Early Tracking of Childhood Health Determinants (ETCHED) Study

The prevalence of childhood obesity (defined by body mass index, BMI greater than or equal to
95th age-sex specific percentile, CDC, 2000) in the United States has plateaued in the last
decade, but the prevalence of more severe degrees of obesity continues to increase,
especially among some minority groups including American Indians and Alaskan Natives. The
purpose of this protocol is to examine the role of adverse prenatal and early-life risk
exposures, both biological and environmental, that contribute to the development of
overweight and obesity in children and increase the risk for associated complications such as
type 2 diabetes and cardiovascular disease. This longitudinal observational study will enroll
primarily American Indian/Alaskan Native pregnant women and their offspring, a population
with a high prevalence of obesity and diabetes. Pregnant mothers 18 years or older and
receiving prenatal care at the Phoenix Indian Medical Center (PIMC) will be eligible if they
agree to the study procedures and plan to follow up for at least 3 years postpartum for
themselves and their offspring. Women, who are unable to consent, are incarcerated, have
non-viable fetuses, or planned pregnancy termination will be excluded. Enrolled participants
will be followed through pregnancy, delivery, and 6 years postpartum, and their offspring
will be followed until their 18th birthday. The primary objective of the study is to explore
the associations of maternal risk measures including prepregnant BMI, gestational weight
gain, and glycaemia with body size, body composition, biochemical measures, and
neuro-cognitive development in the offspring. Family and environmental risk variables that
contribute to obesity and associated metabolic risk will also be assessed. The primary
outcomes include body size and adiposity measures in the offspring: birth weight, age-sex
adjusted weight for length up to 24 months of age, age-sex adjusted BMI at 2-18 years, and
infant body composition (fat mass and fat free mass). During pregnancy, mothers will have 3
visits, and following delivery, they will have 4 visits under the current protocol at 6-12
weeks postpartum, 1 year, 2 years, and 4-5 years postpartum. These visits will include
maternal medical history, dietary history, physical activity and sleep patterns, and
screening questionnaires for perceived stress and depression. We will assess gestational
weight gain and post-pregnancy weight retention. Biochemical tests include periodic measures
of glycemia (fasting plasma glucose, oral glucose tolerance test (OGTT), glycated
hemoglobin), lipids, renal function, and epigenetics. Mothers will be encouraged to breast
feed and follow other recommended post-partum practices. The offspring will be examined at
birth and will have 4 additional visits within the first year of life at 6-12 weeks, 4
months, 6 months and 12 months, then at 18 and 24 months, and at 3 years. Thereafter they
will be scheduled for comprehensive research visits (major visits) at 4-5 years, 6-9 years,
10-13 years and 14-17 years. The major visits include detailed medical history,
anthropometry, developmental assessment, laboratory tests, and ultrasound examination for
subcutaneous and visceral fat. Medical records will be reviewed to assess other health
problems, inter-current illnesses, hospitalizations, and immunizations.

- INCLUSION CRITERIA:

- Pregnant women aged 18 years or older [pregnancy confirmed by urine or serum pregnancy
test, initial gestational age estimation will be based on date of last menstrual
period (LMP).

- Plan to receive prenatal care at PIMC

- Agree to continue with research study participation (both mother and their offspring),
for at least 3 years after delivery

We plan to recruit eligible pregnant women as early as possible, preferably during their
first prenatal visit, but will enroll them any time during pregnancy. These mothers are
expected to be primarily of AI/AN heritage or have infants that are AI/AN. There are
approximately 700 deliveries conducted at PIMC annually. Most pregnant women receive all
their prenatal care and deliver at PIMC, but some deliver elsewhere for reasons such as
proximity at the time of delivery or availability of hospital beds. We anticipate that most
of these pregnant women will meet our recruitment criteria annually; however, there are no
pre-determined limits to the number of participants we can recruit for this study. If the
mother has participated in the ETCHED study during a prior pregnancy, she will still be
eligible for participation in all successive pregnancies, unless incarcerated or unable to
consent or unwilling or is unable to plan for at least 3-years of follow-up of her and her
off-spring after delivery.

STUDY EXCLUSION CRITERIA:

- Maternal age of less than 18 years

- Women who are incarcerated or are unable to consent.

- Unwillingness/inability to plan for at least 3 years of follow-up of mother and her
offspring post-delivery.

- Women whose fetus is not alive or are not planning to continue the pregnancy. We
anticipate that some patients will be lost to follow up for various reasons. However,
if any such research participants return to the well childcare clinic for resuming
care, they would be eligible to re-enroll in ETCHED. For mothers with repeat
pregnancies, her research visit schedule will be based on the delivery of her most
recent offspring. Each child will then have his/her own visit schedule independent of
the mother.

INCLUSION of MOTHER/CHILD DYADS FROM LIFE-MOMS STUDY:

-Mothers and offspring from the Lifestyle Interventions for Expectant Moms (LIFE-Moms)
Phoenix study (Protocol Number 13-DK-N055) will be eligible for participation in the ETCHED
study. There are 39 maternal/child dyads from the Life-Moms study, born between 10/2013 and
11/2014, who will be eligible for participation in ETCHED. The mothers and children will be
followed postpartum as per the ETCHED protocol and data collected during enrollment in the
Life-Moms protocol will be used in ETCHED study data analysis. The mothers in this cohort
will be seen for their initial visit at first

contact. The data collection for each visit will correspond as detailed in Table 2. After
the initial visit, data collection visits will be scheduled as close to the preferred
windows as possible and will correspond with the child s visit according to the data
collected and the preference of the mother.

RECRUITMENT of STAFF MEMBERS (NIH, and IHS):

The study is open to NIH or IHS employees who meet study inclusion and exclusion criteria
except those involved directly with study participants such as data collectors. We will
provide the NIH Information Sheet on Staff Research Participation to NIH employees who are
considering participation in our protocol prior to obtaining consent. In addition, we will
discuss the following applicable safeguards to NIH and IHS staff as a vulnerable class of
subjects:

- Unbiased participation for protocol integrity and participant risk assessment.

- Ensure there is no perceived workplace pressure or expectation on either participation
or deciding not to participate in the protocol in regard to a benefit or adverse
effect on their NIH or HIS employment or staff position.

- Protection of privacy and confidentiality will be maintained, but also with
acknowledgement of the limits due to sensitive information that may be in their NIH or
IHS file.

- Discussion of time commitments of the study and compensation in accordance with NIH
policy 2300-630-3, Leave Policy for NIH Employees Participating in NIH Medical
Research Studies.