Research paperThyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study
Introduction
Postpartum depression is a disabling and heterogeneous disorder with a huge variety in biological, psychological and social risk factors (Howard et al., 2014). In addition, there is substantial difference in the onset timing, severity and course of postpartum depression (Putnam et al., 2017; Fisher et al., 2016). The most important risk factor for postpartum depression is a depressive episode earlier in life or during pregnancy. In a large study among women with postpartum depression, approximately 60% of women reported an onset of their episode before pregnancy or during the antenatal period (Wisner et al., 2013).
Antenatal depression occurs during an entirely different immune and endocrine state than postpartum depression and may therefore have a different origin (Osborne and Monk, 2013). Interestingly, the postpartum period is a high risk period for more severe and first-onset episodes of depression (Munk-Olsen et al., 2016). Therefore, it is important to consider onset timing when studying risk factors for postpartum depression (Wisner et al., 2013). The postpartum period is also associated with an increased risk for the new onset of auto-immune thyroid disorders (Andersen et al., 2016). The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is a clear marker for the occurrence of postpartum auto-immune thyroid dysfunction, induced by the typical postpartum rebound phenomena of TPO-ab titers (Balucan et al., 2013, Fung et al., 1988, Jansson et al., 1984, Stagnaro-Green et al., 1992). Interestingly, TPO has also been named as a predictor for postpartum depression (Dama et al., 2016).
Four studies reported an association between an increased TPO-ab titer during early gestation and depression postpartum (Groer and Vaughan, 2013, Harris et al., 1992, Kuijpens et al., 2001, Lazarus et al., 1996). However, none of these studies focused on first-onset depression and three out of four studies did not take into account antenatal depression (Groer and Vaughan, 2013, Harris et al., 1992, Lazarus et al., 1996), while one study only briefly mentioned this in a sub analysis (Kuijpens et al., 2001). Together, as acknowledged by Dama and colleagues in their recent review, in previous studies antenatal depression may have confounded the association between a TPO-ab positive status during pregnancy and postpartum depression (Dama et al., 2016). Accordingly, the current study was designed to investigate the association between a positive TPO-ab status during early gestation and first-onset postpartum depression. We hypothesized that women are particularly at increased risk for first-onset depression three to four months postpartum, during the typical rebound of TPO-ab titers.
Section snippets
Participants
Participants were included in the Holistic Approach to Pregnancy and the first Postpartum year (HAPPY) study, a large prospective cohort that is described in detail elsewhere (Truijens et al., 2014). In sum, the HAPPY-study focuses on maternal wellbeing during pregnancy and the postpartum period. During a recruitment period of 18 months (2013–2014), Dutch-speaking pregnant women were informed about the study during their first trimester appointment at 17 community midwives offices in the
Study sample
A detailed overview of the participant selection process is presented in Fig. 1. In total, n = 3160 Dutch-speaking pregnant women were informed about the HAPPY-study, of which 71.8% (n = 2269) provided informed consent. A self-reported lifetime history of depression (n = 300) and one or more EDS scores above the trimester specific cut-offs during pregnancy (n = 386) were the most important reasons for exclusion. Of the women that were eligible for this study (n = 1364), follow-up data at four
Discussion
In this large prospective cohort study including n = 1075 women, the cumulative incidence of self-reported first-onset postpartum depression during the first postpartum year was 6.3%. A positive TPO-ab status during pregnancy was associated with a threefold increased risk of self-reported first-onset depression at four months postpartum but not at other postpartum time points. Point prevalence rates of self-reported postpartum depression declined after four months postpartum among women with a
Conclusions
In this large prospective cohort study, we demonstrated that women with a positive TPO-ab status during early gestation are at increased risk for self-reported first-onset depression at four months postpartum. This period coincides with the typical postpartum rebound phenomena of the maternal immune system, which suggests an overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Evaluation of thyroid function is essential in the clinical assessment of
Funding sources
V. Bergink is supported by the Netherlands Organization for Scientific Research (the NWO Innovational Research Incentives Scheme, grant numbers: veni 91616036, clinical fellow 90715620). The other authors do not report funding.
Ethics
The HAPPY-study was approved by the Medical Ethical Committee of the Maxima Medical Centre Veldhoven and the Psychology Ethics Committee of Tilburg University (protocol number EC-2012.25).
Acknowledgements
We thank the participants of the HAPPY-study as well as all midwives of the 17 participating midwifery practices in South-East Brabant (The Netherlands) for their contribution in recruiting participants.
Richard Wesseloo (1986), Erasmus Medical Centre, Rotterdam, The Netherlands. Richard Wesseloo graduated as a medical doctor in 2011, started his residency in psychiatry afterwards and is now finalizing his thesis (Ph.D.) on perinatal psychiatry. Last year, he completed his specialization in clinical epidemiology (M.Sc.). His recent meta-analysis on postpartum relapse rates in women with a history of bipolar disorder or postpartum psychosis (Am. J. Psychiatry) was selected as one of the 10
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Richard Wesseloo (1986), Erasmus Medical Centre, Rotterdam, The Netherlands. Richard Wesseloo graduated as a medical doctor in 2011, started his residency in psychiatry afterwards and is now finalizing his thesis (Ph.D.) on perinatal psychiatry. Last year, he completed his specialization in clinical epidemiology (M.Sc.). His recent meta-analysis on postpartum relapse rates in women with a history of bipolar disorder or postpartum psychosis (Am. J. Psychiatry) was selected as one of the 10 clinically most important research papers in psychiatry of 2015 by the New England Journal of Medicine Journal watch.