The previously mentioned results of the ORACLE children study [48] stress the importance of carrying
out long-term follow up of infants after interventions aimed at prolonging gestational age at
delivery. Pathological processes associated with increased risk of preterm delivery, such as infection,
may affect infant outcome, and may potentially even increase risk of neonatal complications in relation
to pregnancy prolonging treatments [48]. By 2013, information on longer-term follow up of infants
born to mothers treated with progesterone is available for twins until the age of 18 months for
pregnancies treated with vaginal progesterone [38] and for singletons until the age of 48 months for
pregnancies treated with 17-OHPC [49]. These two studies have not shown signs of harmful longerterm
effects of micronised progesterone or 17-OHPC, but further long-term follow-up studies are
needed.
Potential maternal adverse effects of progesterone treatment constitute a possible increased risk of
gestational diabetes [50] corresponding to a known suggested diabetogenic effect of progesterone [51].
The association between progesterone treatment and gestational diabetes has not been confirmed in
subsequent publications [52,53]. Recently, Serra et al. [40] found a non-significant dose-dependenttrend towards higher incidence of intrahepatic cholestasis. This is in accordance with a previously
reported increased risk of intrahepatic cholestasis in association with oral progesterone treatment
during second- and third-trimester pregnancy [54–56].