Lifestyle Intervention in Preparation for Pregnancy (LIPP)

Specific Aim 1: To investigate the physiological significance of lifestyle intervention in
preparation for pregnancy (LIPP) on maternal and neonatal metabolism and adiposity.

We will recruit mothers who delivered their first baby at MHMC. We will conduct the exercise
sessions in local Community Recreation Centers. We will provide childcare and we will support
the cost so participants may bring their babies to the LIPP sessions.

The LIPP program is designed to promote weight loss that is 5-10% of current body weight. The
3-month weight loss phase consists of aerobic exercise training with diet and behavioral
counseling to induce weight loss as was successfully achieved in prior studies. The women
will wear heart rate (HR) monitors (Polar Electro, Woodbury, NY) during each exercise session
so that they have visual feedback of their personalized target heart rate goal. Our Lifestyle
Coaches will enter all foods eaten into our diet database (NDSR, Minneapolis, MN) to
facilitate analysis of calorie, and macro/micro nutrient intake. Subjects will generate
photos from before and after the meal in order to estimate the amount of food that was eaten.
Data will be obtained at baseline, and at 2-week intervals during the initial 12-week
supervised weight loss period.

Lifestyle Intervention - Weight Management/Maintenance:

The pre-pregnancy weight management program (Phases 2A, 2B and 2C) is designed to facilitate
personalized weight loss goals using lifestyle behaviors that include, exercise, diet and
behavioral modification. The intervention includes a "toolbox" concept to help meet weight
loss goals. The Lifestyle Coaches will provide personalized instruction on physical
activity/exercise. Participants randomized to the Control group will receive information on
post-pregnancy diet/weight loss from the nutritionist as distinct from the LIPP nutritionist
to decrease cross contamination between groups.

Weight Management during Pregnancy:

All LIPP and usual care/control groups will be followed by their primary Obstetrical
provider. The OB/GYN department at MHMC has recently revised its clinical guidelines for the
management of the overweight/obese women based on the December 2015 ACOG practice bulletin.
All overweight/obese women will be offered nutrition counseling early in pregnancy by a
registered dietician from the MHMC Nutrition Department with follow-up visits as needed to
support GWG within the IOM guidelines. The Lifestyle Coach will continue to follow-up only
with the LIPP subjects as described in the maintenance phase of the research design.

Specific Aim 2: To determine the molecular effects whereby lifestyle intervention initiated
before pregnancy can improve placental mitochondrial lipid oxidation and accumulation

We will accomplish the objectives of Specific Aim 2 by measuring changes in placental
mitochondrial enzyme activity and lipid metabolism in women enrolled in the Control or LIPP
groups described in Specific Aim 1. Placental tissue will be collected at delivery from all
study participants.

Inclusion Criteria:

- Planning another pregnancy within the next 24 months

- Planning to deliver at MetroHealth Medical Center during their next pregnancy

- A previous full-term singleton pregnancy (gestational age > 37 weeks)

- Vaginal or cesarean delivery

- Normal glucose tolerance or gestational diabetes (GDM), but without evidence of
postpartum diabetes as defined by a 75 g 2-hr oral glucose tolerance test (OGTT)

- Normal blood pressure or mild preeclampsia but normal postpartum blood pressure

- Bottle or breast feeding

- Vaginal or cesarean delivery

- Normal thyroid function (determined by TSH concentration in blood), normal cell blood
count and normal kidney and liver functions. Lipid profile with triglyceride levels
not higher than 400 mg/dl (fasting) and LDL levels less than 180 mg/dL

- No clinical signs or symptoms of cardiovascular disease or any other disease or
condition that may contraindicate participation in exercise training (i.e. COPD,
severe asthma, orthopedic abnormalities)

- Using contraception

Exclusion Criteria:

- Pre- or post-delivery diabetes

- Post-delivery hypertension requiring medication

- Asthma requiring more than occasional use of a sympathomimetic inhaler, but not
chronic inhaled steroids

- Inflammatory bowel disease

- Need for assisted reproductive technologies to become pregnant

- Medical or obstetrical contraindication to the defined exercise program or diet

- Tobacco, excessive alcohol use (greater than 2 drinks/day) or illicit drug use

- Eating disorders such as bulimia

- Gastric surgery to lose weight including banding or bypass procedures

- Any psychological or psychiatric condition which may impair participation in the
lifestyle intervention program

- Multiple pregnancy

- HIV, or hepatitis B or C

- If a LIPP participant becomes pregnant prior to 16 weeks after randomization before
the weight-loss phase for the lifestyle intervention is completed or a control
participant becomes pregnant before the 3 month postpartum randomization, i.e. no
baseline measurement.