A toxicology study in rhesus monkeys resulted in the death of all rhesus fetuses exposed to 1 and 10 times the human dose equivalent of OHPC. As of 2008, OHPC was a category D progestin according to the FDA (that is, there is evidence of fetal harm). There is speculation that the castor oil in the OHPC formulation may not be beneficial for pregnancy. Of note, the above-mentioned NEJM study by Meirs et al. compares the effect of OHPC (with the castor oil component) to castor oil injection as the placebo. A study published in February 2016 in The Lancet stated the below, amongst other findings:
OPPTIMUM strongly suggests that the efficacy of progesterone in improving outcomes is either non-existent or weak. Given the heterogeneity of the preterm labour syndrome we cannot exclude benefit in specific phenotypic or genotypic subgroups of women at risk. However, the subgroups of women who might benefit do not appear to be easily identifiable by current selection strategies, including cervical length measurement and fibronectin testing. Reassuringly, our study suggests that progesterone is safe for those who wish to take it for preterm birth prophylaxis. The overall rate of maternal or child adverse events was similar in the progesterone and placebo groups. There were few differences in the incidence of adverse secondary outcomes in the two groups, with the exception of a higher rate of renal, gastrointestinal, and respiratory complications in childhood in the progesterone groups. Importantly, the absolute rates of these complications was low.
A hypotonic-hyporesponsive episode (HHE) is defined as sudden onset of poor muscle tone, reduced consciousness, and pale or bluish skin occurring within 48 hours after vaccination, most commonly pertussis vaccination. An HHE is estimated to occur after 1 in 4,762 to 1 in 1,408 doses of whole cell pertussis vaccine, and after 1 in 14,286 to 1 in 2,778 doses of acellular pertussis vaccine. == References ==