactured in her body
or coming from other places, that it doesn't matter?
We don't know the answer to that.
But we are concerned about it,
because when we looked at the dietary intake
of 97 low-income women who were pregnant,
their dietary folate intake,
many of the micro-nutrients were under where they should be,
but their choline and their folate,
choline was 100% below, and folate was 66% below.
Now, this is diets,
so if they were using supplements, it may look different.
But in terms of what they were actually taking in by food.
And then, secondly, the obesity itself
creates an environment that is different
than in a non-obese woman.
And here's a model proposed by Herwegen
as a way to help us understand that,
and I'm not going into the detail of it,
the effect of maternal obesity on offspring.
They indicate that obesity and pregancy
are both associated with inflammation and insulin resistance
and that there's a exacerbated effect
when the two happen together.
So when you have obesity
and then you put pregnancy together.
The insulin resistance and inflammation
leads to an increase in maternal circulating lipids,
ultimately results in excess lipid transfer to the fetus,
and this exposure increases the risk for metabolic disease
in the child.
I have one other diagram that I wanna show you
just to give that idea of the inter-generational effect.
And this is one that was,
oh, I didn't put the name,
Plagemann was the author,
it's a manuscript from 2005.
This gets at the programming,
and has been proposed as what's contributing
to the obesity epidemic.
So when you look at this,
I don't know if you can read this all right,
it looked good on my screen, but.
If you look at this, if you have over-nutrition here,
whether it happened when they're still in utero
or afterwards,
it can cause hyperinsulinism in the fetus or infant,
and then you end up with permanent malprogramming
of the neuroendocrine-immune system,
especially around food intake, body weight,
and metabolism.
Therefore, you have a perinatally-acquired disposition
to obesity, diabetes, metabolic syndrome.
So then when you think about that daughter,
now goes on and becomes a mother, her phenotype,
she's overweight with impaired glucose tolerance,
she is pregnant, sets up the same cycle again,
goes on, and you have the next generation transmission,
and a multiplication of your obesity disposition.
So that's just kind of a very simplistic way
of saying how it could go from one generation to the next.
So, to summarize, there's a complexity
in gestational weight gain in terms of
the factors that influence it,
and its influence on both maternal and offspring outcomes.
Gestational weight gain affects obesity
and chronic disease in mothers and their offspring,
and likely future generations through programming.
Pre-pregnancy BMI also has a long-term effect,
and that has implications when we think of obesity epidemic
because there are more and more women
who are obese when they get pregnant,
and then they thus increase that cyclical effect
because they are providing over-nutrition to the child
just by default because they're obese.
So then I'm sitting here saying,
"Okay, well what do we do?"
This is really prevention.
Global obesity is more than diet and exercise.
Ideally, we would decrease the overweight and obesity
before a woman ever got pregnant,
but that's not gonna happen in a lot of cases.
From a care perspective,
my clinician part always has to come out,
from a care perspective,
we have to pay attention to and provide guidance
for healthy gestational weight gain.
We have to provide guidance for healthy dietary intake,
for physical activity,
and we need to develop effective ways
to support healthy gestational weight gain.
And then, from the research side,
more needs to be done
to determine how to limit excessive gestational weight gain,
given the detrimental effects it has.
But also, understanding of the mechanisms
associated with early-life events and environments
is needed to develop effective interventions
to combat obesity and associated diseases.
There's so much we don't know.
We see what we see, but there's so much that we don't know
that's behind the scenes.
For instance, is there a causal link
between epigenetic modifications and metabolic phenotypes
like obesity?
Can these changes be reversible?
Is there the possibility that we can develop
preventive or therapeutic approaches
to address the obesity epidemic at the multiple levels
including the trans-generational obesity?
That's just some of the questions
that we can begin to raise when we start to think about
the underlying mechanisms beyond the behavioral that we see.
That's all I had.
Are there any questions?
Thoughts, comments?
- [Woman In Audience] Sorry if I missed this
piece of information, but when is it determined
that the child is actually obese?
- [Dr. Groth] I didn't mention that?
Obese, overweight is equal to or greater than
the 85th percentile to just under the 95th percentile,
and then—
- [Woman In Audience] Then, at what age of the child
do we say, "You are an obese child," or
"You are not"?
- [Dr. Groth] Steve, you wanna answer that question?
- [Steve] We have growth curves
that use parameters that can start at two or three.
There are even measures you can look at in infants.
It's a slightly different weight-to-length measure
in an infant up to age two,
BMI at age three.
So there are cut-offs for that.
Then there's also different international cut-offs, too.
- [Woman In Audience] Okay,
do we have
do we have a way to measure, or do we measure
when you have an obese mother
who has an average-weight child
and then there's a turning point, perhaps?
Like, where, and I've been to Dr. Cook's presentation
about obesity, stigma and bias,
and that includes information on the children,
where parents say, "Oh, my kid is not obese,"
or, "My kid is regular weight or just slightly chubby,"
So I guess I'm wondering along the timeline of
childhood growth, where the obesity determination happens.
So you said maybe two or three,
but is that—
- That's what happens
from a clinical perspective, is what Steve is saying.
He would be the expert on that piece.
Other comments?
(person speaking off mic)
That their gestational weight gain
influenced their weight later, yes.
Moreso if they were normal weight.
(person speaking off mic)
Both ways.
We looked at it as a continuous,
so the more they gained, the greater the risk.
And then we also looked at it categorically
of whether it was an over-gain
or appropriate gain comparison.
(person speaking off-mic)
But if the risk up toward obesity
or a higher weight.
That's the difference, yeah.
I mean, it's interesting to think about what is behind that.
Is it because the normal-weight women
are expected to gain more,
so if they over-gain, they've gained over 35 pounds,
which is a larger portion of their body weight,
then if an obese woman over-gains at twenty-some pounds.
So, is that part of the explanation?
I don't know, that's one of the things that we posed
as could be part of it.
(person speaking off-mic)
But to me, from a clinical perspective,
then it's like, we need to be paying attention
to our normal-weight women, too,
not just our obese women.
We're worried about them, but you know what?
The normal-weight women, if they gain,
and maybe what we're telling them isn't exactly ideal
from a metabolic perspective for them.
Hi there.
- [Audience Member] So nice chat, thank you.
I know we talked a little bit about this before,
but the recommendations and guidelines
for the appropriate weight gain
during gestational period, the evidence is old, right?
And so, right now, we're seeing that on average,
they're gaining around 30 pounds regardless.
Do you think any of your work
can better inform guidelines?
Do yo see where, perhaps,
we can start getting better information and evidence
to try to inform better outcomes for moms and kids?
- That's ideally what my research would do.
I can say that the work that I did,
and some of the work Diana has done as well in the past,
did influence the Institute of Medicine
in terms of these current guidelines,
in terms of, they used to say adolescents
should gain at the upper end,
and black women should gain at the upper end.
They've taken that out of there now,
and part of that would be that we've found,
cuz we actually broke it apart
for BMI percentiles as opposed to BMI
and all these different things earlier on
with this Memphis sample at six and nine years,
and saw that, really, gaining at the upper end
did not gain the teens anything.
And so we were part of what contributed
to some of the changes that happened.
But I would hope that we can refine them more.
And one of our concerns that our research group has had,
is that those recommendations are great, maybe,
based on the evidence that exists in terms of weight,
but they do not deal with nutrient intake
or what causes the weight gain.
There's a lot that goes into what you eat,
in terms of what you gain,
that we are not really paying attention to,
that is kinda being ignored.
- [Person In Audience] Did the nurse visits
that were part of the longitudinal study
also include any sort of nutritional counselling?
- Harriet, did it specifically?
Did the intervention, the new mother study,
did it include nutrition education?
It did.
Which is why we always included the intervention group,
or made sure we looked in the analysis
to make sure that we were accounting for
something that'd happened there,
and compared the groups.
- [Harriet] That's one of the questions,
in that one may gain the same amount of weight,
but the nutrients that go into that weight gain
may be quite different.
And one cannot detect that
in terms of an impact on the intervention,
unless you do the full dietary recall between them.
- Okay.
Alright, well thank you for coming.
(people chatting off-mic)
- [Man In Audience] Thank you for that.
- You're welcome.
(people chatting off-mic)
Well, I think that's an interesting thing
we need to think about,
because we always think,
"Well, this is what the data's showing me."
And some of the analysis, we haven't figured out.
- [Researcher] But when we found that it wasn't necessarily,
that relationship that occurred in normal-weight women,
but not in the obese women,
and we measured the metric we were using
whether they had over-gained or not,
- [Dr. Groth] We did it both ways.
- [Researcher] We did it both ways,
so that's sort of more compelling
that we did it continuously
it wasn't just an artifact
of where the— - That's what I think
the obese women, prior to pregnancy—
- [Dr. Roth] I don't know how to turn this thing off.
I just turned it off so I wasn't hearing myself.
Yeah. (laughs)
(mechanical screen retracting)
(people chatting off-mic)
- [Dr. Roth] The child thing is interesting too,
in that the actual gestational weight gain retention
has an effect on the child.
And there is some literature out there that supports that.
And there's one study that says that that's true,
specifically, again, in the normal-weight women.
- [Audience Member] You did it continuously, too,
and I was thinking, what if you did it,
y'know, if the average weight gain is 30 pounds,
you look at 30-pound weight gain,
in obese women and non-obese women,
and how that impacts on their children,
their outcome.
So relative percent gain
would be different. - Right,
that was one of the things - the absolute weight gain,
which is the average weight gain, would be the same.
If most people are gaining 30 pounds—
- [Dr. Roth] And I don't know
if that's true across the board.
But I'm beginning to notice that, and kinda wondering.
And then when I saw the PRAMS thing said that,
I was like, "Really?"
(person speaking off-mic)
eMoms is the overweight and the normal weight.
The obese were lower.
But don't forget, we are pushing them to be lower.
But on average, yeah, and PRAMS data is 31 pounds.
And that's 14 states.
I don't know if the number's right,
I didn't go back and look at that.
- [Audience Member] So is the impact
of the 30-pound weight gain
different on the offspring
if the mother is obese pre-pregnancy,
or if she's not?
- [Dr. Roth] Right, that's the issue.
The normal-weight, it's the moms who are not obese
that it had the longer impact.
- [Audience Member] But even just for 30 pounds,
you know what I mean?
Like, if you use above or below the norm,
if you kind of look at that standard amount of weight gain
that women are already gaining