Minipuberty and Its Effects on Preterm Neonates

Infant, Newborn Clinical Trial

Official title:

Preliminary Study on Activation of the Hypothalamic-pituitary-gonadal Axis in Infancy (Minipuberty) and Its Effects on Catch-up Growth and Neurocognitive Outcome in Male Preterm Neonates Born at <32 Weeks of Gestational Age

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03858127
• Other study ID #: GN18ME668P
• Status: Not yet recruiting
• Start date: March 2019
• Est. completion date: August 2020

Study information

• Verified date: February 2019
• Source: NHS Greater Glasgow and Clyde
• Contact: Faisal Ahmed
• Phone: 07765422553
• Email: faisal.ahmed[@]glasgow.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

It is generally known that there are some hormonal changes during puberty, but the knowledge about the activation of the same hormonal axis in the first months of life is relatively recent and it is not completely understood.

From the first weeks of life there is a progressive increase in hormone levels and this post-natal activation is called "minipuberty". Particularly in males, testosterone and androgen levels are associated with development and maturation of the reproductive system as well as changes in the brain structure and behaviours. Recently, it has also been suggested that the increasing testosterone level during the first 6 months of life, as well as during puberty, translates into an increase of linear growth.

In preterm neonates these hormones rise higher and for longer than in full-term newborns, suggesting that its activity is evolutionarily regulated.

With this study researchers would like to investigate these changes and correlate hormone levels with linear growth and neurobehavioral development of preterm infants.

Description:

The activation of the hypothalamic-pituitary-gonadal axis (HPG) develops through three main moments: foetal life, first postnatal months (usually first 6 months of life) and finally during puberty. During the foetal period, there is a peak of gonadotropin secretion starting from the second trimester of gestation, and a subsequent suppression in the last weeks until birth, due to the negative feedback of placental estrogens. In male foetuses, LH levels exceed those of FSH. The foetal testis secretes testosterone and anti-müllerian hormone (AMH) from the 8th week of gestation and this is essential for masculinization. Formation of the active metabolite of testosterone, dihydrotestosterone, is required for the development of the prostate, penis and scrotum. Initial testicular development is intra-abdominal and the descent of the testes into the scrotum occurs in two phases. The first, transabdominal, phase is completed by 15 weeks of gestation. The second, inguinoscrotal, phase is usually completed by the end of the 35th week of gestation and this phase is androgen dependent. Testosterone levels are high in male foetuses between 10 and 20 weeks of gestational age, reaching adult values, and decrease thereafter towards term. In the same way LH and FSH levels decrease towards the end of gestation and are low at term in both sexes, due to the negative feedback of placental oestrogens.

A second post-natal HPG activation, also called "minipuberty", occurs at around 1 week of age, when placental hormones are cleared from the circulation. From the first weeks of life onwards there is a progressive increase in gonadotropins levels with a greater increase of FSH in females and of LH in males. During the "minipuberty" period gonadotropins levels have a peak at 3 months of life and a progressive exhaustion at around 6 months, except for FSH levels in females that can remain high even up to 3 or 4 years. Particularly in males, testosterone and androgen levels are associated with development and maturation of the reproductive system (penis and testis) as well as the androgynous cutaneous manifestations and a different neurobehavioral structure. Postnatal testosterone levels have been associated with male-type behaviour in 14-month-old infants, suggesting a role in neurobehavioral development.6 Recently, it has also been suggested how the increasing testosterone level during the first 6 months of life, as well as during puberty, translates into an increase of linear growth, regardless of the levels of growth hormone (GH) or insulin-like growth factor (IGF1).

Preterm birth does not seem to influence post-natal HPG activation, since that gonadotropin levels seem to raise up at the same time as term infants after the birth. The difference is that in preterm neonates these values last higher and longer than full-term newborns. According to the most recent longitudinal data, the post-natal activity of this axis declines at about the same in term neonates compared to premature infants with the same corrected gestational age, suggesting that the HPG activity is evolutionarily regulated. This higher increase of gonadotropin levels in premature males has been associated with a faster penile and testicular growth after birth compared to full-term boys. At last, in neonates small for gestational age (SGA) there are some evidence that post-natal FSH and testosterone levels are higher compared to infants with an adequate weight (AGA), although it is not known whether this correlates or have any influence on the catch-up growth of this subjects.

Understanding how "minipuberty" can influence linear growth, genitalia development and neurocognitive processes in preterm neonates has a significant scientific impact and could provide more information in understanding auxological and neurobehavioral developmental patterns of this population.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: August 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 72 Hours

Eligibility

Inclusion Criteria:

• Male preterm infants born =32 weeks of gestational age

• Written informed consent provided

Exclusion Criteria:

• Female sex assignment at birth

• Male preterm infants born >32 weeks of gestational age

• Male infants born at term

Related Conditions & MeSH terms

• Infant, Newborn

Intervention

Other:
• Collection of urine sample
Collection of urine sample for measurement of LH and FSH
• Examination of genitalia
Examination of genitalia
• Video messaging
Short video of infant recorded at home by the parents

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of urinary luteinising hormone	Urinary LH measured every week on fresh samples using electro- chemiluminescence immunoassay (ECLIA). Sample analysis will be performed by the Biochemistry Department of the Royal Hospital for Children in Glasgow using Abbott Architect i1600 instrument	18 months
Primary	Measurement of urinary follicle stimulating hormone	Urinary FSH measured every week on fresh samples using electro- chemiluminescence immunoassay (ECLIA). Sample analysis will be performed by the Biochemistry Department of the Royal Hospital for Children in Glasgow using Abbott Architect i1600 instrument	18 months
Secondary	Measurement of weight	Each baby will have a naked weekly weight as part of their routine care, using calibrated weighing scales	18 months
Secondary	Measurement of occipital frontal circumference	Each baby will have a weekly OFC measured as part of their routine care using a measuring tape	18 months
Secondary	Measurement of penile growth	Each baby will have a weekly penile length measured using a measuring tape	18 months
Secondary	Measurement of penile volume	Each baby will have penile volume measured weekly using an orchidometer	18 months
Secondary	Video recording of fidgety movements	Each baby will have a 4-5 minute video recording taken by their parents for Prechtl's Method For The Qualitative Assessment Of General Movements	18 months