Prenatal developmental origins of future psychopathology: mechanisms and pathways

May combine two claims.

Maternal prenatal distress and maternal HPA activation are associated with increased risk for autism spectrum disorder, schizophrenia, depression, anxiety, and ADHD in offspring.

“Human studies relate maternal prenatal distress and maternal HPA activation to an increased risk for autism spectrum disorder (ASD), schizophrenia, depression, anxiety, and ADHD in offspring (Chan et al. 2018).”

• cites Chan et al. 2018Not checked yet

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The quote only partly states this claim.

Prenatal depression is similarly associated with increased risk of probable mental disorder in children, after adjustment for potential confounders including postnatal anxiety and depression, socioeconomic factors, obstetrical risks, and parenting.

“Results were similar for prenatal depression and included potential confounders (i.e., maternal postnatal anxiety and depression, socioeconomic factors, obstetrical risks, and maternal parenting) in the statistical models.”

• cites O’Donnell et al. 2014Not checked yet

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Exposure to ecologically valid social stressors early in gestation often results in pregnancy loss, whereas later exposure appears to have long-lasting cognitive, neurological, and behavioral effects in offspring, including hyperresponsiveness to stress and increased anxiety.

“Exposure to these more ecologically valid social stressors early in gestation often results in pregnancy loss, whereas later exposure appears to have long-lasting cognitive, neurological, and behavioral effects in offspring, including hyperresponsiveness to stress and increased anxiety (Brunton 2013).”

• cites Brunton 2013Not checked yet

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Prenatal stress exposure affects stress neurocircuitry in mice, increasing corticotropin-releasing factor in the amygdala and reducing hippocampal glucocorticoid receptor expression.

“PS exposure affects stress neurocircuitry in mice, including increasing corticotropin-releasing factor in the amygdala and reducing hippocampal glucocorticoid receptor expression (Mueller & Bale 2008).”

• cites Mueller & Bale 2008Not checked yet

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Maternal viral infection during the first trimester and maternal bacterial infection during the second trimester are associated with increased risk of autism spectrum disorder in children.

“a Danish study that included 10,000 children with autism found associations between maternal viral infection during the first trimester and maternal bacterial infection during the second trimester and ASD risk in children (Atladóttir et al. 2010).”

• cites Atladóttir et al. 2010Not checked yet

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Both prenatal maternal depression and cortisol levels during the first and second trimesters were related to emotional reactivity in preschool-age offspring, suggesting independent, sex-specific effects.

“A recent prospective longitudinal study documented that both prenatal maternal depression and cortisol levels during the first and second trimesters were related to emotional reactivity in preschool-age offspring, suggesting that both of these prenatal exposures may have independent, sex-specific effects (Swales et al. 2018).”

• cites Swales et al. 2018Not checked yet

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Offspring sex appears to play a critical role in determining outcomes and interacts with timing and type of prenatal stress exposure.

“An offspring’s sex appears to play a critical role in determining outcomes and, further complicating matters, interacts with the timing and type of PS exposure (Brunton & Russell 2010).”

• cites Brunton & Russell 2010Not checked yet

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Maternal distress may be associated with altered HPA axis regulation and higher circulating glucocorticoids, which can affect placental functioning and cross the placenta to reach the fetus.

“Since prenatal maternal distress may be associated with alterations in HPA axis regulation and higher levels of circulating glucocorticoids—which can affect placenta functioning and cross the placenta and reach the fetus (Monk et al. 2016, Stirrat et al. 2018)”

• cites Monk et al. 2016Not checked yet

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• cites Stirrat et al. 2018Not checked yet

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Maternal socioeconomic adversity is associated with lower placental HSD11B2 methylation, with greater effects in males than females.

“maternal socioeconomic adversity has been associated with lower levels of placental HSD11B2 methylation, with greater effects in males than females (Appleton et al. 2013).”

• cites Appleton et al. 2013Not checked yet

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Classified as probably not a substantial claim. May combine two claims.

The HPA axis is a central component of the hormonal stress response system, secreting glucocorticoids including cortisol, which alerts the organism to threat and maintains homeostasis.

“The hypothalamic–pituitary–adrenal (HPA) axis is a central component of the hormonal stress response system. It is responsible for secreting glucocorticoids, including cortisol, which alerts the organism to potential threat and maintains homeostasis (Herman & Cullinan 1997).”

• cites Herman & Cullinan 1997Not checked yet

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Maternal immune activation indexed by interleukin-6 and C-reactive protein is related to decreased fetal heart rate variability, altered functional connectivity between the medial prefrontal cortex and temporoparietal junction, and larger right amygdala volume with increased amygdala connectivity.

“MIA [indexed via levels of interleukin-6 (IL-6) and C-reactive protein] is related to potentially important intermediate phenotypes in the fetus and infant: decreased fetal heart rate variability (considered a physiological substrate of emotion regulation), alterations in functional connectivity between the medial prefrontal cortex and temporoparietal junction, and larger right amygdala volume and”

• cites Rudolph et al. 2018Not checked yet

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• cites Spann et al. 2018Not checked yet

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Animal studies suggest prenatal stress results in elevated basal and poststressor corticosteroids and decreased negative feedback of the HPA axis.

“Overall, animal studies suggest that prenatal stress (PS for animal models) results in elevated levels of basal and reactivity (i.e., poststressor) corticosteroids and decreased negative feedback of the HPA axis (Maccari et al. 1995).”

• cites Maccari et al. 1995Not checked yet

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Environmental insults can alter placental biology via epigenetic modifications and perturb transport and waste removal, such as nutrient transport deficiency leading to altered fetal growth.

“Environmental insults can alter placental biology, in part via epigenetic modifications, and lead to perturbation of the transport and waste removal functions, such as a deficiency in nutrient transport leading to altered fetal growth (Angiolini et al. 2006).”

• cites Angiolini et al. 2006Not checked yet

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These HPA changes in rats are accompanied by increased cognitive problems, anxiety, and depression-like behaviors through adulthood.

“These changes have been documented in rats alongside increased cognitive problems in offspring, anxiety, and depression-like behaviors, even through adulthood (Brunton & Russell 2010, St-Cyr et al. 2017).”

• cites Brunton & Russell 2010Not checked yet

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• cites St-Cyr et al. 2017Not checked yet

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Maternal cytokines can impact the fetus by crossing the placenta, affecting the placenta and causing inflammation, creating fetal immune dysregulation, or a combination of these.

“maternal cytokines can impact the fetus by (a) crossing the placenta and entering the fetal compartment (see the section titled Placental Functioning: DNA Modification), (b) affecting the placenta itself and causing placental inflammation and associated cytokine production, (c) creating fetal immune dysregulation, or (d) a combination of the three (Meltzer & Van de Water 2016).”

• cites Meltzer & Van de Water 2016Not checked yet

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In many studies, male offspring appear most strongly affected and often present with a dysmasculinized phenotype.

“In many studies, male offspring appear to be the most strongly affected. Interestingly, they often present with what is known as a dysmasculinized phenotype (i.e., with behaviors and gene expression patterns most commonly seen in females) (Bale 2016).”

• cites Bale 2016 sourceNot checked yet

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A study of 116 women with elevated cortisol during the second and third trimesters found increased stress responses in newborns but no association between maternal distress and cortisol.

“one study of 116 women with elevated cortisol levels during the second and third trimesters found increased stress responses in newborns but did not find an association between maternal distress and cortisol (Davis et al. 2011)”

• cites Davis et al. 2011Not checked yet

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Because cytokines are involved in dendritic growth and neuronal survival and differentiation, maternal immune activation may affect offspring outcomes through multiple aspects of brain development.

“Because cytokines are known to be involved in dendritic growth and neuronal survival and differentiation (Marx et al. 2001), MIA may exert its effect on offspring’s outcomes through multiple aspects of brain development”

• cites Marx et al. 2001Not checked yet

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Maternal stress is associated with increased placental DNA methylation of HSD11B2, which in turn is associated with reduced fetal coupling, indicating delayed neurobehavioral development.

“maternal stress was associated with increased placental DNA methylation of HSD11B2, which, in turn, was associated with a reduction in fetal coupling, indicative of delayed neurobehavioral development (N = 61, 51% female) (Monk et al. 2016).”

• cites Monk et al. 2016Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

None of the reviewed papers identified sex effects in infant outcomes.

“None of these papers identified sex effects in infant outcomes.”

May combine two claims.

Placental DNA methylation of NR3C1 and HSD11B2 predicts poorer self-regulation, lower muscle tone, and more lethargy in neonates.

“Placental DNA methylation of these two genes predicted poorer self-regulation, lower muscle tone, and more lethargy in neonates (N = 482, 47% female) (Conradt et al. 2013).”

• cites Conradt et al. 2013Not checked yet

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It is likely that maternal distress affects development of offspring HPA circuitry and brain development, and subsequent risk for psychopathology.

“it is likely that maternal distress affects the development of the offspring’s HPA circuitry and brain development, as well as the subsequent risk for psychopathology.”

Probably not a substantial claim: may not pass S2 (checkable).

Given the array of disorders associated with maternal perinatal inflammation, it is likely that the specific cause of inflammation, timing of exposure, and other environmental and individual factors interact and lead to different processes from maternal immune activation to risk for a range of psychopathologies in offspring.

“Given the array of disorders that have been associated with maternal perinatal inflammation, is it likely that the specific cause of inflammation (i.e., in response to bacterial infection versus experienced stress), the timing of exposure, and other environmental and individual factors (e.g., the offspring’s sex, genetic risk for a specific disease) interact and result in different processes”

May combine two claims.

The critical period of prenatal brain development is characterized by considerable plasticity and vulnerability, yet also opportunity.

“This critical period, also subserving corticogenesis, is characterized by considerable plasticity and, thus, vulnerability, yet also opportunity (Scheinost et al. 2017, Werker & Hensch 2015).”

• cites Scheinost et al. 2017Not checked yet

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• cites Werker & Hensch 2015Not checked yet

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Concordance between maternal prenatal and postpartum depression, versus nonconcordance, was associated with superior Bayley Scales scores at 3, 6, and 12 months.

“In one provocative paper, concordance between maternal prenatal (at 25 gestational weeks) and postpartum depression versus nonconcordance (so, two hits of depression versus only one in a traditional diathesis model) was associated with superior scores on the Bayley Scales of Infant and Toddler Development at 3, 6, and 12 months (Sandman et al. 2012).”

• cites Sandman et al. 2012Not checked yet

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Classified as probably not a substantial claim.

Barker described the fetus as adapting to its environment with programmed changes that potentially put offspring at risk for future disease.

“Barker (1995) describes the fetus as adapting to his or her environment with changes in their biology that become programmed, meaning embedded and long-lasting, with the idea that these programmed changes potentially put the offspring at risk for future disease.”

• cites Barker 1995Not checked yet

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It is likely that the type of infectious agent and timing of maternal inflammation interact with offspring sex and possibly underlie some inconsistency in findings.

“Thus, it is likely that the type of infectious agent and timing of maternal inflammation interact with an offspring’s sex and possibly underlie some of the inconsistency in findings (Rana et al. 2012).”

• cites Rana et al. 2012Not checked yet

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Glover and Sandman et al. suggest fetal adaptations aim at survival and exposure to maternal prenatal distress communicates characteristics of the postnatal world for which the fetus prepares via biological adaptations.

“Glover (2011) and Sandman et al. (2013) suggest that fetal adaptations are aimed at ensuring survival and that exposure to maternal prenatal distress functions as a communication foreshadowing characteristics of the postnatal world for which the fetus can begin to prepare via biological adaptations.”

• cites Glover 2011Not checked yet

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• cites Sandman et al. 2013Not checked yet

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Some studies document blunted HPA axis and stress responses in offspring, while others document the opposite.

“The direction of findings has also varied, with some studies documenting blunted HPA axis and stress responses in offspring (Vedhara et al. 2012) and others documenting the opposite (Capron et al. 2015).”

• cites Vedhara et al. 2012Not checked yet

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• cites Capron et al. 2015Not checked yet

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At 20 weeks, the brain has the necessary structures for mature functioning, although the cortical plate is smooth as gyri and sulci begin to form.

“At the midpoint of gestation, 20 weeks, the end of the early fetal period, the brain has the necessary structures for mature functioning, albeit with a smooth, lissencephalic versus ridged cortical plate, as the ridges (gyri) and depressions (sulci) are just beginning to form (Encha-Razavi & Sonigo 2003, Fogliarini et al. 2005).”

• cites Encha-Razavi & Sonigo 2003Not checked yet

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• cites Fogliarini et al. 2005Not checked yet

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A viral challenge with polyinosinic:polycytidylic acid on gestational day 9 resulted in hindered spatial exploration, whereas the same exposure on gestational day 17 led to poorer performance on a discrimination reversal learning task.

“a viral challenge with polyinosinic:polycytidylic acid on GD9 resulted in hindered spatial exploration in offspring, whereas the same exposure on GD17 led to poorer performance on a discrimination reversal learning task (i.e., increased perseverative behavior) (Meyer et al. 2006).”

• cites Meyer et al. 2006Not checked yet

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There is a significant association between maternal prenatal depression and risk for depression at 18 years old in females but not males.

“a significant association between maternal prenatal depression and risk for depression at 18 years old in females but not males (Quarini et al. 2015).”

• cites Quarini et al. 2015Not checked yet

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Males have a 72% increased risk of developing childhood ADHD if their mother lost a spouse or child during pregnancy.

“some studies show that males are more likely to be affected and have a 72% increased risk of developing childhood attention-deficit/hyperactivity disorder (ADHD) if their mother lost a spouse or child during pregnancy (van den Bergh et al. 2017)”

• cites van den Bergh et al. 2017Not checked yet

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A newer premise in the DOHaD model is that adaptation itself is programmed prenatally; exposure to prenatal distress fosters offspring sensitivity to environmental context, viewed as risk or opportunity depending on the child's life.

“Finally, a newer premise in the DOHaD model is that adaptation itself is being programmed prenatally. Here, exposure to prenatal distress fosters offspring’s sensitivity to the environmental context, which is viewed as a risk or opportunity factor, depending on the qualities of the child’s life (Hartman et al. 2018).”

• cites Hartman et al. 2018Not checked yet

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Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

Prenatal adaptations are hypothesized as inherently coming at a cost, namely a short-term survival benefit associated with future risk for poor neurodevelopmental outcomes.

“Alternatively, prenatal adaptations are hypothesized as inherently coming at a cost—that is, a short-term survival benefit associated with future risk for poor neurodevelopmental outcomes.”

May combine two claims.

High maternal prenatal anxiety is related to greater likelihood of ADHD in 4-year-old males and emotion regulation problems in females.

“high maternal prenatal anxiety related to greater likelihood of ADHD in 4-year-old males and emotion regulation problems in females (O’Donnell et al. 2014).”

• cites O’Donnell et al. 2014Not checked yet

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In rats, prenatal stress is associated with depression-like behavior and reduced PGC-1α protein in the frontal cortex and hippocampus of 3-month-old male offspring.

“In a preclinical study, PS induced in rats was associated with depression-like behavior and with a reduction of PGC-1α protein (a regulator of mitochondrial biogenesis) in the frontal cortex and hippocampus of their 3-month-old male offspring (Glombik et al. 2015).”

• cites Glombik et al. 2015Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Myelin is first detected between 20 and 28 weeks and enhances the speed and accuracy of neuronal communication.

“Myelin, which is first detected at between 20 and 28 weeks, enhances the speed and accuracy of neuronal communication (Tau & Peterson 2010).”

• cites Tau & Peterson 2010Not checked yet

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The vast majority of human maternal immune activation work examined infection-related maternal immune activation, and findings vary depending on timing and type of infectious agent.

“The vast majority of this work has examined infection-related MIA, and as in the rodent literature, findings vary depending on the timing of inflammation and type of infectious agent (Careaga et al. 2017).”

• cites Careaga et al. 2017Not checked yet

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Administering bacterial versus viral insults at the same time in males results in brain and behavioral differences associated with schizophrenia or increases in anxiety and depression-like behaviors.

“administering bacterial versus viral insults at the same time (GD 9) in males results in, respectively, brain and behavioral differences associated with schizophrenia [i.e., enlarged ventricles and reduced prepulse inhibition in males (Li et al. 2009)] or increases in anxiety and depression-like behaviors (Depino 2018).”

• cites Li et al. 2009Not checked yet

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• cites Depino 2018Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Maternal sleep patterns change throughout pregnancy due to alterations in reproductive hormones, increased nocturia, and body aches.

“Maternal sleep patterns undergo changes throughout pregnancy due to alterations in reproductive hormones, increased nocturia, and body aches (Pien & Schwab 2004).”

• cites Pien & Schwab 2004Not checked yet

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MSD impairs hippocampal neurogenesis and synaptic plasticity, which have been causally linked to disruptions in emotional and cognitive functioning.

“MSD has been found to impair hippocampal neurogenesis (Zhao et al. 2015) and synaptic plasticity (Yu et al. 2018), which have been causally linked to disruptions in emotional and cognitive functioning.”

• cites Zhao et al. 2015Not checked yet

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• cites Yu et al. 2018Not checked yet

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Early in pregnancy, deficits in maternal nutrient intake affect cell proliferation, while later deficits affect cell differentiation, synaptogenesis, and dendritic arborization in preclinical studies.

“Early in pregnancy, deficits in maternal nutrient intake have been shown to affect cell proliferation, while deficits later in pregnancy have been shown in preclinical studies to affect cell differentiation, synaptogenesis, and dendritic arborization (Monk et al. 2013, Prado & Dewey 2014).”

• cites Monk et al. 2013Not checked yet

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• cites Prado & Dewey 2014Not checked yet

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Based on a nonnutritive sucking paradigm, 3-day-old infants identified their mother's voice over another woman's and sucked more to elicit hearing it.

“Based on a nonnutritive sucking paradigm, 3-day-old infants showed they identified their mother’s voice (reading Dr. Seuss) over another woman’s and sucked more to elicit hearing it (DeCasper & Fifer 1980).”

• cites DeCasper & Fifer 1980Not checked yet

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Before birth, fetuses register sensory experience, and there is evidence of transnatal learning.

“Before birth, fetuses register sensory experience, and there is evidence of transnatal learning—that is, learning that occurs as a fetus is carried across the birth divide (Busnel et al. 2017, Moon & Fifer 2000).”

• cites Busnel et al. 2017Not checked yet

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• cites Moon & Fifer 2000Not checked yet

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Because the developing brain has high metabolic demand, microbial colonization may significantly influence brain maturation and potentially the risk for neuropsychiatric disease.

“Because the developing brain exerts a high metabolic demand, microbial colonization may significantly influence brain maturation and, potentially, the risk for neuropsychiatric disease (Keunen et al. 2014).”

• cites Keunen et al. 2014Not checked yet

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Poor prenatal sleep is related to elevations in both maternal circulating cytokines and cortisol levels.

“Finally, because poor prenatal sleep is related to elevations in both maternal circulating cytokines (Okun et al. 2009) and cortisol levels (Bleker et al. 2017),”

• cites Okun et al. 2009Not checked yet

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• cites Bleker et al. 2017Not checked yet

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Preference for the maternal voice over another woman's likely subserves bonding, while transnatal memory for language-specific properties may undergird language development.

“this preference for the maternal voice over another woman’s likely subserves bonding while transnatal memory for language-specific properties may undergird language development.”

• cites Busnel et al. 2017Not checked yet

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• cites DeCasper & Fifer 1980Not checked yet

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Rodent models have typically examined a gestational period comparable to third-trimester human MSD, and studies examining first- and second-trimester MSD have been inconsistent in documenting emotional deficits.

“Rodent models have typically examined a gestational period comparable to third-trimester human MSD (Radhakrishnan et al. 2015, Yu et al. 2018, Zhao et al. 2015), and the studies examining first- and second-trimester MSD have been inconsistent in documenting emotional deficits (Calegare et al. 2010).”

• cites Radhakrishnan et al. 2015Not checked yet

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• cites Yu et al. 2018Not checked yet

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• cites Zhao et al. 2015Not checked yet

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Classified as probably not a substantial claim. May combine two claims.

Because childhood sleep problems predict future psychopathology, poor maternal prenatal sleep may increase offspring's risk of mental illness through this pathway.

“Because childhood sleep problems are predictive of future psychopathology (Gregory & O’Connor 2002), it is possible that poor maternal prenatal sleep increases offspring’s risk of mental illness through this pathway.”

• cites Gregory & O’Connor 2002Not checked yet

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Reductions in amino acid concentrations across brain regions in offspring of stressed dams are more pronounced in males, suggesting increased susceptibility to metabolic programming of the developing brain in males.

“These reductions were more pronounced in male offspring, suggesting increased susceptibility to metabolic programing of the developing brain in males (Jašarević et al. 2015),”

• cites Jašarević et al. 2015Not checked yet

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The quote only partly states this claim.

Given fetal imaging studies demonstrating sensory-driven plasticity, these findings suggest the possibility of in utero shaping of fetal neural organization and infant postnatal behavior based on the pairing of varying maternal emotions with external auditory stimuli.

“Given emerging fetal imaging studies demonstrating sensory-driven plasticity (Anderson & Thomason 2013), these findings suggest the possibility of in utero shaping of fetal neural organization and infant postnatal behavior based on the pairing of varying maternal emotions”

• cites Anderson & Thomason 2013Not checked yet

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• cites Tallet et al. 2016Not checked yet

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Infants born via vaginal delivery show a bacterial composition resembling their mothers' vaginal microbiome, whereas babies born via Cesarean section show more skin-like microbiomes.

“For example, infants born via vaginal delivery show a bacterial composition resembling their mothers’ vaginal microbiome, whereas babies born via Cesarean section show more skin-like microbiomes (Dominguez-Bello et al. 2010).”

• cites Dominguez-Bello et al. 2010Not checked yet

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Altered sleep is common, and further sleep loss, including that associated with maternal distress, can place both mother and offspring at risk for negative health trajectories including poor birth outcomes.

“Altered sleep is a common occurrence, yet any further sleep loss—including that associated with maternal distress—can place both mother and offspring at risk for negative health trajectories, including poor birth outcomes (reviewed elsewhere, see Palagini et al. 2014).”

• cites Palagini et al. 2014Not checked yet

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Recent rodent studies challenge the existence of a sterile in utero environment, suggesting earlier mother-infant microbiome transmission likely through the placental barrier or fetal ingestion of amniotic fluid.

“Moreover, recent rodent studies challenge the existence of a sterile in utero environment, suggesting an even earlier mother–infant microbiome transmission, likely through the placental barrier or fetal ingestion of amniotic fluid (Walker et al. 2017).”

• cites Walker et al. 2017Not checked yet

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Both maternal experiences of stress and inadequate nutrition may affect the fetus via related biological pathways.

“Both maternal experiences of stress and inadequate nutrition may affect the fetus via related biological pathways (Monk et al. 2013).”

• cites Monk et al. 2013Not checked yet

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In humans, maternal consumption of a high-fat diet during pregnancy is associated with an increased incidence of behavioral problems, poorer regulatory capacity, and lower surgency in infants and children.

“In humans, maternal consumption of a high-fat diet during pregnancy has been associated with an increased incidence of behavioral problems, poorer regulatory capacity, and lower surgency (i.e., low interest and motivation) in infants and children (Gustafsson et al. 2015, Pina-Camacho et al. 2015, Steenweg-de Graaff et al. 2014).”

• cites Gustafsson et al. 2015Not checked yet

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• cites Pina-Camacho et al. 2015Not checked yet

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• cites Steenweg-de Graaff et al. 2014Not checked yet

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Distress during pregnancy is highly predictive of postpartum distress and future parenting.

“This is especially important given the likelihood that distress during pregnancy is highly predictive of postpartum distress and future parenting (Glover & Capron 2017).”

• cites Glover & Capron 2017Not checked yet

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Probably not a substantial claim: may not pass S4 (based).

Distress in pregnancy is usually a factor that can be changed.

“Maternal prenatal distress is only one of many, many influences on children’s futures; distress during pregnancy is typically a modifiable factor, and interventions with distressed pregnant women can help women and may positively affect their children as well.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

Research into prenatal distress must be considered in context such that prenatal programming via maternal distress occurs as one of a multitude of factors influencing fetal and infant neural organization and brain-behavior development.

“research into prenatal distress must be considered in context such that prenatal programming via maternal distress occurs as one of a multitude of factors influencing fetal and infant neural organization and brain–behavior development.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Women feel immense pressure regarding the mothering role.

“There is no doubt that women feel immense pressure regarding the mothering role (Howorth 2017);”

• cites Howorth 2017Not checked yet

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Classified as probably not a substantial claim.

The identification of maternal distress as a factor in prenatal programming, with implications for future neurobehavioral development, introduces a possible time point for preventative interventions targeting fetal and child adaptations that may signal risk.

“The identification of maternal distress as a factor in prenatal programming, with implications for future neurobehavioral development of the child, introduces a possible time point for providing preventative interventions targeting fetal and child adaptations that may signal risk,”

Probably not a substantial claim: may not pass S4 (based).

Maternal distress may serve as a marker for another variable that is the true agent affecting offspring's outcome, for example, poor nutrition.

“As indicated, maternal distress may serve as a marker for another variable that is the true agent affecting offspring’s outcome, for example, poor nutrition.”

May combine two claims.

The best rodent models of prenatal stress cross-foster pups during rearing because previously stressed dams parent differently and/or their prenatally stressed offspring elicit different caregiving, and these models still identify prenatal stress effects on offspring outcomes.

“Indeed, the best rodent models of PS cross-foster the pups during rearing because previously stressed dams parent differently (and/or their PS-exposed offspring elicit different caregiving) (Weinstock 2017), and these models still identify PS effects on offspring’s outcomes.”

• cites Weinstock 2017Not checked yet

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Prenatal SSRI exposure is associated with gray matter expansion in the amygdala and insula in sleeping newborns and greater connectivity between the two regions, possibly indicating a potential for heightened fear conditioning and risk for future anxiety disorders.

“For example, prenatal SSRI exposure is associated with gray matter expansion in the amygdala and insula in sleeping newborns and greater connectivity between the two regions, possibly indicating a potential for heightened fear conditioning and risk for future anxiety disorders (Lugo-Candelas et al. 2018).”

• cites Lugo-Candelas et al. 2018Not checked yet

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Improvement in mood during pregnancy is thought to diminish risks for postpartum depression and associated effects on the child and to foster more positive representations of the child in utero that carry over into the quality of the mother-child attachment system.

“improvement in mood during pregnancy is thought to diminish risks for postpartum depression and the associated effects on the child and to foster more positive representations of the child in utero that will carry over into the quality of the mother–child attachment system (Glover & Capron 2017).”

• cites Glover & Capron 2017Not checked yet

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Pregestational diabetes and gestational diabetes mellitus have been associated with altered cognitive outcomes in offspring and with an increased risk for autism spectrum disorder.

“Pregestational diabetes and GDM have been associated with altered cognitive outcomes in the offspring (Adane et al. 2016) and with an increased risk for ASD (Sacks et al. 2016, Xiang et al. 2015).”

• cites Adane et al. 2016Not checked yet

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• cites Sacks et al. 2016Not checked yet

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• cites Xiang et al. 2015Not checked yet

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The lack of diversity and representation in research samples is not only an ethical dilemma but also a scientific one, given that the effects of race and ethnicity on disease risk and treatment response are well documented.

“This lack of diversity and representation in research samples is not only an ethical dilemma but also a scientific one, given that the effects of race and ethnicity on disease risk and treatment response are well documented.”

• AssumptionRests on an assumption: The effects of race and ethnicity on disease risk and treatment response are well documented.

May combine two claims.

Psychological stress, anxiety, and depression are risk factors for infection and for diseases such as diabetes and hypertensive disorders such as preeclampsia.

“Psychological stress, anxiety, and depression are risk factors for infection (Cohen et al. 1991) as well as for diseases, such as diabetes (Hackett & Steptoe 2017), and hypertensive disorders, such as preeclampsia (Zhang et al. 2013),”

• cites Cohen et al. 1991Not checked yet

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• cites Hackett & Steptoe 2017Not checked yet

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• cites Zhang et al. 2013Not checked yet

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May combine two claims.

In a study of children conceived via in vitro fertilization compared with controls, there was an independent effect of prenatal maternal distress on children's risk for antisocial behavior and anxiety, present in both related and unrelated children, but not for ADHD, which was seen uniquely in children related to their mother.

“Results indicated there was an independent effect of prenatal maternal distress on children’s risk for antisocial behavior and anxiety (i.e., the risk was present in both related and unrelated children) but not for ADHD (i.e., it was seen uniquely in children related to their mother) (Rice et al. 2010).”

• cites Rice et al. 2010Not checked yet

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May combine two claims.

Exposures and mechanisms may exert an influence on each other, as observed for maternal nutrition and stress and hypothesized for prenatal inflammation and the microbiome.

“Further, it is important to acknowledge that exposures and mechanisms may exert an influence on each other, as we and others have observed to be the case for maternal nutrition and stress (Lindsay et al. 2019, Monk et al. 2013), and others have hypothesized for prenatal inflammation and the microbiome (Kim et al. 2017).”

• cites Lindsay et al. 2019Not checked yet

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• cites Monk et al. 2013Not checked yet

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• cites Kim et al. 2017Not checked yet

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May combine two claims.

Hypertensive disorders during pregnancy are associated with higher risks of offspring developing behavioral problems, ADHD, affective disorder, and schizophrenia.

“Hypertensive disorders during pregnancy are associated with higher risks of offspring developing behavioral problems, ADHD, affective disorder, and schizophrenia (reviewed in Dachew et al. 2018).”

• cites Dachew et al. 2018Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable).

It is terrifically challenging to assess and thereby control for the extent of postnatal influences on children's development that might be foreshadowed by and thus associated with maternal prenatal distress.

“With respect to feasibility and costs, it is terrifically challenging to assess, and thereby control for, the extent of postnatal influences on children’s development that might be foreshadowed by, and thus associated with, maternal prenatal distress.”

May combine two claims.

Experiencing multiple exposures may result in additive or interactive effects that, if unaccounted for, may contribute to mixed findings in the literature.

“Experiencing multiple exposures may result in either additive or interactive effects that, if unaccounted for, may contribute to mixed findings in the literature.”

• AssumptionRests on an assumption: Mothers and therefore their fetuses are exposed to a number of factors simultaneously.

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

Because brain development begins before birth, parenting begins before birth.

“Because brain development begins before birth, parenting begins before birth (Glover & Capron 2017).”

• cites Glover & Capron 2017Not checked yet

  Not checked in the free run.