Régis Coutant

Amplitude of Pubertal Growth in Short Stature Children with Intrauterine Growth Retardation

Objective: Pubertal growth contributes to 15–18% of adult height. A blunted pubertal peak could contribute to short adult height in short children born with intrauterine growth retardation (IUGR). Design and Methods: Pubertal growth, from onset of puberty to final height, was investigated in 75 short IUGR children: 47 were treated with recombinant human growth hormone (GH) (tx) before pubertal onset (mean dose: 0.4 IU/kg/week); 28 were not treated (no-tx). They were compared with 98 normal children. Results: Puberty occurred later in IUGR children than in controls (boys 14.2 ± 1 years vs. 12.1 ± 0.8 years; girls 12 ± 1 years vs. 11.2 ± 0.8 years; p < 0.0001). In girls, total pubertal growth was similar in all three groups (tx: 19.3 ± 4.8 cm; no-tx 19.8 ± 4.9 cm; controls 20.2 ± 3.9 cm; non-significant). IUGR boys had a reduced pubertal growth (tx: 21.3 ± 6.2 cm; no-tx: 23.9 ± 6.1; controls 26.9 ± 3.9 cm; p < 0.05). The age at puberty onset was the major determinant of pubertal growth amplitude (boys: r = 0.53, p < 0.001; girls: r = 0.45, p < 0.001). IUGR children exhibited little catch-up growth during puberty. Conclusions: In the present study, we describe a delayed onset of puberty in short children born with IUGR. Moreover, prepubertal GH treatment was associated in boys with a decrease in the amplitude of the pubertal spurt, a finding that should be further evaluated in clinical trials.

Effect of Single and Multiple Courses of Prenatal Corticosteroids on 17-Hydroxyprogesterone Levels: Implication for Neonatal Screening of Congenital Adrenal Hyperplasia

Measurement of 17-hydroxyprogesterone (17-OHP) from filter-paper blood is widely used to screen for congenital adrenal hyperplasia (CAH). However, in pregnancies with an expected preterm delivery, prenatal treatment with steroids to induce pulmonary maturation could suppress the fetal adrenals and interfere with this screening. In 160 infants who were born between 25 and 35 wk of gestation, we measured 17-OHP in filter-paper blood at 72–96 h and compared the values between those who had not received antenatal steroids (n = 50) and those who had (n = 110). A single course of steroids was two 12-mg injections of betamethasone given within a 24-h interval: 30 infants received a half single course, 45 received a full single course, and 35 received multiple courses. Results are expressed as medians (25th percentile; 75th percentile). Blood 17-OHP differed significantly among groups: 23.7 (14.2; 30.7) nmol/L, 26.1 (15.0; 50.1) nmol/L, 20.1 (13.8; 29.1) nmol/L, and 14.9 (9.5; 26.2) nmol/L (for, respectively, no steroid, half a single course, a full single course, and multiple courses; p < 0.05, multiple comparisons with the Kruskal-Wallis test). However, only infants who were treated with multiple antenatal courses of steroids had lower blood 17-OHP than those who were untreated (p < 0.05 with the Mann-Whitney U test). In multiple regression analysis, steroid treatment and intrauterine growth retardation were significant negative predictors of blood 17-OHP, whereas respiratory distress syndrome was a significant positive predictor (multiple R = 0.50, p < 0.001). Multiple courses of steroids in preterm infants decrease 17-OHP values by ∼30% in filter-paper blood, thus raising the risk of false-negative results in screening programs for CAH.

Special Management of Insulin Lispro in Continuous Subcutaneous Insulin Infusion in Young Diabetic Children: A Randomized Cross-Over Study

Objective: To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII). Study Design: 27 very young diabetic children (age 4.6 ± 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH. Results: Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child’s daily life easier (p = 0.02) and preferred LP (p = 0.01). Conclusions: LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents’ satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time.

Maternal and Cord Blood Ghrelin in the Pregnancies of Smoking Mothers: Possible Markers of Nutrient Availability for the Fetus

Aims: To investigate the role of ghrelin in maternal and fetal metabolism, we determined its value in maternal smoking, a specific cause of reduced placenta function and fetal growth. Methods: In 85 normal term pregnancies, 42 in smoking and 43 in non-smoking mothers, we measured ghrelin in the maternal blood at the onset of labor and in the cord blood of their 85 singletons immediately after birth. We determined the relationships between ghrelin and placental GH (PGH), pituitary GH (pitGH), and IGF-I. Results: The newborns of smoking mothers weighed 0.24 kg less (p < 0.05) than those of non-smoking mothers. Cord blood ghrelin was 71% higher and PGH and cord blood IGF-I were 34% and 32% lower, respectively, in the pregnancies of smoking compared with non-smoking mothers (p < 0.05). Cord blood ghrelin was unrelated to pitGH and cord blood IGF-I. Maternal ghrelin was unchanged in smoking mothers, increased with maternal fasting duration (r = 0.26, p < 0.05), showed no correlation with PGH and negative correlation with cord blood IGF-I (r = –0.42, p < 0.01). Conclusion: The decrease in placental function and fetal growth in smoking mothers is associated with an increase in cord blood ghrelin, and no change in maternal ghrelin. Maternal ghrelin concentration increases with fasting, and is negatively correlated with cord blood IGF-I: it may signal a reduction in the level of nutrients available for placental transfer. No correlation supports a role for ghrelin in PGH or pitGH secretion.

Evolution of IGF-1 in Children Born Small for Gestational Age and with Growth Retardation, Treated by Growth Hormone Adapted to IGF-1 Levels after 1 Year

Aim: This study was designed to estimate the percentage of growth hormone (GH)-treated children born small for gestational age (SGA), with serum IGF-1 >2 SDS before and after GH dose adaptation. Methods: SGA boys aged 4–9 and girls aged 4–7 with a height <–2 SDS and an annual growth rate below the mean received a subcutaneous GH dose of 57 µg/kg/day for 2 years. The GH dose was to be decreased by 30% in children with serum IGF-1 >2 SDS at 12 months and on the previous sample. The GH dose could be reduced a second time to 35 µg/kg·day. IGF-1 and IGFBP-3 dosages were centralized. Results: Among the 49 (21 boys) children included in the study, 8 (16.3%) had an IGF-1 >2 SDS consecutively at 9 and 12 months (95% CI 7.3, 29.7). The GH dose was decreased in 6/8 children. However, IGF-1 levels were elevated at several nonconsecutive determinations in 45% (95% CI 28.4, 56.6) of the patients. Conclusion: A high IGF-1 level is observed in 45% of the GH SGA-treated children with a relatively high dose of GH. A 30% reduction in the GH dose causes a decrease in IGF-1 below 2 SDS in most children.