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.

Study ID	ST002937
Study Title	Deep Metabolic Phenotyping of Newborn Cord Blood Reveals Maternal-Fetal Interactions and Disease Risk
Study Type	Untargeted MS and Targeted MS
Study 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
Submit Date	2023-08-31
Raw Data Available	Yes
Raw Data File Type(s)	wiff, raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2023-11-10
Release Version	1

Select appropriate tab below to view additional metadata details:

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.

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.