**Transcript of Cyberseminar**

**HERC Health Economics Seminar**

**Posttraumatic Stress Disorder, Military Sexual Trauma and Preterm Birth – Evidence from 16,000 VA Pregnancies**

**Presenter: Jonathan Shaw, MD**

**September 18, 2013**

*This is an unedited transcript of this session. As such, it may contain omissions or errors due to sound quality or misinterpretation. For clarification or verification of any points in the transcript, please refer to the audio version posted at www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact herc@va.gov.*

Ciaran Phibbs:My name is Ciaran Phibbs. I’m one of the Senior Economists at HERC. This is the Economics Cyberseminar. I realize that this is not an economics topic, although it is something that has big economic implications. Jonathan Shaw is one of the Fellows here at Palo Alto. He has background in Primary Care and he does have an interest in reproductive issues. He came to me because I have a have a longstanding history in doing Neonatal outcomes work and we put together this little project that he’s taken the lead on that I think is quite interesting. Without further ado, I’ll let Jonathan take over.

Jonathan Shaw:Thank you Ciaran for the introduction, we’ll have you back in a bit. I also want to thank HERC and Todd Wagner for inviting me to present our work today in looking at Posttraumatic Stress Disorder, as well as Military Sexual Trauma as potential risks factors for Preterm Births. This is a retrospective cohort study of over sixteen thousand delivers within the VA in Veterans. Before we move on, I do want to stop to just poll who our listeners are so we have a sense of people’s backgrounds. 

Moderator:Here is our poll question. We’re just looking for your primary professional role as researcher, clinician, quality manager, hospital administration, or other. Jonathan, I hate to throw this at you already, but we have already received a couple of comments that people are having trouble hearing you. Any way that you can project your voice a little better would be much appreciated.

Jonathan Shaw:I will try. Is that a good volume?

Moderator:It is better. Yeah. Here are our results for today’s session. About forty-seven percent researchers, thirty percent clinicians, two percent administration, and almost twenty percent are other. So it’s a nice mix of audience for you here today. I’ll turn it back over to you.

Jonathan Shaw:Thank you. I’d like to begin first off by acknowledging my co-authors. This work as Ciaran stated has been a part of my fellowship in health services research, under his mentorship, as well as in collaboration with Steve Asch, Susan Frayne, and Rachel Kimerling here at the VA in Palo Alto. And last, but not least, I acknowledge the important input of my colleague and wife, Kate Shaw, of Stanford Obstetrics and Gynecology. I also should say that there’s no conflict of interest to report, but I was supported in my fellowship by the VA Office of Academic Affairs and HSR&D. While a leader in health services research, the VA is not the first place that comes to mind when one thinks about maternal and child research. But in addition to unique and copious data as most of this audience is probably aware, the VA is in the midst of a significant demographic shift, which is fortuitous for those of us with an interest in women’s health included in neonatal outcomes. As women are increasingly represented in the military and similarly in the VA system as they take advantage of the health care coverage offered by the VA once they separate from the military. Early on in my fellowship, I was lucky enough to connect with Susan Frayne of the Women’s Health Evaluation Initiative, and with Ciaran Phibbs who as he mentioned has decades of research and expertise in looking at outcomes and economics of preterm birth. 

Maternal stress and depression are recognized as potential risk factors for poor birth outcome. However, the effect of posttraumatic stress in particular is less well-studied and remains uncertain. This is especially relevant now as a growing number of reproductive-age females return from military service. The invisible wounds of war or other trauma endured in the military might impact pregnancy and thus the next generation. Women currently represent approximately fourteen percent of those deployed to active service. Our specific aim in this project was to determine the extent to which posttraumatic stress is associated with spontaneous preterm birth with the hypothesis that PTSD contributes to preterm birth either through direct biological effect and/or through an indirect increase in risky behaviors such as substance abuse. Plausible biological links between PTSD and preterm birth include a number of pathways; Neuroendocrine, Inflammatory, and Vascular changes tend to be shared by PTSD and the premature onset of labor. 

For those who don’t have a background in women’s health, the definition of preterm delivery is birth prior to thirty-seven weeks gestation. Forty weeks is the average length of a normal gestation. Nearly one in eight deliveries in the U.S. ends in preterm birth. Preterm birth can be divided into two broad categories. One is the spontaneous onset, meaning labor begins early for generally unknown reasons. This is about half of preterm births. The other half is medically indicated, meaning that the decision is made to deliver before thirty-seven weeks for maternal health reasons or because of rest or health problems with the fetus. It’s the former that we’re focused on in this study, the spontaneous, abnormal onset of labor prior to thirty-seven weeks. Both forms of preterm birth come with high costs, both financial and emotional. It’s estimated that the societal burden in the U.S. is twenty-six billion dollars a year due to preterm birth. Despite this high prevalence and burden the cause is poorly understood, and were really poor at predicting which pregnancies will end in preterm birth. 

There are several risk factors which have been consistently identified for preterm birth with race in particular. African Americans have nearly double the risk of preterm births in the U.S. This is only partially explained by socioeconomic status differences. A socioeconomic status is a known risk factor, as are extremes of age in both teen pregnancies and in an advanced maternal age with specific substance use. There are several medical risks, most of them specific to pregnancy and unfortunately not largely modifiable. The biology of preterm birth is not well understood, but the maternal-fetal hypothalamic pituitary adrenal axis has been implicated in the placenta in the triggering of labor, and therefore a preterm labor having inflammatory and vascular changes.

Looking at stress in particular there have been several studies implicating it as the potential cause of preterm deliveries, so its role remains unclear. Observational studies have suggested that the second trimester of pregnancy may be particularly sensitive to stress. For example, a class et al found that the death of a close family member during the second trimester was associated with an increased risk of preterm birth, as well as a lower birthrate. In a smaller study following neuroendocrine markers of catecholamine through pregnancy, those women who had higher levels of catecholamine in the second trimester were at an increased risk of preterm birth. Hypothetical pathways through stress in particular that could impact preterm birth include any of the various mechanisms I mentioned before in our limited understanding of the triggers of labor in preterm birth of neuroendocrine, inflammatory, and vascular changes, as well as maternal behavior during the pregnancy that might change because of the stress they’re subjected to. 

Let’s turn to the specific stress we were looking at, Posttraumatic Stress Disorder, which I’ll refer to as PTSD from now on. PTSD is a mental health diagnosis with significant physiologic impact. It’s characterized by persistent distress or impaired function following a severely traumatic experience. Among the most common traumatic experiences that cause PTSD are sexual or physical assaults, combat or war exposure, and natural disasters. But there is no specific requirement that it be any of those. It’s characterized by a triad of symptoms. One is re-experiencing aspects of the trauma, for example flashbacks or nightmares. Secondly is the avoidance of stimuli’s that might act as reminders of the trauma, and thirdly hyper-arousal, for example hyper vigilance, difficulty concentrating, and disordered sleep. I’ll just mention that the DSM-5 has added a fourth symptom of negative mood or cognition, which would include things such as guilt and self-blame. There is a high comorbidity that overlaps with symptoms of depression, as well as anxiety. There’s a high prevalence of substance abuse within those with PTSD, which also can be viewed as self-medicating many of these symptoms. 

Looking specifically at PTSD as a possible link to preterm delivery, there’s been a handful of smaller prior studies. And while suggestive, they’ve been inconclusive. They reflect the difficulty in obtaining a large birth cohort with PTSD. In addition to the sample size limitations, they’ve had heterogeneity in diagnostic criteria and generalized ability concerns in that many are focused on rare disasters such as terrorist attacks. There’s been a study that’s looking at September 11th survivors, as well as Hurricane Katrina, but not really generalized to the more common causes of PTSD. No studies to date have been within a Veteran population. The largest and most suggestive prior studies were both by Julie Seng et al out of Michigan. They demonstrated a moderate increase in the odds observed in preterm birth in those women who had PTSD, but this did not reach the statistical significance. They also had an interesting finding that perhaps those who had PTSD in the context of a childhood abuse, were at most risk for a lower gestational age, or having a delivery earlier in the pregnancy.

The VA presents an ideal setting to examine the association between PTSD and preterm birth. We have a national cohort of unprecedented size. This is because the VA is the largest integrated health system in the U.S., and one in which the female representation has doubled in the post 9/11 era. PTSD is particularly prevalent unfortunately, in female Veterans. Upwards of twenty percent of Veterans receiving care in the VA have a prior PTSD diagnosis. In particular, female representation for pregnancy and delivery has also increased greatly from a few hundred deliveries a year covered by the VA in the year 2000 to now upwards of three thousand deliveries a year covered by the VA Health Care System. I should point out that while military women experience diverse traumas including combat, the most common antecedent of PTSD is still sexual trauma just as it is in the general population. There’s a caveat that the sexual trauma for Veterans often may have occurred while they were in the service. It’s defined as Military Sexual Trauma, MST.

Moving on to the specific methods of our retrospective cohort study, our cohort includes all deliveries paid for by the VA from the year 2000 to 2012 for a total of over sixteen thousand births among fourteen thousand Veteran mothers. The VA does not directly provide obstetric care in its facilities generally, but instead reimburses non-VA providers to ensure that women have access to the care. This so-called Ebid care means that the VA is acting as the insurer. So this means that our data included not only all of the VA provided care including primary care and mental health encounters, but also the billing records, specifically the claims records from the delivery hospitalizations that the VA covers for these sixteen thousand births. I do need to emphasize that we only had access to maternal records, not infant records, as traditionally only the mother is being considered the VA-covered patient. This has changed recently in terms of policies that are aligned with Medicaid where the infant is covered under the mothers insurance for seven days. So we still are yet to have good newborn data. 

This next slide outlines the various VA data sets that we used for those interested in the particulars. Just to summarize, we linked reimbursed delivery claims with the data for all VA provided care, inpatient and outpatient. The VA datasets indicating which Veterans have been deployed to recent operations in Afghanistan and Iraq, as well as the military sexual trauma roster which includes the results of near universal, one time mandatory screening for all incoming VA enrollees. Again, I want to clarify that we’re only looking at discharged Veterans. There are not any active military personnel. 

Our primary outcome was preterm delivery and specifically spontaneous preterm delivery. This was defined by a unique diagnosis code for this outcome. Using this comes with a caveat that we’re not detecting medically indicated. We’re only detecting approximately half of preterm births that result from the spontaneous onset of labor. This is arguably the sample of interest when we’re focusing on potential links between stress and the premature triggering of labor. It notably excludes deliveries for fetal problems or complications of pregnancy such as preeclampsia, which is a hypertensive disorder not uncommon in pregnancy. Before using the diagnosis ICD-9 code for spontaneous preterm delivery, we wanted to validate it externally. So we used California linked data which includes maternal claims data linked to infant birth certificate vital statistics. We found that it was reliable and highly specific, but correlating to a median gestational age of thirty-five weeks. What we also observed was likely under coding the outcome. Among those infants who were known to be preterm, the maternal record only had this code for about forty percent of the preterm births, whereas we’d expect about fifty or sixty-five percent of them to have actually been spontaneous preterm deliveries. This becomes relevant in interpreting the size we observed considering how much misclassification we may have had. 

Our primary predictor was PTSD as defined by the unique ICD-9 diagnosis code for this. And here with the VA we have the advantage of PTSD as now universally screened for within primary care using a standardized tool that’s actually embedded in the electronic medical record. This ICD-9 code has been validated within the VA data and has a high positive predictable value when compared to definitive subsequent clinical diagnosis. We considered anyone who had one or more PTSD diagnoses in the VA encounters prior to delivery as having PTSD. And perhaps most important we further distinguished the diagnosis into Active PTSD for those who had a diagnosis presenting an encounter in the year prior to the delivery date, versus Historical PTSD for those who only had an older diagnosis. The rationale was that those with Active PTSD diagnoses were likely those with clinically relevant symptoms during the prenatal period. I also want to mention as an aside for the researchers that for an insensitivity analysis we did examine them using a more rigorous definition requiring two occurrences of the ICD-9 code for Active PTSD. We did not find that that made much of a difference in our overall findings. 

The sources of trauma for PTSD Veterans are certainly not limited to combat, so just a word about Military Sexual Trauma or MST. To recognize high rates of sexual abuse recurring in the military, the VA introduced in 2002 universal screening for Military Sexual Trauma. The two screening questions are up here on the slide. For those of you who do not have access to it, they are easily available. I’ll just point out that MST is not a medical diagnosis or condition, but rather a screening tool to help identify and direct Veterans to appropriate mental health care. While it’s well validated, the screen can really indicate a wide range of traumatic experience from verbal sexual harassment to a full on sexual assault and rape. They’re relatively nonspecific to the degree of trauma. MST is relevant in this study not only because it strongly correlates with PTSD, but because some prior studies have suggested sexual trauma itself can be a risk factor for preterm birth. 

In addition to the primary predictor of PTSD and outcome of preterm birth, we considered demographic and obstetric risk factors as covariates. Those are listed up here including age, race, marital status, twins pregnancies, and a history of Cesarean sections. Then we looked at potential exposures both to Military Sexual Trauma as I mentioned and an OEF/OIF status. That means that those who were deployed to Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn, those deployed in service to our recent military operations in Iraq and Afghanistan. In addition to looking at those as covariates, we looked at interaction terms of potential interaction between Military Sexual Trauma and PTSD, and between deployment status and PTSD based on a hypothesis that the source of trauma might actually moderate the relationship with PTSD with preterm birth. 

Lastly, in addition to doing those primary demographic adjustments in looking at the trauma sources, we also wanted to explore three possible explanatory pathways. We looked first at preselected chronic comorbidities, specifically hypertension, diabetes, and asthma, which we found to be higher in those with PTSD and could arguably represent intermediate steps in the pathways. That is if the biological impact of chronic PTSD is actually predisposed to these chronic illnesses. All three of these have also been implicated in at least a handful of studies in being risk factors for preterm birth. Next let’s look at behavioral risks as optimal intermediaries. We evaluated models adjusting for drug, alcohol and tobacco use. And lastly we explored whether other mental disorders such as depression and anxiety, which are frequency code diagnoses PTSD, might play a role in the explanatory pathway. We evaluated those disorders, which had prevalence greater than two percent within our cohort. That included anxiety disorders, depression, bipolar disorders, and personality disorders. 

Moving on to our findings, in our cohort of over sixteen thousand deliveries the overall rate of spontaneous preterm birth was seven point eight percent. As a reminder, this would be expected to represent only about half of the total preterm births. For comparison, this prevalence of seven point eight percent is very similar to the eight percent observed in the nationally represented NIS, the National Inpatient Sample. Nineteen percent of our deliveries were in women with PTSD diagnoses any time prior to delivery and more than two thirds of those had Active PTSD. Again, that means that they had a PTSD diagnosis recorded in the year leading up to delivery. So that’s nearly two thousand deliveries in women with Active PTSD. 

The next slide looks at the patient characteristics broken down by PTSD status. We see that those women who had PTSD were more likely to be white, more likely to have been deployed to recent combat operations in Afghanistan or Iraq, and were more likely to screen positive for Military Sexual Trauma. For simplicity’s sake this does not show a breakdown by Active versus Historical PTSD, but I’ll just say that they share similar characteristics, except that those with Active PTSD were even more likely to have been deployed to Afghanistan or Iraq.  

Our unadjusted results show clearly that those with Active PTSD had a higher rate of spontaneous preterm births with over nine percent of deliveries among those women with Active PTSD were spontaneous preterm births. That’s two percent higher than those women with no PTSD. It’s also higher than the estimated national average. I’ll reiterate that we’re likely underestimating the true rates based on our validation of ICD-9 code and the acknowledgement that its likely underestimated for under codes to true spontaneous preterm births. 

For adjustment we performed logic regression using generalized estimating equations to account for correlation for Veterans with repeat deliveries. And in our primary adjusted model we see that Active PTSD is associated with preterm births within an adjusted odds ratio of one point three five. This is highly statistically significant. Those with Historical PTSD have no significant increase compared to those without with the odds ratio being just over one at one point zero six and nonsignificant. Those with Active PTSD had thirty-five percent increases in the odds of preterm births. 

In our analyses of Military Sexual Trauma, we found that Military Sexual Trauma was not associated with preterm births. Independently, MST was not a predictor of preterm births, which is actually not surprising when you recall that the screening questions are nonspecific to the severity or the prelae of the trauma. However, based on our plans to explore the potential interaction of MST and PTSD, when we broke it down into multilevel variables reflecting Veterans PTSD and MST status at the same time, we did find suggestions as this slide shows that those women who had both Active PTSD and screened positive Military Sexual Trauma were at the highest risk for the odds ratio of over one point four. As an interaction term this did not reach statistical significance. But it does suggest that there may be an interaction in those women who have PTSD in the context of sexual trauma may be worse off in terms of the risk of preterm births. 

Next we turn to explore the potential explanatory pathways. This slide is a bit busy, but it’s just showing comorbid medical and comorbid site diagnoses broken down by PTSD status. It shows that across the board those with PTSD had higher prevalence of hypertension, diabetes, asthma, as well as psychiatric diagnoses. In particular I’ll point out that of the women who had any PTSD diagnoses prior to delivery; eighty percent of them also had had a depressive disorder diagnosis at some point prior. Those with PTSD had four times the rate of drugs and alcohol abuse compared to those mothers without it. With this in mind it was really important to look at models adjusting for these to see whether they explained the increased risk of preterm birth associated with PTSD. When we adjusted for hypertension, diabetes, and asthma, even though these conditions were more common in those in those with PTSD, the adjustment made no significant difference. That means that we found no evidence that a higher risk of chronic illness explains these associations with preterm births. We similarly looked at substance abuse, and adjusting for active drug, alcohol, and tobacco use only slightly attenuated the size of Active PTSD. The odds ratio was just about one point three, and this remains highly statistically significant. It just suggests that the increased rates of substance abuse may account for some part of the causal pathway. Alternatively, it may be that we’re simply detecting a marker of a more severe PTSD. And that those that had had more severe PTSD, an increased risk of preterm births are also more likely to be using substances. 

Finally, because PTSD is so often co-diagnosed with other mental health conditions, we wanted to make sure we weren’t misattributing the effects. However, in multivariate adjustments for other active mental health diagnoses, Active PTSD remains robust and the association remains in the odds ratio of one point three or above. Nor were any of the alternative active mental health disorders more significant predictors of preterm birth. In fact, only bipolar disorders reached nominal significance, but did not reach a value of point zero five. I’ll just mention that we performance several additional sensitivity analyses, including stricter diagnosis for confirmed Active PTSD requiring two occurrences of ICD-9. So restricting our analysis to more recent years when the PTSD screening within the VA has been more standardized, adjusting for delivery count, delivery year, etc. Our findings under all of these sensitivity analyses were consistent. 

The conclusions of our main findings in what’s by the far the largest cohort of PTSD exposed deliveries to be studied with over three thousand women with a PTSD history, and nearly two thousand women with Active PTSD in the prenatal period, we found that Active PTSD appears to be a risk factor for preterm birth, increasing the risk to about thirty to thirty-five percent. For comparison, the largest previous study had about four hundred and fifty women. As I mentioned in the beginning, it showed a trend but was unable to reach statistical significance. We also found the suggestion that a subset, those with Military Sexual Trauma and Active PTSD in the context of that, had upwards of a forty percent increase risk of preterm birth. These findings were robust to adjustment for various potential confounders and explorations of various pathways. 

One of the strengths that we had within the VA is that the PTSD code is valid and we were also able to validate our outcome of the ICD-9 code for spontaneous preterm births. We also benefitted from having a design that allowed us to confirm that the PTSD diagnosis preceded the deliveries, and thus were able to move beyond the cross-sectional limitations that several large data analyses looking at mental health associations with birth outcomes have faced. All of this adds evidence to the support of the causal relationship, especially when combined with prior suggestive, but inconclusive studies. This all adds to our early, but limited understanding of the role of stress in triggering premature labor and preterm birth. Certainly more research is needed.

Looking specifically at the potential source of trauma, we did not see any interactions with deployment history and PTSD’s association with preterm birth. But I should point out that deployment itself was associated with a lower risk of preterm delivery. This may reflect a selection process for those who are deployed that result in a subpopulation of healthier, low risk individuals. This has been termed the “healthy warrior effect.” So in other words, those women who had a history of deployment, their overall rates of spontaneous preterm births were slightly lower overall. But the increase in risk was similar if they had access to it. For those women who had Military Sexual Trauma and PTSD, we did see a suggestion that they may have the worst outcomes, although this is not statistically significant. 

Several limitations, as with any observational study, includes that it’s hard to rule out residual confounding. However, the finding is that Active PTSD had a strong effect versus Historical PTSD, which does not have a significant effect might be interpreted as reflecting a biological gradient of a dose effect if we assume that those with Historical PTSD may still have some residual symptoms, but it’s not just reaching clinical diagnosis level. The most sanguine interpretation of this difference between Active PTSD and Historical PTSD would be that it supports the prospect that the treatment and recovery from PTSD could reduce it. In terms of generalizability to non-Veterans, I should point out that this is not a phenomenon unique to combat Veterans in that the majority of our cohorts were actually non-deployed Veterans. Only about a third of Veterans who delivered within our cohort were actually OEF/OIF Veterans. It’s important to add that PTSD is common in non-Veteran populations with five to ten percent of reproductive-aged women having an incident of PTSD. So all obstetric providers will inevitably find themselves caring for women with Active PTSD, regardless of whether they’re caring for a Veteran population. 

This leads to implications suggesting that pregnant patients with Active PTSD should be considered a high risk pregnancy. This is relevant outside the VA as well as within the VA where there’s a growing population of reproductive-aged female Veterans. It also highlights the need for maternal care coordination, especially between VA mental health and primary care providers and the community obstetrical providers caring for the majority of these pregnant vets. It also points to pregnancy as a unique opportunity for engaging patients in mental health care. For some of these young women who may not have much interaction with the health care system, pregnancy represents a time when they’re regularly followed. So it’s a good time to capture people and to offer appropriate mental health support. Within in the VA it may be time to consider prenatal and pre-conception care efforts specifically tailored to those with PTSD given that twenty percent of our cohort overall had had PTSD sometime prior. Actually in looking at the more recent years as more returning combat Veterans are getting pregnant, that rate is upwards of twenty-five percent of Veterans. 

The next steps for our research team are to attempt to link VA-enrolled Veteran parents in California to the birth certificate data that the robust data that California has. This would allow us to have actual detailed information on the gestational age of the birth and to have more specifics of the neonatal outcome, as well as to look at paternal PTSD as a contributing factor, and not just with maternal PTSD. It would allow the opportunity to compare the Veteran cohort overall to the non-Veteran cohort to identify whether as a whole Veteran pregnancies have unique risks. Additional research is also needed looking specifically at whether treatment of PTSD modifies the risks for preterm birth. And if future clinical trials were actually able to confirm that PTSD treatment reduces this risk, we’d have a blueprint for how to prevent the invisible wounds of trauma and more from extending into the next generation by improving birth outcome. PTSD pregnancies in Veterans with PTSD might present a unique study population for looking at biomarkers and stress hormones as we try and further elucidate how stress plays into preterm birth. Finally, the sub-population may be an area to look at for treatment for preventing preterm births. There is only currently one useful medical treatment for preterm birth, 17-OH Progesterone. It’s currently only routinely offered to women who have had a prior preterm birth. We do know that the women who have had it before are at risk of having it again. But it may be worth looking at a PTSD population as a high risk population to trial such an intervention. 

In this last slide I’ve included more as a teaser to show some additional exploratory analyses of other birth outcomes. These were not as hypothesis driven as looking specifically at spontaneous preterm birth. However, we wanted to look at other birth outcomes such as cesarean section rates, gestational diabetes, preeclampsia, fetal abnormality, bleeding complications are higher in those with PTSD. In particular we did have an expectation that you might see higher rates of preeclampsia, which is a hypertensive disorder of pregnancy given that blood pressure pathways are strongly linked with stress. Less expected was that gestational diabetes would be higher in those with PTSD. On the far right it shows that after adjusting for the other covariates that we used in our prior model, as well as adjusting for pre-existing hypertension and pre-existing diabetes, that gestational diabetes and preeclampsia unique stood out as being statistically and significantly different among those with Active PTSD. This would be plausible of a biological pathway for PTSD to affect birth outcomes that might include neuroendocrine, vascular, or inflammatory changes, as those certainly play a role in preeclampsia and in glucose intolerance. Further investigations of these are definetely needed. I’ll wrap up and open to questions. Before I do that, I do just want to acknowledge my co-authors again and to the many other Stanford and VA folks who have had helped me in doing this project. We’ll open up now to questions. As a reminder if you want to ask a question, type it in the Q&A and I will then respond to it orally. 

Moderator:And we do have a few questions out there. Ciaran, do you see those?

Ciaran Phibbs:I see them now. I had the wrong screen up. Okay. Was there screening for mild TBI? We didn’t do that. Someone else asked, “Do medications for depression and/or anxiety play a prior in preterm births?” Jonathan?

Jonathan Shaw:There have been a lot of studies of SSRI’s. It’s difficult because there’s a lot of confounding by indication. Obviously those women who are getting SSRI’s during pregnancy are going to be those who have more severe depression. Overall for SSRI’s, the most recent analysis that I’m familiar with suggested there really wasn’t an increase. If there is it’s very slight. We did not link to all of the pharmacy data for these patients. But to that qualitative assessment is that we would expect that if that was explaining a large chunk of this association, that those women with depression would actually be at a significantly increased risk of preterm birth within our cohort as a cluster of diagnoses compared to PTSD effect on those with depression. We would expect that we would have picked up a signal there. SSRI’s were largely driving the correlation. 

Ciaran Phibbs:We’ve got a couple of technical questions. One was, “Does the woman have to answer yes to both questions in the MST screen?” The answer is no. They only need to answer one. Someone wanted to know if this has been published? The answer is not yet, but it is under review. Someone wants to know if we have access to the slides? Heidi will address that at the end. Another question is, “Are you aware that any of the patients in your study were receiving mental health treatment during or prior to pregnancy?” Jonathan?

Jonathan Shaw:Certainly many were. We thought about adjusting for that, but again it’s really confounding by indication. I’ll point people towards the *Women’s Health Source Book* that are actually now two volumes. Women within the VA make very high use of mental health services. This is also a good time to point out that women covered by the VA, only a subpopulation of them opt to have the VA be their insurer for their pregnancy. A lot of women would be eligible for Medicaid as well. So our sense is that those women who get their deliveries and their pregnancy care covered by the VA are probably those who are most tied into the VA systems. And those tend to be those who are heavily tied into mental health services. So yes, certainly many of these women are getting mental health care, but trying to adjust to that it would be hard to know whether that was reflective that they were getting better care and so their symptoms less, or that they had more severe symptoms and so they were more likely to have the adverse effects. That would have been very difficult to weed out. We cannot simply adjust for those who are getting mental health care. Although I should point out that we required that all women have at least some encounters with the VA health system before their delivery. The advantage of the VA is that on that first primary care visit even if they’ve only had one, it is standard to be universally screened. 

Ciaran Phibbs:Someone asked if you controlled for childhood sexual abuse or adult civilian trauma? We did not have any data on that. We only had data from the VA codes. It could be in both places, so that biases our result towards the null, because it could have been there. As we said, there are several things that could lead us to underestimate the true affect. Someone wanted to know if there’s an increase of postpartum depression and/or psychosis with women with Active PTSD and/or preterm birth? We haven’t looked at that. We do know that there is an association with preterm delivery and postpartum depression.

Jonathan Shaw:Postpartum depression isn’t a PTSD symptom. Richard Shaw at Stanford has done a lot with behavioral health and mental health experience. Depending on how the preterm delivery was, they can have problems with preterm birth. And that’s why it’s really important actually that we were able to distinguish that the PTSD diagnoses predated the delivery and not the other way around. 

Ciaran Phibbs: Somebody else asked what’s the VA doing to help us obtain more data on infants born to our Veterans? I can’t address that directly, except that as the Associate Director of the Women’s Health Evaluation Initiative, we will be trying to include some women distributing data on outcomes of reproductive health in our source book. But that’s for a future plan. A part of it is just that there aren’t that many. So we have to wait until we get sufficient numbers to have meaningful data. As a practitioner, you can practice but it is on an individual basis. But we’re working on it. It’s the same thing with the VA Pregnancy Registry of not yet, but that’s certainly possible. 

Jonathan Shaw:I should point out that there’s.... Laurie Zephyrin....  the head of reproductive health within VA. There’s currently underway an effort for maternal care coordination. Well, there’s a directive and there is an effort to create tools to support that so that all Veterans who have pregnancies chose to be identified. In fact with the goal of specifically of making sure that there is coordination and communication between the VA providers who are more likely to be aware of the psychiatric diagnosis and medical issues. There needs to be communication between them and that the non-VA providers are providing the obstetrical care. That’s very much an active effort right now. 

Moderator:Fantastic. Okay, it looks like that is all of the questions that we have right now. Ciaran and Jonathan, I’m not sure if either of you have any final remarks you’d like to make before we close out today?

Jonathan Shaw:I’ll just say again thank you for opportunity for sharing our research. Ciaran, do you have anything to add?

Ciaran Phibbs:We hope to have this study published soon. We’re preparing a VA grant proposal to extend this work. There are other researchers working in this area, so there will be more information coming. It’s just been recently that there have been sufficient sample sizes of VA-covered pregnancies to start looking at. 

Moderator:Thank you. For our audience, thank you everyone for joining us today. As I close out this session in a minute here you will be prompted with a feedback form. If you could take a few moments to fill that out, we would appreciate it. We really do read through all of your feedback and we do make changes on our current and upcoming sessions based on what we receive in that feedback. Jonathan, thank you very much for presenting today. We really appreciate the time you put into preparing and presenting for us today, and we look forward to seeing your work published shortly. Thank you everyone for joining us for today’s HSR&D Cyberseminar and we look forward to seeing you at a future session. Thank you.

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