Clinical trial NCT04782063: Prevention of Obesity in Infants of Overweight and Obese Women
Official title: Prevention of Obesity in Infants of Overweight and Obese Women
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infant Obesity
Keywords: Obesity
Hyperphagia
Breast Milk
Lead sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Sponsor class: OTHER
First posted: 2021-03-04
Enrollment: 240
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Calibration of infant breast milk and formula intake: We will calibrate (reduce) the pumped breast milk or formula intake of infants of overweight and obese mothers who exceed 75%ile of WHO BMI, in order to prevent infant obesity and subsequent childhood obesity.
Primary purpose: PREVENTION

Brief summary: Maternal and childhood obesity have dramatically increased and continue to present a significant health problem. Studies show that offspring of overweight (body mass index, BMI \>25-29.9) and obese (BMI ≥30) women are at increased risk of newborn and age 1-year adiposity, and infant adiposity predicts childhood and adult obesity. The investigators hypothesize that infants of overweight/obese (OW/OB) mothers have both relative hyperphagia and are provided human milk with increased caloric composition, leading to obesity. The investigators propose an intervention study to calibrate milk or formula intake in infants of OW/OB mothers so as to avoid overweight infants at 6 months of age.

Detailed description: This is a clinical intervention study to calibrate infant milk or formula intake and modulate infant weight gain to prevent the development of infant obesity. The investigators will study only OW/OB women, as these patients are at increased risk of infants with excessive weight gain. The study will be conducted using clinical site at Harbor-UCLA Medical Center and at CTSI, The Lundquist Institute.

OW/OB women (pre-pregnant BMI \>25-29.9 and ≥30) who are providing exclusive human milk via pumping and bottle (n= 120; 50% male and 50% female) will be recruited postpartum in the hospital or at postpartum visit (typically 3-6 weeks). Study women will be randomly assigned to a Standard Feed (SF) or Calibrated Feed (CF) groups. Mother-infant dyads will be seen at 2-week intervals for assessment of infant milk intake, weight gain, supine length, BMI and skinfold thickness till 6 months of age. Continuation of exclusive human milk will be confirmed with questionnaires.

In the SF group, mothers will provide bottled human milk based upon the volume guidelines: Total daily milk intake recommended will be calculated as infant's weight in ounces divided by 6, with individual feed volume calculated as the total daily volume divided by 6 to 8 (maternal discretion as to number of daily feeds). It is understood that mothers may elect an increased or reduced volume of feed dependent upon infant appetite, behavior, etc. throughout the study, at which time recommended feed volume will be adjusted by the standard formula based upon infant weight.

In the CF group, initial feeding volume will be based upon standard volume guidelines as described above. At the 2 week visits, should infants be within the 75%ile of WHO BMI growth curves, standard weight-based recommended feed volumes will be made. Should the infant be equal or greater than 75%ile of WHO BMI, the recommended human milk feed volume will be reduced by 5% of the weight-based determination, following a consultative assessment by our pediatric/neonatal physician. At subsequent visits, adjustments in human milk volume will continue if the infant exceeds 75%ile of WHO BMI, accommodating the normal increase in human milk intake with advancing weight. In no case, will the daily human milk volume be reduced by more than 10% from the weight-based calculation.

Should the infant be less than 10th percentile of WHO BMI, the maternal-infant dyad will be referred for a pediatric and nutrition consults to assess the cause and treatment for potential nutrient deficiency. At 6 months, the investigators will assess the distribution of infant weight BMI between SF and CF groups.

At the final study visit (6 months), prior to infant feeding, a sample of infant urine will be collected, using the Quick-Wee method with samples collected from voids into plastic bags taped to the genital region. Samples will be analyzed for leptin by ELISA (DLP00, R\&D Systems, MN). Urine leptin concentrations correlate significantly with plasma leptin concentration and will provide a non-invasive, semi-quantitative assessment of neonatal hyperleptinemia.

All mothers will quantify and record the daily bottle intake of infants (nearest ml) and will provide a midpumping (8 min) milk sample (10 ml) obtained monthly prior to their visit (morning pumping, frozen) for analysis of protein, carbohydrates and fat (Miris) and total caloric content (bomb calorimetry).

At 6 months, the investigators will assess the distribution of infant weight/BMI between SF and CF groups.

An identical Study (Standard Feed and Calibrated Feed; (n=60 per group; 50% male and 50% female)) will be performed, with the exception that only current formula feed mothers will be enrolled. Daily volume and adjustment of formula feeds will be as described above for human milk. Women will utilize their chosen brand of commercial formula feed, for which total caloric content and composition will be determined.

Data analysis: The proportion of infants whose BMI exceed the 75%ile of WHO BMI at 26 weeks (1st co-primary outcome) will be compared between the two group (SF vs CF) using a pooled z-test or Fisher's exact test. Growth curves for SF and CF over 26 weeks will be estimated and the area under the curve (AUC) compared with the 75%ile curve of WHO BMI. AUCs (secondary outcome) will be computed using the trapezoidal method or integrations of the estimated closed form of the mathematical function. The difference between these AUCs represents the magnitude of how long and much BMI exceed the 75%ile of WHO BMI over the 6 month period. These AUC between the two groups will be compared using a two sample t-test. As exploratory analyses, if potential covariates are found, multivariate analyses (linear and generalized linear regression models) will be used to adjust confounding effects. Sub-group analyses will be also carried out, such as by gender. The investigators will also investigate if early changes in growth curves or maternal human milk composition are associated with infant weight changes, so as to determine the potential for invention prior to exceeding the 75%ile of WHO BMI.

Eligibility criteria: Inclusion Criteria:

* Breast Milk Calibration Study: Study women (pre-pregnant BMI 25-29.9 and ≥30) who are providing exclusive human milk via pumping and bottle (50%/50% male/female) will be recruited at the 3-6 week postpartum visit.
* Formula Milk Calibration Study: Study women (pre-pregnant BMI 25-29.9 and ≥30) who are providing formula via bottle (50%/50% male/female) will be recruited at the 3-6 week postpartum visit.

Exclusion Criteria:

* Breast Milk Calibration Study: breast implants, prior breast surgery, flat/ inverted nipples, tongue-tie or low birth weight infants.
* Formula Milk Calibration Study: low birth weight infants.

Primary outcomes:
measure: Infant normalized weight at 6 months of age
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
Study officials:
References:
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citation: Isganaitis E, Venditti S, Matthews TJ, Lerin C, Demerath EW, Fields DA. Maternal obesity and the human milk metabolome: associations with infant body composition and postnatal weight gain. Am J Clin Nutr. 2019 Jul 1;110(1):111-120. doi: 10.1093/ajcn/nqy334.
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