Our thesis was to use serum oxytocin concentration in the third trimester to predict PPD symptoms in the early postnatal period. We hypothesized that we can draw an inverse correlation between oxytocin concentration in the third trimester and postpartum depression symptoms in the early postnatal period, relying on the available data from older studies. [16, 17] Our aim was to suggest antenatal oxytocin as a specific biomarker capable of predicting PPD in the early postnatal period. By doing this, we would be able to identify potential candidates for PPD and we would treat them even before symptoms development; in order to reduce the adverse effects of PPD symptoms on the mother and on her newborn as well.
Unlike our proposed assumption, we found no significant association between endogenous antenatal serum oxytocin concentration in the late third trimester (34 to 36 weeks) and early postpartum depression symptoms (4 to 6 weeks). Our results partially agreed with (Massey, 2016) who at first found no correlation between antenatal oxytocin and PPD symptoms. But, a direct significant association appeared only among women with a life time history of depression.[18] In fact, when we tested oxytocin with postpartum depression symptoms among women with a lifetime history of depression, similar to (Massey, 2016), we found a non-significant inverse correlation.
Regarding (Skrundz, 2011), their study was the first to show a significant invers correlation between antenatal oxytocin with PPD symptoms. They showed that plasma oxytocin level significantly predicted PPD symptoms 2 weeks after delivery. Also, they found a significant correlation between oxytocin level and the gestational age at delivery.[16] Although the settings of the procedure between (Skrundz,2011) and ours were very similar, we did not find the inverse correlation between oxytocin and PPD symptoms, nor we found any relation between oxytocin and gestational age at delivery. This variance might be attributed to the difference in the number of participants (74:172), difference in the ethnic groups of participants (Switzerland: Jordan), difference of cut-point levels of EPDS (10:13), and difference of the time of assessment of PPD symptoms (2 weeks: 4 to 6 weeks).
In comparison with (Eapen,2014), they found a significant inverse correlation between oxytocin and depression. [17] However, this correlation was drawn between serum oxytocin 3 months after delivery with antenatal and postnatal depression. On the other hand, the significant correlation was lost when the test was conducted between antenatal oxytocin and postpartum depression, ending up with a similar result to ours.
In short, the results obtained by our work and by the aforementioned works testing the association between antenatal oxytocin and PPD are generally inconclusive. This conclusion was previously suggested by two recent systemic reviews by (Moura, 2016; Thul, 2020) testing the association between antenatal and postnatal oxytocin concentration with PPD symptoms. [19, 20] Here in, we are commenting on the inconsistency between the results and why it is not recommended yet to use antenatal serum oxytocin level alone in the prediction of PPD symptoms. First, (Skrundz, 2011) and (Massey, 2016) ended up with contradictory results, although they both found a correlation between antenatal oxytocin and PPD symptoms. By the time (Massey, 2016) suggested a positive correlation between oxytocin and PPD among women with previous major depressive disorders, (Skrundz, 2011) found a negative correlation. [16, 18] Second, (Massey, 2016) found no correlation at first between oxytocin and PPD symptoms, while a direct significant association appeared only among high risk group. This finding is suggesting that oxytocin alone was not capable of predicting PPD, it has needed another factor to interact with it before predicting PPD.
At the same time, it is illogical to ignore all the available evidence showing the link between oxytocin with maternal behavior, mother-infant bonding, and stress related disorders. [21, 22] Therefore, we are proposing few possible available theories that might be able to explain the disintegration between peripheral oxytocin level and its effect centrally. First, (Cyranowski, 2012) suggested that peripheral oxytocin may have a dysregulated pattern of release in depressed women. [23] Second, the genetic variation in the oxytocin receptor gene may play a role in modulating the response of different candidates to the same stimuli, as suggested by (Chen, 2011) and (Jonas 2013). [24, 25] Third, there may be different signals that alter the oxytocin physiological response. This theory was suggested by (Stubue, 2013) after they found that breast feeding had intensified the relation between oxytocin and PPD. [26]
Our study also showed that unlike oxytocin level, there was a statistically significant correlation between PPD and below Bachelor`s degree level of education, below 1000 Jordanian Dinars (≈ 1400 US Dollars) family monthly income, positive family history of depression, positive family issues, a previous history of depression, and absent emotional family support. In fact, association between PPD was a lifetime previous history of depression was noticeable.
Edinburgh Postnatal Depression Scale (EPDS) is the most commonly used validated screening tool for postpartum depression. [15, 27] Many scientific bodies are using it with different degrees of recommendations, where defining a clinically significant cut-off point is the most debatable factor. A score of 13 and above is the most widely used score to define probable depression. [28] We have used 13 as the cut-off point to keep standards consistent with the previously conducted study in 2006 in northern Jordan (the same region of our work) which showed the prevalence of PPD at 22.1%.[2] Our study has shown an alarming rise in the prevalence of PPD to 30.8% over nearly 13 years in the same place and among the same population. It is important to notice here that using a higher cut-off point may increase the specificity at the expense on the sensitivity. Of the total cohort, 13 participants (out of 172, representing 7.5%) admitted that they had had thoughts of harming themselves at different frequencies. One of them, had these thoughts quit often.
To the best of our knowledge, this study is the fourth study that looked at the prediction of PPD symptoms in the first three months after delivery by the third trimester serum oxytocin level, after (Skrundz, 2011; Eapen, 2014; Massy, 2016). Also, this study is the first-of-its-kind that tests the capability of predicting PPD symptoms by antenatal serum oxytocin concentration among Middle Eastern women. Furthermore, our sample is the biggest sample used, consisted of 172 participants.
There were some limitations in the study. The first limitation is that the sample was collected from a single hospital where most women descended from the same ethical, social and environmental background. Therefore, it is difficult to generalize the findings from a single region to be applied on all women. Hence, we advise future researches to collect a sample from different places for better understanding of the physiological changes of oxytocin among different ethnic groups. The second limitation is that EPDS, the most widely used tool for defining PPD symptoms, has limited sensitivity and specificity. For example, a recent estimate of the positive predictive value of EPDS was around 62%, which means that about 38% of women scoring > 13 on the EPDS were incorrectly diagnosed as having major depression. [29]