Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Archives of Gynecology and Obstetrics
Published in: Archives of Gynecology and Obstetrics 3/2019

01-09-2019 | Sectio Ceasarea | Maternal-Fetal Medicine

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

Authors: Engy Shokry, Linda Marchioro, Olaf Uhl, Mercedes G. Bermúdez, Jose Antonio García-Santos, Mª Teresa Segura, Cristina Campoy, Berthold Koletzko

Published in: Archives of Gynecology and Obstetrics | Issue 3/2019

Login to get access

Abstract

Purpose

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.

Methods

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

Results

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.

Conclusions

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.
Appendix
Available only for authorised users
Literature
1.
Strauss RS (1997) Effects of the intrauterine environment on childhood growth. Br Med Bull 33(1):81–89CrossRef
2.
3.
4.
Jacob L, Taskan S, Macharey G, Sechet I, Ziller V, Kostev K (2016) Impact of caesarean section on mode of delivery, pregnancy-induced and pregnancy-associated disorders, and complications in the subsequent pregnancy in Germany. GMS Ger Med Sci 14:Doc06
5.
Cardwell CR, Stene LC, Joner G, Cinek O, Svensson J, Goldacre MJ et al (2008) Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia 51(5):726–735CrossRefPubMed
6.
Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR (2008) A meta-analysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy 38:629–633CrossRefPubMed
7.
Miller NM, Fisk NM, Modi N, Glover V (2005) Stress responses at birth: determinants of cord arterial cortisol and links with cortisol response in infancy. BJOG 112:921–926CrossRefPubMed
8.
Reinhardt C, Reigstad CS, Bäckhed F (2009) Intestinal microbiota during infancy and its implications for obesity. J Pediatr Gastroenterol Nutr 48(3):249–256CrossRefPubMed
9.
Dewey KG, Nommsen-Rivers LA, Heinig MJ, Cohen RJ (2003) Risk factors for suboptimal infant breastfeeding behavior, delayed onset of lactation, and excess neonatal weight loss. Pediatrics 112:607–619CrossRefPubMed
10.
Evans KC, Evans RG, Royal R, Esterman AJ, James SL (2003) Effect of caesarean section on breast milk transfer to the normal term newborn over the first week of life. Arch Dis Child Fetal Neonatal Ed 88:F380–F382CrossRefPubMedPubMedCentral
11.
Hyde MJ, Griffin JL, Herrera E, Byrne CD, Clarke L, Kemp PR (2010) Delivery by caesarean section, rather than vaginal delivery, promotes hepatic steatosis in piglets. Clin Sci 118:47–59CrossRef
12.
Dixon L, Skinner J, Foureur M (2013) The emotional and hormonal pathways of labour and birth: integrating mind, body and behaviour. NZ Coll Midwives J 48:15–23CrossRef
13.
Ward Platt M, Deshpande S (2005) Metabolic adaptation at birth. Semin Fetal Neonatal Med 10:341–350CrossRefPubMed
14.
Burcelin R, Mrejen C, Decaux JF, De Mouzon SH, Girard J, Charron MJ (1998) In vivo and in vitro regulation of hepatic glucagon receptor mRNA concentration by glucose metabolism. J Biol Chem 273:8088–8089CrossRefPubMed
15.
Mitanchez D (2007) Glucose regulation in preterm newborn infants. Horm Res 68:265–271PubMed
16.
17.
Berglund SK, García-Valdés L, Torres-Espinola FJ, Segura MT, Martínez-Zaldívar C, Aguilar MJ et al (2016) Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE). BMC Public Health 16:207CrossRefPubMedPubMedCentral
18.
19.
Harder U, Koletzko B, Peissner W (2011) Quantification of 22 plasma amino acids combining derivatization and ion-pair LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 879:495–504CrossRefPubMed
20.
Hellmuth C, Weber M, Koletzko B, Peissner W (2012) Nonesterified fatty acid determination for functional lipidomics: comprehensive ultrahigh performance liquid chromatography-tandem mass spectrometry quantitation, qualification, and parameter prediction. Anal Chem 84:1483–1490CrossRefPubMed
21.
Rauschert S, Uhl O, Koletzko B, Kirchberg F, Mori TA, Huang RC et al (2016) Lipidomics reveals associations of phospholipids with obesity and insulin resistance in young adults. J Clin Endocrinol Metab 101:871–879CrossRefPubMed
22.
Kirchberg FF, Brandt S, Moß A, Peissner W, Koenig W, Rothenbacher D et al (2017) Metabolomics reveals an entanglement of fasting leptin concentrations with fatty acid oxidation and gluconeogenesis in healthy children. PLoS One 12(8):e0183185CrossRefPubMedPubMedCentral
23.
Sampath H, Ntambi JM (2008) Role of stearoyl-CoA desaturase in human metabolic disease. Future Lipidol 3:163–173CrossRef
24.
Angelini R, Vortmeier G, Corcelli A, Fuchs B (2014) A fast method for the determination of the PC/LPC ratio in intact serum by MALDI-TOF MS: an easy-to-follow lipid biomarker of inflammation. Chem Phys Lipids 183:169–175CrossRefPubMed
25.
Zhang W, Sun G, Aitken D, Likhodii S, Liu M, Martin G et al (2016) Lysophosphatidylcholines to phosphatidylcholines ratio predicts advanced knee osteoarthritis. Rheumatology 55(9):1566–1567CrossRefPubMedPubMedCentral
26.
Pickens CA, Vazquez AI, Daniel Jones A, Fenton JI (2017) Obesity, adipokines, and C-peptide are associated with distinct plasma and phospholipid profiles in adult males, an untargeted lipidomic approach. Sci Rep 7:6335CrossRefPubMedPubMedCentral
27.
Wallner S, Schmitz G (2011) Plasmalogens the neglected regulatory and scavenging lipid species. Chem Phys Lipids 164:573–589CrossRefPubMed
28.
Maeba R, Hara H (2012) Serum choline plasmalogen is a reliable biomarker for atherogenic status. In: Squeri A (ed) Coronary artery disease—new Insights and Novel Approaches. InTech, Rijeka
29.
Fox J, Weisberg S (2011) An R companion to applied regression, 2nd edn. Sage, Thousand Oaks
30.
Mastorakos G, Ilias I (2003) Maternal and fetal hypothalamic–pituitary–adrenal axes during pregnancy and postpartum. Ann N Y Acad Sci 997:136–139CrossRefPubMed
31.
Cheng YH, Nicholson RC, King B, Chan EC, Fitter JT, Smith R (2000) Glucocorticoid stimulation of corticotropin-releasing hormone gene expression requires a cyclic adenosine 3ʹ,5ʹ-monophosphate regulatory element in human primary placental cytotrophoblast cells. J Clin Endocrinol Metab 85(5):1937–1945PubMed
32.
Goldkrand JW, Schulte RL, Messer RH (1976) Maternal and fetal plasma cortisol levels at parturition. Obstet Gynecol 47(1):41–45PubMed
33.
Stjernholm YV, Nyberg A, Cardell M, Höybye C (2016) Circulating maternal cortisol levels during vaginal delivery and elective cesarean section. Arch Gynecol Obstet 294:267–271CrossRefPubMed
34.
Hyde MJ, Mostyn A, Modi N, Kemp PR (2012) The health implications of birth by caesarean section. Biol Rev Camb Philos Soc 87(1):229–243CrossRefPubMed
35.
Stjernholm YV, Nyberg A, Cardell M, Höybye C (2016) Circulating maternal cortisol levels during vaginal delivery and elective cesarean section. Arch Gynecol Obstet 294(2):267–271CrossRefPubMed
36.
37.
Wynne-Edwards KE, Edwards HE, Hancock TM (2013) The human fetus preferentially secretes corticosterone, rather than cortisol. Response to intra-partum stressors. PLoS One 8(6):e63684CrossRefPubMedPubMedCentral
38.
Hundertmark S, Ragosch V, Schein B, Bühler H, Lorenz U, Fromm M et al (1994) Gestational age dependence of 11 beta-hydroxysteroid dehydrogenase and its relationship to the enzymes of phosphatidylcholine synthesis in lung and liver of fetal rat. Biochim Biophys Acta 1210(3):348–354CrossRefPubMed
39.
Sorenson DK, Kelly TM, Murray DK, Nelson DH (1988) Corticosteroids stimulate an increase in phospholipase A2 inhibitor in human serum. J Steroid Biochem 29(2):271–273CrossRefPubMed
40.
Goppelt-Struebe M, Wolter D, Resch K (1989) Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase/PGE isomerse. Br J Pharmacol 98:1287–1295CrossRefPubMedPubMedCentral
41.
Ortsäter H, Sjöholm Å, Rafacho A (2012) Regulation of glucocorticoid receptor signaling and the diabetogenic effects of glucocorticoid excess. In: Magdeldin S (ed) State of the art of therapeutic endocrinology. IntechOpen. https://​doi.​org/​10.​5772/​51759
42.
Anderson AJ, Sobocinski KA, Freedman DS, Barboriak JJ, Rimm AA, Gruchow HW (1988) Body fat distribution, plasma lipids and lipoproteins. Arteriosclerosis 8:88–94CrossRefPubMed
43.
Ginsberg HN (1991) Lipoprotein physiology in non diabetic and diabetic state. Relationship to atherosclerosis. Diabetes Care 14:839–855CrossRefPubMed
44.
Lewis GF (2006) Determinants of plasma HDL concentrations and reverse cholesterol transport. Curr Opin Cardiol 21(4):345–352CrossRefPubMed
45.
Scholler M, Wadsack C, Lang I, Etschmaier K, Schweinzer C, Marsche G et al (2012) Phospholipid transfer protein in the placental endothelium is affected by gestational diabetes mellitus. J Clin Endocrinol Metab 97(2):437–445CrossRefPubMed
46.
Boysen SR, Bozzetti M, Rose L, Dunn M, Pang DSJ (2009) Effects of prednisone on blood lactate concentrations in healthy dogs. J Vet Intern Med 23:1123–1125CrossRefPubMed
47.
48.
Van Aerde JE, Wilke MS, Feldman M, Clandinin MT (2003) Accretion of lipid in the fetus and newborn. In: Polin RA, Fox WW, Abman SH (ed) Fetal and Neonatal Physiology, vol. 1. Saunders, London
49.
Duee PH, Pegorier JP, Quant PA, Herbin C, Kohl C, Girard J (1994) Hepatic ketogenesis in newborn pigs is limited by low mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity. Biochem J 298:207–212CrossRefPubMedPubMedCentral
50.
You X-J, Xu C, Lu J-Q, Zhu X-Y, Gao L, Cui X-R et al (2011) Expression of Cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility. PLoS ONE 6(8):e23788CrossRefPubMedPubMedCentral
51.
Postle AD, Henderson NG, Koster G, Clark HW, Hunt AN (2011) Analysis of lung surfactant phosphatidylcholine metabolism in transgenic mice using stable isotopes. Chem Phys Lipids 164:549–555CrossRefPubMed
52.
Goss V, Hunt AN, Postle AD (2013) Regulation of lung surfactant phospholipid synthesis and metabolism. Biochim Biophys Acta 1831:448–458CrossRefPubMed
53.
Beaconsfield P, Villee C (1979) Placenta—A neglected experimental animal, 1st edn. Pergamon press, Oxford
54.
Vitale SG, Marilli I, Rapisarda AM, Rossetti D, Belluomo G, Iapichino V et al (2014) Cellular and biochemical mechanisms, risk factors and management of preterm birth: state of the art. Minerva Ginecol 66(6):589–595PubMed
55.
Barbara G, Pifarotti P, Facchin F, Cortinovis I, Dridi D, Ronchetti C et al (2016) Impact of mode of delivery on female postpartum sexual functioning: spontaneous vaginal delivery and operative vaginal delivery vs cesarean section. J Sex Med 13(3):393–401CrossRefPubMed
56.
El Sayed HA, Ramadan SA, Moursi HA, Ibrahim HA (2017) The effect of mode of delivery on postpartum sexual function and sexual quality of life in primiparous women. Am J Nurs Sci 6(4):347–357CrossRef
57.
Keag OE, Norman JE, Stock SJ (2018) Long-term risks and benefits associated with cesarean delivery for mother, baby, and subsequent pregnancies: Systematic review and meta-analysis. PLoS Med 15(1):e1002494CrossRefPubMedPubMedCentral
58.
Nordlie RC, Foster JD, Lange AJ (1999) Regulation of glucose production by the liver. Ann Rev Nutr 19:379–406CrossRef
59.
Rafiq N, Younossi ZM (2008) Interaction of metabolic syndrome, nonalcoholic fatty liver disease and chronic hepatitis C. Expert Rev Gastroenterol Hepatol 2:207–215CrossRefPubMed
Metadata
Title
Investigation of the impact of birth by cesarean section on fetal and maternal metabolism
Authors
Engy Shokry
Linda Marchioro
Olaf Uhl
Mercedes G. Bermúdez
Jose Antonio García-Santos
Mª Teresa Segura
Cristina Campoy
Berthold Koletzko
Publication date
01-09-2019
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 3/2019
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-019-05213-w

Other articles of this Issue 3/2019

Archives of Gynecology and Obstetrics 3/2019 Go to the issue

Gynecologic Endocrinology and Reproductive Medicine

Is muscle mechanical function altered in polycystic ovary syndrome?

Review

Cesarean section and the risk of neonatal respiratory distress syndrome: a meta-analysis

Gynecologic Endocrinology and Reproductive Medicine

Clinical outcomes after transfer of blastocysts derived from frozen–thawed cleavage embryos: a retrospective propensity-matched cohort study

Correspondence

Earlier predictors for treatment outcome among single dose methotrexate for an ectopic pregnancy

Maternal-Fetal Medicine

Carpal tunnel syndrome during the third trimester of pregnancy: prevalence and risk factors

Gynecologic Oncology

Clinical significance and oncogene function of long noncoding RNA HAGLROS overexpression in ovarian cancer