Summary of Study ST002937

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001827. The data can be accessed directly via it's Project DOI: 10.21228/M8JQ6C This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002937
Study TitleDeep Metabolic Phenotyping of Newborn Cord Blood Reveals Maternal-Fetal Interactions and Disease Risk
Study TypeUntargeted MS and Targeted MS
Study SummaryMetabolites are small molecules circulating in the mother, placental, and fetal blood that can have a profound effect on a developing fetus (1, 2). Many metabolites from pregnant mothers cross the placenta to provide energy, structural components, essential nutrients, and signals to the developing fetus (3, 4). Issues with proper transmission of metabolites to the fetus, whether through gestational diabetes, placental insufficiency, or other sources can permanently damage the fetus (5-7). However, quantification of many metabolites entering and exiting the fetus are unknown; associations between microbial metabolites in umbilical cords and disease have not been thoroughly investigated; and there remains a lack of quantifiable metabolic effects of some of the most common medications administered during pregnancy and parturition. Here we identified and quantified many metabolites with a gradient between arterial and venous cord blood; we demonstrated that exogenous metabolites in umbilical cords associate with many health outcomes; and we show that medications can profoundly alter the metabolic milieu of the fetus. We greatly expanded the number of metabolites that demonstrate a gradient between arterial and venous blood, indicating absorption by the fetus, including several essential fatty acids. The microbial metabolites 3-indolepropionic acid, hydroxyhippuric acid and others are associated with many newborn diseases. Lastly, we show that exogenous medications like bupivacaine and betamethasone can have a profound impact on newborn metabolic profile. This study is the most comprehensive study of umbilical cord metabolic and disease associations to date. It reveals important aspects of fetal biology, like the reliance on specific essential fatty acid and taurine. It suggests several interventions in pregnant mothers that may help newborn health, including new fatty acids. This study serves as a valuable reference for investigators wishing to better understand the impact of medications on the developing fetus and neonate.
Institute
Stanford University
DepartmentDepartment of Genetics
LaboratorySnyder Lab
Last NameLancaster
First NameSamuel
Address240 Pasteur Dr, BMI bldg 4400, Stanford California, 94305
Emailslancast@stanford.edu
Phone(612)-600-4033
Submit Date2023-08-31
Raw Data AvailableYes
Raw Data File Type(s)wiff, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-11-10
Release Version1
Samuel Lancaster Samuel Lancaster
https://dx.doi.org/10.21228/M8JQ6C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001827
Project DOI:doi: 10.21228/M8JQ6C
Project Title:Deep Metabolic Phenotyping of Newborn Cord Blood Reveals Maternal-Fetal Interactions and Disease Risk
Project Summary:Metabolites are small molecules circulating in the mother, placental, and fetal blood that can have a profound effect on a developing fetus (1, 2). Many metabolites from pregnant mothers cross the placenta to provide energy, structural components, essential nutrients, and signals to the developing fetus (3, 4). Issues with proper transmission of metabolites to the fetus, whether through gestational diabetes, placental insufficiency, or other sources can permanently damage the fetus (5-7). However, quantification of many metabolites entering and exiting the fetus are unknown; associations between microbial metabolites in umbilical cords and disease have not been thoroughly investigated; and there remains a lack of quantifiable metabolic effects of some of the most common medications administered during pregnancy and parturition. Here we identified and quantified many metabolites with a gradient between arterial and venous cord blood; we demonstrated that exogenous metabolites in umbilical cords associate with many health outcomes; and we show that medications can profoundly alter the metabolic milieu of the fetus. We greatly expanded the number of metabolites that demonstrate a gradient between arterial and venous blood, indicating absorption by the fetus, including several essential fatty acids. The microbial metabolites 3-indolepropionic acid, hydroxyhippuric acid and others are associated with many newborn diseases. Lastly, we show that exogenous medications like bupivacaine and betamethasone can have a profound impact on newborn metabolic profile. This study is the most comprehensive study of umbilical cord metabolic and disease associations to date. It reveals important aspects of fetal biology, like the reliance on specific essential fatty acid and taurine. It suggests several interventions in pregnant mothers that may help newborn health, including new fatty acids. This study serves as a valuable reference for investigators wishing to better understand the impact of medications on the developing fetus and neonate.
Institute:Stanford University
Department:Department of Genetics
Laboratory:Snyder Lab
Last Name:Lancaster
First Name:Samuel
Address:240 Pasteur Dr, BMI bldg 4400, Stanford California, 94305
Email:slancast@stanford.edu
Phone:(612)-600-4033

Subject:

Subject ID:SU003050
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id type
SA31843351A
SA318434211AA
SA31843571AA
SA318436147AA
SA318437264AA
SA318438215AA
SA318439329A
SA318440134AA
SA318441108AA
SA31844257AA
SA318443228A
SA318444101AA
SA318445217A
SA318446139AV
SA318447253AV
SA318448465AV
SA318449471AV
SA318450467AV
SA318451469AV
SA318452141AV
SA318453145AV
SA318454143AV
SA318455463AV
SA318456461AV
SA318457459AV
SA318458159AV
SA318459249AV
SA318460155AV
SA318461251AV
SA318462395AV
SA318463151AV
SA318464256AV
SA318465153AV
SA318466149AV
SA318467475AV
SA318468386AV
SA318469116AV
SA318470118AV
SA318471267AV
SA318472121AV
SA318473114AV
SA318474112AV
SA318475108AV
SA318476272AV
SA318477110AV
SA318478224AV
SA318479265AV
SA318480123AV
SA318481457AV
SA318482134AV
SA318483392AV
SA318484136AV
SA318485132AV
SA318486258AV
SA318487263AV
SA318488389AV
SA318489261AV
SA318490477AV
SA318491473AV
SA318492453AV
SA318493203AV
SA318494201AV
SA318495205AV
SA318496428AV
SA318497407AV
SA318498431AV
SA318499236AV
SA318500435AV
SA318501193AV
SA318502195AV
SA318503197AV
SA318504433AV
SA318505426AV
SA318506424AV
SA318507411AV
SA318508417AV
SA318509226AV
SA318510222AV
SA318511414AV
SA318512419AV
SA318513229AV
SA318514409AV
SA318515211AV
SA318516422AV
SA318517213AV
SA318518403AV
SA318519191AV
SA318520398AV
SA318521170AV
SA318522172AV
SA318523449AV
SA318524174AV
SA318525451AV
SA318526247AV
SA318527455AV
SA318528340AV
SA318529381AV
SA318530167AV
SA318531245AV
SA318532176AV
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Collection:

Collection ID:CO003043
Collection Summary:Plasma was collected from umbilical cords at the Lucile Packard Children’s Hospital Stanford with permission from the Institutional Review Board (IRB #46411). All umbilical cords were collected and sent for clinically-indicated testing to Pathology where blood gas analysis was performed following Stanford protocol. Leftover and discarded samples were obtained for research. Arterial and venous blood were extracted from umbilical cords by heparinized syringe and transferred to low binding tubes.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR003059
Treatment Summary:Samples were centrifuged at 1300g for 10 minutes. Plasma was aliquoted in cryovials and frozen at -80°C.

Sample Preparation:

Sampleprep ID:SP003056
Sampleprep Summary:Metabolites and lipids were extracted in 96-well high throughput fashion using a liquid-liquid biphasic separation with cold methyl tert-butyl ether (MTBE), methanol, and water. To begin, 1 mL MTBE was added to 40 μl of plasma and spiked with 40 μl of deuterated lipid internal standards (Sciex, cat# 5040156, lot# LPISTDKIT-103). The samples were agitated at 4°C for 30 minutes. After the addition of 250 μl cold water, samples were vortexed for 1 minute then centrifuged at 3,800 g for 5 minutes at 4°C. The upper organic phase contained the lipids while the lower aqueous phase contained metabolites with precipitated proteins at the bottom of the tube. For quality control, reference plasma samples (40 μl plasma), as well as controls lacking samples (blanks), were processed in parallel. 1) Metabolites: To further precipitate proteins, 500 μl 1:1:1 acetone: acetonitrile: methanol spiked with 16 labeled metabolite internal standards was added to 300 μl of the aqueous phase and 200 μl of the organic phase and incubated overnight at -20°C. After centrifugation at 3,800 g for 10 min at 4°C, the metabolic extracts were dried down under a stream of nitrogen gas and resuspended in 100 μl 50/50 methanol/water for LC-MS. 2) Complex lipids: 700 µl of the organic phase was dried down under a stream of nitrogen and resolubilized in 200 μl of methanol for storage at -20°C until analysis. The day of the analysis, samples were dried down, resuspended in 300 μl of 10 mM ammonium acetate in 90/10 methanol/toluene, and centrifuged at 3,800 g for 5 min at 4°C.

Combined analysis:

Analysis ID AN004817 AN004818 AN004819 AN004820 AN004821 AN004822
Analysis type MS MS MS MS MS MS
Chromatography type Reversed phase Reversed phase HILIC HILIC None (Direct infusion) None (Direct infusion)
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000 Thermo Vanquish Thermo Vanquish Shimazdu LC-30AD Shimazdu LC-30AD
Column Agilent Zorbax SBaq (50 x 2.1mm x 1.7 um) Agilent Zorbax SBaq (50 x 2.1mm x 1.7 um) Merck SeQuant ZIC-HILIC (100 x 2.1mm,3.5um) Merck SeQuant ZIC-HILIC (100 x 2.1mm,3.5um) None None
MS Type ESI ESI ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap Triple quadrupole Triple quadrupole
MS instrument name Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap Thermo Q Exactive HF hybrid Orbitrap Thermo Q Exactive HF hybrid Orbitrap ABI Sciex 5500 QTrap ABI Sciex 5500 QTrap
Ion Mode POSITIVE NEGATIVE POSITIVE NEGATIVE POSITIVE NEGATIVE
Units Relative Abundance Relative Abundance Relative Abundance Relative Abundance Relative Abundance Relative Abundance

Chromatography:

Chromatography ID:CH003640
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Agilent Zorbax SBaq (50 x 2.1mm x 1.7 um)
Column Temperature:60
Flow Gradient:N/A
Flow Rate:0.6 ml/min
Solvent A:0.06% acetic acid in water
Solvent B:0.06% acetic acid in methanol
Chromatography Type:Reversed phase
  
Chromatography ID:CH003641
Instrument Name:Thermo Vanquish
Column Name:Merck SeQuant ZIC-HILIC (100 x 2.1mm,3.5um)
Column Temperature:40
Flow Gradient:N/A
Flow Rate:0.5 ml/min
Solvent A:10 mM ammonium acetate in 50/50 acetonitrile/water
Solvent B:10 mM ammonium acetate in 95/5 acetonitrile/water
Chromatography Type:HILIC
  
Chromatography ID:CH003642
Instrument Name:Shimazdu LC-30AD
Column Name:None
Column Temperature:20
Flow Gradient:N/A
Flow Rate:0.15 ml/min
Solvent A:9:1 Methanol Toluene with 10 mM ammonium acetate
Solvent B:N/A
Chromatography Type:None (Direct infusion)

MS:

MS ID:MS004563
Analysis ID:AN004817
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Data from each mode were independently analyzed using Progenesis QI software (v2.3) (Nonlinear Dynamics, Durham, NC). Metabolic features from blanks and those that did not show sufficient linearity upon dilution in QC samples (r<0.6) were discarded. Only metabolic features present in >2/3 of the samples were kept for further analysis. Missing values were imputed by drawing from a random distribution of low values in the corresponding sample. Intensity drift was corrected using SERRF. Data quality post-normalization was verified by ensuring clustering of pooled sample replicates on a principal component analysis (PCA) plot.
Ion Mode:POSITIVE
  
MS ID:MS004564
Analysis ID:AN004818
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Data from each mode were independently analyzed using Progenesis QI software (v2.3) (Nonlinear Dynamics, Durham, NC). Metabolic features from blanks and those that did not show sufficient linearity upon dilution in QC samples (r<0.6) were discarded. Only metabolic features present in >2/3 of the samples were kept for further analysis. Missing values were imputed by drawing from a random distribution of low values in the corresponding sample. Intensity drift was corrected using SERRF. Data quality post-normalization was verified by ensuring clustering of pooled sample replicates on a principal component analysis (PCA) plot.
Ion Mode:NEGATIVE
  
MS ID:MS004565
Analysis ID:AN004819
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Data from each mode were independently analyzed using Progenesis QI software (v2.3) (Nonlinear Dynamics, Durham, NC). Metabolic features from blanks and those that did not show sufficient linearity upon dilution in QC samples (r<0.6) were discarded. Only metabolic features present in >2/3 of the samples were kept for further analysis. Missing values were imputed by drawing from a random distribution of low values in the corresponding sample. Intensity drift was corrected using SERRF. Data quality post-normalization was verified by ensuring clustering of pooled sample replicates on a principal component analysis (PCA) plot.
Ion Mode:POSITIVE
  
MS ID:MS004566
Analysis ID:AN004820
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Data from each mode were independently analyzed using Progenesis QI software (v2.3) (Nonlinear Dynamics, Durham, NC). Metabolic features from blanks and those that did not show sufficient linearity upon dilution in QC samples (r<0.6) were discarded. Only metabolic features present in >2/3 of the samples were kept for further analysis. Missing values were imputed by drawing from a random distribution of low values in the corresponding sample. Intensity drift was corrected using SERRF. Data quality post-normalization was verified by ensuring clustering of pooled sample replicates on a principal component analysis (PCA) plot.
Ion Mode:NEGATIVE
  
MS ID:MS004567
Analysis ID:AN004821
Instrument Name:ABI Sciex 5500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Lipidyzer data were reported by the Lipidomics Workflow Manager (LWM, v1.0.5.0) software which calculates concentrations for each detected lipid as average intensity of the analyte MRM relative to the average intensity of the most structurally similar internal standard (IS) MRM multiplied by its concentration. Lipids detected in less than 2/3 of the samples were discarded and missing values were imputed by drawing from a random distribution of low values class-wise in the corresponding sample. Data quality was verified by ensuring clustering of the quality control replicates analyzed on a PCA plot. We detected lipid species belonging to 13 classes (e.g. CE, CER, DAG, FFA, HCER, LCER, DCER, LPE, LPC, PC, PE, SM, TAG) and their abundance were reported as concentrations in nmol/g. The Q1 and Q3 mass provided in the metadata were used to target specific lipid classes. Lipids with the designated Q1 mass, also known as the parent ion, are selected from the first quadrupole. The lipids are then fragmented and sent to the third quadrupole. In the third quadrupole, the desired lipid class is selected based on its Q3 mass.
Ion Mode:POSITIVE
  
MS ID:MS004568
Analysis ID:AN004822
Instrument Name:ABI Sciex 5500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Lipidyzer data were reported by the Lipidomics Workflow Manager (LWM, v1.0.5.0) software which calculates concentrations for each detected lipid as average intensity of the analyte MRM relative to the average intensity of the most structurally similar internal standard (IS) MRM multiplied by its concentration. Lipids detected in less than 2/3 of the samples were discarded and missing values were imputed by drawing from a random distribution of low values class-wise in the corresponding sample. Data quality was verified by ensuring clustering of the quality control replicates analyzed on a PCA plot. We detected lipid species belonging to 13 classes (e.g. CE, CER, DAG, FFA, HCER, LCER, DCER, LPE, LPC, PC, PE, SM, TAG) and their abundance were reported as concentrations in nmol/g. The Q1 and Q3 mass provided in the metadata were used to target specific lipid classes. Lipids with the designated Q1 mass, also known as the parent ion, are selected from the first quadrupole. The lipids are then fragmented and sent to the third quadrupole. In the third quadrupole, the desired lipid class is selected based on its Q3 mass.
Ion Mode:NEGATIVE
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