1. Gillman/Intergenerational Cycles of
Obesity
2010: 1/3 obese, ½ overweight/obese
Increased risk of adverse pregnancy outcomes for e.g.
GDM,HTN,C/S
Postpartum weight retention and lower rates of breastfeeding
Offspring are heavier at birth and at increased risk for
childhood obesity
Where and when to intervene
Once pregnancy begins, decrease GWG
Metabolic intervention, treat GDM
Preconception intervention

2. Avoid excessive GWG
RCT of limiting GWGs
LIMIT trial
Healthy MOMS
Treatment of GDM
ACHOIS and MFMU
Pima Indians sib pair studies
Early follow-up of the Achois; no effect on childhood obesity
Pre-pregnancy obesity
More challenging issue
? Adverse outcomes
Gillman/Intergenerational Cycles of
Obesity

3. Butte/Guidelines for IOM GWG
Excessive GWG in overweight and obese
Associations:
C/S, postpartum weight retention
preterm birth, LGA, SGA, childhood obesity
Danish birth cohort data
GWG guidelines outside the US
(13 countries) 7 similar to IOM
Is there a role for gestational weight loss (GWL) to
decrease adverse pregnancy outcomes?
higher in obese women vs. normal weight women
Decreased C/S, LGA, HTN, and ? increased SGA, varies by
obesity class I, II, III
Cochrane review
No (RCTs) effectiveness of GWL need further study to
evaluate benefits/risks

4. GWG-SPECIFIC RISKS FOR PREGNANCY OUTCOMES
BY PREPREGNANCY BMI CATEGORY AMONG
PRIMIPAROUS WOMEN

5. IOM 2009 GWG
Recommendations
Prepregnancy BMI
category
Total weight gain
(lb, kg)
Rate of weight gain
2nd
and 3rd
trimester
(lb/wk, kg/wk)
Underweight
(< 18.5 kg/m2
)
28-40, 12.5-18 1.0 (1.0-1.3),
0.51 (0.44-0.58)
Normal-weight
(18.5-24.9 kg/m2
)
25-35, 11.5-16 1.0 (0.8-1.0),
0.42 (0.35-0.50)
Overweight
(25.0-29.9 kg/m2
)
15-25, 7-11.5 0.6 (0.5-0.7),
0.28 (0.23-0.33)
Obese**
(≥ 30.0 kg/m2
)
11-20, 5-9 0.5 (0.4-0.6),
0.22 (0.17-0.27)
*Calculations assume a first-trimester weight gain of 1.1-4.4 lb (0.5-2.0 kg)
** 1990 IOM Recommendation: for obese women (BMI>29), weight gain at least 6.8 kg (15 lb)

6. Freeman/Obesity: Metabolic Adaptations
to Pregnancy
Metabolic adaptations: normal pregnancy
early pregnancy increased adipogenesis
late pregnancy increased adipose turnover
Turnover higher in subcutaneous vs. visceral fat
high TG; decreased vascular function
high HDL prevents activation of ROS
Metabolic adaptations: obese pregnancy
pre-pregnancy lipid metabolism
decreased metabolic flexibility
Pregnancy complications (HTN)
ectopic fat distribution, increased lipolysis/NEFA
oxidative stress and endothelial dysfunction

7. Perlow/Strategies to Improve Perinatal
Outcomes
Perinatal complications
preeclampsia, IUFD, C/S, operative delivery, GDM,
shoulder dystocia, macrosomia (>4500g)
Increased risk of congenital anomalies (early
first trimester)
SAB, NTD, cardiac malformations
Difficulty with detection of anomalies
limitations of ultrasound
decreased concentrations of cell free DNA
Prenatal management
screen for diabetes, HTN, EKG/ECHO, ultrasound,
MSAFP, antenatal testing, team approach for C/S
e.g. early epidural, evaluate for OSA

8. Friedman/Transgenerational Effects of
Maternal Nutrition
Concepts or fetal programming
epigenome: lipid excess, oxidative stress
stem cells: increased propensity for adipogenesis
Maternal/Fetal: Metabalome/epigenome
Microbiome
changes over the course of pregnancy
different microbiome based on route of delivery
Non-Human Primates (HFD)
fetal fatty liver/inflammation
role of saturated fat (n-6/n-3)
placental cytokines
long-term follow-up: persistent liver TG/macrophage
with maternal HFD

9. Friedman/Transgenerational Effects of
Maternal Nutrition
Long-term follow-up:
persistent liver TG/macrophage with maternal HFD
HUMAN
Increased skinfolds, no increase in visceral fat but
increased liver fat.
Correlate of maternal pregravid BMI
Modifications?
omega-3
Resveratrol

10. Ozanne/Mechanisms Underlying
Metabolic Programming by Maternal
Obesity
Human
Sib-pair studies (GDM/bariatric surgery) GDM RX
Animal (rodent) models
highly palatable diets
gestation/lactation; Mat IGT, hyper-leptin/insulin
Offspring follow up: wean to control diet
(8 weeks): obese
HTN, IGT, IR, fatty liver
Offspring follow up: (4 weeks): Nl weight
cardiac hypertrophy/ IR (hyperinsulinemia)
muscle, liver, adipose; insulin signaling defects

11. Ozanne/Mechanisms Underlying
Metabolic Programming by Maternal
Obesity
Post receptor insulin signaling defects
IRS-1 p110 beta
Mechanism
no difference in m RNA/transcription
? micro RNA increased (IRS-1)/translation
Human data/ what to target?
glucose/insulin/lipids/GWG/inflammation/placenta
Best metabolic markers:
offspring insulin
Maternal Insulin, but not obesity or leptin
Cardiac hypertrophy
cholesterol

12. Hauguel DeMouzon/Molecular Signals at
the Maternal-Featal Interface
Exposome
Leptin stimulates inflammatory pathways in the
placenta, and mitogenesis
Adiponectin
not expressed in the placenta
+ placental adiponectin receptors
decrease placental amino acid transport
Immune pathways
increase LPS concentrations in obese women
increased placental inflammation TLR4
saturated FFA stimulate:
placental TLR4 expression/IL-6 and TNF

13. Hauguel DeMouzon/Molecular Signals at
the Maternal-Fetal Interface
Cell Free DNA
maternal/placenta sources
increases from maternal but not placental sources
? related to adipose cell apoptosis

14. Van Den Bergh/Maternal Obesity and
Child Brain Development
Neurocognitive Overview
review: increased risk of cognitive delay, low
verbal/reading skills as well ADHD and ADS
Mechanisms
stress, nutritional (Vit. D), GDM etc.
Confounders
develop interventional studies, timing of
interventions
DOBHaD paradigm
Bidirectional interactional process: genes and
environment
brain development, neurotransmitters, immune
activity HPA axis/ANS

15. Van Den Bergh/Maternal Obesity and
Child Brain Development
Mechanisms
High fat and high CHO diets, infections
Evaluation of the Child in models of Mat anxiety
EEG response
possibly related to later life appetite and other
behaviors

16. Oken/Fetal Growth and Metabolic Health
of the Offspring
Adverse Perinatal Effects of Maternal Obesity
short-term; congenital anomalies, stillbirth
long-term; metabolic dysfunction
Genes vs. Environment
Pima Indians
postnatal shared risks/common environment
air pollution
Confounders
SES, Smoking
Obese intrauterine environment
diet quality, omega-3, health care disparities,
bariatric surgery

17. Powell/Placental Function in Obese
Mexican American Mothers
Metabolic Phenotype
normal glucose, hyperinsulinemia, hyperleptinemia,
hyperlipidemia lower Adpn, high TNF but not IL-6
Placental physiology
syncytiotrophoblast: BM/MVM
MVM [Glut 1] correlated with birth weight
MVM AA transporters System A and L
increase SNAT 1correlates with birth weight
BM fatty acids FATP2 increased in obese mothers
Regulation of Nutrient transport
insulin/leptin stimulate system A activity
mTOR responds to leptin, insulin, cytokines etc

18. Powell/Placental Function in Obese
Mexican American Mothers
TLR-4
activated with oleic acid in System A activity
TNF alpha
increase AA transport
Omega DHA supplementation
placental DHA correlates with maternal DHA
decreasing System A and L activity
increased GLUT 1 and FATB4
Adiponectin
decreased System A and L and pup size
modulates nutrient transport

19. Vinter/Lifestyle Interventions During
Pregnancy
Types of lifestyle interventions
diet, physical activity, behavioral
Evaluation
GWG, GDM, HTN, birth weight, long-term outcomes
Intervention studies
decreased GWG, decreased anxiety, GDM,
LIP/LIPO studies
Meta-Analyses (quality of data?)
1.4 kg decrease in GWG, HTN, shoulder dystocia
Inter-pregnancy weight loss/gain

20. Webber/Preconception Care in Obese
Women
Educational objectives (primary care for women)
undiagnosed poorly controlled medical conditions,
immunizations, nutrition, genetics, substance abuse,
environmental, social, mental health, isolation
Preconception
weight reduction, bariatric surgery, risks during
pregnancy, nutritional supplements
Weight reduction
goals?
Impact on fertility
decreased conception rate, ovulation/PCOS,
ovulation induction

21. Webber/Preconception Care in Obese
Women
Why
poor quality embryo and implantation
Weight reduction
5% GWL associated with improved ovulation and
pregnancy rate
Supplements
consider folic acid, vitamin D

22. Webber/Preconception Care in Obese
Women
Educational objectives (primary care for women)
undiagnosed poorly controlled medical conditions,
immunizations, nutrition, genetics, substance abuse,
environmental, social, mental health, isolation
Preconception
weight reduction, bariatric surgery, risks during
pregnancy, nutritional supplements
Weight reduction
goals?
Impact on fertility
decreased conception rate, ovulation/PCOS,
ovulation induction

23. Devlieger/Bariatric Surgery
Bariatric surgery has an important and complex
influence on fertility in women
Pregnancy after bariatric surgery is best delayed
until after the period of rapid weight loss.
Obesity surgery reduces the obesity-related risks
during pregnancy like GDM, macrosomia, &
hypertension...but increases the risk for growth
retardation, and prematurity.
Nutritional deficiencies are frequent after all types of
bariatric surgery and need to be actively detected
and corrected.
Surgical complications of bariatric patients during
pregnancy need to be taken seriously.

24. Clinical Recommendations
for Obese Pregnant Women
Questions which were not addressed in depth
specific physical activity recommendations
fetal gender differences
contraception

25. Clinical Recommendations
for Obese Pregnant Women
Gestational Weight Gain
IOM guidelines
other?
Gestational Weight < IOM
0-5 Kg
weight loss?

26. Clinical Recommendations
for Obese Pregnant Women
Physical Activity (lifestyle interventions)
ACOG guidelines
Initiate physical activity during pregnancy
if so what activity and how much
Initiate dietary changes
Low simple sugar, high complex carbohydrates
decrease saturated fats, increase PUFAs and
MUFA’s?
Other factors?
Affordability, culturally sensitive

27. Clinical Recommendations
for Obese Pregnant Women
Breastfeeding
how long is optimal?
what benefits?
Does breast milk vary depending on the mother’s
metabolic status?
Is all human breast milk the same?

28. Clinical Recommendations
for Obese Pregnant Women
Contraception
50% of pregnancies in the US unplanned
What is optimal contraception for obese women

29. Research Questions/Priorities

30. Gillman/Intergenerational Cycles of
Obesity
Where and when to intervene to prevent childhood obesity
Once pregnancy begins, e.g. decrease GWG
Metabolic intervention, treat GDM
Preconception intervention

31. Freeman/Obesity: Metabolic Adaptations
to Pregnancy
Pregnancy complications
ectopic fat distribution, increased lipolysis/NEFA
oxidative stress and endothelial dysfunction
Is there a role for antioxidants?

32. Perlow/Strategies to Improve Perinatal
Outcomes
Prenatal management
screen for diabetes, HTN, EKG/ECHO, ultrasound,
MSAFP, antenatal testing, team approach for C/S
e.g. early epidural, evaluate for OSA.
Nutrient supplements?

33. Ozanne/Mechanisms Underlying
Metabolic Programming by Maternal
Obesity
Early tissue markers
placenta/cord blood
Time windows?
in utero vs. early neonatal period
Targeted interventions
appropriate individuals/ benefits/risks

34. Friedman/Transgenerational Effects of
Maternal Nutrition
Based on the non-human primate work where do we go
in the human?
Resveratrol
Omega-3

35. Hauguel DeMouzon/Molecular Signals at
the Maternal-Featal Interface
Immune pathways
increase LPS concentrations in obese women
increased placental inflammation TLR4
saturated FFA stimulate:
placental TLR4 expression/IL-6 and TNF
Is diet/microbiome the key?

36. Van Den Bergh/Maternal Obesity and
Child Brain Development
DOBHaD paradigm
Bidirectional interactional process: genes and
environment
brain development, neurotransmitters, immune
activity HPA axis/ANS
How much follow-up is necessary/plasticity?

37. Oken/Fetal Growth and Metabolic Health
of the Offspring
Intrauterine environment
environmental exposome
air pollution, PCBs, Phthalates

38. Powell/Placental Function in Obese
Mexican American Mothers
Metabolic Phenotype
normal glucose, hyperinsulinemia, hyperleptinemia,
hyperlipidemia lower Adpn, high TNF but not IL-6
Improve insulin sensitivity
Metformin, TZDs

39. Vinter/Lifestyle Interventions During
Pregnancy
Lifestyle interventions + nutrient supplements
diet, physical activity, behavioral
omega-3, vit D, folic acid
Do we continue with exercise recommendations
during pregnancy?

40. Webber/Preconception Care in Obese
Women
How much gestational weight reduction
5% , 10%, 15% more?

41. Devlieger/Bariatric Surgery
Bariatric surgery has an important and complex
influence on fertility in women
When to recommnend?
How young is too young?