Hair and cord blood element levels and their relationship with air pollution, dietary intake, gestational diabetes mellitus, and infant neurodevelopment.

BACKGROUND & AIMS: Exposure to a range of elements, air pollution, and specific dietary components in pregnancy has variously been associated with gestational diabetes mellitus (GDM) risk or infant neurodevelopmental problems. We measured a range of pregnancy exposures in maternal hair and/or infant cord serum and tested their relationship to GDM and infant neurodevelopment. METHODS: A total of 843 pregnant women (GDM = 224, Non-GDM = 619) were selected from the Complex Lipids in Mothers and Babies cohort study. Forty-eight elements in hair and cord serum were quantified using inductively coupled plasma-mass spectrometry analysis. Binary logistic regression was used to estimate the associations between hair element concentrations and GDM risk, while multiple linear regression was performed to analyze the relationship between hair/cord serum elements and air pollutants, diet exposures, and Bayley Scales of infant neurodevelopment at 12 months of age. RESULTS: After adjusting for maternal age, BMI, and primiparity, we observed that fourteen elements in maternal hair were associated with a significantly increased risk of GDM, particularly Ta (OR = 9.49, 95% CI: 6.71, 13.42), Re (OR = 5.21, 95% CI: 3.84, 7.07), and Se (OR = 5.37, 95% CI: 3.48, 8.28). In the adjusted linear regression model, three elements (Rb, Er, and Tm) in maternal hair and infant cord serum were negatively associated with Mental Development Index scores. For dietary exposures, elements were positively associated with noodles (Nb), sweetened beverages (Rb), poultry (Cs), oils and condiments (Ca), and other seafood (Gd). In addition, air pollutants PM2.5 (LUR) and PM10 were negatively associated with Ta and Re in maternal hair. CONCLUSIONS: Our findings highlight the potential influence of maternal element exposure on GDM risk and infant neurodevelopment. We identified links between levels of these elements in both maternal hair and infant cord serum related to air pollutants and dietary factors.

The relationship between hair metabolites, air pollution exposure and gestational diabetes mellitus: A longitudinal study from pre-conception to third trimester.

Background: Gestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intolerance with first presentation during pregnancy. Many studies suggest that environmental exposures, including air pollution, contribute to the pathogenesis of GDM. Although hair metabolite profiles have been shown to reflect pollution exposure, few studies have examined the link between environmental exposures, the maternal hair metabolome and GDM. The aim of this study was to investigate the longitudinal relationship (from pre-conception through to the third trimester) between air pollution exposure, the hair metabolome and GDM in a Chinese cohort. Methods: A total of 1020 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) birth cohort were included in our study. Metabolites from maternal hair segments collected pre-conception, and in the first, second, and third trimesters were analysed using gas chromatography-mass spectrometry (GC-MS). Maternal exposure to air pollution was estimated by two methods, namely proximal and land use regression (LUR) models, using air quality data from the air quality monitoring station nearest to the participant's home. Logistic regression and mixed models were applied to investigate associations between the air pollution exposure data and the GDM associated metabolites. Results: Of the 276 hair metabolites identified, the concentrations of fourteen were significantly different between GDM cases and non-GDM controls, including some amino acids and their derivatives, fatty acids, organic acids, and exogenous compounds. Three of the metabolites found in significantly lower concentrations in the hair of women with GDM (2-hydroxybutyric acid, citramalic acid, and myristic acid) were also negatively associated with daily average concentrations of PM2.5, PM10, SO2, NO2, CO and the exposure estimates of PM2.5 and NO2, and positively associated with O3. Conclusions: This study demonstrated that the maternal hair metabolome reflects the longitudinal metabolic changes that occur in response to environmental exposures and the development of GDM.

An Evaluation of Different Digestion Methods for the Quantitation of Inorganic Elements in Human Hair Using ICP-MS.

The inorganic elements have unique properties in biochemical processes in humans. An increasing number of pathologies have been associated with essential element ions, such as lead, mercury, and cadmium. Hair has become an attractive clinical specimen for studying the longitudinal exposure to elements from the external environment. Inductively coupled plasma-mass spectrometry (ICP-MS) coupled with nitric acid (HNO3) digestion is the most common approach for determining inorganic elements from human hair. This study aims to optimize the digestion method for the absolute quantitation of 52 elements using ICP-MS, for a large cohort study in human hair. Five different HNO3 (65%) digestion methods were investigated and evaluated for their internal standard solution stability, reproducibility, element coverage, and standard solution recovery efficiency, namely, room temperature for 24 h (RT), 90°C for 4 h (T90), ultrasonic-assisted digestion (UltraS), programmed digestion of microwave digestion (MicroD), and ordinary microwave oven digestion (O-MicroD). Our results demonstrated that O-MicroD, MicroD, and RT were the best performing digestion methods for coefficient of variation (CV) scores, coverage, and recovery efficiency, respectively. In particular, the O-MicroD method detected multiple elements in a small quantity of hair (3 mg), with minimum nitric acid usage (200 µl) and a short digestion time (30 min). The O-MicroD method had excellent reproducibility, as demonstrated by a continuous thousand injections of hair samples with three internal standards (CV: 103Rh = 3.59%, 115In = 3.61%, and 209Bi = 6.31%). Future studies of the elemental content of hair should carefully select their digestion method to meet the primary purpose of their study.

Plasma nervonic acid levels were negatively associated with attention levels in community-living older adults in New Zealand.

The global population is aging. Preserving function and independence of our aging population is paramount. A key component to maintaining independence is the preservation of cognitive function. Metabolomics can be used to identify biomarkers of cognition before noticeable deterioration. Our study investigated the plasma metabolome of 332 community-living New Zealanders between 65 and 74 years of age, using gas chromatography-mass spectrometry. Six cognitive domains were assessed. Of the 123 metabolites identified using an in-house mass spectral libraries of standards, nervonic acid had a significant, inverse association with the attention domain (P-value = 1.52E- 4; FDR = 0.019), after adjusting for covariates (apolipoprotein E -ε4 genotype, sex, body fat percentage (standardised by sex), age, education, deprivation index, physical activity, metabolic syndrome, polypharmacy, smoking status, and alcohol intake) and multiple testing. Attention is defined as the ability to concentrate on selected aspects of the environment while ignoring other stimuli. This is the first study to identify nervonic acid as a potential biomarker of attention in older adults. Future research should confirm this association in a longitudinal study.

An Investigation of the Relationship Between Dietary Patterns in Early Pregnancy and Maternal/Infant Health Outcomes in a Chinese Cohort.

Background: Studies assessing links between maternal diet and pregnancy outcomes have focused predominantly on individual nutrients or foods. However, nutrients are typically consumed in combinations of foods or beverages (i.e., dietary patterns). Taking into account the diet as a whole appreciates that nutrient absorption and metabolism are influenced by other nutrients and the food matrix. Objective: The aim of this study was to investigate the relationship between dietary pattern consumption in early pregnancy and pregnancy/infant outcomes, including gestational diabetes mellitus, gestational weight gain, preeclampsia, placental weight, gestational age at delivery, small-for-gestational-age, large-for-gestational-age, macrosomia, measures of infant body composition, and scores on two main indices of the Bayley Scales of Infant Development [Mental Development Index (MDI) and the Psychomotor Development Index (PDI)] at 12 months. Design: Our study included 1,437 participants from a mother-infant cohort in Chongqing, China. Maternal diet was assessed using a 96-item food frequency questionnaire at 11-14 weeks gestation. Dietary patterns were constructed using principal component analysis. Multivariate regressions were performed to assess associations between maternal dietary pattern scores and pregnancy and infant outcomes, adjusting for confounders. Results: Two dietary patterns were derived: a pattern high in pasta, sweetened beverages, and oils and condiments (PSO-based dietary pattern) and a pattern high in fish, poultry, and vegetables (FPV-based dietary pattern). Higher scores on the PSO-based dietary pattern were associated with lower infant standardized scores on the PDI of the Bayley Scales of Infant Development, ß (95% confidence interval) = -1.276 (-2.392, -0.160); lower placental weight, ß (95% CI) = -6.413 (-12.352g, -0.473); and higher infant's tricep skinfold thickness at 6 weeks of age. ß (95% CI) = 0.279 (0.033, 0.526). Higher scores on the FPV-based dietary pattern were associated with higher gestational weight gain between visit 1 (11-14 week's gestation) and 3 (32-34 week's gestation). ß (95% CI) = 25.612 (13.255, 37.969). No significant associations were observed between dietary pattern scores and the remaining pregnancy/infant outcomes investigated or MDI scores on the Bayley Scales of Infant Development. This was the first study to investigate the association between dietary patterns in early pregnancy and infant neurocognition in a Chinese cohort.

Dietary patterns and cognitive function in older New Zealand adults: the REACH study.

PURPOSE: The global population is ageing. Evidence show dietary patterns may be associated with cognitive status in older adults. This cross-sectional study investigated associations between dietary patterns and cognitive function in older adults in New Zealand. METHODS: The REACH study (Researching Eating, Activity, and Cognitive Health) included 371 participants (65-74 years, 36% male) living independently in Auckland, New Zealand. Valid and reproducible dietary patterns were derived, using principal component analysis, from dietary data collected by a 109-item validated food frequency questionnaire. Six cognitive domains (global cognition, attention and vigilance, executive function, episodic memory, working memory, and spatial memory) were tested using COMPASS (Computerised Mental Performance Assessment System). Associations between dietary patterns and cognitive scores, adjusted for age, sex, education, physical activity, energy, and Apolipoprotein E-ε4 status were analysed using multiple linear regression analysis. RESULTS: Three dietary patterns explained 18% of dietary intake variation-'Mediterranean style' (comprising: salad vegetables, leafy cruciferous vegetables, other vegetables, avocados and olives, alliums, nuts and seeds, white fish and shellfish, oily fish, and berries); 'Western' (comprising: processed meats, sauces and condiments, cakes, biscuits and puddings, meat pies and chips, and processed fish); and 'Prudent' (comprising: dried legumes, soy-based foods, fresh and frozen legumes, whole grains, and carrots). No associations between any cognitive domain and dietary pattern scores were observed. Global cognitive function was associated with being younger and having a university education. CONCLUSION: In this cohort of community-dwelling, older adults in New Zealand, current dietary patterns were not associated with cognitive function.

Associations between dietary patterns and the metabolic syndrome in older adults in New Zealand: the REACH study.

The metabolic syndrome is common in older adults and may be modified by the diet. The aim of this study was to examine associations between a posteriori dietary patterns and the metabolic syndrome in an older New Zealand population. The REACH study (Researching Eating, Activity, and Cognitive Health) included 366 participants (aged 65-74 years, 36 % male) living independently in Auckland, New Zealand. Dietary data were collected using a 109-item FFQ with demonstrated validity and reproducibility for assessing dietary patterns using principal component analysis. The metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III. Associations between dietary patterns and the metabolic syndrome, adjusted for age, sex, index of multiple deprivation, physical activity, and energy intake were analysed using logistic regression analysis. Three dietary patterns explained 18 % of dietary intake variation - 'Mediterranean style' (salad/leafy cruciferous/other vegetables, avocados/olives, alliums, nuts/seeds, shellfish and white/oily fish, berries), 'prudent' (dried/fresh/frozen legumes, soya-based foods, whole grains and carrots) and 'Western' (processed meat/fish, sauces/condiments, cakes/biscuits/puddings and meat pies/hot chips). No associations were seen between 'Mediterranean style' (OR = 0·75 (95 % CI 0·53, 1·06), P = 0·11) or 'prudent' (OR = 1·17 (95 % CI 0·83, 1·59), P = 0·35) patterns and the metabolic syndrome after co-variate adjustment. The 'Western' pattern was positively associated with the metabolic syndrome (OR = 1·67 (95 % CI 1·08, 2·63), P = 0·02). There was also a small association between an index of multiple deprivation (OR = 1·04 (95 % CI 1·02, 1·06), P < 0·001) and the metabolic syndrome. This cross-sectional study provides further support for a Western dietary pattern being a risk factor for the metabolic syndrome in an older population.

Maternal plasma metabolic markers of neonatal adiposity and associated maternal characteristics: The GUSTO study.

Infant adiposity may be related to later metabolic health. Maternal metabolite profiling reflects both genetic and environmental influences and allows elucidation of metabolic pathways associated with infant adiposity. In this multi-ethnic Asian cohort, we aimed to (i) identify maternal plasma metabolites associated with infant adiposity and other birth outcomes and (ii) investigate the maternal characteristics associated with those metabolites. In 940 mother-offspring pairs, we performed gas chromatography-mass spectrometry and identified 134 metabolites in maternal fasting plasma at 26-28 weeks of gestation. At birth, neonatal triceps and subscapular skinfold thicknesses were measured by trained research personnel, while weight and length measures were abstracted from delivery records. Gestational age was estimated from first-trimester dating ultrasound. Associations were assessed by multivariable linear regression, with p-values corrected using the Benjamini-Hochberg approach. At a false discovery rate of 5%, we observed associations between 28 metabolites and neonatal sum of skinfold thicknesses (13 amino acid-related, 4 non-esterified fatty acids, 6 xenobiotics, and 5 unknown compounds). Few associations were observed with gestational duration, birth weight, or birth length. Maternal ethnicity, pre-pregnancy BMI, and diet quality during pregnancy had the strongest associations with the specific metabolome related to infant adiposity. Further studies are warranted to replicate our findings and to understand the underlying mechanisms.

An analysis of omega-3 fatty acid status in a population of pregnant women with obesity, at higher risk of preterm birth.

An updated Cochrane Review showed that maternal supplementation with omega-3 fatty acids reduced preterm birth, offering a potential strategy for prevention. We hypothesised that pregnant women with obesity, at higher risk of preterm birth, would have low omega-3 fatty acid levels and may benefit from supplementation. Our study measured the omega-3 fatty acid levels of 142 participants from the Healthy Mums and Babies study, Counties Manukau, Auckland, New Zealand. Counties Manukau is a multi-ethnic community with high rates of socio-economic deprivation, obesity, and preterm birth. Red blood cell omega-3 fatty acid levels were measured from samples collected between 120 and 176 weeks' gestation. Contrary to our hypothesis, participants in our study had similar or higher levels of omega-3 fatty acids to those reported in pregnant populations in Australia, Norway, China, and Germany. Our findings emphasise the importance of testing omega-3 fatty acid status before supplementing groups at risk of preterm birth.

Author Correction: Analysis of sequential hair segments reflects changes in the metabolome across the trimesters of pregnancy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Omega-3 fatty acids to prevent preterm birth: Australian pregnant women's preterm birth awareness and intentions to increase omega-3 fatty acid intake.

BACKGROUND: Preterm birth is the leading cause of death in children under five. A recent Cochrane review found a 42% reduction in early preterm birth (< 34 weeks' gestation) and 11% reduction in preterm birth (< 37 weeks' gestation) with omega-3 fatty acid supplementation. To assist in the development of implementation strategies to increase pregnant women's omega-3 fatty acid intake, we assessed the awareness of Australian pregnant women about preterm birth, their nutrition and supplementation behaviours during pregnancy, and intentions to increase omega-3 fatty acid intake. METHODS: A ten-minute survey was conducted online to assess the knowledge, attitudes, behaviours, and intentions of Australian pregnant women across three domains: (1) preterm birth; (2) nutrition and supplementation during pregnancy; and (3) omega-3 fatty acid consumption to prevent preterm birth. Participants were recruited from Survey Sampling International's research panels. RESULTS: Of the 763 women who completed the survey, less than two-thirds had heard of preterm birth. Over 55% of respondents had changed their diet during pregnancy and a prenatal dietary supplement was consumed by 82% of the women surveyed. Respondents' main source of information about preterm birth and nutrition during pregnancy was from a health professional. When asked about their intentions to increase their omega-3 fatty acid intake following a health professional's recommendation, the vast majority of participants indicated they would increase their omega-3 fatty acid intake (90%). When a hypothetical scenario was presented of an omega-3 fatty acid supplement being offered from a health service at no cost, the number of respondents who selected they would increase their intake through supplementation increased from 54 to 79%. CONCLUSIONS: The main information source for women about preterm birth and dietary supplementation recommendations during pregnancy is their health professional. Therefore, informing women about ways to prevent preterm birth, including the role of omega-3 fatty acids, should occur during antenatal visits. The results from our study are useful for clinicians caring for pregnant women and for the next stage of translation of the Cochrane review findings - the design of implementation strategies to increase the intake of omega-3 fatty acids during pregnancy where needed.

Trace biomarkers associated with spontaneous preterm birth from the maternal serum metabolome of asymptomatic nulliparous women - parallel case-control studies from the SCOPE cohort.

Prediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks' gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.

Association between maternal exposure to phthalates and lower language ability in offspring derived from hair metabolome analysis.

The fetus undergoes a crucial period of neurodevelopment in utero. The maternal hair metabolome provides an integrated record of the metabolic state of the mother prior to, and during pregnancy. We investigated whether variation in the maternal hair metabolome was associated with neurodevelopmental differences across infants. Maternal hair samples and infant neurocognitive assessments (using the Bayley III Scales of Infant Development at 24 months) were obtained for 373 infant-mother dyads between 26-28 weeks' gestation from the Growing Up in Singapore Towards Healthy Outcomes cohort. The hair metabolome was analysed using gas chromatography-mass spectrometry. Intensity measurements were obtained for 276 compounds. After controlling for maternal education, ethnicity, and infant sex, associations between metabolites and expressive language skills were detected, but not for receptive language, cognitive or motor skills. The results confirm previous research associating higher levels of phthalates with lower language ability. In addition, scores were positively associated with a cluster of compounds, including adipic acid and medium-chain fatty acids. The data support associations between the maternal hair metabolome and neurodevelopmental processes of the fetus. The association between phthalates and lower language ability highlights a modifiable risk factor that warrants further investigation.

Analysis of sequential hair segments reflects changes in the metabolome across the trimesters of pregnancy.

The hair metabolome has been recognized as a valuable source of information in pregnancy research, as it provides stable metabolite information that could assist with studying biomarkers or metabolic mechanisms of pregnancy and its complications. We tested the hypothesis that hair segments could be used to reflect a metabolite profile containing information from both endogenous and exogenous compounds accumulated during the nine months of pregnancy. Segments of hair samples corresponding to the trimesters were collected from 175 pregnant women in New Zealand. The hair samples were analysed using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. In healthy pregnancies, 56 hair metabolites were significantly different between the first and second trimesters, while 62 metabolites were different between the first and third trimesters (p < 0.05). Additionally, three metabolites in the second trimester hair samples were significantly different between healthy controls and women who delivered small-for-gestational-age infants (p < 0.05), and ten metabolites in third trimester hair were significantly different between healthy controls and women with gestational diabetes mellitus (p < 0.01). The findings from this pilot study provide improved insight into the changes of the hair metabolome during pregnancy, as well as highlight the potential of the maternal hair metabolome to differentiate pregnancy complications from healthy pregnancies.

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms. OBJECTIVE: Investigate the maternal hair metabolome for predictive biomarkers of ICP. METHODS: The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography-mass spectrometry. RESULTS: Of 105 metabolites detected in hair, none were significantly associated with ICP. CONCLUSION: Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

Metabolomic biomarkers and novel dietary factors associated with gestational diabetes in China.

INTRODUCTION: Gestational diabetes mellitus (GDM) is impaired glucose tolerance first recognised during pregnancy; its development is associated with many adverse outcomes. Mechanisms of GDM development are not fully elucidated and few studies have used Chinese participants. OBJECTIVES: The aim of this study was to investigate the maternal metabolome associated with GDM in a Chinese population, and explore the relationship with maternal diet. METHODS: Ninety-three participants were recruited at 26-28 weeks' gestation from Chongqing, China. Maternal urine, serum, and hair metabolomes were analysed using gas and liquid chromatography-mass spectrometry. Dietary intake was assessed using a 96-item food frequency questionnaire. RESULTS: Of the 1064 metabolites identified, 73 were significantly different between cases and controls (P < 0.05), but only 2-aminobutyric acid had both a p- and q-value < 0.05. A "snack-based-dietary-pattern" was associated with an increased likelihood of GDM (odds ratio 2·1; 95% confidence interval 1.1-3.9). The association remained significant after adjustment for calorie intake but not food volume. CONCLUSION: This study provides a comprehensive characterization of the maternal metabolome. The snack-based dietary pattern associated with GDM suggests that timing and frequency of consumption are important factors in the relationship between maternal diet and GDM.

A vegetable, fruit, and white rice dietary pattern during pregnancy is associated with a lower risk of preterm birth and larger birth size in a multiethnic Asian cohort: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.

BACKGROUND: Maternal dietary patterns during pregnancy have been shown to influence infant birth outcomes. However, to our knowledge, only a few studies have examined the associations in Asian populations. OBJECTIVE: We characterized maternal dietary patterns in Asian pregnant women and examined their associations with the risk of preterm birth and offspring birth size. DESIGN: At 26-28 wk of gestation, 24-h recalls and 3-d food diaries were collected from the women in the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort. Dietary patterns were derived from exploratory factor analysis. Gestational age was determined by a dating ultrasound scan in the first trimester, and infant birth anthropometric measurements were obtained from hospital records. Associations were assessed by logistic and linear regressions with adjustment for confounding factors. RESULTS: Three maternal dietary patterns were identified: vegetable, fruit, and white rice (VFR); seafood and noodle (SfN); and pasta, cheese, and processed meat (PCP). Of 923 infants, 7.6% were born preterm, 13.4% were born small for gestational age, and 14.7% were born large for gestational age. A greater adherence to the VFR pattern (per SD increase in VFR score) was associated with a lower risk of preterm births (OR: 0.67; 95% CI: 0.50, 0.91), higher ponderal index (ß: 0.26 kg/m3; 95% CI: 0.06, 0.45 kg/m3), and increased risk of a large-for-gestational-age birth (RR: 1.31; 95% CI: 1.06, 1.62). No associations were observed for the SfN and PCP patterns in relation to birth outcomes. CONCLUSIONS: The VFR pattern is associated with a lower incidence of preterm birth and with larger birth size in an Asian population. The findings related to larger birth size warrant further confirmation in independent studies. This trial was registered at clinicaltrials.gov as NCT01174875.

Early pregnancy metabolite profiling discovers a potential biomarker for the subsequent development of gestational diabetes mellitus.

Current early pregnancy screening tools to identify women at risk of developing gestational diabetes mellitus lack both specificity and sensitivity. As a result, the foetus and mother are often subjected to insult during disease progression, prior to diagnosis and treatment in later pregnancy. Metabolomics is an analytical approach, which allows for appraisal of small molecular mass compounds in a biofluid. The aim of this pilot study was to investigate the relationship between the early gestation serum metabolite profile and the subsequent development of gestational diabetes mellitus in the search for early pregnancy biomarkers and potential metabolic mechanisms. Our nested case-control study analysed maternal serum at 20 weeks' gestation, obtained from the New Zealand cohort of the Screening for Pregnancy Endpoints study. Metabolomic profiling was performed using gas chromatography coupled to mass spectrometry, and metabolites were identified using R software and an in-house mass spectral library. Statistical analysis was performed using SPSS version 21.0. Forty-eight metabolites were identified in the serum samples. Itaconic acid (P = 0.0003), with a false discovery rate of 0.012, was found to be significantly more abundant in women who subsequently developed gestational diabetes mellitus, when compared to controls with uncomplicated pregnancies. The current pilot study found that itaconic acid may have potential as a novel biomarker in early pregnancy to predict the subsequent development of gestational diabetes mellitus. However, the findings from this pilot study require validation with a larger, diverse population before translation into the clinical setting.