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.

Introduction/Rationale: Our preliminary data demonstrate that supervised lifestyle intervention leads to significant weight loss, improved insulin sensitivity, glucose tolerance and incretin secretion, together with healthier cardiovascular and body composition outcomes in overweight and obese adults. We expect that timing and implementation of the proposed lifestyle intervention will produce similar health benefits in overweight/obese women planning a second pregnancy, and lead to greater insulin sensitivity, reduced insulin secretion, and less inflammation. These improvements will result in the prevention of excess nutrient availability (glucose and lipids) from contributing to excess fetal growth/adiposity. The working hypothesis for this Aim is that in contrast to GWG, the decreased pre-pregnancy insulin sensitivity in obese mothers accounts for the greatest clinical variance in fat accretion in the infant. Although clinically we anticipate a decrease in weight and BMI in the LIPP group, the improvement in insulin sensitivity and metabolic profile are the key physiological measures related to the primary outcome of decreased neonatal adiposity, and not the weight loss per se.

The rationale is that the optimal time to implement lifestyle intervention that effectively improves maternal health at the physiological, cellular and molecular level, and results in optimal adiposity in the baby, is prior to pregnancy. Women who lose weight postpartum, experience a decrease in neonatal birth weight (primarily adipose tissue) in subsequent pregnancy, whereas women who gain weight, experience an increase in neonatal birth weight and adiposity. We hypothesize that maternal pre-pregnancy metabolic condition determines the obesogenic in-utero environment, which in turn affects placental programming of mitochondrial and lipid pathways (Specific Aim 2), and body composition of the baby. An additional rationale is that there is a need to understand how improved pregravid metabolic condition affects maternal physiological and molecular function. We anticipate that obese women who complete the LIPP program will enter pregnancy with improved insulin regulated metabolism and reduced insulin resistance, thus facilitating a lower neonatal birth weight and adiposity. We will recruit mothers who delivered their first baby at MHMC. We recognize that these mothers represent a demographic that has limited access to exercise facilities or family support systems that would facilitate free time for exercise. In order to reduce barriers to participation, we will conduct the exercise sessions in local Community Recreation Centers. The Centers have child care facilities and we will support the cost so participants may bring their babies to the LIPP sessions. To further increase participation and maximize retention, we will provide transportation to and from the Recreation Centers. Support for transportation will be requested from the Cleveland Mt. Sinai Foundation. Lifestyle Intervention Weight Loss Phase: The LIPP program is designed to promote weight loss that is 5-10% of body weight. The 4-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. Initially, supervised exercise will be prescribed at 55-60% of HRmax and gradually increased so that after 1-2 weeks, the subjects are exercising at 75-85% of HRmax (~65-70% VO2max). Supervised exercise will consist of walking/jogging on a treadmill and stationary cycling, 3 days/week, 60 min/session (i.e., 500 kcal/session). 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. Participants will be advised to reduce caloric intake by ~500 kcal/d in order to support their weight loss goals. The recommended diet will provide ~55% of calories as carbohydrate, 25% as fat, and 20% as protein. Participants will be instructed to consume complex carbohydrates and to avoid simple sugars. Specific caloric needs will be estimated by indirect calorimetry and a sedentary (x1.3) physical activity correction factor. Energy intake will be estimated using the food photo diary app, Meal Snap. Digital photography provides an excellent estimate of energy intake (67). Participants who do not own a smart phone will have one provided through support from the Cleveland Foundation.

Records covering a 72-hour diet period will be shared with the research team for determination of calorie and nutrient intake. Meal Snap has a food database of over 350,000 items. However, some meals will not be in this database, therefore 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 16-week supervised weight loss period.

Lifestyle Intervention - Weight Management/Maintenance: The pre-pregnancy weight management program (phase 2A, 2B and 2C) is designed to facilitate personalized weight loss goals using lifestyle behaviors that include, exercise, diet and behavioral modification, and is based in part on the Look AHEAD trial. The intervention includes a toolbox concept to help meet weight loss goals. The Lifestyle Coaches will provide personalized instruction on physical activity/exercise - 10,000 steps/day, and the participants will use FitBit Flex (Fitbit.com), to track step count and exercise time. During the first phase of weight maintenance (2A) the women will attend 2 supervised group sessions/week. These sessions include structured exercise (e.g., Zumba, jazzercise, stroller walking), review of dietary photo records, where meals have been eaten (home or away; recorded on smart phone app), and behavioral counseling (with their Lifestyle Coach). Participants will be encouraged to eat 1,200-1,500 kcal/d (~55% carbohydrate, 25% fat, 20% protein) if below 113 kg, or 1,500-1,800 kcal/d if >113 kg. Dietary data will be analyzed at 4-week intervals during the weight maintenance period. Importantly, to minimize subject burden and to maximize retention and data acquisition, the Lifestyle Coach will track calorie intake using the participant's photo diary. Behavioral strategies to motivate healthy lifestyle decisions will include: self-monitoring (food, activity, and weight, using FitBit online resources), goal setting (steps/day, weight loss), stimulus control (i.e., social eating, fast food, sitting vs. standing), problem solving (have snacks available, exercise at home), and relapse prevention (i.e., holidays, alcohol, fast food, sweets, problem foods, compulsive eating). After 4 months and the desired weight loss, subjects move to Phase 2B. During this phase subjects maintain an exercise goal of 10,000 steps/day, but will be required to attend only 1 supervised session/week. If a subject fails to maintain weight loss, defined as weight gain of 3% of current body weight, participants will return to Phase 2A for more supervised weight management. Alternatively, if weight loss is maintained after 3 months, subjects will progress to Phase 2C until the subsequent pregnancy. Phase 2C consists of no supervised exercise sessions. However, the subject and Lifestyle Coach will converse weekly by phone to review progress, including Fitbit exercise data and diet. Data suggest that weight management programs delivered by phone are comparable to clinically delivered programs. During the calls participants will be counseled to continue to exercise at the intensity and duration prescribed during Phase 2B. They will be provided with language-specific food and exercise log books. These will be used to guide calorie intake and will provide another record of compliance. Participants randomized to the Control group will receive information on post-pregnancy diet/weight loss from the CRU nutritionist as distinct from the LIPP nutritionist (HB) 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 (2). 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. Nutritional therapy will consider maternal pregravid BMI, ethnic, cultural and social factors in individualizing healthy eating. The electronic health record (EPIC) includes a graphic GWG nomogram and so GWG will be monitored at each visit. All subjects will be encouraged to increase physical activity for at least 30 minutes/day (primarily walking). Clinical management such as, ultrasounds to estimate fetal growth, and fetal surveillance will be based on the ACOG recommendations. The Lifestyle Coach will continue to follow-up only with the LIPP subjects as described in the maintenance phase of the research design.