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Article ; Online: Maternal Mediterranean-Style Diet Adherence during Pregnancy and Metabolomic Signature in Postpartum Plasma: Findings from the Boston Birth Cohort.

Che, Xiaoyu / Hong, Xiumei / Gross, Susan / Pearson, Colleen / Bartell, Tami / Wang, Xiaobin / Wang, Guoying

2024 Volume 154, Issue 3, Page(s) 846–855

Abstract: Background: The health benefits of a Mediterranean-style diet (MSD) are well observed, but the underlying mechanisms are unclear. Metabolomic profiling offers a systematic approach for identifying which metabolic biomarkers and pathways might be ... ...

Abstract	Background: The health benefits of a Mediterranean-style diet (MSD) are well observed, but the underlying mechanisms are unclear. Metabolomic profiling offers a systematic approach for identifying which metabolic biomarkers and pathways might be affected by an MSD. Objectives: This study aimed to identify postpartum plasma metabolites that are associated with MSD adherence during pregnancy and to further test whether these identified metabolites may vary by maternal characteristics. Methods: We analyzed data from 1410 mothers enrolled in the Boston Birth Cohort (BBC). A maternal food frequency questionnaire (FFQ) was administered and epidemiologic information was obtained via an in-person standard questionnaire interview within 24-72 h postpartum. Maternal clinical information was extracted from electronic medical records. A Mediterranean-style diet score (MSDS) was calculated using responses to the FFQ. Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-MS. Linear regression models were used to assess the associations of each metabolite with an MSDS, adjusting for covariates. Results: Among the 380 postpartum plasma metabolites analyzed, 24 were associated with MSDS during pregnancy (false discovery rate < 0.05). Of 24 MSDS-associated metabolites, 19 were lipids [for example, triacylglycerols, phosphatidylcholines (PCs), PC plasmalogen, phosphatidylserine, and phosphatidylethanolamine]; others were amino acids (methionine sulfoxide and threonine), tropane (nor-psi-tropine), vitamin (vitamin A), and nucleotide (adenosine). The association of adenosine and methionine sulfoxide with MSDS differed by race (P-interaction = 0.033) and maternal overweight or obesity status (P-interaction = 0.021), respectively. Conclusions: In the BBC, we identified 24 postpartum plasma metabolites associated with MSDS during pregnancy. The associations of the 2 metabolites varied by maternal race and BMI. This study provides a new insight into dietary effects on health under the skin. More studies are needed to better understand the metabolic pathways underlying the short- and long-term health benefits of an MSD during pregnancy.
MeSH term(s)	Pregnancy ; Female ; Humans ; Birth Cohort ; Diet, Mediterranean ; Postpartum Period ; Adenosine ; Methionine/analogs & derivatives
Chemical Substances	methionine sulfoxide (XN1XVI4B2C) ; Adenosine (K72T3FS567) ; Methionine (AE28F7PNPL)
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1016/j.tjnut.2024.01.022
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Gestational Diabetes Mellitus, Postpartum Lipidomic Signatures, and Subsequent Risk of Type 2 Diabetes: A Lipidome-Wide Association Study.

Wang, Guoying / Buckley, Jessie P / Bartell, Tami R / Hong, Xiumei / Pearson, Colleen / Wang, Xiaobin

Diabetes care

2023 Volume 46, Issue 6, Page(s) 1223–1230

Abstract: Objective: To identify a postpartum lipidomic signature associated with gestational diabetes mellitus (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D).: Research design and methods: This prospective ... ...

Abstract	Objective: To identify a postpartum lipidomic signature associated with gestational diabetes mellitus (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D). Research design and methods: This prospective cohort study enrolled 1,409 women at 24-72 h after delivery of a singleton baby and followed them prospectively at the Boston Medical Center. The lipidome was profiled by liquid chromatography-tandem mass spectrometry. Diagnoses of GDM and incident T2D were extracted from medical records and verified using plasma glucose levels. Results: Mean (SD) age of study women at baseline was 28.5 (6.6) years. A total of 219 (16.4%) women developed incident diabetes over a median follow-up of 11.8 (interquartile range 8.2-14.8) years. We identified 33 postpartum lipid species associated with GDM, including 16 inverse associations (primarily cholesterol esters and phosphatidylcholine plasmalogens), and 17 positive associations (primarily diacyglycerols and triacyglycerols). Of these, four were associated with risk of incident T2D and mediated ∼12% of the progression from GDM to T2D. The identified lipid species modestly improved the predictive performance for incident T2D above classical risk factors when the entire follow-up period was considered. Conclusions: GDM was associated with a wide range of lipid metabolic alterations at early postpartum, among which some lipid species were also associated with incident T2D and mediated the progression from GDM to T2D. The improvements attained by including lipid species in the prediction of T2D provides new insights regarding the early detection and prevention of progression to T2D.
MeSH term(s)	Infant ; Pregnancy ; Female ; Humans ; Adult ; Male ; Diabetes, Gestational ; Diabetes Mellitus, Type 2 ; Lipidomics ; Prospective Studies ; Phosphatidylcholines ; Postpartum Period
Chemical Substances	Phosphatidylcholines
Language	English
Publishing date	2023-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc22-1841
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Article ; Online: Cord Blood Insulin Concentration and Hypertension Among Children and Adolescents Enrolled in a US Racially Diverse Birth Cohort.

Wang, Guoying / Buckley, Jessie P / Bartell, Tami R / Hong, Xiumei / Pearson, Colleen / Wang, Xiaobin

Hypertension (Dallas, Tex. : 1979)

2023 Volume 80, Issue 5, Page(s) 1092–1101

Abstract: Background: Although insulin resistance is closely related to hypertension, the debate continues as to whether insulin resistance is a cause or a consequence of hypertension. This study investigated the associations of cord blood insulin concentration ... ...

Abstract	Background: Although insulin resistance is closely related to hypertension, the debate continues as to whether insulin resistance is a cause or a consequence of hypertension. This study investigated the associations of cord blood insulin concentration with blood pressure (BP) and hypertension in childhood and adolescence. Methods: This study included 951 children enrolled from 1998 to 2012 and followed from birth onwards at the Boston Medical Center, Boston, MA. Cord blood insulin concentration was measured using a sandwich immunoassay. Hypertension in childhood and adolescence was defined based on the 2017 American Academy of Pediatrics Clinical Practice Guidelines. Results: The median (interquartile range) for cord blood insulin concentration was 12.1 (7.2-19.0) µIU/mL. The age range of BP measurements was 3 to 18 years (median, 10.6 years). Cord blood insulin concentration was positively associated with systolic and diastolic BP as well as the risk of hypertension at age 3 to 18 years. Compared with the lowest tertile of cord blood insulin concentration, the top tertile insulin concentration was associated with a 5.18 (95% CI, 1.97-8.39) percentile increase in systolic BP, 4.29 (95% CI, 1.74-6.84) percentile increase in diastolic BP, and 1.62-fold (95% CI, 1.27-2.08) higher risk of hypertension. The association between insulin and hypertension was stronger among children born preterm ( Conclusions: Our results suggest that elevated insulin concentration at birth plays a critical role in the early life origins of hypertension and support the hypothesis implicating insulin resistance in the etiology of hypertension.
MeSH term(s)	Female ; Humans ; Child ; Infant, Newborn ; Adolescent ; Child, Preschool ; Insulin ; Insulin Resistance ; Birth Cohort ; Fetal Blood ; Risk Factors ; Premature Birth ; Hypertension ; Blood Pressure/physiology ; Pediatric Obesity/complications
Chemical Substances	Insulin
Language	English
Publishing date	2023-03-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.122.20347
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Article: Independent and joint association of cord plasma pantothenate and cysteine levels with autism spectrum disorders and other neurodevelopmental disabilities in children born term and preterm.

Raghavan, Ramkripa / Wang, Guoying / Hong, Xiumei / Pearson, Colleen / Xie, Hehuang / Adams, William G / Augustyn, Marilyn / Wang, Xiaobin

Precision nutrition

2023 Volume 2, Issue 2, Page(s) e00036

Abstract: Background: Pantothenate (vitamin B5) is a precursor for coenzyme A (CoA) synthesis, which serves as a cofactor for hundreds of metabolic reactions. Cysteine is an amino acid in the CoA synthesis pathway. To date, research on the combined role of early ... ...

Abstract	Background: Pantothenate (vitamin B5) is a precursor for coenzyme A (CoA) synthesis, which serves as a cofactor for hundreds of metabolic reactions. Cysteine is an amino acid in the CoA synthesis pathway. To date, research on the combined role of early life pantothenate and cysteine levels in childhood neurodevelopmental disabilities is scarce. Objective: To study the association between cord pantothenate and cysteine levels and risk of autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and other developmental disabilities (DD) in children born term and preterm. Methods: The study sample ( Results: Higher cord pantothenate (≥50th percentile Conclusions: In this prospective birth cohort, we showed that higher cord pantothenate individually and in combination with higher cysteine or preterm birth were associated with increased risk of ASD and ADHD. More study is needed to explore this biologically plausible pathway.
Language	English
Publishing date	2023-05-11
Publishing country	Canada
Document type	Journal Article
ISSN	2563-9021
ISSN	2563-9021
DOI	10.1097/PN9.0000000000000036
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Article ; Online: Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort.

Si, Jiahui / Meir, Anat Yaskolka / Hong, Xiumei / Wang, Guoying / Huang, Wanyu / Pearson, Colleen / Adams, William G / Wang, Xiaobin / Liang, Liming

BMC medicine

2023 Volume 21, Issue 1, Page(s) 317

Abstract: Background: Maternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of ... ...

Abstract	Background: Maternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations. Methods: This study included 903 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses. Results: The study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1-18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR] < 0.05). After accounting for the possible interplay of maternal BMI and smoking, 481 CpG sites were discovered for association with maternal BMI. Among them 123 CpGs were associated with childhood OWO, ranging from 42% decrease to 87% increase in OWO risk for each SD increase in DNAm. A total of 14 identified CpG sites showed a significant mediation effect on the maternal BMI-child OWO association (FDR < 0.05), with mediating proportion ranging from 3.99% to 25.21%. Several of these 14 CpGs were mapped to genes in association with energy balance and metabolism (AKAP7) and adulthood metabolic syndrome (CAMK2B). Conclusions: This prospective birth cohort study in a high-risk yet understudied US population found that maternal pre-pregnancy OWO significantly altered DNAm in newborn cord blood and provided suggestive evidence of epigenetic involvement in the intergenerational risk of obesity.
MeSH term(s)	Child ; Pregnancy ; Infant, Newborn ; Infant ; Female ; Humans ; Child, Preschool ; Adolescent ; Pediatric Obesity/epidemiology ; Pediatric Obesity/genetics ; Body Mass Index ; DNA Methylation/genetics ; Birth Cohort ; Epigenome ; Cohort Studies ; Prospective Studies ; Overweight
Language	English
Publishing date	2023-08-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-023-03003-5
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Article ; Online: Umbilical cord DNA methylation is associated with body mass index trajectories from birth to adolescence.

Meir, Anat Yaskolka / Huang, Wanyu / Cao, Tingyi / Hong, Xiumei / Wang, Guoying / Pearson, Colleen / Adams, William G / Wang, Xiaobin / Liang, Liming

EBioMedicine

2023 Volume 91, Page(s) 104550

Abstract: Background: DNA methylation (DNAm) in cord blood has been associated with various prenatal factors and birth outcomes. This study sought to fill an important knowledge gap: the link of cord DNAm with child postnatal growth trajectories from birth to age ...

Abstract	Background: DNA methylation (DNAm) in cord blood has been associated with various prenatal factors and birth outcomes. This study sought to fill an important knowledge gap: the link of cord DNAm with child postnatal growth trajectories from birth to age 18 years (y). Methods: Using data from a US predominantly urban, low-income, multi-ethnic birth cohort (N = 831), we first applied non-parametric methods to identify body-mass-index percentile (BMIPCT) trajectories from birth to age 18 y (the outcome); then, conducted epigenome-wide association study (EWAS) of the outcome, interrogating over 700,000 CpG sites profiled by the Illumina Infinium MethylationEPIC BeadChip. Multivariate linear regression models and likelihood ratio tests (LRT) were applied to examine the DNAm-outcome association in the overall sample and sex strata. Findings: We identified four distinct patterns of BMIPCT trajectories: normal weight (NW), Early overweight or obesity (OWO), Late OWO, and normal to very late OWO. DNAm at CpG18582997 annotated to TPGS1, CpG15241084 of TLR7, and cg24350936 of RAB31 were associated with BMIPCT at birth-to-3 y, 10 y, and 14 y, respectively (LRT FDR < 0.05 for all). Interpretation: In this prospective birth cohort study, we identified 4 distinct and robust patterns of growth trajectories from birth to 18 y, which were associated with variations in cord blood DNAm at genes implicated in inflammation induction pathways. These findings, if further replicated, raise the possibility that these DNAm markers along with early assessment of BMIPCT trajectories may help identify young children at high-risk for obesity later in life. Funding: Detailed in the Acknowledgements section.
MeSH term(s)	Child ; Infant, Newborn ; Pregnancy ; Female ; Humans ; Adolescent ; Child, Preschool ; DNA Methylation ; Body Mass Index ; Epigenesis, Genetic ; Cohort Studies ; Prospective Studies ; Genome-Wide Association Study ; Obesity/genetics ; rab GTP-Binding Proteins/genetics
Chemical Substances	RAB31 protein, human ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2023-04-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104550
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Article: Impact of consuming a Mediterranean-style diet during pregnancy on neurodevelopmental disabilities in offspring: results from the Boston Birth Cohort.

Che, Xiaoyu / Gross, Susan M / Wang, Guoying / Hong, Xiumei / Pearson, Colleen / Bartell, Tami / Wang, Xiaobin

Precision nutrition

2023 Volume 2, Issue 3, Page(s) e00047

Abstract: Background: While consuming a Mediterranean-style diet (MSD) among pregnant women is expected to affect offspring neurodevelopment, the current evidence is limited. This prospective birth cohort study aimed to explore the association of maternal MSD ... ...

Abstract	Background: While consuming a Mediterranean-style diet (MSD) among pregnant women is expected to affect offspring neurodevelopment, the current evidence is limited. This prospective birth cohort study aimed to explore the association of maternal MSD with neurodevelopmental disabilities (NDD) in offspring, especially among children born to mothers with overweight or obesity (OWO) and/or diabetes mellitus (DM) since they have a higher risk for oxidative stress and immune/metabolic disturbances. Methods: We analyzed data from a subgroup of mother-child dyads enrolled in the Boston Birth Cohort. Maternal dietary information ( Results: This study included 3153 mother-child pairs, from which we identified diagnoses of 1362 (43.2%) NDD, including 123 (3.9%) case of autism, 445 (14.1%) ADHD, and 794 (25.2%) other DD. In the overall sample, women with a higher maternal MSDS (per standard deviation increase) were less likely to have offspring with NDD (adjusted odds ratio [OR]: 0.904, 95% confidence interval [CI]: 0.817-1.000; Conclusions: In this prospective birth cohort, a higher maternal MSDS was associated with a lower likelihood of NDD in the offspring. Furthermore, this association of maternal MSDS with offspring NDD was greater in children born to women with OWO/DM. More studies are needed to replicate the findings and further analyze NDD subgroups and explore underlying molecular pathways.
Language	English
Publishing date	2023-07-11
Publishing country	Canada
Document type	Journal Article
ISSN	2563-9021
ISSN	2563-9021
DOI	10.1097/PN9.0000000000000047
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Article ; Online: Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator.

Wang, Guoying / Xu, Richard / Zhang, Boyang / Hong, Xiumei / Bartell, Tami R / Pearson, Colleen / Liang, Liming / Wang, Xiaobin

Clinical epigenetics

2023 Volume 15, Issue 1, Page(s) 59

Abstract: Background: In utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study ... ...

Abstract	Background: In utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero exposure to diabetes was associated with a change in newborn DNA methylation, and whether the identified CpG sites mediate the association between diabetes and preterm birth in a racially diverse birth cohort population. Methods: This study included 954 mother-newborn pairs. Methylation levels in the cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip 850 K array platform. In utero exposure to diabetes was defined by the presence of maternal pregestational or gestational diabetes. Preterm birth was defined as gestational age at birth less than 37 weeks. Linear regression analysis was employed to identify differentially methylated CpG sites. Differentially methylated regions were identified using the DMRcate Package. Results: 126 (13%) newborns were born to mothers with diabetes in pregnancy and 173 (18%) newborns were born preterm, while 41 newborns were born both preterm and to mothers with diabetes in pregnancy. Genomic-wide CpG analysis found that eighteen CpG sites in cord blood were differentially methylated by maternal diabetes status at an FDR threshold of 5%. These significant CpG sites were mapped to 12 known genes, one of which was annotated to gene Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB). Consistently, one of the two identified significant methylated regions overlapped with HLA-DMB. The identified differentially methylated CpG sites mediated the association between diabetes in pregnancy and preterm birth by 61%. Conclusions: In this US birth cohort, we found that maternal diabetes was associated with altered fetal DNA methylation patterns, which substantially explained the link between diabetes and preterm birth.
MeSH term(s)	Humans ; Female ; Pregnancy ; DNA Methylation ; Diabetes Mellitus/genetics ; Diabetes Mellitus/metabolism ; Adult ; Fetal Blood/metabolism ; Diabetes, Gestational ; Premature Birth/metabolism ; Infant, Newborn ; CpG Islands
Language	English
Publishing date	2023-04-07
Publishing country	Germany
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-023-01473-1
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Article ; Online: Plasma Insulin Concentration in Newborns and Children and Age at Menarche.

Wang, Guoying / Radovick, Sally / Buckley, Jessie P / Hauser, Russ / Williams, Paige L / Hong, Xiumei / Pearson, Colleen / Adams, William G / Wang, Xiaobin

Diabetes care

2023 Volume 46, Issue 6, Page(s) 1231–1238

Abstract: Objective: To investigate the association of plasma insulin levels and their trajectories from birth to childhood with the timing of menarche.: Research design and methods: This prospective study included 458 girls recruited at birth between 1998 and ...

Abstract	Objective: To investigate the association of plasma insulin levels and their trajectories from birth to childhood with the timing of menarche. Research design and methods: This prospective study included 458 girls recruited at birth between 1998 and 2011 and followed prospectively at the Boston Medical Center. Plasma nonfasting insulin concentrations were measured at two time points: at birth (cord blood) and in childhood (age 0.5-5 years). Age at menarche was obtained from a pubertal developmental questionnaire or abstracted from electronic medical records. Results: Three hundred six (67%) of the girls had reached menarche. The median (range) age at menarche was 12.4 (9-15) years. Elevated plasma insulin concentrations at birth (n = 391) and in childhood (n = 335) were each associated with an earlier mean age at menarche: approximately 2 months earlier per doubling of insulin concentration (mean shift, -1.95 months, 95% CI, -0.33 to -3.53, and -2.07 months, 95% CI, -0.48 to -3.65, respectively). Girls with overweight or obesity in addition to elevated insulin attained menarche about 11-17 months earlier, on average, than those with normal weight and low insulin. Considering longitudinal trajectories (n = 268), having high insulin levels both at birth and in childhood was associated with a roughly 6 months earlier mean age at menarche (mean shift, -6.25 months, 95% CI, -0.38 to -11.88), compared with having consistently low insulin levels at both time points. Conclusions: Our data showed that elevated insulin concentrations in early life, especially in conjunction with overweight or obesity, contribute to the earlier onset of menarche, suggesting the need for early screening and intervention.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Insulin ; Menarche ; Obesity ; Overweight ; Prospective Studies
Chemical Substances	Insulin
Language	English
Publishing date	2023-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc22-2017
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Article ; Online: Cord Blood Plasma Metabolome-wide Associations With Height From Birth to Adolescence.

Cao, Tingyi / Zhao, Jiaxuan / Hong, Xiumei / Wang, Guoying / Pearson, Colleen / Adams, William G / Hu, Frank B / Wang, Xiaobin / Liang, Liming

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2023 Volume 38, Issue 5, Page(s) 707–718

Abstract: Although the maternal intrauterine metabolic environment has been recognized to have a profound impact on fetal growth and development with lifelong health implications, to our knowledge, there have been few large-scale birth cohort studies linking the ... ...

Abstract	Although the maternal intrauterine metabolic environment has been recognized to have a profound impact on fetal growth and development with lifelong health implications, to our knowledge, there have been few large-scale birth cohort studies linking the cord metabolome (reflecting both the maternal and fetal metabolic state) with postnatal height measurements across the pediatric age range. Using data from the Boston Birth Cohort, an ongoing prospective birth cohort, this study investigated the association of cord plasma metabolites with children's height from birth to adolescence. Height was analyzed as attained height and longitudinal trajectories. Distinctive cord metabolite types were associated with attained height at different developmental windows: triacylglycerols [TAGs], diacylglycerols [DAGs], cholesterol ester [CEs], phospholipids, amino acids [AAs], acylcarnitines [ACs], and nucleotides in early (age 0-4 years) and middle (age 6-12 years) childhood; various metabolite types other than TAGs in later childhood (after age 14 years). Functional principal component analysis on children's repeated height measurements summarized two typical height trajectory components: loadings on first eigenfunction [FPC1] representing overall height by age, and loadings on second eigenfunction [FPC2] representing speed of pubertal height growth. Although only one cord metabolite was correlated with FPC1 after accounting for multiple testing, the study found 27 metabolites with significant overall effect on FPC2 among females and 18 among males. These metabolites were mostly phospholipids (including phosphatidylethanolamines [PEs], phosphatidylethanolamine plasmalogens [PE_Ps], phosphatidylcholines [PCs], lysophosphatidylethanolamines [LPEs], and lysophosphatidylcholines [LPCs]), AAs, and nucleotides. Their associations with height differed between overweight/obesity (OWO) and non-OWO children, especially among females. In this prospective study of US understudied urban, low-income, racially diverse children, we demonstrated that cord plasma metabolites were significantly associated with postnatal attained height at different age windows as well as height trajectories from birth to adolescence. We also revealed how these associations differed by children's sex and OWO status. Our findings help elucidate metabolic pathways underlying fetal origins of height growth across developmental stages. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
MeSH term(s)	Male ; Female ; Humans ; Child ; Adolescent ; Infant, Newborn ; Infant ; Child, Preschool ; Prospective Studies ; Body Mass Index ; Obesity/complications ; Overweight ; Metabolome
Language	English
Publishing date	2023-03-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4790
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