Fetal Brain Care: Therapies for Brain Neurodevelopment in Fetal Growth Restriction

Study Overview
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Brief Summary
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Singleton pregnancies being diagnosed of fetal growth restriction from 24 to 32.6 weeks of gestation will be randomized to two equally sized groups: maternal oral supplementation with Lactoferrin and DHA (Docosahexaenoic acid) or placebo.

Detailed Description
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Randomized controlled trial among pregnant women that have been diagnosed of fetal growth restriction. These women will be randomized in order to evaluate the impact of maternal supplementation with Lactoferrin and DHA on the neurodevelopment outcome of their babies. Main hypothesis: a prenatal intervention based on maternal supplementation with Lactoferrin and DHA improves neurodevelopment in fetal growth restriction. Secondary hypothesis are that a prenatal intervention based on maternal supplementation with Lactoferrin and DHA in fetal growth restriction improves fetal growth and improves perinatal morbidity and mortality.

Official Title
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Fetal Brain Care: Therapies for Brain Neurodevelopment in Fetal Growth Restriction

Conditions
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Fetal Growth Retardation, Intrauterine Growth Restriction

Intervention / Treatment
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* Dietary Supplement: Lactoferrin and DHA
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancies Non-malformed fetus Pregnancies with fetal growth restriction 24-32.6 weeks of gestation Exclusion Criteria: Chromosomal or structural abnormalities diagnosed during pregnancy or in the neonatal period Critical Doppler study suggesting the need for delivery within the next 14 days at the time of diagnosis: reverse end-diastolic velocity in the umbilical artery or ductus venosus pulsatility >95th centile Maternal mental or psychiatric disorders Maternal allergy to cow's milk protein

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Maternal supplementation with Lactoferrin and DHA<br>The intervention consists in the maternal oral administration of 1000mg of Lactoferrin and 1000mg of DHA daily | Dietary Supplement: Lactoferrin and DHA<br>* The intervention consists in the maternal oral administration of 1000mg of Lactoferrin and 1000mg of DHA daily<br>|
| Placebo Comparator: Placebo<br>Product with the same physical appearance and taste as the main intervention but without therapeutic effect | Other: Placebo<br>* Product with the same physical appearance and taste as the main intervention but without therapeutic effect<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bayley III scale at 24 months of age | Bayley III scale is and individually administered instrument that assesses infant development across five domains, including cognitive, language and motor competencies. Parent reported questionnaires are incorporated to assess social-emotional and adaptative behaviors. | 24 months of corrected postnatal age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortical development | Assessed by fetal brain magnetic resonance imaging. | 34 weeks of gestation | 
| Fetal brain volume | Assessed by fetal brain magnetic resonance imaging. | 34 weeks of gestation | 
| Corpus callosum area | Assessed by fetal neurosonography. | Enrolment, 32 and 36 weeks of gestation | 
| Neonatal weight | Birth weight | Delivery | 
| Perinatal morbidity and mortality | Development of one of the following conditions: pregnancy complications, perinatal mortality, metabolic acidosis and major neonatal morbidity. | Perinatal period: period ranging from 32 weeks of gestation (154 days) to the end of the first 4 weeks of neonatal life (28 days) | 
| Postnatal neurodevelopmental assessment | Neurodevelopmental assessment using the Bayley III scale at 6 and 24 months of corrected postnatal age, as described in the primary outcome. A complementary neurodevelopmental assessment will be carried out in collaboration with the Speech Acquisition and Perception Groups of the University Pompeu Fabra Barcelona. | Between 4 and 24 months of corrected postnatal age | 
| Occurrence of adverse effects | Record of side effects that may appear. Since intervention is usually well tolerated, we do not expect major side effects. | Through intervention (supplementation) completion, from enrolment to delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fetal Growth Retardation, Fetal Growth Restriction, Intrauterine Growth Restriction, Neurodevelopment, Lactoferrin, DHA