Antidepressant treatment modifies the association between maternal breastfeeding experience and HPA axis activation

Presented at The Pregnancy Meeting, San Franscisco, CA

Alison M. Stuebe, Roger Mills-Koonce, Samantha Meltzer-Brody, Chelsea Strange, Karen Grewen

Objective: Longer breastfeeding duration is associated with lower rates of postpartum depression, but the underlying mechanism is not known. We sought to quantify the association between maternal experience of breastfeeding and HPA axis activity.

Study Design: We analyzed data from the Mood, Mother, and Infant Study. Feeding intention was assessed in the 3rd trimester, and mood symptoms, antidepressant use, and breastfeeding intensity were assessed monthly in the first postpartum year. Breastfeeding experience was assessed using the Maternal Breastfeeding Evaluation Scale (MBSES). Maternal hair was collected at 6 months and analyzed utilizing liquid chromatography-tandem mass spectrometry to assess cortisol and cortisone levels over the prior 3 months. We used T tests, Pearson correlation, and linear regression to quantify associations between hair corticosteroids and antidepressant use, mood symptoms, breastfeeding intensity, and breastfeeding experience.

Results: Hair steroid levels were available for 179 participants, among whom 44 were taking antidepressants at 6 months postpartum. Antidepressant use was associated with higher hair cortisone than non-use (mean (se) 8.68 (0.97) vs. 6.36 (0.33), T test p=0.03), but not with cortisol or cortisol-to-cortisone ratio (p >0.05, Table). Hair cortisone was correlated with weight at the 6 month visit, and inversely correlated with breastfeeding intensity and MBSES, but it was not associated with mood symptoms. In multivariable regression models, we found that antidepressant use modified the association between MBSES and hair cortisone (interaction p=0.02, figure). Among women using antidepressants, a more positive experience of breastfeeding was associated with lower hair cortisone, whereas among women not using antidepressants, breastfeeding experience was not related to hair cortisone levels.

Conclusion: Among women being treated for depression, we found that maternal experience of breastfeeding was inversely correlated with hair cortisone levels. These data suggest that the affective experience moderates the effect of breastfeeding on maternal physiology.

Associations of postpartum depression symptoms and infant feeding with Hypothalamic Pituitary Adrenal (HPA) axis reactivity

Presented at The Pregnancy Meeting, Grapevine, TX

Anna E. Bauer, Kathryn Wouk, Karen Grewen, Nisha C. Gottfredson, Samantha Meltzer-Brody, Cathi Propper, Roger Mills-Koonce, Brenda Pearson, Julia Whitley, Alison M. Stuebe

Objective: Both oxytocin and depression have been shown to blunt the HPA axis response to stressors. We aimed to determine whether postpartum depression symptoms, infant feeding, and their interaction are associated with HPA axis dysregulation, indexed by loss of expected associations in adrenocorticotropic (ACTH)-cortisol (CRT) coupling.
Study Design: Women intending to breastfeed were recruited in the 3rd trimester of pregnancy, oversampling for past or current anxiety/depression. At 2 months postpartum, dyads attended a lab visit. Following peripheral IV placement, women chose to breast or bottle-feed their infants, as they would at home. After a 10-minute post-feed rest, women participated in the Trier Social Stress Test (TSST), a standardized social stressor that includes a speech and a math task. Blood samples for ACTH and CRT were collected 10 minutes after feeding, during each task, and at 10, 20, and 30 minutes of recovery. Multilevel models were used to evaluate whether associations between ACTH at time j and CRT at time j+1 differed between women with or without current depression symptoms (Beck Depression Inventory ≥14 vs. < 14) and infant feeding type (breast vs. bottle).
Results: A total of 222 women were enrolled; 205 completed the 2 month visit, and 165 breastfed before the TSST (80.5%). Breastfeeding women had lower ACTH (p=0.01) and CRT (p=0.02) than bottle-feeding women, but no differences in ACTH-CRT coupling (p=0.15). ACTH (p=0.37), CRT (p=0.93), and ACTH-CRT coupling (p=0.09) were similar in women with and without depression symptoms. There was a significant interaction (p=0.03) between depression symptoms and infant feeding on ACTH-CRT coupling. Symptomatic women who breastfed had lower ACTH-CRT coupling responses compared with those who bottle-fed, but there were no differences by feeding in asymptomatic women (figure).
Conclusion: We found that breastfeeding blunted HPA axis response only among women with depression symptoms but not among women without. The influence of breastfeeding and oxytocin on HPA axis reactivity may play a role in the pathophysiology of perinatal mood disorders.

Disordered eating symptoms and maternal emotional experience of breastfeeding

Presented at the Breastfeeding and Feminism International Meeting, Chapel Hill, NC March 2019

Alison M. Stuebe, Samantha Meltzer-Brody, Brenda Pearson, Kathryn Wouk, Karen Grewen

Background: Symptoms of disordered eating and body image are common, and may worsen following childbirth. The relationship between disordered eating symptoms and maternal emotional experience of breastfeeding has not been explored.

Methods: Women intending to breastfeed at least two months were recruited into the Mood, Mother and Infant cohort study in the 3rd trimester of pregnancy. Psychiatric history was assessed at enrollment via Structured Clinical Interview, including past or current eating disorder diagnosis, with oversampling of women with a history or current diagnosis of major depressive or anxiety disorder. Eating disorder symptoms were quantified at enrollment and at 2, 6 and 12 months postpartum using the Eating Disorder Examination Questionnaire (EDE-Q), which assesses restraint, eating concern, weight concern, and shape concern, as well as a global score. Early breastfeeding experience was assessed at 1 month with the question, “How would you say you felt about breastfeeding during the first week you were breastfeeding?” (Likert scale, 1=Disliked very much, 5=Liked very much). Emotions during feeding at 2, 6 and 12 months were quantified with the modified Differential Emotions Scale (mDES), which asks women to indicate the greatest amount that they experienced 10 positive emotions and 10 negative emotions while feeding their baby during the past week. We measured overall breastfeeding experience at 12 months using the Maternal Breastfeeding Evaluation Scale (MBFES), including 3 subscales of Maternal Enjoyment/Role Attainment, Infant Satisfaction/Growth, and Lifestyle/Maternal Body Image. We used Spearman correlations to quantify the association between EDE-Q scores and measures of maternal breastfeeding experience, and we used mixed models to assess the association between MBFES score and EDE-Q trajectory from enrollment through 12 months postpartum.

Results: Data were available for 206 women, of whom 25 (12.1%) had a history of an eating disorder diagnosis. Higher baseline EDE-Q score and both shape and weight concern subscales were correlated with not liking breastfeeding in the first week (p<0.05). The EDE-Q score and all 4 subscales were associated with more negative emotions during feeding at 2, 6, and 12 months (p<.01), with the exception of the EDE-Restraint subscale and negative emotions at 6 months. EDE-Q score was also associated with lower MBFES scores on all 3 subscales (p=.02, .002, <.0001), as well as lower total score (p<.001). We found the strongest negative correlation between the EDE-Q Shape Concern subscale and the MBES Lifestyle / Maternal Body Image subscale (r=0.45, p<.0001). In mixed models adjusting for maternal body mass index and past or current depression or anxiety, MBFES scores in the highest tertile were associated with lower EDE-Q scores from enrollment through 12 months postpartum (group p<.01).

Conclusion: Symptoms of disordered eating and body image were associated with negative maternal experiences of breastfeeding. Woman-centered strategies to address these concerns in the context of infant feeding and the perinatal period may improve the lived experience of breastfeeding.

Perinatal mood disorders modify the association between infant feeding and cortisol response to stress

Presented at the Society for Maternal Fetal Medicine, Las Vegas, NV, February 2019.

Alison M. Stuebe, Samantha Meltzer-Brody, Roger Mills-Koonce, Brenda Pearson, Julia Whitley, Karen Grewen

Objective: Oxytocin has been shown to blunt the HPA axis response to stressors. We conducted a longitudinal prospective cohort study to test the hypothesis that perinatal mood disorders are associated with dysregulation of the effects of breastfeeding, a physiologic stimulus for oxytocin, on maternal HPA axis activity.

Study Design: Women intending to breastfeed were recruited in the 3rd trimester of pregnancy. Psychiatric history was assessed at enrollment via Structured Clinical Interview, with oversampling of women with past or current anxiety or depression. Women with an active psychiatric diagnosis at enrollment comprised the prenatal depression/anxiety (PNDA) group. At 2 months postpartum, dyads attended a lab visit. Following peripheral IV placement, women chose to breast or bottle-feed their infants, as they would at home. After a 10-minute post-feed rest, women participated in the Trier Social Stress Test (TSST), a standardized social stressor that includes a speech task and a math task. Blood samples for Cortisol (CRT) were collected 10 minutes after feeding, during the speech and math tasks, and at 10, 20 and 30 minutes of recovery. Repeated measures analysis was used to test the extent to which infant feeding (breast vs. bottle) and PNDA or current depression symptoms, indexed by Beck Depression Inventory >11, were associated with CRT levels during the TSST. P values <0.05 were considered statistically significant.

Results: A total of 222 women were enrolled; 208 completed the 2-month visit, of whom 175 breastfed before the TSST (84.1%). PNDA modified the association between feeding type and CRT levels (group p=0.02, group x time p =0.07) , adjusting for current antidepressant use (figure). We similarly found that current depression symptoms modified the association between feeding type and CRT levels (group p=0.05, group x time p =0.02), adjusting for current antidepressant use. Women with perinatal mood symptoms who were bottle-feeding had the highest CRT levels during the TSST, whereas women with PNDA who were breastfeeding had the lowest CRT levels.

Conclusion: Among women with PNDA, we found larger infant-feeding associated differences in HPA axis response than among women without PNDA. Dysregulation of oxytocin’s effect on HPA axis reactivity may play a role in the pathophysiology of perinatal mood disorders.

Perinatal depression and anxiety and oxytocin

Presented at the Society for Maternal Fetal Medicine, Las Vegas, NV, February 2019

Alison M. Stuebe, Samantha Meltzer-Brody, Roger Mills-Koonce, Brenda Pearson, Julia Whitley, Karen Grewen

Objective: We conducted a longitudinal prospective cohort study to test the hypothesis that perinatal depression is associated with reduced oxytocin during mother-infant interaction.

Study Design: Women intending to breastfeed were recruited in the 3rd trimester of pregnancy. Psychiatric history was assessed at enrollment via Structured Clinical Interview, with oversampling of women with a history or current diagnosis of major depressive disorder or anxiety disorders. Women with an active psychiatric diagnosis at enrollment comprised the prenatal depression/anxiety (PNDA) group. Dyads attended lab visits for a feeding session at 2 and 6 months postpartum; mothers fed their infants as they would at home. Venous maternal blood samples were collected via antecubital IV at baseline, at minutes 1, 4, 7, and 10 of feeding, and 10 minutes after feeding. OT levels were determined by enzyme immunoassay with extraction. Mood symptoms were quantified using the Beck Depression Inventory-II (BDI-II), the Spielberg State-Trait Anxiety Inventory (STAI), and the Edinburgh Postnatal Depression Scale (EPDS). Repeated measures analyses were used to compare OT levels by feeding type and PNDA, adjusting for current symptom score and antidepressant use. P values <.05 were considered statistically significant.

Results: A total of 222 women were enrolled, of whom 208 completed the 2-month visit and 204 completed the 6-month visit. During the 2 month visit, 84.1% breastfed (N=175), and at 6 months, 70.6% breastfed (N=144). Women without PNDA were more likely to breastfeed at the 6 month visit (74.5 vs. 61.0%, p=0.06). At 2 months postpartum, OT levels were highest among breastfeeding women with PNDA and lowest among bottle-feeding women with PNDA, adjusting for current mood symptoms and antidepressant use (group p=0.07, group x time p =0.001, figure). We similarly found that PNDA modified the association between feeding and OT levels at 6 months, adjusting for current mood symptoms and antidepressant use (group p=0.002, group x time p=0.0002, figure).

Conclusion: At 2 months, breastfeeding women with PNDA had the highest OT levels, whereas bottle-feeding women with PNDA had the lowest OT levels. We speculate that this differential OT response to infant feeding may mediate associations between depression and early weaning.

Maternal perception of birth trauma and its association with postpartum mood and parenting stress

Presented at the Society for Maternal Fetal Medicine, Las Vegas, NV, February 2019.

Alison Goulding, Karen Grewen, Samantha Meltzer-Brody, Brenda Pearson, Alison Stuebe

Objective: We sought to examine the association between traumatic birth and measures of mood and parenting stress through 12 months postpartum.

Study Design: We conducted a secondary analysis of participants in the Mood, Mother and Infant (MMI) Study. Women intending to breastfeed were recruited in the 3rdtrimester for a longitudinal cohort study, oversampling for women with current/past depression or anxiety.  A structured clinical interview was performed at baseline to assess for history or current diagnosis of major depressive or anxiety disorders. Baseline anxiety and depression symptoms were measured using the Beck Depression Inventory (BDI) and the Spielberger State-Trait Anxiety Inventory (STAI). Mood was measured at baseline and monthly with the Edinburgh Postnatal Depression Scale (EPDS), and at 2, 6, and 12 months postpartum with the BDI, STAI, and Parenting Stress Index (PSI). Maternal post-traumatic stress disorder (PTSD) symptoms were assessed at 2 months postpartum using the modified Perinatal PTSD Questionnaire (PPQ); birth PTSD was defined using the established threshold of PPQ score ≥ 19. We used repeated measures analysis to quantify the association between birth PTSD and postpartum mood and parenting stress through 12 months postpartum, adjusting for prenatal PPD risk and mood symptoms.

Results: Data were available from 209 women, of whom 15 (7.2%) had birth PTSD. Compared to women without birth PTSD, these women had higher prenatal STAI-Trait (mean 45.1 vs. 33.6, p=0.01) and BDI (mean 18.4 vs. 8.6, p<0.01) scores. In repeated measures analysis adjusting for prenatal STAI-Trait score, BDI score and PPD risk status, we found that birth PTSD was independently associated with higher postpartum EPDS (group p=0.03, group x time p=0.01), BDI (group p<0.0001), state anxiety (group p=0.002, group x time p=0.01) and PSI (group p=0.002) scores through 12 months postpartum.

Conclusions: In our sample, 7% of women had birth PTSD. A traumatic birth experience was associated with postpartum anxiety and depression symptoms and parenting stress, independent of prenatal risk. These findings support efforts to minimize traumatic experiences during childbirth, and to provide additional support to women who endorse PTSD symptoms following birth.

Infant sex modifies associations between breastfeeding intensity and attachment

Presented at the Academy of Breastfeeding Medicine International Conferece, November 2018

Alison Stuebe, Roger Mills-Koonce, Samantha Meltzer‐Brody, Brenda Pearson, Karen Grewen

Background: Maternal-infant bonding is a commonly-cited benefit of breastfeeding.

Objective: We sought to quantify associations between breastfeeding intensity and attachment security at 12 months.

Methods:
We analyzed mother-infant pairs in an ongoing longitudinal cohort study. Women intending to breastfeed were recruited in the 3rd trimester of pregnancy for an ongoing longitudinal study. Psychiatric history was assessed via Structured Clinical Interview, with oversampling of women with a history or current diagnosis of major depressive disorder or anxiety disorders. Infant feeding was assessed monthly, with a 7-day recall of feeding at breast, expressed milk, or breastmilk substitutes. Breastfeeding intensity was calculated as the proportion of milk feedings that were at breast at each assessment. Attachment security was assessed at 12 months using the Ainsworth Strange Situation Paradigm (SSP). We used repeated measures analysis to quantify the extent to which at-breast feeding intensity was associated with attachment. Because infant sex has been reported to modify the effects of maternal behavior on socio-emotional development, we further stratified by infant sex.

Results:
Among 96 mother-infant pairs for whom SSP coding had been completed, 12/45 boys (26.7%) and 17/51 girls (33.3%) were insecurely attached. When we analyzed boys and girls together, we found no association between at-breast feeding intensity and secure attachment (p=0.50). However, the association differed by infant sex (p for interaction =0.03). Higher breastfeeding intensity was associated with secure attachment among girls (p= 0.01). Among boys, breastfeeding intensity was not associated with secure attachment (p=0.21).

Conclusions:
In an ongoing longitudinal cohort study, we found that the association between at-breast feeding intensity and secure attachment varied by infant sex. These findings suggest that stratified analyses by infant sex should be considered in studies of breastfeeding and socioemotional development.

Maternal positive emotions during infant feeding and breastfeeding outcomes

Presented at the Breastfeeding and Feminism International Conference, Chapel Hill, NC, March 21-23, 2018

Wouk K1, Tucker CM1, Pence BW2, Meltzer-Brody S3, Zvara B1, and Stuebe AM1,4

Background: Major medical organizations in the U.S. recommend exclusive breastfeeding for six months, with continued breastfeeding through the first year “or longer as mutually desired by the woman and her infant.” Few studies have explored the role of maternal emotions in breastfeeding outcomes. Dr. Barbara Fredrickson’s broaden-and-build theory of positive emotions suggests that experiences of positive emotions lead to adaptive benefits by broadening one’s thought-action repertoire, allowing the accrual of personal and social resources to improve health and well-being.

Aims/Purpose: To estimate the association between maternal positive emotions during infant feeding at two months and time to any and exclusive breast milk feeding cessation and overall maternal evaluation of breastfeeding at 12 months. Continue reading

Perinatal mood disorders and Hypothalamic Pituitary Adrenal Axis dysregulation

Presented at the Society for Maternal Fetal Medicine Annual Meeting, Dallas, TX, February 2018.

Alison M. Stuebe1,3, Samantha Meltzer-Brody2, Brenda Pearson2, Cheryl Walker2, Karen Grewen2

1Department of Obstetrics and Gynecology, 2Department of Psychiatry, 3Department of Maternal and Child Health,
Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina

Objective: Perinatal depression (PND) affects 1 in 8 women, making it the most common complication of childbirth. Hypothalamic Pituitary Adrenal (HPA) axis dysregulation has been implicated in the pathogenesis of PND, indexed by a blunted Cortisol (CRT) response to Adrenocorticotropic Hormone (ACTH). We hypothesized PND would be associated with dysregulated stress reactivity during lab stressors, indexed by loss of expected associations between ACTH and CRT.

Study Design: Women intending to breastfeed were recruited in the 3rd trimester for an ongoing longitudinal study. Past or current major depressive disorder or anxiety disorders were assessed via Structured Clinical Interview at enrollment; women with a history or current diagnosis of depression or anxiety were classified as high risk. At two months postpartum, dyads attended a lab visit. Following peripheral IV placement, women breastfed their infants and then participated in the Trier Social Stress Test (TSST), a standardized social stressor that includes a speech task and a math task. Blood samples for ACTH and CRT were collected prior to feeding, 10 minutes after feeding, during the speech and math tasks, and at 10, 20 and 30 minutes of recovery. We used repeated measures analysis to quantify associations between risk status and CRT and ACTH during the TSST, and we used linear regression to quantify the extent to which high risk status modified associations between ACTH at time j and cortisol at time j+1. P values <0.05 were considered statistically significant.

Results: ACTH and CRT data were available for 114 women, of whom 69 were high risk for PND and 45 were low risk. In repeated measures analysis (figure), high risk women had higher ACTH levels during the speech and math tasks (p<.05) and lower CRT levels during the recovery (p<.05) than low risk women. When we quantified associations between ACTH at time j and CRT at time j+1, we found that risk status modified this association: higher ACTH during the speech and math tasks, as well as during recovery, was associated with higher CRT among low-risk women, but not among high risk women (p for interaction < .05, figure).

Conclusion: We found a blunted association between ACTH and CRT among women with a history or current diagnosis of depression or anxiety. These findings support our hypothesis that the HPA axis is dysregulated in perinatal depression.

Childhood trauma history, breastfeeding and postpartum depression

Presented at the Academy of Breastfeeding Medicine Annual Meeting. Atlanta, GA, November 2017.

Alison M. Stuebe1,3, Bharathi Zvara3, Samantha Meltzer-Brody2, Brenda Pearson2, Cheryl Walker2, Karen Grewen2

1Department of Obstetrics and Gynecology, 2Department of Psychiatry, 3Department of Maternal and Child Health,
Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina

Background: Adverse childhood experiences are associated with mood disorders and difficulties with early caregiving behaviors. We sought to quantify associations among moderate/severe childhood trauma (MSCT), depression symptoms and breastfeeding intensity.

Methods: Women intending to breastfeed were recruited in the 3rd trimester of pregnancy for an ongoing longitudinal study. Past or current major depressive disorder or anxiety disorders were assessed via Structured Clinical Interview. Trauma history was quantified using the Childhood Trauma Questionnaire. MSCT was quantified using CTQ subscale scores (abuse: emotional≥13, physical≥10, sexual≥8; neglect: emotional≥15, physical≥10).  During monthly interviews, mood was assessed via the Edinburgh Postnatal Depression Scale, and breastfeeding intensity in the past 7 days was assessed via a feeding questionnaire. Mean breastfeeding intensity and EPDS scores over the first 6 months and from birth to 12 months were used to calculate cumulative breastfeeding intensity (CBI) and cumulative EPDS (CEPDS). We used Wilcoxon rank sum tests to quantify the association between MSCT and CBI, and we used linear regression to model associations between CBI and CEPDS. P values <.05 were considered statistically significant.

Results: Among 162 women who had completed data collection, 41 (25.8%) had a history of MSCT. MSCT was associated with lower CBI in the first 6 months postpartum (median vs 0.77 [0.39-0.91] vs [IQR]: 0.87, [0.71-0.97]).  MSCT modified associations between CEPDS and CBI: Among women with MSCT, higher EPDS scores were associated with lower CBI (p for interaction <.01, whereas among women without MSCT, mood scores were not associated with breastfeeding intensity. In the MSCT trauma group, exclusive breastfeeding for 6 months was associated with a 4.4-point reduction in predicted CEPDS score, compared with never breastfeeding.

Conclusions: Among women with a history of MSCT, targeted strategies to reduce mood symptoms and support greater breastfeeding intensity may have synergistic effects on maternal health, wellbeing and early caregiving behavior.