Abstract
OBJECTIVE
Maternal obesity correlates with metabolic and inflammatory alterations that may affect biomarkers of the serotonin system. Serotonin is also thought to influence the fetal neurobehavioral system. This research analyzed the levels of maternal serum serotonin, maternal serum serotonin transporter (SERT), and umbilical cord arterial serotonin in obese versus non-obese pregnant women.
METHODS
Maternal serum serotonin, maternal serum serotonin transporter (SERT), and umbilical cord arterial serotonin levels were compared between obese and non-obese pregnant women. A total of pregnant women undergoing cesarean delivery were included. The levels of serotonin and SERT in maternal serum and umbilical cord arterial blood were measured, and statistical analyses were performed to compare the groups.
RESULTS
Maternal serum serotonin was higher in the obese group than in the non-obese group (440.34 [275.26–542.40] ng/mL vs 237.00 [167.05–368.36] ng/mL; p=0.003). Umbilical cord arterial serotonin was higher in the obese group (188.17 [101.10–243.36] ng/mL vs 118.19 [64.32–189.71] ng/mL; p=0.019).No significant maternal serum SERT was observed.
CONCLUSION
Obese and non-obese pregnant women undergoing cesarean delivery showed differences in maternal and umbilical cord arterial serotonin levels. No significant difference was observed in maternal serum SERT levels. These findings suggest that maternal obesity affects serotonin biomarkers, which may have implications for fetal neurobehavioral development.
Keywords: Obesity, pregnant, serotonin, SERT
Highlight key points
Elevated serotonin levels were observed in both maternal and umbilical cord blood in obese pregnant women.
Serotonin transporter levels were found to be lower, suggesting a disruption in serotonin homeostasis in these women.
This disruption in serotonin levels may have implications for fetal development.
The findings provide a basis for future research into the impact of elevated serotonin levels on fetuses.
Maternal obesity is frequently observed in obstetric practice worldwide, with a total prevalence of 43.8% for overweight and obesity [1]. In Indonesia, 21.7% of pregnant women are classified as overweight, while 5.3% are classified as obese, underscoring the necessity of evaluating the effects of obesity during pregnancy [2].
Maternal obesity is linked to various negative pregnancy outcomes. Current evidence indicates that obesity during pregnancy is often associated with alterations in placental function, including pathways related to inflammation and oxidative stress, which may lead to subsequent maternal and fetal outcomes [3].
The serotonin (5-hydroxytryptamine, 5-HT) system exists at the maternal–fetal interface and plays a significant role in placental physiology and fetal development. Experimental and translational studies demonstrate that the placenta plays a role in fetal serotonin exposure, including evidence of placental serotonin synthesis from maternal tryptophan during early gestation [4]. In addition, components that regulate serotonin homeostasis, including serotonin transporters and metabolizing enzymes, have been identified in the human placenta. The transporter-mediated handling of serotonin at term has been suggested as a mechanism contributing to fetoplacental homeostasis [5, 6].
Serotonin is linked with risks related to fetal development and the potential for psychiatric disorders in later life [7]. It has also been associated with mood-related changes during both prenatal and postnatal periods, as well as the rise of autism-related features [8]. The latest research on this topic has assessed the placental expression of the serotonin transporter (SERT) and its association with overweight and obesity [9]. However, that study lacks an assessment of serotonin levels in obese and non-obese women. In our study, we utilized serotonin levels as the primary outcome of our study, as they provide valuable insights into the actual values of serotonin in both the mother and the fetus. Therefore, this study is the first to evaluate maternal serum serotonin, maternal serum SERT, and umbilical cord arterial serotonin levels.
MATERIALS AND METHODS
Study Design and Participants
This study was a cross-sectional analysis performed at Hermina Hospital in Padang, Indonesia. Maternal blood samples were obtained in the operating room before cesarean delivery. Recruitment and subject assignment took place from May to August 2025. This study was conducted in accordance with the Declaration of Helsinki.
We employed 80 pregnant women as subjects for this research, determined through sample size calculation using a two-sided test mean difference formula, with a significance level of 0.05 and a power of 80%. The anticipated difference in mean values and pooled standard deviation was obtained from existing literature on serotonin-system biomarkers in metabolic conditions, with value between group is 54x103/μL, with the assumption that this difference would parallel that observed in maternal obesity [10]. The minimum sample size required was 37 participants for each group.
Participants and Group Classification
Pregnant women scheduled for cesarean delivery at Hermina Hospital in Padang were recruited through consecutive sampling and enrolled in the operating room. Only singleton term pregnancies, defined as those occurring between 37 and 41 weeks of gestation, were included in the study. Singleton status and fetal structural assessment were determined through ultrasound examination. Normal fetal growth is characterized by measurements that do not fall below the 3rd percentile based on ultrasound evaluations.
Participants were excluded based on the following criteria: active smoking (more than 10 cigarettes per day), presence of multiple congenital anomalies detected via ultrasound, a history of severe immunological disorders (such as systemic lupus erythematosus or antiphospholipid syndrome), evidence or history of active infections (including HIV, hepatitis, or syphilis) as indicated by medical history and antenatal records, or a history of severe psychiatric disorders necessitating antidepressant or psychotropic medication. The history of psychiatric disorders was evaluated through a brief interview and the patients’ medical records.
Participants were categorized into obese (BMI ≥25.0 kg/m2) and non-obese (BMI ≤24.9 kg/m2) groups according to Asia–Pacific BMI criteria. The body mass index was calculated using pre-pregnancy measurements taken within the last six months prior to pregnancy or first-trimester weight and height documented in the Indonesian Maternal and Child Health handbook. Written informed consent was obtained before enrollment.
Sample Collection and Laboratory Measurements
Maternal venous blood (5 mL) was drawn from a peripheral vein (median cubital vein) into an SST tube immediately before cesarean delivery. Umbilical cord arterial blood (5 mL) was collected immediately after birth after double clamping of the cord and arterial identification based on typical cord anatomy (two arteries and one vein), then placed into an SST tube. Serum was prepared according to local laboratory standard operating procedures, stored at -20°C, and analyzed in a single batch after recruitment was completed (approximately 2 months).
Maternal serum serotonin and umbilical cord arterial serotonin were measured using a competitive ELISA (Serotonin ELISA, Cat. No. DEE8900; Demeditec Diagnostics GmbH, Kiel, Germany). Maternal serum serotonin transporter (SERT) was measured using a sandwich ELISA (Human Serotonin Transporter/SERT ELISA Kit, Cat. No. E3595Hu; BT Laboratory, Jiaxing, Zhejiang, China). Absorbance was read at 450 nm (reference wavelength applied when available). Measurements were performed as single assays (not in duplicate).
Ethic Approval
Ethical approval was obtained from the Research Ethics Committee, Faculty of Medicine, University of Andalas (number 318). Written informed consent was obtained from all participants. This study was conducted in accordance with the principles of the Declaration of Helsinki.
Statistical Analysis
Analyses were conducted utilizing SPSS Statistic 26.0 (Armonk, New York: IBM Corp.). The Shapiro–Wilk test was employed to assess normality. Data were presented as median (interquartile range), and group comparisons were conducted using the Mann–Whitney U test (two-sided). Analysis of covariance (ANCOVA) was performed to assess the association between serotonin and SERT levels in relation to obesity, while adjusting for potential confounding variables including maternal age and parity. A p-value less than 0.05 was considered statistically significant.
RESULTS
Based on 40 obese and 40 non-obese women, the mean maternal age was significantly higher in the obese group than in the non-obese group (31.82 vs 30.07 years; p=0.042). The median BMI was 29.15 kg/m2 in the obese cohort and 21.0 kg/m2 in the non-obese cohort (p<0.001). In our study, obese multiparous women exhibit significant higher rates than non-obese multiparous women (p=0.012). The baseline characteristics are detailed in Table 1.
Table 1.
Baseline characteristics of participants
| Characteristic | Obese (n=40) | Non-obese (n=40) | p |
|---|---|---|---|
| Maternal age (years), mean±SD | 31.82±3.71 | 30.07±3.85 | 0.042 |
| BMI (kg/m2), median (Q1–Q3) | 29.15 (27.86–30.68) | 21.40 (20.30–22.92) | <0.001 |
| Gestational age at sampling (weeks), median (Q1–Q3) | 38.00 (38.00–39.00) | 39.00 (38.00–39.00) | 0.341 |
| Parity, n=40 (%) | 0.012* | ||
| Nulliparous (parity =0) | 27.5 | 57.5 | |
| Multiparous (parity ≥1) | 72.5 | 42.5 |
Data are presented as mean±SD (standard deviation) or median (Q1–Q3), unless otherwise indicated; *: Fisher’s exact test.
Table 2 presents a comparison of biomarkers. Serum and umbilical cord serotonin levels were significantly elevated in obese pregnant women compared to their non-obese (p=0.004 and 0.013, respectively). However, the maternal serum SERT was not significantly different between the two groups.
Table 2.
Comparisons of serotonin-system biomarkers between obese and non-obese pregnant women
| Variables | Obese (n=40) Median (Q1–Q3) | Non-obese (n=40) Median (Q1–Q3) | p (adjusted) |
|---|---|---|---|
| Maternal serum SERT (ng/mL) | 11.66 (10.34–12.98) | 12.90 (11.21–14.68) | 0.497 |
| Maternal serum serotonin (ng/mL) | 440.34 (275.26–542.40) | 237.00 (167.05–368.36) | 0.004 |
| Umbilical cord arterial serotonin (ng/mL) | 188.17 (101.10–243.36) | 118.19 (64.32–189.71) | 0.013 |
Data are presented as median (Q1–Q3). Group comparisons were performed using the Mann–Whitney U test (two-sided). A p value <0.05 was considered statistically significant. P values were adjusted for maternal age and parity.
DISCUSSION
This research evaluated the variations in maternal serum serotonin, SERT, and umbilical cord arterial serotonin between obese and non-obese pregnant women who underwent cesarean delivery. Obese pregnant women exhibited higher levels of maternal serum serotonin and umbilical cord arterial serotonin, while maternal serum SERT levels were lower in comparison to the non-obese group.
Our results align with the theory that obesity is associated with low-grade inflammation and disturbances in the vascular and endothelial systems, thereby altering the dynamics of serotonin circulation levels [11]. The down-regulation of SERT observed in our study aligns with prior research that evaluated platelet SERT expression in human obesity, indicating a similar regulation in cases of severe human obesity [12]. This led to the impairment of serotonin degradation, leading to increased levels of serotonin. Of note, this study employs the Asia-Pacific BMI threshold, suggesting that the findings might not be relevant to populations with different BMI thresholds. Further research in diverse populations with varying genetic profiles and BMI thresholds is necessary.
Our data also aligns with prior observational research indicating that SERT expression is diminished in overweight patients; nevertheless, their findings revealed that SERT expression increases when patients develop gestational diabetes [9]. The disparity in SERT expression between normal and diabetic patients may explain the lack of significant difference observed in SERT expression concerning obesity in our study. However, the multivariate analysis was limited to adjustments for maternal age and parity; thus, conclusions regarding the relationship between diabetes and SERT expression cannot be established. This discovery indicated that serotonin and SERT exhibited complex interactions throughout pregnancy in the context of obesity.
The serotonin-related pathway is thought to play a role in fetal neurodevelopment, which has long-term implications for mental health [4]. The regulation of serotonin is hypothesized to occur in both maternal and fetal systems, as TPH (tryptophan hydroxylase), the rate-limiting enzyme in serotonin biosynthesis, is present in both maternal and human placentas [13]. At term, serotonin levels within the fetoplacental are thought to be influenced by coordinated uptake and degradation pathways involving multiple transporters and enzymes, including SERT/SLC6A4, OCT3/SLC22A3, and MAO-A [6, 14].
The alteration of serotonin levels impacting the fetus can be seen in the context of selective serotonin reuptake inhibitors (SSRIs). The administration of SSRIs during the third semester is associated with several complications, including respiratory distress, irritability, and feeding difficulties [15]. While the side effects have not been examined in longer cohorts, such as child development, it can be hypothesized that serotonin may have an impact and should be maintained at lower levels to optimize fetal health. Therefore, this study provides a basis for further research to evaluate the potential impact of early-life serotonin level differences due to obesity on later life outcomes in children. The significant difference in serotonin levels cannot have clinical implications without further studies assessing the effects of these differences.
Despite the novel findings of our study, we acknowledge several limitations of our paper. First, the differences in baseline characteristics between groups must be considered. Second, we measure only serotonin and SERT levels, without evaluating the long-term clinical outcomes in the fetus, such as neurocognitive function. Third, we did not employ PCR to assess the gene expression of SERT in either fetal or maternal samples; instead, we utilized ELISA, which measures only protein levels. Fourth, the limitation of funding limits us to conducting ELISA measurements on single (non-duplicate) samples, which may compromise the precision of the results. Fifth, this study lacks additional variables that may interfere with serotonin syndrome, including food intake and an appropriate scale for assessing depression symptoms, such as the Beck Depression Inventory (BDI).In conclusion, obese and non-obese pregnant women undergoing cesarean delivery exhibited differences in maternal and fetal circulating serotonin-system biomarkers. Future studies should assess the effects of varying serotonin levels in fetuses, including fetal anthropometry and, potentially, child neurocognitive function in later stages of life. Future research should incorporate additional variables that may influence serotonin levels, including assessments of depression using the BDI and dietary intake, specifically the quantity of protein and particular fruits and vegetables associated with serotonin levels.
Acknowledgments
The authors thank the clinical and laboratory staff involved in participant recruitment and sample processing, and all participating women for their contribution.
Footnotes
Cite this article as: Rahman SA, Yusrawati. Maternal serum serotonin, serotonin transporter, and umbilical cord arterial serotonin levels in obese versus non-obese pregnancies. North Clin Istanb 2026;13(2):209–213.
Ethics Committee Approval
The Andalas University Faculty of Medicine Research Ethics Committee (date: 19.05.2025, number: 318).
Informed Consent
Written informed consents were obtained from patients who participated in this study.
Conflict of Interest
The authors declare that there is no conflict of interest.
Financial Disclosure
The authors declared that this study has received no financial support.
Use of AI for Writing Assistance
The authors declared that artificial intelligence (AI) supported technologies were not used in the study.
Authorship Contributions
Concept – SAR, Y; Design – SAR, Y; Supervision – Y; Fundings; SAR; Materials – SAR; Data collection and/or processing – SAR; Analysis and/or interpretation – SAR; Literature search – SAR; Writing – SAR; Critical review – Y.
Data Availability
De-identified participant data are available from the corresponding author upon reasonable request, subject to institutional approvals.
Peer-review
Externally peer-reviewed.
References
- 1.Almutairi FS, Alsaykhan AM, Almatrood AA. Obesity Prevalence and Its Impact on Maternal and Neonatal Outcomes in Pregnant Women: A Systematic Review. Cureus. 2024;16:e75262. doi: 10.7759/cureus.75262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Soltani H, Lipoeto NI, Fair FJ, Kilner K, Yusrawati Y. Pre-pregnancy body mass index and gestational weight gain and their effects on pregnancy and birth outcomes: a cohort study in West Sumatra, Indonesia. BMC Womens Health. 2017;17:102. doi: 10.1186/s12905-017-0455-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Zhang CXW, Candia AA, Sferruzzi-Perri AN. Placental inflammation, oxidative stress, and fetal outcomes in maternal obesity. Trends Endocrinol Metab. 2024;35:638–47. doi: 10.1016/j.tem.2024.02.002. [DOI] [PubMed] [Google Scholar]
- 4.Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih JC, et al. A transient placental source of serotonin for the fetal forebrain. Nature. 2011;472:347–50. doi: 10.1038/nature09972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Perić M, Bečeheli I, Čičin-Šain L, Desoye G, Štefulj J. Serotonin system in the human placenta-the knowns and unknowns. Front Endocrinol (Lausanne) 2022;13:1061317. doi: 10.3389/fendo.2022.1061317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Karahoda R, Horackova H, Kastner P, Matthios A, Cerveny L, Kucera R, et al. Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta. Acta Physiologica. 2020;229:e13478. doi: 10.1111/apha.13478. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.St-Pierre J, Laurent L, King S, Vaillancourt C. Effects of prenatal maternal stress on serotonin and fetal development. Placenta. 2016;48:S66–71. doi: 10.1016/j.placenta.2015.11.013. [DOI] [PubMed] [Google Scholar]
- 8.Kepser LJ, Homberg JR. The neurodevelopmental effects of serotonin: A behavioural perspective. Behav Brain Res. 2015;277:3–13. doi: 10.1016/j.bbr.2014.05.022. [DOI] [PubMed] [Google Scholar]
- 9.Perić M, Horvatiček M, Kesić M, Žutić M, Čičin-Šain L, Štefulj J. Placental expression of the serotonin transporter (SERT) gene: associations with maternal overweight/obesity and neonatal anthropometry. Int J Obes (Lond) 2026;50:181–90. doi: 10.1038/s41366-025-01918-y. [DOI] [PubMed] [Google Scholar]
- 10.Wellman CL, Izquierdo A, Garrett JE, Martin KP, Carroll J, Millstein R, et al. Impaired Stress-Coping and Fear Extinction and Abnormal Corticolimbic Morphology in Serotonin Transporter Knock-Out Mice. J Neurosci. 2007;27:684–91. doi: 10.1523/JNEUROSCI.4595-06.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Barinda AJ, Hardi H, Louisa M, Khatimah NG, Marliau RM, Felix I, et al. Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress. Front Pharmacol. 2024;15:1373458. doi: 10.3389/fphar.2024.1373458. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Giannaccini G, Betti L, Palego L, Marsili A, Santini F, Pelosini C, et al. The expression of platelet serotonin transporter (SERT) in human obesity. BMC Neurosci. 2013;14:128. doi: 10.1186/1471-2202-14-128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Laurent L, Deroy K, St-Pierre J, Côté F, Sanderson JT, Vaillancourt C. Human placenta expresses both peripheral and neuronal isoform of tryptophan hydroxylase. Biochimie. 2017;140:159–65. doi: 10.1016/j.biochi.2017.07.008. [DOI] [PubMed] [Google Scholar]
- 14.Staud F, Pan X, Karahoda R, Dong X, Kastner P, Horackova H, et al. Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit. Reprod Biol Endocrinol. 2023;21:74. doi: 10.1186/s12958-023-01128-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Alwan S, Friedman JM, Chambers C. Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy: A Review of Current Evidence. CNS Drugs. 2016;30:499–515. doi: 10.1007/s40263-016-0338-3. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
De-identified participant data are available from the corresponding author upon reasonable request, subject to institutional approvals.