Fetal thermal dose considerations during the obstetrician's watch: Implications for the pediatrician's observations

Abstract

There are a number of seemingly "usual" thermal episodes during pregnancy for which it is relatively easy to determine a rudimentary aspect of thermal dose; these episodes include fever, labor, labor plus epidural, and the normally-occurring 0.5 degrees C temperature elevation above maternal core temperature of the fetus during the entirety of the third trimester. Complications can involve, for instance, fever during the third trimester. We consider the thermal doses of five different but "usual" or "normal" hyperthermic episodes during human pregnancy and compare those doses with the thermal doses involved with both single and cohort exposures of pregnant guinea pigs throughout their gestational period. The end-point studied in the guinea pigs was microencephaly. In nine of the 10 comparisons (human fetal thermal dose vs. guinea pig fetal thermal dose) the human dose is substantially larger than that of the guinea pig thermal dose, which was substantially teratogenic. This situation is essentially the inverse of the type of information contained in the Physician's Desk Reference (PDR) on drugs, in which it is not unusual to discern that at high drug levels there may be teratogenic effects in laboratory animals, but such effects were not observed at "clinical" drug levels in animals or subsequent clinical trials. With hyperthermic events, however, it appears that the teratogenically-effective thermal dose levels associated with animal testing are quite low relative to those thermal doses associated with relatively "normal" obstetric observations during a pregnancy.

Fever and sickness behavior: Friend or foe?

“…Nonetheless, there are reports that high fever early in pregnancy is associated with adverse fetal outcomes (Chambers et al, 1998;Li et al, 2007;Moretti et al, 2005). In keeping with this Edwards and colleagues have calculated that the thermal load associated with a 24 h fever of 2.5˚C is sufficient to be teratogenic (Miller et al, 2007). Possible teratogenic effects may especially occur at parturition, as there are reports that intrapartum maternal fever, although rare, is associated with adverse outcome in the infants (Lieberman et al, 2000;Petrova et al, 2001).…”

Developmental pathways of motor dysfunction

“…Forms of developmental plasticity can be observed at multiple levels of investigation, from pruning and rearrangement at the cellular level (Miller, Church, Miller, & Edwards, ), to changes at the functional level in both animal models (Brumley, Kauer, & Swann, ; Sharp, this issue) and human infants (Siekerman, Barbu‐Roth, Anderson, Donnelly, Goffinet, & Teulier, ; Yang, Mitton, Musselman, Patrick, & Tajino, ). In the field of teratology, plasticity historically has been discussed in terms of its role in recovery of function with emphasis on the outcome or endpoint of a developmental process (Butcher, Wootten, & Vorhees, 1980; Vorhees, ).…”

Studying the effects of maternal febrile exposures on neurological outcomes in offspring: conceptual and methodological issues

“…Therefore, data on the dose or ‘severity’ of the exposure, often reported in terms of the ‘highest temperature recorded’, may suffer from recall bias. However, thermal dose is a function not just of the temperature but also of the duration and frequency of exposures . Retrospective ascertainment of the duration and frequency, along with highest temperature attained, is difficult and often results in missing data points or unreliable estimates.…”