Our unique project is based on an ongoing European prenatal stress research focusing on the effect of prenatal stress on early sensory-cognitive development. We capitalize on the methodologically sound maternal and infant physiological measures…
ID
Source
Brief title
Condition
- Other condition
- Pregnancy, labour, delivery and postpartum conditions
- Cognitive and attention disorders and disturbances
Synonym
Health condition
Aangeboren kwetsbaarheid gerelateerd aan het stresssysteem (HPA-as en autonoom zenuwstelsel)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1.Birth outcome:. Gestational length at birth and birth weight and length are
important outcome measures (T4). 2.Psychological measures of mother. The State
Trait Anxiety Inventory (STAI) and Perceived Stress Scale (PSS) are used to
select women at recruitment and, together with the Pregnancy Anxiety
Questionnaire (PRAQ-short) and the Five Factor Mindfulness Questionnaire
(FFMQ), will also be completed to measure the effect of the MBSR and examine
their association with the physiological stress measures. The STAI consists of
20 items measuring state anxiety (transient emotional condition) and trait
anxiety (dispositional anxiety). The PSS, contains 10 items measuring the
perception of stress. The FFMQ , has 39 items measuring five facets of
mindfulness skills. The PRAQ-short measures anxieties related to pregnancy and
contains 10 items. 3.Physiological measures and biochemical assays of the
woman, fetus and infant 3.1. HPA-axis and ANS activity. Basal and
stress-related activity is measured before, during, and after the standard
TSST, which combines a mental arithmetic task with a free speech task in front
of a critical audience and which has been shown to induce reliable
physiological stress responses. Salivary cortisol is measured four times from
before to one hour after the stressor. ANS activity is recorded using the
validated Vrije Universiteit Ambulatory Monitoring System (UV-AMS;
http://www.psy.vu.nl/vu-ams/) throughout the laboratory session. This device
measures heart rate, heart rate variability, skin temperature, skin conductance
and respiration frequency. In addition, in order to assess acute responses to
mindfulness exercises, HR(V) will be measured during 50% of the MBSR sessions,
i.e. 2-weekly at T2. Finally, to assess the cortisol awakening response (CAR)
and diurnal profile, on the day before the laboratory stress test (TSST), the
mothers will provide 6 saliva samples: at awakening, 30, 45 and 60 minutes
after awakening (to measure the CAR), and app. 4 hours later (noon) and app. 12
hours later (evening). We will use electronic monitoring devices to know the
exact hour when the mothers took the saliva samples. Saliva samples will also
be analyzed for alpha-amylase levels, an enzyme considered to reflect changes
in the ANS during stress. In the infants, saliva samples will be taken two
times before the ERP assessment (at arrival in the lab and 15* later), and 3
times after the assessment (at 0, 15 and 30 minutes). 3.2 Heart rate monitoring
in the fetus and infant. We use a simple and powerful non-invasive methodology
by using Monica Healthcare*s AN24 fetal monitor. This device placed on the
maternal abdomen enables reliable detection of the fetal heart*s RR-intervals,
thus providing a fetal ECG. It has been shown that prolonged fECG recordings of
good quality can be obtained during the night, when the mother is asleep],
between 20 and 30 weeks GA. We will perform fetal heart rate monitoring for 8
hours during the night (11 PM to 7 AM) at the pregnant woman*s home,
synchronously with performing maternal heart rate. At 2 months after birth, the
infant*s heart rate and HRV is measured during the lab visit, with BIOSEMI
equipment. The fetal and infant electric heart rate signals, like those of the
mother, will be subjected to HRV analysis in the time and frequency domains .
3.3 HRV parameters. Maternal HRV parameters are standardized by the Task Force
of the European Society of Cardiology and the North American Society of Pacing
and Electrophysiology. In time domain the following measures will be
calculated: the standard deviation of the 5 minute average of RR intervals
(SDANN), the square root of the mean of the sum of the squares of differences
between consecutive RR-intervals (rMSSD) and the percentage of intervals that
vary more than 50 ms from the previous interval (pNN50). The latter two are
strongly related to parasympathetic control [143-144]. In the frequency domain,
low frequency power (LF: 0.04 - 0.15 Hz), high frequency power (HF: 0.16 - 0.40
Hz), total power (0.01 - 1.00 Hz), and the LF/
HF ratio will be calculated. Vagal activity is the major contributor to the HF
component, while the LF component may be seen as reflecting both sympathetic
and vagal activities. In addition, various non-linear parameters of HRV will be
evaluated to search for non-linear fluctuations in heart rate. 3.4 Auditory ERP
in the infant. The auditory mismatch negativity (MMN) paradigm used in an
ongoing study of ours and the infant equivalent mismatch response (MMR) were
designed in collaboration with Istvan Winkler, an internationally recognized
ERP expert (Hungarian Academy of Sciences, Budapest). These measures assess
whether and how strongly infants react to novel and other deviant sounds. At
two months after birth, ERPs will be recorded during a passive auditory oddball
paradigm involving 4 types of sounds of 200ms duration at a uniform 300ms
pre-stimulus interval: (1) 1050 frequent standard complex tones (500Hz); (2)
150 tones with 100ms pre stimulus (ds1); (3) 150 white noise segments (ds2 );
and (4) 150 various environmental sounds (ds3). MMR-related difference waves
are calculated by subtracting responses elicited by the standard tones
separately from those elicited by each of the deviants (ds1,ds2, ds3).
Secondary outcome
Relevant covariates. Maternal age, parity, gravidity, education,
socio-economic status (SES), ethnicity, smoking, alcohol, glucocorticoid
exposure, prescription drug use (i.e., antidepressant (SSRI),
anti-hypertensive, anti-asthmatic, anti-epileptic, steroids) will be gathered
from the medical files of the mothers and from questionnaires completed by the
mother. These data will be used as covariates in analyses (T1 to T5) as
appropriate.
Background summary
A large body of research provides empirical evidence for the hypothesis that
the risk of a shorter length of gestation and of late preterm birth is
increased when high levels of maternal anxiety or chronic stress are present
during pregnancy. The interaction between the maternal stress system and the
physiology of pregnancy and parturition is seen as one of the
pathophysiological mechanism explaining preterm birth. There is also evidence
for an association between high levels of maternal stress and anxiety during
pregnancy and birth defects in the offspring, including cognitive functioning.
Moreover it is hypothesized that antenatal exposure to maternal chronic stress
may induce morphological and functional changes in the hippocampus, amygdala
and prefrontal cortex by which a neurobiological vulnerability is acquired
already prenatally. There still is, however, a lack of knowledge about the
underlying mechanisms. On the one hand a better understanding of the biology of
preterm parturition and of (subtle) birth defects and their underlying
pathophysiological processes is necessary to set up preventive and curative
treatment of women at enhanced risk for giving birth to babies with birth
defects and/or for preterm parturition. On the other hand, by examining in
pregnant women the effectiveness of a standardized stress reduction
intervention program on maternal stress systems and also the infant stress
system and cognitive functioning, hypotheses about the proposed underlying
mechanisms will have a chance to be tested
Study objective
Our unique project is based on an ongoing European prenatal stress research
focusing on the effect of prenatal stress on early sensory-cognitive
development. We capitalize on the methodologically sound maternal and infant
physiological measures that were finalized in this study. A first aim of the
new project is to study the stress system of the pregnant woman (i.e. the
hypothalamus-pituitary-adrenal cortex (HPA)-axis and autonomic nervous system
(ANS)), with physiological measures, to identify those atypical responses in
highly stressed pregnant women which increase the risk of negative outcomes for
the fetus. A second aim is to examine, by means of a randomized controlled
trial, the effects of a standardized mindfulness-based stress reduction (MBSR)
intervention on HPA-axis and ANS of the mother and ANS of the fetus, as well as
on length of gestation at birth, birth weight and HPA-axis, ANS and
sensory-cognitive functioning at two months of age. We expect that effective
interventions during pregnancy will facilitate optimal growth and development
of the offspring. The primary hypotheses to be tested in our study concern the
effects of the MBSR intervention. We will determine whether the MBSR
intervention is associated with: a) a decrease in stress symptoms (anxiety,
depression and distress) of the pregnant woman reflecting a better coping with
stress; b) favorable changes in HPA-axis activity in the pregnant mother (e.g,
steeper diurnal cortisol profile and lower cortisol awakening response); c)
favorable changes in ANS activity in the pregnant woman (e.g., higher heart
rate variability); d) favorable changes in ANS activity in the fetus and infant
(e.g., higher heart rate variability); e) favorable birth outcomes (e.g.,
increased gestational age at birth and increased birth weight); f) more optimal
early sensory-cognitive development, reflecting optimal brain function.
Study design
General procedure and subjects Sample (n=140). After obtaining permission from
a nationally recognized medical ethics committee, eligible women, aged 18-40,
will be recruited at 10-12 weeks* gestation for longitudinal study with infant
follow-up. Women will be approached for participation at the Obstetrical and
Gynecological Board consultations of several hospitals in the cities of Tilburg
and Eindhoven and at midwife consultation institutes. Inclusion criteria are:
(a) scores at least higher than the 67th percentile on standardized stress and
anxiety questionnaires, (b) no current substance abuse problems, (c) no severe
psychiatric problems, (e.g., psychoticism, current suicidal ideation), and (d)
no pregnancy-associated medical problems such as diabetes or hypertension.
Assessment time points (T): TI to T5 (see Table 1) and time table of the study
(see Table 2) T1: once between 11 and 14 weeks gestational age (GA):
pre-testing of maternal HPA-axis and ANS, before MBSR intervention sessions.
T2: 2-weekly between 15 and 23 weeks GA, assessment of maternal HPA-axis and
ANS and fetal ANS during the period of MBSR intervention sessions; T3: once at
29 weeks GA: post-testing of maternal stress system and of infant ANS, 6 weeks
after completion of the MBSR intervention sessions; T4: two days after birth,
postnatal follow-up immediately after birth T5: two months after birth; long
term postnatal follow-up of mother and infant.
Intervention
A stress reduction intervention is given to the experimental group, weekly
between week 15 and 23 of gestation and each session lasts 150 minutes, We will
examine the short-term and long-term effects of a MBSR intervention given to
pregnant women, using a randomized controlled trial in which the IG (n=70)
receives a MBSR intervention and the matched CG (n=70) receives standard
prenatal care. We will follow both groups of women and their infants up until
two months after birth. After having given informed consent, women will be
randomly assigned to the MBSR IG or matched CG. Women of the CG will receive
care as usual and will be given a chance to participate in an MBSR intervention
after T5. At baseline, before the intervention (T1), all participants will
complete psychological measurements (i.e., questionnaires) and physiological
measurements. The latter will include basal HPA-axis and ANS measurements
(i.e., salivary cortisol and alpha-amylase) on the day before the stress
assessment and HPA-axis (i.e., cortisol) and ANS-functioning (i.e., heart rate
variability (HRV)) during the standardized laboratory stress protocol, i.e. the
Trier Social Stress Test (TSST). After randomization, the IG starts a
standardized MBSR training [101] adapted for pregnant women [116]. The training
consists of eight weekly sessions (about 7 women per group) with a duration of
150 minutes from week 15 to 23 of gestation (T2). In addition, participants are
instructed to practice daily for at least 40 min; a booklet is provided
containing relevant information. Six weeks after the training, i.e. at 29 weeks
of gestation (T3), questionnaires, physiological measures (and biochemical
assays), including at least a version of a mental arithmetic task of the TSST.
Some of these measurements are also taken at T4 (2 days after birth) and/or T5
(2 months after birth). Moreover, fetal heart rate will be monitored at 22 (T2)
and 29 (T3) weeks GA for 8 hrs continuously during the night. Finally,
infant-HPA-axis (cortisol), ANS (alpha-amylase and HRV) and sensory-cognitive
functioning (using an auditory event related potential paradigm), are measured
at two months after birth (T5).
Study burden and risks
Completing the questionnaires takes 15 to 30 minutes; taking the saliva samples
takes a few minutes every time; to attach and detach the VU-ambulant monitoring
system will take 10 minutes. The observations in the university lab (2 times
during pregnancy) take about 60 minutes For the Mindfulness-training (to reduce
stress) there are 8 sessions that last 150 minutes each The final observation
in the lab (including the baby and the mother) takes 60 to 75 minutes and
completion of the questionnaires takes 30 minutes.
Postbus 905153
5000 LE Tilburg
NL
Postbus 905153
5000 LE Tilburg
NL
Listed location countries
Age
Inclusion criteria
Pregnant woman: -18 to 40 year old -score higher then Pc 67 on standardised stress and anxiety questionnaires -no substance abuse problems -no severe psychiatric problems -no pregnancy-related medical problems (e.g. diabetes, hypertension) or obstetrical problems
Exclusion criteria
Pregnant woman: -other medical or obstetrical complications during this pregnancy -18 to 45 year old -score lower then Pc 67 on standardised stress and anxiety questionnaires -substance abuse problems -severe psychiatric problems -pregnancy-related medical problems (e.g. diabetes, hypertension) or obstetrical problems
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL38557.008.11 |