Analysis of the Transmission of Overweight/Obesity in the Mother-breastmilk-child Triad in Relation to Maternal Cardiometabolic Status and Diet
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 165
- 试验地点
- 4
- 主要终点
- Difference between groups and change from 1 to 6 months postpartum in human milk High-Sensitivity C-Reactive Protein (hs-CRP)
研究概览
简要总结
The prospective 5-month follow-up study will involve 150 mother-infant dyads grouped based on maternal baseline BMI category (normal weight, overweight, obesity). The investigators plan 3 study visits (1, 3, and 6 months postpartum) with analysis the following parameters and outcomes:
- maternal anthropometry and body composition;
- maternal dietary intake and dietary patterns (with results of biomarker-based validation);
- maternal status of lipophilic antioxidants, selected vitamins, and fatty acids profile that may be related to adipose tissue metabolism, inflammation, and cardiometabolic status;
- maternal metabolomics, adipokines, insulin, selected biomarkers of inflammation, altered glucose metabolism, and oxidation;
- breastmilk composition assessed by systemic approach (macronutrients, fatty acids profile, lipophilic antioxidants, adipokines, hormones, immunological profile, and preliminary lipidomic analysis in part of the study group);
- infant growth trajectory, body composition, urine metabolomics, and biomarkers of oxidative stress.
Additionally, maternal and infant stool, buccal swabs, and human milk samples will be banked for further microbiome analysis studies.
详细描述
The global obesity pandemic continues to escalate, with projections showing 1 in 5 women and 1 in 7 men obese by 2030. Maternal obesity raises the risk of childhood obesity by 264%, and overweight/obese children are more prone to become obese adults.
Obesity-associated metabolic dysfunctions (inflammation, insulin resistance, dyslipidemia) heighten morbidity and mortality risks. Breastfeeding mitigates overweight/obesity risks, yet mothers with overweight/obesity often encounter challenges in initiation, continuation, and altered milk composition, showing elevated levels of leptin, insulin, and n-6/n-3 fatty acids. However, findings on other components, like total fat, fatty acids, insulin, adipokines, carotenoids, and immune factors, remain inconsistent due to methodological limitations and lack of comprehensive analysis. Nonetheless, the potential pro-inflammatory and obesogenic properties of milk produced by mothers with overweight/obesity have been discussed. Recent systematic reviews link breastmilk protein, fat, leptin, and IL-6 to infant growth and adiposity. Findings for other components remain unclear due to small samples, methodological limitations, and lack of a systemic approach to analyze breastmilk as a complex biological system. Alterations in breastmilk composition may stem from disrupted de novo synthesis, transport across the blood-breastmilk barrier, or altered circulating levels. Recent studies showed impaired de novo synthesis of C15:0 and C16:1 fatty acids, probably caused by insulin resistance and reduced long-chain fatty acid transfer linked to inflammation (suppress lipoprotein lipase activity essential for transporting lipid compounds). Hence, poor cardiometabolic status may mediate altered breastfeeding outcomes and milk composition, but it requires further studies. Studies among non-lactating individuals suggested lifestyle and diet play crucial roles in mitigating overweight/obesity metabolic implications (e.g., metabolically healthy obese (MHO) and metabolically obese with normal weight (MONW) phenotypes). Maternal diet can influence breastmilk concentration of certain diet-dependent nutrients and bioactives (e.g., fatty acids, vitamins A, D, and carotenoids). Similarly, prohealthy/unhealthy dietary patterns seem to have beneficial/unfavorable effects on breastmilk composition and breastfeeding outcomes, but results remain inconclusive. Nonetheless, some suggest that diet may mitigate the effects of maternal overweight/obesity on breastmilk composition in mothers with overweight/obesity. The mechanisms linking obesity-related changes in breastmilk to infant development remain unclear. This study addresses this gap by studying the mother-breastmilk-infant triad, focusing on maternal cardiometabolic status, diet, breastmilk composition as a complex biological system, and anthropometric and metabolic outcomes.
This study aims to elucidate the intricate interplay between maternal adiposity, cardiometabolic status, diet, and breastmilk composition and to understand the role of breastmilk in the transmission of obesity and the shaping of infant metabolic health.
Our research questions will aim to determine/explore the following questions:
Q1. How does the maternal BMI category differentiate breastmilk composition from a systemic perspective? Q2. How does maternal cardiometabolic status mediate OW/OB-related alterations in breastmilk composition? Q3. Whether (and how) maternal diet moderates OW/OB-related alterations in breastmilk composition? Q4. Whether (and how) maternal OW/OB differentiates infant metabolomic profile? Q5. Whether (and how) OW/OB-related alterations in breastmilk composition influence infant outcomes and obesity risk? Q6. Whether (and how) maternal dietary patterns moderate adverse health outcomes of maternal OW/OB in infants?
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •for mother:
- •at least 19 years,
- •plan of exclusively or predominantly breastfeeding for 6 months,
- •consent to a sampling of biological material and participate in all planned procedures (for both mother and infant),
- •willingness to finish the follow-up,
- •well-understanding of the Polish language (for non-Polish nationalities); for infants:
- •1 month or less,
- •clinically healthy,
- •none or one formula feeding per day
排除标准
- •for mother:
- •type 1 or 2 diabetes diagnosed before pregnancy,
- •uncontrolled thyroid disease,
- •breastfeeding more than 1 child or being a milk donor,
- •tobacco/alcohol use during pregnancy or currently,
- •inability to express a sufficient amount of milk; for infants:
- •congenital disease,
- •birth from a multiple pregnancy,
- •preterm birth (<37 Hbd).
研究组 & 干预措施
Normal weight (NW)
n=55 (maternal BMI at baseline 18.5-24.9 kg/m²)
Overweight (OW)
n=55 (maternal BMI at baseline 25-29.9 kg/m²)
Obesity (OB)
n=55 (maternal BMI at baseline >29.9 kg/m²)
结局指标
主要结局
Difference between groups and change from 1 to 6 months postpartum in human milk High-Sensitivity C-Reactive Protein (hs-CRP)
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk hsCRP assessed by ELISA method.
Difference between groups and change from 1 to 6 months postpartum in maternal body fat percentage
时间窗: 1, 3, and 6 months postpartum
Assessment of changes in total body fat content, assessed by a bioelectrical impedance analysis (BIA) and a dual-energy X-ray absorptiometer (DXA). Results will be reported as a percentage (%).
Difference between groups and change from 1 to 6 months postpartum in maternal fat-free mass percentage
时间窗: 1, 3, and 6 months postpartum
Assessment of changes in fat-free mass, assessed by a bioelectrical impedance analysis (BIA) and a dual-energy X-ray absorptiometer (DXA). Results will be reported as a percentage (%).
Difference between groups and change from 1 to 6 months postpartum in maternal Visceral Fat Area
时间窗: 1, 3, and 6 months postpartum
Assessment of changes in visceral fat area, assessed by DXA. Results will be reported as square centimeters (cm\^2).
Difference between groups and change from 1 to 6 months postpartum in maternal Subcutaneous Fat Area
时间窗: 1, 3, and 6 months postpartum
Assessment of changes in subcutaneous fat area, assessed by DXA. Results will be reported as square centimeters (cm\^2).
Difference between groups and change from 1 to 6 months postpartum in maternal Body Mass Index (BMI)
时间窗: 1, 3, and 6 months postpartum
Weight and height will be combined to report BMI in kg/m\^2.
Difference between groups and change from 1 to 6 months postpartum in maternal Waist-Hip Ratio (WHR)
时间窗: 1, 3, and 6 months postpartum
Assessment of fat distribution calculated as the waist measurement divided by the hip measurement (dimensionless ratio).
Difference between groups and change from 1 to 6 months postpartum in maternal Waist-to-Height Ratio (WHtR)
时间窗: 1, 3, and 6 months postpartum
Assessment of fat distribution calculated as the waist measurement divided by height (dimensionless ratio).
Difference between groups and change from 1 to 6 months postpartum in metabolic syndrome (MetS) incidence
时间窗: 1, 3, 6 months postpartum
Assessment of MetS incidences diagnosed based on the occurence of three from five metabolic abnormalities diagnosed based on International Diabetes Federation-established cut-off points for women for waist circumference (≥80 cm), fasting blood glucose (≥100 mg/dL), triglicerides (≥150 mg/dL), HDL cholesterol (\<50 mg/dL), blood pressure (systolic SBP ≥ 130 or diastolic ≥ 85 mmHg) as a marker of cardiometabolic health.
Difference between groups and change from 1 to 6 months postpartum in maternal glycated haemoglobin (HbA1c)
时间窗: 1, 3, 6 months postpartum
Assessment of changes in HbA1c (reported in %) as a marker of maternal cardiometabolic health.
Difference between groups and change from 1 to 6 months postpartum in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR)
时间窗: 1, 3, 6 months postpartum
Assessment of HOMA-IR calculated as the product of fasting insulin \[µIU/mL\] and fasting glucose \[µIU/mL\] divided by 22.5 (dimensionless ratio) as an indicator of maternal cardiometabolic health.
Difference between groups and change from 1 to 6 months postpartum in maternal serum leptin
时间窗: 1, 3, 6 months postpartum
Assessment of maternal serum leptin assessed by the ELISA method as an indicator of maternal cardiometabolic health.
Difference between groups and change from 1 to 6 months postpartum in maternal serum adiponectin
时间窗: 1, 3, 6 months postpartum
Assessment of maternal serum adiponectin assessed by the ELISA method as an indicator of maternal cardiometabolic health.
Difference between groups and change from 1 to 6 months postpartum in maternal serum and infant urine Retinol-Binding Protein-4 (RBP4)
时间窗: 1, 3, 6 months postpartum
Assessment of maternal serum and infant urine RBP-4 assessed by the ELISA method as an indicator of maternal and infant cardiometabolic health.
Difference between groups and change from 1 to 6 months postpartum in human milk macronutrients
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk macronutrients (fat, carbohydrate, dry material, protein, true protein) concentration assessed by mid-infrared (mid-IR) transmission spectroscopy method. Results will be reported in grams per 100 mL.
Difference between groups and change from 1 to 6 months postpartum in human milk energy value
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk energy value assessed by mid-infrared (mid-IR) transmission spectroscopy method. Results will be reported in kcal per 100 mL.
Difference between groups and change from 1 to 6 months postpartum in human milk secretory immunoglobulin A (S-IgA)
时间窗: 1, 3, and 6 months postpartum
Assessment of human milk S-IgA assessed by Enzyme-Linked Immunosorbent Assay (ELISA) method. Results will be reported in grams per liter \[g/L\].
Difference between groups and change from 1 to 6 months postpartum in human milk lactoferrin
时间窗: 1, 3, and 6 months postpartum
Assessment of human milk lactoferrin assessed by ELISA method. Results will be reported in grams per liter \[g/L\].
Difference between groups and change from 1 to 6 months postpartum in human milk leptin
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk leptin assessed by ELISA method.
Difference between groups and change from 1 to 6 months postpartum in human milk adiponectin
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk adiponectin assessed by ELISA method.
Difference between groups and change from 1 to 6 months postpartum in human milk insulin
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk insulin assessed by ELISA method.
Difference between groups and change from 1 to 6 months postpartum in human milk interleukin 1 (IL-1)
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk IL-1 assessed by ELISA method.
Difference between groups and change from 1 to 6 months postpartum in human milk interleukin 6 (IL-6)
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk IL-6 assessed by ELISA method.
Difference between groups and change from 1 to 6 months postpartum in human milk Tumor Necrosis Factor-alpha (TNF-alfa)
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk TNF-alfa assessed by ELISA method.
Difference between groups and change from 1 to 6 months postpartum in human milk fatty acid profile
时间窗: 1, 3, 6 months of postpartum
Assessment of human milk fatty acid profile analyzed as methyl ester (FAME) by gas chromatography. Results will be reported as concentration within a total fat \[% wt/wt\].
Difference between groups and the change from 1 to 6 months of life in infant anthropometric development
时间窗: 1, 3, 6 months of life
Assessment of anthropometric development calculated as weight-, length-, BMI-, and head circumference z-scores for age and sex, analyzed based on WHO standards.
Difference between groups and the change from 1 to 6 months of life in infant body fat-free mass percentage
时间窗: 1, 6 months of life
Assessment of changes in total body fat-free mass content, assessed by the whole-body DXA scans with a vacuum cushion to prevent movement. Results will be reported as a percentage (%).
Difference between groups and the change from 1 to 6 months of life in infant body fat percentage
时间窗: 1, 6 months of life
Assessment of changes in total body fat content, assessed by the whole-body DXA scans with a vacuum cushion to prevent movement. Results will be reported as a percentage (%).
次要结局
- Difference between groups and the change from 1 to 6 months postpartum in maternal dietary habits(1, 3, 6 months postpartum)
- Difference between groups and the change from 1 to 6 months postpartum in the maternal resting metabolic rate (RMR)(1, 3, 6 months postpartum)
- Difference between groups and the change from 1 to 6 months postpartum in maternal dietary intake(1, 3, 6 months postpartum)
- Difference between groups and change from 1 to 6 months postpartum in maternal short- and long-term fatty acid status(1, 3, 6 months postpartum)
- Difference between groups and change from 1 to 6 months postpartum in maternal and human milk lipophilic antioxidants and vitamins(1, 3, 6 months postpartum)
- Difference between groups and the change from 1 to 6 months of life in infant skin carotenoid status(1, 3, 6 months of life)
- Difference between groups and change from 1 to 6 months postpartum in maternal and infant urine 8-isoprostane(1, 3, 6 months postpartum)
- Difference between groups and change from 1 to 6 months postpartum in maternal serum hsCRP(1, 3, 6 months postpartum)
- Difference between groups and change from 1 to 6 months postpartum in maternal serum IL-1(1, 3, 6 months postpartum)
- Difference between groups and change from 1 to 6 months postpartum in maternal serum IL-6(1, 3, 6 months postpartum)
- Difference between groups and change from 1 to 6 months postpartum in maternal serum TNF-alfa(1, 3, 6 months postpartum)
- Difference between groups and change from 1 to 3 months postpartum in human milk lipidomics(1, 3 months postpartum)
- Difference between groups and change from 1 to 6 months postpartum in metabolomic profile of maternal serum blood and infant urine(1, 3, 6 months postpartum)
研究者
Monika Zielinska-Pukos
Principal Investigator
Warsaw University of Life Sciences