CO-OP Trial: Community-based Outreach on Obesity in Pregnancy

Phase 1 will recruit 8-12 obese women from the target population. Initially, 4-6 women will
explore dietary guidance and study interventions and to determine how best to tailor the
intervention. A repeat set of structured interviews will be conducted with the
community-based modifications to provide an assessment of the perceived efficacy of the
intervention. Structured interviews will provide feedback on dietary interventions including
specific advice on caloric recommendations during pregnancy, level of reassurance by negative
ketonuria on urine specimens (which indicates the diet is supplying the nutrition necessary
to maintain a healthy pregnancy), general level of trust/interaction with providers,
maintaining food diary, and how obesity issues directly affect their lifestyles and health.

Phase 2 will be a prospective randomized trial in which obese women will be recruited in the
first trimester. Study participants will be identified by providers in the Truman Medical
Center clinic population and includes obese pregnant women less than 16 weeks in gestational
age during the pregnancy. Dates will be confirmed by standard practices including using last
menstrual period and obstetric ultrasound. Once potential women are identified they will be
directed to study coordinators who will determine study eligibility (BMI >30, 16 weeks or
less pregnant, willing to participate, singleton pregnancy, normal 1 hour glucola) and
consent patients for the study. Women will be randomized to usual care or dietary
intervention using opaque numbered envelopes that are generated by blinded statistician.

The dietary intervention will be conducted by a registered dietician once. Patients in the
study arm will receive a detailed intake and specific dietary guidelines. The dietary
guidelines for study participants will be similar to those for gestational diabetes including
18 to 24 kcal/kg diet with 40% carbohydrates, 30% protein, 30% fat. No participant will be
given a diet that is less than 2,000 kcal per day. Recording daily food/beverage intake in a
diary has been associated with improved adherence to dietary recommendations and is one of
the more effective interventions for behavioral modification. Therefore, study participants
will be asked to record a food/beverage diary and to bring it to prenatal visits. Recent
evidence suggests that highly dense and acellular processed foods are associated with an
inflammatory state that leads to more absorption of lipids and deposition of fat.18,19 Study
participants will be counseled to limit intake of highly calorie dense and acellular
processed foods and beverages to 1-2 times per week if at all and to increase total
percentage of fruits and vegetables to 5-9 items per day.

It is expected that some women may lose weight during this clinical trial as 40% of women
lost weight in a similar trial8. Although those women lost weight, there were no instances of
starvation or ketonuria on routine screening and there was no difference in infant birth
weights between the two groups.8 Routine urinalysis is performed during pregnancy and
screening for ketonuria can indicate metabolic evidence of starvation.

Therefore, to monitor safety during our study, routine urinalysis will be inspected and
evidence of starvation ketonuria (2+ on urine dip, or 40mg/dl) will prompt investigation by
study staff on the cause and determine whether it is related to the study protocol. No
evidence of maternal ketonuria was documented in over 200 women in the previous study.8

Data safety and monitoring will be conducted every 6 months by the medical monitor for the
study, Michael Sheehan, MD (neonatologist). The medical monitor is specifically chosen
outside of the department of ob/gyn to allow for objectivity. Adverse events which would
require immediate suspension of the study for review would include maternal death, maternal
ICU admission, or a total of 2 perinatal deaths in the study group. Unanticipated adverse
events will be reported immediately to the Human Subjects Committee, and its recommendations
for temporary cessation or continuation of the study will be followed. The natural frequency
of perinatal death at Truman after 16 weeks in obese women is a maximum of 2 perinatal deaths
in the 50 women in the study group. If we assume the intervention is no better than current
standard of practice then a maximum of 2 perinatal death cases should serve as the rule for
study suspension and review. If more than 4 perinatal deaths occur then the study should be
concluded as this is more than the expected deviation.

Women will complete an intake assessment including maternal height and weight, food frequency
and quality of life questionnaires and these will be repeated in the 3rd trimester and at 12
months postpartum.

Missing data will be handled in two separate ways for analysis. Numerical values such as
missing weight, height, birth weight, etc. will be handled as follows. Three separate
attempts will be made to locate the data. For instance, if a patient delivered at another
hospital then the patient and hospital will be contacted on 3 separate occasions to obtain
the delivery records. Initially, missing data will be excluded from the analysis. Second,
missing data will be imputed from last values reported for study participant (for maternal
weight, height if within 2 weeks) or the average value for the group will be imputed as the
value (ex: birth weight, maternal weight at delivery) if feasible to determine if missing
values alter the analysis. Both methods will be reported.

Inclusion Criteria:

- Less than 16 weeks pregnant

- Obese (defined as BMI >30)

- Willing to participate in the study

Exclusion Criteria:

- Multiples (twins, triplets, etc.)

- Abnormal 1 hour glucola prior to 16 weeks of pregnancy

- Pregestational diabetes

- Stillbirth or miscarriage prior to 20 weeks of pregnancy