Placenta research group

We study molecular biological changes in the placenta in relation to different disorders like maternal diseases or pregnancy complications like poor fetal growth. We have for example found that the placental expression of leptin in obese women have a U shaped association with the child's birthweight and that the protein expression in placenta changes when the mother is smoking during the pregnancy. By increasing our knowledge of the mechanisms involved in aberrant fetal growth new treatments can be developed in the future. Normal fetal growth and development have positive health effects both in the neonatal period and later in life, in accordance with the theory of fetal programming, also called Developmental Origins of Health and Disease. The overall aim for our research is to optimize fetal growth and alleviate pregnancy complications.

The placenta and cord blood sample collection at Örebro University Hospital, Örebro, Sweden

Aims, principal investigators and ethical approvals

Professor emeritus Jens Schollin, former head of the Department of Paediatrics, Örebro University Hospital, and vice-chancellor at Örebro University, initiated the collection of placental tissue and cord blood samples aiming at studying associations between inflammation in these tissues and preterm birth and the later risk for development of cerebral palsy in the offspring. The project was approved by the Research Ethics Committee at Örebro University Hospital in December 2003 (D-nr 340/03).

Schollin transmitted the responsibility for the project and the sample collection to Ph.D. and consultant in paediatrics Maria Björkqvist, who broadened the research questions to also include foetal and postnatal growth. These changes were approved by the Regional Board of Ethics, Uppsala, Sweden, in June 2010 (D-nr 2010/189). Later on, the responsibility for the study and the sample collection were transferred to Ph.D. and consultant in paediatrics Maria Lodefalk, who further broadened the purpose of the study to include epigenetic, gene expression and protein expression changes in relation to pregnancy complications, intrauterine exposures and maternal and foetal characteristics. This alteration was approved by the Regional Board of Ethics, Uppsala, in September 2016 (D-nr 2010/189-1).   

Methods and materials

After written informed consent was received from each pregnant woman, placental tissue and cord blood samples were collected immediately after the delivery at the Department of Women’s Health, Örebro University Hospital, during 2004–2012. In total, approximately 10,000 samples have been collected.

After removal of the membranes, two pieces (approximately 1 cm³ each) were taken from the maternal side of the placenta. The samples were rinsed in cold phosphate buffered saline to remove blood and then stored frozen (-80°C) in 3 mL RNAlater. Before April 2009, 30 mL tubes were used for the storage of the placenta samples and after that time point, 5 mL tubes were used.

A cord venous blood sample was collected from each child at the time of delivery in 10 mL clot activator tubes (BD Vacutainer, Plymouth, UK). Each sample was centrifuged at 2000 x g for 7 min and the serum was stored frozen (-80°C) in separate aliquots (2 mL tubes).

For the capture of data on the pregnant woman, the pregnancy, the delivery and the newborn infant, a background data form was used during 2004–2007. At the beginning of 2008, electronic medical records (Obstetrix®) were introduced at the Department of Women’s Health and from then, the background data on each mother-infant pair was collected from these records.

The data collected during 2004–2007 lacked some information (for example the height of the woman, the birth length of the infant, and Apgar score at 5 min of age). This missing data was collected from the Swedish Medical Birth Register at the National Board of Health and Welfare in October 2017.  

Birth weight, length and head circumference of the infants have been transformed to z-scores using Swedish reference data (Niklasson A et al, BMC Pediatrics, 2008).

Publications
Bakoyan Z, Cao Y, Hansson SR, Patriksson Karlsson J, Lodefalk M. Childhood atopic disorders in relation to placental changes – A systematic review and meta-analysis. Pediatr Allergy Immunol  35:e14141, 2024. 

Östling H, Lodefalk M, Bergman L, Zaigham M, Andersson O, Carlsson Y, Veje M, Wikström AK, Domelöf M, Sengpiel V, Backman H, Kruse R. Placental inflammatory and cardiovascular markers following SARS-CoV-2 infection in early and late pregnancies. A Swedish prospective cohort study. Placenta. 2024 Oct 4:158:78-88. doi: 10.1016/j.placenta.2024.09.017. Online ahead of print.

Allbrand M, Bjorkqvist M, Nilsson K, Ostlund I, Aman J. Placental gene expression of inflammatory markers and growth factors - a case control study of obese and normal weight women. J Perinat Med. 2015; 43: 159-64. PMID: 25014513. DOI: 10.1515/jpm-2013-0343

Allbrand M, Aman J, Lodefalk M. Placental ghrelin and leptin expression and cord blood ghrelin, adiponectin, leptin, and C-peptide levels in severe maternal obesity. J Matern Fetal Neonatal Med. 2018; 31: 2839-46. PMID: 28783996. DOI: 10.1080/14767058.2017.1358262

Allbrand M, Aman J, Nilsson K, Cao Y, Lodefalk M. Expression of genes involved in inflammation and growth - does sampling site in human full-term placenta matter? J Perinat Med. 2019; 47: 539-46. PMID: 30920955. DOI: 10.1515/jpm-2018-0290

Ostling H, Kruse R, Helenius G, Lodefalk M. Placental expression of microRNAs in infants born small for gestational age. Placenta. 2019; 81: 46-53. PMID: 31138431. DOI: 10.1016/j.placenta.2019.05.001

Allbrand, M. (2020). Gene expression of inflammatory markers and growth factors in placenta in relation to maternal obesity and foetal and postnatal growth. Örebro: Örebro University. Dissertation.

Lodefalk M, Allbrand M, Montgomery S. Duration of the pushing phase of labour is inversely associated with the expression of TNF, IL6, IGF1 and IGF2 in human placenta. The Journal of Maternal-Fetal & Neonatal HealthThe Journal of Maternal-Fetal & Neonatal Health, https://doi.org/10.1080/14767058.2021.1916459

Roxenlund F, Kruse R, Östling H, Lodefalk M. Differential microRNA expression in placentas of small-for-gestational age neonates with and without exposure to poor maternal gestational weight gain. https://doi.org/10.1515/jpm-2020-0597

Allbrand M, Eklund D, Cao Y, Nilsson K, Lodefalk M. Gene expression of leptin, leptin receptor isoforms, and inflammatory cytokines in placentas of obese women – associations to birth weight and foetal sex. https://doi.org/10.1016/j.placenta.2021.10.002

Chelslín F, Lodefalk M, Kruse R. Smoking during pregnancy is associated with the placental proteome. Reprod Toxicol 2023; 119: 108409. doi: 10.1016/j.reprotox.2023.108409

Lodefalk, M. , Chelslín, F. , Patriksson Karlsson, J. & Hansson, S. R. (2023). Placental Changes and Neuropsychological Development in Children-A Systematic Review. Cells, 12 (3).

Östling, H. , Lodefalk, M. , Backman, H. & Kruse, R. (2022). Global microRNA and protein expression in human term placenta. Frontiers in Medicine, 9.