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Abstract

No other period in a child's life matches the speed of brain development than the first nine months in the womb. Rapid growth goes hand in hand with enormous potential, but also with great vulnerability. This policy-focused review focuses on maternal mental health as a key factor for fetal brain development. Already during pregnancy, the fetal brain wires differently when exposed to maternal stress, and children prenatally exposed to stress have a higher risk of developing neurodevelopmental disorders. Maternal prenatal stress is preventable, treatable, and tractable by policy. Research-based, policy recommends: (1) screening for maternal mental health issues throughout pregnancy, (2) encourage talking about prenatal mental health, (3) evidence-based interventions for pregnant women with mental health issues, (4) avoiding stress-inducing communication towards pregnant women, and (5) stimulating positive postnatal parenting. Investing in healthy pregnancies will improve fetal brain growth, and, ultimately lead to a healthier next generation.

Keywords

prenatal brain development fetus pregnancy early life adversity

Maternal stress, depression, and anxiety are associated with later child behavioral and mental health issues. Investing in maternal mental health during pregnancy will improve healthy fetal brain growth, and, ultimately lead to a happier and healthier next generation.

Highlights

Maternal stress, depression, and anxiety are associated with later child behavioral and mental health issues;

Screening for mental health issues during pregnancy, including depression, anxiety, and stress, is recommended;

Preventive actions should be taken to decrease stigma and encourage talking about prenatal maternal mental health with health care providers;

There is a need for evidence-based intervention programs for pregnant women with mental health issues;

Policy should avoid stress-inducing communication towards pregnant women;

Investing in maternal mental health during pregnancy will improve healthy fetal brain growth, and, ultimately lead to a happier and healthier next generation.

Pregnancy is often viewed as a period of happiness and joy. Mothers are expected to be “glowing” and grateful for the opportunity to bring new life into the world. For a vast number of women, however, this is not the case. Meta-analyses showed that between 18.2% and 24.6% of women reported elevated anxiety symptoms during pregnancy, with higher symptom severity in the third trimester (Dennis et al., 2018). Moreover, about 14.4% of pregnant women in the United State of America reported the use of psychiatric medication during pregnancy (Huybrechts et al., 2013). Similar rates (15%) plague the Netherlands (Browne et al., 2020).

Self-reported percentages likely underestimate the true burden of mental health issues in pregnant women. Most pregnant women meeting the criteria for mental disorders are undiagnosed and untreated (Andersson et al., 2003; Glover, 2014). In one study, only 5.5% of women in need of treatment actually received it (Andersson et al., 2003). Care for the emotional well-being of pregnant women clearly seems to be a neglected part of obstetric medicine (Glover, 2014).

Besides burdening pregnant women, maternal stress during pregnancy can also affect the unborn child (Monk et al., 2019; Van den Bergh et al., 2020). Prenatal exposure to maternal anxiety increases risk for child anxiety disorders, attention deficit hyperactivity disorder (ADHD), autism, schizophrenia, behavioral problems, and depression (Lahti et al., 2017; McLean et al., 2018; Szekely et al., 2020; Yamada et al., 2021), also health complications, such as obesity (Burgueño et al., 2020) and infectious disease (Bush et al., 2021). Maternal anxiety and depression during pregnancy may contribute 10%–15% of the attributable load for child emotional and behavioral outcomes (Glover, 2014).

The Fetal Brain and Maternal Stress

The rapidly developing fetal brain may be particularly sensitive to maternal stress during pregnancy (Andersen, 2003; Bock et al., 2015; van den Bergh et al., 2018). Animal research supports this (Bock et al., 2015), as does human research. Neuroimaging in utero (rs-fMRI; van den Heuvel & Thomason, 2016) demonstrated that fetal brains exposed to maternal stress wire differently (De Asis-Cruz et al., 2020; Thomason et al., 2021; van den Heuvel et al., 2021)—alterations that may cause behavioral problems and alter neurocognitive functioning after birth (Meredith, 2015; van den Bergh et al., 2018, 2020).

Mechanisms: How Does Prenatal Exposure to Maternal Stress Affect the Fetal Brain?

How maternal stress during pregnancy gets “under the skin” of the unborn child, is still largely unknown. Five prominent mechanisms follow (for more information, see Beijers et al., 2014; Jašarević et al., 2015; Rakers et al., 2015; Van den Bergh et al., 2020). Understanding the mechanisms helps develop interventions for maternal stress during pregnancy and its negative impact on the unborn child.

Maternal Stress Hormones

Most often proposed is the maternal stress system (Beijers et al., 2014), releasing multiple hormones, including stress hormones (i.e., cortisol). Maternal and fetal cortisol correlate (Sarkar et al., 2007). Although some exposure to cortisol is essential for normal maturation, excessive levels may alter fetal brain development (Harris & Seckl, 2011; van den Bergh et al., 2018, 2020), ultimately resulting in developmental delays, psychopathology, and health issues later in life. However plausible, systematic review Zijlmans et al. (2015) concluded that cortisol may not be the main underlying mechanism.

The Placenta

The placenta protects the fetus (Shallie & Naicker, 2019). For example, a specific enzyme (i.e., 11β-HSD2) prevents most maternal stress hormones from crossing the placenta (Glover et al., 2009; Wyrwoll et al., 2011). Maternal anxiety may also alter the function of the placenta in other ways, such as via alterations in uterine blood flow, but the evidence is mixed (Kent et al., 2002; Monk, Newport, et al., 2012a; Teixeira et al., 1999). The precise role of the placenta in fetal brain development warrants further investigations (Beijers et al., 2014; O'Donnell et al., 2009). Still, placental functioning could mediate the association between maternal stress during pregnancy and negative child outcomes, such as lower birth weight in girls (Togher et al., 2018), higher stress responses in infants (Jahnke et al., 2021), and ADHD in boys (Shao et al., 2020).

Epigenetics: Changing Gene Expression

Epigenetic modifications are molecular mechanisms that alter gene activity without changing the DNA sequence (Babenko et al., 2015). Prenatal exposure to maternal stress can alter gene expression in multiple tissues, including the fetal brain or the placenta, potentially obstructing normal functioning and development (Babenko et al., 2015; Conradt et al., 2018; Monk, Spicer, et al., 2012b). Epigenetic changes have appeared in children prenatally exposed to maternal anxiety (Cao-Lei et al., 2015, 2021; Hompes et al., 2013; Mulligan et al., 2012; Schroeder et al., 2012), supporting prenatal exposure to maternal anxiety as altering gene expression in the fetus. Furthermore, epigenetic modifications may also alter fetal gene expression in interaction with other mechanisms; for example, via altering placental functioning (Monk, Spicer, et al., 2012b). Reported epigenetic changes of the placenta emerged in mothers suffering from psychological stress (e.g., Capron et al., 2018; Jensen Peña et al., 2012; Lund et al., 2021).

Changed Health Behaviors

When stressed, most people sleep less, eat unhealthy, and exercise less. For pregnant women, these changed health behaviors may negatively affect fetal development (De Weerth, 2018; Monk et al., 2013). Similarly, pregnant women with mental health issues and psychiatric disorders sleep less, sleep worse, and experience more exhaustion (Polo-Kantola et al., 2017; Qiu et al., 2012). Additionally, stressed pregnant women reported higher intake of fatty foods and snacks, a higher intake of micronutrients such as zinc and iron (Hurley et al., 2005), and a lower intake of important vitamins (Lobel et al., 2008). Furthermore, higher pregnancy-related stress is linked to less exercise (Lobel et al., 2008). Depressed women also reported a less active lifestyle during their pregnancy (Teofilo et al., 2014). Although stressed pregnant women alter health behavior and health behaviors alter fetal development (e.g., De Weerth, 2018), not much research has focused on this mechanism (De Weerth, 2018; Monk et al., 2013).

Postnatal Parenting

Many mothers stressed, anxious, or depressed during birth will develop postnatal mental health issues after birth (e.g., Grant et al., 2008; Heron et al., 2004; Sutter-Dallay et al., 2004). In turn, these mental health issues can negatively affect maternal parenting and mother–infant interaction quality (e.g., Hakanen et al., 2019; Ierardi et al., 2019; MacMillan et al., 2021). Prenatal and postnatal stress can have separate, potentially additive effects (Grant et al., 2009).

Women's brains change during pregnancy, likely preparing them to become better mothers (Barba-Müller et al., 2018; Gholampour et al., 2020; Hoekzema et al., 2016; Kim et al., 2010). However, in women stressed during pregnancy, the brain seems to respond less accurately to infant signals. For example, the brains of mothers with depression and anxiety were less responsive to happy infant faces (Arteche et al., 2011).

Policy Recommendations: What Can We Do About It?

Screen for Maternal Mental Health Issues Throughout Pregnancy

Any relevant policy must identify those women suffering or at risk (Austin, 2004; Trussell et al., 2018), yet screening is rare and often focused on postpartum depression only. Screening should start early and persist, to capture varied trajectories throughout prenatal and early postnatal years (Boekhorst et al., 2019; Korja et al., 2018).

A successful screening tool needs to be brief (< 5 min), easy to score (Trussell et al., 2018), ideally before a prenatal visit, and effectively translated (Shrestha et al., 2016). Practitioners should respond to mother's elevated symptoms immediately during the visit (Trussell et al., 2018).

Decrease Stigma and Talk About Prenatal Maternal Mental Health

Self-disclosure can be difficult for women due to experienced stigma of mental health issues and cultural norms about how women should feel during pregnancy. For instance, over 70% of women did not self-disclose symptoms of anxiety and depression because they regarded their feelings as a natural part of pregnancy (Browne et al., 2020). The main reason for women to self-disclose their symptoms was because their midwife asked about their mental health, whereas the main reason not to self-disclose was because their midwife did not ask about mental health issues (Browne et al., 2020). Mothers experiencing mental health issues during pregnancy indicated midwives as key to self-disclose and to facilitate uptake of treatment (Viveiros & Darling, 2018). Thus, midwifes and gynecologists break barriers for self-disclosure and should be well-trained to talk about mental health issues with their patients.

Nevertheless, midwifes and other health practitioners experience obstacles in referring their patients to effective treatment, especially at the beginning of the care-accessing process (Viveiros & Darling, 2019). For instance, midwifes reported that they are unaware of referral pathways and community resources or that these services are often unapproachable for various reasons (e.g., broken referral, not enough time to contact services, restrictive eligibility criteria). In one study, more than 50% of midwifes were unable to identify any services for their patients (Stanley et al., 2006). Indeed, to date, no clear protocols exist for referring women with mental health issues during pregnancy in most clinical settings (Glover et al., 2018). Additionally, many midwives reported that they felt insecure about bringing up mental health support because they either were afraid of insulting or shaming the mother or felt they lacked knowledge and skills to do so (Viveiros & Darling, 2019).

Other primary care providers, such as obstetricians, pediatricians, and family medicine practitioners reported similar barriers and lack of skills and training (Leiferman et al., 2008). In the same study, > 90% of the primary care providers expressed willingness to learn more about ways to enhance mental wellbeing in their patients. They preferred online education (CME/CEU) and clear guidelines as a method for receiving new information and training. Taken together, policy should focus on training primary care providers to talk openly about mental health issues, decrease the stigma, and support them with clear referral protocols.

Offer Evidence-Based Interventions for Pregnant Women's Mental Health

After identifying pregnant women at risk or already suffering from prenatal mental health problems, providing effective services promptly is key. Preferably, the interventions should start as early as possible to relieve the mother's suffering and to protect the fetal brain most effectively. Nevertheless, interventions in late pregnancy are likely to still be beneficial (Glover, 2014). Preventive interventions for women at risk could even start before pregnancy, focusing on self-care, such as sleep quality, regular exercise, and balanced dietary intake (Hurley et al., 2005). Social support and partner involvement also buffer against developing mental health issues during pregnancy (Boekhorst et al., 2019; Hughes et al., 2020; Takács et al., 2021).

Unfortunately, providing effective intervention has many barriers. First, only few evidence-based programs for pregnant women with (higher risk for) mental health issues exist (Glover et al., 2018). While numerous programs are developed, few underwent rigorous scientific investigation in well-controlled large randomized controlled trials (RCTs). A promising program dedicated to perinatal mental health issues is, among others, the Mindfulness-based Childbirth and Parenting (MBCP) program—a fully manualized childbirth preparation program adapted from Mindfulness-based Stress Reduction (Duncan & Shaddix, 2015). Recent RCT studies and qualitative studies so far support the effectiveness of this program in decreasing prenatal depression, stress, and anxiety and its acceptability in pregnant women and their partners (Lönnberg et al., 2018, 2020). Still, larger RCTs are necessary, as is testing these programs in different cultural contexts.

Access to these services is another issue. Women living in rural and underserved areas could encounter physical problems with accessing health care programs, such as lack of transport (Trussell et al., 2018). Online treatment services could form a solution here, but private internet access is an issue. Also, translating face-to-face programs into online formats requires great care and fresh validation; online versions might well be less effective (Boekhorst et al., 2021). Providing online services, especially unguided, might not be the best solution, even though easy and cheap.

Financial access is another barrier since many pregnant women with high stress, anxiety, and depression do not have insurance that covers mental healthfully or at all (Trussell et al., 2018). Minority and underserved women are more often lacking properly insurance and at higher risk for experiencing mental health issues during pregnancy (Gavin et al., 2011). Many midwives reported “insurance constraints” as a major barrier for effective referral (Viveiros & Darling, 2019). One solution would provide free prenatal mental health services.

Avoid Stress-Inducing Communication Towards Pregnant Women

Pregnant women are not responsible for negative outcomes of their unborn child due to their own stress or mental disorder. Pregnant women are already bombarded with advice on what not to do, eat, or feel by family, friends, media, and community. A whole list of foods and health practices already incur societal disapproval, such as smoking or drinking alcohol. For pregnant women already struggling, health care providers’ advice can be overwhelming and discouraging.

Effective training of health care providers, increased time during visits, and more continuous care could tackle this issue. Midwives reported time constraints as a major barrier for properly discussing mental health problems with their patients (Viveiros & Darling, 2019). Continued care, from the same professionals during pregnancy and at birth, can build a relationship safe for discussing mental health issues (Simcock et al., 2018; Viveiros & Darling, 2018).

Stimulate Positive Postnatal Parenting

Positive parenting after birth (“postnatal moderation”) can offset the negative effects of prenatal exposure to maternal depression or anxiety. Children exposed to elevated maternal distress during pregnancy did not display negative outcomes (decreased cognitive functioning and higher negative emotionality) if they received high-quality caregiving from their mother after birth (Grande et al., 2021). Secure attachment of the child to its mother and maternal sensitivity toward the child also protected the child from negative influences of maternal mental health issues during pregnancy (Bergman et al., 2008; Grant et al., 2010). This has major implications for policy since it suggests that investing in positive parenting in the early postnatal period can improve outcomes for children of mothers with prenatal mental health issues.

Conclusion

To provide children with the best start possible, invest in the emotional wellbeing of their mothers during and after pregnancy. (This is also good for the mother.) The child brain wires differently when prenatally exposed to maternal psychological stress; children born of mothers that experienced high levels of prenatal stress have a higher risk of neurodevelopmental disorders, such as autism, ADHD, and mood disorders. Fortunately, maternal mental health issues during pregnancy are preventable and treatable and, thus, targetable by policy. This policy-focused review provided several recommendations to improve maternal mental health during pregnancy. Investing in healthy pregnancies will improve fetal brain growth and, ultimately, lead to a healthier next generation.

Footnotes

Acknowledgments

This project was supported by awards to MvdH from the Dutch Research Council (NWO), Veni.VI.191G.025.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Nederlandse Organisatie Voor Wetenschappelijk Onderzoek (grant no Veni.VI.191G.025).

ORCID iD

Marion I. van den Heuvel

References

Andersen

S. L.

(2003). Trajectories of brain development: Point of vulnerability or window of opportunity? Neuroscience & Biobehavioral Reviews, 27(1–2), 3–18. http://ac.els-cdn.com/S0149763403000058/1-s2.0-S0149763403000058-main.pdf?_tid = e1b80198-ad51-11e4-a3c1-00000aab0f27&acdnat = 1423152971_941ad3b44f03103f191af6a85b640cf8 https://doi.org/10.1016/S0149-7634(03)00005-8

Andersson

., Sundstrom-Poromaa

Bixo

Wulff

Bondestam

åStröm

(2003). Point prevalence of psychiatric disorders during the second trimester of pregnancy: A population-based study. American Journal of Obstetrics and Gynecology, 189(1), 148–154, https://doi.org/10.1067/mob.2003.336

Arteche

Joormann

Harvey

Craske

Gotlib

I. H.

Lehtonen

Counsell

Stein

(2011). The effects of postnatal maternal depression and anxiety on the processing of infant faces. Journal of Affective Disorders, 133(1), 197–203. https://doi.org/10.1016/j.jad.2011.04.015

Austin

M. P.

(2004). Antenatal screening and early intervention for “perinatal” distress, depression and anxiety: Where to from here? Archives of Women’s Mental Health, 7(1), 1–6. https://doi.org/10.1007/s00737-003-0034-4

Babenko

Kovalchuk

Metz

G. A. S.

(2015). Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health. Neuroscience & Biobehavioral Reviews, 48(1), 70–91. https://doi.org/10.1016/j.neubiorev.2014.11.013

Barba-Müller

Craddock

Carmona

Hoekzema

(2018). Brain plasticity in pregnancy and the postpartum period: Links to maternal caregiving and mental health. Archives of Women's Mental Health,, 22(2), 289–299. https://doi.org/10.1007/s00737-018-0889-z

Beijers

Buitelaar

J. K.

de Weerth

(2014). Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: Beyond the HPA axis. European Child & Adolescent Psychiatry, 23(10), 943–956. https://doi.org/10.1007/s00787-014-0566-3

Bergman

Sarkar

Glover

O'Connor

T. G.

(2008). Quality of child-parent attachment moderates the impact of antenatal stress on child fearfulness. Journal of Child Psychology and Psychiatry, 49(10), 1089–1098. https://doi.org/D-NLM:NIHMS108266

Bock

Wainstock

Braun

Segal

(2015). Stress in utero: Prenatal programming of brain plasticity and cognition. Biological Psychiatry, 78(5), 315–326. https://doi.org/10.1016/j.biopsych.2015.02.036

10.

Boekhorst

Beerthuizen

Endendijk

J. J.

van Broekhoven

K. E. M.

van Baar

Bergink

Pop

V. J. M.

(2019). Different trajectories of depressive symptoms during pregnancy. Journal of Affective Disorders, 248, 139–146. https://doi.org/10.1016/j.jad.2019.01.021

11.

Boekhorst

M. G. B. M.

Hulsbosch

L. P.

Nyklíček

Spek

Kastelein

Bögels

Pop

V. J. M.

Potharst

E. S.

(2021). An online mindful parenting training for mothers raising toddlers: Assessment of acceptability, effectiveness, and personal goals. Mindfulness, 12(2), 519–531. https://doi.org/10.1007/s12671-020-01542-z

12.

Browne

P. D.

Bossenbroek

Kluft

van Tetering

E. M. A.

de Weerth

(2020). Prenatal anxiety and depression: Treatment uptake, barriers, and facilitators in midwifery care. Journal of Women's Health, 30(8), 1116-1126. https://doi.org/10.1089/jwh.2019.8198

13.

Burgueño

A. L.

Juarez

Y. R.

Genaro

A. M.

Tellechea

M. L.

(2020). Systematic review and meta-analysis on the relationship between prenatal stress and metabolic syndrome intermediate phenotypes. International Journal of Obesity, 44(1), 1–12. https://doi.org/10.1038/s41366-019-0423-z

14.

Bush

N. R.

Savitz

Coccia

Jones-Mason

Adler

Boyce

W. T.

Laraia

Epel

(2021). Maternal stress during pregnancy predicts infant infectious and noninfectious illness. The Journal of Pediatrics, 228, 117–125. e112. https://doi.org/10.1016/j.jpeds.2020.08.041

15.

Cao-Lei

Elgbeili

Massart

Laplante

D. P.

Szyf

King

(2015). Pregnant women's cognitive appraisal of a natural disaster affects DNA methylation in their children 13 years later: Project Ice storm. Translational Psychiatry, 5, e515. https://doi.org/10.1038/tp.2015.13

16.

Cao-Lei

van den Heuvel

M. I.

Huse

Platzer

Elgbeili

Braeken

M. A. K. A.

Otte

R. A.

Witte

O. W.

Schwab

Van den Bergh

B. R. H.

(2021). Epigenetic modifications associated with maternal anxiety during pregnancy and children’s behavioral measures. Cells, 10(9). https://doi.org/10.3390/cells10092421

17.

Capron

L. E.

Ramchandani

P. G.

Glover

(2018). Maternal prenatal stress and placental gene expression of NR3C1 and HSD11B2: The effects of maternal ethnicity. Psychoneuroendocrinology, 87, 166–172. https://doi.org/10.1016/j.psyneuen.2017.10.019

18.

Conradt

Adkins

D. E.

Crowell

S. E.

Monk

Kobor

M. S.

(2018). An epigenetic pathway approach to investigating associations between prenatal exposure to maternal mood disorder and newborn neurobehavior. Development and Psychopathology, 30(3), 881–890. https://doi.org/10.1017/S0954579418000688

19.

De Asis-Cruz

Krishnamurthy

Zhao

Kapse

Vezina

Andescavage

Quistorff

Lopez

Limperopoulos

(2020). Association of prenatal maternal anxiety with fetal regional brain connectivity. JAMA Network Open, 3(12), e2022349–e2022349. https://doi.org/10.1001/jamanetworkopen.2020.22349

20.

Dennis

C.-L.

Falah-Hassani

Shiri

(2018). Prevalence of antenatal and postnatal anxiety: Systematic review and meta-analysis. British Journal of Psychiatry, 210(5), 315–323. https://doi.org/10.1192/bjp.bp.116.187179

21.

De Weerth

(2018). Prenatal stress and the development of psychopathology: Lifestyle behaviors as a fundamental part of the puzzle. Development and Psychopathology, 30(3), 1129–1144. https://doi.org/10.1017/S0954579418000494

22.

Duncan

L. G.

Shaddix

(2015). Mindfulness-based childbirth and parenting (MBCP): Innovation in birth preparation to support healthy, happy families. International Journal of Birth and Parent Education, 2(2), 30–33. https://pubmed.ncbi.nlm.nih.gov/29051821; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645068/.

23.

Gavin

A. R.

Melville

J. L.

Rue

Guo

Dina

K. T.

Katon

W. J.

(2011). Racial differences in the prevalence of antenatal depression. General Hospital Psychiatry, 33(2), 87–93. https://doi.org/10.1016/j.genhosppsych.2010.11.012

24.

Gholampour

Riem

M. M. E.

van den Heuvel

M. I.

(2020). Maternal brain in the process of maternal-infant bonding: Review of the literature. Social Neuroscience, 15(4), 380–384. https://doi.org/10.1080/17470919.2020.1764093

25.

Glover

(2014). Maternal depression, anxiety and stress during pregnancy and child outcome; what needs to be done. Best Practice & Research Clinical Obstetrics & Gynaecology, 28(1), 25–35. https://doi.org/10.1016/j.bpobgyn.2013.08.017

26.

Glover

Bergman

Sarkar

O'Connor

T. G.

(2009). Association between maternal and amniotic fluid cortisol is moderated by maternal anxiety. Psychoneuroendocrinology, 34(3), 430–435. http://ac.els-cdn.com/S0306453008002655/1-s2.0-S0306453008002655-main.pdf?_tid = 250237f0-6544-11e2-b74f-00000aacb35e&acdnat = 1358935592_999682928d0abe81e7ceea0f2949ce53 https://doi.org/10.1016/j.psyneuen.2008.10.005

27.

Glover

O'Donnell

K. J.

O'Connor

T. G.

Fisher

(2018). Prenatal maternal stress, fetal programming, and mechanisms underlying later psychopathology—A global perspective. Development and Psychopathology, 30(3), 843–854. https://doi.org/10.1017/S095457941800038X

28.

Grande

L. A.

Swales

D. A.

Sandman

C. A.

Glynn

L. M.

Davis

E. P.

(2021). Maternal caregiving ameliorates the consequences of prenatal maternal psychological distress on child development. Development and Psychopathology, 1–10. Online ahead of print. https://doi.org/10.1017/s0954579421000286

29.

Grant

K.-A.

McMahon

Austin

M.-P.

(2008). Maternal anxiety during the transition to parenthood: A prospective study. Journal of Affective Disorders, 108(1), 101–111. https://doi.org/10.1016/j.jad.2007.10.002

30.

Grant

K.-A.

McMahon

Austin

M.-P.

Reilly

Leader

Ali

(2009). Maternal prenatal anxiety, postnatal caregiving and infants’ cortisol responses to the still-face procedure. Developmental Psychobiology, 51(8), 625–637. https://doi.org/10.1002/dev.20397

31.

Grant

K.-A.

McMahon

Reilly

Austin

M.-P.

(2010). Maternal sensitivity moderates the impact of prenatal anxiety disorder on infant responses to the still-face procedure. Infant Behavior and Development, 33(4), 453–462. https://doi.org/10.1016/j.infbeh.2010.05.001

32.

Hakanen

Flykt

Sinervä

Nolvi

Kataja

E.-L.

Pelto

Karlsson

Korja

(2019). How maternal pre- and postnatal symptoms of depression and anxiety affect early mother-infant interaction? Journal of Affective Disorders, 257, 83–90. https://doi.org/10.1016/j.jad.2019.06.048

33.

Harris

Seckl

(2011). Glucocorticoids, prenatal stress and the programming of disease. Hormones and Behavior, 59(3), 279–289. https://doi.org/10.1016/j.yhbeh.2010.06.007

34.

Heron

O'Connor

T. G.

Evans

Golding

Glover

(2004). The course of anxiety and depression through pregnancy and the postpartum in a community sample. Journal of Affective Disorders, 80(1), 65–73. https://doi.org/10.1016/j.jad.2003.08.004

35.

Hoekzema

Barba-Müller

Pozzobon

Picado

Lucco

García-García

Soliva

J. C.

Tobeña

Desco

Crone

E. A.

Ballesteros

Carmona

Vilarroya

(2016). Pregnancy leads to long-lasting changes in human brain structure [article]. Nature Neuroscience, 20(2), 287. https://doi.org/10.1038/nn.4458. https://www.nature.com/articles/nn.4458#supplementary-information.

36.

Hompes

Izzi

Gellens

Morreels

Fieuws

Pexsters

Schops

Dom

Van Bree

Freson

Verhaeghe

Spitz

Demyttenaere

Glover

Van den Bergh

Allegaert

Claes

(2013). Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Research, 47(7), 880–891. https://doi.org/10.1016/j.jpsychires.2013.03.009

37.

Hughes

Devine

Foley

Ribner

Mesman

Blair

(2020). Couples becoming parents: Trajectories for psychological distress and buffering effects of social support. Journal of Affective Disorders, 265, 372–380. https://doi.org/10.1016/j.jad.2020.01.133

38.

Hurley

K. M.

Caulfield

L. E.

Sacco

L. M.

Costigan

K. A.

Dipietro

J. A.

(2005). Psychosocial influences in dietary patterns during pregnancy. Journal of the American Dietetic Association, 105(6), 963–966. https://doi.org/10.1016/j.jada.2005.03.007

39.

Huybrechts

K. F.

Palmsten

Mogun

Kowal

Avorn

Setoguchi-Iwata

Hernandez-Diaz

(2013). National trends in antidepressant medication treatment among publicly insured pregnant women. General Hospital Psychiatry, 35(3), 265–271. https://doi.org/D - NLM: NIHMS587334

40.

Ierardi

Ferro

Trovato

Tambelli

Riva Crugnola

(2019). Maternal and paternal depression and anxiety: Their relationship with mother-infant interactions at 3 months. Archives of Women's Mental Health, 22(4), 527–533. https://doi.org/10.1007/s00737-018-0919-x

41.

Jahnke

J. R.

Terán

Murgueitio

Cabrera

Thompson

A. L.

(2021). Maternal stress, placental 11β-hydroxysteroid dehydrogenase type 2, and infant HPA axis development in humans: Psychosocial and physiological pathways. Placenta, 104, 179–187. https://doi.org/10.1016/j.placenta.2020.12.008

42.

Jašarević

Rodgers

A. B.

Bale

T. L.

(2015). A novel role for maternal stress and microbial transmission in early life programming and neurodevelopment. Neurobiology of Stress, 1, 81–88. https://doi.org/10.1016/j.ynstr.2014.10.005

43.

Jensen Peña

Monk

Champagne

F. A.

(2012). Epigenetic effects of prenatal stress on 11β-hydroxysteroid dehydrogenase-2 in the placenta and fetal brain. PLoS One, 7(6), e39791. https://doi.org/10.1371/journal.pone.0039791

44.

Kent

Hughes

Ormerod

Jones

Thilaganathan

(2002). Uterine artery resistance and anxiety in the second trimester of pregnancy. Ultrasound in Obstetrics & Gynecology: The Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, 19(2), 177–179. https://doi.org/10.1046/j.0960-7692.2001.00546.x

45.

Kim

Leckman

J. F.

Mayes

L. C.

Newman

M.-A.

Feldman

Swain

J. E.

(2010). Perceived quality of maternal care in childhood and structure and function of mothers’ brain. Developmental Science, 13(4), 662–673. https://doi.org/10.1111/j.1467-7687.2009.00923.x

46.

Korja

Nolvi

Kataja

E.-L.

Scheinin

Junttila

Lahtinen

Saarni

Karlsson

(2018). The courses of maternal and paternal depressive and anxiety symptoms during the prenatal period in the FinnBrain birth cohort study. PLoS One, 13(12), e0207856. https://doi.org/10.1371/journal.pone.0207856

47.

Lahti

Savolainen

Tuovinen

Pesonen

A.-K.

Lahti

Heinonen

Hämäläinen

Laivuori

Villa

P. M.

Reynolds

R. M.

Kajantie

Räikkönen

(2017). Maternal depressive symptoms during and after pregnancy and psychiatric problems in children. Journal of the American Academy of Child & Adolescent Psychiatry, 56(1), 30–39.e37. https://doi.org/10.1016/j.jaac.2016.10.007

48.

Leiferman

J. A.

Dauber

S. E.

Heisler

Paulson

J. F.

(2008). Primary care physicians’ beliefs and practices toward maternal depression. Journal of Women's Health, 17(7), 1143–1150. https://doi.org/10.1089/jwh.2007.0543

49.

Lobel

Cannella

D. L.

Graham

J. E.

DeVincent

Schneider

Meyer

B. A.

(2008). Pregnancy-specific stress, prenatal health behaviors, and birth outcomes. Health Psychology, 27(5), 604–615. https://doi.org/10.1037/a0013242

50.

Lönnberg

Jonas

Unternaehrer

Bränström

Nissen

Niemi

(2020). Effects of a mindfulness based childbirth and parenting program on pregnant women's perceived stress and risk of perinatal depression—results from a randomized controlled trial. Journal of Affective Disorders, 262, 133–142. https://doi.org/10.1016/j.jad.2019.10.048

51.

Lönnberg

Nissen

Niemi

(2018). What is learned from mindfulness based childbirth and parenting education?—Participants’ experiences. BMC Pregnancy and Childbirth, 18(1), 466. https://doi.org/10.1186/s12884-018-2098-1

52.

Lund

R. J.

Kyläniemi

Pettersson

Kaukonen

Konki

Scheinin

N. M.

Karlsson

Ekholm

(2021). Placental DNA methylation marks are associated with maternal depressive symptoms during early pregnancy. Neurobiology of Stress, 15, 100374. https://doi.org/10.1016/j.ynstr.2021.100374

53.

MacMillan

K. K.

Lewis

A. J.

Watson

S. J.

Bourke

Galbally

(2021). Maternal social support, depression and emotional availability in early mother-infant interaction: Findings from a pregnancy cohort. Journal of Affective Disorders, 292, 757–765. https://doi.org/10.1016/j.jad.2021.05.048

54.

McLean

M. A.

Cobham

V. E.

Simcock

Elgbeili

Kildea

King

(2018). The role of prenatal maternal stress in the development of childhood anxiety symptomatology: The QF2011 Queensland flood study. Development and Psychopathology, 30(3), 995–1007. https://doi.org/10.1017/S0954579418000408

55.

Meredith

R. M.

(2015). Sensitive and critical periods during neurotypical and aberrant neurodevelopment: A framework for neurodevelopmental disorders. Neuroscience & Biobehavioral Reviews, 50, 180–188. https://doi.org/10.1016/j.neubiorev.2014.12.001

56.

Monk

Georgieff

M. K.

Osterholm

E. A.

(2013). Maternal prenatal distress and poor nutrition—mutually influencing risk factors affecting infant neurocognitive development. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 54(2), 115–130. https://doi.org/10.1111/jcpp.12000

57.

Monk

Lugo-Candelas

Trumpff

(2019). Prenatal developmental origins of future psychopathology: Mechanisms and pathways. Annual Review of Clinical Psychology, 15, 317–344. https://doi.org/10.1146/annurev-clinpsy-050718-095539

58.

Monk

Newport

D. J.

Korotkin

J. H.

Long

Knight

Stowe

Z. N.

(2012a). Uterine blood flow in a psychiatric population: Impact of maternal depression, anxiety, and psychotropic medication. Biological Psychiatry, 72(6), 483–490. https://doi.org/10.1016/j.biopsych.2012.05.006

59.

Monk

Spicer

Champagne

F. A.

(2012b). Linking prenatal maternal adversity to developmental outcomes in infants: The role of epigenetic pathways. Development and Psychopathology, 24(4), 1361–1376. https://doi.org/10.1017/s0954579412000764

60.

Mulligan

C. J.

D'Errico

N. C.

Stees

Hughes

D. A.

(2012). Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics, 7(8), 853–857. https://doi.org/10.4161/epi.21180

61.

O'Donnell

O'Connor

T. G.

Glover

(2009). Prenatal stress and neurodevelopment of the child: Focus on the HPA axis and role of the placenta. Developmental Neuroscience, 31(4), 285–292, https://doi.org/10.1159/000216539

62.

Polo-Kantola

Aukia

Karlsson

Paavonen

E. J.

(2017). Sleep quality during pregnancy: Associations with depressive and anxiety symptoms. Acta Obstetricia et Gynecologica Scandinavica, 96(2), 198–206. https://doi.org/10.1111/aogs.13056

63.

Qiu

Gelaye

Fida

Williams

M. A.

(2012). Short sleep duration, complaints of vital exhaustion and perceived stress are prevalent among pregnant women with mood and anxiety disorders. BMC Pregnancy and Childbirth, 12(1), 104. https://doi.org/10.1186/1471-2393-12-104

64.

Rakers

Bischoff

Schiffner

Haase

Rupprecht

Kiehntopf

Kühn-Velten

W. N.

Schubert

Witte

O. W.

Nijland

M. J.

Nathanielsz

P. W.

Schwab

(2015). Role of catecholamines in maternal-fetal stress transfer in sheep. American Journal of Obstetrics and Gynecology, 213(5), 684.e1–9. https://doi.org/10.1016/j.ajog.2015.07.020

65.

Sarkar

Bergman

Fisk

N. M.

O'Connor

T. G.

Glover

(2007). Ontogeny of foetal exposure to maternal cortisol using midtrimester amniotic fluid as a biomarker. Clinical Endocrinology, 66(5), 636–640. https://doi.org/10.1111/j.1365-2265.2007.02785.x

66.

Schroeder

J. W.

Smith

A. K.

Brennan

P. A.

Conneely

K. N.

Kilaru

Knight

B. T.

Newport

D. J.

Cubells

J. F.

Stowe

Z. N.

(2012). DNA methylation in neonates born to women receiving psychiatric care. Epigenetics, 7(4), 409–414. https://doi.org/10.4161/epi.19551

67.

Shallie

P. D.

Naicker

(2019). The placenta as a window to the brain: A review on the role of placental markers in prenatal programming of neurodevelopment. International Journal of Developmental Neuroscience, 73, 41–49. https://doi.org/10.1016/j.ijdevneu.2019.01.003

68.

Shao

Wang

Huang

Wang

Liu

Wan

Yan

Hao

Zhu

Tao

(2020). Prenatal pregnancy-related anxiety predicts boys’ ADHD symptoms via placental C-reactive protein. Psychoneuroendocrinology, 120, 104797. https://doi.org/10.1016/j.psyneuen.2020.104797

69.

Shrestha

S. D.

Pradhan

Tran

T. D.

Gualano

R. C.

Fisher

J. R.

(2016). Reliability and validity of the Edinburgh postnatal depression scale (EPDS) for detecting perinatal common mental disorders (PCMDs) among women in low-and lower-middle-income countries: A systematic review. BMC Pregnancy and Childbirth, 16, 72. https://doi.org/10.1186/s12884-016-0859-2

70.

Simcock

Kildea

Kruske

Laplante

D. P.

Elgbeili

King

(2018). Disaster in pregnancy: Midwifery continuity positively impacts infant neurodevelopment, QF2011 study. BMC Pregnancy and Childbirth, 18(1), 309. https://doi.org/10.1186/s12884-018-1944-5

71.

Stanley

Borthwick

Macleod

(2006). Antenatal depression: Mothers’ awareness and professional responses. Primary Health Care Research & Development, 7(3), 257–268. https://doi.org/10.1191/1463423606pc295oa

72.

Sutter-Dallay

A. L.

Giaconne-Marcesche

Glatigny-Dallay

Verdoux

(2004). Women with anxiety disorders during pregnancy are at increased risk of intense postnatal depressive symptoms: A prospective survey of the MATQUID cohort. European Psychiatry, 19(8), 459–463. https://doi.org/10.1016/j.eurpsy.2004.09.025

73.

Szekely

Neumann

Sallis

Jolicoeur-Martineau

Verhulst

F. C.

Meaney

M. J.

Pearson

R. M.

Levitan

R. D.

Kennedy

J. L.

Lydon

J. E.

Steiner

Greenwood

C. M. T.

Tiemeier

Evans

Wazana

(2020). Maternal prenatal mood, pregnancy-specific worries, and early child psychopathology: Findings from the DREAM BIG consortium. Journal of the American Academy of Child & Adolescent Psychiatry, 60(1), 186–197. https://doi.org/10.1016/j.jaac.2020.02.017

74.

Takács

Štipl

Gartstein

Putnam

S. P.

Monk

(2021). Social support buffers the effects of maternal prenatal stress on infants’ unpredictability. Early Human Development, 157, 105352. https://doi.org/10.1016/j.earlhumdev.2021.105352

75.

Teixeira

J. M.

Fisk

N. M.

Glover

(1999). Association between maternal anxiety in pregnancy and increased uterine artery resistance index: Cohort based study. BMJ, 318(7177), 153–157, https://doi.org/10.1136/bmj.318.7177.153

76.

Teofilo

M. M. A.

Farias

D. R.

Pinto

T. d. J. P.

Vilela

A. A. F.

Vaz

J. d. S.

Nardi

A. E.

Kac

(2014). HDL-cholesterol concentrations are inversely associated with Edinburgh postnatal depression scale scores during pregnancy: Results from a Brazilian cohort study. Journal of Psychiatric Research, 58, 181–188. https://doi.org/10.1016/j.jpsychires.2014.07.030

77.

Thomason

M. E.

Hect

J. L.

Waller

Curtin

(2021). Interactive relations between maternal prenatal stress, fetal brain connectivity, and gestational age at delivery. Neuropsychopharmacology, 46, 1839–1847. https://doi.org/10.1038/s41386-021-01066-7

78.

Togher

K. L.

O’Keeffe

G. W.

Khashan

A. S.

Clarke

Kenny

L. C.

(2018). Placental FKBP51 mediates a link between second trimester maternal anxiety and birthweight in female infants. Scientific Reports, 8(1), 15151. https://doi.org/10.1038/s41598-018-33357-3

79.

Trussell

T. M.

Ward

W. L.

Conners Edge

N. A.

(2018). The impact of maternal depression on children: A call for maternal depression screening. Clinical Pediatrics, 57(10), 1137–1147. https://doi.org/10.1177/0009922818769450

80.

van den Bergh

B. R. H.

Dahnke

Mennes

. (2018). Prenatal stress and the developing brain: Risks for neurodevelopmental disorders. Development and Psychopathology, 30(3), 743–762. https://doi.org/10.1017/S0954579418000342

81.

Van den Bergh

B. R. H.

van den Heuvel

M. I.

Lahti

Braeken

de Rooij

S. R.

Entringer

Hoyer

Roseboom

Räikkönen

King

Schwab

(2020). Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy. Neuroscience & Biobehavioral Reviews, 117, 26–64. https://doi.org/10.1016/j.neubiorev.2017.07.003

82.

van den Heuvel

M. I.

Hect

J. L.

Smarr

B. L.

Qawasmeh

Kriegsfeld

L. J.

Barcelona

Hijazi

K. E.

Thomason

M. E.

(2021). Maternal stress during pregnancy alters fetal cortico-cerebellar connectivity in utero and increases child sleep problems after birth. Scientific Reports, 11(1), 2228. https://doi.org/10.1038/s41598-021-81681-y

83.

van den Heuvel

M. I.

Thomason

M. E.

(2016). Functional connectivity of the human brain in utero. Trends in Cognitive Sciences, 20(12), 931–939. https://doi.org/10.1016/j.tics.2016.10.001

84.

Viveiros

C. J.

Darling

E. K.

(2018). Barriers and facilitators of accessing perinatal mental health services: The perspectives of women receiving continuity of care midwifery. Midwifery, 65, 8–15. https://doi.org/10.1016/j.midw.2018.06.018

85.

Viveiros

C. J.

Darling

E. K.

(2019). Perceptions of barriers to accessing perinatal mental health care in midwifery: A scoping review. Midwifery, 70, 106–118. https://doi.org/10.1016/j.midw.2018.11.011

86.

Wyrwoll

C. S.

Holmes

M. C.

Seckl

J. R.

(2011). 11β-Hydroxysteroid dehydrogenases and the brain: From zero to hero, a decade of progress. Frontiers in Neuroendocrinology, 32(3), 265–286. https://doi.org/10.1016/j.yfrne.2010.12.001

87.

Yamada

Tanaka

Arakawa

Miyake

(2021). Perinatal maternal depressive symptoms and risk of behavioral problems at five years. Pediatric Research. https://doi.org/10.1038/s41390-021-01719-9

88.

Zijlmans

M. A.

Riksen-Walraven

J. M.

de Weerth

(2015). Associations between maternal prenatal cortisol concentrations and child outcomes: A systematic review. Neuroscience & Biobehavioral Reviews, 53, 1–24. https://doi.org/10.1016/j.neubiorev.2015.02.015

From the Womb into the World: Protecting the Fetal Brain from Maternal Stress During Pregnancy

Abstract

Keywords

Tweet

Highlights

The Fetal Brain and Maternal Stress

Mechanisms: How Does Prenatal Exposure to Maternal Stress Affect the Fetal Brain?

Maternal Stress Hormones

The Placenta

Epigenetics: Changing Gene Expression

Changed Health Behaviors

Postnatal Parenting

Policy Recommendations: What Can We Do About It?

Screen for Maternal Mental Health Issues Throughout Pregnancy

Decrease Stigma and Talk About Prenatal Maternal Mental Health

Offer Evidence-Based Interventions for Pregnant Women's Mental Health

Avoid Stress-Inducing Communication Towards Pregnant Women

Stimulate Positive Postnatal Parenting

Conclusion

Footnotes

Acknowledgments

Declaration of Conflicting Interests

Funding

ORCID iD

References