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Year: 2006 | Volumen: 43 # Sup
Authors: Mauro Bozzola, Paola Travaglino and Graciela A. Martínez
Intrauterine growth retardation (IUGR), which is defined as less than 10 percent of predicted foetal weight for gestational age, may result in significant foetal morbidity and mortality if not properly diagnosed. The condition is most commonly caused by inadequate maternal-foetal circulation, with a resultant decrease in foetal growth. Less common causes include intrauterine infections such as cytomegalovirus and rubella, and congenital anomalies such as trisomy 21 and trisomy 18. When IUGR is recognized, it is important to try to correct reversible causes, although many of the conditions responsible for
IUGR are not amenable to antenatal therapy. Foetal growth is dependent on genetic, placental and maternal factors. The maternal-placental-foetal units act in harmony to provide the needs of the foetus while supporting the physiologic changes of the mother. Limitation of growth potential in the foetus is analogous to failure to thrive in the infant. Foetal growth restriction is the second leading cause of perinatal morbidity and mortality, followed only by prematurity. The incidence of intrauterine growth restriction is estimated to be approximately 5 percent in the general population. However, the incidence varies depending on the population under examination and the standard growth curves used as reference. If the growth-restricted foetus is identified and appropriate management instituted, perinatal mortality can be reduced, underling the need for assessment of foetal
growth at each prenatal visit. IUGR is the pathologic
counterpart of small-for-gestational-age. The latter includes foetuses that are small but have reached their appropriate growth potential. Many babies are simply genetically small and are otherwise normal. Growth-restricted babies, however, are often malnourished or dismorphic. Some women have a tendency to have constitutionally small babies. The most widely used definition of IUGR is a foetus whose estimated weight is below the 10th percentile for its gestational age. Approximately 70 percent of foetuses with a birth weight below the 10th percentile for gestational age are constitutionally small; in the remaining 30 percent, the cause of IUGR is pathologic. IUGR is usually classified as symmetric and asymmetric. Symmetric growth restriction implies a foetus whose entire body is proportionally small. Asymmetric growth restriction implies a foetus who is undernourished and is directing most of its energy to maintaining growth of vital organs, such as the brain and
heart, at the expenses of the liver, muscle and fat. This
type of growth restriction is usually the result of placental insufficiency. Accurate dating early in pregnancy
is essential for a diagnosis of IUGR. Ultrasound biometry is the gold standard for assessment of foetal size. Serial ultrasonograms are important for monitoring growth restriction, and management must be individualized. General management measures include treatment of maternal disease and good nutrition. Doppler velocimetry, previously discussed as a diagnostic technique for IUGR, has not found a place in routine antenatal surveillance. Epidemiological data indicate that 15-20% of infants born with intrauterine growth retard (IUGR) do not reach in adulthood the height of contemporaries born of appropriate weight for gestational age, thus comprising 14-22% of adults of low stature. Their final height, which is calculated to be about 161±8.0 cm in males and 147.6±7.2 cm in females, also results inferior to the target height determined on the basis of parents’ stature. Most infants born with IUGR (70-80%) present a catch-up growth at 6-12 months of age, or at least within their first two years of life. As a general rule, if the catch-up is completed within the second year, the final height may be within normal range, albeit at the lower limit. Otherwise, infants born with IUGR will not have ulterior chances of statural catch-up and will maintain until adulthood the percentile reached at the age of two or, in the case of early puberty, will compromise even further their growth rate. Many patients with IUGR present an increase in
secretion of growth hormone (GH) and of proteins transporting insulin-like growth factor-I (IGF-I), such as IGF-binding protein-1 (IGFBP-1), with low levels of insulin, IGF-I, IGF-II and IGFBP-3. This condition may be viewed as a form of GH-resistance secondary to malnutrition in utero. On the other hand, a decrease in the secretion of GH has been observed in these patients, consisting in alterations of its physiological rhythm of secretion, such as abnormal pulsatility and/or decreased integrated concentrations of the hormone, due to frequent but less intense peaks of release; these differences are often not detectable by classic stimulation tests. A disruption of the hypophysis- somatomedin axis has been found in IUGR patients that do not present a spontaneous catch-up in growth, thus justifying the first attempts of GH therapy. At the moment, no definitive conclusion may be
drawn on the efficacy of this treatment on final height, as case studies of a consistent number of patients with IUGR followed until adulthood are not yet available.
Children born SGA showing no spontaneous catch-up growth are known to be at risk for short stature in adulthood. The therapy with hGH results in improved growth rate and has been approved independently of GH deficiency. Previous studies have shown the growth promoting effect of two years of GH therapy in short prepubertal children born SGA.
At the start of treatment GH can be initiated with a dosage of 33 μg/Kg per day in children 3 year-aged, 45-50 μg/Kg per day at the age of 6-7 years or 67 μg/Kg
per day in the older ones. An Italian multicenter study suggested a double dosage of hGH during the second year of therapy to maintain a good growth rate. Among the metabolic side effect of GH therapy, insuline resistence has been proposed in SGA children mainly treated with GH with a normalization of glucose metabolism after a discontinuation of GH therapy. Asimilar effect on the lipidic metabolism has been observed in treated patients. Improved intellective performance was recently observed in SGA subjects after long-term GH treatment. The modest response in growth rate found in many IUGR patients treated with GH has led to the hypothesis that stunted growth of intrauterine origin may not be a single, well-defined condition, but rather the result of a hormonal resistance involving, in addition to GH, IGF-I and insulin.
The presence of metabolic sequels to IUGR has recently been highlighted by the finding, in adults born with an IUGR, of a higher incidence of coronary disease, hypertension and non-insulin-dependent diabetes, which has been linked to the insulin resistance mentioned above.
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