Kieran J. O'Donnell, PhD: The biological embeading of prenatal activity: pregnancy well-being and child development

December 01, 2020

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Assistant Professor, Yale Child Study Center and Department of Obstetrics, Gynecology and Reproductive Sciences

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00:00My name is Kieran O'Donnell an I am a very
00:03recent addition to the Child Study Center.
00:06Having started virtually on July 1st
00:09and then finally arriving in person
00:12in New Haven at the end of September
00:14and I am delighted to be here now.
00:17I lead the health or Mixon perinatal
00:19Epidemiology research group here at
00:21the Child Study Center and my research
00:23group capitalizes on our ability
00:25to characterize complex biological
00:27systems at greater depth and a greater
00:30breath than ever previously possible.
00:32And we mobilize these data on complex
00:34biological systems to improve perinatal
00:36health outcomes for both mother and child.
00:38Now, one of the biological systems that
00:40we spend a lot of time characterizing
00:43is the epigenome,
00:44and epigenetics quite simply means
00:46on top of genetics,
00:47and you can think of it as a series
00:50of chemical marks or modifications
00:52that sit on or close to the DNA.
00:55The building blocks of life.
00:57Now indeed,
00:58I like to think in more simple terms
01:00and when I think about the epigenome.
01:03I think of it as the biological interface
01:05between the environment and the genome.
01:08In fact,
01:08we can think about epigenetics as
01:10acting as a translator or as an
01:13interpreter to communicate between
01:14the environmental signals to the
01:16genome and effect lasting change
01:18in the function of the genome.
01:20And as I mentioned at the start
01:23of my presentation,
01:24we seek to mobilize data on
01:26these complex biological systems
01:27to improve health outcomes.
01:29So I'd like to tell you a little
01:31bit about some of the health
01:33outcomes that I'm particularly.
01:35Interested in and they can be summed
01:37up in three very simple numbers
01:40that frustrate me and fascinate
01:42me in equal measure.
01:44And for those of you who
01:46have heard me speak before,
01:48you'll know that I obsess
01:50about these numbers.
01:51I obsess about how we can
01:54make them even smaller.
01:55So what are these numbers?
01:57While these numbers are 414 and 4414 and 40,
02:01and these numbers reflect one in four,
02:03that's the number of women that struggle.
02:06With their mental health
02:08in an around pregnancy,
02:09it is a myth that pregnant women are
02:12protected from mental health problems.
02:14Indeed,
02:14many women struggle in or after
02:17pregnancy and fewer still receive
02:19adequate treatment and with less
02:20than 5% achieving remission,
02:22one in four.
02:23When I look around my family members
02:25when I look around my community,
02:28that statistic holds true on
02:30sadly so and I imagine that it
02:32would if you were to think about
02:34your community and your family.
02:37Also,
02:37So what are those other numbers
02:40while those other numbers refer to
02:42the costs associated with untreated
02:45perinatal mental health problems?
02:4714.2 billion US dollars per year,
02:5014.2 billion US dollars and 40%
02:53of those costs are derived from
02:56the adverse effects of maternal
02:58mental health problems on child
03:01outcomes and are my own research has
03:04shown that children born to women.
03:07We struggle with adverse mental
03:09health outcomes in or in pregnancy,
03:11have double the risk for mental health
03:13problems themselves and these effects
03:15are evident in early childhood and
03:17really persist until early adulthood.
03:19Now, one thing to note about these
03:22castings from the United States is that
03:25that 40% number actually refers to the
03:27costs from only zero to four years of age.
03:30So you can imagine what those costs
03:33are likely to be if we extend the
03:36follow up with those children.
03:38From 5 to 10 to 15 to 20
03:41years after pregnancy,
03:44so 414 and 40 are the numbers to remember.
03:49Now of course,
03:50everything I've just told you
03:52predates the ongoing global pandemic
03:54and in a Cordova thousand women
03:56that I lead in Montreal,
03:58the Montreal antenatal well being study.
04:00We've seen a profound in a tremendous impact
04:03of covid related stress on maternal anxiety.
04:06Indeed, before the pandemic,
04:07around 30% of women showed
04:09high levels of anxiety,
04:10which is already too many.
04:12And after the onset of the pandemic,
04:15we now see that number to be over 40%,
04:18almost one in two women.
04:20Showing high levels of anxiety post pandemic.
04:23Now we simply do not know what are the
04:26feedforward effects on child outcomes,
04:28but that is something that we want
04:31to address and we will be conducting
04:33a follow up study of the children
04:36born to these women at one year
04:39of age where will carry a detailed
04:41phenotyping of child development,
04:43developmental milestones,
04:44and indeed structure and function
04:46of the infant brain.
04:48Now,
04:48what else can we do to try and
04:51reduce those numbers?
04:52Reduced that 414 and 40?
04:54Well,
04:54one is to develop better screening tools,
04:57better identify those women that are at risk,
05:00and two projects that I'd like to
05:02share with you that are ongoing
05:04in my laboratories that I plan to
05:06extend and expand here at Yale
05:09include molecular screening tools for
05:11perinatal mental health problems.
05:12This was received Young investigator
05:14Grant from the brain and Behavior
05:16Research Foundation,
05:17for which I'm very grateful.
05:19For an on this,
05:20the premise of this screening tool
05:22is very simple.
05:23We know that some women show
05:25heightened sensitivity to the hormones
05:27of pregnancy and those women that
05:30you'll heightened sensitivity to.
05:31The performance of pregnancy maybe
05:33a greater risk for postpartum
05:35depression when those high levels of
05:37pregnancy hormones drop precipitously.
05:39Now we just don't have a way of
05:42quantifying at this at the moment,
05:44and we've been developing a novel
05:46blood test to assess hormone
05:48sensitivity in first trimester.
05:50Pregnant women so early in pregnancy
05:52so we can better understand which
05:54women are likely to be at risk.
05:56And the second aspect of our work
05:58in the screening arena is looking
06:00at the information that's contained
06:02in your back pocket.
06:03So within your smartphone and
06:05we're using passive data capture,
06:07so this is collecting data in the
06:09background from a smart phone and
06:11what we're seeking to do is develop
06:13digital index of social support.
06:15So how can we better quantify
06:17social support from using
06:19background data from a smart phone?
06:21And because we know that social support
06:23is critically important for preventing
06:25or reducing the risk of adverse mental
06:27health problems in and around pregnancy,
06:30now turning our focus to the child.
06:32The question is how we can better identify
06:35which children are likely to be impacted.
06:38As you remember from
06:39earlier in my presentation,
06:41I mentioned the children born to
06:43women that experience high levels of
06:45anxiety or depression in pregnancy
06:46have doubled the risk for adverse
06:49mental health outcomes themselves.
06:50But the key message too.
06:52Anyone that may be pregnant out there
06:54is that most children are not affected
06:57and those children that are affected
06:59can be affected in very different ways.
07:01And we've been turning our
07:03attention to the genome.
07:05Indeed,
07:05the regulation of the genome to
07:07better understand which children
07:09are likely to be affected and
07:10together with a group of colleagues,
07:13we have created a pediatric epigenetic Clock.
07:15So this is essentially a way of
07:17measuring biological age by assessing
07:19DNA methylation MP genetic change
07:21that occurs across the genome.
07:23And we quantify epigenetic age in children
07:25and we see it to be associated with autism.
07:29With children diagnosed with autism
07:31spectrum disorder showing accelerated
07:33epigenetic aging and very recent
07:35data from my student Megan Mcgill's
07:37showing the prenatal anxiety is
07:39associated with accelerated biological
07:41aging and we see these effects in
07:44mid childhood for the extend all the
07:46way back to the first year of life.
07:50So now that we've established
07:52proof of principle.
07:53That maternal, that this epigenetic biomarker
07:55is sensitive to the early environment.
07:57The question is how can we mobilize this
08:00information to improve outcomes for children.
08:03And that's where I'm very pleased to say that
08:06we're partnering with Doctor Megan Smith,
08:09who I believe you heard from yesterday.
08:12It was developed really phenomenal
08:14intervention to support vulnerable
08:16women in the Bridgeport area where
08:18their mental health will be supported.
08:20Mother Infant interaction will be
08:22supported as well as supporting.
08:24An multiple aspects of child development
08:27and we're seeking to implement this
08:29measure of biological aging at birth at
08:33one year of age and a two years of age,
08:36primarily to understand which
08:37children may not be responding as
08:40well to the intervention,
08:41and that will help us guide additional
08:44top of targeted interventions.
08:46So we're very excited to really move this
08:49into the experimental space where we can
08:52really probe cause and effect by using.
08:54A randomized control trial like 123 moms,
08:57and this adds to a growing number of
09:00interventions that we're implementing.
09:02These epigenetic biomarkers,
09:03including work in rural Vietnam,
09:05where as many as one in three women
09:08struggle with their mental health,
09:10and ultimately when we put this all together,
09:13the goal of my research program is to
09:17support pregnant women and ensure the
09:19best start in life for all children because.
09:23I firmly believe and agree with the
09:25statement an that Ann is illustrated
09:27here in this image that if we
09:29can change the beginning of the story,
09:32we can change the whole story and I
09:34believe that is true for both maternal
09:37mental health and child mental health.