Margaret H. Bublitz

Maternal Smoking During Pregnancy and Offspring Brain Structure and Function: Review and Agenda for Future Research

INTRODUCTION Maternal smoking during pregnancy (MSDP) has been associated with long-term neurobehavioral and cognitive deficits in offspring. Animal models demonstrate alterations in brain structure and function following prenatal nicotine exposure. However, few studies have assessed the relationship between MSDP and brain development in humans. Therefore, the aims of this review are (a) to synthesize findings from the small number of human studies investigating effects of MSDP on offspring brain development and (b) to outline an agenda for future research in this nascent area. METHODS We searched MEDLINE and Psychinfo databases for human studies of MSDP and offspring brain structure and/or function. RESULTS Eleven studies meeting our search criteria were identified; 6 studies investigated effects of MSDP on brain structure; 5 examined effects on brain function. Across studies, MSDP was associated with decreased volume/thickness of the cerebellum and corpus callosum, increased auditory brainstem responses, and lack of coordination across brain regions during information and auditory processing. CONCLUSIONS Results from the small number of human studies revealed effects of MSDP on brain structure and function, highlighting potential neural pathways linking MSDP and offspring neurobehavioral and cognitive deficits. Given the limited amount of research in this area, we propose an agenda for future research. Gold standard studies would utilize longitudinal designs, integrated biological and maternal report measures of MSDP, and repeated measures of brain structure/function and neurobehavioral deficits across key developmental periods.

Childhood sexual abuse is associated with cortisol awakening response over pregnancy: Preliminary findings

INTRODUCTION Childhood sexual abuse (CSA) has been associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in non-pregnant samples. However, it is not yet known whether CSA is associated with HPA dysregulation over pregnancy. In the present study we assessed whether maternal cortisol levels across pregnancy differed in women with CSA histories compared to women with histories of non-sexual child abuse (CA) and no abuse (NA). METHODS 135 pregnant mothers (CSA=30, CA=58, NA=47) provided salivary cortisol samples at wakeup, wake +30 min, and bedtime for 3 consecutive days at 1-3 time points over second and third trimester. Cortisol awakening responses and slopes were computed. RESULTS Women with CSA histories displayed increasing cortisol awakening response over pregnancy compared to women with CA and NA histories. Group differences were not observed for slope. CONCLUSIONS This is the first study to show that cortisol awakening responses increase over pregnancy in women with CSA histories compared to women with CA and NA histories.

Maternal history of child abuse moderates the association between daily stress and diurnal cortisol in pregnancy: a pilot study.

Abstract Previous research on the association between maternal daily stress and cortisol in pregnancy has yielded inconsistent findings. However, past studies have not considered whether stressful experiences in childhood impact maternal cortisol regulation in pregnancy. In this pilot study, we aimed to examine whether the association between maternal daily stress and cortisol differed according to maternal history of child abuse. Forty-one women provided salivary cortisol samples at wake-up, 30 min after wake-up, and bedtime for 3 days at three times over second and third trimesters of pregnancy. On each day of cortisol collection women reported their daily stress. Women reported child abuse experiences prior to age 18 years by completing 15 items from the Adverse Childhood Experiences Scale. Twenty-one percent (N = 9) of women reported a history of child sexual abuse (CSA), 44% (N = 18) reported a history of non-sexual child abuse and 34% (N = 14) reported no history of child abuse. Hierarchical Linear Modeling (HLM) analyses revealed that stress in the day prior was associated with increases in morning cortisol in women with CSA histories compared to women with non-sexual abuse histories or no history of child abuse. Increases in evening cortisol were associated with increases in daily stress in women with CSA histories compared to women with non-sexual abuse histories or no history of child abuse. Results reveal a dynamic association between daily stress and cortisol in pregnancy and suggest that patterns differ according to maternal child abuse history.

Pre-pregnancy obesity and maternal circadian cortisol regulation: Moderation by gestational weight gain

We investigated main and interactive effects of maternal pre-pregnancy obesity and gestational weight gain on circadian cortisol from the second to third trimester. A diverse sample of 215 pregnant women was enrolled. Maternal height and most recent pre-pregnancy weight were collected at study initiation (22% obese). Weight and circadian salivary cortisol samples were measured during second (24±4) and third (35±1 weeks) trimesters. During the third trimester, women who were obese prior to conception showed elevated evening cortisol versus normal weight women. This pattern was moderated by weight gain in excess of Institute of Medicine guidelines, such that women who were obese prior to conception and gained greater than 7.94kg by the 35±1 week visit displayed greatest elevations in evening cortisol. Given links between excessive prenatal glucocorticoid exposure and both poor maternal and offspring health outcomes, elevated maternal cortisol may be one mechanism underlying links between maternal obesity and adverse perinatal outcomes.

The effects of childhood sexual abuse on cortisol trajectories in pregnancy are moderated by current family functioning

The goal of this study was to understand the roles of maternal history of childhood sexual abuse (CSA) and current family functioning on the cortisol awakening response (CAR) in pregnancy. Participants were 185 pregnant women (ages 18-40) who completed items from the Adverse Childhood Experiences scale to measure child maltreatment history and the Family Assessment Device to measure current family functioning. Participants provided saliva samples at wake-up and 30min after wake-up at 25, 29, and 35 weeks gestation to measure CAR. A moderation effect was found such that participants with more severe CSA histories and poorer perceived family functioning had increasing CAR in pregnancy compared to participants with less severe CSA histories and better family functioning. These findings highlight the importance of considering stress in both childhood and current environments in predicting maternal cortisol in pregnancy.

Childhood maltreatment and inflammation among pregnant women with gestational diabetes mellitus: A pilot study:

Background Women with childhood maltreatment histories are at increased risk for adverse birth outcomes. Mechanisms explaining this link are poorly understood. Past research is limited by sampling pregnant women at low risk for adverse maternal and neonatal outcomes. Methods This pilot study was a secondary data analysis of 24 women with gestational diabetes mellitus; 17% of the sample also reported a maltreatment history. Women provided a blood sample to measure inflammatory cytokines and insulin resistance, and saliva samples to measure diurnal cortisol. Birth outcomes for past and current pregnancies were recorded. Results Histories of maltreatment were associated with elevated interleukin-15 and a marginally greater incidence of preterm delivery in current and past pregnancies. Conclusions This pilot study was the first to demonstrate an association between childhood maltreatment history and inflammatory cytokine levels in pregnant women diagnosed with gestational diabetes mellitus.

Obstructive Sleep Apnea in Gestational Diabetes: A Pilot Study of the Role of the Hypothalamic-Pituitary-Adrenal Axis

STUDY OBJECTIVES Obstructive sleep apnea (OSA) in pregnancy is associated with gestational diabetes mellitus (GDM). This propensity toward heightened insulin resistance in OSA patients has not been well characterized and may be related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to (1) assess the prevalence of OSA in pregnant women with GDM, (2) evaluate whether HPA axis dysregulation relates to OSA, and (3) investigate the relation between insulin resistance and OSA. We hypothesized that OSA is prevalent among pregnant women with GDM and that women with OSA will have higher levels of insulin resistance and dysregulation of the HPA axis. METHODS Twenty-five pregnant women in whom GDM was diagnosed were enrolled. Subjects answered sleep questionnaires and underwent in-home sleep studies using a level III device. The presence of OSA was defined by apnea-hypopnea index ≥ 5 events/h. Homeostasis Model Assessment of insulin resistance was derived from measurements of fasting glucose and C-peptide levels. Three salivary cortisol levels were obtained across 1 day to assess circadian variation. Multivariable linear regression analyses were used to assess associations between variables. RESULTS The sample consisted of 54% Caucasian pregnant women with a median body mass index of 36.1 and interquartile ratio of 10.6 kg/m2. OSA was diagnosed in 17% of participants. Circadian variation of cortisol was preserved in women with OSA. Women with OSA displayed blunted cortisol awakening responses. CONCLUSIONS OSA is prevalent in women with GDM. OSA is associated with preserved circadian variation and blunted cortisol awakening responses.

Residual Renal Function Affects Severity of Sleep Apnea in Peritoneal Dialysis: A Pilot Study

PurposeObstructive sleep apnea is common in patients with end-stage renal disease, and there is increasing evidence that clinical factors specific to end-stage renal disease contribute pathophysiologically to obstructive sleep apnea. It is not known whether circumstances specific to dialysis modality, in this case peritoneal dialysis, affect obstructive sleep apnea. Our study aimed to investigate the prevalence of obstructive sleep apnea in the peritoneal dialysis population and the relevance of dialysis-specific measures and kidney function in assessing this bidirectional relationship.MethodsParticipants with end-stage renal disease who were treated with nocturnal automated peritoneal dialysis for at least 3 months were recruited from a hospital-based dialysis center. Laboratory measures of dialysis adequacy, peritoneal membrane transporter status, and residual renal function were gathered by chart review. Patients participated in a home sleep apnea test using a level III sleep apnea monitor.ResultsOf fifteen participants recruited, 33% had obstructive sleep apnea diagnosed by apnea-hypopnea index ≥ 5 events per hour of sleep. Renal creatinine clearance based upon 24-h urine collection was negatively correlated with apnea-hypopnea index (ρ = − 0.63, p = 0.012). There were no significant associations between anthropometric measures, intra-abdominal dwell volume, or peritoneal membrane transporter status and obstructive sleep apnea measures.ConclusionsThe prevalence of obstructive sleep apnea and sleep disturbances is high in participants receiving peritoneal dialysis. Elevated apnea-hypopnea index is associated with lower residual renal function, whereas dialysis-specific measures such as intra-abdominal dwell volume and peritoneal membrane transporter status do not correlate with severity of obstructive sleep apnea.

Maternal Sleep Quality and Diurnal Cortisol Regulation Over Pregnancy

ABSTRACT Poor sleep in pregnancy is related to adverse neonatal health. Elevated maternal cortisol has been proposed as a pathway, yet the association in pregnancy is not well understood. The goals of the current study were to examine associations between (a) sleep and cortisol, (b) sleep, cortisol, and neonatal outcomes, and (c) variables that could explain these associations. Two hundred pregnant women completed the Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk, Berman, & Kupfer, 1989) and provided diurnal salivary cortisol samples at two times over pregnancy. Poor sleep quality was associated with greater evening cortisol concentrations at 36 weeks’ gestation. This association was mediated by anxiety symptoms. Higher evening cortisol at 36 weeks’ gestation was associated with shorter gestation.

The influence of maternal care and overprotection on youth adrenocortical stress response: a multiphase growth curve analysis

Abstract We examined the association between two dimensions of maternal parenting style (care and overprotection) and cortisol response to an acute laboratory-induced stressor in healthy youth. Forty-three participants completed the Parental Bonding Instrument and an adapted version of the Trier Social Stress Test-Child (TSST-C). Nine cortisol samples were collected to investigate heterogeneity in different phases of youth’s stress response. Multiphase growth-curve modeling was utilized to create latent factors corresponding to individual differences in cortisol during baseline, reactivity, and recovery to the TSST-C. Youth report of maternal overprotection was associated with lower baseline cortisol levels, and a slower cortisol decline during recovery, controlling for maternal care, puberty, and gender. No additive or interactive effects involving maternal care emerged. These findings suggest that maternal overprotection may exert a unique and important influence on youth’s stress response.