Length Standard Deviation Score Research Articles

Endocrine and metabolic disorders in adolescent and adult patients born small for gestational age.

Children born small for gestational age (SGA), defined by a birth weight and/or length standard deviation score (SDS) of < -2 based on an appropriate reference population, represent a diverse group due to multiple underlying causes of reduced growth. This classification results in a heterogeneous patient cohort. SGA children are prone to endocrinological and metabolic issues not only in childhood but also extending into adolescence and adulthood. This population faces elevated health risks, including persistent short stature, premature adrenarche, pubertal development alterations, neurocognitive problems, and metabolic syndrome. Insulin resistance emerges as a pivotal factor c nht6j7ikontributing to these metabolic complications, prominently featuring obesity, insulin resistance, hypertension, and an increased risk of type 2 diabetes mellitus in adulthood. These medium- to long-term complications significantly impact their quality of life. Growth hormone (GH) therapy for short children born SGA facilitates height normalization throughout childhood, adolescence, and into adulthood. Catch-up growth, however, correlates with heightened risks of obesity, insulin resistance, and metabolic syndrome. Conversely, those without catch-up growth tend to exhibit pronounced short stature and cognitive dysfunction. Given these determinants, comprehensive management and clinical monitoring of SGA children should commence in the neonatal period and extend into adulthood. Recognizing and addressing these challenges early in life can mitigate the long-term impact on health and well-being, emphasizing the importance of a lifelong approach to their care.

Effects of early recombinant human growth hormone treatment in young Chinese children with Prader–Willi syndrome

BackgroundPrader–Willi syndrome (PWS) is a rare and multisystemic genetic disorder that is characterized by severe hypotonia, hyperphagia, short stature, and global developmental delay. Although early recombinant human growth hormone (rhGH) treatment has been proven to rescue some symptoms and bring additional benefits to PWS patients, studies in patients under 2 years old are scarce. Thus, this study aims to investigate the effectiveness and safety of rhGH treatment for young children.MethodsA total of 96 genetically confirmed Chinese PWS infants or toddlers (47 males) followed between 2013 and 2022 were retrospectively analyzed. Sixty-five infants (early treatment group) started rhGH treatment during their first year, and 31 toddlers (later treatment group) started at the age of 1–2 years. Auxological parameters, carbohydrate metabolism parameters, thyroid function, liver function, insulin-like growth factor-1 (IGF-1), and radiographs were acquired before the initiation of the treatment and every 3–6 months thereafter. Height/length, weight, and weight for height were expressed as standard deviation scores (SDSs) according to WHO child growth standards.ResultsThe mean SDS of length/height in the early treatment group was significantly higher than that in the later treatment group throughout the observation period (all P < 0.001). The change in the length SDS between the two groups at 1 year old and 4 years old was 1.50 (95% CI, 0.88–2.13) and 0.63 (95% CI, 0.16–1.10), respectively. Compared to the later treatment group, the weight SDS in the early treatment group increased by 0.94 (95% CI, 0.37–1.52) at 1 year old and 0.84 (95% CI, 0.28–1.39) at 2 years old. No statistical significance was found after 2.5 years of age. No significant differences were observed in IGF-1, incidence of liver dysfunction, hypothyroidism or spinal deformity between the two groups.ConclusionsrhGH treatment improved growth and body composition in infants and toddlers. Furthermore, an early start of rhGH treatment is expected to have more efficacy than the later treatment group without an increase in adverse effects.

Effects of relaxation therapy on maternal psychological status and infant growth following late preterm and early-term delivery: a randomized controlled trial

BackgroundMaternal stress is one modifiable variable that could influence mother–infant signaling and negatively affect breastfeeding and infant growth. ObjectivesThis study aimed to test the hypothesis that relaxation therapy would reduce maternal stress and improve infant growth, behavior, and breastfeeding outcomes after late preterm (LP) and early-term (ET) delivery. MethodsA single-blind randomized controlled trial was conducted in healthy Chinese primiparous mother–infant pairs after LP or ET delivery (34+0–37+6 gestation weeks). Mothers were randomly assigned to the intervention group (IG, listening to relaxation meditation at least once a day) or control group (CG, normal care). Primary outcomes—changes in maternal stress (perceived stress scale), anxiety (Beck Anxiety Inventory), and infant weight and length standard deviation score—were assessed at 1 wk and 8 wks postpartum. Secondary outcomes—breast milk energy and macronutrient composition, maternal breastfeeding attitudes, infant behaviors (3-d diary), and 24-hour milk intake—were assessed at 8 wks. ResultsIn total, 96 mother–infant pairs were recruited. There was a significantly greater reduction in maternal perceived stress (Perceived Stress Scale score) (mean difference [MD] = 2.65; 95% CI: 0.8, 4.5) and significantly greater infant weight standard deviation score gain (MD = 0.51; 95% CI: 0.2, 0.9) from 1 wk to 8 wks in the IG than those in the CG. Exploratory analyses showed a significant interaction between intervention and sex, with greater effects on weight gain in female infants. Mothers of female infants used the intervention more frequently with significantly higher milk energy observed at 8 wks. ConclusionsThe relaxation meditation tape is a simple, effective practical tool that could easily be used in clinical settings to support breastfeeding mothers after LP and ET delivery. The findings need confirmation in larger groups and in other populations.

Abstract 2: Effectiveness and safety of early growth hormone treatment in children born small for gestational age: Long-term data from NordiNet® International Outcome Study (IOS) and ANSWER program

Background: Growth hormone (GH) is indicated for the treatment of short stature in children born small for gestational age (SGA) who fail to show catch-up growth. In pilot studies, early initiation of GH has been associated with favorable growth responses in short SGA children. However, few studies have examined the short- and long-term effects of initiating GH in children born SGA who are <4 years (yr) of age, compared with those starting later. This analysis therefore investigated the effect of age at GH initiation on long-term effectiveness and safety in children born SGA.Methods: The NordiNet IOS (NCT00960128) and ANSWER (NCT01009905) programs are complementary, noninterventional, multicenter studies that evaluated the long-term effectiveness and safety of Norditropin (somatropin; Novo Nordisk A/S, Denmark) as prescribed in real-life clinical practice. In this analysis, children born SGA who were prepubertal at GH initiation were grouped according to age at GH start: <4 yr, 4-6 yr, and ≥6 yr. Patient characteristics at birth and at GH start, auxological measurements, and adverse events were evaluated in each group.Results: Overall, 3351 SGA patients were included in the effectiveness set (age at GH start: <4 yr [n=389, 54.8% male]; 4-6 yr [n=1048, 57.6% male]; and ≥6 yr [n=1914, 56.6% male]). The proportion of patients born pre-term (<37-week gestation) was 38.6% in the <4 yr group, 36.1% in the 4-6 yr group, and 28.2% in the ≥6 yr group. Mean (SD) birth length standard deviation score (SDS) and birth weight SDS were: −2.9 (1.6) and −2.3 (1.2) in the <4 yr group, −2.8 (1.3) and −2.2 (1.1) in the 4-6 yr group, and −2.5 (1.4) and −2.0 (1.2) in the ≥6 yr group. Mean (SD) age at GH start was 3.1 (0.7), 4.9 (0.6), and 9.3 (2.2) years in the <4 yr, 4-6 yr, and ≥6 yr groups, respectively. Mean (SD) GH duration and daily GH dose in the study were: 3.5 (3.1) yr and 0.044 (0.016) mg/kg in the <4 yr group, 4.1 (3.1) yr and0.039 (0.012) mg/kg in the 4-6 yr group, and 3.5 (2.5) yr and 0.042 (0.012) mg/kg in the ≥6 yr group. Mean (SD) height SDS (HSDS) at GH start was −3.3 (1.2) in the <4 yr group, −3.1 (0.9) in the 4-6 yr group, and −2.8 (0.8) in the ≥6 yr group. After 4 and 8 yr of GH, mean (SD) ÄHSDS from baseline was 1.7 (0.7) and 2.5 (0.6) in the <4 yr group, 1.6 (0.7) and 2.2 (0.8) in the 4-6 yr group and 1.3 (0.7), and 1.7 (0.6) in the ≥6 yr group. Among patients who reached near-adult height in the study, mean (SD) HSDS was −1.9 (0.6) in the <4 yr group (n=3), −1.9 (0.8) in the 4-6 yr group (n=10), and −1.8 (1.0) in the ≥6 yr group (n=220). In the safety set (n=5643), the most commonly reported non-serious adverse reactions (AR) were headache (n=20) and arthralgia (n=5). The most common serious ARs were headache (n=3) and epiphysiolysis (n=4). ARs and serious ARs were distributed equally among groups.Conclusions: This analysis of real-world data confirms the effectiveness and safety of GH in children born SGA, irrespective of patient age at treatment initiation.

Effects of Neonatal Feeding Patterns on Infant Health.

Objective Early and reasonable feeding mode can not only ensure the good nutritional condition of infants but also enhance the infant immunity and resistance, which has a certain role in promoting health and preventing the occurrence of chronic diseases in adulthood. In this study, the effect of neonatal feeding methods on the infant body, the influence of early feeding on the growth rate, and development of infants aged 0-3. Method From January 2016 to June 2019, a total of 600 infants who have been systematically managed in our hospital since birth were selected. All newborns were 37-40 weeks old, weighing 2350-4100 g, without congenital diseases. They were grouped according to feeding methods. 194 infants were exclusively breastfed, 32.3%; 207 people were artificially fed, 34.5%; 199 people were mixed fed, 33.2%. The Kaup index method was used to judge the nutritional status. Developmental Screening Test for ages 0 to 6 (DST) and Bailey Infant Development Scale (BIDS) were used to rate the intellectual and behavioral development of infants and children. According to the growth and development reference standard of 0 ~ 4-year-old children recommended by who in 2006, the age weight standard deviation score (WAZ), age length (height) standard deviation score (HAZ), and body (long) height-weight standard deviation score (WHZ) were performed, and the statistical analysis was performed with SPSS24.0 software. The height, weight, intelligence, and motor development of infants in the three groups at 1 month, 3 months, 6 months, 12 months, 24 months, and 36 months were analyzed and compared, and the test results were recorded in detail. Result There was no significant difference in 3-month-old WAZ and HAZ among the three groups (P > 0.05). Within 6 months, the WAZ and HAZ values of the pure breastfeeding group and mixed feeding group were higher than those of the artificial feeding group (P < 0.05). From 6 months to 12 months, the WAZ and HAZ values of the artificial feeding group were better than those of artificial feeding group and mixed feeding group (P < 0.05). The scores of MI, DQ, PDI, and MDI in the mixed feeding group within 12-36 months were slightly higher than those in the breastfeeding group and significantly better than those in the artificial feeding group (P < 0.05). The prevalence of the breastfeeding group was 22.2% (43/194) and mixed feeding group was 19.8% (39/199), which was lower than that of the artificial feeding group 57.8% (120/207), P < 0.01. The number of people with normal psychological development was 88.7% (172/194) in the breastfeeding group and 88.9% (177/199) in the mixed feeding group, which was higher than 76.3% (158/207) in the artificial feeding group (P < 0.01). Conclusion When there is little colostrum secretion in the first 2-3 days of delivery, appropriate addition of formula milk can reduce the incidence of diseases in newborn infants. Breast milk is the most perfect natural food. The immune substance in breast milk is an important element for infants to resist diseases. The communication between mother and child is the first condition for the development of infant mental health.

Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height.

ObjectivesGrowth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children.MethodsRetrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with PTPN11 mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement.ResultsANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (p<0.001), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from −3.10 ± 0.84 to −2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH.ConclusionsrhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of PTPN11 gene and in the less common genotypes.

Scrotal base distance: A new key genital measurement in males with hypospadias and cryptorchidism.

Background:Anogenital distance (AGD) in both humans and animals is a known reflection of fetal endocrine effect on genital virilization and the related abnormalities, including cryptorchidism and hypospadias. However, we introduce here and investigate scrotal base distance (SBD) as a sensitive genital anthropometric biomarker in human infants with cryptorchidism and hypospadias, which are considered early manifestations of testicular dysgenesis syndrome. We aim to assess SBD in patients with cryptorchidism or hypospadias against healthy subjects.Material and methods:Patients with hypospadias (n = 61, age 17.4 ± 6.3 months) or cryptorchidism (n = 51, age 11.4 ± 4.8 months) were enrolled for assessment of SBD, AGD, and penile length; and compared with a cohort of 102 full-term healthy boys for standard ritual circumcision by measuring age-specific standard deviation scores.Results:Patients having hypospadias had lower mean SBD, AGD, and penile length standard deviation scores than the control group (p < 0.01). These values in patients with cryptorchidism were longer than mean values in boys with hypospadias (p < 0.01) and shorter than mean values in the control group.Conclusions:We showed that SBD, AGD, and penile length were lower in patients with cryptorchidism or hypospadias compared to normative data measured from a control group of healthy boys for ritual circumcision. These results enforce the use of SBD as an objective anthropometric measurement and a viable biomarker to assess the effects of fetal endocrine imbalance on male external genitalia development.

Effectiveness and Safety of Early Growth Hormone Treatment in Children Born Small for Gestational Age: Long-Term Data From NordiNet® International Outcome Study (IOS) and ANSWER Program

Background: Growth hormone (GH) is indicated for the treatment of short stature in children born small for gestational age (SGA) who fail to show catch-up growth. In pilot studies, early initiation of GH has been associated with favorable growth responses in short SGA children. However, few studies have examined the short- and long-term effects of initiating GH in children born SGA who are <4 years (yr) of age, compared with those starting later. This analysis therefore investigated the effect of age at GH initiation on long-term effectiveness and safety in children born SGA. Methods: The NordiNet IOS (NCT00960128) and ANSWER (NCT01009905) programs are complementary, non-interventional, multicenter studies that evaluated the long-term effectiveness and safety of Norditropin (somatropin; Novo Nordisk A/S, Denmark) as prescribed in real-life clinical practice. In this analysis, children born SGA who were prepubertal at GH initiation were grouped according to age at GH start: <4 yr, 4-6 yr, and ≥6 yr. Patient characteristics at birth and at GH start, auxological measurements, and adverse events were evaluated in each group. Results: Overall, 3351 SGA patients were included in the effectiveness set (age at GH start: <4 yr [n=389, 54.8% male]; 4-6 yr [n=1048, 57.6% male]; and ≥6 yr [n=1914, 56.6% male]). The proportion of patients born pre-term (<37-week gestation) was 38.6% in the <4 yr group, 36.1% in the 4-6 yr group, and 28.2% in the ≥6 yr group. Mean (SD) birth length standard deviation score (SDS) and birth weight SDS were: −2.9 (1.6) and −2.3 (1.2) in the <4 yr group, −2.8 (1.3) and −2.2 (1.1) in the 4-6 yr group, and −2.5 (1.4) and −2.0 (1.2) in the ≥6 yr group. Mean (SD) age at GH start was 3.1 (0.7), 4.9 (0.6), and 9.3 (2.2) years in the <4 yr, 4-6 yr, and ≥6 yr groups, respectively. Mean (SD) GH duration and daily GH dose in the study were: 3.5 (3.1) yr and 0.044 (0.016) mg/kg in the <4 yr group, 4.1 (3.1) yr and 0.039 (0.012) mg/kg in the 4-6 yr group, and 3.5 (2.5) yr and 0.042 (0.012) mg/kg in the ≥6 yr group. Mean (SD) height SDS (HSDS) at GH start was −3.3 (1.2) in the <4 yr group, −3.1 (0.9) in the 4-6 yr group, and −2.8 (0.8) in the ≥6 yr group. After 4 and 8 yr of GH, mean (SD) ΔHSDS from baseline was 1.7 (0.7) and 2.5 (0.6) in the <4 yr group, 1.6 (0.7) and 2.2 (0.8) in the 4-6 yr group and 1.3 (0.7), and 1.7 (0.6) in the ≥6 yr group. Among patients who reached near-adult height in the study, mean (SD) HSDS was −1.9 (0.6) in the <4 yr group (n=3), −1.9 (0.8) in the 4-6 yr group (n=10), and −1.8 (1.0) in the ≥6 yr group (n=220). In the safety set (n=5643), the most commonly reported non-serious adverse reactions (AR) were headache (n=20) and arthralgia (n=5). The most common serious ARs were headache (n=3) and epiphysiolysis (n=4). ARs and serious ARs were distributed equally among groups. Conclusions: This analysis of real-world data confirms the effectiveness and safety of GH in children born SGA, irrespective of patient age at treatment initiation.

Is quantitative ultrasound a measure for metabolic bone disease in preterm-born infants? A prospective subcohort study

In this study, we aimed to (a) evaluate postnatal changes in bone development in relation to growth and (b) to determine factors associated with bone development, from birth to 24 months of corrected age. The metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT) were used to evaluate bone development in 98 preterm infants, during hospitalization and follow-up. The mcSOS and mcBTT values not only declined in the first 6 weeks of hospitalization but also during follow-up. The mcSOS reached its lowest point at 12 months (β=-34.64), while the mcBTT reached a plateau between 12 and 24 months (β=0.06). Univariable analysis showed that gender (p=0.28), time (p<0.001), and growth parameters (p<0.001) were significant negative associated factors with mcSOS, whereas with mcBTT, time (p=0.009), length (p=0.063), length standard deviation scores (SDS) (p=0.027), head circumference (p=0.005), and head circumference SDS (p=0.007) were significant positive. The multivariable model revealed that time (β= -3.364, p=<0.001), weight (β=-0.007, p<0.001) and length (β=1.163, p<0.001) for mcSOS and length (β=-0.021, p<0.001), and length SDS (β= 0.066, p<0.001) and head circumference (β=0.049, p<0.001) for mcBTT remained highly significant associated factors.Conclusion: The most important finding is that mcSOS decreased and the mcBTT reached a plateau to 24 months. In both mcSOS and mcBTT, the growth parameters were significant factors.Clinical Trial Registration: N/AWhat is known:• Metabolic bone disease is one of the possible long term adverse outcomes after preterm birth.• Metacarpal speed of sound (mcSOS) and metacarpal bone transmission time (mcBTT) decline in the early postnatal period.What is new:• During follow-up, mcSOS further decreased and reached its lowest point at 12 months, while the mcBTT reached a plateau up to 24 months.• Postnatal nutrition in relation to comorbidity does not meet the optimal mineralization rate of the developing preterm bone.

Growth patterns over 2 years after birth according to birth weight and length percentiles in children born preterm.

PurposeTo analyze growth patterns over 2 years after birth according to preterm infant birth weight and length percentiles.MethodsAnthropometric measurements of 82 preterm infants were retrospectively reviewed. Preterm infants with birth weight or length below the 10th percentile were classified as small for gestational age (SGA) (n=19) and those between the 10th and 89th percentile as appropriate for gestational age (AGA) (n=63). The association between the length standard deviation score (SDS) at 2 years of corrected age and clinical factors were analyzed.ResultsThe length SDS of the SGA group was significantly increased at 6 months (-1.30±1.71) and 24 months (-0.97±1.06) of corrected age. The length SDS was lower in the SGA group than those in the AGA group at 6 months (-1.30±1.71 vs. -0.25±1.15, P=0.004), 18 months (-0.97±1.39 vs. -0.03±1.29, P=0.015), and 24 months (-0.97±1.06 vs. -0.29±1.12, P=0.022,). The percentage of children with a length SDS of <-2 (growth failure) at 24 months was 15.8% in the SGA group and 4.8% in the AGA group (P=0.108). Multiple linear regression analysis demonstrated that length at 24 months of corrected age was negatively correlated with birth length below the 10th percentile (coefficient β=-0.91, P=0.001) and duration of stay in the neonatal intensive care unit (NICU) (coefficient β=-0.01, P=0.001).ConclusionsDespite the fact that catch-up growth occurs during the early period of infancy in a large portion of preterm SGA infants, a significant portion of these infants show growth failure at 24 months of age. Growth over 2 years after birth is affected by birth length and duration of stay in the NICU in preterm children.

Clinical presentations, Laboratory analysis and Linear Growth in 50 Neonates and Young Infants with Acute Meningitis: One Year Experience of a Single Center in Qatar.

BackgroundMeningitis frequently occurs in neonates and can lead to a number of acute, severe complications and long-term disabilities. Although, long term growth delay and abnormal weight gain appear to be risk factors following an acute attack of both bacterial and aseptic meningitis in children, especially during the fast phase of infantile growth, the long-term effects of acute meningitis occurring during the neonatal and early infantile periods on linear growth (length, weight and head growth) have not fully reported.Aim of the studyThe objective of this study is to describe the clinical presentation of neonates and young infants with acute meningitis with different etiologies and to determine the clinical impact of the effect of acute meningitis on growth parameters.Material and methodsWe analyzed the clinical data and the growth parameters of 50 newborns and young infants (age: 1.6 ± 0.9 months) admitted to our hospital (Al Wakhra Hospital, Department of Pediatrics, Doha, Qatar), between 1-1-2016 to 1-1-2017, with acute meningitis. Anthropometric measurements included weight, length, and head circumference. Length SDS (L-SDS) and body-mass-index (BMI) were calculated and recorded at every clinic visit, every 3 months for 8 ± 2 months.ResultsIn this age group of neonates and young infants with acute meningitis fever (84%) and hypoactivity (64%) were the major presenting manifestations. Acute bacterial meningitis (n: 10) was associated with higher morbidity [shock (n: 1), subdural empyema (n: 1) and hydrocephalus (n: 1)]. Cerebrospinal fluid (CSF) examinations showed that infants with bacterial meningitis had significantly higher pleiocytosis of mainly polymorphic leukocytes and protein levels, compared to those with aseptic meningitis.All infants showed normal linear growth and weight gain during the follow-up period (8 ± 2 months). The annualized growth rate of infants was 25.3 ± 3.5 cm per year. All had normal length standard deviation scores (LSDS) (−0.2 ± 0.9) and none of them had LSDS < −2. All infants had a normal BMI (16.7 ± 1.8 kg/m2). Head circumference growth was normal in 49/50 infants (43.8 ± 1.8 cm) at 8 ± 2 months. One infant developed hydrocephalus after group B streptococcus (GBS) meningitis. There was no statistical difference in linear growth between infants with aseptic and bacterial meningitis.ConclusionAcute bacterial meningitis in newborns and young infants is still associated with considerably high morbidity and complications. Infantile linear growth appears to be normal in all newborns and young infants with both bacterial and aseptic meningitis.

SUN-261 Growth Patterns over Two Years after Birth According to the Birth Weight and Length Percentile in Children Born Preterm

Purpose : This study aimed to analyze growth patterns during the first two years after birth according to the birth weight and length percentile in children born preterm, and to investigate factors affecting postnatal growth of these children. Methods : Eighty-two preterm neonates with a gestational age below 37 weeks who followed up until 24 months of corrected age (CA) were retrospectively reviewed. Length, weight and head circumference were measured at birth, 6, 12, 18, and 24 months. Data were analyzed between children born small for gestational age (SGA) and those born appropriate for gestational age (AGA). Results : Most preterm infants born SGA grew higher than -2 SDS in length during the first 6 months. Compared to AGA group, SGA group had a low length SDS at 24 months of CA(-0.87±1.11 vs -0.09±1.06, P=0.01). There was no significant difference in the rate of growth failure (length standard deviation score [SDS] <-2 at 24 months of CA) between SGA and AGA group (15.8 % vs 4.3%, P=0.13). Multivariable logistic regression analysis showed that length below 10th percentile at birth (odds ratio [OR], 47.47; 95% CI, 2.02-1117.13, P=0.02) and longer duration of in neonatal intensive care (NICU) (OR, 1.06; 95% CI, 1.01-1.11, P=0.02) were associated with a decrease of length SDS (lower than -1) at 24 months of CA. Conclusion : Whether SGA or not, most of preterm infants grow higher than -2 SDS during first 2 years. Birth length SDS and length velocity are one of the important factors affecting length SDS at 24 moths of CA in children born SGA.

SUN-244 Birth and Perinatal Characteristics of Children with Congenital GH Deficiency (GHD) Due to Abnormal Pituitary Development: Data from a Prospective, Multinational Observational Study

Perinatal characteristics of children with non-acquired GHD are highly variable. Children with structural hypothalamic-pituitary abnormalities such as ectopic posterior pituitary (EPP) with/without pituitary stalk interruption syndrome, septo-optic dysplasia (SOD), or isolated anterior pituitary aplasia/hypoplasia (AP/HP) usually display more severe GHD than those with normal hypothalamic-pituitary magnetic resonance imaging (MRI) findings, and a higher prevalence of multiple pituitary hormone deficiencies (MPHD). Birth and perinatal characteristics in patients with structural hypothalamic-pituitary findings were assessed using data from the Genetics and Neuroendocrinology of Short Stature International study (GeNeSIS). Patients were grouped according to investigator-provided diagnoses: 1) EPP (N=396; including interrupted pituitary stalk; reported MPHD 57%); 2) SOD (N=202; MPHD 78%); 3) AP/HP (N=509; MPHD 36%); and 4) Other GHD (N=10470; non-acquired, non-pituitary abnormality associated; MPHD 9%). Birth/perinatal characteristics for EPP were compared to other diagnoses by ANOVA (all other diagnoses) and pairwise using Dunnett adjustment for continuous variables, and Chi-Square (all other diagnoses) and Fisher’s exact test (pairwise) for categorical variables. Gestation duration was ≈39 weeks for all diagnoses. Mean birth weight standard deviation scores (SDS) were 0.02 for EPP, -0.11 for SOD (p value for difference from EPP=0.651), -0.26 for AP/HP (p=0.020), and -0.38 for Other (p<0.001), while birth length SDS were -0.44, -0.17 (p=0.257), -0.60 (p=0.370) and -0.74 (p=0.003) respectively. Breech presentation was reported for 15% in the EPP group vs 3% SOD, 7% AP/HP and 5% Other (p<0.001 pairwise from EPP for all), with higher rates of reported Caesarean section for EPP (21%) vs SOD (17% [p=0.280]), AP/HP (17% [p=0.104]), and Other (14% [p<0.001]) or instrument assisted delivery (5%, 2% [p=0.167], 2% [p=0.033], and 2% [p=0.001] respectively). Perinatal asphyxia, then pregnancy, delivery, and neonatal complications were most prevalent for EPP and/or SOD, with values for EPP vs Other of 10% vs 3%, 18% vs 8%, 11% vs 4%, 35% vs 8%, respectively (p<0.001 for all) and 13% (p=0.027), 10% (p=0.911), 8% (p=0.249), 20% (p<0.001) respectively for AP/HP. In conclusion, among children with GHD, those with structural hypothalamic-pituitary abnormalities had delivery and perinatal complications more frequently than those without such MRI findings, but had birth weight and length SDS closer to the general population average. These findings from a large cohort of children with GHD reinforce previous smaller series suggesting that patients with congenital CNS midline defects and ultimately GHD or MPHD were more likely to have had complications during pregnancy and delivery, although causality is not established.

SUN-LB041 Clinical and Molecular Characteristics, Genotype-Phenotype Correlation in 113 Chinese Children with SRD5A2 Gene Mutations

Objective: Studies on 5α-reductase type 2 deficiency (5α-RD) are limited and the genotype-phenotype correlation has not been elucidated. The aim of the study was to analyze clinical and molecular characteristics, genotype-phenotype correlation in a large Chinese 5α-RD cohort. Design: Database registration study. Method: We analyzed clinical and genetic data of gene confirmed 5α-RD Children, comparing their phenotypes by using external masculinization score (EMS),the position of urethral meatus and gonads as well as penis length-standard deviation score (PL-SDS). Results: 85.84% of patients presented hypospadias while 14.16% had normal urethral meatus. When the cut-off value of stimulated T/DHT was 10 or 15, 98.48% and 92.42% of patients were diagnosed respectively. 8 patients with isolated micropenis were diagnosed as 5α-RD by higher T/DHT ratio and SRD5A2 gene mutations. There was no significant correlation between T/DHT and phenotypes (p>0.05). We identified 31 different variants including 10 unreported ones. The p.R227Q was the most prevalent variant (38.50%). The phenotypic indicators of patients with p.R227Q were higher than those without the mutation in multiple comparisons (p<0.05). Patients with the homozygous p.R227Q had milder phenotypes and larger standard deviation of phenotypic scores than those with other homozygotes. Conclusions: Subjects with 5α-RD can present isolated micropenis and T/DHT cannot foretell the severity of phenotypes. As a founder mutation in Chinese, the p.R227Q seems to link to relatively milder phenotypes and greater phenotypic variability. Variants can explain, at least partially, the heterogeneity of phenotypes, while other factors may also contribute to the phenotypes. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Maternal vitamin D and neonatal anthropometrics and markers of neonatal glycaemia: Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks' gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks' gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

Patterns of Infancy Growth and Metabolic Hormonal Profile Are Different in Very-Low-Birth-Weight Preterm Infants Born Small for Gestational Age Compared to Those Born Appropriate for Gestational Age

Background/Aims: An increased preterm birth survival rate is associated with long-term neurological and metabolic risks; thus, our aim was to evaluate whether early patterns of infancy anthropometry and metabolic hormonal profile differ in preterm infants born small for gestational age (SGA) or appropriate for gestational age (AGA) from birth to 36 months of corrected age (CA). Methods: We recruited 110 very-low-birth-weight (VLBW) preterm infants (AGA = 60 and SGA = 50) with a mean birth weight of –2.39 ± 0.77 versus 0.57 ± 0.54 standard deviation scores (SDS) (p < 0.01) and birth length of –2.1 ± 1.05 versus –0.44 ± 0.82 SDS (p < 0.01), respectively. Anthropometry and blood sampling for insulin, insulin-like growth factor (IGF)-II, IGF-I, and leptin were performed for up to 3 years. Results: All neonates increased their weight, length, and head circumference SDS during the early inpatient period. Up to 90% reached a normal length within this period. The IGF-II, insulin, and glycemia concentrations changed in parallel with weight. In the first year of CA, only SGA infants gained weight and height SDS. The homoeostatic model assessment had a trend toward higher values in SGA infants at 24 and 36 months (p = 0.06 and p = 0.07). Conclusion: Being SGA is the strongest predictor of early recovery of height in VLBW preterm infants. Follow-up will allow us to determine whether the differences in the growth patterns of VLBW preterm infants by birth weight SDS persist.

First-year growth in children with Noonan syndrome: Associated with feeding problems?

Children with Noonan syndrome show rapid decline of growth in the first year of life and feeding problems are present in over 50%. The aim of this study was to explore whether growth decelerates because of feeding problems or other Noonan syndrome-related factors. We performed a retrospective, longitudinal cohort study of clinically and genetically diagnosed subjects with Noonan syndrome (n = 143). Questionnaires about the phenotypic-genotypic profile and reported feeding problems were sent to eligible subjects. Data on first-year growth was obtained from growth charts. Ninety-one participants were excluded because of different criteria. A total of 52 subjects with Noonan syndrome were included. The largest decline in weight and length standard deviation score (SDS) occurred in the first 2.5 months after birth (-1.93 and -1.15, respectively), with feeding problems causing a decline of 0.57 SDS in the remaining months. At 1 year, children with feeding problems were on average 290 g lighter and 0.8 cm shorter than children without feeding problems. Weight gain was also negatively influenced by having a PTPN11 mutation (n = 39) and a higher gestational age, whereas children of parents with Noonan syndrome and with a higher birth weight gained more weight. Growth in length was reduced by having cardiac surgery and a higher gestational age, but positively influenced by birth length and maternal height. Growth in children with Noonan syndrome is impaired right after birth and only partially associated with feeding problems. In addition, several specific Noonan syndrome-related factors seem to influence growth in the first year.

Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight gain and growth

We investigated if maternal body burdens of perfluoroalkyl acids (PFAAs) at the time of delivery are associated with birth outcome and if early life exposure (in utero/nursing) is associated with early childhood growth and weight gain. Maternal PFAA body burdens were estimated by analysis of serum samples from mothers living in Uppsala County, Sweden (POPUP), sampled three weeks after delivery between 1996 and 2011. Data on child length and weight were collected from medical records and converted into standard deviation scores (SDS). Multiple linear regression models with appropriate covariates were used to analyze associations between maternal PFAA levels and birth outcomes (n=381). After birth Generalized Least Squares models were used to analyze associations between maternal PFAA and child growth (n=200). Inverse associations were found between maternal levels of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and birth weight SDS with a change of −0.10 to −0.18 weight SDS for an inter-quartile range (IQR) increase in ng/g PFAA. After birth, weight and length SDS were not significantly associated with maternal PFAA. However, BMI SDS was significantly associated with PFOA, PFNA, and PFHxS at 3 and 4years of age, and with PFOS at 4 and 5years of age. If causal, these associations suggest that PFAA affects fetal and childhood body development in different directions.

Long-Term Skeletal Disproportion in Childhood-Onset Crohn’s Disease

Background: It is unclear whether Crohn’s disease (CD) is associated with skeletal disproportion in adulthood. Methods: Height (Ht), sitting height (SHt) and leg length were studied in 44 children (male: 22), 23 adults (male: 10) with childhood-onset (CO) CD and 26 adults (male: 9) with adult-onset (AO) CD with a median (range) age of 13.7 (10, 17.3), 21.5 (18, 32) and 31.0 (22, 40) years, respectively. Results: Adults with CO-CD had a median Ht standard deviation score (SDS) of –0.9 (–2.3, 0.0) compared to 0.6 (–0.8, 1.0) in those with AO-CD (p < 0.05). Compared to a normal population, men, but not women, with CO-CD also had lower median SHt SDS at –1.1 (2.5, –0.5) (p < 0.05). The expected positive association that is normally found between leg length and SHt SDS was not evident in the adults with CO-CD. Conclusion: Short stature in adults with CO-CD is more pronounced in men and may be associated with poor spinal growth.

Growth patterns of patients with Noonan syndrome: correlation with age and genotype.

Growth patterns of patients with Noonan syndrome (NS) were established before the involved genes were identified. The goal of this study was to compare growth parameters according to genotype in patients with NS. The study population included 420 patients (176 females and 244 males) harboring mutations in the PTPN11, SOS1, RAF1, or KRAS genes. NS-associated PTPN11 mutations (NS-PTPN11) and NS with multiple lentigines-associated PTPN11 mutations (NSML-PTPN11) were distinguished. Birth measures and height and body mass index (BMI) measures at 2, 5, 10 years, and adulthood were compared with the general population and between genotypes. Patients with NS were shorter at birth (mean birth length standard deviation score (SDS): -1.0 ± 1.4; P < 0.001) and throughout childhood than the healthy population, with height SDS being -2.1 ± 1.3 at 2 years, and -2.1 ± 1.2 at 5 and 10 years and adulthood (P < 0.001). At birth, patients with NS-PTPN11 were significantly shorter and thinner than patients with NSML-PTPN11, SOS1, or KRAS. Growth retardation was significantly less severe and less frequent at 2 years in patients with NSML-PTPN11 and SOS1 than in patients with NS-PTPN11 (P < 0.001 and P = 0.002 respectively). Patients with NS had lower BMI at 10 years (P < 0.001). No difference between genotypes was demonstrated. Determining the growth patterns of patients with NS according to genotype should better inform clinicians about the natural course of growth in NS so that they can optimize the follow-up and management of these patients.