High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children.
Open accessAbstract
Summary Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults. There is evidence that maternal stress and anxiety during pregnancy influences birth outcome but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology. In the current prospective longitudinal study we included 35 women for whom serial data on pregnancy anxiety was available at 19 (±0.83), 25 (±0.9) and 31 (±0.9) weeks gestation. When the offspring from the target pregnancy were between six to nine years of age, their neurodevelopmental stage was assessed by a structural MRI scan. With the application of voxel based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress. Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus. High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume. This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology. Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.
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- Findingown data
Pregnancy anxiety at 25 and 31 weeks was not significantly related to localized gray matter volume reductions.
“High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume.”
Quote in the paperNot a substantial claim - Findingown data
At 19 weeks gestation, pregnancy anxiety was linked to lower gray matter volume in prefrontal, premotor, medial temporal, lateral temporal, postcentral, cerebellar, middle occipital, and fusiform regions, independently of postnatal stress.
“Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus.”
Quote in the paperSubstantial claim - Findingown data
High pregnancy anxiety at 19 weeks was associated with significant, mostly bilateral, gray matter volume reductions in anterior, orbitofrontal, dorsolateral, and ventrolateral prefrontal cortex.
“High pregnancy anxiety at 19 weeks gestation was associated with significant, mostly bilateral, gray matter volume reductions in the anterior (Brodmann Area (BA) 10), orbitofrontal (BA 11 and BA 47), dorsolateral (BA 46 and BA 9) and ventrolateral prefrontal cortex (BA 45).”
Quote in the paperSubstantial claim - Findingown data
The VBM analysis found lower gray matter density in several brain areas associated with high pregnancy anxiety.
“The VBM analysis revealed lower gray matter density in several brain areas in association with high pregnancy anxiety.”
Quote in the paperSubstantial claim - Findingown data
Pregnancy anxiety was not significantly associated with maternal sociodemographic characteristics.
“As shown in Table 2, pregnancy anxiety was not significantly associated with maternal sociodemographic characteristics”
Quote in the paperNot a substantial claim
- Findingown data
Pregnancy anxiety at all gestational time points was highly significantly correlated with postpartum perceived stress.
“while highly significant correlations between pregnancy anxiety at all time points during gestation and postpartum perceived stress were observed.”
Quote in the paperNot a substantial claim - Findingown data
In children of mothers with high pregnancy anxiety at 19 weeks, pronounced bilateral gray matter volume reduction was found in the cerebellum extending to the middle occipital gyrus (BA19) and fusiform gyrus (BA37).
“Furthermore, in children of mothers with high pregnancy anxiety at 19 weeks gestation, pronounced bilateral gray matter volume reduction was found in the cerebellum extending to the middle occipital gyrus (BA 19) and to the fusiform gyrus (BA 37).”
Quote in the paperSubstantial claim - Findingown data
Pregnancy anxiety was not significantly correlated with the number of medical risk conditions at any of the three assessments.
“At none of the assessments, significant correlations could be observed (19 weeks: r= -0.14, p= 0.42; 26 weeks: r= -0.14, p= 0.44, 31 weeks: r= 0.02, p= 0.92).”
Quote in the paperSubstantial claim - Findingown data
The study did not observe a significant reduction in gray matter density in the hippocampus.
“Still, we did not observe a significant reduction in gray matter density in this region.”
Quote in the paperSubstantial claim - Findingown data
Children whose mothers reported higher pregnancy anxiety had bilateral gray matter volume reductions in lateral temporal cortex extending from superior temporal gyrus (BA22) to middle temporal gyrus (BA21) and on the right side to postcentral gyrus.
“Bilateral reductions in gray matter volume were found in children whose mothers reported higher pregnancy anxiety in the lateral temporal cortex extending from the superior temporal gyrus (BA 22) to the middle temporal gyrus (BA 21) and on the right side to the postcentral gyrus.”
Quote in the paperSubstantial claim - Findingown data
High pregnancy anxiety at 19 weeks was associated with lower gray matter density in the left precentral gyrus extending to the middle frontal gyrus (BA6).
“Also, lower gray matter density was observed with high pregnancy anxiety at 19 weeks gestation in the left precentral gyrus extending to the middle frontal gyrus (BA 6).”
Quote in the paperSubstantial claim - Findingown data
Pregnancy anxiety at 19 weeks was associated with gray matter volume reductions in prefrontal cortex, premotor cortex, medial temporal lobe, lateral temporal cortex, postcentral gyrus, cerebellum extending to middle occipital gyrus, and fusiform gyrus.
“Specifically, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus.”
Quote in the paperSubstantial claim - Findingown data
The strength of the relationship between pregnancy anxiety and gray matter volume reduction differed across gestation.
“The significance of the relation between pregnancy anxiety and gray matter volume reductions varied across gestation (see Table 4 and Figure 2).”
Quote in the paperSubstantial claim - Findingown data
Clusters of reduced gray matter density associated with high pregnancy anxiety at 25 and 31 weeks did not survive FDR correction.
“Clusters of voxels with reduced gray matter density were found in association with high pregnancy anxiety at 25 and 31 weeks (see Table 4) but these did not survive FDR correction and are therefore not reported here.”
Quote in the paperNot a substantial claim - Findingown data
High pregnancy anxiety at 19 weeks was associated with reduced gray matter volume in the left medial temporal lobe, uncus extending to entorhinal cortex (BA28) and parahippocampal gyrus (BA36), left temporal pole (BA38), and left inferior temporal gyrus (BA20).
“Reduced gray matter volume in association with high pregnancy anxiety at 19 weeks gestation was furthermore observed in the left medial temporal lobe, uncus, extending to the entorhinal cortex (BA 28) and the parahippocampal gyrus (BA 36) as well as in the left temporal pole (BA 38) and the left inferior temporal gyrus (BA 20).”
Quote in the paperSubstantial claim - Findingown data
Pregnancy anxiety at none of the three pregnancy time points was correlated with total gray matter volume.
“Pregnancy anxiety at any of the three time points during pregnancy was not correlated with total gray matter volume (T1: r=0.05, p=0.81; T2: r=0.06, p=0.75; T3: r=-0.27, p=0.15).”
Quote in the paperNot a substantial claim - Interpretationown data
This was the first prospective study to demonstrate that a particular timing pattern of pregnancy anxiety corresponds to specific brain morphology changes.
“This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology.”
Quote in the paperSubstantial claim- Rests on an assumption: No prior human study has investigated the association between prenatal stress exposure and brain morphology in offspring.
- Interpretationreasoning
Gray matter volume changes in regions influenced by prenatal maternal anxiety might increase the child's later vulnerability to neurodevelopmental and psychiatric disorders and to cognitive and intellectual impairment.
“Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.”
Quote in the paperSubstantial claim - Premisecitation
Animal models show brain morphology changes in offspring of mothers exposed to prenatal stress.
“In animal models, changes in brain morphology have been observed in offspring of mothers exposed to prenatal stress.”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationnone given
Periods with specific neurodevelopmental events create windows of particular vulnerability to adverse influences.
“The presence of periods with specific neurodevelopmental events results in windows of specific vulnerability for adverse influences.”
Quote in the paperSubstantial claim - Premisecitation
Rodent evidence indicates prenatal stress alters rat hippocampal cytoarchitecture.
“Several lines of evidence from studies in rodents indicate that the cytoarchitecture of the rat hippocampus is altered as a consequence of prenatal stress (Hayashi et al., 1998; Gould & Tanapat, 1999; Lemaire et al., 2000).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Pregnancy-specific stress measures predict developmental outcomes better than general psychological distress measures.
“Further evidence suggests that measures of pregnancy specific stress are better than measures of generalized psychological distress for predicting developmental outcomes including, fetal behavior (DiPietro et al., 2002), infant cognitive and motor development (Huizink et al., 2003; Dipietro et al., 2006; Davis & Sandman, in press) and infant emotional regulation (Dipietro et al., 2006).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationcitation
The timing effect may also relate to different brain regions having unique developmental timetables and specific periods of neural vulnerability.
“The effect of timing may also be related to the fact that different brain regions have a unique timetable for development and therefore specific periods of neural vulnerability.”
Quote in the paperNot a substantial claim- Rests on an assumption: Different brain regions have a unique timetable for development and specific periods of neural vulnerability.
- Premisecitation
Pregnancy anxiety has higher predictive quality for birth outcomes and fetal/child development than general stress scales.
“This is emphasized by observations of pregnancy anxiety having a higher predictive quality for birth outcomes and fetal/child development than general stress scales (Wadhwa et al., 1993; Huizink et al., 2003; DiPietro et al., 2004; Roesch et al., 2004; Dipietro et al., 2006; Kramer et al., 2009; Davis & Sandman, in press)”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationcitation
Reduced gray matter density in precentral and postcentral gyrus associated with pregnancy anxiety is consistent with evidence for disturbed development of the nociceptive system and associated behavioral changes with prenatal stress.
“Reduced gray matter density in the precentral and postcentral gyrus in association with pregnancy anxiety is consistent with evidence for disturbed development of the nociceptive system and associated behavioral changes in association with prenatal stress (Smythe et al., 1994; Rokyta et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationreasoning
The brain regions affected by pregnancy anxiety are areas specifically associated with cognitive performance.
“The brain regions that we have found to be affected by pregnancy anxiety are areas specifically associated with cognitive performance.”
Quote in the paperSubstantial claim - Interpretationreasoning
High maternal prenatal anxiety may increase risk for higher stress susceptibility and reactivity in developing individuals through its effect on these brain regions.
“Thus, by its effect on these brain regions, high maternal prenatal anxiety may increase the risk for higher stress susceptibility and reactivity in the developing individuals.”
Quote in the paperSubstantial claim - Interpretationcitation
Occipital-temporal areas (middle occipital gyrus BA19 and fusiform gyrus), involved in visual processing, are affected by pregnancy anxiety.
“Occipital-temporal areas (middle occipital gyrus (BA19) and fusiform gyrus), involved in visual processing, are furthermore affected by pregnancy anxiety (Brandt et al., 2000).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Brandt et al., 2000 source
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- Interpretationown data
The study provides the first human evidence that prenatal maternal anxiety is associated with brain morphology in the developing individual within specific sensitive time periods.
“We present the first evidence in humans that prenatal maternal anxiety is associated with brain morphology in the developing individual within specific sensitive time periods.”
Quote in the paperSubstantial claim - Premisecitation
This possibility is supported by rhesus monkey observations where prenatal exposure to the same stressor had greater effects on postnatal motor development if earlier in gestation when neuronal migration peaked than mid-to-late when synaptogenesis peaked.
“This possibility has been supported by observations in rhesus monkeys, where prenatal exposure to the same stressor had greater effects on postnatal motor development if it occurred earlier in gestation, when neuronal migration was at its peak, than if it occurred in mid- to late gestation, when synaptogenesis was at its peak (Schneider et al., 1999).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Schneider et al., 1999 source
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- Premisecitation
Pregnancy anxiety scales better assess pregnancy-specific anxieties and worries than general stress, depression, and anxiety scales.
“Scales measuring pregnancy anxiety have been suggested to better assess anxieties and worries related specifically to pregnancy than general scales of stress, depression and anxiety (Huizink et al., 2004; Dipietro et al., 2006).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Prefrontal regions affected by high pregnancy anxiety are involved in regulation of stress hormone secretion.
“Interestingly, a recent functional MRI study in humans found that prefrontal regions, that we found are affected by high pregnancy anxiety, are involved in the regulation of stress hormone secretion (Pruessner et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pruessner et al., 2008 source
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- Interpretationreasoning
The results suggest that earlier in pregnancy, effects of pregnancy anxiety on offspring gray matter volume are most pronounced.
“The results of the current study suggest that earlier in pregnancy, the effects of pregnancy anxiety on offspring’s gray matter volume are most pronounced.”
Quote in the paperSubstantial claim - Premisecitation
These same brain regions appear particularly vulnerable under chronic stress due to high density of glucocorticoid receptors.
“These same brain regions appear to be particularly vulnerable under conditions of chronic stress due to their high density of glucocorticoid receptors (Sapolsky et al., 1990).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sapolsky et al., 1990 source
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- Premisecitation
The findings are consistent with animal evidence that medial temporal and prefrontal cortical regions are shaped by early experience.
“Our findings are consistent with accumulating evidence from animal studies that medial temporal and prefrontal cortical regions are shaped by early experience (e.g. Coe et al., 2003; Salm et al., 2004; Fujioka et al., 2006; Murmu et al., 2006).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationreasoning
The implication is that impact of stress during pregnancy is not uniform; stress earlier in pregnancy may have more pronounced consequences for brain development than later.
“The implication of these findings is that the impact of stress during pregnancy is not uniform but that stress earlier in pregnancy may have more pronounced consequences for brain development than at a later gestational stage.”
Quote in the paperSubstantial claim - Study design and conductown data
By controlling for several relevant variables including postnatal maternal stress and socioeconomic status, it can be concluded that observed effects of pregnancy anxiety on brain structure were not mediated by these postnatal factors.
“By controlling for several relevant variables including postnatal maternal stress and socioeconomic status, it can be concluded though that the observed effects of pregnancy anxiety on brain structure were not mediated by these postnatal factors.”
Quote in the paperSubstantial claim - Interpretationown data
This is the first study in healthy children to show that prenatal maternal anxiety is related to distinctive patterns of structural brain development.
“This is the first study in healthy children to show that prenatal maternal anxiety is related to distinctive patterns of structural brain development.”
Quote in the paperNot a substantial claim - Study design and conductreasoning
The possibility of an undiagnosed disorder cannot be ruled out because clinical diagnostic assessments were not conducted.
“the possibility of an undiagnosed disorder cannot be ruled out because clinical diagnostic assessments were not conducted.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The results suggest that, independent of postnatal maternal stress, prenatal stress has an impact on offspring brain morphology.
“Thus, the results suggest that, independent of postnatal maternal stress, prenatal stress has an impact on the offspring’s brain morphology.”
Quote in the paperSubstantial claim
- May combine two claims. 21
- Classified as probably not a substantial claim. 49
May combine two claims.
Findingown dataUsing voxel-based morphometry, the authors observed lower gray matter density in several regions linked to pregnancy anxiety, with total gray matter volume, age, gestational age at birth, handedness, and postpartum perceived stress held constant.
“With the application of voxel based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataPregnancy anxiety scores showed significant rank stability across the three pregnancy visits.
“Spearman’s rho correlation coefficients suggested significant rank stability in pregnancy anxiety scores over the course of gestation.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataPregnancy anxiety scores decreased significantly as gestation advanced, with lower scores at the second and third visits than at the first.
“With advancing gestational age pregnancy anxiety scores significantly decreased (F(1.8, 56.8)=5.4, p=0.01) resulting in lower scores at the second and third assessments as compared to the first.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataChildren who participated in the follow-up did not differ from the initial sample in maternal age, education, or annual household income.
“Women whose children participated in the follow-up study of brain development did not differ in sociodemographic characteristics (maternal age and education, annual household income) from women in the initial sample (all p’s >0.4).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe associations with gray matter density were confined to pregnancy anxiety at 19 weeks; anxiety at 25 and 31 weeks was not significantly associated with gray matter volume.
“These associations with gray matter density were confined to pregnancy anxiety reported at 19 weeks gestation, as reports of pregnancy anxiety at 25 and 31 weeks gestation were not significantly associated with gray matter volume.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThere was no indication of psychiatric disorders and no report of treatment for any disorders in structured interviews.
“It has to be noted that while there was no indication of psychiatric disorders and there was no report of treatment for any disorders in the structured interviews that probed such issues”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationPrenatally stressed animals repeatedly show impaired neurogenesis and related cognitive impairment.
“Impaired neurogenesis and associated cognitive impairment have been repeatedly reported in prenatally stressed animals (Lemaire et al., 2000; Fujioka et al., 2006; Lemaire et al., 2006).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAdverse birth outcomes may indicate in utero stress exposure.
“Adverse birth outcomes may be markers of in utero stress exposure (e.g. Wadhwa, 2005)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wadhwa, 2005 source
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PremisecitationPregnancy anxiety is a more sensitive predictor of birth outcomes than general anxiety.
“Pregnancy anxiety has been suggested to be a more sensitive predictor of birth outcomes than general anxiety (Wadhwa et al., 1993; DiPietro et al., 2004; Roesch et al., 2004; Kramer et al., 2009)”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningBrain morphology changes in preterm individuals may also result from perinatal complications often accompanying premature delivery.
“but the changes in brain morphology may also be due to perinatal complications that are often associated with premature delivery.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrenatal stress is linked to enlarged lateral amygdala nucleus in offspring.
“For example significantly expanded dimensions of the lateral nucleus of the amygdala were observed in prenatally stressed offspring (Salm et al., 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Salm et al., 2004 source
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PremisecitationIn humans, low birth weight and preterm birth are linked to regional brain volume changes.
“Thus, low birth weight as well as preterm birth have been related to changes in regional brain volumes (e.g. Peterson et al., 2000; Abernethy et al., 2002; Nosarti et al., 2002; Huizink et al., 2004; Buss et al., 2007; Beauchamp et al., 2008).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPrenatal stress can alter synaptic plasticity by impairing long-term potentiation and facilitating long-term depression.
“Furthermore, prenatal stress has the potential to alter synaptic plasticity by impairing long-term potentiation but facilitating long-term depression (Yaka et al., 2007; Yang et al., 2007).”
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PremisecitationBecause the rodent brain is less mature at birth than the human brain, rat early postnatal maturation is considered analogous to human late gestation maturation.
“Since the rodent brain is less mature at birth than the human brain, it has been suggested that brain maturation occurring in the early postnatal period in the rat is analogous to maturational changes that occur in humans in late gestation (Clancy et al., 2001).”
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PremisecitationPregnancy anxiety has been proposed as a distinct syndrome.
“and has been suggested as a distinctive syndrome (Huizink et al., 2004).”
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PremisecitationAbnormal brain development during gestation contributes to many neurological disorders across the lifespan.
“Growing evidence suggests that abnormal development of the brain during gestation contributes to many neurological disorders that are manifested throughout the entire lifespan (Rees et al., 2008).”
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PremisecitationIn non-human primates, prenatal stress is linked to altered corpus callosum size.
“as well as altered size of the corpus callosum (Coe et al., 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Coe et al., 2002 source
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InterpretationreasoningEarly life experiences can shape brain morphology.
“Considering the extended pre- and postnatal developmental trajectory of the brain, it is apparent that early life experiences have the potential to sculpt brain morphology.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Premisenone givenThe brain changes dramatically during fetal development and is vulnerable to environmental insults.
“Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults.”
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PremisecitationIn non-human primates, daily acute prenatal stress is linked to 10-12% smaller hippocampal volume and suppressed dentate gyrus neurogenesis.
“In non-human primates, daily acute prenatal stress is associated with 10-12% reductions in hippocampal volume and inhibition of neurogenesis in the dentate gyrus (Coe et al., 2003)”
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PremisecitationPrenatal stress is linked to lower spine density and shorter dendritic length of pyramidal neurons in dorsal anterior cingulate and orbitofrontal cortex.
“Also, reduced spine densities and significant reduction of dendritic length of pyramidal neurons in the dorsal anterior cingulate and orbitofrontal cortex have been reported in offspring of mothers exposed to stress during pregnancy (Murmu et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Murmu et al., 2006 source
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PremisecitationRodent studies show brain morphology changes after manipulation of the early postnatal environment.
“Therefore, it is interesting to note that there is an impressive body of evidence from rodent studies showing changes in brain morphology in association with manipulation of the early postnatal environment (e.g. Meaney et al., 1991; Pham et al., 1999; Helmeke et al., 2001; Huot et al., 2002; Roceri et al., 2002; Bredy et al., 2003; Ovtscharoff et al., 2006; Fabricius et al., 2008).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationThe timing effect may be due to pregnancy anxiety being highest at 19 weeks and decreasing over gestation, consistent with previous observations of reduced stress reactivity as pregnancy advances.
“This effect of timing may be due to the fact that pregnancy anxiety is highest at 19 weeks gestation and decreases over the course of gestation, which is in line with previous observations of reduced physiological and psychological stress reactivity as pregnancy advances (Schulte et al., 1990; Glynn et al., 2001; Glynn et al., 2004; de Weerth & Buitelaar, 2005; Glynn et al., 2008)”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationA small but growing literature indicates that prenatal stress influences both cognitive development and temperament.
“Importantly and consistent with the primary functions of the affected brain regions, a small but growing literature indicates that prenatal stress influences both cognitive development as well as temperament.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMaternal exposure to natural disasters, war, or stressful life events is associated with increased prevalence of psychopathology in offspring.
“and maternal exposure to natural disasters, war or stressful life events have been associated with increased prevalence of psychopathology in the offspring (van Os & Selten, 1998; Selten et al., 1999; Watson et al., 1999; Beversdorf et al., 2005; Khashan et al., 2008).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLimbic structures, especially hippocampus, are prominent targets for early life stress.
“Limbic structures, especially the hippocampus, have been shown to be prominent targets for early life stress (e.g. Coe et al., 2003; Buss et al., 2007).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationElevated prenatal maternal stress/anxiety is associated with emotional/behavioral problems that persisted until adolescence.
“and emotional/ behavioral problems that persisted until adolescence (Van den Bergh et al., 2005; Van den Bergh et al., 2008).”
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Study design and conductcitationImages were smoothed with a 12 mm kernel to make the data normally distributed and reduce false positives.
“The normalized, segmented, and modulated images were then smoothed using a 12 mm kernel to ensure that the data were normally distributed and to limit the number of false positive findings (Salmond et al., 2002).”
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PremisecitationAnother network affected by pregnancy anxiety (inferior frontal gyrus BA45, middle temporal gyrus BA21, parahippocampal gyrus) seems involved in language learning.
“Also involved in language learning seems to be another network of brain regions affected by pregnancy anxiety (the inferior frontal gyrus (BA 45), the middle temporal gyrus (BA 21) and the parahippocampal gyrus, Mestres-Misse et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mestres-Misse et al., 2008 source
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InterpretationreasoningThis increased stress susceptibility may result in higher concentrations of stress hormones which could further delay brain development.
“This may result in higher concentrations of stress hormones which could further delay brain development.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe temporal polar cortex is involved in social and emotional processing including recognition and semantic memory.
“The temporal polar cortex appears to be involved in social and emotional processing including recognition and semantic memory (Nakamura & Kubota, 1996; Hoistad & Barbas, 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Nakamura & Kubota, 1996
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- cites Hoistad & Barbas, 2008
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Study design and conductown dataAutomatic brain segmentation software was tested on pilot scans to ensure gray-white matter segmentation with minimal errors.
“Automatic brain segmentation software was tested on these pilot scans to ensure gray-white matter segmentation with minimal errors.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA temporal-parietal network including middle temporal gyrus (BA21), superior temporal gyrus (BA22), and angular gyrus (BA39) is important in auditory language processing in children.
“A network in the temporal-parietal cortex consisting of the middle temporal gyrus (BA 21), the superior temporal gyrus (BA 22) and the angular gyrus (BA 39) has been shown to be important in processes related to auditory language processing in children (Ahmad et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ahmad et al., 2003 source
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Study design and conductcitationThe 10-item pregnancy anxiety scale is reliable (α=0.75-0.85) and was developed specifically for pregnancy research.
“This reliable measure (α=0.75-0.85) was specifically developed for use in pregnancy research (Rini et al., 1999; Glynn et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenA neurologist visually assessed images for normal anatomic appearance.
“Images were visually assessed by a neurologist for normal anatomic appearance.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe prefrontal cortex is involved in executive cognitive functions such as reasoning, planning, attention, working memory, and some aspects of language.
“The prefrontal cortex is sometimes described as the “highest” structure of the brain because it is involved in executive cognitive functions such as reasoning, planning, attention, working memory, and some aspects of language (e.g. Connolly et al., 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Connolly et al., 2002 source
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Study design and conductown dataMRI acquisition parameters were tested on volunteers to achieve optimal gray-white matter contrast, sharpness, high resolution, and no discernible artifacts.
“Variations of these parameters were tested on volunteers to obtain an optimal set that gave us the best gray-white matter contrast, sharpness and high resolution while ensuring that there were no discernible artifacts.”
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PremisecitationMedial temporal lobe structures including entorhinal, perirhinal, and parahippocampal cortex constitute a memory system for storage and recall of facts and events.
“Structures in the medial temporal lobe, including areas connected to the hippocampus (entorhinal, perirhinal, parahippocampal cortex), have been proposed to constitute a “medial temporal lobe memory system” with the primary functions of these areas related to the storage and recall of facts and events (Squire et al., 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Squire et al., 2004 source
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PremisecitationElevated prenatal maternal stress/anxiety is associated with higher infant behavioral reactivity.
“higher infant behavioral reactivity (Davis et al., 2004; Davis et al., 2005; Davis et al., 2007)”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationElevated prenatal maternal stress/anxiety is associated with infant inability to attend and delayed cognitive development.
“Thus, elevated prenatal maternal stress/anxiety is associated with infant inability to attend and with delayed cognitive development (Brouwers et al., 2001; Huizink et al., 2002; O’Connor et al., 2002; Buitelaar et al., 2003; Huizink et al., 2003; Davis & Sandman, in press)”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationElevated prenatal maternal stress/anxiety is associated with lower academic achievement in school.
“lower academic achievement in school (Niederhofer & Reiter, 2004)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Niederhofer & Reiter, 2004
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataExcluding either child of the sibling pair did not significantly change the reported results.
“Excluding either child of the sibling pair did not significantly change the reported results.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationOffspring of women exposed to a natural disaster during pregnancy had poorer general intellectual functioning and language development.
“Furthermore, offspring of women who were exposed to a natural disaster during their pregnancies had poorer general intellectual functioning and language development (Laplante et al., 2004; Laplante et al., 2008)”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
Study design and conductcitationThe analysis controlled for gestational age at birth because preterm delivery has been associated with reductions in gray matter volume.
“Also, gestational age at birth was controlled for in these analyses because preterm delivery has been shown to be associated with reductions in gray matter volume (e.g. Gimenez et al., 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gimenez et al., 2004 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningBy controlling for total gray matter volume, differences in overall brain size that vary by sex were accounted for.
“By controlling for total gray matter volume, differences in overall brain size were accounted for that varies by sex.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningPregnancy anxiety may be higher in women with undiagnosed psychiatric disorders and accompanying endocrine alterations could impact neurodevelopment of offspring.
“Pregnancy anxiety may be higher in women with undiagnosed psychiatric disorders and accompanying endocrine alterations could impact on neurodevelopment of the offspring.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningPostpartum stress was included as an additional covariate to address the association between prenatal stress and gray matter volume independent of postnatal stress.
“Because pregnancy anxiety and postpartum stress were highly correlated, we included postpartum stress as an additional covariate in order to address the association between prenatal stress and gray matter volume independent of postnatal stress.”
Quote in the paperSubstantial claim- Rests on an assumption: Pregnancy anxiety and postpartum stress were highly correlated.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningObserved consequences of prenatal programming depend on timing of insult, brain region of interest, and stage of assessment.
“It important to acknowledge that the observed consequences of prenatal programming not only depend on the timing of the insult and the brain region of interest but also on the stage of assessment.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningWhat was observed in children of this age range may not be final.
“This implies that what we observed and reported here in children of this age range may not be final.”
Quote in the paperNot a substantial claim- Rests on an assumption: Studies on postnatal brain development show regional and temporal patterns of dynamic maturational change continuing through childhood and adolescence.
Classified as probably not a substantial claim.
Study design and conductown dataThe analysis controlled for child's age at assessment.
“We furthermore controlled for child’s age at assessment.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataAnalyses were performed at p<0.001 uncorrected, but only voxels within a cluster of at least 100 voxels that reached FDR p<0.05 are reported.
“Analyses for detection of brain regions that showed significantly reduced gray matter density in association with high pregnancy anxiety were performed at p<0.001 uncorrected, but only those voxels within a cluster of at least 100 voxels that reached a False Discovery Rate (FDR) threshold of p<0.05 are reported.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductreasoningThe analysis controlled for total gray matter volume to normalize for global differences in gray matter concentration across subjects, so it detected regional rather than overall large-scale variations.
“Normalization for global differences in gray matter concentration across subjects was performed by controlling for total gray matter volume. Consequently, the analysis detected regional difference rather than overall, large-scale variations in gray matter concentrations.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningAt a later maturational stage, prenatal stress exposure may confer a different morphological pattern.
“It is possible that at a later maturational stage, prenatal stress exposure will confer a different morphological pattern.”
Quote in the paperNot a substantial claim- Rests on an assumption: Studies on postnatal brain development show regional and temporal patterns of dynamic maturational change continuing through childhood and adolescence.
Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.
InterpretationreasoningThese morphological patterns may increase vulnerability for certain neurodevelopmental disorders and impair cognitive function.
“These morphological patterns may increase vulnerability for certain neurodevelopmental disorders and impair cognitive function.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenRelative threshold masking (threshold >0.3) was used to minimize gray-white matter boundary effects, and implicit masking disregarded voxels with zero values.
“Relative threshold masking (threshold >0.3) was used to minimize gray-white matter boundary effects, and implicit masking was used to disregard voxels with zero values.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationThe analysis controlled for child's handedness because structural brain asymmetries may be associated with handedness.
“In addition, handedness of the child was controlled for because structural asymmetries of the brain may be associated with handedness (Toga & Thompson, 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Toga & Thompson, 2003
Not checked in the free run.
The paper relies on this without support.
No prior human study has investigated the association between prenatal stress exposure and brain morphology in offspring.
“but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology.”
“To the best of our knowledge no study to date in humans has investigated the association between prenatal stress exposure and brain morphology in the offspring.”
The authors state this as an assumption.
Biological systems undergoing rapid developmental changes are especially vulnerable to organizing and disorganizing influences.
“One key assumption of the programming hypothesis is that biological systems undergoing rapid developmental changes are especially vulnerable to organizing and disorganizing influences (Nathanielsz et al., 2003; Seckl & Meaney, 2004).”
The paper relies on this without support.
Pregnancy anxiety and postpartum stress were highly correlated.
“Because pregnancy anxiety and postpartum stress were highly correlated”
The paper relies on this without support.
The fetus participates in a dynamic exchange of environmental information with the maternal host over gestation.
“The fetus participates in a dynamic exchange of environmental (intrauterine) information with the maternal host over the course of gestation.”
The paper relies on this without support.
All communication between maternal and fetal compartments is mediated via the placenta.
“All communication between the maternal and fetal compartments is mediated via the placenta, an organ of fetal origin.”
The paper relies on this without support.
With production and release of CRH from the placenta, regulation of the HPA axis changes dramatically during pregnancy.
“With the production and release of CRH from the placenta, regulation of the HPA axis changes dramatically during pregnancy.”
The paper relies on this without support.
Studies on postnatal brain development show regional and temporal patterns of dynamic maturational change continuing through childhood and adolescence.
“Studies on postnatal brain development have clearly shown regional and temporal patterns of dynamic maturational change continuing through childhood and adolescence.”
The paper relies on this without support.
Different brain regions have a unique timetable for development and specific periods of neural vulnerability.
“The effect of timing may also be related to the fact that different brain regions have a unique timetable for development and therefore specific periods of neural vulnerability.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Exposure to prenatal maternal stress has enduring and wide-ranging consequences on brain development in the offspring, including altered regional brain volumetric growth, cortical folding, metabolism, microstructure, and functional connectivity.
“Importantly, exposure to prenatal maternal stress is shown to have enduring and wide-ranging consequences on brain development in the offspring, including altered regional brain volumetric growth, cortical folding, metabolism, microstructure, and functional connectivity [4, 15, 19, 23–27, 35–39].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [23]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredElevated maternal psychological distress during mid-gestation is associated with a decrease in the regional cerebrum and cerebellum gray matter volumes of children at 6-9 years of age.
“a decrease in the regional cerebrum and cerebellum gray matter volumes of children at 6–9 years of age [23]”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [23]
The Results (page unavailable) associate pregnancy anxiety at 19 weeks with regional gray matter volume reductions in cerebral areas and the cerebellum of children aged 6–9. The Methods specify that the measure was pregnancy-specific anxiety, not psychological distress generally; the claim broadens that exposure. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrenatal maternal stress exposure has enduring consequences on offspring brain development and long-term neurodevelopment.
“Prenatal maternal stress exposure has been shown to have enduring consequences on brain development in the offspring”
From Association of Elevated Maternal Psychological Distress, Altered Fetal Brain, and Offspring Cognitive and Social-Emotional Outcomes at 18 Months (2022) · cites this paper as [2]
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- ConsistentF(1.8, 56.8) = 5.4reported p = .01 · recomputed p = .007
“F(1.8, 56.8)=5.4, p = .01”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Second anxiety assessment is dated both 25 and 26 weeks
MinorThe assessment schedule places the second visit at 25 weeks, but the medical-risk correlation results label it 26 weeks.
“Pregnancy anxiety was assessed over the course of gestation at 19 (±0.83, SD), 25 (±0.9) and 31 (±0.9) weeks gestation”
“19 weeks: r= -0.14, p= 0.42; 26 weeks: r= -0.14, p= 0.44, 31 weeks: r= 0.02, p= 0.92”
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“…prenatal maternal stress/anxiety is associated with infant inability to attend and with delayed cognitive development (Brouwers et al., 2001; Huizink et al., 2002; O’Connor et al., 2002; Buitelaar et al., 2003; Huizink et al., 2003; Davis & Sandman, in press), lower academic achievement in…”
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“…exposure to prenatal maternal stress is shown to have enduring and wide-ranging consequences on brain development in the offspring, including altered regional brain volumetric growth, cortical folding, metabolism, microstructure, and functional connectivity [4, 15, 19, 23 – 27 , 35 – 39 ].”
BackgroundPositive maternal mental health, parenting, and child development
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- Authors
- Buss, C., Davis, E. P., Muftuler, L. T., Head, K., & Sandman, C. A.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Sandman, Curt A.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 35
- Issue
- 1
- Pages
- 141-153
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC2795128
- OpenAlex
- W1970717430
- Semantic Scholar
- d4a0e6500619de35a50b7663c76abb23c519ed24
- Cited by
- 435
- References
- 134
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 24 · 2023: 19 · 2022: 24 · 2021: 35 · 2020: 35 · 2019: 28 · 2018: 25 · 2017: 36 · 2016: 27 · 2015: 35 · 2014: 29 · 2013: 19 · 2012: 28
- FWCI
- 22.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-41298;, R01NS041298)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD028413, HD 51852, R01HD051852, HD-28413)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- prenatal anxiety, maternal stress, prenatal stress, gray matter density, brain structure, second trimester, children, prefrontal cortex, medial temporal lobe, cerebellum, brain development
- MeSH terms
- Adult, Anxiety, Brain, Child, Female, Gestational Age, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Prospective Studies, Risk, Socioeconomic Factors, Postpartum Period
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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