08/03/2017
Weight trends among women
of reproductive age:
Beyond Big Babies:
The Influence of Obesity on Mom and Baby's
Health Risks Before, During
and After Pregnancy
Hillary Wright, MEd, RDN, LDN
Director of Nutrition
Domar Center for Mind Body Health at Boston IVF
Obesity varies by race/ethnicity and age:
Most common in non-Hispanic black women and least in Asians
Prevalence of obesity in women 12-44 yo has more than doubled since 1976
Two-thirds of women age 20 and older in the US have a BMI > 25
Thirty-six percent are obese (BMI > 30)
Also common among adolescent females
BMI > 85th percentile
33.8% of 12-19 yo females have a
National data from Pregnancy Risk Assessment and Monitoring System (PRAMS)
suggests 1 in 5 (22.6%) women aged 20 years and older who delivered a live-born
infant in 2009 were obese prior to becoming pregnant
“Fetal origins of disease” hypothesis:
“The behavior of a person's genes doesn't just depend on the genes' DNA sequence - it's also
affected by so-called epigenetic factors.” Danielle Simmons, Ph.D., Epigenetic Influences and
Disease, Nature Education, 2008
Pre-pregnancy obesity rates:
= 31% among non-Hispanic black women
= 24% among Hispanic women
= 21% non-Hispanic white women
= 13% among women of other race/ethnic categories
Epigenetics is the study of cellular and physiological phenotype traits and variations that are
caused by external or environmental factors that switch genes on and off and affect how
cells read genes (instead of being caused by changes in the DNA sequence)
Increases with age among all groups 21% of 18-24 year olds, 23%
of 25-34 year olds, 24% of 35-44 year olds.
Fetal programming can also affect reproductive function and outcomes, potentially altering the
health of future generations.
What exactly is fetal programming?
An emerging concept linking environmental conditions during
embryonic/fetal development with risk of diseases later in life
Epi, clinical and experimental studies support fetal programming as
the origin of a number of diseases - obesity, T2DM, HTN, depression
and allergies)
Influenced by several factors, including intake of macro- and
micronutrients and toxic compounds by the mother
The genome as such is not changed, but causative factors may
affect the expression of genes in a way that have lasting effects on
the metabolic functions, that may even be transmitted to future
generations.
Weight and nutritional status of a women before and during pregnancy can affect the long-term
health of their children through programming of the adrenal-pituitary-hypothalamic axis during
gestation.
Research Rooted in Undernutrition:
Barker Hypothesis/ Dutch Famine Study
In 1980’s David Barker proposed over a series of studies that an adverse
fetal environment followed by plentiful food in adulthood may be a recipe
for adult chronic disease
Roots in the Dutch famine study - “Hungerwinter” November 1944
through May 1945. German occupation limited rations such that people,
including pregnant women, in the western region of The Netherlands,
including Amsterdam, received as little as 400–800 calories/d (less than a
quarter of the recommended adult caloric intake)
Children of pregnant women exposed to famine were more susceptible
to diabetes, obesity (“thrifty phenotype”), cardiovascular
disease, microalbuminemia and other health problems
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08/03/2017
Fetal programming and maternal obesity
deBoo HA, The developmental origins of fetal disease (Barker) hypothesis, Aust N Z J Obstet Gynecol,
2006 (model for undernutrition)
Relationship between birth weight and adult obesity, hypertension, and/or insulin
resistance is a U-shaped curve*
Approximately 50% of all cell divisions for growth occur conception to birth
(environmental stress may impact cell number)
Theorized 25% - 36% increase in maternal BMI over the last decade has translated to ~ 25%
increase in the incidence of high-birth-weight babies with increased fat mass and higher risk
of adult obesity, CVD and diabetes in later life
Other medical d/o potentially influenced by in utero environment
psychological/behavioral disturbances, autism, cognitive limitations, Alzheimer disease,
childhood asthma, autoimmune disorders, and osteoporosis, among others
* http://contemporaryobgyn.modernmedicine.com/contemporary-obgyn/content/tags/fetal-programming/fetal-programming-and-adult-obesity?page=full
Complicating Factors in the Study of Influence of
Maternal Weight on Offspring Health
Obesity and fertility/conception
Shared genes and behaviors between mother and child
Adipose tissue is a metabolically active organ
fertility
Unclear influence of father’s genes and child’s future health
Involved in metabolism of sex hormones and related enzymes
Maternal weight at various stages – preconception, stage of gestation,
influences passed on through breastfeeding – may effects offspring weight
and future disease risk to different degrees or in different ways.
obesity associated with reduced
Production of estrogen and sex hormone binding globulins are correlated with
the presence and distribution of body fat (higher rates of infertility with visceral
adiposity)
Compared to women with BMI < 25, OW women have a fundicity ratio of 0.72,
obese 0.60 and very obese 0.48 after controlling for waist circumference
More studies on prepregnancy BMI than on weight gain during pregnancy
Women who gain > 15 kg (33#) weight gain after age 17 had a lower fundicity
rate (0.72) than those who remained more weight stable in early adulthood
Obesity and Ovulation
Major cause of anovulatory infertility
infertility rises 4% per unit of BMI
among obese women estimated that
Well recognized factor in the infertility seen in women with polycystic ovary
syndrome (PCOS)
= effects up to 18% of women of reproductive age
= anovulation related to insulin
resistance/hyperinsulinemia/hyperandrogenism aggravated by central
= IR seen in women with PCOS independent of obesity, but weight
significantly aggravates hormonal imbalances/infertility
Obesity affects fertility in other ways as well
rates of infertility (egg quality).
adiposity
gain
obese ovulatory women have higher
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Obesity and Assisted Reproduction
Preconception lifestyle and egg quality
Success rates fall with increase in BMI in both overweight and obese women
Live births down 9% among overweight, 20% among obese women
Miscarriage rates 24% higher among overweight, 36% higher among obese
women following assisted reproduction
Conception rates higher when donor eggs used egg quality ? effected
by differences in follicular fluid insulin, triglycerides, free fatty acids,
proinflammatory cytokines, oxidized low density lipoprotein, and fatty
acid composition;* uterine lining issues can still effect implantation.
Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod 2011;26:245-52
“Success rates and pregnancy outcomes were most favorable
in cohorts of recipients with low and normal BMI, but
progressively worsened as BMI increased” – Anaylsis of 22,317 IVF
donor cycles
-
Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh
donor/recipient cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry.. Fertil Steril
2016 Feb;105(2):364-8
“Women with obesity or poorly controlled diabetes have an
increased risk of infertility, miscarriage, obstetric complications,
neonatal morbidity and mortality, and birth defects in their
offspring” - Ling G, Metabolic control of oocyte development: linking maternal nutrition and reproductive outcomes, Cell Mol
Life Sci Jan 2015, Vol 72 (2):pp 251-271
Obesity and Unintended Pregnancy
Rates of unintended pregnancy may be higher among obese
women for several reasons:
May be less likely to use reliable contraception
May avoid use of OCP due to fear of weight gain (though not
substantiated by data)
Not clear whether OCPs less effective in obesity, however a 24%
reduction in effective in low-dose OCPs has been reported; also
possibly less emergency contraception
Fertility in Obese Men
Obesity and fetal outcomes
Increases risks to both mother and baby
Correlations seen between BMI/waist circumference and sperm
count, concentration, motility and morphology
Other potential contributors reduced androgens and sex
hormone-binding globulins, increased estrogens
Diet and lifestyle influences that can effect the health of any cells in
your body can effect reproductive cells smoking, substance
abuse, pro-inflammatory diet/lifestyle
For mother higher rates of gestational
hypertension, pre-eclampsia (3 x higher risk), gestational
diabetes, need for cesarean section
For baby poor fetal outcomes like preterm birth,
macrosomia/LGA (>8# 13 oz higher risks at 9# 15 oz),
shoulder dystocia, birth defects and still birth
Epigenetic influences can come from the paternal side as well
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08/03/2017
Obesity and hypertensive
disorders of pregnancy
HTN is a very common and one of the top three causes of maternal
mortality
Seen in 10% of women of reproductive age (18 – 44 yo) and
increase with age (15% of 35-44 year olds)
Highest rates in non-Hispanic black women (19%), 9% in nonHispanic white women, and 8% among other racial/ethnic groups
Pre-existing HTN higher risk of serious maternal-fetal
complications like pre-eclampsia, placental abruption, GDM,
preterm delivery, SGA and fetal mortality.
- risk of pre-eclampsia in obese women twice that of nonobese
- odds of developing gestational HTN 6 x higher in obese
Pre-eclampsia rates by weight
prior to pregnancy (Canada)
Weight Classification
Risk of Pre-eclampsia
Normal weight
3.4%
Class I Obesity (BMI >30)
10%
Class II Obesity (BMI >35)
12.8%
Class III Obesity (BMI >40)
16.3%
•
Gestational HTN, Pre-eclampsia and
Long-term Health
Gestational Diabetes
= 2% of women report DM before pregnancy (3% by age 35-44)
= Obese women up to 6 times as likely to develop GDM
Weight Classification
Due to association with insulin resistance, both gestational
HTN and pre-eclampsia double the risk of developing T2DM
within 17 years post-partum, even without GDM during
pregnancy
Normal weight
6.1%
Class I obesity (30-34.9)
9.7%
Class II obesity (35-39.9)
Women with pre-eclampsia (without GDM) 3 x risk of
T2DM within 1 year of delivery suggesting the IR a/w
gestational HTN and pre-eclampsia can linger after delivery
* JADA, April 2016, Vol 116(4): 677-691
Gestational Diabetes
GDM almost 13 x risk of developing T2DM
Study of 485 women between 18-42 abdominal ultrasound at 11-14 weeks; increased
levels of visceral and abdominal adipose tissue (not subcutaneous) associated with
increased risk of GDM at 34-38 weeks - De Souza LR, First-Trimester Maternal Abdominal Adiposity Predicts
Incidence of GDM
13.7%
16.6%
Class III obesity (BMI >40)
*Position: Obesity, reprod and preg outcomes,
JAND, April 2015, Vol 16(4):677-691
Obesity and delivery complications
Almost twice as likely to need induction (more if also
comorbidities) and have a cesarean delivery (rates up to 49.7%
in class III obesity)
Dysglycemia and Gestational Diabetes Mellitus in Midpregnancy”. Diabetes Care. 2015
Of 635 subjects at risk of GDM, 92 gained within, 175 less than, 368 more than IOM recs;
risk of C-section and med-tx GDM higher in excess weight group.
Main driver of post-partum hemorrhage/maternal mortality
(obese women at double the risk regardless of vaginal vs
cesarean)
With GDM, for every 1# gained after GDM dx there was a 36-83% increased
risk of c-section, preeclampsia - IOM Guidelines for GWG after Diagnosis of GD and
Pregnancy
Outcomes, Am J Perinatol, 2015 Feb; 32(2):239-246
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08/03/2017
Obesity, Gestational Weight Gain
and Weight Retention
National Academy of Medicine Recommendations for Total and
Rate of Weight Gain During Pregnancy, by Prepregnancy BMI 2009
The National Academy of Medicine (former IOM) makes weight gain
recommendations based on pre-gravid BMI
Designed to optimize fetal growth while minimizing post-partum
weight retention
Data suggests that 66% of first time mothers, 56% of multiparous
women exceed these guidelines
Less than half of women will revert to pre-gravid weight; more than
1 in 4 will retain at least 10# at 12 months post-partum (? increased
risk with subsequent pregnancies)
Risk of weight retention based on
gestational weight gain
Meta-analysis of over 65,000 women found, compared to those
who gained within the guidelines, gestational weight gain in
excess of NAM recommendations associated with:
3 kg (6.6#) increase in post-partum weight retention at 3 years
4.7 kg (10.34#) increase at 15 years
* Nehring I, Gestational weight gain and long-term postpartum weight retention: A Meta-analysis, Am J Clin
Nutr, 2011:94(5):1225-1231
Fetal outcomes: obesity,
preterm birth and infant mortality
Preterm birth is a leading cause of LBW significant risk factors for infant
mortality
Pregravid obesity at higher risk of preterm birth per population study of >
226,000 women:*
BMI < 29.9 7.1%
Class I obesity 8.4%
Class II 8.8%
Class III 10.3%
This study BMI not a/w increased rupture of membranes, but increased risk of
medical indication for preterm delivery
Mechanisms: gestational HTN/diabetes/insulin resistance; inflammatory response
* Torloni MR, Maternal BMI and preterm birth: A systematic review of the literature with meta-analysis, J Matern Fetal Neonatal Med, 2009;22(11):957-970
Weight retention and postpartum depression
Mental health can be a confounder
higher
risks of postpartum depression
high prepregnancy BMI a/w
Compared to women with normal pregravid weight, risk of postpartum depression at 6-8 weeks and degree of obesity:
Class 1 no increased risk
Class II 3 x risk
Class III 4 x risk
deBoo HA, The developmental origins of adult disease (Barker) hypothesis, Aust N Z J Obstet
Gynecol, 2006;46(1):4-14
Neonatal and infant death
Meta-analysis found a 21% increase in risk of fetal death per five BMI
units above ideal (risk more dramatic at higher BMIs)
= Thirty eight studies; 10,147 fetal deaths,16,274 stillbirths, 4311
perinatal deaths, 11,294 neonatal deaths, and 4983 infant deaths
included.
CONCLUSIONS: “Even modest increases in maternal BMI were
associated with increased risk of fetal death, stillbirth, and neonatal,
perinatal, and infant death.”
Aune D, Maternal body mass index and the risk of fetal death, stillbirth, and infant death: a
systematic review and meta-analysis. JAMA 2014 Apr 16;311(15):1536-46
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08/03/2017
So what can we do about this?
Ideally health care professionals would start discussions with their
overweight and obese patients long before they contemplate
pregnancy!
RDNs are better positioned than anyone to help women mediate
some of these risks by supporting them through lifestyle
interventions
Lifestyle interventions should be aimed at preconception phase,
during gestation, and post-partum to discourage weight retention
Reasonable, achievable weight loss can make a difference (5-10%)!
The impact of food intake and social habits on embryo quality and the likelihood of
blastocyst formation
= Braga DP, Reprod Biomed Online. 2015 Jul;31(1):30-8
- 2659 embryos recovered from 269 women undergoing ICSI
(intrasytoplasmic sperm injection) between Jan 2012 – July 2013
- Interview and validated questionnaire at start on food frequency
and social habits over previous year
- Effects of diet/social habits on embryo quality day 3 evaluated, as
well as pregnancy rates
- Food categories investigated: cereals, vegetables, legumes, fruit, red
meat (including pork), chicken, fish, dairy, chocolate, soda (including
caffeinated), alcohol, artificial sweeteners and coffee
- Separate questionnaire on exercise, weight loss dieting over
previous 3 months, # meals eaten per day, and smoking; BMI
measured
Theories behind findings:
Red meat - ? effects of advanced glycation end products (AGE) on
eggs and sperm
Plant foods - ? lower oxidative stress/improved anti-oxidant status
Fish – interesting because of concerns about toxins; ? balanced with
positive effects of omega 3s
Weight loss diet – well known that reproductive function extremely
sensitive to calorie availability (excess activity/underweight can
lower estrogen, leptin).
BMI – inversely correlates with treatment success
Limitation: lack of data on men
Preconception: Impact of diet and lifestyle on
embryo quality and blastocyst formation
Irrespective of weight, in IVF most high quality in-vitro produced embryos
still don’t implant
Obesity known to negatively affect IVF outcome; physical activity
enhances implantation and pregnancy rates
Diet quality may affect reproductive outcome in both males and females
Lifestyle factors may influence whether embryos may progress to
blastocyst formation before transfer
2015 study sought to evaluate whether lifestyle factors and eating habits
can influence embryo quality, blastocyst formation, clinical outcomes
The impact of food intake and social habits on embryo quality
and the likelihood of blastocyst formation: RESULTS
Embryo quality/blastocyst formation
Cereals, vegetables and fruits
positively influenced embryo
quality at cleavage stage
Day 3 embryo quality negatively
associated with ETOH/smoking
Conversion of embryos into
blastocysts increased with fruit
and fish intake
Weight loss diet, ETOH and red
meat had negative influence on
blastocyst formation
Pregnancy rates
Red meat consumption, BMI
and being on a weight loss
diet had a negative effect on
pregnancy rates
Unclear the characteristics of
reported “weight loss diet”
A retrospective cohort study to evaluate the impact of meaningful weight loss on
fertility outcomes in an overweight population with infertility.
Kort JD, Fertil Steril 2014 May;101(5):1400-3 2014 Feb 26.
52 overweight and obese women studied to see if weight loss
of
> 10% could improve pregnancy and live birth rates
followed by an endocrinologist who provided diet and exercise
recommendations, metabolic screening, and pharmacologic
intervention when indicated
Results: Thirty-two percent of patients achieved >10% weight
loss, which correlated with significantly higher conception (88%
vs. 54%) and live birth rates (71% vs. 37%) than those who did
not
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Weight loss improves reproductive outcomes in obese women
undergoing fertility treatment: a randomized controlled trial.
Sim KA, Clin Obes. 2014 Apr;4(2):61-8
49 obese women age 37 or less seeking fertility tx 27 to
intervention, 22 control
Control printed material for weight loss
Intervention 6 weeks of medically supervised very low cal diet
followed by 6 weeks on an RD-prescribed diet, weekly group
education, 10,000 steps monitored walking
Results: 80% completed the intervention; intervention group lost 5 kg
more; reduced BMI by 1.8 units more than control (2.4 units total);
waist circumference dropped by 8.7 cm (controls only 0.7)
Pregnancy rates were 48% among intervention (three naturally),
14% among control (intervention group avg 2 tx cycles vs 4 for
controls!!!!! )
Diet or exercise, or both, for preventing excessive weight gain in
pregnancy, Muktabhant B, Cochrane Database Syst Rev, 2015, Jun 15
49 RCTs involving 11,444 women contributed data to meta-analysis
Interventions = mainly diet only, exercise only, and combined diet
and exercise interventions, usually compared with standard care
Diet or exercise, or both, interventions reduced the risk of excessive
GWG on average by 20%
High-risk women (overweight or obese women, or women with or at
risk of gestational diabetes) receiving combined diet and exercise
counseling interventions experienced a 15% reduced risk of infant
macrosomia
Exercise appears to be an important part of
controlling weight gain in pregnancy
The treatment of obese pregnant women study (TOPS): A randomized controlled trial
of the effects of physical activity intervention assessed by pedometer with or without
dietary intervention in obese pregnant women*
Goal: to control wt gain in 425 pregnant women with BMI > 30
2 Interventions and a control – primary outcome assessing gestational
weight gain; secondary pregnancy complications and outcomes
Interventions physical activity and PA plus diet; both counseled by an
RDN to walk 11,000 steps/d – PA plus diet counseled every 2 weeks on
1200 -1675 cal Mediterranean diet (as per trimester)
55% of PA+diet, 49% of PA and 37% in control stayed w/in IOM weight gain
guidelines of 11-20#. (PA+diet lower emergency c-sections)
* Renault KM, Am J Obstet Gynecol 2014;210(2): 134e 1-9
Exercise during pregnancy and risk of preterm birth in overweight and obese
women: a systematic review and meta-analysis of randomized controlled trials
- Magro-Malosso ER , et al
Meta-analysis including only RCTs 9 trials including 1502 OW or obese
singleton pregnancies with or without aerobic activity assigned prior to 25
weeks assigned
Primary outcome incidence of preterm birth
Results:
= women randomized in early pregnancy to aerobic exercise for about 3060 minutes 3-7 times per week had a lower percentage of PTB
<37weeks compared to controls.
= women in control group had lower incidence of GDM
= no differences in birth weight, stillbirth or C-section between groups
Acta Obstet Gynecol Scand. 2016 Dec 28.
Take-aways on preventing excess weight gain
and maternal/fetal complications:
Interventions that utilize RDN counseling, food journaling, light intensity
resistance training, aerobic activity for 30-60 minutes three or more times
weekly, goal setting, weight monitoring, and self-monitoring with
feedback have all been found effective (frequent contact critical).
Post-partum weight retention
Studies on predominantly low income women
between pregnancies is ~ 5 kg
mean weight retention
Contributes to lifelong weight retention with higher parity associated
with higher BMIs at age 40-50
Breastfeeding for 3 mo or longer a/w less weight retention
Self-monitoring using pedometers, food and activity records, food scales,
and follow up in person, by phone or post cards all found helpful
Bottom line: for greatest impact on maternal/fetal health, interventions
should begin before conception to optimize placental health and metabolic
function as the disturbed metabolic environment of obese women exerts
its effect on reproductive function starting before conception.
Obese women may have lower intentions to breastfeed and more
difficulty initiating and continuing
PA plus diet, goal setting and use of monitoring technologies/mailings to provide ongoing
support may provide best results
* AND Position paper on Obesity, Reproduction, and Pregnancy Outcomes JADA, April 2016,
Vol 116(4): 677-691
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08/03/2017
What does AND Recommend? Position of the Academy of
Nutrition and Dietetics: Obesity, Reproduction, and Pregnancy
Outcomes
JADA, April 2016, Vol 116(4): 677-691
Preconception: all women should have weight status assessed and
referred for counseling/lifestyle interventions
Obese with infertility: intensive weight loss counseling; 800 mcg folic
acid due to increased risk of NTD
During pregnancy: all women educated on healthy weight gain and
risk a/w with excess weight gain; obese women should have access to
nutrition/lifestyle counseling; MNT for GDM
= tools My Plate for Moms, pedometers, monitoring technologies
Post-partum: support for 12-18 mo to encourage weight loss;
breastfeeding support; remote programs; WIC if eligible
The Impact of Physician Weight Discussion on Weight Loss in US Adults,
Pool AC, Obes Res Clin Pract. 2014 Mar-Apr; 8(2): e131–e139
What do I do with these women?
Sensitively discuss the risks associated with excess weight gain while
emphasizing that 10% weight loss can make a significant difference
Educate them of managing insulin resistance via carb-controlled diet
(not low carb)
Encourage them to be active in context of managing underlying IR
Summary
N = 5054 adults between 2005 - 2008
A LOT more research is needed, but evidence is growing programs
that include both diet and exercise components appear more
successful
Glaring gap in data in women who have more difficulty accessing care
low income, varying ethnic and/or socioeconomic groups and
varying health literacy abilities
Reasonable weight loss (10%) can make a big difference;
Mediterranean dietary pattern may help egg quality
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