Lifestyle Interventions for Expectant Mothers (LIFE-Moms Phoenix) - Phoenix

LIFE-Moms (Phoenix center) is a randomized clinical trial in overweight and obese pregnant
women that will test the effects of an intensive lifestyle intervention on gestational weight
gain, control of maternal hyperglycemia, and post-partum return to pre-pregnancy weight. The
Phoenix center will be conducted in collaboration between the Phoenix Indian Medical Center
(PIMC) nurse midwifery and obstetrics services and the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK). It is part of the LIFE-Moms Consortium consisting of
six other clinical centers that will follow similar protocols and a research coordination
unit.

American Indians are at high risk for developing obesity and type 2 diabetes mellitus (T2DM)
and its complications. A major factor responsible for this finding is exposure of the fetus
in the womb to its mother s diabetes, which increases the risk of diabetes in the offspring
particularly during childhood and adolescence. This study is designed to evaluate the effects
of an intensive lifestyle intervention (ILI) in at least 200 adult (age greater than or equal
to 18 years) pregnant women who are eligible for prenatal care at PIMC. Interventions will be
provided to overweight and obese pregnant women who do not have pregestational diabetes but
may have (GDM), i.e., diabetes that first develops or is first recognized in pregnancy, or
are at high risk of developing GDM. The lifestyle intervention will be patterned after the
Diabetes Prevention Program (DPP) that prevented or delayed the onset of diabetes in non
pregnant adults; the interventions will be modified to be appropriate in pregnancy. For women
who develop diabetes, interventions will include coaching to optimize glycemic control.

Women will be randomly assigned to one of two intervention groups, assigned with equal
probability: an enhanced standard of care group or an intensive lifestyle intervention group
(ILI). Following delivery, all the mothers and infants will be treated in the same way
regardless of their initial treatment group. For example, all mothers will be encouraged to
breast feed and follow other recommended practices for the health of themselves and their
babies. After delivery the mother will be invited to bring the infant to the research clinic
five times during the first 6 months and again at 1 year of age. These follow up visits for
the infant are timed 1) to understand the patterns of change in neonatal body composition and
2) to coincide, when possible, with well-child pediatric visits. We will also question the
mothers and abstract data from the medical record regarding the child s feeding practice,
overall health, hospitalizations, immunizations, and medicine use.

Outcomes will be assessed on the same schedule for both intervention groups. Prenatal
measurements include demographic, anthropometric, and biochemical data. The latter will focus
on periodic measures related to blood glucose (sugar), including glucose tolerance tests.
Diet and physical activity will be assessed by questionnaires and objective activity
monitors. Many of these tests will be repeated in the mother at 6-12 weeks and 12 months
post-partum. Infant data at or shortly after birth and at months 1 through 6 and 12 will
include weight, length, head size, estimated body fat, feeding practices, and medical record
abstraction.

- INCLUSION CRITERIA:

Adult pregnant women of any race or ethnicity may participate if they meet each of the
following inclusion criteria:

1. At least 18 years of age.

2. Receive prenatal care at the nurse midwifery/obstetrics service of PIMC and plan to
continue receiving such care throughout the pregnancy.

3. Able to have an OGTT prior to 16 weeks gestation. Hyperemesis can preclude some
pregnant women from successfully completing the OGTT; these women will not be excluded
if the fasting blood samples can be obtained.

4. Able to have an ultrasound examination to estimate fetal age.

5. Complete initial run-in screening visits to determine whether the woman can manage the
tasks required of participation in an intensive intervention if randomized to the
intervention group.

6. Able to commit the time required for the interventions and follow-up.

7. Singleton viable pregnancy. A twin pregnancy reduced to singleton before 14(0) weeks
by project gestational age is acceptable. An ultrasound must be conducted before
randomization that shows a fetal heartbeat; there should be no evidence of more than
one fetus on the most recent pre-randomization ultrasound.

8. Gestational age at randomization no earlier than 9 weeks 0 days and no later than
15(6) weeks based on an algorithm that compares the LMP date and data from the
earliest ultrasound.

9. Body mass index greater than or equal to 25 kilogram / square meter based on first
trimester measured weight and on measured height. The earliest weight measurement
before randomization, measured specifically for the study, will be used. Reported
pre-pregnancy weight will not be used to determine eligibility because of the
potential for inaccuracy. If the earliest weight measurement is conducted at 14(0) to
14(6) weeks or 15(0) to 15(6) weeks, 1 pound or 2 pounds will be subtracted from the
measured weight, respectively, to adjust to a first trimester weight. This weight and
the resultant BMI are defined as the baseline weight and BMI, respectively.

EXCLUSION CRITERIA:

- Diagnosis of diabetes prior to pregnancy or any of the following results of the
oral glucose tolerance test at visit #1 that suggest diabetes prior to pregnancy:
HbA1c greater than or equal 6.5 %, FPG greater than or equal 126 milligrams per
deciliter, or 2-hour post-load plasma glucose greater than or equal 200
milligrams per deciliter (75 grams oral glucose tolerance test). All potential
participants will have HbA1c and a 75 grams oral glucose tolerance test performed
prior to randomization.

- Women who meet the above criteria for diagnosed or presumed diabetes prior to
pregnancy will be excluded. Others who meet criteria for GDM will be eligible.
Criteria for GDM diagnosis will be based on ADA 2012 criteria (at least one of
FPG greater than or equal to 92 milligrams per deciliter, 1 hour PG greater than
or equal 180 milligrams per deciliter, or 2 hour PG greater than or equal to 153
milligrams per deciliter.)

- Known fetal anomaly

- Planned termination of pregnancy

- History of three or more consecutive first trimester miscarriages

- Past history of anorexia or bulimia by medical history or patient report. Binge
eating disorder (BED) is not an exclusion.

- Current eating disorder diagnosed by EDE-Q questions 2-4 and confirmed after
discussion with the participant by study staff

- Actively suicidal defined as a value greater than or equal 2 on the BDI-II
question 9

- Prior or planned (within 1 year of expected delivery) bariatric surgery

- Current use of one or more of the following medications:

- Metformin

- Systemic steroids

- Antipsychotic agents (e.g., Abilify (apriprazole), Haldol (haloperidol),
Risperdal (resperidone), Seroquel (quetipapine), Zyprexa (olanzapine))

- Anti-seizure medications or mood stabilizers that would be expected to have
a significant impact on body weight (e.g., Depakote (valproic acid),
Lamictal (lamotrigine), Lithium, Neurontin (gabapentin), Tegretol
(carbamazepine), Topamax (topiramate), Keppra (levetiracetam)

- Medications for ADHD including amphetamines and methylphenidate

- Any teratogenic agent Class D or X (site specific)

- Continued use of weight loss medication including OTC and dietary supplements for
weight loss (e.g., Adipex (phentermine), Suprenza(phentermine) Tenuate
(dietheylpropion), Xenical (orlistat), Alli (orlistat), conjugated linoleic acid,
Hoodia, Green tea extract, Guar gum, HydroxyCut, Sensa, Corti-slim, Chromium,
chitosan, Bitter orange)

- Contraindications to aerobic exercise in pregnancy specified in the ACOG
Committee Opinion #267, 2002

- Hemodynamically significant heart disease defined as an AHA class II (short
of breath with exercise) or greater

- Restrictive lung disease (e.g. pulmonary fibrosis)

- Poorly controlled hyperthyroidism

- Poorly controlled seizure disorder

- Poorly controlled hypertension defined as a blood pressure greater than or
equal 160/110 millimeters of mercury

- History of extreme sedentary lifestyle (e.g. bed bound)

- Orthopedic limitations to aerobic exercise

- Severe anemia defined as a hemoglobin less than 8 grams per deciliter

- Any condition that requires follow-up at specialty care clinics outside of
PIMC (e.g., pregnancies at high risk for maternal or fetal demise)

- Participation in another interventional study that influences weight control

- Enrollment in this trial in a previous pregnancy

- Intention of the participant or of the care provider for the delivery to be
outside the greater Phoenix metropolitan area.

- Participant s unwillingness or inability to commit to a 1 year follow-up of
herself or her child, including planning to move away.

- Inability or unwillingness to provide informed consent, in the English language,
including consent for study staff to abstract data from all prenatal and delivery
records (for the current pregnancy) whether the care or delivery occur at PIMC or
elsewhere. English is the common language of the participants who receive care at
PIMC. Some also speak tribal languages or Spanish. English is the language used
in the intervention materials, the screening forms, and online documents. English
is also the primary language of study staff.

- Any condition that in the opinion of the investigators would interfere with
consent, treatment or follow-up.