Letter to Editor: Maternal depression and inflammation during pregnancy

Abstract

Pulkkinen et al. raises interesting points on how depressive symptoms during pregnancy, or a diagnosis of depression prior to pregnancy, may be associated with a pro-inflammatory state (Lahti-Pulkkinen et al., 2019). They also found that pre-pregnancy obesity has a significant interaction with this relationship, potentiating the body's inflammatory response. The association between inflammatory cytokines and adverse pregnancy outcomes, such as preterm labour, has been well established (Goldenberg, Hauth, & Andrews, 2000), highlighting the importance of this study. The strengths of the study, including the large sample size and the multiple blood samples taken throughout gestation, provide valuable information to the field of maternal mental health. The authors used high sensitivity CRP (hsCRP) and glycoprotein acetyl as surrogate markers for the low-grade inflammation seen in depression. Depression is associated with an elevated CRP in the general population, however, it is unknown whether in pregnancy, these low levels are significant enough to generate a pathological outcome (Kashanian, Aghbali, & Mahali, 2013; Valkanova, Ebmeier, & Allan, 2013). There is still much debate regarding the role of inflammation in complications of pregnancy such as pre-eclampsia and intrauterine growth restriction. For example, preeclampsia may directly lead to oxidative stress, leading to inflammation and raised CRP (Sánchez-Aranguren et al., 2014). On the other hand, a chronic level of inflammation itself may lead to altered placental formation thus predisposing to pre-eclampsia (Ferguson et al., 2017). There is also a complex bidirectional relationship between maternal mental health and physiological well-being. Inflammatory biomarkers can be affected by patient factors including gestational weight gain, metabolic syndrome and antidepressant use; therefore inflammatory markers must be interpreted with caution (Howren, Lamkin, & Suls, 2009; Pearson et al., 2003). The study does not comment on maternal and neonatal outcomes due to the nature of their methodology. Therefore, we cannot observe the possible effects of increased CRP or glycoprotein acetyl on adverse outcomes of pregnancy. Further studies, including postpartum follow-up may be necessary to determine a causal relationship. It may also be interesting to investigate the effect of depression on inflammatory markers whose roles have already been implicated in pathways affecting preterm labour, such as IL-6 and PGE2 (Sykes et al., 2012). Albeit more invasive, samples of biomarkers could also be taken directly from cervical mucus or vaginal fluid (Sawada et al., 2006), which may provide a superior representation of how maternal psychological health affects inflammatory markers within the reproductive environment. We agree with the authors' conclusion that antenatal depression or depression prior to pregnancy may lead to low grade inflammation. It is well understood that depression may be an independent risk factor for adverse outcomes during pregnancy (Alder et al., 2007). Th...

Lahti-Pulkkinen et al. respond to the letter to the editor: Maternal depression and inflammation during pregnancy by Fujitake and Chen

“…We believe the associations of maternal inflammation during pregnancy with obstetric and neonatal outcomes we report in this letter to the editor and in our article further emphasize the clinical relevance of these inflammatory biomarkers, which were used as indicators of chronic low-grade inflammation during pregnancy. However, as pointed out by Fujitake and Chen (2019), since in our study inflammatory measurements were taken across pregnancy, for many of these associations, the direction of the associations still remains to be elucidated.…”

“…Regarding the potential confounders for our study, mentioned by Fujitake and Chen (2019), we had data on maternal weight gain in pregnancy for 307 women. In our sample, weight gain in pregnancy was correlated negatively with mean hsCRP [ r (305) = −0.21, p < 0.001] and glycoprotein acetyl levels [ r (280) = −0.25, p < 0.001].…”

“…In their letter, Fujitake and Chen (2019) also mention the importance of extending the analyses to other inflammatory biomarkers in pregnant women, including interleukin-6 and prostaglandin E2 and that inflammatory biomarkers could be measured from the cervical mucus or vaginal fluid. We agree that these are important points which should definitively be addressed in further studies.…”

“…First, we thank Fujitake and Chen (2019) for their interest in our research and the letter to the editor on our recent article Maternal Depression and Inflammation during Pregnancy published in Psychological Medicine , where we showed in the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) – pregnancy cohort, that diagnosis of depression before pregnancy and depressive symptoms during pregnancy was associated with higher levels of inflammatory biomarkers hsCRP and glycoprotein acetyls across pregnancy among 379 women (Lahti-Pulkkinen et al, 2019).…”

“…Recently, we completed a follow-up of the children at ages 7–11 years, and we will continue following them up as they age and reach adolescence. Hence, we will be able to provide additional information on child development and health outcomes, and address the important knowledge gaps and questions raised in the letter by Fujitake and Chen (2019).…”