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

December 01, 2020

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

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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.