Low-Risk Pregnant Women at Full-Term GestationREMS-BONENCT06750523
Advancing Early Bone Health: New Frontiers for Osteoporosis Prevention
A study testing Cord blood sampling, urine sampling and Life style questionnaire in people with Low-Risk Pregnant Women at Full-Term Gestation and Healthy Fetal Population, run by University of Parma at 2 sites in Italy.
Trial summary
All factors that influence the peak bone mass achieved at skeletal maturity are important in determining an individual's risk of developing osteoporosis later in life. Bone health begins with maternal health and nutrition, which influence skeletal mass and bone density in utero. Read more about this study
- Who is it for?
- Ages 37 to 42 weeks
- Conditions the study is for
- Low-Risk Pregnant Women at Full-Term Gestation, Healthy Fetal Population, Healthy Neonatal Population
- What is being tested?
- Cord blood sampling, urine sampling and Life style questionnaire
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 2 sitesItaly
- Study dates
- 17 May 2023to Nov 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 37 to 42 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- term infants from low-risk pregnancy
- (37-42 weeks gestational age)
- Single pregnancy
- Absence of current or previous maternal diseases that could potentially interfere with bone metabolism (e.g., thyroid, kidney, liver disease)
- Absence of motor disability of the mother
- No previous history of recent, previous bone fractures or traumatic fractures (in the mother)
Show all 9Show fewer
- No intake of vitamin D or other medications during pregnancy
- Maternal age >18 years
- No diagnosis of osteopenia or osteoporosis according to the criteria of the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)
Who cannot join
- preterm infants
- Infants hospitalized since birth for special conditions
- infants with metabolic disorders
- infants with genetic syndromes
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Azienda Ospedaliero Universitaria "Gaetano Martino" di Messina
Messina, ME, 98125
Azienda Ospedaliero-Universitaria di Parma
Parma, 43126
About this study
Official title: Getting Bone Health Right From the Start: Innovative Technology and New Mechanims of Mother-fetus Cross Talk for Osteopenia and Osteporosis Prevention
All factors that influence the peak bone mass achieved at skeletal maturity are important in determining an individual's risk of developing osteoporosis later in life. Bone health begins with maternal health and nutrition, which influence skeletal mass and bone density in utero. The mechanisms underlying the effect of the intrauterine environment on bone health are currently unknown, but certainly include 'fetal programming' of oxidative stress and endocrine systems, as these influence skeletal growth and development later in life.
For the prevention of bone health, the challenges rely 1) in the need for new technology and software specific and applicable to the fetus and newborn; 2) in establishing the effect of environmental contaminants, in particular endocrine disruptors, oxidative stress and subsequent epigenetic changes in mothers and subsequently on the fetus, newborn and infant.
Read the detailed description
Maximising bone mass during skeletal growth has become the goal of primary prevention of osteopenia and osteoporosis. Any factor that might influence the peak bone mass attained during skeletal maturation is important in determining an individual's risk of developing osteoporosis later in life. Bone health begins with maternal health and nutrition, which influence skeletal mass and bone density in the foetus. The acquisition of peak bone mass is also genetically influenced by both parents. To date, there is some evidence that the risk of osteoporosis in later life may be determined by environmental exposures during intrauterine or early postnatal life. The mechanisms underlying the long-term effects of the intrauterine environment on bone health are currently unknown, but certainly include "fetal programming" of oxidative stress and endocrine systems that influence skeletal growth and development in utero and after birth.
Osteopenia is increasingly diagnosed in low birth weight infants. Intrauterine growth restriction (IUGR) further increases the risk of obesity and metabolic syndrome, conditions that significantly compromise bone quality. Recent studies have highlighted the central role of microRNAs (miRNAs) in bone growth and mineralisation, alongside peptides such as irisin and HMGB-1. These peptides are involved in glucose metabolism and the regulation of adipose and muscle tissue and have recently been linked to bone metabolism. MicroRNAs and long non-coding RNAs (lncRNAs) have gained attention for their ability to regulate gene expression post-transcriptionally, providing epigenetic modifications that influence growth plate and bone development. It remains unclear how maternal nutritional factors affect fetal bone mineral density (BMD) or how variations in fetal BMD may influence birth outcomes, such as spontaneous clavicle or skull fractures during operative delivery, and long-term bone mineralisation.
These findings highlight the importance of assessing skeletal status during the perinatal period. Early identification of conditions that affect bone mass or mineralisation and ongoing monitoring of bone development are essential to improve outcomes.
Radiofrequency echographic multi-spectrometry (REMS) technology has demonstrated its utility in the assessment of BMD in pregnant women. While few studies have investigated the use of transmission ultrasound to assess bone status in neonates, REMS technology shows great promise. Its advantages include the absence of ionising radiation, ease of use and, most importantly, the potential to conduct longitudinal studies of REMS patterns from the intrauterine period into the first year of life.
This innovative approach offers new opportunities to understand the maternal-fetal factors that influence bone health and to develop strategies to optimise bone development from the earliest stages of life.
The aims of the present study are A) To determine the feasibility of using REMS as a precise and innovative technology to assess the skeletal status of fetuses, neonates and children.
- To assess how maternal REMS patterns and her anthropometric and gestational data influence REMS parameters in the fetus, newborn and during the first year of life.
- To elucidate the relationships between early exposure to endocrine disrupters, oxidative stress and maternal diet as part of the in utero exposome and later body composition and bone health.
- Conditions
- Low-Risk Pregnant Women at Full-Term Gestation, Healthy Fetal Population, Healthy Neonatal Population
- Being tested
- Cord blood sampling, urine sampling, Life style questionnaire
- Keywords
- Bone mineral Density, Fetus, Newborns, Children, Osteoporosis, Environment, Oxidative stress, Endocrine disruptors
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cord blood samplingDiagnostic test
A cord blood sample will be taken at birth for analysis of oxidative stress markers, endocrine disruptors, and microRNAs.
urine samplingDiagnostic test
At one month of age, urine samples will be collected from newborns to analyze oxidative stress markers and endocrine disruptors.
Life style questionnaireBehavioural
At the time of enrollment, mothers will complete a specialized questionnaire designed to assess potential exposure to endocrine disruptors (EDCs) through diet, clothing, and the use of cosmetics and detergents.
| Study group | Role | What they receive |
|---|---|---|
| Mother and infants at term of physiologically gestation (<37 weeks) | Experimental | Assessment of bone mineral density (BMD) of the femur in the mother and fetus at term gestational age, and subsequently in the newborns at 48 hours after birth, at 1 month, at 3 months, at 6 months, and at 12 months of life, using REMS technology. Receives: Diagnostic Test: Cord blood sampling; Diagnostic Test: urine sampling; Behavioral: Life style questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Mineral Density (BMD)
The novel application of REMS technology in the fetal and neonatal population requires the construction of a reference database. Data from the first 100 enrolled fetuses will form the basis of this database, and the same approach will apply to newborns, with the initial 100 cases corresponding to the same fetal cohort. Echographic acquisitions of fetuses and newborns, obtained using REMS devices, will be anonymized and transferred to the subcontractor, who will adapt REMS configurations for pediatric use. This adaptation will enable the identification of target bone structures and provide densitometric outputs.
BMD values will be calculated for each age group, and from the first 100 cases, mean and standard deviation will be derived to construct a 6-point BMD reference curve, comprising fetuses (>37 and <42 weeks) and newborns (48 hours, 1, 3, 6, and 12 months). Z-scores will be used to assess bone growth, and separate gender-specific curves will be developed.
Measured: >37 and <42 weeks; 48 hours; 1, 3, 6, and 12 months
MicroRNA assay on umbilical cord blood
By TaqMan Advanced miRNA assays (Applied Biosystems) miRNAs will be quantified and normalized using hsa-miR-16-5p (Assay ID: 477860_mir) as endogenous control. Real-Time qRT-PCR will be used for the specific candidate miRNAs: miR-199a-5p, miR-140, miR-335-5p, mir-503-5p, miR-494-3p, mir-369-3p, mir-379-5p, as it has been recently shown that they vary in relationship to GH status, and are related to growth response.
Measured: at birth
Endocrine disruptors (EDCs) on umbilical cord blood at birth.
Thirteen different EDCs are assayed, namely: Di(2-ethylhexyl) phthalate and its oxidised metabolites (MEHP, 6-OH-MEHP, 5-carboxy-MEPP, 5-oxo MEHP, 5-OH-MEHP), Bisphenol (BP) A, BPS, BPF, polyciclic aromatic hydrocarbons, polychorodibenzophuranes and polichorodibenzo-p-dioxins, perfluoro-alchilic substances, gliphosate, and its main metabolite, parabens (methyl-, ethyl-, propyl-, butyl- esters of 4-Hydroxybenzoic acid), piretroid insecticides,heavy metals (Pb, Cr).
Measured: at birth
Endocrine disruptors (EDCs) on urine at 1 months of age.
Thirteen different EDCs are assayed, namely: Di(2-ethylhexyl) phthalate and its oxidised metabolites (MEHP, 6-OH-MEHP, 5-carboxy-MEPP, 5-oxo MEHP, 5-OH-MEHP), Bisphenol (BP) A, BPS, BPF, polyciclic aromatic hydrocarbons, polychorodibenzophuranes and polichorodibenzo-p-dioxins, perfluoro-alchilic substances, gliphosate, and its main metabolite, parabens (methyl-, ethyl-, propyl-, butyl- esters of 4-Hydroxybenzoic acid), piretroid insecticides,heavy metals (Pb, Cr).
Measured: 1 month
Oxidative stress (OS) profile
Oxidative stress (OS) profile will be evaluated by biomarkers of oxidative protein damage (Advanced Oxidation Protein Products, AOPP) and lipid peroxidation (Isoprostanes, IsoPs, malondialdehyde, MDA).
Measured: at birth, 1 month
Oxidative stress (OS) molecules
Non-enzymatic antioxidant molecules (vitamin E; glutathione, GSH, and ascorbic acid, AA) and enzymatic antioxidant molecules (superoxide dismutase, SOD, catalase, CAT, and glutathione peroxidase, GPx) will be evaluated by highly specific and sensitive methods, such as high resolution liquid chromatography (HPLC), and gas chromatography interfaced mass spectrometry (GC-MS).
Measured: at birth, 1 month
Lipid mediators involved in oxidative stress
The ELISA test will be used for the investigation of lipid metabolism and will evaluate specialised pro-resolving lipid mediators (Resolvin D1).
Measured: at birth, 1 month
Standard biochemical tests
calcium, phosphorus, alkaline phosphatase, PTH, vitamin D (25 OH), and IGF-I
Measured: at birth, 1 month
Exposure to endocrine disruptors (EDCs) related to diet, clothing and the use of cosmetics and detergents.
The questionnaire is an adaptation of the questionnaire drafted and already used as part of two previous projects "Phthalates and bisphenol A biomonitoring in Italianmother-childpairs: link between exposure and juvenile diseases' (LIFE PERSUADED) LIFE13 ENV/IT/000482; and 'Mother and infants dyads: lowering the impact of endocrine disrupting chemicals in milk for a healthy life2 (LIFE MILCH-LIFE18 ENV/EN/000460).
Measured: at the enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2024
- Study start17 May 2023
- Primary completionJun 2025 (estimated)
- Study completionNov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Low-Risk Pregnant Women at Full-Term GestationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Parma
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliero-Universitaria di Parma, Azienda Ospedaliera Universitaria Policlinico "G. Martino"
- Responsible party
- Principal investigator, Serafina Perrone, University of Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06750523
- Sponsor's protocol ID
- ID SIRER 5484
- Other IDs
- PNRR-MAD-2022-12376819
- Acronym
- REMS-BONE
- Status last verified
- Dec 2024
- First submitted
- 19 Dec 2024
- Last updated
- 1 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Heaney RP. BMD: the problem. Osteoporos Int. 2005 Sep;16(9):1013-5. doi: 10.1007/s00198-005-1855-y. Epub 2005 Mar 18. No abstract available.
PubMed 15776218Godfrey K, Walker-Bone K, Robinson S, Taylor P, Shore S, Wheeler T, Cooper C. Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy. J Bone Miner Res. 2001 Sep;16(9):1694-703. doi: 10.1359/jbmr.2001.16.9.1694.
PubMed 11547840Lanham SA, Roberts C, Perry MJ, Cooper C, Oreffo RO. Intrauterine programming of bone. Part 2: alteration of skeletal structure. Osteoporos Int. 2008 Feb;19(2):157-67. doi: 10.1007/s00198-007-0448-3. Epub 2007 Aug 18.
PubMed 17704965Dirkes RK, Welly RJ, Mao J, Kinkade J, Vieira-Potter VJ, Rosenfeld CS, Bruzina PS. Gestational and lactational exposure to BPA, but not BPS, negatively impacts trabecular microarchitecture and cortical geometry in adult male offspring. Bone Rep. 2021 Nov 3;15:101147. doi: 10.1016/j.bonr.2021.101147. eCollection 2021 Dec.
PubMed 34820485Papaioannou G. miRNAs in Bone Development. Curr Genomics. 2015 Dec;16(6):427-34. doi: 10.2174/1389202916666150817202425.
PubMed 27019617Bocheva G, Boyadjieva N. Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis. Interdiscip Toxicol. 2011 Dec;4(4):167-72. doi: 10.2478/v10102-011-0026-6.
PubMed 22319250Holroyd C, Harvey N, Dennison E, Cooper C. Epigenetic influences in the developmental origins of osteoporosis. Osteoporos Int. 2012 Feb;23(2):401-10. doi: 10.1007/s00198-011-1671-5. Epub 2011 Jun 9.
PubMed 21656266Zhang L, Tang Y, Zhu X, Tu T, Sui L, Han Q, Yu L, Meng S, Zheng L, Valverde P, Tang J, Murray D, Zhou X, Drissi H, Dard MM, Tu Q, Chen J. Overexpression of MiR-335-5p Promotes Bone Formation and Regeneration in Mice. J Bone Miner Res. 2017 Dec;32(12):2466-2475. doi: 10.1002/jbmr.3230. Epub 2017 Aug 28.
PubMed 28846804Perrone S, Santacroce A, Picardi A, Buonocore G. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases. World J Clin Pediatr. 2016 May 8;5(2):172-81. doi: 10.5409/wjcp.v5.i2.172. eCollection 2016 May 8.
PubMed 27170927Street ME, Bernasconi S. Endocrine-Disrupting Chemicals in Human Fetal Growth. Int J Mol Sci. 2020 Feb 20;21(4):1430. doi: 10.3390/ijms21041430.
PubMed 32093249Predieri B, Alves CAD, Iughetti L. New insights on the effects of endocrine-disrupting chemicals on children. J Pediatr (Rio J). 2022 Mar-Apr;98 Suppl 1(Suppl 1):S73-S85. doi: 10.1016/j.jped.2021.11.003. Epub 2021 Dec 15.
PubMed 34921754Degennaro VA, Brandi ML, Cagninelli G, Casciaro S, Ciardo D, Conversano F, Di Pasquo E, Gonnelli S, Lombardi FA, Pisani P, Ghi T. First assessment of bone mineral density in healthy pregnant women by means of Radiofrequency Echographic Multi Spectrometry (REMS) technology. Eur J Obstet Gynecol Reprod Biol. 2021 Aug;263:44-49. doi: 10.1016/j.ejogrb.2021.06.014. Epub 2021 Jun 15.
PubMed 34167032Basu S, Michaelsson K, Olofsson H, Johansson S, Melhus H. Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun. 2001 Oct 19;288(1):275-9. doi: 10.1006/bbrc.2001.5747.
PubMed 11594785Wang X, Liang T, Zhu Y, Qiu J, Qiu X, Lian C, Gao B, Peng Y, Liang A, Zhou H, Yang X, Liao Z, Li Y, Xu C, Su P, Huang D. Melatonin prevents bone destruction in mice with retinoic acid-induced osteoporosis. Mol Med. 2019 Aug 28;25(1):43. doi: 10.1186/s10020-019-0107-0.
PubMed 31462213Perrone S, Laschi E, Buonocore G. Oxidative stress biomarkers in the perinatal period: Diagnostic and prognostic value. Semin Fetal Neonatal Med. 2020 Apr;25(2):101087. doi: 10.1016/j.siny.2020.101087. Epub 2020 Jan 23.
PubMed 32008959
Study at a glance
From the registry record, last updated by the sponsor on 1 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Getting Bone Health Right From the Start: Innovative Technology and New Mechanims of Mother-fetus Cross Talk for Osteopenia and Osteporosis Prevention
- ClinicalTrials.gov ID
- NCT06750523
- Acronym / sponsor ID
- REMS-BONE / ID SIRER 5484
- Conditions
- Low-Risk Pregnant Women at Full-Term Gestation, Healthy Fetal Population, Healthy Neonatal Population
- Keywords
- Bone mineral Density, Fetus, Newborns, Children, Osteoporosis, Environment, Oxidative stress, Endocrine disruptors
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of ParmaUniversity, hospital or other
- Collaborators
- Azienda Ospedaliero-Universitaria di Parma, Azienda Ospedaliera Universitaria Policlinico "G. Martino"
- Study start
- 17 May 2023 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 27 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
All factors that influence the peak bone mass achieved at skeletal maturity are important in determining an individual's risk of developing osteoporosis later in life. Bone health begins with maternal health and nutrition, which influence skeletal mass and bone density in utero. The mechanisms underlying the effect of the intrauterine environment on bone health are currently unknown, but certainly include 'fetal programming' of oxidative stress and endocrine systems, as these influence skeletal growth and development later in life.
For the prevention of bone health, the challenges rely 1) in the need for new technology and software specific and applicable to the fetus and newborn; 2) in establishing the effect of environmental contaminants, in particular endocrine disruptors, oxidative stress and subsequent epigenetic changes in mothers and subsequently on the fetus, newborn and infant.
Detailed description
Maximising bone mass during skeletal growth has become the goal of primary prevention of osteopenia and osteoporosis. Any factor that might influence the peak bone mass attained during skeletal maturation is important in determining an individual's risk of developing osteoporosis later in life. Bone health begins with maternal health and nutrition, which influence skeletal mass and bone density in the foetus. The acquisition of peak bone mass is also genetically influenced by both parents. To date, there is some evidence that the risk of osteoporosis in later life may be determined by environmental exposures during intrauterine or early postnatal life. The mechanisms underlying the long-term effects of the intrauterine environment on bone health are currently unknown, but certainly include "fetal programming" of oxidative stress and endocrine systems that influence skeletal growth and development in utero and after birth.
Osteopenia is increasingly diagnosed in low birth weight infants. Intrauterine growth restriction (IUGR) further increases the risk of obesity and metabolic syndrome, conditions that significantly compromise bone quality. Recent studies have highlighted the central role of microRNAs (miRNAs) in bone growth and mineralisation, alongside peptides such as irisin and HMGB-1. These peptides are involved in glucose metabolism and the regulation of adipose and muscle tissue and have recently been linked to bone metabolism. MicroRNAs and long non-coding RNAs (lncRNAs) have gained attention for their ability to regulate gene expression post-transcriptionally, providing epigenetic modifications that influence growth plate and bone development. It remains unclear how maternal nutritional factors affect fetal bone mineral density (BMD) or how variations in fetal BMD may influence birth outcomes, such as spontaneous clavicle or skull fractures during operative delivery, and long-term bone mineralisation.
These findings highlight the importance of assessing skeletal status during the perinatal period. Early identification of conditions that affect bone mass or mineralisation and ongoing monitoring of bone development are essential to improve outcomes.
Radiofrequency echographic multi-spectrometry (REMS) technology has demonstrated its utility in the assessment of BMD in pregnant women. While few studies have investigated the use of transmission ultrasound to assess bone status in neonates, REMS technology shows great promise. Its advantages include the absence of ionising radiation, ease of use and, most importantly, the potential to conduct longitudinal studies of REMS patterns from the intrauterine period into the first year of life.
This innovative approach offers new opportunities to understand the maternal-fetal factors that influence bone health and to develop strategies to optimise bone development from the earliest stages of life.
The aims of the present study are A) To determine the feasibility of using REMS as a precise and innovative technology to assess the skeletal status of fetuses, neonates and children.
- To assess how maternal REMS patterns and her anthropometric and gestational data influence REMS parameters in the fetus, newborn and during the first year of life.
- To elucidate the relationships between early exposure to endocrine disrupters, oxidative stress and maternal diet as part of the in utero exposome and later body composition and bone health.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mother and infants at term of physiologically gestation (<37 weeks) | Experimental | Diagnostic Test: Cord blood sampling, Diagnostic Test: urine sampling, Behavioral: Life style questionnaireAssessment of bone mineral density (BMD) of the femur in the mother and fetus at term gestational age, and subsequently in the newborns at 48 hours after birth, at 1 month, at 3 months, at 6 months, and at 12 months of life, using REMS technology. |
Who may qualify
- Ages
- 37 to 42 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- term infants from low-risk pregnancy
- (37-42 weeks gestational age)
- Single pregnancy
- Absence of current or previous maternal diseases that could potentially interfere with bone metabolism (e.g., thyroid, kidney, liver disease)
- Absence of motor disability of the mother
Key exclusion criteria (4 listed)
- preterm infants
- Infants hospitalized since birth for special conditions
- infants with metabolic disorders
- infants with genetic syndromes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cord blood samplingA cord blood sample will be taken at birth for analysis of oxidative stress markers, endocrine disruptors, and microRNAs. | Diagnostic test | Mother and infants at term of physiologically gestation (<37 weeks) |
| urine samplingAt one month of age, urine samples will be collected from newborns to analyze oxidative stress markers and endocrine disruptors. | Diagnostic test | Mother and infants at term of physiologically gestation (<37 weeks) |
| Life style questionnaireAt the time of enrollment, mothers will complete a specialized questionnaire designed to assess potential exposure to endocrine disruptors (EDCs) through diet, clothing, and the use of cosmetics and detergents. | Behavioural | Mother and infants at term of physiologically gestation (<37 weeks) |
Primary outcome
Bone Mineral Density (BMD)
Time frame: >37 and <42 weeks; 48 hours; 1, 3, 6, and 12 months
The novel application of REMS technology in the fetal and neonatal population requires the construction of a reference database. Data from the first 100 enrolled fetuses will form the basis of this database, and the same approach will apply to newborns, with the initial 100 cases corresponding to the same fetal cohort. Echographic acquisitions of fetuses and newborns, obtained using REMS devices, will be anonymized and transferred to the subcontractor, who will adapt REMS configurations for pediatric use. This adaptation will enable the identification of target bone structures and provide densitometric outputs. BMD values will be calculated for each age group, and from the first 100 cases, mean and standard deviation will be derived to construct a 6-point BMD reference curve, comprising fetuses (>37 and <42 weeks) and newborns (48 hours, 1, 3, 6, and 12 months). Z-scores will be used to assess bone growth, and separate gender-specific curves will be developed.
MicroRNA assay on umbilical cord blood
Time frame: at birth
By TaqMan Advanced miRNA assays (Applied Biosystems) miRNAs will be quantified and normalized using hsa-miR-16-5p (Assay ID: 477860_mir) as endogenous control. Real-Time qRT-PCR will be used for the specific candidate miRNAs: miR-199a-5p, miR-140, miR-335-5p, mir-503-5p, miR-494-3p, mir-369-3p, mir-379-5p, as it has been recently shown that they vary in relationship to GH status, and are related to growth response.
Endocrine disruptors (EDCs) on umbilical cord blood at birth.
Time frame: at birth
Thirteen different EDCs are assayed, namely: Di(2-ethylhexyl) phthalate and its oxidised metabolites (MEHP, 6-OH-MEHP, 5-carboxy-MEPP, 5-oxo MEHP, 5-OH-MEHP), Bisphenol (BP) A, BPS, BPF, polyciclic aromatic hydrocarbons, polychorodibenzophuranes and polichorodibenzo-p-dioxins, perfluoro-alchilic substances, gliphosate, and its main metabolite, parabens (methyl-, ethyl-, propyl-, butyl- esters of 4-Hydroxybenzoic acid), piretroid insecticides,heavy metals (Pb, Cr).
Endocrine disruptors (EDCs) on urine at 1 months of age.
Time frame: 1 month
Thirteen different EDCs are assayed, namely: Di(2-ethylhexyl) phthalate and its oxidised metabolites (MEHP, 6-OH-MEHP, 5-carboxy-MEPP, 5-oxo MEHP, 5-OH-MEHP), Bisphenol (BP) A, BPS, BPF, polyciclic aromatic hydrocarbons, polychorodibenzophuranes and polichorodibenzo-p-dioxins, perfluoro-alchilic substances, gliphosate, and its main metabolite, parabens (methyl-, ethyl-, propyl-, butyl- esters of 4-Hydroxybenzoic acid), piretroid insecticides,heavy metals (Pb, Cr).
Oxidative stress (OS) profile
Time frame: at birth, 1 month
Oxidative stress (OS) profile will be evaluated by biomarkers of oxidative protein damage (Advanced Oxidation Protein Products, AOPP) and lipid peroxidation (Isoprostanes, IsoPs, malondialdehyde, MDA).
Oxidative stress (OS) molecules
Time frame: at birth, 1 month
Non-enzymatic antioxidant molecules (vitamin E; glutathione, GSH, and ascorbic acid, AA) and enzymatic antioxidant molecules (superoxide dismutase, SOD, catalase, CAT, and glutathione peroxidase, GPx) will be evaluated by highly specific and sensitive methods, such as high resolution liquid chromatography (HPLC), and gas chromatography interfaced mass spectrometry (GC-MS).
Lipid mediators involved in oxidative stress
Time frame: at birth, 1 month
The ELISA test will be used for the investigation of lipid metabolism and will evaluate specialised pro-resolving lipid mediators (Resolvin D1).
Standard biochemical tests
Time frame: at birth, 1 month
calcium, phosphorus, alkaline phosphatase, PTH, vitamin D (25 OH), and IGF-I
Exposure to endocrine disruptors (EDCs) related to diet, clothing and the use of cosmetics and detergents.
Time frame: at the enrollment
The questionnaire is an adaptation of the questionnaire drafted and already used as part of two previous projects "Phthalates and bisphenol A biomonitoring in Italianmother-childpairs: link between exposure and juvenile diseases' (LIFE PERSUADED) LIFE13 ENV/IT/000482; and 'Mother and infants dyads: lowering the impact of endocrine disrupting chemicals in milk for a healthy life2 (LIFE MILCH-LIFE18 ENV/EN/000460).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2025.
- Background: PubMed 15776218Heaney RP. BMD: the problem. Osteoporos Int. 2005 Sep;16(9):1013-5. doi: 10.1007/s00198-005-1855-y. Epub 2005 Mar 18. No abstract available.
- Background: PubMed 11547840Godfrey K, Walker-Bone K, Robinson S, Taylor P, Shore S, Wheeler T, Cooper C. Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy. J Bone Miner Res. 2001 Sep;16(9):1694-703. doi: 10.1359/jbmr.2001.16.9.1694.
- Background: PubMed 17704965Lanham SA, Roberts C, Perry MJ, Cooper C, Oreffo RO. Intrauterine programming of bone. Part 2: alteration of skeletal structure. Osteoporos Int. 2008 Feb;19(2):157-67. doi: 10.1007/s00198-007-0448-3. Epub 2007 Aug 18.
- Background: PubMed 34820485Dirkes RK, Welly RJ, Mao J, Kinkade J, Vieira-Potter VJ, Rosenfeld CS, Bruzina PS. Gestational and lactational exposure to BPA, but not BPS, negatively impacts trabecular microarchitecture and cortical geometry in adult male offspring. Bone Rep. 2021 Nov 3;15:101147. doi: 10.1016/j.bonr.2021.101147. eCollection 2021 Dec.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cord blood sampling, urine sampling and Life style questionnaire in people with Low-Risk Pregnant Women at Full-Term Gestation and Healthy Fetal Population, run by University of Parma at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone Mineral Density (BMD) (time frame: >37 and <42 weeks; 48 hours; 1, 3, 6, and 12 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06750523, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2025.