COPENHAGEN Minipuberty Study

NCT02784184 | Unknown

• 2 other identifiers: RH-H-15014876RH-2015-210-04146
• Study Type: observational
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

Minipuberty is a term used to describe the transient activation of the pituitary-gonadal axis 2-3 months after birth in both boys and girls. It is, however, not known why infants reach adult levels of reproductive hormones in early life, nor is the exact timing of the peak known. Furthermore, what determines the timing of peaks and suppressions of reproductive hormones from infancy throughout childhood and into adolescence remains to be elucidated. The study aims to described and evaluate dynamic changes in the hypothalamic-pituitary- gonadal axis in early postnatal life.

Conditions

Child Development; Disorders of Sex Development

Keywords

Hypothalamic-pituitary-gonadal axis

Outcome Measures

Primary Outcomes (9)

• Serum and urinary metabolites of reproductive hormones (e.g. steroid hormone metabolites and gonadotropins) (newborn)

  change/course serum and urinary metabolites

  3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth plus 40 days daily measurement (urine, female 40 days diaper study subgroup)

• Urinary metabolites of endocrine disrupting chemicals (e.g. phthalates, phenols, perfluorinated compounds and parabens) (newborn)

  change/course urinary metabolites

  3-7d, & 1,3,5,7,12m or 2,4,6,8,12m after birth plus 40 days daily measurement (urine, female 40 days diaper study subgroup)

• Basic clinical examination (newborn) (size and proportions)

  change/course: measurements of length, weight, skin folds and hip-waist ratio

  3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth

• Basic clinical examination (newborn) (pubertal staging)

  change/course: pubertal staging using Tanners classification (including testicular size in boys assessed by Prader's orchidometer and ultrasound

  3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth

• Basic clinical examination (newborn) (genitalia)

  change/course: classification of external genitalia (classification of genital tubercle, location of gonads, position of urethra, labia/scrotal fusion)

  3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth

• Basic clinical examination (newborn) (penile measurement)

  change/course: penile measurement with a ruler (in boys)

  3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth

• Basic clinical examination (newborn) (AGD)

  change/course: ano-genital distance (AGD) measured with a ruler

  3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth

• Genetic profiling

  Genotyping of different genetic loci (genetic variation of loci regulating hormone signalling, e.g. FSHB, etc.)

  single determination or 3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth

• Epigenetic profiling

  change/course: epigenetic variation of loci regulating hormone signalling

  single determination or 3-7d, and 1,3,5,7,12m or 2,4,6,8,12m after birth

Secondary Outcomes (8)

• Basic clinical examination (parents) (height)

  postpartal (within first 3 months)

• Basic clinical examination (parents) (weight)

  postpartal (within first 3 months)

• Basic clinical examination (parents)

  postpartal (within first 3 months)

• Pregnancy and perinatal outcome (newborn and mother)

  before birth and perinatal phase

• Medical history and exposure (parents) (basic)

  postpartal (within first year)

Study Arms (2)

1 year follow-up group

1 year follow-up group including 6 measurements

40 days diaper study subgroup

Subgroup of the "1 year follow-up group" including 15 girls undergoing daily measurement of urinary hormone excretion

Eligibility Criteria

• Age: Up to 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women, meeting the inclusion criteria, and the fathers-to-be followed at the Department of Obstetrics, Rigshospitalet. Further, parents and infants with disordered sexual development (DSD). These patients will be recruited via The Department of Growth and Reproduction, Rigshospitalet. Parents whose fetuses have been diagnosed prenatally with any DSD diagnosis or during the first 6 months of life will be invited to participate. Three groups of participants in this study: 1. A group of healthy infants 2. All infant patients diagnosed with or under evaluation for DSD 3. The parents of the healthy infants and DSD patients Number (approximately) of participants: 1. 200 healthy infants (100 boys and 100 girls) 2. unknown number of DSD infants that will be referred within a year to the Department of Growth and Reproduction; estimation: 15 DSD infants. 3. 400 parents of healthy infants (200 fathers and 200 mothers) - unknown number of parents of DSD patients

You may qualify if:

• Singleton pregnancy
• Maternal and paternal Caucasian origin
• Maternal pre-pregnancy BMI between 18 and 35 kg/m2
• No serious maternal illness, including no pre-existing maternal diabetes nor thyroid gland diseases
• Term pregnancy (week 37+0 to 41+7)
• No gestational diabetes
• No fetal malformations or chromosomal disorders
• Birth weight of child between 3rd and 97th percentile
• Only healthy infants born at term will be included in the study which all prospective participants will be informed of.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Department of Growth and Reproduction, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (2)

• Ljubicic ML, Busch AS, Upners EN, Fischer MB, Petersen JH, Raket LL, Frederiksen H, Johannsen TH, Juul A, Hagen CP. A Biphasic Pattern of Reproductive Hormones in Healthy Female Infants: The COPENHAGEN Minipuberty Study. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2598-2605. doi: 10.1210/clinem/dgac363.

  PMID: 35704034 DERIVED

• Ljubicic ML, Busch AS, Upners EN, Fischer MB, Main KM, Andersson AM, Johannsen TH, Hagen CP, Juul A. Dynamic changes in LH/FSH ratios in infants with normal sex development. Eur J Endocrinol. 2022 Jun 1;187(1):135-142. doi: 10.1530/EJE-21-0999.

  PMID: 35521767 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA EDTA-Blood Serum

MeSH Terms

Conditions

Disorders of Sex Development

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Anders Juul, Prof.

  Rigshospitalet, Denmark

  STUDY CHAIR

• Alexander S Busch, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anders Juul, MD, PhD, DmSc

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: May 27, 2016
• Study Start: August 1, 2016
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: February 15, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)