Differential DNA methylation profile in infants born small-for-gestational-age: association with markers of adiposity and insulin resistance from birth to age 24 months

Díaz, Marta; Garde, Edurne; López‐Bermejo, Abel; Zegher, Francis de; Ibáñez, Lourdes

doi:10.1136/bmjdrc-2020-001402

Cited by 15 publications

(8 citation statements)

References 48 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The exact mechanism of the association of SGA with diabetes and cardiovascular disease is unknown, although various hypotheses have been proposed, such as a mis-match between the prenatal and postnatal environments. Fetal nutrition may be poor whereas neonatal nutrition may be better, resulting in low birth weight and subsequent rapid weight gain, which may affect pancreatic function ( 38 ), possibly through epigenetic changes in DNA methylation ( 39 ). Children born SGA are at risk for rapid development of decreased insulin sensitivity compared with those born appropriate for gestational age (AGA), particularly in those who have catch-up growth ( 40 – 43 ).…”

Section: Effect Of Being Born Sga On Growth and Metabolism In Adolescence And Young Adulthoodmentioning

confidence: 99%

New Horizons in Short Children Born Small for Gestational Age

Netchine

Steen²,

López‐Bermejo

et al. 2021

Front. Pediatr.

View full text Add to dashboard Cite

Children born small for gestational age (SGA) comprise a heterogeneous group due to the varied nature of the cause. Approximately 85–90% have catch-up growth within the first 4 postnatal years, while the remainder remain short. In later life, children born SGA have an increased risk to develop metabolic abnormalities, including visceral adiposity, insulin resistance, and cardiovascular problems, and may have impaired pubertal onset and growth. The third “360° European Meeting on Growth and Endocrine Disorders” in Rome, Italy, in February 2018, funded by Merck KGaA, Germany, included a session that examined aspects of short children born SGA, with three presentations followed by a discussion period, on which this report is based. Children born SGA who remain short are eligible for GH treatment, which is an approved indication. GH treatment increases linear growth and can also improve some metabolic abnormalities. After stopping GH at near-adult height, metabolic parameters normalize, but pharmacological effects on lean body mass and fat mass are lost; continued monitoring of body composition and metabolic changes may be necessary. Guidelines have been published on diagnosis and management of children with Silver-Russell syndrome, who comprise a specific group of those born SGA; these children rarely have catch-up growth and GH treatment initiation as early as possible is recommended. Early and moderate pubertal growth spurt can occur in children born SGA, including those with Silver-Russell syndrome, and reduce adult height. Treatments that delay puberty, specifically metformin and gonadotropin releasing hormone analogs in combination with GH, have been proposed, but are used off-label, currently lack replication of data, and require further studies of efficacy and safety.

show abstract

Section: Effect Of Being Born Sga On Growth and Metabolism In Adolescence And Young Adulthoodmentioning

confidence: 99%

New Horizons in Short Children Born Small for Gestational Age

Netchine

Steen²,

López‐Bermejo

et al. 2021

Front. Pediatr.

View full text Add to dashboard Cite

show abstract

“…We recently reported that GPR120 -a key regulator of adipogenesis-is hypermethylated in cord blood of SGA newborns and also in peripheral blood at age 1 year and is associated with lower fat mass at the age of 1 and 2 years. 12,13 Thus, it is tempting to speculate that the increased levels of DBI in SGA infants could be a compensatory mechanism to promote lipogenesis and adipocyte differentiation. Along these lines, it has been reported that DBI knock-down inhibits the ability of murine 3T3-L1 pre-adipocytes to undergo differentiation and to induce key adipogenic transcription factors like PPARγ.…”

Section: Discussionmentioning

confidence: 99%

“…The study cohort was composed of 103 infants [70 AGA (49% girls) and 33 SGA (48% girls)] who were recruited into two previous longitudinal, prospective studies (Supplemental Figure S1, flow chart). Study 1 assessed body composition and endocrine-metabolic variables of SGA vs AGA-breastfed infants in the first 2 years of life 11 ; study 2 assessed DNA methylation of SGA vs AGA infants in placenta and cord blood, as well as at age 12 months, together with endocrinemetabolic and body composition markers 12,13 ; in a subpopulation of infants enrolled in both study 1 and study 2, growth-anddifferentiation factor-15 had also been measured longitudinally. 14 The present study focused on DBI measurement, with the following inclusion criteria: (1) uncomplicated, singleton pregnancy; (2) Caucasian origin; (3) term birth (37-42 weeks) at Hospital Sant Joan de Déu, Barcelona; birth weight between 2.9 and 3.8 kg for AGA (range À 1.1 and + 1.1 SD) and between 1.9 and 2.6 kg for SGA (below À2 SD); (4) exclusive breastfeeding or formula feeding in the first 4 months; (5) spontaneous catch-up in weight and length in SGA subjects, defined as weight and length Z-score > À2.0 by age 1 year 15 ;…”

Section: Study Populationmentioning

confidence: 99%

Circulating diazepam‐binding inhibitor in infancy: Relation to markers of adiposity and metabolic health

et al. 2021

View full text Add to dashboard Cite

Background: Diazepam-binding inhibitor (DBI) controls feeding behaviour and glucose homeostasis. Individuals born small-for-gestational-age (SGA) with excessive postnatal catch-up in weight are at risk for obesity and type 2 diabetes.Objective: To assess serum concentrations of DBI (0-2 years) in appropriate-for-gestational-age (AGA, n = 70) vs SGA infants (n = 33) with spontaneous catch-up and their relationship with endocrine-metabolic and adiposity markers.Methods: Longitudinal assessments included auxology, fasting glucose, insulin, insulin-like growth factor, high-molecular-weight adiponectin, DBI and body composition (absorptiometry). DBI was measured cross-sectionally in pregnant and nonpregnant women and in 2-day-old newborns. DBI mRNA expression levels were assessed in adult and neonatal tissues.Results: Cord blood DBI concentrations were similar in AGA and SGA newborns and about fivefold higher than those in women. Serum DBI levels decreased by age 2 days, were higher in SGA vs AGA infants at age 2 years and associated negatively with markers of adiposity and insulin resistance and positively with high-molecularweight adiponectin. DBI mRNA expression was lower in placenta than in other tissues. Conclusion:The increased DBI concentrations at birth are unrelated to prenatal growth. The higher DBI levels in SGA subjects at age 2 years may be related to catchup growth or represent an adaptive mechanism to promote lipogenesis.

show abstract

“…Current research to establish better ways to determine which infants are pathologically small might help us to prevent perinatal morbidity and mortality [ 22 ]. Recently, genes in SGA infants, which are related to B cell development, metabolism, and obesity, were found to be hypomethylated compared to those in non-SGA infants [ 23 ]. Thus, DNA methylation profiles may prove to be a useful diagnostic tool if epigenetic changes are indeed the key mechanism underlying DoHAD and the pathogenesis behind SGA.…”

Section: Physiologic Mechanisms Linking Low Birth Weight and Adult Diseasementioning

confidence: 99%

Epigenetic Modifications at the Center of the Barker Hypothesis and Their Transgenerational Implications

Ryznar

Phibbs

Winkle

2021

IJERPH

View full text Add to dashboard Cite

Embryo/fetal nutrition and the environment in the reproductive tract influence the subsequent risk of developing adult diseases and disorders, as formulated in the Barker hypothesis. Metabolic syndrome, obesity, heart disease, and hypertension in adulthood have all been linked to unwanted epigenetic programing in embryos and fetuses. Multiple studies support the conclusion that environmental challenges, such as a maternal low-protein diet, can change one-carbon amino acid metabolism and, thus, alter histone and DNA epigenetic modifications. Since histones influence gene expression and the program of embryo development, these epigenetic changes likely contribute to the risk of adult disease onset not just in the directly affected offspring, but for multiple generations to come. In this paper, we hypothesize that the effects of parental nutritional status on fetal epigenetic programming are transgenerational and warrant further investigation. Numerous studies supporting this hypothesis are reviewed, and potential research techniques to study these transgenerational epigenetic effects are offered.

show abstract

Differential DNA methylation profile in infants born small-for-gestational-age: association with markers of adiposity and insulin resistance from birth to age 24 months

Cited by 15 publications

References 48 publications

New Horizons in Short Children Born Small for Gestational Age

New Horizons in Short Children Born Small for Gestational Age

Circulating diazepam‐binding inhibitor in infancy: Relation to markers of adiposity and metabolic health

Epigenetic Modifications at the Center of the Barker Hypothesis and Their Transgenerational Implications

Contact Info

Product

Resources

About