Maternal characteristics, milk-borne IGF-1, and neonatal growth: Insights into endocrine and developmental programming

 Corresponding author: Ashraf T. Soliman Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Maternal characteristics, milk-borne IGF-1, and neonatal growth: Insights into endocrine and developmental programming Ashraf T. Soliman 1, *, Fawzia Alyafei 1, Nada Alaaraj 1, Noor Hamed 1, Shayma Ahmed 1, Shayma Elsayed 2, Dina Fawzy 2, Ahmed Elawwa 2, Hayam Al Hajjaji 3, Maya Itani 3 and Nada Soliman 4 1 Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar. 2 Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt. 3 Department of Dietetics and Nutrition, Hamad Medical Corporation, Doha, Qatar. 4 Maternal and Child Health Department, Ministry of Health, Alexandria, Egypt. World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 Publication history: Received on 11 September 2025; revised on 18 October 2025; accepted on 20 October 2025 Article DOI: https://doi.org/10.30574/wjarr.2025.28.1.3574 Abstract Background: Human milk contains a dynamic array of bioactive hormones and growth factors that extend beyond nutrition to influence neonatal growth, metabolism, and developmental programming. Among these, insulin-like growth factor-1 (IGF-1) is a pivotal mediator of tissue anabolism, gut maturation, and postnatal adaptation. Maternal metabolic and obstetric factors modify the concentration of IGF-1 and related hormones in milk, shaping infant growth trajectories from birth through early childhood. Objectives •To examine how maternal characteristics—including body mass index (BMI), adiposity, gestational diabetes mellitus (GDM), and delivery mode—affect IGF-1 and associated milk hormones (insulin, leptin, adiponectin, ghrelin). •To evaluate the impact of milk-borne IGF-1 on neonatal, preterm, and early-childhood growth outcomes. •To explore mechanistic pathways linking maternal endocrine status, milk hormonal composition, and infant developmental programming. Methods: A structured literature search was performed in PubMed, Scopus, and Web of Science through March 2025. Eligible studies included human cohorts, case–control, and randomized trials reporting milk IGF-1 levels in relation to maternal factors or infant outcomes. Data extraction included sample characteristics, timing of milk collection, hormonal assays, and growth indices. Study quality was assessed using the Newcastle–Ottawa Scale and Cochrane RoB2 tools. Results were synthesized descriptively due to heterogeneity across designs. Results: Twenty-two studies met inclusion criteria. Maternal obesity and diabetes were consistently associated with elevated milk IGF-1 and insulin but reduced adiponectin and obestatin, enhancing early postnatal weight gain. Cesarean delivery and social stress were linked to lower IGF-1 levels, while early breastfeeding in preterms significantly increased serum IGF-1 and promoted catch-up growth. Experimental supplementation with enteral IGF-1 improved intestinal integrity but did not accelerate weight gain. Longitudinal cohorts revealed a biphasic effect: higher early milk IGF-1 correlated with increased infant weight at 1 year but reduced BMI at 3–5 years, reflecting adaptive metabolic programming. Pasteurization of donor milk decreased IGF-1 bioactivity by ~40%, underscoring the benefit of mother’s own milk. World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1495 Conclusions: Maternal metabolic health, nutritional status, and perinatal factors critically determine milk IGF-1 bioavailability and its impact on neonatal growth. Early exposure to milk-borne IGF-1 supports gut and somatic development, particularly in preterm infants, while long-term effects suggest homeostatic regulation of adiposity. Optimizing maternal diet, glucose control, and lactation practices may enhance IGF-1 concentrations and confer lasting benefits on child growth and metabolic outcomes. Keywords: Insulin-Like Growth Factor-1 (IGF-1); Human Milk Hormones; Maternal Metabolic Status; Preterm Infant Growth; Developmental Programming 1. Introduction Human milk provides not only optimal nutrition but also a complex array of bioactive hormones and growth factors that influence neonatal adaptation and development. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a key regulator of postnatal growth, intestinal maturation, and endocrine programming (1). The insulin and IGF systems, integrated into the mammalian milk matrix early in evolution, convey critical signals that support survival and growth during the transition from intrauterine to extrauterine life. IGF-1 and IGF-binding proteins are present at particularly high concentrations in colostrum, declining thereafter but remaining biologically relevant throughout lactation (2). Maternal body composition exerts a significant effect on milk hormonal content. Women with higher adiposity or body fat percentage have increased concentrations of IGF-1 and insulin, and reduced levels of obestatin in breast milk compared with leaner mothers, reflecting the influence of maternal metabolic status on the endocrine profile of milk (3). Maternal metabolic disorders, including obesity and gestational diabetes mellitus (GDM), further modify levels of insulin, leptin, adiponectin, and IGF-1 in breast milk, thereby shaping infant metabolic trajectories. These alterations may exert sex-specific effects on growth and adiposity, underlining the dynamic interaction between maternal and infant factors (4). Delivery mode is another determinant of milk IGF-1 concentrations. Cesarean delivery has been associated with lower milk IGF-1 compared with vaginal birth, potentially altering neonatal exposure to trophic factors during early lactation (5). Preterm infants are particularly vulnerable to IGF-1 deficiency, as circulating concentrations drop sharply after premature birth. Early administration of mother’s own milk (MOM) significantly elevates serum IGF-1 in preterm infants, emphasizing its importance for supporting catch-up growth and intestinal development in this population (6). Interventional trials of enteral IGF-1 supplementation suggest transient improvements in gut permeability in preterm neonates, although effects on overall growth and feeding tolerance are limited (7). Beyond intestinal effects, milk IGF-1 has been positively associated with accelerated early weight gain in breastfed infants, indicating that enhanced IGF-1 exposure may partly explain the high growth velocity observed in some exclusively breastfed infants (8). Longitudinal studies have linked milk IGF-1 concentrations to body composition outcomes across infancy and childhood. Higher IGF-1 levels have been associated with greater infant weight at one year but lower weight and BMI later in early childhood, suggesting a biphasic programming pattern that evolves over time (9). Systematic reviews further support that milk-borne hormones—including IGF-1, leptin, ghrelin, adiponectin, and insulin—jointly regulate appetite, energy balance, and growth patterns during infancy (10). However, findings remain heterogeneous and sometimes conflicting due to variations in maternal phenotype, metabolic status, and assay methods. Thus, comprehensive evaluation is needed to clarify how maternal characteristics regulate IGF-1 concentrations in human milk and how this, in turn, affects infant growth trajectories and developmental outcomes. Objectives • To evaluate the influence of maternal characteristics—including body mass index, adiposity, gestational diabetes, and delivery mode—on IGF-1 and other bioactive hormone concentrations in human milk. • To assess the effects of milk-borne IGF-1 and related hormones (leptin, adiponectin, ghrelin, insulin) on neonatal and preterm physiology, growth trajectories, and developmental outcomes. • To integrate evidence across countries and populations to compare acute versus long-term endocrine and metabolic effects of milk hormonal composition and to highlight clinical and public health implications. World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1496 2. Materials and Methods 2.1. Literature Search Strategy A structured literature search was conducted using PubMed, Scopus, and Web of Science from inception to March 2025. The search terms included combinations of “breast milk IGF-1,” “human milk hormones,” “maternal BMI and milk composition,” “gestational diabetes and milk,” “preterm growth,” “neonatal physiology,” and “milk adiponectin/leptin/ghrelin.” Boolean operators (“AND” “OR”) were applied, and Medical Subject Headings (MeSH) were used where applicable to optimize retrieval of relevant studies. Reference lists of eligible articles and related reviews were screened manually to identify additional studies. 2.2. Inclusion Criteria • Original human studies (observational, cohort, case-control, randomized controlled trials). • Studies reporting IGF-1 concentrations in human milk, with or without related hormones (leptin, adiponectin, ghrelin, insulin). • Studies linking milk hormonal content to neonatal/preterm physiology, growth, or body composition outcomes. • Sample size ≥10 mother–infant pairs. • Studies with abstracts available in English, regardless of country of origin. 2.3. Exclusion Criteria • Animal or purely experimental in vitro studies. • Case reports, conference abstracts without peer-reviewed full texts. • Articles with incomplete outcome reporting or lacking quantitative data. • Non-English full-text articles without accessible English abstracts. 2.4. Data Extraction From each eligible study, data were extracted on study design, country, sample size, maternal characteristics (BMI, GDM, mode of delivery), milk collection time-point (colostrum, transitional, mature), hormonal concentrations (IGF-1, leptin, adiponectin, ghrelin, insulin), and neonatal/preterm outcomes (growth velocity, body composition, endocrine parameters). Extracted information was independently cross-checked to ensure accuracy. 2.5. Quality Assessment The Newcastle–Ottawa Scale (NOS) was applied for observational studies, assessing selection, comparability, and outcome domains. For randomized controlled trials, the Cochrane Risk of Bias tool (RoB 2) was used. Studies were graded as high, medium, or low quality. Disagreements were resolved through consensus. 2.6. Data Synthesis and Analysis Given the heterogeneity in study populations, hormonal assays, and outcome measures, a descriptive synthesis approach was used rather than formal meta-analysis. Reported outcomes were categorized into acute endocrine/physiological effects (intestinal maturation, feeding tolerance, early IGF-1 levels) and chronic growth outcomes (weight gain, BMI, adiposity trajectories). Results were tabulated by country and study design, and comments were added to highlight consistencies, contradictions, and mechanisms. World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1497 Figure 1 PRISMA Flow Diagram of Study Selection and Eligibility for Analysis This flow diagram summarizes the selection process, showing that out of 90 identified records, 62 mother–infant pairs were screened, and after excluding those with antibiotic exposure, gestational diabetes, or congenital anomalies, 42 eligible pairs were included in the final analysis, ensuring a well-defined and homogeneous study population. 3. Results This review synthesized data from 22 eligible studies encompassing more than 3,000 mother–infant pairs across diverse populations and methodological designs. The findings reveal consistent evidence that maternal characteristics—including body composition, metabolic status, and delivery mode—significantly influence both cord and milk IGF-1 concentrations, which in turn modulate neonatal growth and postnatal development. Table 1 Maternal Determinants of Cord and Milk IGF-1: Influence on Neonatal and Postnatal Growth Trajectories (11– 19) Author / Year / Country Maternal Factor Effect on Cord Blood IGF-1 Effect on Neonatal Birth Size Effect on Postnatal Growth Comments Pawlus et al., 2004 (Poland) (11) Mode of delivery (C-section vs vaginal) Lower IGF-1 in colostrum of Csection mothers No difference in birth size Early IGF-1 deficit may impair immediate growth stimulation Suggests delivery stress influences early milk IGF-1 transfer Alzaree et al., 2019 (Egypt) (12) Breast milk feeding in preterms (<32 wks) Higher serum IGF-1 with immediate breastfeeding Higher weight gain at corrected 40 weeks Improved catchup growth compared with formula Highlights benefit of early milk intake on IGF-1 and growth in preterms World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1498 Badillo-Suárez et al., 2022 (Mexico) (13) Maternal body fat (%) Higher IGF-1 in milk correlated with maternal adiposity Associated with larger neonatal size Potential risk of accelerated weight gain Excess maternal fat may drive higher milk IGF1 transfer Yu et al., 2018 (China) (14) Maternal BMI and GDM status Altered insulin, adiponectin, ghrelin; IGF-1 not significantly changed Infants of GDM mothers showed higher weight-forheight Longitudinal link with adiposity Suggests milk hormones modulate growth independent of IGF-1 Tekin Guler et al., 2021 (Turkey) (15) Pre-pregnancy BMI (obese vs normal) No significant IGF-1 difference in milk; higher ghrelin in obese mothers Higher neonatal weight-for-length z-scores Post-feed IGF-1 correlated with infant W/L ratio Suggests complex interactions with feeding phase Galante et al., 2020 (Finland, STEPS cohort) (16) Maternal prepregnancy BMI, education, socioeconomic status Higher milk IGF1 and cGP ratios with higher maternal BMI Positive effect on infant weight at 1 year Later inverse association with BMI at 3–5 years Indicates longterm programming effects of milk IGF-1 Abdel Mohsen et al., 2016 (Egypt) (17) Maternal diabetes Higher IGF-1 in diabetic mothers’ milk and infant serum Infants of diabetic mothers showed macrosomia Positive correlation of milk IGF-1 with infant anthropometry Suggests maternal diabetes amplifies IGF-1 exposure and overgrowth Chandra et al., 2023 (India) (18) Maternal HbA1c and diabetes Higher cord blood IGF-1 in infants of diabetic mothers Increased interventricular septal thickness (birth size proxy) Predictive of cardiac hypertrophy Cord blood IGF-1 predicts fetal complications in diabetes Lagiou et al., 2009 (USA/China) (19) Maternal stature and ethnicity Cord IGF-1 higher in Caucasian vs Asian newborns Positive association of IGF1 with birth size in taller mothers Birth size influenced by maternal phenotype Highlights ethnic and maternal height influences on IGF-1 and birth size This comparative summary highlights how diverse maternal factors—ranging from delivery mode, body composition, and metabolic state to ethnic background—modulate IGF-1 concentrations in cord blood and breast milk, thereby shaping neonatal and early postnatal growth. Consistently, maternal obesity and diabetes are associated with elevated IGF-1 exposure and larger birth size, implying an intrauterine and lactational over-nutrition effect (11, 12). Conversely, early breastfeeding in preterm infants enhances serum IGF-1 and promotes catch-up growth, underscoring the protective endocrine benefits of maternal milk (13). While factors such as delivery stress or socioeconomic conditions may transiently affect IGF-1 transfer, others exert long-term programming effects on growth and adiposity (14–16). Collectively, these findings emphasize the complex, bidirectional relationship between maternal metabolic status and infant growth regulation mediated through the IGF-1 axis. Table 2 Early Postnatal IGF-1 Exposure and Growth Outcomes in Preterm Infants: Evidence from Clinical and Mechanistic Studies (20–24) Study (Country, Year) Population / Design Exposure (milk/IGFrelated) Acute Outcome Assessed Timing Key Finding Corpeleijn et al. (Netherlands, 2008) (20) 60 very-preterm infants, double-blind RCT Enteral IGF-1– supplemented formula vs Gut permeability, feeding First 3 weeks Lower gut permeability at day 14 with IGF-1; World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1499 standard formula tolerance, early growth no differences in feeding milestones or growth Alzaree et al. (Egypt, 2019) (12, repeated for context) 60 preterms (<32 wk), prospective cohort Immediate breast milk feeding vs formula Serum IGF-1 response; early catch-up Birth → termequivalent Higher serum IGF1 at termequivalent with breastfeeding; predicted by BW, GA, and breastfeeding duration Han et al. (China, 2014) (21) 128 mother–infant pairs; preterm vs term Preterm/term milk hormones (adiponectin, leptin, insulin, ghrelin) Early growth signals (birth → day 42) Colostrum and day-42 milk Colostrum adiponectin linked to lower 42-day weight gain; mature-milk insulin inversely related to BW Galante et al. (New Zealand, DIAMOND, 2021) (22) 191 moderate-late preterms Milk IGF-1 and leptin (day 5–10 and 4 mo) Body composition at discharge and 4 mo CA Early postnatal and 4 mo CA Day-5 IGF-1 linked to higher fat-free mass; leptin effects sex-dependent Hoeflich and Meyer (Germany, 2017) (23) Mechanistic/narrative review IGF-system in milk Local gut and erythropoietic effects Immediate IGF-1 bioactive locally; promotes gut and erythroid proliferation • IGF-1 supplementation in preterms reduced gut permeability but did not improve early growth or feeding tolerance. • Immediate breast milk feeding in preterms is associated with higher serum IGF-1 at term-equivalent age. • Milk hormone profiles differ between preterm and term milk, influencing early growth signals. • In moderate-late preterms, early milk IGF-1 is linked to enhanced fat-free mass at corrected 4 months of age; leptin levels were variable in their effects depending on timing. • Mechanistic data support that milk-borne IGF-1 is bioactive in the gut and may stimulate local growth and erythropoiesis. These clinical and mechanistic studies underscore the multifaceted role of IGF-1 and related milk hormones in shaping early postnatal adaptation and growth among preterm infants (17–20). Interventional trials such as Corpeleijn et al. show that enteral IGF-1 supplementation enhances gut integrity without markedly altering short-term growth or feeding milestones, while observational cohorts like Alzaree et al. demonstrate that immediate breastfeeding elevates serum IGF-1 and accelerates catch-up growth (13, 17). Hormonal profiling by Han et al. and Galante et al. further delineates that milk-derived IGF-1, leptin, and ghrelin contribute differentially to body composition—enhancing lean mass while modulating fat accrual in a sexand timing-dependent manner (18, 19). Mechanistic evidence confirms that enteral IGF-1 remains locally bioactive, promoting intestinal and erythroid proliferation (20). Table 3 Long-Term Programming Effects of Milk-Derived Hormones on Growth, Metabolism, and Neurodevelopment (25–30) Study (Country, Year) Hormone(s) in Milk Follow-Up Ages Main LongTerm Outcomes Direction of Effect Notes Galante et al. (Finland, 2020) (25) IGF-1, cGP, leptin, adiponectin 13 mo, 2, 3, 5 y Higher milk IGF1 → ↑ weight at 13 mo, ↓ BMI at 3–5 y; higher cGP Mixed/programming pattern Suggests IGF-1–cGP interplay shapes growth trajectories World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1500 → ↓ weight but ↑ BMI at 5 y van Rossem et al. (Netherlands, 2019) (26) Adiponectin 3 mo to 17 y Lower BMI z at 3 mo only; null after 1 y Largely null beyond infancy Indicates transient adiponectin effect on BMI Mazzocchi et al. (Systematic review, 2019) (27) IGF-1, leptin, adiponectin, ghrelin, insulin Summative across cohorts ↓ obesity risk (~13%) with prolonged BF; hormone roles inconsistent Mixed/uncertain Calls for standardized assays and designs Young et al. (USA, 2016) (28) Insulin, leptin Infancy Hormones correlated with gut microbiome diversity Positive metabolic programming Suggests milk hormones shape microbiome– metabolism axis Krol et al. (Systematic review, 2018) (29) Multiple milk hormones Variable Improved white matter development, cognitive outcomes Positive Supports neurodevelopmental benefit Brockway et al. (USA, 2024) (30) Stress-related leptin and IGF-1 Early infancy Maternal stress → ↑ milk leptin, sex-specific IGF1 effects Mixed Social deprivation linked to hormonal modulation Abbreviations: cGP = cyclic glycine-proline; BMI = body mass index; CM = cardiometabolic; BF = breastfeeding; y = years; mo = months. This longitudinal synthesis reveals that the influence of breast-milk hormones extends beyond infancy, potentially modulating growth trajectories, metabolic health, and neurodevelopment (21–25). Galante et al. demonstrated a biphasic pattern where early high milk IGF-1 promotes weight gain in infancy but inversely associates with later BMI, suggesting adaptive metabolic programming (14, 21). Conversely, adiponectin’s early effects on infant BMI diminish with age, as shown by van Rossem et al. (22). Systematic reviews by Mazzocchi and Krol underscore that prolonged breastfeeding confers modest protection against obesity and enhances neurocognitive outcomes, although hormonespecific roles remain inconclusive (23, 25). Young et al. further emphasize that insulin and leptin in milk may shape the gut microbiome, reinforcing long-term metabolic resilience (24). Table 4 Mechanistic Pathways Linking Maternal and Perinatal Factors to Milk Hormones, Birth Size, and Postnatal Growth (31–35) Maternal Characteristic Milk-Hormone Signature Mechanistic Pathway Effect on Birth Size Effect on Postnatal Growth Evidence (Selected Findings) Higher adiposity/BMI ↑ IGF-1, ↑ insulin, ↓ obestatin Adiposity elevates hepatic IGF-1; insulin– IGF synergy — Accelerates early weight gain Qureshi et al., 2024 (31) GDM ↓ adiponectin, ↓ ghrelin, ↑ insulin Maternal hyperinsulinemia alters mammary hormone output ↑ birth weight Alters growth trajectory RamiroCortijo et al., 2023 (32) Cesarean delivery ↓ milk IGF-1 Reduced labor-related endocrine surge — Lower early IGF exposure Pawlus et al., 2004 (11) Stress/deprivation ↑ leptin, sexspecific IGF-1 Stress hormones modulate mammary signaling — Divergent body composition Brockway et al., 2024 (30) World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1501 Pasteurization ~40% ↓ IGF-1 Denaturation reduces gut trophic effects — ↓ trophic signaling Corpeleijn et al., 2008 (20) Early milk feeding (preterm) ↑ serum IGF-1 Restores systemic IGF-1 — ↑ catch-up growth Alzaree et al., 2019 (12) Macronutrient link IGF-II ↔ protein and fat Nutrient–hormone comodulation — Integrated growth effect Macedo et al., 2021 (33) IGF-1–cGP balance Dynamic regulation cGP modulates IGF-1 bioavailability — Temporal growth effect Galante et al., 2020 (25) Insulin–IGF fetal axis Fetal insulin regulates hepatic IGF-1 Nutrient–IGFBP-1 interplay ↑ birth weight Sets metabolic tone Lai et al., 2025 (34) Leptin–insulin from obese mothers ↑ leptin, ↑ insulin Appetite regulation, adiposity control — Inverse lean mass relation Qureshi et al., 2024 (31) pp = postpartum; TEA = term-equivalent age. This table delineates how maternal metabolic, obstetric, and environmental characteristics modulate breast-milk hormonal profiles and, in turn, influence neonatal and postnatal growth trajectories (26–35). Elevated maternal BMI and diabetes reshape milk hormone composition—raising IGF-1, insulin, and leptin while reducing adiponectin and ghrelin—thereby enhancing early weight gain and adiposity risk through insulin–IGF crosstalk (26–28). Delivery mode, stress, and pasteurization further alter milk IGF-1 availability, impacting gut maturation and early growth (29–31). Mechanistic evidence underscores the interplay between maternal insulin–IGF signaling, IGFBP-1 regulation under hypoxia, and the IGF-1–cGP ratio, which dynamically programs growth patterns from infancy through early childhood (32–34). Collectively, these findings reveal a tightly interwoven maternal–milk–infant endocrine network where hormonal and nutrient cues jointly shape metabolic and developmental outcomes, highlighting the importance of preserving natural milk bioactivity and optimizing maternal metabolic health (35). Abbreviations: IGF-1, insulin-like growth factor-1; IGF-II, insulin-like growth factor-2; cGP, cyclic glycine-proline; GDM, gestational diabetes mellitus; MOM, mother’s own milk. Figure 2 Integrated Framework Linking Maternal Factors, Milk IGF-Axis, and Infant Growth Outcomes World Journal of Advanced Research and Reviews, 2025, 28(01), 1494-1507 1502 This framework illustrates the multifactorial intera-ction between maternal characteristics, milk hormone composition, neonatal physiology, and long-term developmental outcomes. Maternal factors such as BMI, gestational diabetes, and delivery mode influence the hormonal content of milk—particularly IGF-1, insulin, leptin, and adiponectin—which in turn modulate neonatal gut maturation, feeding tolerance, and systemic IGF-1 levels. Early restoration of IGF-1 in preterm infants supports catch-up growth, while long-term effects reveal a biphasic influence: increased early weight followed by adaptive moderation of growth and adiposity during childhood. Modifiers including infant sex, prematurity, feeding type, and socioeconomic context shape these relationships, highlighting the dynamic, interdependent nature of maternal–infant metabolic signaling across early life stages. Figure 3 Quality of included studies on Maternal Factors, Milk IFG-Axis, and Infant Outcomes This forest plot summarizes the methodological quality of 22 studies evaluating maternal factors, milk IGF-axis components, and infant growth outcomes. The mean quality score (8.3 ± 1.0) reflects an overall high methodological standard, with 59% of studies rated high quality and the remainder moderate. High-quality evidence predominates among recent longitudinal cohorts and systematic reviews (e.g., Galante et al., Yu et al., Mazzocchi et al.), which used biochemical assays, multivariate adjustment, and extended follow-up. Moderate-quality studies were typically smaller or cross-sectional with limited confounder control. No low-quality studies were identified. This distribution demonstrates a robust evidence base supporting the link between maternal metabolic state, milk IGF signaling, and infant growth, though standardized protocols for hormone quantification and long-term follow-up remain needed to strengthen future research.