Small For Gestational Age Girls Research Articles

Catch-Up Growth as a Risk Factor for Rapid Weight Gain, Earlier Menarche and Earlier Pubertal Growth Spurt in Girls Born Small for Gestational Age (SGA)—A Longitudinal Study

Most children born small for gestational age (SGA) have rapid postnatal growth. Despite its positive aspects, catch-up growth may affect the level of adipose tissue in the pre-pubertal and pubertal periods and therefore affect the age of puberty. The aim of this study was to determine the associations between size at birth, catch-up growth in infancy, BMI in peripubertal period, age at menarche, and the parameters of adolescent growth spurt of body height in girls born SGA. For 297 girls (22.6% SGA; 77.4% appropriate for gestational age (AGA)) complete body weight and height measurements and age at menarche were obtained. Adolescent growth spurt parameters were estimated using the JPA2 model (AUXAL SSI 3.1). Calculations were made in the Statistica 13 program using the Kruskal-Wallis and Kaplan-Meier tests. Girls born SGA with catch-up had the highest BMIs at the age of 8 years (H = 94.22, p < 0.001) and at menarche (H = 58.21, p < 0.001), experienced menarche earliest (H = 21.77, p < 0.001), same as the onset (H = 6.54, p = 0.012) and peak height velocity (H = 11.71, p = 0.003) of their adolescent growth spurt compared to SGA girls without catch-up and AGA girls. In SGA girls, catch-up growth has far-reaching consequences such as increased risk of fat accumulation and a rapid transition to puberty.

Demographic and Clinical Features of Small-for-Gestational-Age Infants Born to Mothers With Gestational Diabetes Mellitus.

We studied the demographic and clinical characteristic, risk factors, outcomes of full-term small-for-gestational-age (SGA) infants born to mothers with gestational diabetes mellitus (GDM) in China. A retrospective case-control study that included 1981 SGA infants was conducted; the demographic and clinical data between SGA infants born to mothers with and without GDM were compared. Of 383 SGA infants born to mothers with GDM, 221 (57.7%) were female, and the incidence of these infants was 1 in 155 live births. The risk of SGA siblings (RR, 1.88; 95% CI, [1.23–2.86]), low 1- and 5-min Apgar scores (RR,2.04 and 4.21; 95%CI [1.05–4.00] and [1.05–16.89], respectively), early thrombocytopenia (RR, 3.39; 95%CI, [1.33–8.64]), hypoglycemia(RR, 2.49; 95%CI, [1.55–3.98]), and hypoxic-ischemic encephalopathy (RR,5.61; 95%CI, [1.25–25.18]) were increased in SGA infants born to mothers with GDM compared to SGA infants born to mothers without GDM. SGA girls born to mothers with GDM had a significantly higher ratio of catch-up growth (CUG) (RR, 1.73; 95%CI, [1.18–2.54]) in the first year of life. These results show that genetic factors may be one of the etiologies of SGA infants born to mothers with GDM; and these infants have more adverse perinatal outcomes compared to SGA infants born to mothers without GDM. SGA girls born to mothers with GDM had accelerated CUG in the first year of life.

Maternal selenium deficiency during gestation is positively associated with the risks for LBW and SGA newborns in a Chinese population.

Maternal selenium (Se) deficiency is associated with some adverse pregnant outcomes. However, it remains controversial whether maternal Se deficiency during gestation enhances the risks for low-birth-weight (LBW) and small-for-gestational-age (SGA) newborns. For our cohort study, total 3133 mother-and-infant pairs were selected. Maternal serum Se concentration was detected by graphite furnace atomic absorption spectrometry. According to international references for maternal serum Se concentration, subjects were divided into Se deficiency (<45.0 μg/L), Se insufficiency (45.0-94.9 μg/L) and Se sufficiency (≥95.0 μg/L). There was a positive relation of maternal serum Se concentration in gestation and neonatal birth weight. Further analysis showed that the risks for LBW and SGA in SD group were significantly higher than that in SI and SS group, the adjusted ORs for LBW and SGA newborns were 1.87 (95%CI: 1.02, 3.45; P = 0.04) and 1.47 (95%CI: 1.07, 2.02; P = 0.02) in SI group, and 3.92 (95%CI: 2.03, 7.57; P < 0.001) and 2.77 (95%CI: 1.92, 4.02; P < 0.001) in SD group compared to SS group. In different gender subgroup, positive relations were observed between maternal Se deficiency and the risk for LBW girls, as well as the risks for both SGA girls and boys. Maternal Se deficiency in gestation was positively associated with the risk for LBW girls, as well as the risks for both SGA girls and boys.

Sex Hormones, Gonad Size, and Metabolic Profile in Adolescent Girls Born Small for Gestational Age with Catch-up Growth.

To characterize and compare sex hormone concentrations, and uterine and ovarian volumes in adolescent girls born small for gestational age (SGA) who had experienced catch-up growth and girls born at a size appropriate for gestational age (AGA), and to investigate the association between these parameters and glucose metabolism, perinatal factors, and early growth. A prospective, longitudinal, observational study from birth until adolescence. Mean age at final assessment was 12.7±0.1years. We followed 55 girls (20 SGA, 35 AGA). Sex hormone concentrations (gonadotropins, estradiol, testosterone, and sex hormone binding globulin) were analyzed, and the oral glucose tolerance test conducted. Uterine and ovarian sizes were assessed using pelvic ultrasound. Uterine and ovarian volumes were smaller in SGA-born compared with AGA-born girls (P=.013 and P=.039, respectively). SGA girls had lower sex hormone binding globulin levels (P=.039) and higher testosterone levels (P=.003), free androgen index (P<.001), and glycemia 2hours post glucose load (P=.005) compared with AGA-born girls. Birth weight and early infancy height velocity explained 37.4% of variation in ovarian volume (P=.004), and body mass index at birth, increase in peripheral skinfold thickness during second year of life, and early childhood height velocity explained 43.2% of variation in testosterone levels in adolescence (P=.006). SGA-born girls who experienced catch-up growth remain at risk of biochemical hyperandrogenism in adolescence, and have reduced uterine and ovarian volumes, which might influence future reproductive function. Ovarian size and androgen levels in adolescence might be influenced by early growth and subcutaneous fat deposition.

MON-241 Relationship between Final Height and Birth Weight after Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Central Precocious Puberty

Objectives: Small for gestational age (SGA) children may present an earlier onset of pubertal development, advanced bone maturation and reduced final height. The aim of this study was to compare the clinical parameters such as final adult height (FAH) and menarche with birth weight in girls with idiopathic precocious puberty (PP) treated with gonadotropin releasing hormone agonist (GnRHa). Subjects and methods: We retrospectively reviewed the medical records of 69 girls with PP who have reached FAH in a long-term trial of GnRHa treatment. The subjects were divided into SGA group and appropriated for gestational age (AGA) group. Anthropometric and endocrine parameters were obtained at diagnosis, at 6 months, and at cessation of GnRHa treatment. We investigated chronological age (CA), bone age (BA), BA / CA ratio, height and height SDS, predicted adult height (PAH-calculated with average table of BP method), PAH SDS, PAHa (calculated with advanced table of BP method), basal and stimulated gonadotropin levels, duration of treatment, duration of menarche, and FAH after treatment. The statistical significances of the clinical parameters between the two groups were compared. Results: The BA at the time of diagnosis was higher in SGA than in AGA (p <0.05). In the SGA, PAH SDS and PAHa were lower than those of AGA (p <0.05), but there was no significant difference in FAH between two groups. The FAH after GnRHa treatment was higher than PAH at diagnosis between SGA and AGA groups (p <0.05) . Body mass index was higher at the end of treatment in SGA group than in AGA (p <0.05). In addition, it was confirmed that the menarche was fast after treatment in SGA than in AGA (p <0.05). Target height, height SDS at diagnosis, PAH at diagnosis, and height SDS at end of treatment were found to be factors affecting FAH (p <0.05) . Conclusion: SGA girls with PP have increased bone age and rapid menarche than those of AGA group. But FAH after GnRHa treatment was not difference between the SGA and AGA groups. GnRHa treatment in SGA with PP may be helpful in improving FAH, and further large - scale studies will be needed in the future.

Brown adipose tissue in prepubertal children: associations with sex, birthweight, and metabolic profile.

Individuals born small-for-gestational age (SGA), especially those who experience postnatal catch-up growth, are at increased risk for developing endocrine-metabolic abnormalities before puberty. In adults, brown adipose tissue (BAT) has been associated with protection against metabolic disorders, such as obesity, type 2 diabetes, and dyslipidaemia. Here, we assessed for the first time whether BAT activation differs between prepubertal children born SGA or appropriate-for-gestational age (AGA). The study population consisted of 86 prepubertal children [41 AGA and 45 SGA; age (mean ± SEM), 8.5 ± 0.1 years], recruited into two prospective longitudinal studies assessing endocrine-metabolic status and body composition in infancy and childhood. The temperature at the supraclavicular region (SCR) before and after a cold stimulus was measured by infrared thermal imaging, and the area of thermally active SCR (increase after cold challenge, ΔAreaSCR) was calculated as a surrogate index of BAT activation. The results were correlated with clinical, endocrine-metabolic, and inflammation variables, and with visceral and hepatic adiposity (assessed by Magnetic Resonance Imaging). No differences in BAT activation index, as judged by ΔAreaSCR, were found between AGA and SGA children. However, girls showed higher baseline and post-cold induction AreaSCR than boys (both p ≤ 0.01). An interaction between gender and birth weight subgroup was observed for BAT activation; AGA girls increased significantly the ΔAreaSCR as compared to AGA boys; this increase did not occur in SGA girls vs SGA boys. Cold-induced ΔAreaSCR negatively correlated with HOMA-IR, us-CRP, liver volume, and liver fat. Prepubertal AGA girls had significantly greater BAT activation index as compared to AGA boys; this difference was not observed in SGA subjects. Higher BAT activation associated with a lower amount of visceral fat and with a favorable metabolic profile. Long-term follow-up is needed to determine whether those differences relate to pubertal timing, and to the development of obesity and metabolic disorders.

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age

To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. Not applicable. A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. EudraCT 2005-001507-19.

Intrauterine growth restriction - a population-based study of the association with academic performance and psychiatric health.

To investigate whether intrauterine growth restriction (IUGR), resulting in small for gestational age (SGA) infants, is associated with increased susceptibility to psychiatric problems and academic impairment in late teens. A cohort of all 10th-grade students in Oslo, Norway, followed up between 2001 and 2004 (n=2131), was linked with foetal growth data. IUGR was considered equal to SGA at the lowest 2.5th, 5th, and 10th percentiles and appropriate for gestational age (AGA) as the highest 90th percentile. Mental health was evaluated using the Hopkins Symptoms Check List and the Strength and Difficulties Questionnaire, and academic achievements and ambitions were self-reported by the students. Psychiatric problems were equally prevalent in all groups. However, the SGA girls performed inferiorly compared to their AGA peers in the school subjects English [3.6 vs 3.9 (p=0.03)], mathematics [4.0 vs 4.3 (p=0.01)] and social science [4.2 vs 4.4 (p=0.05)], but not for Norwegian. This association was not observed in boys. There was an association between academic impairment and prematurity, occurring more frequently among immigrants (p<0.001). SGA had a small negative impact on academic achievements in adolescent girls, but not boys. There was no association between SGA and psychiatric problems in either gender.

Leptin may enhance hepatic insulin sensitivity in children and women born small for gestational age

ObjectiveChildren born small for gestational age (SGA) are at risk for developing type 2 diabetes. Lipodystrophy leads to early type 2 diabetes and leptin reverses the metabolic consequences of the disease. Low IGF-binding protein 1 (IGFBP1) can predict the development of type 2 diabetes. The aim of this study was to determine leptin, insulin, and IGFBP1 in children and adult women born preterm or SGA to evaluate the role of leptin as a compensatory mechanism in insulin resistance development.MethodsSeventy-six children (8.5–10 years, 41 girls and 35 boys) and 45 women (23–30 years) were studied. The children comprised subjects born appropriate for gestational age (<30 gestational weeks) (n=22), born SGA at term (n=23), and full-term normal-weight controls (n=31). Among the women, the corresponding figures were, n=10, n=18, and n=17 respectively. Fasting levels of IGFBP1, leptin, insulin, and IGF1 were determined and total adiponectin only in women.ResultsIn girls and women, term SGA subjects had higher leptin levels in relation to BMI SDS (P=0.042 and P=0.03 respectively). More than half of IGFBP1 variability was explained by leptin and insulin in children. In term SGA women, IGFBP1 level was lower compared with controls (P=0.012) and the regression line of IGFBP1 on insulin was suppressed below −1 s.d. of a reference material.ConclusionLeptin levels were elevated in term SGA girls and women, in particular in adult women, but not found in preterm girls and women. IGFBP1 was lower in term SGA women. In children, leptin and insulin were strong suppressors of IGFBP1. We speculate that higher leptin levels could be a protective event to enhance hepatic insulin sensitivity.

Catch-up growth in girls born small for gestational age precedes childhood progression to high adiposity

To study across childhood the features of small for gestational age (SGA) girls with spontaneous catch-up growth. Longitudinal study (age 2-8 years). University hospital. Post-catch-up SGA girls (n = 18) versus healthy control girls born appropriate for gestational age (AGA; n = 13). None. Height, weight, fasting glucose, insulin, IGF-I, high-molecular-weight (HMW) adiponectin, LDL and HDL cholesterol, triglycerides, body composition by absorptiometry (2-8 years); visceral fat by magnetic resonance imaging (6-8 years); bone age (by automated reading), sex hormone-binding globulin, DHEAS, and leptin (8 years). At age 2 years, AGA and SGA girls were comparable for all study markers. Between 2 and 8 years, girls were prepubertal; AGA and SGA girls gained height, lean mass, and bone mineral content similarly; other outcomes diverged so that, at age 8, SGA girls had markedly higher levels of circulating insulin, IGF-I, DHEAS, LDL cholesterol, and leptin; lower HMW adiponectin and SHBG levels; more total and visceral fat (without being obese); and an older bone age. After completing catch-up growth and before starting puberty, SGA girls develop an ensemble that includes not only central adiposity, hyperinsulinemia, and hypoadiponectinemia but also hyperleptinemia, dyslipidemia, lower SHBG and higher DHEAS levels, and faster bone maturation.

Anti-Mullerian hormone in short girls born small for gestational age and the effect of growth hormone treatment

Background Fetal growth restriction is thought to negatively influence reproductive function in later life. Serum anti-Müllerian hormone (AMH) is a marker of the primordial follicle pool. The objectives of this study were to evaluate the effect of being born small for gestational age (SGA) on serum AMH levels and to investigate the effect of growth hormone (GH) treatment on serum AMH levels in short SGA girls. METHODS Serum AMH levels were investigated in 246 prepubertal girls aged 3-10 years: 119 untreated short SGA and 127 healthy controls. Associations between AMH levels and clinical characteristics were analysed using multiple regression analyses. In addition, we investigated the effect of GH treatment on serum AMH levels in short SGA girls. RESULTS Serum AMH levels were similar in short SGA and healthy control girls (P= 0.95). In short SGA girls, AMH levels were not significantly influenced by birth weight standard deviation score (SDS), birth length SDS and gestational age, even after adjustment for age, height SDS and body mass index (BMI) SDS at sampling, socio-economic status and maternal smoking during gestation. Serum AMH levels did not change during 4 years of GH treatment in short SGA girls (P= 0.43). ConclusionS Serum AMH levels in prepubertal short SGA girls are similar to healthy controls, indicating that the follicle pool is not compromised due to SGA birth. GH treatment has no effect on AMH levels in short SGA girls.

Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA)

Several studies showed a decrease in height velocity during GnRH analogue (GnRHa) treatment. No information is available on GH levels during GnRHa treatment in short SGA girls. To study overnight GH profiles and IGF-I and IGFBP-3 levels in girls with Tanner stage 2 and stage 3, before and after 3 months of GnRHa treatment, and to compare levels with those found in prepubertal short SGA girls. Twenty-four pubertal and 16 prepubertal short SGA girls. After baseline overnight GH profiles, pubertal girls received leuprorelide acetate depots of 3.75 mg subcutaneously every 4 weeks. GH, IGF-I and IGFBP-3 levels. At baseline, GH levels were comparable to levels found in prepubertal short SGA girls and IGF-I and IGFBP-3 SDS were significantly below the population mean. After 3 months of GnRHa treatment, AUC(0) (P = 0.02), mean (P = 0.02) and maximum GH levels (P = 0.008) had significantly decreased. Mean GH levels were significantly lower than in prepubertal short SGA girls (P = 0.03). Eight girls with more than 40% decrease in mean GH levels also had a significantly greater decrease in IGF-I and IGFBP-3 levels. Mean and maximum GH levels at baseline correlated significantly with those after 3 months of GnRHa treatment. Short SGA girls lack the normal increase in GH levels seen in puberty and have reduced IGF-I and IGFBP-3 levels, which might explain their reduced pubertal growth spurt. GnRHa treatment led to a significant reduction in GH levels. Therefore, combining GnRHa treatment with GH treatment might improve adult height of short SGA girls.

Preterm birth or foetal growth impairment and psychiatric hospitalization in adolescence and early adulthood in a Swedish population‐based birth cohort

Preterm birth and restricted foetal growth are related to symptoms of psychiatric disorder. Our aim was therefore to investigate possible relations between being born preterm and/or small for gestational age (SGA) and later psychiatric hospitalization. A population-based registry study of psychiatric hospitalization of in total 155,994 boys and 148,281 girls born in Sweden in 1973-1975. The risk of hospitalization for all mental disorders was increased for preterm SGA boys (OR 2.19, 95% CI 1.49-3.21); at-term SGA boys (OR 1.55, 95% CI 1.34-1.79); at-term SGA girls (OR 1.31, 95% CI 1.15-1.50). At-term SGA boys and girls suffered increased risk of anxiety and adjustment disorders (OR 1.70, 95% CI 1.18-2.45 and OR 1.49, 95% CI 1.14-1.94). Preterm SGA boys were at risk of personality disorders (OR 3.30, 95% CI 1.16-9.41) and psychotic disorders (OR 4.36, 95% CI 1.85-10.30). The results show a relationship between being born SGA and later psychiatric hospitalization, where preterm birth and male gender seem to increase the risk.

Circulating renin–angiotensin system and catecholamines in childhood: is there a role for birthweight?

There have been only a few reports on the sympathoadrenal and renin-angiotensin systems in children of small gestational age. The purpose of the present study was to investigate plasma levels of ACE (angiotensin-converting enzyme) activity, angiotensin and catecholamines in 8- to 13-year-old children and to determine whether there are correlations between the components of these systems with both birthweight and BP (blood pressure) levels. This clinical study included 66 children (35 boys and 31 girls) in two groups: those born at term with an appropriate birthweight [AGA (appropriate-for-gestational age) group, n=31] and those born at term but with a small birthweight for gestational age [SGA (small-for-gestational age) group, n=35]. Concentrations of angiotensin, catecholamines and ACE activity were determined in plasma. Circulating noradrenaline levels were significantly elevated in SGA girls compared with AGA girls (P=0.036). In addition, angiotensin II and ACE activity were higher in SGA boys (P=0.024 and P=0.050 respectively). There was a significant association of the circulating levels of both angiotensin II and ACE activity with BP levels in our study population. Although the underlying mechanisms that link restricted fetal growth with later cardiovascular events are not fully understood, the findings in the present study support the link between low birthweight and overactivity of both sympathoadrenal and renin-angiotensin systems into later childhood.

Comparison of leptin levels, body composition and insulin sensitivity and secretion by OGTT in healthy, early pubertal girls born at either appropriate- or small-for-gestational age

Small for gestational age (SGA) has been associated with decreased insulin sensitivity (IS). A possible mechanism is the postnatal development of a metabolically disadvantageous body composition (BC). To determine whether there are differences between IS and BC in girls in early puberty who were SGA (birth weight < 10th percentile) or appropriate for gestational age (AGA, 10th-90th percentile). Age-matched (SGA/AGA) early pubertal girls (Tanner II) were recruited from local schools. We determined waist circumference (WC), the sum of four skinfolds (S4S), and per cent fat mass (fat %) by impedanciometry. Leptin and OGTT assays were performed. The insulinogenic index (I-In), HOMA-IR (homeostasis model assessment of insulin resistance) and WBISI (whole body insulin sensitivity) were calculated. Median age (interquartile range) for 30 SGA and 35 AGA girls was 10.2 (1.1) vs. 9.8 (0.9), respectively (P = NS). BMI percentiles were 62.6 (56) vs. 67.4 (39); WC 60.5 (9.5) vs. 62.2 (6.5) cm; S4S 52 (30) vs. 52.2 (29.5) cm, and fat %[26.2 (6.7) vs. 28.5 (6.3)] was similar in both groups. SGA girls had higher leptin levels [15.4 (9.7) vs. 9.6 (11) ng/ml; P = 0.01] and I-In [2.05 (1.86) vs. 1.47 (1.27) microU/ml* mg/dl; P = 0.02]. No differences between HOMA-IR [2.07 (1.26) vs. 2.04 (1.4)] and WBISI [5.3 (3.3) vs. 5.1 (3.1)] were found between groups. The higher leptin level and I-In in girls born SGA at the beginning of puberty may be early indicators of an underlying subtle degree of insulin resistance, despite similar BMI and BC to AGA girls.

Comparison of Clinical, Ultrasonographic, and Biochemical Differences at the Beginning of Puberty in Healthy Girls Born Either Small for Gestational Age or Appropriate for Gestational Age: Preliminary Results

There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.

Puberty and prenatal growth

There is increasing evidence for a link between puberty and prenatal growth. Here we highlight a selection of pubertal characteristics in children who were born small-for-gestational-age (SGA). Boys born SGA are at risk for high FSH and low inhibin B levels, and a small testicular volume in adolescence. In girls born SGA, the age at pubertal onset and the age at menarche are advanced by about 5–10 months; prenatal growth restraint may be associated with higher FSH levels and with small internal genitalia in adolescence. The ovulation rate was found to be low in SGA adolescents, and an insulin-sensitizing therapy was capable of raising this low ovulation rate. Menarche is definitely advanced in SGA girls with precocious pubarche. Current evidence suggests that insulin resistance is a key mechanism linking a post-SGA state to early menarche; hence, insulin sensitization may become a valid approach to prevent early menarche and early growth arrest in SGA girls.

Neutrophil Count in Small-for-Gestational Age Children: Contrasting Effects of Metformin and Growth Hormone Therapy

A minority of children born small for gestational age (SGA) maintain a slow weight gain and a short stature (SS). At the other end of the spectrum are SGA children who show rapid postnatal weight gain and catch-up growth; these subjects may develop hyperinsulinemia, exaggerated adrenarche with precocious pubarche (PP), and an associated proinflammatory state with raised IL-6 and reduced adiponectin levels. Metformin therapy in SGA-PP girls attenuates the hyperinsulinemia, the adrenal androgen excess, and the proinflammatory state. In contrast, GH therapy in SGA-SS children promotes height gain but may induce hyperinsulinemia. Both groups are associated with increased risk markers for future cardiovascular disease. Therefore, we studied markers of inflammation in both SGA subpopulations at baseline and after their respectively corrective therapies. SGA-PP girls (n = 33; mean age, 8 yr; body mass index, 18.5 kg/m(2)) were randomized to remain untreated or to receive metformin (425 mg/d) for 6 months. SGA-SS children (n = 29; mean age, 7 yr; body mass index, 14.7 kg/m(2)) were randomly assigned to remain untreated or to receive GH (60 mug/kg/d). In SGA-PP girls, the mean neutrophil count (4.0 x 1000/mm(3)) was more than 2 sd above the mean reference level (2.8 x 1000/mm(3), P < 0.001); this remained stable over 6 months in untreated girls but dropped in metformin-treated girls by -1.1 x 1000/mm(3) (P = 0.002). In SGA-SS children, neutrophil counts were also higher at baseline (3.3 x 1000/mm(3), P < 0.01). This remained stable in untreated children but rose in GH-treated children by +1.1 x 1000/mm(3) (P = 0.004). GH-treated children also showed a rise in circulating IL-6 and dehydroepiandrosterone-sulfate levels and a fall in adiponectin levels. In conclusion, neutrophil counts were elevated in SGA children. In SGA girls with PP, the present results corroborate the antiinflammatory benefits of metformin therapy. In contrast, high-dose GH therapy in short SGA children may increase neutrophil counts and lead to a less favorable adipocytokine profile. Future studies with combined GH plus metformin treatment in short SGA children may clarify whether insulin resistance is a mechanism linking GH therapy to markers of inflammation.

Influencia del peso al nacer sobre el inicio y progresión de la pubertad y la talla final en la pubarquia precoz

Girls born small for gestational age (SGA), with a birth weight < 1.5 SDS, are at increased risk of early onset and rapid progression of puberty, with reduced final height. In contrast, idiopathic precocious pubarche (PP) does not seem have negative effects on the onset of puberty or final height. We evaluated the relationship between birthweight, the onset and progression of puberty and final height in girls with PP. We performed a retrospective study of girls at the onset of puberty with a history of PP (pubic hair before the age of 8 years). A total of 124 girls (37 SGA) were investigated; 61 had presented menarche and 44 had reached final height. The mean ( SD) age was 6.8 0.8 years at pubarche, 9.5 0.9 at the onset of puberty and 11.7 6 0.9 at menarche. No significant differences were found in the correlation between birth weight expressed in SDS and age at presentation of pubarche, bone age at presentation of pubarche, age at telarche or age at menarche. A positive correlation was found between birthweight and height at pubarche, telarche, and menarche and final height. These data suggest that pubertal progression is faster in SGA girls. All patients reached the familial target height but only those with an appropriate birthweight were taller than their mothers. PP does not seem to modify age of onset or progression of puberty or final height in girls with adequate birth weight. In contrast, in SGA girls, PP is associated with faster puberal development and shorter final height. Therefore, SGA girls with PP require periodic monitoring.

Pubertal Development in Children Born Small for Gestational Age

Reduced fetal growth appears to be associated with precocious adrenarche, early puberty and polycystic ovary syndrome with subsequent fertility problems. We investigated pubertal development and DHEAS levels in children born small for gestational age (SGA) and children born appropriate for gestational age (AGA). Physical examination was carried out twice. Mean age (+/-SD) at the first visit: SGA group, 9.1+/-1.1 yr; AGA group, 9.0+/-1.1 yr. AT FOLLOW-UP: SGA group, 11.6+/-1.0 yr; AGA group, 11.6 +/-1.1 yr. Pubertal stages of the children were assessed. Pubic hair was recorded as a measure of androgenization. Chronological age (CA) was expressed as a percentage of the age corresponding to the pubertal stage (CA/pubertal age [PA] x 100%). Estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) were measured in all children. FIRST VISIT: All children were prepubertal without signs of pubarche. DHEAS concentrations were higher in SGA children than in AGA children (p = 0.004). Twenty SGA children and 15 AGA children were pubertal. CA/PA x 100% was lower in SGA girls than in AGA girls (p = 0.004). Since 2.5 years earlier all girls had been prepubertal, this means a more rapid progression in the SGA girls. CA/PA x 100% was similar in SGA and AGA boys (p = 0.1). DHEAS levels tended to be higher in SGA children than in AGA children (p = 0.06). These data support that a low birth weight may have long-lasting effects on pubertal development, as observed in a more rapid progression in SGA girls. In prepubertal SGA children, an exaggerated adrenarche is observed compared to AGA children, which tended to persist through puberty.