Treating life-threatening diseases and those associated with
morbidities
There is a considerable increase in maternal comorbidity including
obesity, hyperlipidemia, diabetes, and hypertension in recent years
worldwide. Many of these comorbid conditions have been linked to higher
rates of pregnancy-related morbidity and mortality [30]. Asthma for
example can be common in pregnancy and in some cases worsens due to
physiological changes. In one study, it has been shown that there has
been a reduction in prescriptions of asthma medication during the first
trimester of pregnancy [31, 32]. However, it is important to control
asthma symptoms during pregnancy despite the safety profile of some
medications used. Uncontrolled asthma can lead to complications
including preeclampsia, preterm delivery and low birth weight [33].
This is a compelling example where risks of uncontrolled asthma outweigh
potential risks of neonatal fetotoxicity from exposure. Another example
are oral steroids like prednisone. Prior observational studies have
reported cleft lip and cleft palate when prednisone was used early in
pregnancy but those results were not consistent over time [34].Table 2 highlights controversial medications that need
additional counseling given their possible or known adverse effects on
the fetus. There is much controversy in interpreting population-based
studies and animal studies when it comes to teratogenicity and
fetotoxicity. Some drugs that showed adverse effects in animal models
were not matched when studying human population and vice versa. Statins,
which are now being investigated as potential drugs to prevent
preeclampsia have been previously contraindicated in pregnancy. However,
a recent meta-analysis including 16 human studies showed no relationship
between statins and teratogenicity [35]. More recently, the FDA has
requested removal of the contraindication of statins in pregnancy
[36].
Improving the infrastructure of research seems to be something that
would benefit the moral imperative to incorporate pregnant women into
clinical drug trials. Pharmacoepidemiologic studies are limited by the
fact that often disease and severity are related to exposure and adverse
outcome and that systematic bias is not usually accounted for when the
pharmacologic exposure or the disease itself was the cause of
fetotoxicity. For example, autoimmune diseases like rheumatoid
arthritis, inflammatory bowel disease or lupus might exacerbate during
pregnancy. In these diseases it has been noted that there is an
increased risk of low birth weight, preterm birth and associated
morbidities with current treatment options, but whether this is in an
effect of the treatment per se or the disease itself is hard to decipher
[37-39].