Investigating Factors Influencing Prenatal Stress, Anxiety, and Fear of Childbirth During the COVID-19 Pandemic in Germany and Switzerland: An Online Survey.

OBJECTIVES: Pregnant women are likely to experience high levels of stress during the COVID-19 pandemic. However, the factors that might influence the extent of experienced emotional distress are poorly understood. Therefore, we aimed to investigate potential correlates of prenatal emotional distress during the COVID-19 pandemic. METHODS: In total, N = 1437 pregnant women from Germany and Switzerland participated in an online study during the first wave of the COVID-19 pandemic (May-August 2020). The survey assessed prenatal distress, pandemic-related pregnancy stress, general anxiety, fear of childbirth, and several socio-demographic, pregnancy- and COVID-19-related factors. Linear multivariate regression models were the main analytical strategy. RESULTS: The results highlight that several factors such as full-time employment, nulliparity, high-risk pregnancy, emotional problems, cancelled prenatal appointments, and stating that COVID-19 affected the choice of birth mode were significantly associated with elevated prenatal distress, anxiety, pandemic-related pregnancy stress, and fear of childbirth. Conversely, access to an outdoor space was a protective factor for pandemic-related pregnancy stress and prenatal distress. CONCLUSIONS FOR PRACTICE: Overall, the study highlights significant correlates influencing the levels of emotional distress pregnant women experienced during the COVID-19 pandemic. These findings may contribute to the improvement of maternal prenatal medical and psychological care during a public health crisis of international concern, such as the COVID-19 pandemic.

Common model of stress, anxiety, and depressive symptoms in pregnant women from seven high-income Western countries at the COVID-19 pandemic onset.

OBJECTIVE: Increases in stress, anxiety, and depression among women pregnant during the COVID-19 pandemic have been reported internationally. Yet rigorous comparison of the prevalence of maternal mental health problems across countries is lacking. Moreover, whether stress is a common predictor of maternal mental health during the pandemic across countries is unknown. METHODS: 8148 pregnant women from Germany, Israel, Italy, Poland, Spain, Switzerland, and the United States were enrolled in the International COVID-19 Pregnancy Experiences (I-COPE) Study between April 17 and May 31, 2020. Sociodemographic characteristics, pandemic-related stress, pregnancy-specific stress, anxiety, and depression were assessed with well-validated instruments. The magnitude of stress and mood disturbances was compared across countries. A path model predicting clinically significant levels of anxiety and depression from maternal characteristics and stress was tested for all study participants and then examined separately in each country with >200 participants. RESULTS: Countries differed significantly in magnitude of pandemic-related pregnancy stress and pandemic-unrelated pregnancy-specific stress, and in prevalence of clinically significant anxiety and depression levels. A well-fitting common path model for the entire sample indicated that mood and anxiety disturbances were strongly predicted by pandemic-related and pregnancy-specific stress after accounting for maternal characteristics. The model was replicated in individual countries. CONCLUSIONS: Although pregnant women in high-income Western countries experienced different levels of stress resulting from the COVID-19 pandemic, stress is a strong, common predictor of anxiety and depressive symptoms in these individuals. The common model can be used to inform research and clinical interventions to protect against adverse consequences of prenatal maternal stress, anxiety, and depression for mothers and infants.

Endocannabinoid and steroid analysis in infant and adult nails by LC-MS/MS.

A common method to quantify chronic stress is the analysis of stress markers in keratinized matrices such as hair or nail. In this study, we aimed to validate a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the combined quantification of steroid hormones and endocannabinoids (eCBs) in the keratinized matrix nail. Furthermore, we aimed to investigate the suitability of the nail matrix for the detection of these stress markers in a pilot study. An LC-MS/MS method was used for the simultaneous identification and quantification of four eCBs (2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA)) and five steroid hormones (cortisol, cortisone, androstenedione, progesterone, testosterone) in human nails using a surrogate analyte method for each analyte. The method was validated in terms of selectivity, response factor, linearity, limit of quantification (LOQ), precision, accuracy, matrix effect, recovery, robustness, and autosampler stability. Nail samples were extracted for 1 h with methanol following a clean-up with a fully automated supported liquid extraction (SLE). The influence of nail weight on the quantification was investigated by using 0.5-20 mg of nail sample. As a proof of concept, nail samples (N = 57) were analyzed from a cohort representing newborns (1 month old), children (between 1 and 10 years), and adults (up to 43 years). It could be shown that the established workflow using a 1 hour extraction and clean-up by SLE was very robust and resulted in a short sample preparation time. The LC-MS/MS method was successfully validated. Matrix effects with ion enhancement occurred mainly for 2-AG. Sample weights below 5 mg showed variations in quantification for some analytes. Certain analytes such as PEA and progesterone could be accurately quantified at a sample weight lower than 5 mg. This is the first study where steroids and eCBs could be simultaneously detected and quantified in infant and adult nails. These results show that nails may serve as an alternative keratinized matrix (compared to hair) for the retrospective monitoring of cumulative eCB and steroid hormone levels. The combined assessment of eCBs and steroids from nails could provide a new approach to gain new insights into stress exposure in newborns and adults.

Cortisol and estriol responses to awakening in the first pregnancy trimester: Associations with maternal stress and resilience factors.

BACKGROUND: Little is known about the maternal cortisol awakening response (CAR) in the first pregnancy trimester. Similarly unknown is how the CAR in early gestation relates to other steroid hormones, such as estriol. Maternal estriol in blood and urine is used to monitor fetal well-being since it is produced by the fetoplacental unit from fetal precursors. Low levels have been associated with maternal-fetal complications. We were recently able to show that estriol is measurable in maternal saliva from 6 weeks' gestation onwards. However, its pattern following morning awakening and potential links with salivary cortisol in early gestation is relatively unknown. In this prospective study, we explored the cortisol and estriol responses to morning awakening in first-trimester pregnant women, the potential association of these endocrine variables with maternal stress and resilience factors, and their predictive value for the further pregnancy course. METHODS: Fifty-one women with an uncomplicated, singleton pregnancy responded to questionnaires measuring chronic and pregnancy-specific stress, emotional support, and daily uplifts at 6 weeks' gestation. At 8 and 10 weeks, the women collected saliva samples immediately, 30, and 60 min after morning awakening. After 12 weeks, 40 women reported on the further pregnancy course, of whom 6 had developed complications. RESULTS: In response to morning awakening, cortisol levels increased significantly at 10 weeks (p = .04), while estriol levels decreased significantly at both 8 and 10 weeks (p < .001). A stronger cortisol increase was linked to a stronger estriol decrease at 8 (p = .03), but not at 10 weeks. Then, perceived emotional support at 6 weeks was negatively associated with cortisol baseline at 8 (p = .01) and positively with estriol baseline at 10 weeks (p = .03). Moreover, higher pregnancy-specific stress was related to a lower estriol baseline at 8 weeks (p = .047). Furthermore, compared to healthy women, those with complications at follow-up had already reported less emotional support (p = .03) and fewer daily uplifts (p = .03) at 6 weeks. These women also seemed to lack a significant estriol response to morning awakening at 8 weeks (p > .10). DISCUSSION: These findings advance our knowledge of cortisol and estriol secretion following morning awakening and encourage the investigation of E3 in addition to cortisol when researching prenatal stress and its consequences for maternal and fetal health.

Creative Music Therapy with Premature Infants and Their Parents: A Mixed-Method Pilot Study on Parents' Anxiety, Stress and Depressive Symptoms and Parent-Infant Attachment.

Premature birth is stressful for infants and parents and can adversely affect the parent-infant dyad. This mixed-methods pilot study evaluates whether creative music therapy (CMT) can alleviate anxiety, stress, and depressive symptoms in parents and support the bonding process with their infant. Sixteen parent couples were included. Ten couples were randomly allocated to the music therapy group (MTG) and six to the control group (CG). All couples completed psychological questionnaires measuring anxiety and depressive symptoms as well as an implicit measure of parent-infant attachment at two weeks postpartum (T1), at approximate neonatal intensive care unit (NICU) hospitalization halftime (T2), and two weeks after the infant had been discharged (T3). At T1 and T2, the parents additionally completed a questionnaire assessing the degree of stress they experienced at the NICU. Qualitative data were collected through a semi-structured, problem-centered interview with MTG parents at T3. The results of the quantitative analyses revealed reductions in anxiety levels from T1 to T2 (p = 0.002) as well as decreases in depressive symptoms from T2 to T3 (p = 0.022). No such changes were apparent in the CG. In fact, parental stress increased from T1 to T2 (p = 0.016). Significant increases in attachment across time were also observed within the MTG, but not in the CG. The qualitative inquiry confirmed that CMT can support the parent-infant relationship. Being in musical interaction evoked feelings of joy and relaxation in the parents and encouraged them to interact more profoundly with their infant. The results call for a more extensive powered follow-up study to further investigate CMT's potential for parental well-being and parent-infant bonding.

Steroid profiling in nails using liquid chromatography-tandem mass spectrometry.

The retrospective analysis of endogenous steroid hormones in nails can be used to elucidate endocrine diseases and thus help with their diagnosis and treatment. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) based method was developed for the simultaneous identification and quantification of 12 steroid hormones (aldosterone, cortisone, cortisol, corticosterone, 11-deoxycortisol, androstenedione, 11-deoxycorticosterone, testosterone, dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17-OHP), dihydrotestosterone (DHT) and progesterone) in human fingernails. Steroid hormones were extracted from 0.5 mg to 10 mg pulverized nail clippings by methanolic extraction, followed by a liquid-liquid extraction. The analysis was conducted with LC-MS/MS in electrospray ionization positive mode. The method was validated in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, matrix effect, recovery and robustness. It was successfully applied for steroid profiling in nails of mothers and their infants where cortisol, cortisone, testosterone, progesterone, androstenedione and 11-deoxycorticosterone could be detected. Furthermore, it could be shown that there is no significant difference in concentrations between left and right hand for cortisol, cortisone and progesterone. A positive linear correlation between cortisol and cortisone in nails was found. In conclusion, it could be shown that nails are a suitable matrix for the retrospective monitoring of cumulative steroid hormone levels.

Women's Word Use in Pregnancy: Associations With Maternal Characteristics, Prenatal Stress, and Neonatal Birth Outcome.

Background: Experiencing high levels of stress during pregnancy can impair maternal well-being and fetal development. Consequently, unbiased assessment of maternal psychological state is crucial. Self-report measures are vulnerable to social desirability effects. Thus, implicit measures, such as word choice analysis, may offer an alternative. Methods: In this longitudinal online-study, 427 pregnant women described their emotional experiences in writing and additionally responded to self-report questionnaires assessing symptoms of prenatal stress and depression. The written texts were analyzed with a computerized text analysis program. After birth, 253 women provided information on birth outcome. Results: Word use differed significantly depending on maternal socioeconomic (e.g., marital status) and pregnancy-related characteristics (e.g., parity). Prenatal stress and depressive symptoms were associated with more frequent use of negative emotion words and words of anxiety, as well as with less first-person plural, but not singular pronoun use. Negative emotion and cognitive mechanism words predicted birth outcome, while self-report measures did not. Conclusion: In addition to self-report measures, word choice may serve as a useful screening tool for symptoms of depression and stress in pregnant women. The findings on pronoun use may reflect women's changing experience of self-identity during the transition to motherhood.

Second-trimester amniotic fluid corticotropin-releasing hormone and urocortin in relation to maternal stress and fetal growth in human pregnancy.

This study explored the association between the acute psychobiological stress response, chronic social overload and amniotic fluid corticotropin-releasing hormone (CRH) and urocortin (UCN) in 34 healthy, second-trimester pregnant women undergoing amniocentesis. The study further examined the predictive value of second-trimester amniotic fluid CRH and UCN for fetal growth and neonatal birth outcome. The amniocentesis served as a naturalistic stressor, during which maternal state anxiety and salivary cortisol was measured repeatedly and an aliquot of amniotic fluid was collected. The pregnant women additionally completed a questionnaire on chronic social overload. Fetal growth parameters were obtained at amniocentesis using fetal ultrasound biometry and at birth from medical records. The statistical analyzes revealed that the acute maternal psychobiological stress response was unassociated with the amniotic fluid peptides, but that maternal chronic overload and amniotic CRH were positively correlated. Moreover, amniotic CRH was negatively associated with fetal size at amniocentesis and positively with growth in size from amniocentesis to birth. Hardly any studies have previously explored whether acute maternal psychological stress influences fetoplacental CRH or UCN levels significantly. Our findings suggest that (i) chronic, but not acute maternal stress may affect fetoplacental CRH secretion and that (ii) CRH is complexly involved in fetal growth processes as previously shown in animals.

Is salivary estriol detectable in very early pregnancy?

OBJECTIVE: Estriol (E3) is produced by the placenta and is important for early pregnancy maintenance. In blood, E3 can be detected from the 8th week of pregnancy. Under the influence of the hypothalamic-pituitary-adrenal (HPA) axis hormone ACTH, E3 levels increase sharply after the 10th week. Although E3 can be reliably analyzed in saliva, till now information about the concentrations during the first trimester is missing. The aim of this study was to verify whether the sensitivity of a newly developed enzyme immunoassay is sufficient for the determination of salivary E3 (sE3) in very early pregnancy. METHODS: Saliva samples were collected at home, once weekly in 25 healthy pregnant women from the 6th week of gestation to the end of the first trimester. RESULTS: sE3 was detectable from the beginning of the 6th pregnancy week (M = 3.17 pg/ml, SD = 2.13). A steep significant increase between the 7th and the 8th week (p = 0.029) and again between the 10th and the 11th week (p = 0.001) was apparent. CONCLUSION: Low concentrations of sE3 can be measured during very early pregnancy and may serve as a promising, easily assessable marker for future research on the mechanisms of healthy pregnancy.

Mixed Expectations: Effects of Goal Ambivalence during Pregnancy on Maternal Well-Being, Stress, and Coping.

BACKGROUND: We hypothesised that experiencing ambivalence toward the childbearing goal would be related to indicators of well-being, stress, and coping among women with planned pregnancies. METHODS: Study 1 (N = 208) tested cross-sectional associations between goal ambivalence and measures of well-being, stress, and coping. It also included a postpartum measurement point (N = 71) to examine prospective effects of goal ambivalence. Study 2 (N = 109) extended the investigation to within-person effects in a three-week daily diary assessment. RESULTS: In Study 1, goal ambivalence in pregnant women was positively associated with depressive symptoms, perceived stress, and pregnancy-specific avoidance-oriented coping, and negatively associated with coping self-efficacy. Goal ambivalence also predicted changes in life satisfaction, depressive symptoms, perceived stress, and coping self-efficacy postpartum. Study 2 revealed within-person effects of daily fluctuations in goal ambivalence on day-to-day changes in positive emotions, negative activation, and avoidance-oriented coping. CONCLUSIONS: Ambivalence towards the childbearing goal is a source of significant distress to pregnant women with planned pregnancies and its effects seem to extend into the postpartum period. These findings may have important clinical implications for maternal and child well-being. Future studies should examine whether goal ambivalence during pregnancy affects the maternal-child relationship in the long term.

The acute autonomic stress response and amniotic fluid glucocorticoids in second-trimester pregnant women.

OBJECTIVE: The maternal autonomic nervous system (ANS) has received little attention in the investigation of biological mechanisms linking prenatal stress to fetal cortisol (F) excess. In vitro, norepinephrine and epinephrine inhibit placental 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), which protects the fetus from F overexposure by inactivating it to cortisone (E). Here, we investigated the acute ANS stress response to an amniocentesis and its association with amniotic fluid F, E, and E/(E + F) as a marker of fetoplacental 11ß-HSD2 activity. METHODS: An aliquot of amniotic fluid was obtained from 34 healthy, second-trimester pregnant women undergoing amniocentesis. Repeated assessment of mood states served to examine the psychological stress response to amniocentesis. Saliva samples were collected to measure stress-induced changes in salivary α-amylase concentrations in response to amniocentesis. Cardiac parameters were measured continuously. RESULTS: Undergoing amniocentesis induced significant psychological and autonomic alterations. Low-frequency (LF)/high-frequency (HF) baseline, suggested to reflect sympathovagal balance, was negatively correlated with amniotic E/(E + F) (r=-0.53, p = .002) and positively with F (r = 0.62, p < .001). In contrast, a stronger acute LF/HF response was positively associated with E/(E + F) (r = 0.44, p = .012) and negatively with F (r=-0.40, p = .025). CONCLUSIONS: These findings suggest that the maternal ANS is involved in the regulation of the fetoplacental barrier to stress. Allostatic processes may have been initiated to counterbalance acute stress effects. In contrast, higher LF/HF baseline values, possibly indicative of chronic stress exposure, may have inhibited 11ß-HSD2 activity in the fetoplacental unit. These results parallel animal findings of up-regulated placental 11ß-HSD2 in response to acute stress but impairment under chronic stress.

The association between perceived emotional support, maternal mood, salivary cortisol, salivary cortisone, and the ratio between the two compounds in response to acute stress in second trimester pregnant women.

OBJECTIVE: Little is known about the effect of social support on the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy. Moreover, when investigating the HPA axis most studies do not consider the activity of 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), an enzyme within the salivary glands that inactivates cortisol to cortisone. This study explores the association between perceived emotional support and the maternal psychobiological stress response to a standardized naturalistic stressor by assessing maternal mood and the reactivity of salivary cortisol (SalF), salivary cortisone (SalE), and the SalE/(E+F) ratio as a marker of 11ß-HSD2 activity. METHODS: Repeated saliva samples and measures of maternal mood were obtained from 34 healthy second trimester pregnant women undergoing amniocentesis which served as a psychological stressor. The pregnant women additionally responded to a questionnaire of perceived emotional support and provided sociodemographic (e.g., maternal educational degree) and pregnancy-specific data (e.g., planned versus unplanned pregnancy). RESULTS: Perceived emotional support neither showed a significant effect on mood nor on the SalF or SalE response to stress. However, a moderately strong positive association was found between perceived emotional support and SalE/(E+F) (r=.49). Additionally, the final regression analysis revealed a significant negative relationship between educational degree, planned/unplanned pregnancy and SalE/(E+F). CONCLUSION: Findings suggest a higher metabolization of cortisol to cortisone in pregnant women with higher emotional support. In contrast, higher maternal education and unplanned pregnancy appear to be associated with decreased salivary 11ß-HSD2 activity. The current study emphasizes the importance of taking the activity of 11ß-HSD2 into account when examining SalF.