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Abstract Background Major depressive disorder (MDD) affects 10% of pregnancies. Because transcranial magnetic stimulation (TMS) is a nonmedication option, psychiatric patients who do not tolerate or prefer to avoid antidepressants are good candidates for TMS. Method In a randomized controlled trial of twenty-two women with MDD in the second or third trimester of pregnancy, subjects were randomized to active TMS (n=11) or sham TMS (n=11). This study took place at a single academic center. Subjects received 20 sessions of TMS to the right dorsolateral prefrontal cortex at 1 Hz as a single train of 900 pulses per session at 100% motor threshold. Estradiol and progesterone and were measured before session 1 and after session 20. Results Results demonstrated significantly decreased Hamilton Depression Rating Scale (HDRS-17) scores for the active compared to the sham group (p=0.003). Response rates were 81.82% for the active and 45.45% for the sham coil (p=0.088). Remission rates were 27.27% for the active 18.18% for the sham coil (p=0.613). Late preterm birth (PTB) occurred in three women receiving active TMS. All other maternal and delivery outcomes were normal. Conclusions Right-sided, low frequency TMS was effective in reducing depressive symptoms in this sample of pregnant women. There may be a possibility that TMS is associated with late PTB although a larger sample size would be needed for adequate power to detect a true difference between groups. This study demonstrated that TMS is low risk during pregnancy although larger trials would provide more information about the efficacy and safety of TMS in this population. This trial shows that an RCT of a biologic intervention in pregnant women with psychiatric illness can be conducted. Highlights • MDD during pregnancy is common but women experience challenges regarding treatment. • Transcranial magnetic stimulation is a non-pharmacologic treatment option for pregnant women with depression. • In an RCT of LF-TMS over the right DLPFC, women in the active TMS group showed a larger decrease in depressive symptoms than the sham group. • There were 3 late pre-term births in the active group which was statistically non-significant. • There was no change difference in hormone levels between the active and sham groups. [ABSTRACT FROM AUTHOR]

Background: Recent recommendations urge increased depression screening in pregnant and postpartum women, potentially increasing demand for treatment. Computer-based psychotherapy treatments may address some of perinatal women's unique mental health treatment needs and barriers. Materials and Methods: We conducted a quantitative survey of pregnant women (≥12 weeks of gestation) on preferences regarding computer-based therapies compared with traditional therapies (psychotherapy and medication). Nonpregnant women and men served as comparison groups. Participants were provided descriptions of three computer-based therapies: video telehealth therapy (VTT), computer-assisted therapy (CAT), and self-guided online therapy (SGO). Participants were asked to select all options that they would consider for treatment as well as first choice preference. The Patient Health Questionnaire-9 (PHQ-9) assessed current depressive symptomatology, and the Mini International Neuropsychiatric Interview (MINI) assessed psychiatric history. Results: Participants included pregnant females ( n = 111), nonpregnant females ( n = 147), and males ( n = 54). Among pregnant women, 77.5% ( n = 86) indicated that they would consider some form of computer-based therapy for mental health treatment during pregnancy; VTT was the most commonly considered, followed by CAT and SGO. When asked to select their preferred intervention, traditional talk therapy was the first choice among all three groups, controlling for treatment history and PHQ-9 score. About one-third of pregnant women chose some form of computer-based therapy as their top choice. Conclusions: While computer-based therapies were acceptable to most pregnant women in this sample, traditional talk therapy was the preferred option. Future research should consider how to tailor computer-based therapies to the unique needs of perinatal women. [ABSTRACT FROM AUTHOR]

Fetal adrenal gland volumes on 3‐dimensional sonography have been studied as potential predictors of preterm birth. However, no consistent methodology has been published. This article describes the methodology used in a study that is evaluating the effects of maternal early life stress on fetal adrenal growth to allow other researchers to compare methodologies across studies. Fetal volumetric data were obtained in 36 women at 20 to 22 and 28 to 30 weeks' gestation. Two independent examiners measured multiple images of a single fetal adrenal gland from each sonogram. Intra‐ and inter‐rater consistency was examined. In addition, fetal adrenal volumes between male and female fetuses were reported. The intra‐ and inter‐rater reliability was satisfactory when the mean of 3 measurements from each rater was used. At 20 weeks' gestation, male fetuses had larger average adjusted adrenal volumes than female fetuses (mean, 0.897 versus 0.638; P =.004). At 28 weeks' gestation, the fetal weight was more influential in determining values for adjusted fetal adrenal volume (0.672 for male fetuses versus 0.526 for female fetuses; P =.034). This article presents a methodology for assessing fetal adrenal volume using 3‐dimensional sonography that can be used by other researchers to provide more consistency across studies. [ABSTRACT FROM AUTHOR]

As serotonin reuptake inhibitor (SRI) use may decrease platelet function, previous research has shown a relationship between SRI use and an increased risk for bruising and bleeding. The literature regarding the association between SRI use during pregnancy and increased bleeding at delivery, referred to as postpartum hemorrhage (PPH), is mixed. In secondary analyses from two prospective observational studies of pregnant women with mood disorders, 263 women were exposed to an SRI (n = 51) or not (n = 212) in the third trimester. To be precise, we used the terminology estimated blood loss (EBL) >600 cc rather than the term PPH because the current definition of PPH differs. The occurrence of EBL >600 cc was determined using the Peripartum Events Scale (PES) completed from obstetrical records by a blinded medically trained member of the study team. EBL >600 cc occurred in 8.7% of women in this cohort. There was no statistically significant difference in the rates of EBL >600 cc in the 24 h after delivery in women taking SRIs during the third trimester (9.8%) compared to non-exposed women (8.5%). Utilizing generalizing estimating equations, the odds of EBL >600 cc in each group were not significantly different (OR 1.17, CI-0.41-3.32, p = 0.77). When the SRI group was limited to women with exposure at the time of delivery, the difference in the odds of EBL >600 cc was unchanged (OR 1.16, CI = 0.37–3.64, p = 0.79). In population, both third trimester and use at delivery of SRIs during pregnancy was not associated with an increased risk of excessive blood loss. [ABSTRACT FROM AUTHOR]

Background: Depression during pregnancy affects 5%-8% of women. While the percentage of women in the US taking serotonin reuptake inhibitors during pregnancy has risen over the last decade, pregnant women continue to report that they prefer non-pharmacologic interventions. Objective: We review the literature regarding neuromodulation techniques for major depressive disorder during pregnancy. The rationale for their use in this population, new developments, and future directions are discussed. Methods: A literature search was conducted in PubMed Plus, Ovid Medline, and Embase to collect all articles on neuromodulation for the treatment of depression during pregnancy. Key search words included electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation, transcranial direct current stimulation, neuromodulation, depression, and pregnancy. Given the sparse literature, all articles from 1960 to 2014 that addressed the use of neuromodulation in pregnancy were included. Conclusion: The data support the use of electroconvulsive therapy in all trimesters of pregnancy for major depressive disorder. New data are emerging for the use of transcranial magnetic stimulation in pregnancy, which is likely safe, but more data are needed before it can be recommended as a primary treatment modality during pregnancy. Other neuromodulation techniques have not been well studied in this population. [ABSTRACT FROM AUTHOR]

Background: Pregnant women with major depressive disorder (MDD) report that psychotherapy is a more acceptable treatment than pharmacotherapy. However, although results of several studies suggest that psychotherapy is an effective treatment for pregnant women, logistical barriers-including cost and traveling for weekly visits-can limit real-world utility. We hypothesized that computer-assisted cognitive behavior therapy (CCBT) would be both acceptable and would significantly decrease depressive symptoms in pregnant women with MDD. Methods: As a preliminary test of this hypothesis, we treated 10 pregnant women with MDD using a standardized CCBT protocol. Results: The pilot results were very promising, with 80% of participants showing treatment response and 60% showing remission after only eight sessions of CCBT. Conclusion: A larger, randomized controlled trial of CCBT in pregnant women with MDD is warranted. [ABSTRACT FROM AUTHOR]

Objective: Brain derived neurotrophic factor (BDNF) is a neuroprotective peptide crucial to the development and function of the nervous system that is important for both a healthy mood and pregnancy. The aim of this study was to definitively characterize serum BDNF levels in 3rd trimester pregnant women as compared to follicular phase, non-pregnant women who had been carefully screened for the absence of psychiatric illness. Method: Twenty healthy pregnant women ≥ 28 weeks gestational age with a healthy, singleton pregnancy and 20 non-pregnant, healthy women in the follicular phase of their menstrual cycle were consecutively recruited from a general obstetrics clinic at the University of Pennsylvania from March 2010 through October 2010. Peripheral serum BDNF levels were evaluated in 20 pregnant women and 20 non-pregnant women in the follicular phase of their menstrual cycle. Results: Median serum BDNF in the pregnant group was 11781.1 pg/ml (IQR 9435.2, 15936.4) and in the non- pregnant group was 23212.5 pg/ml (IQR 14644.0, 26287.9). Serum BDNF was significantly lower in the pregnant group compared to the non-pregnant group (p = .0029). Conclusions: This study confirms that serum BDNF is significantly lower in pregnant women compared to non- pregnant, follicular phase women even in the absence of psychiatric illness. In a subset of vulnerable women, low BDNF levels may precipitate an environment that puts women and their babies at increased risk for affective or neurodevelopmental disturbances. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Given the data that depression is common during pregnancy and that pregnant women prefer non-medication treatment options, we hypothesize repetitive transcranial magnetic stimulation (TMS) may be a treatment option. Given the novelty of TMS, we sought to assess whether patient acceptability would be a barrier to enrolling pregnant women in TMS studies. Methods: In Study 1, 500 pregnant women were surveyed in an outpatient, urban obstetrics clinic using the Edinburgh Depression Rating Scale (EPDS) and a treatment acceptability survey. In Study 2, 51 women were surveyed with the EPDS and acceptability survey using an informational video to increase participant knowledge about TMS. Results: Approximately 25% of participants had an EPDS score of ≥12 in both studies. Psychotherapy was identified as the most acceptable treatment option. TMS was considered an unacceptable treatment option to virtually all women before the informational video. After the video, 15.7% considered TMS an acceptable treatment option. Conclusion: Psychotherapy is the most acceptable treatment option for depression to pregnant women. Increasing participant knowledge about TMS increased its acceptability significantly. Large-scale multi-center trials are needed for confirmation of these results. [Copyright &y& Elsevier]

Objective: Despite the data that major depressive disorder (MDD) is common during pregnancy and that pregnant women prefer nonmedication treatment options, there is a paucity of research examining alternative treatments for this special population. We present the results of an open label pilot study examining treatment with transcranial magnetic stimulation (TMS) in pregnant women with MDD. Methods: Ten women with MDD in the second or third trimester of pregnancy were treated with 20 sessions of 1-Hz TMS at 100% of motor threshold (MT) to the right dorsolateral prefrontal cortex. The total study dose was 6000 pulses. Antenatal monitoring was performed during treatment sessions 1, 10, and 20. Results: Seven of ten (70%) subjects responded (decrease ≥50% in Hamilton Depression Rating Scale [HDRS-17] scores). No adverse pregnancy or fetal outcomes were observed. All infants were admitted to the well baby nursery and were discharged with the mother. Mild headache was the only common adverse event and was reported by 4 of 10 (40%) subjects. Conclusions: TMS appears to be a promising treatment option for pregnant women who do not wish to take antidepressant medications. [ABSTRACT FROM AUTHOR]

Abstract: In our studies of transcranial magnetic stimulation in pregnant women with major depressive disorder, two subjects had an episode of supine hypotensive syndrome and one subject had an episode of dizziness without hypotension. Prevention of the supine hypotensive syndrome in pregnant women receiving transcranial magnetic stimulation is described. [Copyright &y& Elsevier]

Background Adverse childhood experiences (ACEs) are one of the greatest predictors of affective disorders for women. Periods of dynamic hormonal flux, including pregnancy, exacerbate the risk for affective disturbance and promote hypothalamic-pituitary-adrenal (HPA) axis dysregulation, a key feature of affective disorders. Little is understood as to how stress experienced in late childhood, defined as preadolescence, alters the programming unique to this period of brain maturation and its interaction with the hormonal changes of pregnancy and postpartum. Methods Preadolescent female mice were exposed to chronic stress and examined for changes in their HPA axis during pregnancy and postpartum, including assessment of maternal-specific stress responsiveness and transcriptomics of the paraventricular nucleus of the hypothalamus. Translationally, pregnant women with low or high ACEs were examined for their maternal stress responsiveness. Results As predicted, preadolescent stress in mice resulted in a significant blunting of the corticosterone response during pregnancy. Transcriptomic analysis of the paraventricular nucleus revealed widespread changes in expression of immediate early genes and their targets, supporting the likely involvement of an upstream epigenetic mechanism. Critically, in our human studies, the high ACE women showed a significant blunting of the HPA response. Conclusions This unique mouse model recapitulates a clinical outcome of a hyporesponsive HPA stress axis, an important feature of affective disorders, during a dynamic hormonal period, and suggests involvement of transcriptional regulation in the hypothalamus. These studies identify a novel mouse model of female ACEs that can be used to examine how additional life adversity may provoke disease risk or resilience. [ABSTRACT FROM AUTHOR]

Women with a history of adverse childhood experiences (ACEs) enter pregnancy and the postpartum with a physiologic system programmed by early life stress, potentially reflected in psychophysiologic reactivity. We enrolled pregnant, psychiatrically healthy women ≥18 years old. Using the ACE Questionnaire, women were categorized as high (≥2 ACEs; n = 77) or low ACE (<2 ACEs; n = 72). Participants completed an affective modulation of acoustic startle response (ASR) task during pregnancy and postpartum, in which ASR magnitude was measured while participants viewed pleasant, unpleasant, and neutral pictures. Two types of control trials were included (habituation trials presented at baseline and intertrial interval trials presented when no picture was present). Among high ACE women, ASR was significantly higher postpartum compared with pregnancy in the unpleasant (p = 0.002, β = 0.46, 95% CI [0.18, 0.74], χ 2 = 10.12, z = 3.18) and intertrial interval trials (p = 0.002, β = 0.44, 95% CI [0.16, 0.73], χ 2 = 9.25, z = 3.04), accounting for multiple comparisons using a Bonferroni correction at p < 0.005. Among low ACE women, ASR was similar in pregnancy and postpartum. Physiological reactivity increased in high ACE women from pregnancy to postpartum, but no change was observed in low ACE women. [ABSTRACT FROM AUTHOR]