Associations between childhood maltreatment, poor sleep, and prenatal distress in pregnant adolescents.

Childhood maltreatment (CM) is a known risk factor for adolescent pregnancy. Sleep disturbances and psychological distress, both common negative sequelae of CM, often co-occur during pregnancy, although directionality remains unclear. Furthermore, little is known about how CM affects sleep-distress associations during pregnancy. In pregnant adolescents, we examined: (a) whether there are significant predictive associations from CM to sleep quality and distress and (b) bidirectional influences of distress and sleep quality. Healthy pregnant adolescents (n = 204) were recruited before or during the 2nd trimester. CM was assessed at enrollment; sleep quality and distress were assessed in the 2nd and 3rd trimesters. Hypotheses were tested using path analysis. Findings revealed that CM was associated with worse 2nd trimester sleep quality and distress (ß = .19, p < .05 for sleep; ß = .30, p < .001 for distress). Higher levels of 2nd trimester distress were associated with lower 3rd trimester sleep quality (ß = .19, p < .05). Findings provide novel information about (a) associations from CM to prenatal mood and sleep in pregnant adolescents, and (b) sleep-distress directionality over the course of pregnancy. These results have implications for better understanding the ways in which CM potentially exerts influences later in life, and for targeting interventions to address physical and mental health during pregnancy.

Maternal prenatal stress phenotypes associate with fetal neurodevelopment and birth outcomes.

Maternal prenatal stress influences offspring neurodevelopment and birth outcomes including the ratio of males to females born; however, there is limited understanding of what types of stress matter, and for whom. Using a data-driven approach with 27 variables from questionnaires, ambulatory diaries, and physical assessments collected early in the singleton pregnancies of 187 women, 3 latent profiles of maternal prenatal stress emerged that were differentially associated with sex at birth, birth outcomes, and fetal neurodevelopment. Most women (66.8%) were in the healthy group (HG); 17.1% were in the psychologically stressed group (PSYG), evidencing clinically meaningful elevations in perceived stress, depression, and anxiety; and 16% were in the physically stressed group (PHSG) with relatively higher ambulatory blood pressure and increased caloric intake. The population normative male:female secondary sex ratio (105:100) was lower in the PSYG (2:3) and PHSG (4:9), and higher in the HG (23:18), consistent with research showing diminished male births in maternal stress contexts. PHSG versus HG infants were born 1.5 wk earlier (P < 0.05) with 22% compared to 5% born preterm. PHSG versus HG fetuses had decreased fetal heart rate-movement coupling (P < 0.05), which may indicate slower central nervous system development, and PSYG versus PHSG fetuses had more birth complications, consistent with previous findings among offspring of women with psychiatric illness. Social support most strongly differentiated the HG, PSYG, and PHSG groups, and higher social support was associated with increased odds of male versus female births. Stress phenotypes in pregnant women are associated with male vulnerability and poor fetal outcomes.

Pregnancy-specific stress and sensitive caregiving during the transition to motherhood in adolescents.

BACKGROUND: Maternal prenatal stress is associated with worse socio-emotional outcomes in offspring throughout childhood. However, the association between prenatal stress and later caregiving sensitivity is not well understood, despite the significant role that caregiving quality plays in child socio-emotional development. The goal of this study was to examine whether dimensions of pregnancy-specific stress are correlated with observer-based postnatal maternal caregiving sensitivity in pregnant adolescents. METHODS: Healthy, nulliparous pregnant adolescents (n = 244; 90 % LatinX) reported on their pregnancy-specific stress using the Revised Prenatal Distress Questionnaire (NuPDQ). Of these 244, 71 participated in a follow-up visit at 14 months postpartum. Videotaped observations of mother-child free play interactions at 14 months postpartum were coded for maternal warmth and contingent responsiveness. Confirmatory factor analysis of the NuPDQ supported a three-factor model of pregnancy-specific stress, with factors including stress about the social and economic context, baby's health, and physical symptoms of pregnancy. RESULTS: Greater pregnancy-specific stress about social and economic context and physical symptoms of pregnancy was associated with reduced maternal warmth but not contingent responsiveness. CONCLUSIONS: Heightened maternal stress about the social and economic context of the perinatal period and physical symptoms of pregnancy may already signal future difficulties in caregiving and provide an optimal opening for early parenting interventions.

The impact of childhood trauma on psychological interventions for depression during pregnancy and postpartum: a systematic review.

Women who have experienced childhood trauma (CT) are at increased risk for depression during pregnancy and postpartum, pregnancy complications, and adverse child outcomes. There are effective psychotherapeutic interventions to treat depression during pregnancy and postpartum, yet there is a paucity of literature on the impact of CT on treatment outcomes. This review aims to determine whether and how maternal CT history affects the outcomes of psychological interventions for depression during pregnancy and postpartum. PubMed, PsycINFO, and Cochrane Library searches were conducted to identify papers on psychological interventions designed to treat depression during pregnancy and postpartum in women with CT. Seven manuscripts, describing six studies, met the inclusion criteria (N = 1234). Three studies utilized core principles of interpersonal psychotherapy (IPT). Two studies investigated interventions based on cognitive behavioral therapy (CBT). One study was based on a psychoeducation component. Results suggest that IPT-based interventions are beneficial for women with CT. The evidence regarding CBT-based interventions is less conclusive. This review is written in light of the paucity of research addressing the question systematically. The Childhood Trauma Questionnaire (CTQ) was the main measure used to assess CT. Trauma related to accidents, illness, and political violence was not included. The results are only applicable to interventions based on either IPT or CBT and cannot be generalized to other forms of psychotherapy. Psychotherapeutic interventions are beneficial for depressed women with history of CT during pregnancy and postpartum; however, further systematic research is needed.

Impacts of an egg intervention on nutrient adequacy among young Malawian children.

Eggs are a rich source of multiple nutrients that support child growth and development. Provision of eggs as a complementary food may improve dietary adequacy among young children at risk for undernutrition. Our objective was to test the impact of an egg intervention on the adequacy of total nutrient intakes and micronutrient density among 6- to 15-month-old Malawian children. Children 6 to 9 months old, living in Mangochi District, Malawi, were randomly assigned to the intervention group (n = 331) receiving an egg per day or a control group (n = 329) consuming their usual diet. Dietary intakes of macronutrients, vitamins and minerals were assessed using 24-h recalls at baseline, 3-month midline and 6-month endline, with repeat recalls in a subsample. Usual nutrient intake and micronutrient density distributions were modelled to estimate group means and prevalence of inadequacy. Group differences at midline and endline were tested using unequal variance t tests with bootstrapped standard errors. The egg intervention resulted in higher intakes of fat and protein and lower intakes of carbohydrates. The egg group had lower prevalence of inadequacy for selenium, vitamin A, riboflavin, vitamin B5 , vitamin B12 and choline. Micronutrient density inadequacy was lower in the egg group for vitamin A and choline at midline and endline, riboflavin at midline and vitamin B5 at endline. Inadequacy of nutrient intakes or density remained highly prevalent in both groups for multiple micronutrients. Though the egg intervention increased intakes of protein and several micronutrients, total intakes and micronutrient density of multiple micronutrients remained far below recommendations.

Maternal abuse history and reduced fetal heart rate variability: Abuse-related sleep disturbance is a mediator.

The consequences of childhood maltreatment are profound and long lasting. Not only does the victim of abuse suffer as a child, but there is mounting evidence that a history of maltreatment places the next generation at risk for significant psychopathology. Research identifies postnatal factors as affecting this intergenerational transmission of trauma. However, emerging evidence suggests that part of this risk may be transmitted before birth, passed on via abuse-related alterations in the in utero environment that are as yet largely unidentified. To date, no study has directly assessed the influence of pregnant women's abuse history on fetal neurobehavioral development, nor considered trauma-associated poor sleep quality as a mediator reflecting established physiological dysregulation. Using data from 262 pregnant adolescents (ages 14-19), a population at elevated risk for childhood maltreatment, the current study examined maternal emotional abuse history and sleep quality in relation to third-trimester fetal resting heart rate variability, an index of parasympathetic nervous system functioning. The results indicate that maternal emotional abuse history is indirectly associated with lower fetal heart rate variability via abuse-related sleep disturbances. These data demonstrate an association between maternal abuse histories and fetal development, showing that at least part of the intergenerational transmission of risk occurs during pregnancy.

The mobile conjugate reinforcement paradigm in a lab setting.

The mobile conjugate reinforcement task was administered to 4-month-old infants in a lab rather than a home setting where it is usually administered. Learning and retention patterns were comparable to those of infants tested in their homes, suggesting flexibility in where this task can be administered. These results pave the way for this task to be used with a broader range of infants for whom home visits are not practical or convenient (e.g., infants in child care). Developmental research conducted with a more diverse population of infants would facilitate our understanding of cognitive development very early in life.

Associations Among Child Abuse, Depression, and Interleukin-6 in Pregnant Adolescents: Paradoxical Findings.

OBJECTIVE: Limited data exist on child abuse-related immune variation during pregnancy, despite implications for maternal and infant health and extensive data showing that abuse history and depression are related to increased inflammation in other populations. This study examined associations among child abuse, depression, circulating levels of inflammatory markers, and perinatal health in pregnant adolescents, a group at high risk for childhood abuse and poor birth outcomes. METHODS: Pregnant teenagers (n = 133; 14-19 years; 89.5% Latina) reported on abuse and depression and had two blood draws (24-27 and 34-37 gestational weeks, second and third trimesters, respectively) for interleukin-6 (IL-6) and C-reactive protein; birth outcomes were collected. RESULTS: Abuse and depression interacted to predict higher IL-6 at second trimester (B = 0.006, p = .011) such that severely abused adolescents with high depression had higher IL-6 relative to severely abused adolescents with low depression; depression did not differentiate IL-6 levels for those with low abuse severity. Abuse and IL-6 also interacted to predict gestational age at birth (B = 0.004, p = .040) such that those with low abuse and high IL-6 and those with high abuse and low IL-6 had infants with earlier gestational age at birth. Cortisol at the second trimester mediated the association between IL-6 and gestational age at birth (indirect effect estimate=-0.143, p < .039). CONCLUSIONS: Depression severity distinguished IL-6 levels among more severely abused pregnant Latina adolescents, but it was unrelated to IL-6 among less severely abused adolescents. Cortisol explained the relationship between IL-6 and earlier gestational age at birth. Multiple adversities and inflammation may influence birth outcomes and potentially affect intergenerational health.

PREPP: postpartum depression prevention through the mother-infant dyad.

Most interventions to prevent postpartum depression (PPD) focus on the mother rather than the mother-infant dyad. As strong relationships between infant sleep and cry behavior and maternal postpartum mood have been demonstrated by previous research, interventions targeted at the dyad may reduce symptoms of PPD. The goal of the current study was to examine the effectiveness of Practical Resources for Effective Postpartum Parenting (PREPP). PREPP is a new PPD prevention protocol that aims to treat women at risk for PPD by promoting maternally mediated behavioral changes in their infants, while also including mother-focused skills. Results of this randomized control trial (RCT) (n = 54) indicate that this novel, brief intervention was well tolerated and effective in reducing maternal symptoms of anxiety and depression, particularly at 6 weeks postpartum. Additionally, this study found that infants of mothers enrolled in PREPP had fewer bouts of fussing and crying at 6 weeks postpartum than those infants whose mothers were in the Enhanced TAU group. These preliminary results indicate that PREPP has the potential to reduce the incidence of PPD in women at risk and to directly impact the developing mother-child relationship, the mother's view of her child, and child outcomes.

Maternal dietary fat intake during pregnancy is associated with infant temperament.

Research with rodents and nonhuman primates suggests that maternal prenatal dietary fat intake is associated with offspring behavioral functioning indicative of risk for psychopathology. The extent to which these findings extend to humans remains unknown. The current study administered the Automated Self-Administered 24 hr Dietary Recall Questionnaire three times in pregnancy (n = 48) to examine women's dietary fat intake in relation to infant temperament assessed using the Infant Behavior Questionnaire at 4-months old. The amount of saturated fat that the mother consumed was considered as a moderator of the association between total fat intake and child temperament. Results from a series of multiple linear regressions indicate that greater total fat intake was associated with poorer infant regulation and lower surgency. However, this second effect was moderated by maternal saturated fat intake, such that total fat intake was only related to infant surgency when mothers consumed above the daily recommended allowance of saturated fat. Under conditions of high total fat and high saturated fat, infants were rated as lower on surgency; under conditions of low total fat yet high saturated fat, infants were rated as higher on surgency. There were no associations between maternal prenatal fat intake and infant negative reactivity. These findings provide preliminary evidence that pregnant women's dietary fat intake is associated with infants' behavioral development, though future research is needed to address this report's limitations: a relatively small sample size, the use of self-report measures, and a lack of consideration of maternal and infant postnatal diet.

Preventing postpartum depression: review and recommendations.

Nearly 20 % of mothers will experience an episode of major or minor depression within the first 3 months postpartum, making it the most common complication of childbearing. Postpartum depression (PPD) is significantly undertreated, and because prospective mothers are especially motivated for self-care, a focus on the prevention of PPD holds promise of clinical efficacy. This study is a qualitative review of existing approaches to prevent PPD. A PubMed search identified studies of methods of PPD prevention. The search was limited to peer-reviewed, published, English-language, randomized controlled trials (RCTs) of biological, psychological, and psychosocial interventions. Eighty articles were initially identified, and 45 were found to meet inclusion criteria. Eight RCTs of biological interventions were identified and 37 RCTs of psychological or psychosocial interventions. Results were mixed, with 20 studies showing clear positive effects of an intervention and 25 showing no effect. Studies differed widely in screening, population, measurement, and intervention. Among biological studies, anti-depressants and nutrients provided the most evidence of successful intervention. Among psychological and psychosocial studies, 13/17 successful trials targeted an at-risk population, and 4/7 trials using interpersonal therapy demonstrated success of the intervention versus control, with a further two small studies showing trends toward statistical significance. Existing approaches to the prevention of PPD vary widely, and given the current literature, it is not possible to identify one approach that is superior to others. Interpersonal therapy trials and trials that targeted an at-risk population appear to hold the most promise for further study.

Pregnancy distress gets under fetal skin: Maternal ambulatory assessment & sex differences in prenatal development.

Prenatal maternal distress is associated with an at-risk developmental profile, yet there is little fetal evidence of this putative in utero process. Moreover, the biological transmission for these maternal effects remains uncertain. In a study of n = 125 pregnant adolescents (ages 14-19), ambulatory assessments of daily negative mood (anger, frustration, irritation, stress), physical activity, blood pressure, heart rate (every 30 min over 24 hr), and salivary cortisol (six samples) were collected at 13-16, 24-27, 34-37 gestational weeks. Corticotropin-releasing hormone, C-reactive protein, and interleukin 6 from blood draws and 20 min assessments of fetal heart rate (FHR) and movement were acquired at the latter two sessions. On average, fetuses showed development in the expected direction (decrease in FHR, increase in SD of FHR and in the correlation of movement and FHR ("coupling")). Maternal distress characteristics were associated with variations in the level and trajectory of fetal measures, and results often differed by sex. For males, greater maternal 1st and 2nd session negative mood and 2nd session physical activity were associated with lower overall FHR (p < .01), while 1st session cortisol was associated with a smaller increase in coupling (p < .01), and overall higher levels (p = .05)-findings suggesting accelerated development. For females, negative mood, cortisol, and diastolic blood pressure were associated with indications of relatively less advanced and accelerated outcomes. There were no associations between negative mood and biological variables. These data indicate that maternal psychobiological status influences fetal development, with females possibly more variously responsive to different exposures.

Higher maternal prenatal cortisol and younger age predict greater infant reactivity to novelty at 4 months: an observation-based study.

Distress-linked activation of the maternal hypothalamic-pituitary-adrenal (HPA)-axis is considered a pathway by which affect regulation impacts the fetal milieu and neurodevelopment. There is little direct evidence for this conceptual model. In 103 women [mean age 27.45 (±5.65) years] at 36-38 weeks gestation, salivary cortisol was measured before/after stress tasks; distress questionnaires were completed. At 18.49 (±1.83) weeks, infants underwent the Harvard Infant Behavioral Reactivity Protocol assessing cry/motor responses to novelty; women reported on infant behavior and postnatal distress. Prenatal cortisol and distress were not significantly correlated (all ps > .10). Proportional odds logistic regressions showed that neither prenatal nor postnatal distress was associated with infant responses to the Harvard Protocol yet pre-stress cortisol and maternal age were: The odds of being classified as High Reactive were 1.60 times higher [95% CI: 1.04, 2.46] for each unit of added cortisol and .90 times lower [95% CI: .82, .99] for every additional year in maternal age. No associations were found between cortisol or prenatal distress and mother-rated infant behavior; postnatal distress was positively associated with mother-rated infant negative behavior (p = .03). Observer and mother-rated infant behavior were not associated (all ps > .05). Based on independent observations of infants in contrast to maternal perceptions, these results lend support to the hypothesis that pregnant women's HPA-axis activity influences infant behavior. The impact of maternal distress was not supported, except in so far as postnatal distress may increase the likelihood of making negative judgments about infant behavior.

Third Trimester Fetuses Demonstrate Priming, a Form of Implicit Memory, In Utero.

Research examinations of changes in fetal heart rate (HR) to operationalize fetal memory suggests that human memory capacities emerge in utero. However, there is little evidence for a form of implicit memory or priming. The present aim was to determine if priming is evident in utero. Fetal HR, maternal HR and maternal respiratory rate (RR) were examined in 105 women during the third trimester of pregnancy. Women experienced two counterbalanced laboratory tasks, the Stroop task and the paced breathing task, and their cardiorespiratory activity functioned as a stimulus for fetuses. Repeated measures ANOVAs revealed maternal HR increased during the Stroop task but only when the Stroop task was presented first (89.64 bpm to 92.39 bpm) (p = 0.04). Maternal RR increased during the Stroop task, regardless of task order (17.72 bpm to 21.11 bpm; 18.50 bpm to 22.60 bpm) (p < 0.01). Fetal HR increased during the paced breathing task, but only when it followed maternal exposure to the Stroop task (141.13 bpm to 143.97 bpm) (p < 0.01). Fetuses registered maternal HR and RR reactivity to the Stroop task, which influenced their response during maternal engagement with a related task, suggesting priming. Further study of fetal memory may suggest another pathway by which prenatal exposures impact future development.

Mood disorders and their pharmacological treatment during pregnancy: is the future child affected?

Nearly half the US population will meet criteria for a neuropsychiatric disorder at some point in their lives, and 1 in 17 has a seriously debilitating illness. Although not all affected adults had an identified disorder as a child, increasingly these psychopathologies are conceptualized as the late-stage culmination of aberrant developmental processes shaped by a complex interplay of genes and experience, including experiences in utero. Decades of studies with pregnant animals demonstrate that stress-elicited perturbations in maternal biology affect offspring neurodevelopment. Studies of stress in pregnant women largely mirror these findings. Pregnant women with anxiety and/or depression experience greater life stress, and illness-related alterations in their neurobiology, with a potential to impact fetal neurobehavioral development via associated changes in the intrauterine environment and/or pharmacologic interventions. This article critically reviews findings on child development (including fetal neurobehavior) related to maternal depression, anxiety, and pharmacological treatments, primarily selective serotonin reuptake inhibitors (SSRIs). The hypothesis under review is that, in addition to genetics and characteristics of the postnatal environment, the familial transmission of risk for neuropsychiatric disorders involves a "third path"-prenatal exposure to psychiatric illness and its treatment.

Perinatal depression prevention through the mother-infant dyad: The role of maternal childhood maltreatment.

BACKGROUND: Prevention studies for perinatal depression rarely focus on the mother-infant dyad or consider the impact of maternal childhood maltreatment (CM). METHODS: A secondary analysis of two combined randomized controlled trials of Practical Resources for Effective Postpartum Parenting (PREPP) examined the moderating role of CM on the efficacy of preventing perinatal depression and effects on infant behavior at six weeks. RESULTS: 32% of 109 pregnant women endorsed CM (CM+). At six weeks postpartum, women who received PREPP compared to enhanced treatment as usual (ETAU) had significant reductions in depression and anxiety based on the observer-rated Hamilton Rating Scale for Depression (HRSD) and Hamilton Rating Scale for Anxiety (HRSA) (mean difference of M=-3.84 (SD= 0.14, p<0.01) and M=- 4.31 (SD= 0.32, p <0.001) respectively). When CM was added to the models, there no longer was a significant PREPP versus ETAU treatment effect on HRSD and HRSA outcomes in CM+ women though effects remained for CM- women. However, CM+ women who received PREPP vs ETAU reported a mean increase in infant daytime sleep of 189.8 min (SE= 50.48, p = 0.001). LIMITATIONS: Self-report measures of infant behavior were used. CONCLUSIONS: CM+ women versus CM- had limited response to an intervention to prevent perinatal depression yet still reported an increase in infant daytime sleep. This study adds to the growing literature that prevention studies may need to incorporate approaches tailored to fit women with childhood trauma histories while also considering infant functioning as both may be treatment targets relevant to maternal mood.

Preventing maternal mental health disorders in the context of poverty: pilot efficacy of a dyadic intervention.

BACKGROUND: The United States Preventive Services Task Force recommends that clinicians provide or refer pregnant and postpartum women who are at an increased risk of perinatal depression to counseling interventions. However, this prevention goal requires effective interventions that reach women at risk of, but before, the development of a depressive disorder. OBJECTIVE: We describe a pilot efficacy trial of a novel dyadic intervention to prevent common maternal mental health disorders, that is, Practical Resources for Effective Postpartum Parenting, in a sample of women at risk of maternal mental health disorders based on poverty status. We hypothesized that Practical Resources for Effective Postpartum Parenting compared with enhanced treatment as usual would reduce symptoms of maternal mental health disorders after birth. STUDY DESIGN: A total of 60 pregnant women who were recruited from obstetrical practices at Columbia University Irving Medical Center were randomized to the Practical Resources for Effective Postpartum Parenting (n=30) or enhanced treatment as usual (n=30) intervention. The Edinburgh Postnatal Depression Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Patient Health Questionnaire were used to compare maternal mood at 6 weeks, 10 weeks, and 16 weeks after delivery. RESULTS: At 6 weeks after delivery, women randomized to Practical Resources for Effective Postpartum Parenting had lower mean Edinburgh Postnatal Depression scores (P=.018), lower mean Hamilton Depression scores (P<.001), and lower mean Hamilton Anxiety scores (P=.041); however, the incidence of postpartum mental disorders did not differ by treatment group. CONCLUSION: The Practical Resources for Effective Postpartum Parenting, which is an intervention integrated within obstetrical care, improves subclinical symptomology for at-risk dyads at a crucial time in the early postpartum period; however, our study did not detect reductions in the incidence of postpartum mental disorders.

Bilateral Primary Marginal Zone Lymphoma of the Breast - A Rare Breast Malignancy.

Extranodal marginal zone lymphoma (EMZL) presents only rarely within the breast, although the incidence of breast EMZL has increased in the past decade for unclear reasons. Due to its rarity, the etiology, course, and treatment response of this cancer are less studied. Case Report: We present the case of a 64-year-old female who had bilateral diffuse irregularity in a trabecular pattern on screening mammogram. Random ultrasound-guided breast biopsy of the right breast demonstrated an extra-nodal marginal zone B-cell lymphoma. She also had approximately 25% marrow involvement by mucosa-associated lymphoid tissue-type marginal zone lymphoma and splenomegaly. Clinically she remained asymptomatic during a 1-year follow-up. Although she presented with advanced-stage disease involving both breasts, spleen and bone marrow, given her lack of associated symptoms, she was observed with active surveillance. Conclusion: Asymptomatic cases of breast EMZL can be managed with close observation as exemplified by our case.

Addressing mental health in patients and providers during the COVID-19 pandemic.

The pandemic, and the associated changes to pregnancy and postpartum experiences, can lead to profound psychological reactions including panic, hyperarousal, sleep disturbance, anxiety, depression, and traumatic stress disorders. Providers face compassion fatigue and shared trauma. In this article, we describe the mental health outcomes known to date in regard to the novel coronavirus disease 2019 pandemic for obstetric patients and their providers as well as therapeutic approaches, including our novel embedded mental health service, to address these mental health needs.

DNA methylation patterns in T lymphocytes are generally stable in human pregnancies but CD3 methylation is associated with perinatal psychiatric symptoms.

OBJECTIVES: To determine whether DNA methylation patterns in genes coding for selected T-lymphocyte proteins are associated with perinatal psychiatric distress or with complications of pregnancy. METHODS: T lymphocyte DNA was obtained from pregnant women across three time points in pregnancy and the postpartum period and epigenetic patterns were assessed using Illumina 450 â€‹K Methylation Beadchips. Seven selected genes critical for T cell function were analyzed for methylation changes during pregnancy and for associations of methylation patterns with psychiatric distress or with pregnancy complications, with particular attention paid to spatial aggregations of methyl groups, termed 'hotspots,' within the selected genes. RESULTS: In the candidate gene approach, DNA methylation density within a single cluster of 9 contiguous CpG loci within the CD3 gene was found to be strongly associated with anxiety and depression in mid- and late pregnancy, and weakly associated with the presence of complications of pregnancy. Average DNA methylation density across each of the seven genes examined, and assay-wide, was found to be relatively stable across pregnancy and postpartum, but methylation within the CD3 hotspot was more malleable and changes over time were coordinated across the nine cytosines in the hotspot. CD3 CpGs did not pass array-wide tests for significance, but CpG clusters in two other genes, DTNBP1 and OXSR1, showed array-wide significant associations with anxiety. CONCLUSIONS: Despite the need for tolerating the fetal hemi-allograft, overall DNA methylation patterns in T lymphocytes are generally stable over the mid to late course of human pregnancies and postpartum. However, site-specific changes in DNA methylation density in CD3 appear linked to both symptoms of depression and anxiety in pregnancy and, less strongly, to adverse pregnancy outcomes.