Micronutrient Levels Shift Dramatically Across Pregnancy Trimesters, Chinese Cohort Shows

Pregnancy transforms the maternal body into a sophisticated biological support system, and behind the scenes, the levels of vitamins and trace elements that sustain both mother and developing fetus are in constant flux. A new prospective longitudinal study conducted in Lianyungang, a coastal city in Jiangsu Province, China, has now mapped these shifts with unusual precision, tracking a group of healthy pregnant women from early gestation through the postpartum period and revealing distinct trimester-specific patterns in essential micronutrients. The findings, published in PLOS One, offer preliminary evidence that could help clinicians establish reference intervals tailored to both region and stage of pregnancy.

The research team, led by Lianshuai Zheng and colleagues, recruited 51 healthy pregnant women at 6 to 8 weeks of gestation, confirming early pregnancy through ultrasound visualization of the fetal heart and embryonic bud. Participants were followed prospectively throughout their pregnancies, with pregnancy complications, delivery outcomes, and neonatal health assessed at day 42 after birth. To ensure that the micronutrient data reflected healthy physiology rather than disease-related distortions, the final analysis was restricted to 43 women who completed all assessments and experienced uncomplicated pregnancies with favorable outcomes for both mother and child.

What sets this study apart from much of the existing literature is its longitudinal design combined with high-resolution analytical chemistry. Whole-blood trace elements were quantified using inductively coupled plasma mass spectrometry, or ICP-MS, a technique capable of detecting metals and metalloids at extremely low concentrations with high accuracy. Serum vitamins, meanwhile, were measured with ultra-high-performance liquid chromatography coupled to tandem mass spectrometry, known as UHPLC-MS/MS, which allows precise separation and quantification of individual vitamin species in complex biological matrices. Blood samples were collected at three defined time points: the first trimester at an average of 12.3 weeks of gestation, the second trimester at 25.6 weeks, and the third trimester at 32.7 weeks.

The results revealed a striking choreography of rising and falling concentrations. Copper, calcium, and vitamin D all peaked during the second trimester before declining thereafter. This pattern is physiologically plausible: copper plays a central role in fetal development and maternal iron metabolism, calcium demand surges as fetal skeletal mineralization accelerates, and vitamin D status is closely tied to calcium homeostasis. The mid-pregnancy peak in these three analytes suggests a coordinated biological response to the heightened demands of the second trimester, when fetal growth is rapid and placental transfer of minerals intensifies.

In contrast, iron, zinc, magnesium, and lead reached their lowest concentrations, or nadir, during the second trimester. The dip in iron is consistent with the well-documented hemodilution of pregnancy, in which plasma volume expands faster than red cell mass, effectively diluting circulating iron even as total body iron may be conserved. Zinc and magnesium follow similar trajectories, likely reflecting the same dilutional effect combined with active fetal uptake. The parallel decline in lead is noteworthy, because it suggests that maternal blood lead concentrations may fall as pregnancy progresses, possibly through redistribution into maternal tissues and the fetal compartment, though the study was not designed to test mechanisms directly.

Not every micronutrient followed a peak-and-valley pattern. Manganese and vitamins E and K increased progressively throughout gestation, rising steadily from the first trimester through the third. Vitamin E, a lipid-soluble antioxidant, is known to travel with lipids in the bloodstream, and lipid concentrations naturally rise in pregnancy, which may partly explain the upward trend. Vitamin K is essential for blood coagulation, and the hypercoagulable state of pregnancy, which prepares the body for delivery, could drive increased demand and circulating levels. Manganese serves as a cofactor for numerous enzymes involved in metabolism and antioxidant defense, and its gradual accumulation may reflect both dietary intake and fetal developmental needs.

The B vitamins told a different story. Several members of this water-soluble family showed an overall downward trend across gestation, a pattern that may reflect increasing utilization by the fetus and placenta as well as the expanding maternal blood volume. Vitamin B12, however, remained relatively stable throughout pregnancy, standing out as an exception to the general decline. This stability is clinically relevant because B12 deficiency during pregnancy has been associated with adverse neurodevelopmental outcomes, and a stable baseline suggests that maternal stores or intake were sufficient to maintain circulating levels in this healthy cohort.

The authors emphasize that these findings demonstrate clear trimester-specific changes in maternal micronutrient levels during healthy pregnancy, a point with direct clinical implications. Many laboratories currently interpret micronutrient results in pregnant women using reference intervals derived from non-pregnant populations or from pooled data that do not distinguish between trimesters. If copper, calcium, and vitamin D naturally peak in mid-pregnancy while iron, zinc, and magnesium naturally dip, then applying a single static reference range could misclassify healthy women as deficient or excessive at particular stages of gestation. Trimester-specific reference intervals would allow clinicians to distinguish physiological adaptation from genuine deficiency or toxicity with far greater accuracy.

The regional dimension is equally important. Micronutrient status is shaped by local diet, soil and water composition, supplementation practices, and environmental exposures, all of which vary considerably across geographic areas. Lianyungang, as a coastal city with its own dietary and environmental profile, may not be representative of other regions of China or of other countries. The study’s authors therefore frame their data as preliminary evidence to inform the establishment of region-specific and trimester-specific reference intervals and deficiency thresholds for micronutrients in healthy pregnant women, rather than as universal standards.

Several caveats temper the conclusions. The sample size of 43 women in the final analysis is relatively small, which limits the statistical power to detect subtle changes and to stratify results by factors such as maternal age, parity, diet, or supplementation habits. The cohort was restricted to healthy women with uncomplicated pregnancies, so the trajectories observed here may differ in women with gestational diabetes, hypertensive disorders, anemia, or other complications. Nevertheless, the longitudinal design, the use of state-of-the-art analytical methods, and the careful confirmation of favorable maternal and neonatal outcomes lend credibility to the observed patterns. As the authors note, these longitudinal data provide a foundation upon which larger, multi-center studies can build to refine micronutrient reference standards for pregnancy, ultimately supporting more precise nutritional monitoring and care for expectant mothers worldwide.

Subject of Research: Trimester-specific fluctuations of maternal micronutrients during healthy pregnancy

Article Title: Fluctuations of micronutrients during pregnancy in Lianyungang, Jiangsu, China: A prospective longitudinal cohort study

Article References: Zheng, L., Xu, X., Rong, X., Luo, J., Chen, G., & Zhao, C. (2026). Fluctuations of micronutrients during pregnancy in Lianyungang, Jiangsu, China: A prospective longitudinal cohort study. PLOS One, 21(10), e0360813. https://doi.org/10.1371/journal.pone.0360813

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0360813

Keywords: pregnancy, micronutrients, trace elements, vitamins, longitudinal cohort study, ICP-MS, UHPLC-MS/MS, trimester-specific reference intervals, maternal health, fetal development, PLOS One, Lianyungang