Metallomics (DOI): https://doi.org/10.1093/mtomcs/mfaf031
What the study examined
The UK Pregnancies Better Eating and Activity Trial (UPBEAT) was a randomised controlled trial of a diet and physical activity intervention in pregnant women with obesity, conducted across UK centres between 2009 and 2014. In this 2025 secondary analysis published in Metallomics, Agostinho de Sousa and colleagues used stored mid-gestation serum to characterise the maternal metallome — the full complement of metal and metalloid elements circulating in blood — in 755 participants with a body mass index of 30 kg/m2 or greater.
The objective was descriptive and exploratory: to establish reference concentrations for 18 elements in a high-risk obstetric population that had never before been metallomically profiled, and to test whether individual element concentrations at 15 to 18 weeks of gestation were associated with maternal characteristics (BMI, age, parity, ethnicity, dietary pattern) and with adverse pregnancy outcomes. The authors describe it as the first study to assess the metallomic profile of pregnant women living with obesity.
Methods: measuring the maternal metallome
Serum samples collected at a single mid-gestation timepoint (15+0 to 18+6 weeks) were analysed by inductively coupled plasma quadrupole mass spectrometry (ICP-QMS), operated in Dynamic Reaction Cell and Kinetic Energy Discrimination modes to suppress polyatomic interferences. This allowed simultaneous quantification of eighteen elements: aluminium, boron, barium, calcium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, sodium, phosphorus, rubidium, antimony, selenium, strontium, and zinc.
Associations between each element and maternal or neonatal outcomes were examined using regression models adjusted for potential confounders. Because the design is observational and cross-sectional with respect to element measurement, the analyses identify correlations rather than causal effects. The metal panel spans essential trace elements (iron, zinc, copper, manganese, selenium), electrolyte-scale macrominerals (sodium, potassium, calcium, phosphorus, magnesium), and non-essential or potentially toxic elements (aluminium, antimony, strontium, barium).
Key findings: manganese, phosphorus, and outcome associations
The most striking association involved manganese. Women who went on to experience antepartum haemorrhage after 34 weeks (22 participants, 3.2%) had markedly higher mid-gestation serum manganese (median 8.1 ug/L) than unaffected women (median 4.8 ug/L), corresponding to an odds ratio of 4.62 (95% CI 2.06 to 12.4, P<0.001). Strontium showed a weaker association with the same outcome (OR 1.55, 95% CI 1.11 to 2.17).
Higher maternal phosphorus was associated with admission of the neonate to intensive care (56 neonates, 8.0%; OR 2.83, 95% CI 1.75 to 4.67, P<0.001), while higher magnesium was associated with reduced NICU admission (OR 0.61, 95% CI 0.39 to 0.94).
Several elements tracked with maternal characteristics. Copper rose with increasing BMI (+21.4 ug/L per BMI unit) whereas iron fell (−15.86 ug/L per BMI unit), a divergence consistent with obesity-associated systemic inflammation, which raises the copper-carrying protein ceruloplasmin and lowers circulating iron via hepcidin. Calcium declined with parity, and selenium rose modestly with maternal age. Dietary pattern and ethnicity significantly modified several element concentrations.
Mechanistic interpretation
Metal homeostasis in pregnancy is under active physiological remodelling: plasma volume expansion, altered renal handling, placental transport, and shifting binding-protein concentrations all reshape the circulating metallome. Against that backdrop, obesity introduces a chronic low-grade inflammatory state that perturbs metalloregulation — the coordinated sensing and buffering of metal ions that keeps essential elements within safe, functional ranges (metallostasis).
The copper-up, iron-down pattern with rising BMI is the clearest mechanistic signal in the dataset, mirroring the well-established inflammatory axis in which interleukin-6 drives hepcidin, sequestering iron, while ceruloplasmin (an acute-phase copper protein) increases. The manganese and phosphorus associations are novel and hypothesis-generating: elevated manganese could reflect altered hepatobiliary excretion or transporter expression, and both elements may be markers of an underlying vascular or placental process rather than direct causes of haemorrhage or neonatal compromise. The authors are explicit that mechanism cannot be inferred from this observational design.
Relevance to the metal-microbiome-disease axis
This UPBEAT analysis measured serum metals and pregnancy outcomes only; it did not assay the microbiome, so any link to the gut microbial community is contextual and hypothesis-level, not a finding of the paper. We flag that boundary explicitly to avoid overstating the evidence.
That said, the results sit at one end of a mechanistic pathway of interest to this site. Circulating trace-element status both shapes and is shaped by the gut microbiota: manganese, iron, copper, and zinc are contested resources at the host-microbe interface, governed by nutritional immunity and microbial metal-acquisition systems such as siderophores and broader metallophores. Maternal obesity is independently associated with a shifted, often less diverse gut microbiome, and pregnancy itself reshapes microbial composition. A plausible, testable extension of the metal-microbiome-disease axis is that obesity-driven changes in metal handling and microbiome composition are coupled, jointly contributing to inflammation and adverse obstetric outcomes. Establishing whether the manganese-haemorrhage or phosphorus-NICU signals involve microbial mediation would require studies that measure the metallome and the microbiome in the same cohort — which this one did not.
Limitations and clinical takeaway
The analysis is observational and confined to a single mid-gestation timepoint, so it cannot establish causation, temporal sequence, or whether elevated elements precede or accompany the outcomes. The population is restricted to women with obesity, limiting generalisability, and the number of events for rarer outcomes such as late antepartum haemorrhage is small, widening confidence intervals. Multiple comparisons across 18 elements and several outcomes raise the possibility of chance associations.
Clinically, the value of the study is as a reference map and a signal generator: it provides the first metallomic baseline for pregnant women with obesity and highlights manganese and phosphorus as elements deserving prospective, mechanistically informed investigation before any screening or intervention could be justified.
Key findings
- First metallomic profile of pregnant women with obesity: 18 serum elements measured by ICP-QMS in 755 UPBEAT participants at 15-18 weeks' gestation.
- Elevated mid-gestation manganese was strongly associated with antepartum haemorrhage after 34 weeks (OR 4.62, 95% CI 2.06-12.4; median 8.1 vs 4.8 ug/L).
- Higher maternal phosphorus was associated with neonatal intensive care admission (OR 2.83, 95% CI 1.75-4.67); higher magnesium was protective (OR 0.61).
- Copper increased and iron decreased with rising BMI, consistent with obesity-related inflammation acting through ceruloplasmin and hepcidin.
- Calcium declined with parity and selenium rose with maternal age; diet and ethnicity modified several element concentrations.
- Findings are correlational only; the study did not measure the microbiome, and the authors call for mechanistic follow-up.
Frequently asked questions
What did the UPBEAT metallomic analysis find?
In 755 pregnant women with obesity, mid-gestation serum manganese was strongly associated with late antepartum haemorrhage (OR 4.62) and phosphorus with neonatal intensive care admission (OR 2.83). Copper rose and iron fell with increasing BMI. It is the first metallomic profile of this high-risk population and reports correlations, not causes.
Which metals were measured and how?
Eighteen elements were quantified by inductively coupled plasma quadrupole mass spectrometry (ICP-QMS): aluminium, boron, barium, calcium, cobalt, chromium, copper, iron, potassium, magnesium, manganese, sodium, phosphorus, rubidium, antimony, selenium, strontium, and zinc, from serum collected at 15-18 weeks of gestation.
Does this study prove metals cause pregnancy complications?
No. The analysis is observational and cross-sectional, so it identifies associations rather than causal effects. Elevated manganese or phosphorus may be markers of an underlying process rather than its cause. The authors explicitly call for mechanistic research before any clinical action.
How does this relate to the microbiome?
The UPBEAT analysis did not measure the microbiome, so any microbiome link is context, not a finding. However, trace elements such as manganese, iron and copper are contested at the host-microbe interface via nutritional immunity, and maternal obesity is associated with a shifted gut microbiome. Whether metal and microbiome changes are coupled in obese pregnancy remains an open, testable question.