Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow

Abstract

Background: Selective intrauterine fetal growth restriction (sIUGR) in monochorionic diamniotic twins, especially types 2&3 with abnormal umbilical artery Doppler, results in increased risk of fetal/perinatal mortality and postnatal disability. We investigate whether the hair metabolome profiles of neonates were associated with the pathophysiological differences across the different clinical forms of sIUGR in twins. Methods: Hair samples were collected at delivery from 10 pairs of type 1 sIUGR twins, 8 pairs of types 2&3 sIUGR twins, and 11 pairs of twins without sIUGR. The hair metabolome was characterized using gas chromatographymass spectrometry. Results: Our results demonstrated that the hair metabolite profiles of the different sIUGR subclinical forms were associated with the averaged fetal growth rate after 28 weeks of gestation but not with birthweight. The hair profiles were capable of discriminating type2&3 sIUGR twins from twins without sIUGR. In particular, the metabolites 2-aminobutyric acid, cysteine, alanine, and tyrosine all displayed areas under the receiver operating characteristic curve were above 0.9. The metabolic pathway analysis highlighted the associations of sIUGR twins with abnormal umbilical artery flow with increased metabolites from a nutrient depletion pathway, glutathione metabolism, and nerve development. Conclusion: This study offers novel insight into the severity of intrauterine ischemia and hypoxia for T2&3 sIUGR twins, through evaluation of the neonatal hair metabolome.

Critical Factors in Sample Collection and Preparation for Clinical Metabolomics of Underexplored Biological Specimens

“…For this reason, this specimen can be a good alternative for metabolomic studies, providing a broader view of the metabolic profile. Thus, in the last five years, hair samples have been widely used to study pregnancy complications, such as pre-eclampsia [ 127 ], fetal growth restriction [ 128 ], gestational T2DM [ 129 ], and diet restrictions [ 130 ]. Additional clinical investigations include the search for biomarkers in cervical cancer [ 131 ] and Alzheimer’s disease [ 132 , 133 ] and the monitoring of chronic conditions such as androgenetic alopecia [ 134 ] and baldness [ 135 ].…”

“…Metabolite extraction is performed with or without alkaline hydrolysis, using NaOH 4 mol L −1 [ 139 ] or, more frequently, KOH 1 mol L −1 , followed by neutralization with H 2 SO 4 (3 mol L −1 ) [ 127 , 128 , 131 ]. Proteins are usually precipitated by the addition of pure methanol [ 125 , 129 , 134 , 135 ], methanol/phosphate saline buffer (PBS) [ 132 , 133 , 140 ], or methanol/water/acetone (1:1:1, v / v / v ) [ 141 ].…”

Characterization of Hair Metabolome in 5xFAD Mice and Patients with Alzheimer’s Disease Using Mass Spectrometry-Based Metabolomics

“…Hair has emerged as a promising biospecimen for investigating the metabolic perturbations of body burden over extended periods. − The hair matrix provides a retrospective measurement of the metabolome associated with months to even years. − Furthermore, collecting hair samples is less invasive than collecting cerebrospinal fluid, making it more feasible and practical for routine sampling in clinical practices. The noninvasive nature of hair sample collection reduces patient discomfort and allows for easier and more frequent sampling.…”

Identifying Hair Biomarker Candidates for Alzheimer’s Disease Using Three High Resolution Mass Spectrometry-Based Untargeted Metabolomics Strategies

“…Plasma, saliva, and urine have been commonly exploited to discover novel AD biomarkers in HRMS-based untargeted metabolomics studies. − For example, AD patients were differentiated from cognitively normal controls with the five metabolites in plasma, including cholic acid, chenodeoxycholic acid, allocholic acid, indolelactic acid, and tryptophan, with 76.7% sensitivity and 83.3% specificity . However, the chemical compositions of these biological samples are affected by circadian rhythms, daily activities, and even sleep patterns. − Hair has emerged as a potential alternative biospecimen for biomarker discovery in previous studies, as it might reflect the chemical composition in the circulatory system for the previous several months. − For instance, the hair samples have been used to investigate the alternations of metabolite profiles between women with pregnancies complicated by fetal growth restriction and healthy controls . A metabolic panel comprising 5 metabolites, including lactate, levulinate, 2-methyloctadecanate, tyrosine, and margarate, achieved an area under the receiver operating curve of 0.998 .…”