Placental nutrient and transport system in fetus with small for gestational age and growth restriction compared to appropriate for gestational age
DOI:
https://doi.org/10.13181/mji.oa.247361Keywords:
fetal growth restriction, nutrient, placenta, small for gestational age, transport systemAbstract
BACKGROUND Fetal growth restriction (FGR) has multifactorial etiology, including nutrition. Fetal nutrient status depends not only on an adequate supply of key nutrients but also optimal delivery, served by the placenta as a major metabolic and transport organ. This study aimed to evaluate the status of placental oxygen and nutrient concentration and their transporters between appropriate for gestational age (AGA), small for gestational age (SGA), and FGR.
METHODS This cross-sectional study was conducted at Cipto Mangunkusumo Hospital, Jakarta, from July 2018 to December 2020. Patients were divided into 3 groups, namely AGA, SGA, and FGR. The placental samples were taken following delivery. Placental concentration of glucose, amino acids (AAs), and fatty acids (FAs) were measured by calorimetric assay, liquid chromatography-tandem mass spectrometry, and gas chromatography-mass spectrometry, respectively. Placental concentration of vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT1), system y+L, and fatty acid transport protein 1 (FATP1) were examined using enzyme-linked immunosorbent assay.
RESULTS A total of 57 subjects participated in the study. Compared with the AGA group, the SGA and FGR groups had lower placental AA concentration (p = 0.004), higher placental FA concentration (p = 0.048), higher placental expression of VEGF (p = 0.003), system y+L (p = 0.07), and FATP1 (p = 0.021). No difference in placental glucose and GLUT1 concentration was observed among all groups (p = 0.301).
CONCLUSIONS The similar profile of macronutrient concentration with increased expression of oxygen and several nutrient transporters in SGA and FGR groups might indicate similar pathogenesis between these groups.
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Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016;48(3):333-9. https://doi.org/10.1002/uog.15884
Levine TA, Grunau RE, McAuliffe FM, Pinnamaneni R, Foran A, Alderdice FA. Early childhood neurodevelopment after intrauterine growth restriction: a systematic review. Pediatrics. 2015;135(1):126−41. https://doi.org/10.1542/peds.2014-1143
Melamed N, Baschat A, Yinon Y, Athanasiadis A, Mecacci F, Figueras F, et al. FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynaecol Obstet. 2021;152 Suppl 1(Suppl 1):3−57. https://doi.org/10.1002/ijgo.13522
United Nations Children's Fund (UNICEF), World Health Organization (WHO). UNICEF-WHO Low birthweight estimates: levels and trends 2000-2015 [Internet]. Geneva: World Health Organization; 2019 [cited 2024 Jan 19]. Available from: https://www.who.int/publications/i/item/WHO-NMH-NHD-19.21.
Basic Health Research. [National report of the 2018 Basic Health Research]. National Institute of Health Research and Development, Ministry of Health, Republic of Indonesia; 2018. Indonesian.
Zhang S, Regnault TR, Barker PL, Botting KJ, McMillen IC, McMillan CM, et al. Placental adaptations in growth restriction. Nutrients. 2015;7(1):360−89. https://doi.org/10.3390/nu7010360
Lager S, Powell TL. Regulation of nutrient transport across the placenta. J Pregnancy. 2012;2012:179827. https://doi.org/10.1155/2012/179827
Devaskar SU, Chu A. Oxygen consumption and general carbohydrate metabolism of the fetus. In: Polin RA, Fox WW, Abman SH, editors. Fetal and neonatal physiology. 5th ed. Philadelphia: Elsevier Saunders; 2016. p. 535-47.
Illsley NP, Baumann MU. Human placental glucose transport in fetoplacental growth and metabolism. Biochim Biophys Acta Mol Basis Dis. 2020;1866(2):165359. https://doi.org/10.1016/j.bbadis.2018.12.010
Dubova EA, Pavlov KA, Kulikova GV, Shchegolev AI, Sukhikh GT. Glucose transporters expression in the placental terminal villi of preeclampsia and intrauterine growth retardation complicated pregnancies. Health. 2013;5(7D):100-4. https://doi.org/10.4236/health.2013.57A4014
Cleal JK, Lofthouse EM, Sengers BG, Lewis RM. A systems perspective on placental amino acid transport. J Physiol. 2018;596(23):5511−22. https://doi.org/10.1113/JP274883
Walker N, Filis P, O'Shaughnessy PJ, Bellingham M, Fowler PA. Nutrient transporter expression in both the placenta and fetal liver are affected by maternal smoking. Placenta. 2019;78:10−7. https://doi.org/10.1016/j.placenta.2019.02.010
Huang X, Anderle P, Hostettler L, Baumann MU, Surbek DV, Ontsouka EC, et al. Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia. BMC Genomics. 2018;19(173). https://doi.org/10.1186/s12864-018-4518-z
Devarshi PP, Grant RW, Ikonte CJ, Hazels Mitmesser S. Maternal omega-3 nutrition, placental transfer and fetal brain development in gestational diabetes and preeclampsia. Nutrients. 2019;11(5):1107. https://doi.org/10.3390/nu11051107
Duttaroy AK, Basak S. Maternal dietary fatty acids and their roles in human placental development. Prostaglandins Leukot Essent Fatty Acids. 2020;155:102080. https://doi.org/10.1016/j.plefa.2020.102080
Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med. 2013;35(2):121−6. https://doi.org/10.4103/0253-7176.116232
Burton GJ, Sebire NJ, Myatt L, Tannetta D, Wang YL, Sadovsky Y, et al. Optimising sample collection for placental research. Placenta. 2014;35(1):9−22. https://doi.org/10.1016/j.placenta.2013.11.005
Liu L, Ma Y, Wang N, Lin W, Liu Y, Wen D. Maternal body mass index and risk of neonatal adverse outcomes in China: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2019;19(1):105. https://doi.org/10.1186/s12884-019-2249-z
Khalifa EA, Hassanein SA, Eid HH. Ultrasound measurement of fetal abdominal subcutaneous tissue thickness as a predictor of large versus small fetuses for gestational age. Egypt J Radiol Nucl Med. 2019;50(80). https://doi.org/10.1186/s43055-019-0088-6
Sharma D, Shastri S, Sharma P. Intrauterine growth restriction: antenatal and postnatal aspects. Clin Med Insights Pediatr. 2016;10:67−83. https://doi.org/10.4137/CMPed.S40070
Kesavan K, Devaskar SU. Intrauterine growth restriction: postnatal monitoring and outcomes. Pediatr Clin North Am. 2019;66(2):403−23. https://doi.org/10.1016/j.pcl.2018.12.009
Sawant LD, Venkat S. Comparative analysis of normal versus fetal growth restriction in pregnancy: the significance of maternal body mass index, nutritional status, anemia, and ultrasonography screening. Int J Reprod Med. 2013;2013:671954. https://doi.org/10.1155/2013/671954
Malhotra A, Allison BJ, Castillo-Melendez M, Jenkin G, Polglase GR, Miller SL. Neonatal morbidities of fetal growth restriction: pathophysiology and impact. Front Endocrinol (Lausanne). 2019;10:55. https://doi.org/10.3389/fendo.2019.00055
Monier I, Blondel B, Ego A, Kaminski M, Goffinet F, Zeitlin J. Does the presence of risk factors for fetal growth restriction increase the probability of antenatal detection? A French national study. Paediatr Perinat Epidemiol. 2016;30(1):46−55. https://doi.org/10.1111/ppe.12251
Bolehovská P, Sehnal B, Driák D, Halaška M, Magner M, Novotný J, et al. Changes in placental angiogenesis and their correlation with foetal intrauterine restriction. Ceska Gynekol. 2015;80(2):144−50.
Regnault TR, Orbus RJ, de Vrijer B, Davidsen ML, Galan HL, Wilkening RB, et al. Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Placenta. 2002;23(2−3):132−44. https://doi.org/10.1053/plac.2001.0757
Herraiz I, Dröge LA, Gómez-Montes E, Henrich W, Galindo A, Verlohren S. Characterization of the soluble fms-like tyrosine kinase-1 to placental growth factor ratio in pregnancies complicated by fetal growth restriction. Obstet Gynecol. 2014;124(2 Pt 1):265−73. https://doi.org/10.1097/AOG.0000000000000367
Aiko Y, Askew DJ, Aramaki S, Myoga M, Tomonaga C, Hachisuga T, et al. Differential levels of amino acid transporters System L and ASCT2, and the mTOR protein in placenta of preeclampsia and IUGR. BMC Pregnancy Childbirth. 2014;14:181. https://doi.org/10.1186/1471-2393-14-181
Barta E. Transport of docosahexaenoic acid via the human placenta: a theoretical study. J Membr Biol. 2019;252(6):617−26. https://doi.org/10.1007/s00232-019-00097-y
Assumpção RP, Mucci DB, Fonseca FC, Marcondes H, Sardinha FL, Citelli M, et al. Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies. Prostaglandins Leukot Essent Fatty Acids. 2017;125:24−31. https://doi.org/10.1016/j.plefa.2017.08.011
Segura MT, Demmelmair H, Krauss-Etschmann S, Nathan P, Dehmel S, Padilla MC, et al. Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition. Placenta. 2017;57:144−51. https://doi.org/10.1016/j.placenta.2017.07.001
Chang YL, Chao AS, Chang SD, Cheng PJ. Placental glucose transporter 1 and 3 gene expression in monochorionic twin pregnancies with selective fetal growth restriction. BMC Pregnancy Childbirth. 2021;21(1):260. https://doi.org/10.1186/s12884-021-03744-2
Hay WW Jr. Placental-fetal glucose exchange and fetal glucose metabolism. Trans Am Clin Climatol Assoc. 2006;117:321−39; discussion 339−40.
Day PE, Cleal JK, Lofthouse EM, Hanson MA, Lewis RM. What factors determine placental glucose transfer kinetics? Placenta. 2013;34(10):953−8. https://doi.org/10.1016/j.placenta.2013.07.001
Wu G. Functional amino acids in growth, reproduction, and health. Adv Nutr. 2010;1(1):31−7. https://doi.org/10.3945/an.110.1008
Zhang S, Zeng X, Ren M, Mao X, Qiao S. Novel metabolic and physiological functions of branched chain amino acids: a review. J Anim Sci Biotechnol. 2017;8:10. https://doi.org/10.1186/s40104-016-0139-z
Kudo Y, Boyd CA. Human placental amino acid transporter genes: expression and function. Reproduction. 2002;124(5):593−600. https://doi.org/10.1530/rep.0.1240593
Cetin I. Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo. Pediatr Res. 2001;49(2):148−54. https://doi.org/10.1203/00006450-200102000-00004
Burton GJ, Yung HW, Cindrova-Davies T, Charnock-Jones DS. Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia. Placenta. 2009;30 Suppl A(Suppl):S43−8. https://doi.org/10.1016/j.placenta.2008.11.003
Cusick SE, Georgieff MK. The role of nutrition in brain development: the golden opportunity of the "first 1000 days". J Pediatr. 2016;175:16-21. https://doi.org/10.1016/j.jpeds.2016.05.013
Meher A, Randhir K, Mehendale S, Wagh G, Joshi S. Maternal fatty acids and their association with birth outcome: a prospective study. PLoS One. 2016;11(1):e0147359. https://doi.org/10.1371/journal.pone.0147359
Perazzolo S, Hirschmugl B, Wadsack C, Desoye G, Lewis RM, Sengers BG. The influence of placental metabolism on fatty acid transfer to the fetus. J Lipid Res. 2017;58(2):443−54. https://doi.org/10.1194/jlr.P072355
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