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Early-Life Nutrition Interventions and Associated Long-Term Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Journal

ADVANCES IN NUTRITION
Volume 12, Issue 2, Pages 461-489

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1093/advances/nmaa107

Keywords

maternal and child nutrition; nutrition intervention; randomized controlled trials; early life; DOHaD; life course; cardiometabolic diseases; noncommunicable diseases; longitudinal studies; cohort studies

Funding

  1. NIH [HD075784]

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Early-life nutrition interventions can have lifelong cardiometabolic benefits, with lower fasting glucose concentration observed in intervention groups compared to control groups. However, there are potential unintended consequences such as higher BMI. Initiating interventions earlier may confer greater benefits. Personalized dietary counseling has shown positive effects on glucose and cholesterol levels, endothelial function, and metabolic syndrome risk reduction.
Early-life nutrition interventions can have lifelong cardiometabolic benefits. Most evidence on this topic is derived from observational studies. We evaluated the association of randomized controlled nutritional trials in early life and long-term cardiometabolic outcomes. Through literature search of PubMed, CABI Global Health, Embase, and Cochrane, with manual reference check and weekly alert from PubMed, we identified 8312 records, and included 53 records from 40 cohorts in 21 countries. The total number of participants was 33,551. Interventions were initiated as early as conception, and the longest until 7 y (except 1 study from infancy to 20 y). The cohorts were followed up for between 3 and 73 y. We identified 7 types of interventions (protein-energy supplements, long-chain PUFAs, single micronutrient, multiple micronutrients, infant and young child feeding, dietary counseling, and other) and 4 categories of cardiometabolic outcomes (biomarkers, cardiovascular, body size and composition, and subclinical/clinical outcomes). Most findings were null. Fasting glucose concentration was 0.04 mmol/L lower (95% CI: -0.05, -0.02 mmol/L; I-2 = 0%) in the intervention groups than in the control groups (15 studies). BMI (kg/m(2)) was 0.20 higher (95% CI: 0.12, 0.28; I-2 = 54%) in the intervention groups than control groups (14 studies). No significant effect was observed for total cholesterol (12 studies) or blood pressure (17 studies). Ongoing and personalized dietary counseling was associated with lower glucose and cholesterol, better endothelial function, and reduced risk of metabolic syndrome. The timing of intervention mattered, with earlier initiation conferring greater benefit (improved lipid profile and marginally lower glucose concentration) based on 2 studies. In sum, glucose concentration was lower following early-life nutrition interventions, but there is a risk of unintended consequences, including higher BMI. Maternal and child nutrition interventions must be evidence-based and tailored to each population to promote long-term cardiometabolic health.

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Reganit, Valeria Regecova, Luis Revilla, Abbas Rezaianzadeh, Robespierre Ribeiro, Elio Riboli, Adrian Richter, Fernando Rigo, Tobias F. Rinke de Wit, Raphael M. Ritti-Dias, Cynthia Robitaille, Fernando Rodriguez-Artalejo, Maria del Cristo Rodriguez-Perez, Laura A. Rodriguez-Villamizar, Ulla Roggenbuck, Rosalba Rojas-Martinez, Dora Romaguera, Elisabetta L. Romeo, Annika Rosengren, Joel G. R. Roy, Adolfo Rubinstein, Jean-Bernard Ruidavets, Blanca Sandra Ruiz-Betancourt, Maria Ruiz-Castell, Iuliia A. Rusakova, Paola Russo, Marcin Rutkowski, Charumathi Sabanayagam, Hamideh Sabbaghi, Harshpal S. Sachdev, Alireza Sadjadi, Ali Reza Safarpour, Sare Safi, Saeid Safiri, Olfa Saidi, Sibel Sakarya, Nader Saki, Benoit Salanave, Eduardo Salazar Martinez, Diego Salmeron, Veikko Salomaa, Jukka T. Salonen, Massimo Salvetti, Jose Sanchez-Abanto, Susana Sans, Diana A. Santos, Ina S. Santos, Lelita C. Santos, Maria Paula Santos, Rute Santos, Jouko L. Saramies, Luis B. Sardinha, Giselle Sarganas, Nizal Sarrafzadegan, Thirunavukkarasu Sathish, Kai-Uwe Saum, Savvas Savva, Norie Sawada, Mariana Sbaraini, Marcia Scazufca, Beatriz D. Schaan, Herman Schargrodsky, Sabine Schipf, Carsten O. Schmidt, Peter Schnohr, Ben Schoettker, Sara Schramm, Constance Schultsz, Aletta E. Schutte, Sylvain Sebert, Aye Aye Sein, Abhijit Sen, Idowu O. Senbanjo, Sadaf G. Sepanlou, Jennifer Servais, Svetlana A. Shalnova, Teresa Shamah-Levy, Morteza Shamshirgaran, Coimbatore Subramaniam Shanthirani, Maryam Sharafkhah, Sanjib K. Sharma, Jonathan E. Shaw, Amaneh Shayanrad, Ali Akbar Shayesteh, Zumin Shi, Kenji Shibuya, Hana Shimizu-Furusawa, Dong Wook Shin, Majid Shirani, Rahman Shiri, Namuna Shrestha, Khairil Si-Ramlee, Alfonso Siani, Rosalynn Siantar, Abla M. Sibai, Caroline Ramos de Moura Silva, Diego Augusto Santos Silva, Mary Simon, Judith Simons, Leon A. Simons, Michael Sjostrom, Jolanta Slowikowska-Hilczer, Przemyslaw Slusarczyk, Liam Smeeth, Hung-Kwan So, Fernanda Cunha Soares, Eugene Sobngwi, Stefan Soderberg, Agustinus Soemantri, Reecha Sofat, Vincenzo Solfrizzi, Mohammad Hossein Somi, Emily Sonestedt, Yi Song, Thorkild I. A. Sorensen, Elin P. Sorgjerd, Maroje Soric, Charles Sossa Jerome, Aicha Soumare, Bente Sparboe-Nilsen, Karen Sparrenberger, Jan A. Staessen, Gregor Starc, Bill Stavreski, Jostein Steene-Johannessen, Peter Stehle, Aryeh D. Stein, George S. Stergiou, Jochanan Stessman, Jutta Stieber, Doris Stoeckl, Tanja Stocks, Jakub Stokwiszewski, Karien Stronks, Maria Wany Strufaldi, Machi Suka, Chien-An Sun, Johan Sundstrom, Yn-Tz Sung, Paibul Suriyawongpaisal, Rody G. Sy, Holly E. Syddall, Rene Charles Sylva, Moyses Szklo, E. Shyong Tai, Mari-Liis Tammesoo, Abdonas Tamosiunas, Eng Joo Tan, Xun Tang, Frank Tanser, Yong Tao, Mohammed Rasoul Tarawneh, Carolina B. Tarqui-Mamani, Anne Taylor, Julie Taylor, William R. Tebar, Grethe S. Tell, Tania Tello, Yih Chung Tham, K. R. Thankappan, Holger Theobald, Xenophon Theodoridis, Lutgarde Thijs, Mikael Thinggaard, Nihal Thomas, Barbara Thorand, Betina H. Thuesen, Erik J. Timmermans, Dwi H. Tjandrarini, Anne Tjonneland, Ulla Toft, Hanna K. Tolonen, Janne S. Tolstrup, Murat Topbas, Roman Topor-Madry, Maria Jose Tormo, Michael J. Tornaritis, Maties Torrent, Laura Torres-Collado, Giota Touloumi, Pierre Traissac, Areti Triantafyllou, Dimitrios Trichopoulos, Antonia Trichopoulou, Oanh T. H. Trinh, Atul Trivedi, Lechaba Tshepo, Shoichiro Tsugane, Azaliia M. Tuliakova, Marshall K. Tulloch-Reid, Fikru Tullu, Tomi-Pekka Tuomainen, Jaakko Tuomilehto, Maria L. Turley, Gilad Twig, Per Tynelius, Christophe Tzourio, Peter Ueda, Eunice Ugel, Hanno Ulmer, Hannu M. T. Uusitalo, Gonzalo Valdivia, Damaskini Valvi, Rob M. van Dam, Bert-Jan van den Born, Johan Van der Heyden, Yvonne T. van der Schouw, Koen Van Herck, Hoang Van Minh, Natasja M. Van Schoor, Irene G. M. van Valkengoed, Elisabeth M. van Zutphen, Dirk Vanderschueren, Diego Vanuzzo, Anette Varbo, Senthil K. Vasan, Tomas Vega, Toomas Veidebaum, Gustavo Velasquez-Melendez, Giovanni Veronesi, W. M. Monique Verschuren, Roosmarijn Verstraeten, Cesar G. Victora, Lucie Viet, Salvador Villalpando, Paolo Vineis, Jesus Vioque, Jyrki K. Virtanen, Sophie Visvikis-Siest, Bharathi Viswanathan, Tiina Vlasoff, Peter Vollenweider, Ari Voutilainen, Alisha N. Wade, Janette Walton, Elvis O. A. Wambiya, Wan Mohamad Wan Bebakar, Wan Nazaimoon Wan Mohamud, Rildo de Souza Wanderley Junior, Ming-Dong Wang, Ningli Wang, Qian Wang, Xiangjun Wang, Ya Xing Wang, Ying-Wei Wang, S. Goya Wannamethee, Nicholas Wareham, Wenbin Wei, Aneta Weres, Bo Werner, Peter H. Whincup, Kurt Widhalm, Indah S. Widyahening, Andrzej Wiecek, Rainford J. Wilks, Johann Willeit, Peter Willeit, Emmanuel A. Williams, Tom Wilsgaard, Bogdan Wojtyniak, Roy A. Wong-McClure, Andrew Wong, Tien Yin Wong, Jean Woo, Mark Woodward, Frederick C. Wu, Shouling Wu, Justyna Wyszynska, Haiquan Xu, Liang Xu, Nor Azwany Yaacob, Weili Yan, Ling Yang, Xiaoguang Yang, Yang Yang, Tabara Yasuharu, Xingwang Ye, Panayiotis K. Yiallouros, Moein Yoosefi, Akihiro Yoshihara, San-Lin You, Novie O. Younger-Coleman, Ahmad Faudzi Yusoff, Ahmad A. Zainuddin, Seyed Rasoul Zakavi, Farhad Zamani, Sabina Zambon, Antonis Zampelas, Maria Elisa Zapata, Ko Ko Zaw, Tomasz Zdrojewski, Kristyna Zejglicova, Tajana Zeljkovic Vrkic, Yi Zeng, Luxia Zhang, Zhen-Yu Zhang, Dong Zhao, Ming-Hui Zhao, Shiqi Zhen, Yingfeng Zheng, Bekbolat Zholdin, Dan Zhu, Marie Zins, Emanuel Zitt, Yanina Zocalo, Nada Zoghlami, Julio Zuniga Cisneros

Summary: Global prevalence of hypertension doubled from 1990 to 2019, with significant improvements in detection, treatment, and control rates. In 2019, 59% of women and 49% of men with hypertension were previously diagnosed, while treatment rates were 47% for women and 38% for men, with control rates at 23% for women and 18% for men. Disparities exist across countries, with some middle-income nations now outperforming high-income countries in hypertension management.

LANCET (2021)

Article Medicine, General & Internal

Association between early child development trajectories and adult cognitive function in a 50-year longitudinal study in Guatemala

Ines Gonzalez Casanova, Ann DiGirolamo, Maria F. Kroker-Lobos, Laura Ochaeta, Manuel Ramirez-Zea, Reynaldo Martorell, Aryeh D. Stein

Summary: This study examined predictors of cognitive development trajectories from 6 months to 7 years, and how these trajectories were associated with adult cognitive function in a birth cohort from Guatemala. The findings revealed three trajectories of cognitive development, with taller mothers, more years of schooling, and higher household socioeconomic scores being associated with higher trajectories. These childhood trajectories were found to predict adult non-verbal intelligence and literacy scores.

BMJ OPEN (2021)

Article Public, Environmental & Occupational Health

Socioeconomic position over the life-course and subjective social status in relation to nutritional status and mental health among Guatemalan adults

Jithin Sam Varghese, Rachel Waford Hall, Ann M. DiGirolamo, Reynaldo Martorell, Manuel Ramirez-Zea, Aryeh D. Stein

Summary: The study found that objective socioeconomic position is associated with subjective social status and health outcomes, with subjective social status independently influencing happiness and psychological distress in middle adulthood. Additionally, the association between objective socioeconomic position and health outcomes is not mediated by subjective social status, suggesting potential independent pathways.

SSM-POPULATION HEALTH (2021)

Article Nutrition & Dietetics

Protein-Energy Supplementation in Early-Life Decreases the Odds of Mental Distress in Later Adulthood in Guatemala

Ann M. DiGirolamo, Jithin Sam Varghese, Maria F. Kroker-Lobos, Monica Mazariegos, Manuel Ramirez-Zea, Reynaldo Martorell, Aryeh D. Stein

Summary: This study found that receiving protein-energy supplementation during the first 1000 days of life in Guatemala is associated with a lower prevalence of mental distress in adulthood. This effect appears to be direct and not mediated by life course variables.

JOURNAL OF NUTRITION (2022)

Review Medicine, General & Internal

Health and development from preconception to 20 years of age and human capital

Robert E. Black, Li Liu, Fernando P. Hartwig, Francisco Villavicencio, Andrea Rodriguez-Martinez, Luis P. Vidaletti, Jamie Perin, Maureen M. Black, Hannah Blencowe, Danzhen You, Lucia Hug, Bruno Masquelier, Simon Cousens, Amber Gove, Tyler Vaivada, Diana Yeung, Jere Behrman, Reynaldo Martorell, Clive Osmond, Aryeh D. Stein, Linda S. Adair, Caroline H. D. Fall, Bernardo Horta, Ana M. B. Menezes, Manuel Ramirez-Zea, Linda M. Richter, George C. Patton, Eran Bendavid, Majid Ezzati, Zulfiqar A. Bhutta, Joy E. Lawn, Cesar G. Victora

Summary: Optimal health and development throughout various stages from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework highlights the major influences that affect human capital during different periods of development, including preconception, childhood, and adolescence. Mortality rates in children and adolescents are important indicators to consider. While the global rate of deaths in individuals younger than 20 has decreased substantially since 2000, an estimated 8.6 million deaths occurred between 28 weeks of gestation and 20 years of age in 2019, with more than half occurring before 28 days of age. The first 1000 days from conception to 2 years of age have a significant impact on human capital development.

LANCET (2022)

Review Medicine, General & Internal

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs

Cesar G. Victora, Fernando P. Hartwig, Luis P. Vidaletti, Reynaldo Martorell, Clive Osmond, Linda M. Richter, Aryeh D. Stein, Aluisio J. D. Barros, Linda S. Adair, Fernando C. Barros, Santosh K. Bhargava, Bernardo L. Horta, Maria F. Kroker-Lobos, Nanette R. Lee, Ana Maria B. Menezes, Joseph Murray, Shane A. Norris, Harshpal S. Sachdev, Alan Stein, Jithin S. Varghese, Zulfiqar A. Bhutta, Robert E. Black

Summary: The survival and nutrition of children and adolescents have significantly improved in the past two decades, but disparities still exist between and within countries. This study analyzes the relationship between the health, nutrition, and cognitive development of children and adolescents and early-life poverty using data from low-income and middle-income countries. Additionally, it shows the long-term impact of early-life poverty on health and human capital. Therefore, implementing comprehensive anti-poverty policies and programs is crucial, especially during the ongoing disruptions caused by COVID-19.

LANCET (2022)

Article Obstetrics & Gynecology

Age at childbirth and change in BMI across the life-course: evidence from the INCAP Longitudinal Study

Monica Mazariegos, Jithin Sam Varghese, Maria F. Kroker-Lobos, Ann M. DiGirolamo, Manuel Ramirez-Zea, Usha Ramakrishnan, Aryeh D. Stein

Summary: According to this study, women who give birth to three or more children during early adulthood tend to gain more weight. However, the association between childbirth and BMI may vary depending on the mother's age.

BMC PREGNANCY AND CHILDBIRTH (2022)

Article Environmental Sciences

Infant Young Child Feeding Practices in an Indian Maternal-Child Birth Cohort in Belagavi, Karnataka

Shweta Khandelwal, Dimple Kondal, Anindita Ray Chakravarti, Soumam Dutta, Bipsa Banerjee, Monica Chaudhry, Kamal Patil, Mallaiah Kenchaveeraiah Swamy, Usha Ramakrishnan, Dorairaj Prabhakaran, Nikhil Tandon, Aryeh D. Stein

Summary: Poor infant young child feeding (IYCF) practices can lead to malnutrition, poor psychosocial development, poor school performance, and lower productivity in later life, perpetuating a vicious cycle. This study examined IYCF practices in a maternal-child birth cohort in Belagavi, Karnataka, India. The findings showed that only 77.9% of infants were breastfed within 1 hour of delivery, and 52.4% were exclusively breastfed at 6 months. At 12 months, while most infants were breastfed (90%), 39% also received formula. Although a majority of infants met the minimum meal frequency (94.4%), only 55% had a minimum acceptable diet. The mean dietary diversity score was 4.7 +/- 1.1. Furthermore, a large proportion of infants did not consume vegetables and/or fruits until 12 months of age (33.8%). The consumption of ultra-processed foods high in trans-fats, sugars, and salt was high (85.8%). Therefore, there is an urgent need for high-quality, sustainable, and scalable interventions to improve IYCF practices and enhance diet diversity and overall nutritional intake among young children in low- and middle-income group settings.

INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH (2022)

Article Nutrition & Dietetics

A 3-Year Longitudinal Study of Effects of Parental Feeding Practices on Child Weight Status: The Childhood Obesity Study in China Mega-Cities

Lu Ma, Na Yan, Zumin Shi, Yixin Ding, Siran He, Zhengqi Tan, Bo Xue, Yating Yan, Cai Zhao, Youfa Wang

Summary: This study examined the associations between parental feeding practices and child weight status, and found that higher concern and lower pressure to eat were associated with increased risk of obesity among children. Control was associated with increased risk of obesity among children with maternal education of college and above.

NUTRIENTS (2022)

Article Health Care Sciences & Services

Conditional wealth to estimate association of wealth mobility with health and human capital in low- and middle-income country cohorts

Jithin Sam Varghese, Clive Osmond, Aryeh D. Stein

Summary: Temporally harmonized asset indices allow the study of changes in relative wealth over time and its association with adult health and human capital. Using conditional measures, specific life stages during which changes in relative wealth are important for adult health in longitudinal studies can be identified.

BMC MEDICAL RESEARCH METHODOLOGY (2022)

Article Anthropology

Early life predictors of body composition trajectories from adolescence to mid-adulthood

Natalia E. Poveda, Linda S. Adair, Reynaldo. Martorell, Shivani A. Patel, Manuel Ramirez-Zea, Aryeh D. Stein

Summary: Rapid increases in adult obesity have been observed in Guatemala. Parental characteristics, early life factors, and a nutrition intervention were found to predict body composition trajectories from adolescence to mid-adulthood. Parents' age and schooling, as well as self's schooling attainment, were significant predictors of adult body composition.

AMERICAN JOURNAL OF HUMAN BIOLOGY (2023)

Review Nutrition & Dietetics

Roles of Diet-Associated Gut Microbial Metabolites on Brain Health: Cell-to-Cell Interactions between Gut Bacteria and the Central Nervous System

Chong-Su Kim

Summary: The gut microbiota plays a crucial role in brain function through the gut-brain axis. This review highlights the effects of gut microbiota-derived dietary metabolites on cell-to-cell interactions in the central nervous system, particularly microglia, astrocytes, and neuronal cells, affecting cognitive function, mood, and behavior. The review also discusses the potential of diet-induced microbial metabolite-based therapies as novel approaches to mental health treatment.

ADVANCES IN NUTRITION (2024)