Portal de Periódicos da CAPES

Preterm Growth Restraint: A Paradigm That Unifies Intrauterine Growth Retardation and Preterm Extrauterine Growth Retardation and Has Implications for the Small-for-Gestational-Age Indication in Growth Hormone Therapy

2006; American Academy of Pediatrics; Volume: 117; Issue: 4 Linguagem: Inglês

10.1542/peds.2005-1705

1098-4275

Jan M. Wit, Martijn J.J. Finken, Monique Rijken, Francis de Zegher,

Gestational Diabetes Research and Management

Small for gestational age (SGA) is defined as a birth weight and/or length >2 SDs below the gender-specific population reference mean for gestational age. However, there is confusion about various aspects of this term, as recently discussed.1,2 The term “intrauterine growth retardation” (IUGR) is often used for the same condition but preferably should be restricted to poor growth during pregnancy according to intrauterine growth diagrams used in obstetrics.3 SGA after a normal duration of gestation (37–42 weeks) is usually followed by rapid growth after birth (catch-up growth). It has been demonstrated that almost 90% of term SGA infants catch up in height in the first 2 years of postnatal life.4,5On average, the human male has a birth length of 51 cm after term gestation and a final height, in the Netherlands, of 184 cm. Thus, in the 9 months before birth, he has reached almost 30% of his adult height potential. Fetal length velocity at midgestation is >10-fold higher than pubertal peak height velocity (Fig 1).Thus, very preterm infants are exposed to extrauterine life during a period that normally is characterized by rapid intrauterine growth. To survive, their energy expenditure shifts from growth-promoting actions to survival strategies to cope with the increased requirements of unintended postnatal life. Extrauterine growth retardation (EUGR) is often the result. Preterm infants whose mothers suffered from conditions such as preeclampsia are usually already growth-retarded at birth. Nonetheless, regardless of whether the child is born SGA, very preterm infants tend to be small at term, and a considerable proportion of them even meet criteria for SGA by that age. A study among 52 children born before 29 weeks' gestation showed that 13 (25%) had length at term below −2 SDs.6Thus, among nonsyndromatic children with growth retardation before term age, 3 major groups can be differentiated: According to current legislation across Europe, the second of these groups is excluded from growth hormone (GH) therapy in case of persistent short stature, because these children were excluded (for unspecified reasons) from the pivotal studies that were initiated around 1990 and were maintained up to adult height.7 Here, we question whether the time has come to update the SGA indication for GH therapy, which requires a birth weight or length below −2 SDs for gestational age, into a preterm-growth-restraint (PGR) indication, so that this group is no longer excluded. Approximately 10% of very preterm children have a height below −2 SDs at 4 to 5 years of age.6,8 This is similar to the number of term SGA infants who do not show postnatal catch-up growth.4Because neonatal intensive care is a relatively recent and rapidly evolving discipline, there was until now a virtual “absence of evidence” for analogies among the 3 aforementioned groups. Thanks to a set of recent data, this absence of evidence is gradually changing into “evidence of absence” of major differences between the endocrinologic-metabolic state of the second group versus that of the other 2 groups. To date, this evidence already includes key features such as body composition,9,10 insulin sensitivity,11 and blood pressure.12 Beyond the age of ∼6 to 8 years, the children in these 3 groups seem to resemble each other so closely that, in the absence of a perinatal history, they are virtually indistinguishable from each other on clinical, biochemical, endocrinologic, and metabolic grounds.Given that the short-term growth response to exogenous GH in this context may not be indicative of the long-term response,7 there are now 2 major ways to explore GH therapy in former premature infants with short stature: We suggest that pediatric societies including the American Academy of Pediatrics, the American Pediatric Society/Society for Pediatric Research, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Pediatric Endocrinology issue a statement on this specific topic. Below are a few elements to consider in the anticipated debate.