Secondary Logo

Journal Logo

Contents: Original Research

Association Between Fatty Acid Supplementation and Prenatal Stress in African Americans

A Randomized Controlled Trial

Keenan, Kate PhD; Hipwell, Alison E. PhD; Bortner, Jenna BA; Hoffmann, Amy BA; McAloon, Rose BA

Author Information
doi: 10.1097/AOG.0000000000000559
  • Free

Consistent with the prenatal programming hypothesis,1 there is now evidence from multiple studies using a variety of methodologies and across different species that the mother's level of psychosocial stress during pregnancy is significantly associated with suboptimal developmental outcomes in their offspring including disturbances in attention,2,3 impaired learning and disruption in neurogenesis,4,5 and increased anxiety-like behaviors.2 The strength of the causal claim is based on rigorous controlled experiments in which the prenatal effect is distinguished from postnatal effects by using methods such as cross-fostering or nursery rearing. The pattern of findings in humans closely mirrors those from controlled animal studies.6–9 The strongest candidate for the mechanism by which prenatal stress confers risk to the offspring is the maternal hypothalamic–pituitary–adrenal axis. Prenatal stress causes long-term alterations in the functioning of the offspring's hypothalamic–pituitary–adrenal axis,10,11 and each of the phenotypic outcomes identified can be linked with disruptions in the hypothalamic–pituitary–adrenal axis.

A few investigators have examined the effects of docosahexaenoic acid (DHA) supplementation during pregnancy on later developmental functioning. Neuroprotective effects of DHA supplementation during pregnancy on the offspring has been reported in controlled animal studies.12–14 In humans, fatty acid supplementation is also associated with reductions in stress reactivity in controlled studies.15–18 Given this strong evidence, it is important to initiate studies of the prevention of the negative effects of prenatal stress in humans. This is especially important for women living in poverty, who are at higher risk for adverse birth outcomes,19 and whose offspring are at higher risk for poor developmental outcomes.20,21 Notably, DHA intake and blood levels of DHA are approximately a quarter to a third of the recommended levels for pregnant women living in low-income environments.22 African American women living in dense, urban poverty appear to have the highest risk for adverse birth outcomes.23 These data converge to support the hypothesis that prenatal DHA supplementation among women living in stressful environments would lead to reductions in perceived stress and greater modulation of the activation of the hypothalamic–pituitary–adrenal axis in response to stress.


Pregnant women were recruited from Obstetrics Clinics within the University of Pittsburgh Medical Center from 2010 to 2012. Sample size was determined based on power calculations using existing data on perceived stress and cortisol response to the Trier Social Stress Test among pregnant women. Given the goals of the study, only demographically eligible women were approached for screening. Demographic eligibility included Medicaid insurance or Medicaid eligible, African American race, age between 20 and 30 years, and 16–21 weeks of gestation.

In addition to African American women being disproportionately represented among families living in inner-city poverty in the United States and having higher rates of suboptimal birth outcomes,19 there are race differences in cortisol reactivity to stress and pregnancy.24–26 To control for these group differences, either adequate numbers of participants of different races would need to be included or the study would have to be limited to a single race. Given the scope of the study, we chose to study African Americans only. We limited the sample to ages 20–30 years, which comprises more than 60% of pregnancies among African Americans.27 This range excluded younger and older ages of mothers during which the risk for suboptimal pregnancy outcomes increases.

Power calculations were computed using published data; the standard deviation of perceived stress using the Perceived Stress Scale was estimated to be 7.4.28 Forty participants in the supplement group and 20 in the placebo group yielded 80% power to detect a difference in stress levels of approximately four between the two groups using a two-sided test at the .05 significance level. The standard deviation of the cortisol response to the Trier Social Stress Test at 20 minutes was estimated to be equal to 8 nmol/L.29 Forty participants in the supplement group and 20 in the placebo group yielded 80% power to detect a difference in peak response of approximately 6 nmol/L between the two groups using a two-sided test at the .05 significance level.

Women were recruited using two methods. First, research assistants attended obstetric clinics and provided flyers to patients that listed the demographic inclusion criteria (ie, African American race, Medicaid insurance, gestational age between 16 and 21 weeks, and maternal age between 20 and 30 years) asking those eligible to complete the screening. Second, demographically eligible patients identified through electronic medical records were contacted by mail and phone to assess interest in the study. Telephone screenings were then conducted to assess eligibility. Exclusion criteria included two or more servings of sea fish per week, known medical complications (gestational diabetes, preeclampsia, subchorionic hematoma), regular use of steroid medications, regular alcohol use, cigarettes or use of illegal substances (by maternal report), use of blood thinners or anticoagulants, use of psychotropic medications, body mass index (calculated as weight (kg)/[height (m)]2) higher than 40, and allergy to iodine or soy. One hundred forty-six participated in screening for eligibility. Of those screened, 26 were ineligible, 64 were eligible and enrolled, 48 were eligible at the time of screening but could not be enrolled before the enrollment window (ie, 16–21 weeks of gestation), and eight refused to participate (Fig. 1).

Fig. 1
Fig. 1:
Nutrition and pregnancy study participation rates. *Eligible at the time of screening but unable to schedule baseline within gestational age criterion.Keenan. Effects of DHA Supplementation on Prenatal Stress. Obstet Gynecol 2014.

Participants were reimbursed on an accelerated schedule with $40 for their first visit and an increase in payments of $10 for each subsequent visit. The institutional review boards of the University of Chicago and University of Pittsburgh approved all study procedures. This study also was a registered clinical trial (NCT01158976).

Once enrolled, women were randomly assigned on a two-to-one ratio to receive the omega-3 nutritional supplement (n=43) or a corn and soybean oil placebo (n=21) beginning at enrollment and up through the end of pregnancy. We expected greater variability in the dependent measures (eg, stress reactivity) among the experimental participants than the control patients. Thus, to optimize power to test the hypotheses, we enrolled a higher number of participants in the experimental group to adequately capture that variability. Women randomized to the study group received the supplement through two gel capsules providing: 450 mg DHA; 40 mg docosapentaenoic acid and eicosatetranoic acid; 90 mg eicosapentaenoic acid; and 15 international units of vitamin E supplied by Nordic Naturals. Women receiving the placebo received two capsules supplied by Nordic Naturals that were matched in size, color, and smell to the study drug. The pharmacist at the University of Pittsburgh used computer-generated random assignment of identification numbers to active supplement or placebo in blocks of nine: six identification numbers were randomized to active supplement and three to placebo. To maintain the double-blind, the pharmacist divided each randomization block of nine identification numbers into groups of three: three identification numbers were assigned to group A (placebo) and the remaining six were assigned to either group B or C, both of which received identical doses of active supplement. This approach allowed the pharmacist to randomize on a two-to-one ratio without having the unbalanced design break the blind. Once the study was complete, the blind was broken and the two groups receiving identical doses of active supplement were combined for analyses.

Cortisol response to a social evaluative stressor was measured at baseline and 24 and 30 weeks of gestation. Participants completed questionnaires covering stressful life events, perceived stress, and symptoms of depression at baseline and 24 and 30 weeks of gestation. Research assistants contacted participants by phone three times per week to ask the time of day that the supplement was taken and gathered data on perception of taste and possible gastrointestinal side effects to increase compliance.

Symptoms of depression were assessed using the Edinburgh Postnatal Depression Scale,30 a 10-item measure designed to assess pre- and postnatal depression without confounding the assessment of depression with somatic symptoms of pregnancy (eg, weight gain, loss of energy). Internal consistency in this sample was high: α=0.88 at baseline; 0.86 at 24 weeks of gestation; and 0.87 at 30 weeks. The Difficult Life Circumstances Scale31 is a set of 28 yes–no questions about difficult circumstances at home or work that may be a problem for the primary caregiver. The measure was designed to include items that would be applicable to women living in poverty such as difficulty with finances and housing. The internal consistency of the scale as measured by α ranged from 0.73 to 0.80. The Perceived Stress Scale32 is a 14-item scale designed to measure the degree to which situations in one's life are appraised as stressful. The internal consistency of the scale as measured by α was high: 0.85 at baseline; 0.88 at 24 weeks of gestation; and 0.87 at 30 weeks of gestation.

Following published recommendations for assessing physiologic stress reactivity during pregnancy,33 the Trier Social Stress Test34 was used as a psychological stressor. The Trier Social Stress Test procedure consists of a 2-minute preparation time followed by a 5-minute speech (as if for a job interview) and then a 5-minute mental arithmetic task. The latter two tasks are performed in front of a video camera and an audience. The Trier Social Stress Test typically elicits individual differences in cortisol reactivity, even during pregnancy.29,35

Saliva was collected at three time points at the baseline and 24 and 30 weeks of gestation assessments: 20 minutes after arrival to the laboratory and 20 and 45 minutes post-Trier Social Stress Test. To collect saliva samples, an absorbent, unflavored dental roll was applied to the tongue, cheek, and gums for several minutes. The dental roll was then placed in a labeled plastic salivette. Samples were immediately transferred to a freezer and stored at −20°C until assayed. On the day of testing, samples were thawed and centrifuged at 3,000 rpm for 10 minutes allowing for a clear sample to be pipetted into appropriate test wells. All samples from each participant were assayed in the same batch to minimize variability and assayed with reagents from the same lot. Samples with sufficient saliva were assayed in duplicate using the Salimetrics HS Salivary Cortisol EIA Kit for unbound cortisol. This assay has a lower limit of sensitivity from 0.007 to 1.2 micrograms per deciliter. The average between-assay variance is 3.9% and 7.1%, and the average within-assay variance is 6.7% and 6.9% for high and low concentrations, respectively. The correlation between saliva and serum using the Salimetrics HS Salivary Cortisol EIA Kit and the Coat-a-Count Serum Cortisol RIA kit is 0.96 (P<.001). Analyses were conducted with log10-transformed cortisol values but are presented as untransformed micrograms per deciliter for ease of interpretation.


Of the 64 participants who completed the baseline assessment, four (6.3%) withdrew from the study: two participants from each study arm. Two participants randomized to placebo withdrew as a result of adverse events: one miscarried, and the other withdrew as a result of mood changes. Two participants randomized to active supplement withdrew as a result of adverse events: one reported headaches and the other an upset stomach. Forty-seven participants (73.4%) attended all three sessions. Descriptive statistics are presented in Table 1 for depression, negative life events, and perceived stress at baseline and at 24 and 30 weeks of gestation. Data collected from all participants, including those who withdrew, are included in the analyses. Baseline self-report data for one participant in the active group were lost. One participant, with undetectable cortisol values for five of the nine samples, was not included in the analyses of cortisol response.

Table 1
Table 1:
Descriptive Statistics for Depression, Negative Life Events, and Perceived Stress Scores at Baseline and at 24 and 30 Weeks of Gestation for the Total Sample and the Active and Placebo Groups

The first goal was to examine group differences in level of depression, negative life events, and perceived stress by conducting analyses of variance for each measure controlling for the other two measures. At baseline and 24 weeks of gestation, there were no group differences in any of the three measures. At 30 weeks of gestation, perceived stress was significantly lower among the participants receiving supplementation (mean 27.4) compared with those receiving placebo (mean 29.5) controlling for negative life events and depression scores at 30 weeks of gestation (F [1, 47] 5.06, P=.029, Cohen's d=0.65; Fig. 2), a difference of more than half of a standard deviation for the sample.

Fig. 2
Fig. 2:
Effect of omega-3 supplementation on perceived stress score, controlling for negative life events and depression scores.Keenan. Effects of DHA Supplementation on Prenatal Stress. Obstet Gynecol 2014.

Cortisol response to the Trier Social Stress Test was examined as a function of group status (supplementation versus placebo) at baseline and 24 and 30 weeks of gestation by repeated-measures analysis of variance using a Greenhouse-Geisser correction to account for lack of sphericity. Time of day was significantly associated with initial cortisol levels at baseline but not at 24 and 30 weeks of gestation; time of day was controlled in analyses involving cortisol levels at baseline.

Cortisol levels before and after the Trier Social Stress Test did not vary as a function of supplementation at baseline or at 24 weeks of gestation. At 30 weeks of gestation, cortisol levels over time significantly differed as a function of supplementation (F [1.78, 83.85]=6.24, P=0.004, Cohen's d=0.76). As shown in Figure 3, women who received placebo had higher levels of cortisol on arrival to the laboratory compared with women receiving omega-3 supplementation. Levels for women receiving placebo were characterized by a relatively steep decline, whereas levels for women receiving omega-3 supplement evidenced a slight increase in response to the stressor, on average, followed by decline during the period of recovery. To further probe the differences in levels on arrival to the laboratory, the two groups were compared at baseline and 24 weeks and 30 weeks of gestation. As shown in Figure 4, cortisol levels on arrival to the laboratory were similar for the two groups at baseline but diverged over time such that by 30 weeks of gestation, women who received placebo had levels that were on average 20% higher than women receiving supplement (mean 0.35 compared with 0.27; F [1.74, 74.63] 3.51, P=.041, Cohen's d=0.56).

Fig. 3
Fig. 3:
Cortisol levels before and after the Trier Social Stress Test (TSST) at 30 weeks of gestation (F [1.78, 83.85] 6.24, P=.004; Cohen's d=0.76); error bars indicate standard error at each time point within each group.Keenan. Effects of DHA Supplementation on Prenatal Stress. Obstet Gynecol 2014.
Fig. 4
Fig. 4:
Cortisol levels 20 minutes after arrival to the laboratory at baseline, at 24 weeks of gestation, and at 30 weeks of gestation (F [1.74, 74.63], P=.041; Cohen's d=0.56); error bars indicate standard error at each time point within each group.Keenan. Effects of DHA Supplementation on Prenatal Stress. Obstet Gynecol 2014.


The present study was conducted from the perspective of the prenatal programming hypothesis.1 Specifically, a primary hypothesized mechanism by which prenatal stress affects offspring development is through exposure of the fetus to high levels of glucocorticoids released by the mother. This exposure, in turn, affects the fetal stress architecture in part by adjusting the set point for mounting a stress response and interfering with the feedback mechanisms for maintaining homeostasis. Although the postpartum environment continues to affect brain development, it is plausible that this initial insult sets the stage for a poor developmental trajectory that begins with poorly modulated response to stress in infancy.

Results from the present study provide preliminary evidence that changes in prenatal nutrition may be one way to interrupt the suboptimal prenatal programming of the fetus developing in the context of high levels of maternal stress. Pregnant women living in a high-stress, low-income, urban environment who received a fatty acid supplement reported lower levels of perceived stress than women who received placebo despite a lack of change in exposure to stressors. Moreover, the reduction of perceived stress was independent of depression, which was not associated with fatty acid supplementation. The lack of an association between DHA supplementation and depression symptoms is consistent with the literature on perinatal depression. In several randomized controlled trials, DHA was not associated with depression scores,36,37 but supplementation did appear to enhance the efficacy of psychopharmacologic treatment for depression,38 suggesting that systems associated with depressed mood and affect neurotransmission such as the hypothalamic–pituitary–adrenal axis are affected by fatty acid supplementation.

In fact, evidence from the present study suggests that DHA supplementation does affect the functioning of the hypothalamic–pituitary–adrenal axis by modulating response to a social stressor. This was demonstrated primarily through a lower cortisol response to arriving at the laboratory. By 30 weeks of gestation, participants who received DHA supplementation had lower levels of cortisol on arrival to the laboratory and on average demonstrated a slight increase in cortisol in response to the stressor, a pattern typically observed late in pregnancy.29,33 In contrast, participants who had received placebo evidenced high levels of cortisol on arrival to the laboratory followed by a steep decrease in cortisol levels during and after exposure to the Trier Social Stress Test. One interpretation of this pattern is that an exaggerated response to anticipatory stress leads to a less flexible response to the stressor. The high levels of cortisol on arrival to the laboratory followed by a lack of responsiveness to the stressor has been described as a pattern of dysregulated hypothalamic–pituitary–adrenal axis functioning associated with depression both in adults39 and children.40 Lack of cortisol response to a social stressor also has been observed among adults reporting high levels of early life adversity, especially females.41 Docosahexaenoic acid supplementation appears to protect pregnant women living in low-income environments from manifesting this type of dysregulation.

Demonstrating associations between of fatty acid supplementation and lower prenatal stress, however, is not sufficient. The next step will be to test the hypothesis that alterations in maternal stress levels through fatty acid supplementation improves developmental outcomes in the offspring. Data from other studies support the testing of this hypothesis. For example, Bolten and colleagues35 reported that cortisol reactivity to the Trier Social Stress Test at 32–34 weeks of gestation, but not basal cortisol levels, was associated with neonatal self-regulation. Similarly, Werner and colleagues42 found that neonates of women with high levels of maternal cortisol 25 minutes after arrival to the laboratory during late gestation were more likely to be classified as “high reactive” (ie, more motor activity and crying) in response to novel stimuli.

Thus, several important links among prenatal stress, cortisol levels, and neonate neurodevelopment have been demonstrated. Data from our preliminary study are compelling in terms of the potential effect on health disparities in maternal and neonatal health, a significant public health problem that is poorly understood. The findings, however, are in need of replication. In addition, a number of limitations should be noted. First, the small sample size and attrition of participants over time likely affect the reliability of the findings; thus, replication and timing of effects need to be explored in a larger study population. Although retention across study visits was comparable for the two groups, there may have been some differential selection bias across the two groups. Second, given the preliminary nature of the study, we did not control for multiple testing, and of the 13 tests of significance, we could expect that one may be the result of chance. The effect sizes for the significant results were medium to large, however, providing some indication that the results are not spurious. Third, we relied on maternal report of uptake as opposed to a rigorous assessment of blood levels of fatty acids across pregnancy. In addition to the possibility that uptake varied, blood levels may have varied among individuals with the same level of supplementation as a result of other dietary factors or individual differences in metabolism. Fourth, although we did not readminister the Trier Social Stress Test after 30 weeks of gestation, it would be important to examine whether differences in cortisol levels as a function of supplementation are maintained. Moreover, in the context of improving neonate outcomes, it may be important to supplement earlier in gestation. The third trimester is a period of fetal development that may be particularly sensitive to prenatal stress given the increase in maternal cortisol and decrease in placental corticosteroid 11β-hydroxysteroid dehydrogenase type 2, yet exposure earlier in gestation may also confer risk.43

In conclusion, the results reported here extend earlier work on the association between fatty acid supplementation and improved obstetric outcomes and complement existing research on prenatal stress and offspring neurodevelopment by providing preliminary evidence for nutritional moderation of prenatal stress.


1. Barker DJ. Intrauterine programming of adult disease. Mol Med Today 1995;1:418–23.
2. Schneider ML, Moore CF, Kraemer GW, Roberts AD, DeJesus OT. The impact of prenatal stress, fetal alcohol exposure, or both on development: perspectives from a primate model. Psychoneuroendocrinology 2002;27:285–98.
3. Keenan K, Bartlett TQ, Nijland M, Rodriquez J, Nathanliez P, Zürcher N. Poor nutrition during pregnancy and lactation negatively impacts neurodevelopment of the offspring: evidence from a translational primate model. Am J Clin Nutr 2013;98:396–402.
4. Chapillon P, Patin V, Roy V, Vincent A, Caston J. Effects of pre-and postnatal stimulation on developmental, emotional, and cognitive aspects in rodents: a review. Dev Psychobiol 2002;41:373–87.
5. Coe CL, Lulbach GR, Schneider ML. Prenatal disturbance alters the size of the corpus callosum in young monkeys. Dev Psychol 2002;41:178–85.
6. Huizink AC, de Medina PG, Mulder EJ, Visser GH, Buitelaar JK. Psychological measures of prenatal stress as predictors of infant temperament. J Am Acad Child Adolesc Psychiatry 2002;41:1078–85.
7. Hibbeln JR, Davis JM, Steer C, Emmett P, Rogers I, Williams C, et al.. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet 2007;369:578–85.
8. Kohlboeck G, Glaser C, Tiesler C, Demmelmair H, Standl M, Romanos M, et al.. Effect of fatty acid status in cord blood serum on children's behavioral difficulties at 10 y of age: results from the LISAplus Study. Am J Clin Nutr 2011;94:1592–9.
9. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics 2003;111:e39–44.
10. Henry C, Kabbaj M, Simon H, Le Moal M, Maccari S. Prenatal stress increases the hypothalamic–pituitary–adrenal axis response to stress in young and adult rats. J Endocrinol 1994;6:341–5.
11. Weinstock M. Does prenatal stress impair coping and regulation of hypothalamic-pituitary-adrenal axis? Neurosci Biobehav Rev 1997;21:1–10.
12. Sable PS, Dangat KD, Joshi AA, Joshi SR. Maternal omega 3 fatty acid supplementation during pregnancy to a micronutrient-imbalanced diet protects postnatal reduction of brain neurotrophins in the rat offspring. Neuroscience 2012;217:46–55.
13. Jayashankar S, Glover CN, Folven KI, Brattelid T, Hogstrand C, Lundebye AK. Cerebral gene expression and neurobehavioural responses in mice pups exposed to methylmercury and docosahexaenoic acid through the maternal diet. Environ Toxicol Pharmacol 2012;33:26–38.
14. Zhao J, Del Bigio MR, Weiler HA. Maternal arachidonic acid supplementation improves neurodevelopment in young adult offspring from rat dams with and without diabetes. Prostaglandins Leukot Essent Fatty Acids 2011;84:63–70.
15. Maes M, Christophe A, Bosmans E, Lin A, Neels H. In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress. Biol Psychiatry 2000;47:910–20.
16. Hellhammer J, Hero T, Franz N, Contreras C, Schubert M. Omega-3 fatty acids administered in phosphatidylserine improved certain aspects of high chronic stress in men. Nutr Res 2012;32:241–50.
17. Yehuda S, Rabinovitz S, Mostofsky DI. Mixture of essential fatty acids lowers test anxiety. Nutr Neurosci 2005;8:265–7.
18. Delarue J, Matzinger O, Binnert C, Schneiter P, Chioléro R, Tappy L. Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Diabetes Metab 2003;29:289–95.
19. Giscombé CL, Lobel M. Explaining disproportionately high rates of adverse birth outcomes among African Americans: the impact of stress, racism, and related factors in pregnancy. Psychol Bull 2005;131:662–83.
20. Noble KG, McCandliss BD, Farah MJ. Socioeconomic gradients predict individual differences in neurocognitive abilities. Dev Sci 2007;10:464–80.
21. Reiss F. Socioeconomic inequalities and mental health problems in children and adolescents: a systematic review. Soc Sci Med 2013;90:24–31.
22. Stark KD, Beblo S, Murthy M, Buda-Abela M, Janisse J, Rockett H, et al.. Comparison of bloodstream fatty acid composition from African-American women at gestation, delivery, and postpartum. J Lipid Res 2005;46:516–25.
23. Kent ST, McClure LA, Zaitchik BF, Gohlke JM. Area-level risk factors for adverse birth outcomes: trends in urban and rural settings. BMC Pregnancy Childbirth 2013;13:129.
24. DeSantis AS, Adam EK, Doane LD, Mineka S, Zinbarg RE, Craske MG. Racial/ethnic differences in cortisol diurnal rhythms in a community sample of adolescents. J Adolesc Health 2007;41:3–13.
25. Glynn LM, Schetter CD, Chicz-DeMet A, Hobel CJ, Sandman CA. Ethnic differences in adrenocorticotropic hormone, cortisol and corticotropin-releasing hormone during pregnancy. Peptides 2007;28:1155–61.
26. Wilcox S, Bopp M, Wilson DK, Fulk LJ, Hand GA. Race differences in cardiovascular and cortisol responses to an interpersonal challenge in women who are family caregivers. Ethnic Dis 2005;15:17–24.
27. Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Matthews TJ. Births: final data for 2011. Natl Vital Stat Rep 2013;62:1–69, 72.
28. Young DR, He X, Genkinger J, Sapun M, Mabry I, Jehn M. Health status among urban African American women: associations among well-being, perceived stress, and demographic factors. J Behav Med 2004;27:63–76.
29. Nierop A, Bratsikas A, Klinkenberg A, Nater UM, Zimmermann R, Ehlert U. Prolonged salivary cortisol recovery in second-trimester pregnant women and attenuated salivary alpha-amylase responses to psychosocial stress in human pregnancy. J Clin Endocrinol Metab 2006;91:1329–35.
30. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression: development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry 1987;150:782–6.
31. Barnard KE, Johnson S, Booth CL, Bee H. Difficult life circumstances scale. Seattle (WA): NCAST Publications; 1989.
32. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav 1983;24:385–96.
33. De Weerth C, Wied CC, Jansen LM, Buitelaar JK. Cardiovascular and cortisol responses to a psychological stressor during pregnancy. Acta Obstet Gynecol Scand 2007;86:1181–92.
34. Kirschbaum C, Pirke KM, Hellhammer DH. The “Trier Social Stress Test”: a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993;28:76–81.
35. Bolten M, Nast I, Skrundz M, Stadler C, Hellhammer DH, Meinlschmidt G. Prenatal programming of emotion regulation: neonatal reactivity as a differential susceptibility factor moderating the outcome of prenatal cortisol levels. J Psychosom Res 2013;75:351–7.
36. Marangell LB, Martinez JM, Zboyan HA, Kertz B, Seung Kim HF, Puryear LJ. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 2003;160:996–8.
37. Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P; DOMInO Investigative Team. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA 2010;304:1675–83.
38. Deligiannidis KM, Freeman MP. Complementary and alternative medicine for the treatment of depressive disorders in women. Psychiatr Clin North Am 2010;33:441–63.
39. Burke HM, Davis MC, Otte C, Mohr DC. Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology 2005;30:846–56.
40. Suzuki H, Belden AC, Spitznagel E, Dietrich R, Luby JL. Blunted stress cortisol reactivity and failure to acclimate to familiar stress in depressed and sub-syndromal children. Psychiatry Res 2013;210:575–83.
41. Lovallo WR. Early life adversity reduces stress reactivity and enhances impulsive behavior: implications for health behaviors. Int J Psychophysiol 2013;90:8–16.
42. Werner E, Zhao Y, Evans L, Kinsella M, Kurzius L, Altincatal A, et al.. Higher maternal prenatal cortisol and younger age predict greater infant reactivity to novelty at 4 months: an observation-based study. Dev Psychobiol 2013;55:707–18.
43. Davis EP, Sandman CA. The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev 2010;81:131–48.
© 2014 by The American College of Obstetricians and Gynecologists.