Clinical trial NCT06876051: Prenatal Intervention of Maternal Stress - Breastfeeding & Infant Neurodevelopment
Official title: The Impact of Prenatal Stress Management Program on Maternal Breastfeeding and Neonatal Neurodevelopmental Parameters
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress
Relaxation
Breastfeeding
Infant Behavior
Prenatal Stress
Keywords: breastfeeding
BDNF
Reelin
pregnancy
relaxation techniques
stress management
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
Collaborators: name: General and Maternity Hospital of Athens Elena Venizelou
First posted: 2025-03-14
Enrollment: 162
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Primipara Pregnant women are randomly assigned to one of three groups: (1) an intervention group receiving relaxation techniques combined with breastfeeding education, (2) an active control group receiving only breastfeeding education, and (3) a control group receiving standard maternity care.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal of this clinical trial is to determine whether antenatal maternal stress management using relaxation techniques improves breastfeeding effectiveness and neonatal neurodevelopmental outcomes. It is hypothesized that reducing maternal stress during pregnancy will enhance the initiation and continuation of exclusive breastfeeding until six months postpartum.

The management of antenatal maternal stress is expected to be reflected in both the newborn's behavior and proteins associated with neurodevelopment, such as Brain-Derived Neurotrophic Factor (BDNF) and Reelin.

The main research questions of this study include the following:

1. Does stress management in pregnant women using relaxation techniques increase the likelihood of exclusive breastfeeding at one and six months postpartum?
2. Does it impact neonatal and infant growth and behavior?
3. Does it alter neurotrophin levels in the fetus? This trial will provide insight into the potential benefits of prenatal stress reduction for both maternal and infant health outcomes.
4. "If prenatal stress management leads to changes in neurotrophins in the fetus, could these changes be linked to the success and duration of breastfeeding, as well as the infant's growth and behavior?

Detailed description: METHODOLOGY Researchers will compare three groups of pregnant women who will receive three different types of information during pregnancy.

* The first group, or intervention group (IG), will be trained in 8-10 structured individual sessions of relaxation techniques that they will apply throughout the pregnancy, along with structured information about breastfeeding.
* The second group, or Active Control group (ACG), will receive 8 individual structured educational courses about breastfeeding, childbirth and the needs of the newborn, and
* The third group, or Control Group (CG), will receive a standard use information provided by the hospital midwife stuff about childbirth and breastfeeding in 3-4 group meetings .

Participants will be primipara pregnant women native speaking of the Greek language and they will be included in the study after randomization based on the electronic system random.org , between the 15th and 20th week of gestation They will be studied in 4 time periods (phases) .

* The first phase, will be prenatally at the beginning of the study between 15th -20th week of gestation,
* the second phase, will be prenatally at the end of the study between the 34th and 36th week of gestation,
* the third phase, will be in the first month after childbirth and
* the fourth phase, will be in the 6th month of their baby's life. The study as well, will include the newborns of the participants in the third and fourth phase of the study, corresponding them to the group of their mothers.

Comparisons will be in each group and between the groups investigating the alteration of stress, anxiety and depression during the four time periods pre and postnatally . Concurrently the change in the belief of successful breastfeeding during the two first periods of time (phase 1 and 2 ) , prenatally, will be compared with the real outcome at the phase 3 and 4.

For each participant, the following data will be recorded:

Phases 1 and 2:

1. Demographic data
2. Pregnancy stress, assessed using the Prenatal Experience Brief Scale
3. Pregnancy anxiety, assessed using the Pregnancy Anxiety Questionnaire
4. Prenatal breastfeeding self-efficacy, assessed using the Prenatal e. Breastfeeding Self-Efficacy Scale

Phases 1, 2, 3, and 4:

1. Perceived stress, assessed using the Perceived Stress Scale-14 (PSS-14)
2. Postpartum depression, assessed using the Edinburgh Postpartum Depression Scale (EPDS)
3. Anxiety, assessed using the Spielberger State-Trait Anxiety Inventory (STAI)

Phases 3 and 4:

1. Breastfeeding self-efficacy, assessed using the Breastfeeding Self-Efficacy Scale
2. Breastfeeding-related questions from the Pregnancy Risk Assessment Monitoring System (PRAMS) of the CDC

Phase 4 only :

1. Maternal attachment, assessed using the Maternal Attachment Scale
2. Infant behavior, assessed using the Infant Behavior Questionnaire

For each newborn, the following data will be recorded:

1. Anthropometric measurements at birth (3rd phase) and at six months of age (4th phase).
2. Neonatal behavior, assessed between the 4th and 7th day of life (3rd phase) using the Neonatal Behavioral Assessment Scale (NBAS). The evaluation will be conducted by a healthcare professional trained and familiar with the use of this specific behavioral assessment tool.
3. Developmental milestones at six months of age (4th phase).
4. Infant behavior assessment at six months of age (4th phase), conducted using the Infant Behavior Questionnaire, which will be completed by the parents based on their own observations and assessment

Biological Markers Collection and Analysis

The collection of biological markers is structured according to the study phase:

* In phases 1 and 2, salivary cortisol will be measured in pregnant participants. Participants will be asked to collect saliva using Salivettes (Sarstedt), following specific instructions provided by the manufacturer.
* In phases 1 and 3, maternal serum neurotrophins (BDNF and Reelin) will be analyzed. Additionally, in phase 3, umbilical cord serum neurotrophins will be measured.

Saliva Collection and Analysis

Saliva collection will be conducted at four time points throughout the day to assess the circadian rhythm of each pregnant participant:

* Morning, immediately upon awakening
* 30 minutes after awakening
* Afternoon, before lunch (around 3:00 PM)
* Night, before bedtime (around 12:00 AM) Pregnant participants will store the collected samples in the refrigerator until they bring them to the laboratory the following day. At the laboratory, the samples will undergo centrifugation followed by measurement using Chromatography/Mass Spectrometry.. The saliva samples will be centrifuged for 2 minutes at 1,000 × g, following the manufacturer's instructions.

Neurotrophin Measurement (BDNF \& Reelin) - Phases 1 and 3

The measurement of BDNF and Reelin neurotrophins will be performed on serum blood samples collected at three time points:

1. Phase 1: At the start of the intervention (between 15-20 weeks of gestation) - maternal blood serum.
2. Phase 3: Before delivery (at hospital admission, marking the end of the prenatal intervention) - maternal blood serum.
3. Phase 3: During delivery - umbilical cord serum only. All blood samples will undergo centrifugation at 3500 rpm for 5-6 minutes. The separated serum will then be transferred into Eppendorf tubes and stored at -80°C until further analysis. Neurotrophin levels (BDNF \& Reelin) will be measured using the ELISA method.

Eligibility criteria: Inclusion Criteria:

* Primiparous pregnant women
* 14-20 weeks of Gestational Age
* Intention to give birth at the specific maternity hospital
* Greek women or foreigners who know the Greek language very well
* Place of residence: Greece

Exclusion Criteria:

* Use of benzodiazepines, major neuroleptics, or psychostimulant medications.
* Pregnant women diagnosed with incurable physical or mental diseases.
* Pregnant women carrying fetuses or newborns with major congenital anomalies or criteria for perinatal asphyxia.
* Pregnant women with stillbirths or newborns who do not survive.
* All mothers and their newborns born before 34 weeks of gestation or requiring hospitalization in the Neonatal Intensive Care Unit (NICU) for more than 7 days.

Primary outcomes:
measure: Prenatal Breastfeeding Self-Efficacy Across Study Groups
timeFrame: 1) between 15 - 20 week of gestation and 2) between 35-38 weeks gestation before child birth
measure: Breastfeeding Self-Efficacy across the study groups and the time frames
timeFrame: At 1 and 6 months postpartum
measure: Breastfeeding Outcomes Across Study Groups
timeFrame: at 1 and 6 Months Postpartum
measure: Neurotrophin Levels as Neurodevelopmental Parameters in Maternal Serum and Umbilical Cord Blood across the study groups
timeFrame: In Maternal serum: 1) between the 15th -20th weeks of gestation and 2) at 36-37 weeks of gestation .Additionally Neurotrophins will be measured In Umbilical cord blood: At birth
measure: Neonatal Behavioral Assessment Across Study Groups
timeFrame: 4-7 days postpartum
measure: Infant Behavioral Assessment Across Study Groups
timeFrame: IBQ-R SF will be measured at 6 months postpartum
Secondary outcomes:
measure: Correlation Between Maternal age and Breastfeeding success
timeFrame: breastfeeding outcomes : at 1 and 6 month postpartum.
measure: Correlation Between Maternal Socioeconomic Status and Breastfeeding success
timeFrame: Household income will be assessed between the 15th and 20th week of gestation, while breastfeeding outcomes will be measured at 1 and 6 months postpartum.
measure: correlation of maternal Body Mass Index (BMI) and Breastfeeding success across the three study groups.
timeFrame: BMI assessment: Pre-pregnancy (self-reported) and at delivery (clinically measured) Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Correlation Between Anxiety and Breastfeeding success
timeFrame: STAI assessment: prenatally at 15-20 and 35-38 weeks of gestation . Postnatally, Breastfeeding outcomes assessment: at 1 and 6 months postpartum.
measure: Correlation Between Pregnancy-Related Anxiety (PRAQ-R2) and Breastfeeding Success across study groups
timeFrame: PRAQ-R2 assessment: Between 15-20 and 35-38 weeks of gestation Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Influence of Neonatal Behavior on Breastfeeding Outcomes
timeFrame: NBAS is evaluating between the first 4-7 days of life. Breastfeeding assessment will be at 1 and 6 months postpartum
measure: Correlation Between Neurotrophin Levels and Breastfeeding Self-Efficacy across the study groups
timeFrame: Neurotrophin levels: Maternal serum (15-20 and 36-37 weeks gestation), Umbilical cord blood (at birth) Breastfeeding self-efficacy: 1 and 6 months postpartum
measure: Correlation between Prenatal Breastfeeding Self-Efficacy and Breastfeeding Outcomes Across Study Groups
timeFrame: PBSES assessment: 15-20 weeks and 35-38 weeks of gestation Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Correlation between Postnatal Breastfeeding Self-Efficacy and Breastfeeding Outcomes Across Study Groups
timeFrame: BSES assessment: 1 and 6 months postpartum Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Correlation between Salivary Cortisol levels and Breastfeeding outcomes across the study groups
timeFrame: Salivary cortisol levels at 35-38 week of gestation . Breastfeeding success at 1 month postpartum
measure: Correlation Between Infant Behavior and Breastfeeding Success across the three study groups
timeFrame: IBQ-R SF assessment: 6 months postpartum Breastfeeding outcomes assessment: 6 months postpartum
measure: correlation between newborn hospitalization and breastfeeding success across the study groups
timeFrame: Neonatal hospitalization assessment: At birth Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Correlation of Breastfeeding difficulties and postpartum breastfeeding support with breastfeeding success across the study groups
timeFrame: Assessment of breastfeeding difficulties and postpartum support: 4 days postpartum Breaffeidng success at 1 and 6 months after birth
measure: Correlation Between Mode of Delivery and Breastfeeding Success across the study groups
timeFrame: Mode of delivery assessment: At birth Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Correlation Between Postpartum Depression (EPDS) and Breastfeeding Success across the study groups
timeFrame: EPDS assessment: postnatally 1 and 6 months postpartum nad prenatally at 35-38 week of gestation Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Correlation Between Stressful Life Events (Holmes and Rahe Stress Scale) and Breastfeeding Success
timeFrame: Assessment of stressful life events: During pregnancy for the last year . Breastfeeding outcomes assessment: 1 and 6 months postpartum
Other outcomes:
measure: Correlation of Mother-child attachment and breastfeeding success
timeFrame: At 6 months postpartum
measure: Correlation of Neonatal and Infant Anthropometric parameters with breastfeeding success across the study groups
timeFrame: Neonatal anthropometric measurements: At birth Infant anthropometric measurements: 1 and 6 months postpartum Breastfeeding outcomes assessment: 1 and 6 months postpartum
measure: Correlation Between prenatal Cortisol Levels and Perceived Stress (PSS-14)
timeFrame: Prenatal cortisol & PSS-14 assessment: 15-20 and 35-38 weeks of gestation. Postnatal PSS-14 assessment: 1 and 6 months postpartum
measure: Relationship Between Cortisol Levels and Prenatal Maternal Stress
timeFrame: prenatally : between 15-20 week of gestation and 2) between 35-38 of gestation
measure: Correlation Between Neurotrophin Levels and Infant Behavior across study groups
timeFrame: Neurotrophin levels: Maternal serum (15-20 and 36-37 weeks gestation), Umbilical cord blood (at birth) Infant behavior: 6 months postpartum
measure: Correlation Between Neurotrophin Levels and Neonatal Behavior across the study groups
timeFrame: Neurotrophin levels: Maternal serum (15-20 and 36-37 weeks gestation), Umbilical cord blood (at birth) Neonatal behavior: First week of life
measure: Correlation Between Mother-Child Attachment and Infant Behavior
timeFrame: MPAS assessment: 6 months postpartum IBQ-R SF assessment: 6 months postpartum
Locations:
city: Athens
country: Greece
facility: Maternity Hospital "ELENA VENIZELOU"
state: Attica
Study officials:
affiliation: 1st_Dept.of Pediatrics_Athens_University_Medical School_Aghia Sophia_Children's Hosp_Athens_11527_GR
name: Tania Siahanidou Associate Professor in Pediatrics - Neonatology, MD, PhD
role: STUDY_DIRECTOR
affiliation: Neonatal Dept_Maternity Hosp_Elena Venizelou_2_Plateia Elenas Venizelou Str_Athens 115 21_GR
name: Aikaterini Fotiou, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: National & Kapodistrian Univ. of Athens_Research_Inst. for Mother-Child Health_Aghia Sophia_Hosp.
name: George P. Chrousos Prof. Emeritus of Pediatrics & Endocrinology_Academician, MD, MACP, MACE
role: STUDY_CHAIR
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