Impact of maternal emotional state during pregnancy on fetal heart rate variability.

Background: The fetal autonomic nervous system (ANS) is believed to be negatively affected by maternal adverse emotional states. In this study, we evaluated how depression, anxiety and stress during pregnancy are related to fetal heart rate variability (HRV) as recorded with magnetocardiography (MCG). We also considered metabolic factors such as maternal adiposity and circulating levels of cortisol during gestation. Furthermore, we followed up these fetuses after birth, recording HRV and saliva levels of cortisol in these infants to establish any effects postpartum. Methods: We calculated HRV in spontaneous MCG recordings from 32 healthy fetuses between 32 and 38 weeks of gestational age. Maternal emotional state was assessed using standardized questionnaires about anxiety, depression and stress. An overall indicator of maternal well-being was calculated by z-scoring each individual questionnaire and summation. We used a median split to divide the group into high and low z-scores (HZS and LZS), respectively. Standard HRV measures were determined in the time and frequency domain. T-test analyses were performed between LZS and HZS, with the HRV and the metabolic measures as the dependent variables. Results: We found an impaired HRV in the HZS group both during pregnancy and after birth. No differences were observed between LZS and HZS for metabolic factors. Depression and anxiety symptoms seem to affect HRV differently. No relationship was found between maternal and infant cortisol levels. Conclusions: On the basis of our results on different HRV parameters, we propose that maternal emotional state might affect the development of the fetal nervous system in utero.

Maternal Weight Gain during Pregnancy and the Developing Autonomic Nervous System-Possible Impact of GDM.

OBJECTIVE: The intrauterine environment is known to affect the offspring's long-term risk for obesity and diabetes. Previous data show that maternal metabolism and gestational weight gain (GWG) are associated with fetal autonomic nervous system (ANS) function, which can be assessed with heart rate variability (HRV). We investigated whether this association is also present in 2-year-old children and addressed the impact of gestational diabetes (GDM). RESEARCH DESIGN AND METHODS: We examined the 2-year-old offspring of mothers who had undergone a 5-point, 75 g oral glucose tolerance test during pregnancy. To assess HRV, a 10-minute ECG was recorded, and time domain and frequency domain parameters were analyzed. Body composition was assessed using bioelectrical impedance testing. RESULTS: We examined 67 children (33 girls, 34 boys), 30 of whom were born to mothers with treated GDM and normoglycemic pregnancies (NGT), respectively. No differences were found between the groups with regard to birth weight, weight at the age of 2 years, and body fat content. We observed that GWG was associated with heart rate and HRV, indicating that children of mothers with low GWG had a lower parasympathetic tone. This association was detected in NGT-exposed-but not in GDM-exposed-children. HR and HRV correlated with body fat and fat-free mass in children from normoglycemic pregnancies only. CONCLUSION: We found that the impact of maternal GWG on offspring ANS function was missing in the presence of treated GDM. The balance of the ANS was related to offspring body composition in children from NGT pregnancies only. Our results suggest that maternal weight gain during pregnancy has a critical impact on the developing ANS, which might be disturbed in the presence of GDM.

COVID-19 and Perinatal Stress Experience - a Study Conducted as Part of the COVGEN Initiative.

Introduction During the COVID-19 pandemic, stress and anxiety in the population increased due to concerns about people's own health and that of their relatives, as well as changes in everyday life due to measures taken to reduce the infection rate. Pregnant women are particularly stressed. The present study examines how the COVID-19 pandemic affects the stress experience and mental health of pregnant women and mothers of newborns and how care could be optimized. Methods As part of the international COVGEN initiative ( https://www.covgen.org ) to investigate the effects of the COVID-19 pandemic on the peripartum period, pregnant and postpartum women were asked about their experience with stress using the COPE-IS (Coronavirus Perinatal Experiences - Impact Survey) questionnaire developed for this purpose and translated from the English. In addition, demographic data, pre-existing diseases, pregnancy complications and the care situation were recorded. The questionnaire was either administered as hardcopy to inpatients at the Department of Women's Health, University Hospital Tübingen, Germany, or online. All pregnant women and mothers who were pregnant or had given birth after the official start of the COVID-19 pandemic (11 March 2020) were eligible to participate. Results Complete data sets of n = 156 pregnant women and n = 221 postpartum women were available for evaluation. The general stress level assessed with the COPE-IS was significantly increased by the COVID-19 pandemic in both, pregnant and postpartum women, with pre-existing conditions such as respiratory diseases and pregnancy-related diseases like gestational diabetes adding to the stress. The subjectively perceived quality of care/support during pregnancy also influenced the stress level. Conclusions Fears of a COVID-19 infection and changes in preventive and aftercare services were a burden for the women surveyed. Intensified care during pregnancy and puerperium could help to stabilize the mental situation and reduce stress.

Pre-pregnancy BMI but not mild stress directly influences Interleukin-6 levels and insulin sensitivity during late pregnancy.

BACKGROUND: This study investigates the influence of maternal stress during pregnancy on maternal insulin sensitivity and Interleukin-6 (IL-6) levels in pregnant women (N = 277) in dependence of pre-pregnancy Body-Mass-Index (BMI). METHODS: Gestational diabetes was diagnosed in 80 women. We used the Patient Health Questionnaire (PHQ-D) to investigate maternal stress during pregnancy with a higher scoring indicating higher maternal stress level. IL-6 and cortisol were measured and maternal insulin sensitivity was assessed with the non-esterified fatty acid insulin sensitivity index (NEFA-ISI). Generalized Linear Model analysis was used to analyze effects within different stress groups. RESULTS: Maternal low stress symptoms during pregnancy showed no significant association with maternal insulin sensitivity or IL-6. Higher cortisol levels during pregnancy were associated with elevated IL-6 concentrations. Pre-pregnancy BMI had the strongest positive effect on IL-6 levels and was negatively associated with insulin sensitivity during pregnancy. CONCLUSIONS: Therefore, preconceptional interventions to reduce BMI are needed to improve maternal metabolism during pregnancy.

The German Gestational Diabetes Study (PREG), a prospective multicentre cohort study: rationale, methodology and design.

INTRODUCTION: Even well-treated gestational diabetes mellitus (GDM) might still have impact on long-term health of the mother and her offspring, although this relationship has not yet been conclusively studied. Using in-depth phenotyping of the mother and her offspring, we aim to elucidate the relationship of maternal hyperglycaemia during pregnancy and adequate treatment, and its impact on the long-term health of both mother and child. METHODS: The multicentre PREG study, a prospective cohort study, is designed to metabolically and phenotypically characterise women with a 75-g five-point oral glucose tolerance test (OGTT) during, and repeatedly after pregnancy. Outcome measures are maternal glycaemia during OGTTs, birth outcome and the health and growth development of the offspring. The children of the study participants are followed up until adulthood with developmental tests and metabolic and epigenetic phenotyping in the PREG Offspring study. A total of 800 women (600 with GDM, 200 controls) will be recruited. ETHICS AND DISSEMINATION: The study protocol has been approved by all local ethics committees. Results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: The PREG study and the PREG Offspring study are registered with Clinical Trials (ClinicalTrials.gov identifiers: NCT04270578, NCT04722900).

Acute relaxation during pregnancy leads to a reduction in maternal electrodermal activity and self-reported stress levels.

BACKGROUND: Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women. METHODS: In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels. RESULTS: All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, ηp2 = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, ηp2 = .128. CONCLUSION: Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxation after the intervention than women later in gestation. Hence, gestational age may influence perceived stress levels and should be considered when evaluating relaxation or stress management interventions during pregnancy. TRIAL REGISTRATION: Not applicable.

Spotlight on the fetus: how physical activity during pregnancy influences fetal health: a narrative review.

Before and during pregnancy, women often aim to improve their lifestyle so as to provide a healthier environment for their developing child. It remains unresolved, however, as to whether physical activity (PA) during pregnancy poses a possible risk or whether it might even have beneficial effects on the developing child. There is increasing evidence that PA during pregnancy is indeed beneficial to maternal physiological and psychological health and that it is generally not detrimental to the fetal cardiovascular system and neuronal function in the developing child. This also led to international recommendations for PAs during pregnancy. In the current review, we aimed to comprehensively assess the evidence of beneficial and harmful effects of maternal PA, including high-performance sports, on fetal development. The different mental and body-based relaxation techniques presented here are frequently performed during pregnancy. We found a considerable number of studies addressing these issues. In general, neither low key, moderate maternal PA nor relaxation techniques were observed to have a harmful effect on the developing child. However, we identified some forms of PA which could have at least a transient unfavourable effect. Notably, the literature currently available does not provide enough evidence to enable us to make a general conclusive statement on this subject. This is due to the lack of longitudinal studies on the metabolic and cognitive effects of regular PA during pregnancy and the wide diversity of methods used. In particular, the kind of PA investigated in each study differed from study to study.

Changes in event-related brain responses and habituation during child development - A systematic literature review.

OBJECTIVE: This systematic review highlights the influence of developmental changes of the central nervous system on habituation assessment during child development. Therefore, studies on age dependant changes in event-related brain responses as well as studies on behavioural and neurophysiological habituation during child development are compiled and discussed. METHODS: Two PubMed searches with terms "(development evoked brain response (fetus OR neonate OR children) (electroencephalography OR magnetoencephalography))" and with terms "(psychology habituation (fetal OR neonate OR children) (human brain))" were performed to identify studies on developmental changes in event-related brain responses as well as habituation studies during child development. RESULTS: Both search results showed a wide diversity of subjects' ages, stimulation protocols and examined behaviour or components of event-related brain responses as well as a demand for more longitudinal study designs. CONCLUSIONS: A conclusive statement about clear developmental trends in event-related brain responses or in neurophysiological habituation studies is difficult to draw. Future studies should implement longitudinal designs, combination of behavioural and neurophysiological habituation measurement and more complex habituation paradigms to assess several habituation criteria. SIGNIFICANCE: This review emphasizes that event-related brain responses underlie certain changes during child development which should be more considered in the context of neurophysiological habituation studies.

Impact of Intrauterine Growth Restriction on Cognitive and Motor Development at 2 Years of Age.

Intrauterine growth restriction (IUGR), which is already known to be a risk factor for pathological intrauterine development, perinatal mortality, and morbidity, is now also assumed to cause both physical and cognitive alterations in later child development. In the current study, effects of IUGR on infantile brain function were investigated during the fetal period and in a follow-up developmental assessment during early childhood. During the fetal period, visual and auditory event-related responses (VER and AER) were recorded using fetal magnetoencephalography (fMEG). VER latencies were analyzed in 73 fetuses (14 IUGR fetuses) while AER latencies were analyzed in 66 fetuses (11 IUGR fetuses). Bayley Scales of Infant Development, Second Edition (BSID-II) were used to assess the developmental status of the infants at the age of 24 months. The Mental Development Index (MDI) was available from 66 children (8 IUGR fetuses) and the Psychomotor Development Index (PDI) from 63 children (7 IUGR fetuses). Latencies to visual stimulation were more delayed in IUGR than in small for gestational age (SGA) or appropriate for gestational age (AGA) fetuses, albeit not to any significant extent (p = 0.282). The MDI in former IUGR infants was significantly lower (p = 0.044) than in former SGA and AGA infants. However, IUGR had no impact on PDI (p = 0.213). These findings support the hypothesis that IUGR may constitute a risk factor for neurodevelopmental delay. Further investigation of the possible underlying mechanisms, as well as continued long-term developmental research, is therefore necessary.

Neuromagnetic signatures of syllable processing in fetuses and infants provide no evidence for habituation.

BACKGROUND: Habituation, as a basic form of learning, is characterized by decreasing amplitudes of neuronal reaction following repeated stimuli. Recent studies indicate that habituation to pure tones of different frequencies occurs in fetuses and infants. AIMS: Neural processing of different syllables in fetuses and infants was investigated. STUDY DESIGN: An auditory habituation paradigm including two different sequences of syllables was presented to each subject. Each sequence consisted of eight syllables (sequence /ba/: 5× /ba/, 1× /bi/ (dishabituator), 2× /ba/; sequence /bi/: 5× /bi/, 1× /ba/ (dishabituator), 2× /bi/). Each subject was stimulated with 140 sequences. Neuromagnetic signatures of auditory-evoked responses (AER) were recorded by fetal magnetoencephalography (fMEG). SUBJECTS: Magnetic brain signals of N=30 fetuses (age: 28-39weeks of gestation) and N=28 infants (age: 0-3months) were recorded. Forty-two of the 60 fetal recordings and 29 of the 58 infant recordings were included in the final analysis. OUTCOME MEASURES: AERs were recorded and amplitudes were normalized to the amplitude of the first stimulus. RESULTS: In both fetuses and infants, the amplitudes of AERs were found not to decrease with repeated stimulation. In infants, however, amplitude of syllable 6 (dishabituator) was significantly increased compared to syllable 5 (p=0.026). CONCLUSIONS: Fetuses and infants showed AERs to syllables. Unlike fetuses, infants showed a discriminative neural response to syllables. Habituation was not observed in either fetuses or infants. These findings could be important for the investigation of early cognitive competencies and may help to gain a better understanding of language acquisition during child development.