Effects of maternal hyperthermia on neurodevelopment: a literature review
Keywords:Neurodevelopment, Fever, Neurodevelopmental disorders, NTDs, Pregnancy, Maternal hyperthermia
Maternal hyperthermia, defined as a body temperature above 38°C (100.4°F) is due to various etiologies during pregnancy, and has been a subject of growing research interest. This phenomenon is considered a potential environmental teratogen contributing to the development of neural tube defects (NTDs) and other neurodevelopmental disorders. NTDs such as anencephaly and spina bifida, are known to be multifactorial in origin, resulting from a complex interplay between genetic and environmental factors. In this review, we aim to comprehensively analyze the effect of maternal hyperthermia on neurodevelopmental disorders and associated congenital anomalies. In addition, we will highlight both the infectious and noninfectious causes of maternal hyperthermia, as well as any risks and potential preventive measures. The literature search identified studies reporting associations between maternal hyperthermia and adverse fetal outcomes. We have evaluated the link between maternal fever due to infections during pregnancy and the increased likelihood of NTDs, particularly anencephaly and spina bifida, as well as Neurodevelopmental disorders. In addition, the effects of non-infectious causes of maternal hyperthermia, including exercise and exposure to heat sources like saunas and hot tubs, on neurodevelopment have also been studied with varying degrees of evidence. Maternal hyperthermia elevates the risk of NTDs and neurodevelopmental disorders in infants, with folic acid offering partial protection, while other factors elevate this risk. However, further research is needed to define the precious association of these factors.
Le Gouez A, Benachi A, Mercier FJ. Fever and pregnancy. Anaesth Crit Care Pain Med. 2016;35(1):S5-12.
Sultan P, David AL, Fernando R, Ackland GL. Inflammation and Epidural-Related Maternal Fever: Proposed Mechanisms. Anesth Analg. 2016;122(5):1546-53.
Apantaku O, Mulik V. Maternal intra-partum fever. J Obstet Gynaecol. 2007;27(1):12-5.
Antoun S, Ellul P, Peyre Hl. Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis. Mol Autism. 2021;12(1):60.
Croen LA, Qian Y, Ashwood P. Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development. Autism Res. 2019;12(10):1551-61.
Croen LA, Qian Y, Ashwood P, Ousseny Z, Diana S, Jennifer PM, et al. Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development. Autism Res. 2019;12(10):1551-61.
Sass L, Urhoj SK, Kjærgaard J, Dreier JW, Strandberg-Larsen K, Nybo Andersen AM. Fever in pregnancy and the risk of congenital malformations: a cohort study. BMC Pregnancy Childbirth. 2017;17(1):413.
Isaković J, Šimunić I, Jagečić D, Hribljan V, Mitrečić D. Overview of Neural Tube Defects: Gene-Environment Interactions, Preventative Approaches and Future Perspectives. Biomedicines. 2022;10(5):965.
Graham JM Jr. Update on the gestational effects of maternal hyperthermia. Birth Defects Res. 2020;112(12):943-52.
Hutson MR, Keyte AL, Hernández-Morales M, Eric G, Zachary AK, Ioannis A, et al. Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects. Sci Signal. 2017;10(500):eaal4055.
Kerr SM, Parker SE, Mitchell AA, Tinker SC, Werler MM. Periconceptional maternal fever, folic acid intake, and the risk for neural tube defects. Ann Epidemiol. 2017;27(12):777-82.
Easter SR, Molina RL, Venkatesh KK, Kaimal A, Tuomala R, Riley LE. Clinical Risk Factors Associated with Peripartum Maternal Bacteremia. Obstet Gynecol. 2017;130(4):710-17.
Kuwar Chhetri P, M Das J. Neuroanatomy, Neural Tube Development and Stages. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2023.
Finnell RH, Caiaffa CD, Kim SE, Yunping L, John S, Xuanye C, et al. Gene Environment Interactions in the Etiology of Neural Tube Defects. Front Genet. 2021;12:659612.
Palomaki GE, Bupp C, Gregg AR, Mary EN, Devin O, Robert GB, et al. Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(3):462-74.
Avagliano L, Massa V, George TM, Qureshy S, Bulfamante GP, Finnell RH. Overview on neural tube defects: From development to physical characteristics. Birth Defects Res. 2019;111(19):1455-67.