Investigation of the impact of birth by cesarean section on fetal and maternal metabolism

  • Engy Shokry
  • Linda Marchioro
  • Olaf Uhl
  • Mercedes G. Bermúdez
  • Jose Antonio García-Santos
  • Mª Teresa Segura
  • Cristina Campoy
  • Berthold KoletzkoEmail author
Maternal-Fetal Medicine



Elective cesarean section (CS) was related to long-term adverse health effects in the offspring, but little is known about underlying mechanisms. Our study investigates the metabolic changes in both maternal and cord blood associated with CS in comparison to vaginal delivery (VD) to explore potential causal pathways.


Samples obtained from PREOBE study participants were subjected to LC–MS/MS-targeted metabolomics comprising > 200 metabolites.


Elective CS showed an impact on both maternal and cord blood metabolomes. In maternal blood, the CS group showed lower levels of phospholipids (PL), principally ether-linked phosphatidylcholines (aaPC), pyruvic acid, branched chain keto-acids (BCKA), and other gluconeogenic substrates, but since the CS group showed different HDL levels in comparison to the VD group, we could not exclude contribution of the latter in the findings. In cord blood, the most remarkable finding in the CS group was the high levels of Cys; conversely, the lower levels of non-esterified fatty acids (NEFA), some tricarboxylic acid (TCA) cycle metabolites, gluconeogenic substrates, markers of β-oxidation, and the sum of hexoses were lower in CS-born babies in addition to tendentially lower levels of PL.


We speculate that lower levels of maternal and fetal corticosteroids in CS, due to less stressful condition, cause metabolic perturbations at birth initiating future negative health outcomes. This further supports the early programming hypothesis.


Mode of delivery Metabolomics Cord blood Metabolic adaptation Stress hormones 



The authors thank the study participants, the obstetricians, pediatricians and technicians of the EURISTIKOS team, and the PREOBE team at the University of Granada, Spain, for their support of the study. We are grateful to Stephanie Winterstetter, Alexander Haag and Tina Honsowitz (Division of Metabolic and Nutritional Medicine, Dr von Hauner Children’s Hospital, University of Munich, Munich, Germany) for their support in the analysis of the blood plasma samples. We would also like to thank Dr. Stefan Hutter (Department of Obstetrics and Gynecology, University of Munich, Munich, Germany) for his consultation.

Author contributions

MGB, JAG, and MTS coordinated and conducted the data and sample collection. OU performed the metabolic analysis. LM conducted the statistical analyses. ES discussed the results and wrote the paper. CC and BK are the principal investigators, responsible for the design and coordination of the research. BK and CC are also the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data, accuracy of the data analysis, and the final content of the manuscript. All the authors reviewed, edited and approved the manuscript.


This work was supported by Supported by the Andalusian Ministry of Economy, Science and Innovation, PREOBE Excellence Project (Ref. P06-CTS-02341), Spanish Ministry of Economy and Competitiveness (Ref. BFU2012-40254-C03-01 and Ref. SAF2015-69265-C2-2-R), the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG 322605), and the European Commission research projects EarlyNutrition, FP7-FP7 KBBE-2011-1 (289346 y), and DynaHEALTH (63359). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

None of the authors report conflicts of interest.

Ethical approval

The study was approved by the Bioethical Committees for Clinical Research of the Clinical University Hospital San Cecilio, the Mother-Infant University Hospital of Granada, Spain.

Adherence to EQUATOR network guidelines

The authors declare compliance with the EQUATOR (Enhancing the QUAlity and Transparency of Research) network guidelines available at:

Informed consent

Participation was voluntary and written informed consent was obtained from participants at study entry.

Supplementary material

404_2019_5213_MOESM1_ESM.docx (49 kb)
Supplementary file1 (DOCX 49 kb)
404_2019_5213_MOESM2_ESM.docx (39 kb)
Supplementary file1 (DOCX 39 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Engy Shokry
    • 1
  • Linda Marchioro
    • 1
  • Olaf Uhl
    • 1
  • Mercedes G. Bermúdez
    • 2
  • Jose Antonio García-Santos
    • 2
  • Mª Teresa Segura
    • 2
  • Cristina Campoy
    • 2
  • Berthold Koletzko
    • 1
    Email author
  1. 1.Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, LMU Medical CenterLMU-Ludwig-Maximilians-Universität MunichMunichGermany
  2. 2.Department of Paediatrics, School of Medicine, EURISTIKOS Excellence Centre for Paediatric ResearchUniversity of GranadaGranadaSpain

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