Does Fetal Malignant Hyperthermia-Related Intrauterine Thermal Stress Contribute to Cerebral Palsy Risk?

Fetal hyperthermia has been documented to lower the threshold for minor intrapartum hypoxic-ischemic events to cause significant brain injury. Excess heat production during the “human stress syndrome,” malignant hyperthermia (MH), is still an unproven phenomenon in the fetus. This paper discusses the possibility that such reactions can be induced in susceptible fetuses by fetal hypoxia, reactive oxygen species and heat itself. An indicated prevalence in the Genome Aggregation Database (gnomAD) of 1/300-1075 individuals carrying RYR1 MH alleles, raises valid concerns over the possible overlooked importance of such heat stress reactions. The identification of pathogenic MH gene variants in several children with severe, non-progressive cerebral palsy (CP) referred to a South African clinic from diverse sources, may indicate a need to further investigate a possible relationship between antenatal/intrapartum MH and cerebral palsy (CP). Some of the birth defects and comorbid neurodevelopmental disorders described in CP clinical surveys may represent remnants of intrauterine heat stress in susceptible fetuses. Climatic heat, Infections and fetal hyperthermia due to compromise of the fetomaternal heat gradient caused by placental pathology can be expected to variably interact with Intrinsic fetal hyperthermia when studying the effects of heat stress in pregnancy.