Minipuberty and Its Effects on Preterm Neonates
Minipuberty and Its Effects on Preterm Neonates
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.
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.
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