Childhood stress and birth timing among African American women: cortisol as biological mediator

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

Sixty percent of participants gave birth after spontaneous labor onset.

“Fifty-three (60.0%) participants gave birth following the spontaneous onset of labor processes.”

May combine two claims.

In sensitivity analyses among the spontaneous labor subgroup, all findings held except that the total effect of role disruption-related childhood stress became statistically significant.

“Among the spontaneous labor subgroup, all findings held with the exception of a progression of the total effect of role disruption-related childhood stress on birth timing from statistically marginal (c′ = 0.08, t(50) = 1.89, p = .07) to statistically significant (c′ = 0.10, t(48) = 2.31, p = .03).”

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

Among women with induction or pre-labor cesarean, most reached 39 weeks before delivery.

“the majority (28/36) of these women reached 39 weeks of pregnancy (i.e., full term) prior to induction of labor/pre-labor cesarean section.”

May combine two claims.

Among women with spontaneous labor onset, cumulative childhood stress had a total effect on birth timing, while cumulative adulthood stress did not.

“there was a total effect of cumulative childhood stress (c = 0.03, t(50) = 2.11, p = .04) but not cumulative stress in adulthood (c = −0.004, t(50) = −0.48, p = .63) on birth timing.”

May combine two claims.

Cumulative childhood stress was positively correlated with cumulative adulthood stress and with stress per adult year.

“Cumulative childhood stress and cumulative stress in adulthood (rs = .36, p < .01) as well as stress per adult year (rs = .42, p < .01) showed positive rank order correlations of moderate strength.”

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

Maternal cortisol was negatively associated with maternal age and pre-pregnancy BMI.

“maternal cortisol level was negatively associated with maternal age (rs = −.26, p = .01) and pre-pregnancy BMI (rs = −.22, p = .04) among our participants.”

May combine two claims.

The direct effect of childhood stress on birth timing, controlling for adulthood stress, was marginal and not statistically significant.

“The direct effect of childhood stress on birth timing, controlling for stress in adulthood, approached but did not reach statistical significance (c′ = 0.02, t(85) = 1.86, p = .07).”

May combine two claims.

Among women with spontaneous labor onset, role disruption-related childhood stress had a marginal total effect and a significant indirect effect on birth timing.

“a marginal total effect (c′ = 0.08, t(50) = 1.88, p = .07) and significant indirect effect (ab = 0.03, 95% CI [0.005, 0.074]) of role disruption-related childhood stress on birth timing.”

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

The study sample was mostly of lower socioeconomic status.

“The sample was primarily of lower socioeconomic status.”

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

Forty percent of participants gave birth after induction of labor or pre-labor cesarean section.

“36 (40%) participants gave birth as a result of induction of labor or pre-labor cesarean section.”

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

Most participants had not completed a bachelor's degree.

“the majority of women (73%) had not completed a bachelor’s degree”

May combine two claims.

Physical danger-, humiliation-, entrapment-, and role disruption-related childhood stress were less common than interpersonal loss.

“Physical danger-, humiliation-, entrapment-, and role disruption-related childhood stress were less commonly experienced (lack of exposure among 52.8%, 46.1%, 58.4%, and 73.0%, respectively).”

May combine two claims.

At average adulthood stress, birth was estimated to occur 2.8 days earlier for childhood stress one standard deviation above the mean and 5.8 days earlier for two standard deviations above the mean.

“birth would be expected to occur 2.8 days earlier among women with a score one standard deviation above the mean and 5.8 days earlier among women with a score two standard deviations above the mean as compared to women with childhood stress at the mean.”

May combine two claims.

In this sample, poor sleep quality was not associated with greater childhood stress but was associated with greater adulthood stress and with birth timing.

“In our sample, poor sleep quality was not associated with greater childhood stress but was associated with greater stress in adulthood as well as birth timing.”

May combine two claims.

The enrolled sample was mostly of low socioeconomic status, and many women reported significant life-course stress exposure.

“the enrolled sample was primarily of low socioeconomic status, with a number of women reporting significant exposure to stress across the life course.”

May combine two claims.

Medically initiated birth occurred in few women and for varied reasons, preventing examination of individual pathways.

“medically-initiated birth occurred in few women (n = 36) and for varied reasons (e.g., hypertensive disorders, non-reassuring fetal wellbeing, oligohydramnios), prohibiting examination of these individual pathways.”

May combine two claims.

With a 28-32 week sampling window, gestational age had a negligible effect on plasma cortisol, possibly increasing the ability to link single-time-point variation to birth timing.

“With a 28–32 week sampling window, we witnessed a negligible effect of gestational age on plasma cortisol, which may have increased our ability to link individual variation at a single time point to birth timing.”

Classified as probably not a substantial claim.

The accelerated placental clock theory proposes that stress-induced HPA activation speeds the normal pregnancy rise in maternal cortisol, which increases placental CRH production through feed-forward mechanisms.

“In pregnancy, a popular theory proposed to explain stress-related PTB is that of the accelerated “placental clock,” which posits that stress-induced hypothalamic-pituitary-adrenal (HPA) activation hastens the expected pregnancy-associated rise in maternal cortisol, upregulating placental corticotropin-releasing hormone (CRH) production via feed-forward mechanisms (Sandman et al., 2006).”

• cites Sandman et al., 2006 sourceNot checked yet

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

According to the ecobiodevelopmental framework, strong, repeated, or prolonged childhood activation of stress systems causes lasting neurobiological changes, and chronic stress-system activation and exaggerated adult stress reactivity contribute to adult disease.

“Per the ecobiodevelopmental framework, robust, repeated, or extended activation of stress systems in childhood lead to lasting neurobiological changes, with both chronic activation of stress systems and exaggerated responsivity to adult stressors implicated in adult disease (Shonkoff et al., 2012).”

• cites Shonkoff et al., 2012 sourceNot checked yet

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May combine two claims.

Childhood stress raises the risk of adult health conditions, including pregnancy complications such as preterm birth.

“There is growing evidence that childhood stress also increases risk for health conditions in adulthood (Murphy et al., 2017; Nusslock and Miller, 2016), including complications of pregnancy such as PTB (Blackmore et al., 2016; Christiaens et al., 2015; Hillis et al., 2004; Smith et al., 2016).”

• cites Murphy et al., 2017 sourceNot checked yet

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• cites Nusslock and Miller, 2016 sourceNot checked yet

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• cites Blackmore et al., 2016 sourceNot checked yet

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

Preterm birth affects approximately 1 in 11 white women and 1 in 7.5 African American women in the United States.

“Preterm birth (PTB) occurs among 1:11 U.S. white women and 1:7.5 African American women”

• Also stated in: § 1. Introduction · plain

  “with 1 in 11 United States (U.S.) white women and 1 in 7.5 African American women giving birth preterm (Martin et al., 2017).”

• cites Martin et al., 2017Not checked yet

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

Plasma cortisol was quantified in duplicate by ELISA, with intra-assay CV 3.7%, inter-assay CV 9.7%, and lower limit of detection 23.3 ng/ml.

“Intra- and inter-assay coefficients of variation were 3.7% and 9.7%, respectively. The lower limit of detection was 23.3 ng/ml.”

May combine two claims.

Dating ultrasound was documented for 94.4% of prenatal records, and the mean gestational age at that ultrasound was 10 weeks 0 days (SD 3 weeks 1 day).

“A dating ultrasound could be confirmed in 94.4% of the prenatal records secured for enrolled participants, with an average gestational age at dating ultrasound of 10 weeks 0 days (SD 3 weeks 1 day).”

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

The STRAIN provides a comprehensive estimate of childhood stress, adult stress, and five core characteristic subscales.

“The Stress and Adversity Inventory was administered, which provides a comprehensive estimate of childhood stress, stress in adulthood, and five core characteristic subscales (interpersonal loss, physical danger, humiliation, entrapment, role disruption).”

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

Seven enrolled participants were excluded for reasons including venipuncture outside the study window, unsuccessful venipuncture, tobacco use, loss to follow-up, and outlying cortisol values, leaving a final sample of 89.

“Seven enrolled participants were excluded from analyses for the following reasons: venipuncture outside of study visit window (n = 1), unsuccessful venipuncture (n = 2), tobacco use after the first trimester (n = 1), loss to follow-up (n = 1), and outlying maternal cortisol value >3 SD above the mean (n = 2). Therefore, hypotheses were tested among a final sample of 89 women.”

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

Diagnostics after estimation checked whether each model's assumptions were met.

“We performed post-estimation diagnostics to review assumption satisfaction for each model.”

Classified as probably not a substantial claim.

The analyses adjusted for stress in adulthood.

“Analyses controlled for stress in adulthood.”

• Also stated in: § 2.7 Statistical analyses · plain

  “Given our interest in the effects of childhood stress independent of stress in adulthood, cumulative stress in adulthood was included as an a priori covariate in all models.”

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

Sleep quality was measured using the PSQI, an instrument validated in pregnant women across socioeconomic levels.

“Sleep quality over the past month was assessed using the Pittsburgh Sleep Quality Index (PSQI), with a range of 0–21 and higher scores indicating poorer sleep quality (Buysse et al., 1989). The PSQI is validated for use among pregnant women of varying socioeconomic statuses (Skouteris et al., 2009).”

• cites Buysse et al., 1989 sourceNot checked yet

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• cites Skouteris et al., 2009 sourceNot checked yet

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May combine two claims.

HPA hyperactivity may also contribute to overall preterm birth risk, as some studies link it to placental pathology such as preeclampsia, which raises risk for medically indicated preterm birth.

“HPA hyperactivity may also underlie overall risk for PTB, as some studies have identified a potential role in placental pathology (e.g., in preeclampsia; Harville et al., 2008; Petsas et al., 2012), which increases risk for medically-indicated PTB.”

• cites Harville et al., 2008 sourceNot checked yet

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• cites Petsas et al., 2012 sourceNot checked yet

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

Childhood stress has been linked with differential stress responsivity during adulthood stressors.

“However, childhood stress has also been linked with differential stress responsivity (e.g., Kuras et al., 2017) during stressful exposures in adulthood.”

• cites Kuras et al., 2017 sourceNot checked yet

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May combine two claims.

Childhood stress and adulthood stress covary, as also observed in this sample.

“Given that childhood stress and stress in adulthood exhibit covariation (Kingston et al., 2012), which we also witnessed in our sample”

• cites Kingston et al., 2012 sourceNot checked yet

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

The STRAIN was developed using well-validated, gold-standard life stress interview systems, including the LEDS.

“Development of the STRAIN was guided by well-validated, gold-standard life stress interview systems, including the Life Events and Difficulties Schedule (LEDS; Brown and Harris, 1978).”

• cites Brown and Harris, 1978Not checked yet

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

A more nuanced depiction of different childhood stress exposures may be informative.

“Our findings suggest that a more nuanced depiction of various childhood stress exposures may be informative.”

May combine two claims.

The study provides preliminary support for the accelerated placental clock theory, consistent with some but not all prior studies.

“We also provide preliminary support for the accelerated “placental clock” theory, which is consistent with some (Guendelman et al., 2008; Hobel et al., 1999; Hoffman et al., 2016; Mancuso et al., 2004; Moog et al., 2016), but not all (Himes and Simhan, 2011; Karakash et al., 2016; Kramer et al., 2009; Kramer et al., 2013; Noll et al., 2007; Owen et al., 2017), prior studies.”

• cites Guendelman et al., 2008 sourceNot checked yet

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• cites Hobel et al., 1999 sourceNot checked yet

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• cites Hoffman et al., 2016 sourceNot checked yet

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May combine two claims.

Days gestation at birth was significantly negatively skewed, causing non-normality and heteroskedasticity of error terms when birth timing was the criterion; it was reflected and square-root transformed for all analyses.

“As expected, days gestation at birth was significantly negatively skewed (χ2 = 12.8, p < 0.01), resulting in non-normality and heteroskedasticity of error terms when birth timing served as the criterion variable. To correct this violation, days gestation at birth was reflected (i.e., -(days gestation at birth) + 288 + 1) and a square root transformation applied, with this transformed variable used”

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

In adulthood, HPA activity tends to return to subnormal levels as time passes after a stressor, especially if the stressor is gone.

“in adulthood, as time passes following the first emergence of a stressor, HPA activity tends to rebound to subnormal levels, particularly if the stressor is no longer present (Miller et al., 2007).”

• cites Miller et al., 2007 sourceNot checked yet

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

The cortisol values in the final sample satisfied normality checks using visual inspection and the D'Agostino K2 test (χ2 = 3.16, p = 0.21), so no transformation was applied.

“The distribution of plasma cortisol level for the final sample met normality assumptions by visualization and D’Agostino K2 testing (χ2 = 3.16, p = 0.21). No transformations were required to meet modeling assumptions.”

May combine two claims.

With adult stress held constant, certain forms of childhood stress may influence when birth occurs, and cortisol elevation may mediate that influence.

“We provide preliminary evidence that, independent of stress in adulthood, childhood stress of specific core characteristics may shape birth timing, with cortisol elevation as a biological mediator.”

• AssumptionRests on an assumption: Participants' retrospective reports of childhood stress accurately reflect their actual childhood stress exposure.
• AssumptionRests on an assumption: The final sample of 89 women provided sufficient statistical power to detect the tested associations.
• AssumptionRests on an assumption: A single plasma cortisol measurement at 28–32 weeks gestation adequately represents the HPA activity that mediates childhood stress effects on birth timing.

Classified as probably not a substantial claim.

Statistical inference for the indirect effect used 10,000 bias-corrected bootstrap confidence intervals with replacement.

“For the indirect effect, statistical inference involves the construction of 10,000 bootstrap confidence intervals, bias-corrected and with replacement.”

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

An augmented backward elimination approach was used to select variables for final adjusted models; this approach has been found to reduce bias in variable selection.

“An augmented backward elimination approach, which has been found to reduce bias in variable selection, was used to identify variables for the final adjusted models (Dunkler et al., 2014).”

• cites Dunkler et al., 2014 sourceNot checked yet

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May combine two claims.

African American women are more likely than white women to show maternal stress in the context of preterm birth and to have pregnancy-associated cortisol patterns that differ significantly from white women.

“Of additional importance is the fact that African American women are significantly more likely to show evidence of maternal stress in the context of PTB as well as pregnancy associated maternal cortisol patterns that differ significantly from white women (Christian et al., 2016; Glynn et al., 2007).”

• cites Christian et al., 2016 sourceNot checked yet

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• cites Glynn et al., 2007 sourceNot checked yet

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Classified as probably not a substantial claim.

Eligible participants had to report a dating ultrasound before 15 weeks gestation to reduce error in estimating birth timing.

“In order to minimize the potential for error in estimation of birth timing, eligible participants were required to report a dating ultrasound at < 15 weeks gestation, at which time crown-rump length or composite fetal biometric measurements are expected to predict estimated date of delivery within 7 days (American College of Obstetricians and Gynecologists, 2014).”

• cites American College of Obstetricians and Gynecologists, 2014Not checked yet

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May combine two claims.

Only three studies have examined childhood stress effects on prenatal HPA activity; one supported lasting biological effects and two contested them.

“To our knowledge, only three studies have examined the effect of childhood stress on prenatal HPA activity, with a potential role of lasting biological effects supported (n = 295; Moog et al., 2016) and contested (n = 123; Noll et al., 2007; n = 58; Karakash et al., 2016).”

• cites Moog et al., 2016 sourceNot checked yet

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• cites Noll et al., 2007 sourceNot checked yet

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• cites Karakash et al., 2016 sourceNot checked yet

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

Childhood stress is commonly measured with a cumulative score of a limited set of generally traumatic experiences.

“Childhood stress is commonly assessed by producing a cumulative score of exposures to a limited set of experiences generally considered traumatic (Kalmakis and Chandler, 2015).”

• cites Kalmakis and Chandler, 2015 sourceNot checked yet

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

The final adjusted model controlled for sleep quality and hours awake before venipuncture.

“Therefore, the final adjusted model controlled for sleep quality and hours awake prior to venipuncture.”

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

Because cortisol varies by time of day and gestation, the interval since waking and gestational age at blood draw were also assessed.

“Given diurnal and gestational effects on cortisol levels, hours awake prior to venipuncture and gestational age at venipuncture were also examined.”

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

Maternal age, pre-pregnancy BMI, and sleep quality were assessed as potential confounders along with hours awake before venipuncture and gestational age at venipuncture.

“maternal age, pre-pregnancy BMI, and sleep quality were identified as potential confounders and assessed alongside hours awake prior to venipuncture and gestational age at venipuncture for inclusion in the final adjusted model.”

May combine two claims.

Maternal age, pre-pregnancy BMI, and gestational age at venipuncture did not show evidence of confounding and were removed from the final model.

“maternal age (p values > .33; change in estimates < 3.8%), pre-pregnancy BMI (p values > .17; change in estimates < 8.6%), and gestational age at venipuncture (p values > .19; change in estimates < 4.1%) did not show evidence of confounding for any model and were removed.”

May combine two claims.

The findings support prior work linking stress and distress to birth timing and add to work implicating childhood stress specifically.

“Findings lend support to a large literature linking various forms of stress and distress to birth timing (e.g., Manuck et al., 2015) and add to a small literature implicating childhood stress in particular (Christiaens et al., 2015; Smith et al., 2016).”

• cites Manuck et al., 2015 sourceNot checked yet

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• cites Christiaens et al., 2015 sourceNot checked yet

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• cites Smith et al., 2016 sourceNot checked yet

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Classified as probably not a substantial claim.

Multiple comparisons were made in a relatively small sample.

“multiple comparisons were made among a relatively small sample.”

May combine two claims.

The sample characteristics may have increased the ability to detect childhood stress effects in a small sample but also limit generalizability.

“This may have increased our ability to detect effects of childhood stress in a relatively small sample but also impacts generalizability.”

Classified as probably not a substantial claim.

The data rely on cortisol measured at only one time point.

“our data relies on cortisol assessed at a single time point.”

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

The STRAIN is relatively new compared with systems such as the LEDS, and its childhood and adulthood stress estimates depend on participant recall.

“in comparison to systems such as the LEDS, the instrument is relatively new and estimates of childhood stress and stress in adulthood are dependent upon participant recall.”

Classified as probably not a substantial claim.

The study contributes to understanding stress effects on birth timing among U.S.-born African American women, a literature generally lacking racial stratification.

“The presented work was also interested in furthering understanding of the effects of stress on birth timing among U.S.-born African American women, a considerable contribution to a literature generally lacking racial stratification.”

May combine two claims.

Autobiographical memory tends to remain accurate after a significant time-lapse, with no difference between traumatized and non-traumatized individuals.

“Evidence does suggest that autobiographical memory tends to be quite accurate even following a significant time-lapse, with no difference among traumatized and non-traumatized individuals (Wittekind et al., 2017).”

• cites Wittekind et al., 2017 sourceNot checked yet

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Classified as probably not a substantial claim.

Stress assessment was standardized to occur during healthy pregnancy to reduce the systematic effect of pregnancy outcome on recall.

“Stress assessment was also standardized to occur during healthy pregnancy to minimize the systematic effect of pregnancy outcome on recall.”

May combine two claims.

Enrollment criteria targeting seemingly healthy pregnancy increased the ability to observe spontaneously initiated birth, with a lower induction/pre-labor cesarean rate than the U.S. overall.

“our enrollment criteria, which targeted seemingly healthy pregnancy, did increase our ability to observe spontaneously-initiated birth, as the rate of induction of labor/pre-labor cesarean was 40% in our sample compared to an overall U.S. rate of greater than 50% (Laughon et al., 2012; Zhang et al., 2010).”

• cites Laughon et al., 2012 sourceNot checked yet

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• cites Zhang et al., 2010 sourceNot checked yet

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

Recall bias cannot be fully excluded.

“However, the potential for recall bias cannot be fully excluded.”

May combine two claims.

Maternal stress assessment is considered important in prenatal care, but screening recommendations cover only intimate partner violence and maternal depression.

“while maternal stress assessment is considered an important component of prenatal care, recommendations for screening cover only intimate partner violence and maternal depression (American College of Obstetricians and Gynecologists, 2010; Moyer and U.S. Preventive Services Task Force, 2013).”

• cites American College of Obstetricians and Gynecologists, 2010Not checked yet

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• cites Moyer and U.S. Preventive Services Task Force, 2013 sourceNot checked yet

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

The STRAIN offers advantages over alternative stress measures in the breadth of information it captures.

“the STRAIN offers significant advantages over alternative stress measures in terms of the breadth of information gained.”

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

HPA output can be measured in many ways, including CRH, ACTH, plasma cortisol, salivary cortisol, and hair cortisol.

“HPA output can be measured in numerous ways (e.g., CRH, ACTH, plasma cortisol, salivary cortisol, hair cortisol).”

May combine two claims.

The null hypothesis was rejected more often than expected by chance, and Type I error is possible, making the work preliminary.

“The null hypothesis was rejected more frequently than expected by chance; however, the potential for Type I error is noted, highlighting the preliminary nature of this work.”

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

It is difficult to tell whether the change in the indirect effect reflects confounding or reduced power.

“It is difficult to determine whether this change is indicative of confounding or diminished power.”

May combine two claims.

The sample size may have produced null findings when small effects existed and prevented examining age differences in childhood stress effects.

“The sample size may have resulted in null findings when small effects were indeed present and also prohibited examination of differential effects of childhood stress according to age”

May combine two claims.

The study provides data on generalized risk in the full sample because stress-induced endocrine dysregulation may plausibly accelerate both spontaneous and medically indicated birth.

“We provide data on generalized risk among the full sample (n = 89), as it is biologically plausible that stress-induced endocrine dysregulation may expedite spontaneous birth as well as medically-indicated birth.”

• AssumptionRests on an assumption: Stress-induced endocrine dysregulation can accelerate both spontaneous and medically indicated birth.

May combine two claims.

Cortisol rises across pregnancy, most sharply in the early second trimester, then stabilizes across the late second and early third trimesters.

“cortisol rises progressively across pregnancy, the most pronounced rise occurs during the early 2nd trimester, with a relative stabilization across late 2nd and early 3rd trimesters (D’Anna-Hernandez et al., 2011; Smy et al., 2016).”

• cites D’Anna-Hernandez et al., 2011Not checked yet

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• cites Smy et al., 2016 sourceNot checked yet

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May combine two claims.

HPA markers tend to correlate well during pregnancy, and each has been linked to early birth in prior work.

“Markers tend to correlate well during pregnancy (e.g., Glynn et al., 2007; O’Keane et al., 2011), with each linked to early birth in prior work”

• cites Glynn et al., 2007 sourceNot checked yet

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• cites O’Keane et al., 2011Not checked yet

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May combine two claims.

Childhood stress effects may occur independently of adulthood stress, and HPA hyperactivity during pregnancy may be a notable mediator of childhood stress-related preterm birth.

“Further, effects may occur independent of stress in adulthood and, during pregnancy, HPA hyperactivity may be a notable biological mediator in the development of childhood stress-related PTB.”