Effect of treatment with growth hormone on body composition and metabolic profile of short children born small for gestational age / Efeito do tratamento com hormônio de crescimento na composição corporal e no perfil metabólico de crianças nascidas pequenas para a idade gestacional com baixa estatura

ABSTRACT Objective: To assess the effect of recombinant growth hormone (rGH) on body composition and metabolic profile of prepubertal short children born small for gestational age (SGA) before and after 18 months of treatment. Methods: It is a clinical, non-randomized, and paired study. Children born SGA, with birth weight and/or length <-2 standard deviations (SD) for gestational age and sex, prepubertal, born at full term, of both genders, with the indication for treatment with rGH were included. The intervention was performed with biosynthetic rGH at doses ranging from 0.03 to 0.05 mg/kg/day, administered subcutaneously, once a day at bedtime. Total lean mass (LM) and total fat mass (FM) were carried out using dual-energy X-ray absorptiometry (DXA), and the metabolic profile was assessed for insulin, glycemia, IGF-1 levels and lipid profile. Results: Twelve patients (nine girls, 8.17±2.39 y) were evaluated; three patients dropped out of the study. There was an increase of LM adjusted for length (LMI) (p=0.008), LMI standard deviation score (SDS) adjusted for age and sex (p=0.007), and total LM (p<0.001). The percentage of body fat (BF%) and abdominal fat (AF) remained unaltered in relation to the beginning of treatment. Among the metabolic variables, blood glucose remained within normal levels, and there was a reduction in the number of participants with altered cholesterol (p=0.023). Conclusions: The effect of rGH treatment was higher on LM than in FM, with increased LM adjusted for length and standardized for age and sex. Glycemia remained within the normal limits, and there was a decreased number of children with total cholesterol above the recommended levels.

RESUMO Objetivo: Avaliar o efeito do hormônio de crescimento recombinante (rHC) na composição corporal e no perfil metabólico de crianças pré-púberes com baixa estatura, nascidas pequenas para a idade gestacional (PIG) antes e depois de 18 meses de tratamento. Métodos: Estudo clínico, não randomizado e pareado. Foram incluídas crianças nascidas PIG, com peso e/ou altura ao nascer <-2 desvios padrão (DP) para idade gestacional e sexo, pré-púberes, nascidas a termo, de ambos os sexos, com indicação de tratamento com rGH. A intervenção foi realizada com rGH biossintético com doses variando de 0,03 a 0,05 mg/kg/dia, administrado por via subcutânea, uma vez ao dia ao deitar-se. A massa magra total (LM) e a massa gorda total (MG) foram determinadas por meio de absorciometria de raios X de dupla energia (DXA), e o perfil metabólico foi avaliado com dosagens de insulina, glicemia, IGF-1 e perfil lipídico. Resultados: Doze pacientes (nove meninas, 8,17±2,39 anos) foram avaliados; três pacientes abandonaram o estudo. Houve aumento da LM ajustada para estatura (LMI) (p=0,008), LMI standard deviation scores (SDS) ajustada para idade e sexo (p=0,007) e LM total (p<0,001). O percentual de gordura corporal (GC%) e gordura abdominal (AF) permaneceu inalterado em relação ao início do tratamento. Entre as variáveis metabólicas, a glicemia manteve-se na normalidade, e houve redução do número de participantes com colesterol alterado (p=0,023). Conclusões: O efeito do tratamento com HCr foi maior na MM do que na MG, com o aumento da MM ajustada para altura e padronizada para idade e sexo. A glicemia permaneceu normal e houve redução do número de crianças com colesterol total acima do recomendado.

Warning Signs on Short Hammersmith Neonatal Neurological Examination and Correlation With Hammersmith Infant Neurological Examination Global Score in Preterm Infants: A Prospective Cohort Study

Objective: To describe the findings of short Hammersmith Neonatal Neurologic examination (HNNE) in preterm small for gestational age (SGA) and appropriate for gestational age (AGA) infants at term equivalent age (TEA) and to correlate it with the global score of Hammersmith Infant Neurologic Examination (HINE) performed at 4-6 months of corrected age. Methods: This prospective cohort study was conducted at the high risk follow-up clinic of our center. 52 preterm infants born <35 weeks gestation were examined using HNNE at TEA and followedup till 4-6 months of corrected age to estimate HINE. Results: 20 infants (38.5%) had warning signs and 9 (17.3%) had abnormal signs on short HNNE. 12 (37.5%) AGA infants and 6 (30%) SGA infants had global score <65 at mean corrected age (SD) of 4.3 (0.7) weeks and 4.5 (0.8) weeks, respectively. Very preterm, birth weight <1000 g and SGA was significantly associated with global scores <65. Conclusion: Early identification of warning signs among SGA infants using Short HNNE screening at TEA can be useful to initiate early intervention. There was no statistically significant difference in global scores by HINE among AGA and SGA infants in early infancy.

Growth hormone effect on body composition of children born small for gestational age: a systematic review

Abstract Objective The present study aimed to evaluate the effects of GH treatment on the body composition of children born with SGA. Methods This study is a systematic review of the literature. CINAHL, Embase; Medline/Pubmed, Scopus and Web of Science were searched from inception to March 2022. Results Four studies met the inclusion criteria, with an intervention time of 1 to 3 years, using doses from 0.03 to 0.07 mg/kg/day of GH. Bone densitometry by dual-energy X-ray absorptiometry (DXA) with whole-body scans was the most used method to assess body composition. Most studies (n= 3) had SGA children as a control group with the same characteristics as the case group; the mean age was similar between the groups (minimum of 5.1 ± 1.4 years and maximum of 6.7 ± 1 0.8 years) and all participants had an average height ≤ -3DP. The Lean Mass (LM) and Fat Mass (FM) outcomes of the studies were not presented in a standardized manner; thus, they cannot be compared. There was a significant increase in LM in the group treated with GH in relation to the pre-treatment period and in comparison, to the untreated control group. Three studies showed a significant decrease in FM at the end of the intervention period, and in two studies, this decrease occurred in the control group. Conclusions Despite the differences in the presentation of results and in the evaluation periods, the results of the studies showed that growth hormone favors the gain and maintenance of lean mass, and it also affects fat mass reduction and redistribution.

Distribución espacial y tendencia secular (1991-2014) de nacidos pequeños para la edad gestacional en Jujuy / Spatial distribution and secular trend (1991­2014) of small for gestational age infants born in Jujuy

Introducción. El feto que no alcanza el potencial de crecimiento esperado en el útero se considera pequeño para la edad gestacional (PEG). Esta restricción depende de factores genéticos y/o ambientales; la altura geográfica es uno muy relevante. Este trabajo analiza la distribución espacial de las prevalencias de PEG y su tendencia secular en Jujuy (1991-2014). Materiales y métodos. Se analizaron los registros de 308 469 nacidos vivos de Jujuy (Dirección de Estadísticas e Información de Salud). Se estimaron prevalencias de PEG (peso/edad gestacional

Introduction. A fetus that does not reach the expected growth potential in utero is considered small for gestational age (SGA). Such restriction depends on genetic and/or environmental factors, being altitude a very relevant factor. This study analyzes the spatial distribution of the prevalence of SGA and its secular trend in Jujuy (1991­2014). Materials and methods. The records of 308 469 live births in Jujuy (Health Statistics and Information Department) were analyzed. The prevalence of SGA (weight/gestational age < P10 and < P3) was estimated for sex according to the INTERGROWTH-21 st standard in the ecoregions of Jujuy (Valle and Ramal ­less than 2000 MASL­, Puna, and Quebrada) across 3 periods (1991­2000, 2001­2009, 2010­2014) and proportions were compared. The secular trend was assessed using the Joinpoint regression analysis. Results. The overall prevalence of SGA was 2.3% (< P3) and 7% (< P10). Significantly higher values were observed in Puna and Quebrada in both SGA categories and across all periods. Only in Valle, significant differences were observed between sexes across all periods. The prevalence of SGA showed a significant downward secular trend at a provincial and regional level, and this was greater in Quebrada (5.2% < P3 and 3.5% < P10). Conclusions. A consistent and significant decrease in the prevalence of SGA has been observed since the 1990s in Jujuy, where altitude is itself a determining factor of size at birth, since the Puna and Quebrada regions showed the highest prevalence of SGA during the entire period.

Poor nutritional status of fifteen-year-old or younger adolescent mothers enhances the risk of small-for-gestational-age newborns

Introduction: To analyze the factors (socio-demographic, clinical, prenatal care, delivery, postpartum data and anthropometric measures) associated with the birth of small for gestational age newborns.Methods: A cross-sectional study was performed with 15 years old or younger postpartum adolescents divided into small-for-gestational-age newborn (SGA) and non-small-for-gestational age newborn groups (NSGA). Socio-demographic, clinical, prenatal care, delivery, postpartum data and anthropometric measures (triceps skinfold (TS), and mid-arm circumference, (MAC)) were collected.Results: 8,153 women gave birth at the obstetric ward and 364 (4.46%) ≤ 15 years old adolescents were enrolled in the study. The proportion of SGA newborns was 34.61%. The SGA group attended fewer prenatal visits (p = 0.037), had a higher prevalence of nutritional status classified as "very low weight" (p < 0.001) and vaginal delivery (p = 0.023), compared to the NSGA group. The nutritional status and vaginal delivery remained significant even after adjustment for confounders. The prevalence risk for SGA birth was 30% higher in the group of mothers with nutritional status classified as "very low weight" (odds ratio 1.30, 95% confidence interval 1.13 to 1.50) (p < 0.001).Conclusions: 15.4% of adolescents ≤ 15 years of age had an arm circumference compatible with the "very low weight" condition, demonstrating the high prevalence of poor maternal nutritional status in this group. The birth of SGA among adolescents ≤ 15 years of age is independently associated with maternal nutritional status classified as "very low weight" by the mid-arm circumference measures (MAC).

Auditory Pathway Maturation in Full-term Small for Gestational Age Children: A Systematic Review with Meta-analysis

Abstract Introduction Factors of intrauterine growth restriction have been responsible for the births of full-term babies small for their gestational age (SCA). Scientific evidence points that this restriction can cause changes in the neural maturation process. Objectives To analyze the absolute latencies and interpeak intervals of brainstem auditory evoked potential waves in full-term and SCA children to investigate whether there are changes of neural maturation in this population. Data Synthesis The search for articles that reported the assessment of brainstem auditory evoked potential in SCA newborns compared with a control, appropriate for their gestational age, both born full-term, for the entire period available in the database research until October31, 2021 was performed based on the MEDLINE/PubMed Central and on the Latin America and the Caribbean Health Sciences Literature and Virtual Health Library electronic databases. A total of 311 studies were found in the database research. Out of this total, 10 studies were included in the review, 5 of which were eligible for the meta-analysis, involving a total of 473 participants of both genders, with 193 participants belonging to the study group and 280 to the control group. Differences between the groups were only observed in the absolute latency of wave V (95% confidence interval [CI]: 0.02-0.15; p<0.01). Conclusion The SCA condition is responsible for the appearance of brainstem neural conduction dysfunction measured by the brainstem auditory evoked potentials, probably by the maturation process of the auditory pathway of this population.

Evaluación de la antropometría en neonatos sanos. No todas las medidas son relevantes / Anthropometry assesment in healthy neonates. Not all measurements are relevant

Resumen Las medidas antropométricas se han usado para evaluar el crecimiento fetal y neonatal, además de determinar factores de riesgo de forma temprana. Clásicamente se han tomado el peso, talla, perímetro cefálico, torácico y abdominal. Son usadas para establecer condiciones como peso bajo o elevado para la edad gestacional, y con base en esto poder definir riesgos tempranos y tardíos. Otra medida sumamente importante es el perímetro cefálico, misma que determina neonatos con potencial riesgo neurológico. Estas tres medidas son clave como parte de la evaluación inicial neonatal, además de que se incluyen en el seguimiento del crecimiento y desarrollo infantil. No obstante, otras mediciones rutinarias como el perímetro torácico y abdominal, en neonatos con adaptación espontánea y exploración física normal (neonatos sanos), puede que aporten poco acerca del estado de salud neonatal. Estas últimas medidas no forman parte de los parámetros de seguimiento del crecimiento infantil, ni cuentan con gráficas de percentiles extrapolables para género y edad gestacional. Todas estas medidas están condicionadas por múltiples factores como genética, raza y nutrición, entre otros. Es momento de analizar las medidas rutinarias al momento del nacimiento de neonatos sanos, y priorizar las extrapolables a implicaciones clínicas relevantes.

Abstract Anthropometric measurements are used to assess fetal and neonatal growth and determine early risk factors. Classically, weight, height, head circumference, thoracic and abdominal circumference are the usual measures. They are used to identify conditions such as low or high weight for gestational age and, based on this, to determine early and late risks. Another important measurement is head circumference, which determines neonates with potential neurological risk. These three measures are key as part of the initial neonatal evaluation, and they are also a part of the child's growth monitoring and development. However, other routine measurements such as chest and abdominal circumferences, in newborns with spontaneous adaptation and normal physical examination (healthy neonates) may provide little information about the neonatal health status. These last measurements are not part of the child growth monitoring parameters, nor do they have percentile graphs that can be extrapolated to gender and gestational age. All these measures are conditioned by multiple factors such as genetics, race, and nutrition, among others. It is time to analyze routine measures at the time of birth of healthy newborns and prioritize those that can be extrapolated to relevant clinical implications.

Secular Trends in Birthweights in Two Epochs Over 40 Years in a Tertiary Care Center

Objective: To compare the average birthweights and the weight centiles of the ‘new’ growth charts with the ‘old’ (1974) charts developed in the same unit four decades ago. Methods: Birthweight and gestation data of the eligible 12,355 singleton neonates born between 2009 and 2016 at a level-3 neonatal unit at a public sector hospital were used to develop the new growth chart. We then compared the prevalence of small for gestational age (SGA) and large for gestational age (LGA) classified by the new charts and the old charts, the incidence of short-term adverse outcomes among them, and the diagnostic performance of both the charts to identify the adverse outcomes in a separate validation cohort. Results: The mean birthweights of boys and girls across all gestations were higher by 150-200 g and 100-150 g, respectively, in the new chart. The prevalence of SGA doubled (9.8% vs 4.7%), but LGA decreased by one-third (17.5% vs 25.9%) with the new chart. However, the proportion of SGA and LGA having one or more short-term adverse outcomes, and the diagnostic performance of both the charts to identify neonates with shortterm adverse outcomes, were comparable. Conclusion: There was an upward shift in the birthweights by about 150 g across all gestations in the new chart compared to the old chart developed 40 years ago. The findings imply the need to consider using updated growth charts to ensure accurate classification of size at birth of neonates.

Eficácia e segurança de Somatropina para o tratamento de crianças nascidas pequenas para a idade gestacional: revisão rápida de evidências / Efficacy and safety of Somatropine for the treatment of children born small for gestational age: a rapid response review of evidence

Tecnologia: Somatropina. Indicação: Transtorno de crescimento em crianças nascidas pequenas para a idade gestacional (PIG). Pergunta: A somatropina é eficaz e segura para promover aumento da curva de crescimento em crianças nascidas PIG? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Resultados: Foi selecionada uma revisão sistemática que atendeu aos critérios de inclusão. Conclusão: evidências de moderada certeza indicam que somatropina é eficaz e segura para tratamento de crianças nascidas PIG, pois promove recuperação do crescimento e não há relatos de eventos adversos graves na literatura científica

Technology: Somatropin. Indication: Growth disorder in children born small for gestational age (SGA). Question: Is somatropin effective, safe and cost effective for promoting height gain in children born SGA? Methods: A bibliographic search was done in PUBMED database, following predefined search strategies. The methodological quality of systematic reviews was evaluated using the AMSTAR-2 tool (A MeaSurement Tool to Assess systematic Reviews version 2). Results: Only a systematic review met the inclusion criteria and was selected. Conclusion: Evidence of moderate certainty indicates that somatropin is effective and safe for the treatment of children born SGA, because the treatment improve the growth and there are no reports of serious adverse events in the scientific literature

Advance in postnatal catch-up growth and insulin resistance in small for gestational age infants / 中华围产医学杂志

Small for gestational age (SGA) infants usually result from fetal growth restriction. After eliminating harmful factors, catch-up growth occurs in most SGA as a compensatory mechanism of children's growth and development. Many studies conclude that catch-up growth could lead to insulin resistance early in life. However, the mechanism remains unclear, which results in a lack of clinical intervention to reduce or even avoid insulin resistance. This review sums up studies on catch-up growth and insulin resistance. It describes the possible mechanism of suppressed thermogenesis and catch-up fat, stress, inflammation, DNA methylation, etc., to provide a theoretical foundation for clinical practice.

Exploration on appropriate fetal weight of twin pregnancies at different gestational weeks and pregnancy complications and outcomes / 中华妇产科杂志

Objective:To explore the appropriate fetal weight of twin pregnancies at different gestational weeks and the association with pregnancy complications and outcomes.Methods:Fetal weight at different gestational weeks and related pregnancy complications and outcomes from 1 225 twin pregnancies, who gave birth at Peking University First Hospital from January 2004 to December 2020, were analyzed in this study, including hypertensive disorders in pregnancy, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), fetal distress, preterm birth and neonatal asphyxia. The appropriate fetal weight of twin pregnancies at different gestational weeks were analysed based on the information from 616 twin pregnancies without complications (except preterm birth), and were expressed as P10~ P90. The chi-square test was used to compare the risk of pregnancy complications and adverse outcomes in large for gestational age (LGA), appropriate for gestational age (AGA) and small for gestational age (SGA) twin pregnancies and the difference in incidence of pregnancy complications and adverse outcomes in different years. Results:The appropriate fetal weights of normal twin pregnancies at 28 to 37 weeks and 38-40 weeks of gestation were 910-1 255 g, 996-1 518 g, 1 105-1 785 g, 1 295-1 825 g, 1 336-2 000 g, 1 754-2 321 g, 1 842-2 591 g, 1 913-2 615 g, 2 150-2 847 g, 2 350-3 130 g and 2 450-3 250 g, respectively. The incidences of hypertensive disorders in pregnancy, FGR, fetal distress and neonatal asphyxia related to SGA twin pregnancies were significantly higher than AGA twin pregnancies (all P<0.05). The incidence of GDM in twin pregnant from 2017 to 2020 was higher than that from 2004 to 2009 or from 2010 to 2016, but the incidence of fetal distress and neonatal asphyxia were lower than those from 2010 to 2016, and the differences were statistically significant (all P<0.05). Conclusions:The appropriate weights of twin fetuses at different gestational weeks are different from singleton. The incidence of pregnancy complications and adverse outcomes in AGA fetuses is significantly lower than that in SGA fetuses under the specific weight standard for twin fetuses, which could provide a practical basis for clinical management of twin pregnancy.

Research progress on the relationship between Klotho and the growth of children and newborns / 中国综合临床

Klotho is a gene associated with aging, the transmembrane protein encoded by this gene is highly expressed in the kidney, and is also expressed in tissues such as the brain, parathyroid and pituitary glands. The extracellular domain of Klotho can also be cleaved and shed to form soluble Klotho, which acts as a circulating hormone and can be detected in blood, cerebrospinal fluid, and urine. More and more studies have shown that Klotho protein plays an important role in the complex regulation of growth hormone (GH)-insulin-like growth factor 1(IGF1) axis. The interaction between Klotho protein and GH-IGF1 axis is bidirectional, which regulates each other, and then regulates the normal linear growth of children. In addition, Klotho protein can also affect the growth and development of fetus and newborn through different ways, and its mechanism is not very clear.

Investigation on the IGF-1 and lipid level in term small for gestational age infants within 24 hours postnatally / 中国新生儿科杂志

Objective:To study the insulin-like growth factors-1 (IGF-1) and lipid level of term small for gestational age (SGA) infants within 24 hours postnatally and to explore the correlation between IGF-1 and blood lipids.Methods:A prospective study was conducted on singleton term SGA and appropriate for gestational age infant (AGA) who were delivered and admitted to the neonatal ward of Guangdong Women and Children Hospital within 24 hours after birth from May 2020 to January 2021, and the infants were divided into SGA and AGA groups to compare the differences in IGF-1 and lipid levels within 24 hours after birth and to analyze the correlation between IGF-1 and lipids.Results:A total of 95 cases in the SGA group and 84 cases in the AGA group were included in the study. The proportion of infants with IGF-1 <25 ng/ml was significantly higher in SGA group (87.4%) than in the AGA group (52.4%). It was also found that the proportion of infants with IGF-1 <25 ng/ml in SGA was significantly higher than that in AGA within different gender composition groups, early-term and full-term births groups. The triglyceride (TG) level was higher in the SGA group than that in the AGA group, but the high-density lipoprotein cholesterol (HDL-C) level was lower than that in the AGA group ( P<0.05). IGF-1 level within 24 hours postnatally in SGA and AGA was positively correlated with HDL-C levels ( P<0.01) and negatively correlated with TG ( P<0.01), and HDL-C level was a predictor of IGF-1. Conclusions:Compared with term AGA, SGA term infants showed insufficient IGF-1 and HDL-C secretion and high TG within 24 hours after birth. Nutritional support for SGA should be given promptly after birth to avoid hypoglycemia and to stimulate IGF-1 secretion.

The Invisible Struggles: A Qualitative Study in Understanding Mothers’ Perceptions and Experiences in Nurturing Small for Gestational Age Infants

@#Introduction: Small for gestational age (SGA) infants have been linked to poor growth trends and nutritional status. SGA infants that do not reach their full growth potential must be supervised by a multidisciplinary medical team. Parents devote more time, energy, and money for raising of the SGA infants. The objective of this present study is to explore the perceptions and the experiences of the mother in nurturing the small for gestational age infants in their first year of life. Method: A qualitative exploratory descriptive study via in-depth interview was conducted in the primary health clinics in urban areas in Malaysia to explore the mothers’ perceptions and experiences in SGA infant’s care. 13 SGA infant’s mothers participated in the study after the children achieved the age of one year old. Thematic analysis was conducted using software ATLAS.ti version 8. Results: The average mothers’ age in this study were 33 years old, majority was Malay ethnicity. Only one mother was a housewife and others were working mother. Four out of 13 SGA infants were born prematurely. This study found that homogenous experiences throughout the pregnancy and baby nurturing phase, perceptions on husband involvement and external supports in infant care, infant health status and health services provided, were highlighted as important contributor to infant survival. Conclusion: The importance of monitoring SGA infant growth and nutritional status have been highlighted. Maternal psychological support needs to be enhanced to ease the burden in SGA infant care. Targeted program intervention for family and community social support during postnatal and empowering mothers in nurturing their infants are crucial.

Identifying susceptible exposure windows for ambient nitrogen dioxide before and during pregnancy and increased risks of small/large for gestational age / 环境与职业医学

Background Exposure to ambient nitrogen dioxide (NO2) could increase the risks of small for gestational age (SGA) and large for gestational age (LGA). Nevertheless, previous published studies usually use a time period over relatively long durations as the exposure window, such as trimester-specific or gestational months, to identify adverse pregnancy outcomes related susceptible exposure windows for ambient air pollution. At present, no study has explored associations of weekly-specific ambient air NO2 exposure around pregnancy with SGA and LGA. Objective To evaluate the associations of exposure to ambient NO2 over the preconception and entire pregnancy period with risks of SGA and LGA, as well as to explore critical windows of NO2 exposure by refining exposure period to specific weeks. Methods Based on a birth cohort established by the project Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) situated in Tianjin, 10 916 singleton pregnant women whose dates of the last menstrual period and delivery were both between June 2014 and June 2016, and whose gestational age were within 24-42 completed gestational weeks were included in this study. Each pregnant woman's exposures to ambient NO2 throughout 12 weeks before pregnancy and pregnancy period were matched with daily average NO2 concentrations obtained from the Chinese air quality reanalysis datasets (CAQRA). Distributed lag models incorporated in Cox proportional hazard regression models were applied to explore the associations of maternal exposure to weekly ambient NO2 throughout 12 weeks before pregnancy and pregnancy period with risks of SGA and LGA after controlling for potential confounders including maternal age, ethnicity, educational level, occupation, body mass index before pregnancy, residence, times of gravidity and parity, smoking, alcohol consumption, husband smoking, and season of conception. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated per 3 μg·m−3 increase in ambient NO2 concentrations. Results The average levels of maternal exposure to NO2 over the preconception, first trimester, second trimester, third trimester, and entire pregnancy periods were (39.6±10.8), (42.7±10.5), (44.8±12.7), (37.7±11.1), and (41.6±4.8) μg·m−3, respectively. For a 3 μg·m−3 increase in NO2 over the first trimester, the risk of SGA increased by 19.0% (95%CI: 8.0%-32.0%). For a 3 μg·m−3 increase in NO2 over the preconception, first trimester, and entire pregnancy, the associated risks of LGA increased by 7.0% (95%CI: 1.0%-13.0%), 37.0% (95%CI: 29.0%-46.0%) and 19.0% (95%CI: 9.0%-31.0%), respectively. For SGA, the susceptible exposure windows for NO2 were observed during the 7th to 12th preconceptional weeks and the 6th to 12th gestational weeks, with the strongest association found at the 12th preconceptional week, when the risk of SGA increased by 6.0% (95%CI:3.2%-8.9%) for a 3 μg·m−3 increase in NO2. For LGA, the susceptible exposure windows for NO2 were observed during the 1st to 12th preconceptional weeks and the 1st to 6th gestational weeks, with the strongest association found at the 12th preconceptional week, when the risk of LGA increased by 6.1% (95%CI: 4.5%-7.8%) for a 3 μg·m−3 increase in NO2. Conclusion Exposure to ambient NO2 is associated with increased risks of both SGA and LGA, and the most susceptible weekly exposure windows are nested within the 12 weeks before pregnancy and early pregnancy.

In-hospital outcomes in preterm and small-for-gestational-age newborns: a cohort study

ABSTRACT Objective To compare in-hospital outcomes between small-for-gestational-age and appropriate-for-gestational-age preterm neonates who needed intensive care. Methods A retrospective cohort study with preterm newborns, from January to December 2017. The results are presented as median, frequency, and odds ratio. Numerical variables were compared using the Wilcoxon test. Categorical variables were compared using the χ2 test. We considered p<0.05 as significant. Results Out of 129 preterm newborns included, 20.9% were small-for-gestational-age. Median gestational age was 31 2/7 weeks, birthweight was 1,450g, and length of hospital stay was 39 days. Preterm small-for-gestational-age newborns presented a higher chance of peri-intraventricular hemorrhage (odds ratio of 3.23; p=0.02), retinopathy of prematurity (odds ratio of 2.78 p=0.02), patent ductus arteriosus (odds ratio of 2.50; p=0.04) and a lower chance of presumptive early-onset sepsis (odds ratio of 0.37; p=0.03). Conclusion Preterm small-for-gestational-age neonates were associated with peri-intraventricular hemorrhage, retinopathy of prematurity and patent ductus arteriosus. This emphasizes the need of special care for these neonates.

Evidence of changes in the oral language in children born full-term and small for gestational age: a systematic review / Evidências de alterações na linguagem oral de crianças nascidas a termo pequenas para a idade gestacional: uma revisão sistemática

Abstract Objective: To perform a systematic review in order to verify the association between full-term birth of small for gestational age (SGA) children and the outcomes in the development of oral language. Data source: Articles from MEDLINE/PubMed, Web of Science, Embase, Lilacs, SciELO and Cochrane Library databases were identified, selected and critically evaluated by two independent reviewers and a judge, blindly, without language restriction and publication period. The PRISMA tool was used, and original studies with a theme involving children born full-term and SGA were included, outcome related to aspects of oral language development, as well as the use of tests, scales and/or specific questionnaires for the investigation, whose methodology was described in full, with children as the target population. Data synthesis: The researchers included nine articles based on the eligibility criteria. Studies have shown that being born SGA can interfere in aspects related to language and reported greater chances of under performance in SGA children when compared to children with appropriate size for gestational age. It was observed that the different studies did not have a uniform design, and the objectives were quite diverse. Furthermore, few of them had as focus issues related to the assessment of language, as well as the variability of instruments used to investigate this domain. Conclusions: The effects of low weight for gestation age in full-term infants continue beyond the neonatal period and may impact on children's performance, mainly with regard to oral language development.

Resumo Objetivo: Realizar uma revisão sistemática para verificar a associação entre o nascimento a termo de crianças pequenas para a idade gestacional (PIG) e os desfechos no desenvolvimento da linguagem oral. Fontes de dados: Artigos dos bancos de dados MEDLINE/PubMed, Web of Science, Embase, LILACS, SciELO e Cochrane Library foram identificados, selecionados e avaliados criticamente por dois revisores independentes e um juiz, às cegas, sem restrições de idioma e período de publicação. A ferramenta PRISMA foi utilizada e foram incluídos estudos originais envolvendo crianças nascidas a termo e PIG, desfechos relacionados a aspectos do desenvolvimento da linguagem oral, bem como o uso de testes, escalas e/ou questionários específicos para a investigação, cuja metodologia estava descrita na íntegra, com crianças como população-alvo. Síntese dos dados: Nove artigos foram incluídos a partir dos critérios de elegibilidade. Os estudos demonstraram que nascer PIG pode interferir em aspectos relacionados à linguagem e relataram que as chances de crianças PIG apresentarem um desempenho inferior são maiores quando comparadas as com tamanho adequado para a idade gestacional. Observou-se que os diferentes estudos não tinham um delineamento uniforme e seus objetivos eram bastante diversificados. Além disso, poucos focavam em questões relacionadas à avaliação da linguagem e foi possível notar uma variabilidade de instrumentos utilizados para investigar esse domínio. Conclusões: Os efeitos do baixo peso ao nascer em nascidos a termo persistem além do período neonatal e podem ter impacto no desempenho infantil, principalmente no que se refere ao desenvolvimento da linguagem oral.

Processos fonológicos produtivos em escolares nascidos a termo e pequenos para a idade gestacional: estudo caso-controle / Phonological productive processes in full-term schoolchildren and small for gestational age: a case-control study

RESUMO Objetivo Caracterizar o uso de processos fonológicos produtivos no grupo de crianças nascidas a termo e pequenas para a idade gestacional e compará-lo com crianças adequadas para a idade gestacional. Método Estudo observacional, analítico, do tipo caso-controle, não pareado, aninhado a uma coorte com o desfecho alteração fonológica. Foram avaliadas 36 crianças de acordo com o cálculo amostral pré-estabelecido, sendo 24(66,7%) sem alterações fonológicas e 12(33,3) com alteração fonológica. Dessas, 24(66,7%) crianças foram classificadas como pequeno para a idade gestacional (PIG) e 12(33%), como adequada para a idade gestacional (AIG). Os aspectos fonológicos da linguagem oral foram avaliados pelo teste de linguagem infantil ABFW (2004). Os resultados foram submetidos à análise descritiva e a fim de avaliar a existência de associação entre as variáveis categóricas, foi utilizado o teste exato de Fisher de associação. Resultados O grupo PIG apresentou significativamente maior número de processos fonológicos que alteram a estrutura da sílaba quando comparado ao grupo AIG. Observou-se que os processos fonológicos presentes e não esperados para idade na população PIG foram: plosivação de fricativa, simplificação de líquidas, posteriorização e frontalização de palatal, ensurdecimento de plosivas e fricativas, além da simplificação do encontro consonantal e simplificação de consoante final, que foram os de maior ocorrência em ambos os grupos. Conclusão Embora não tenha sido encontrada associação entre alterações fonológicas e crianças PIG, observou-se maior uso de processos fonológicos produtivos neste grupo.

ABSTRACT Purpose To characterize the use of phonological productive processes in a group of full-term children and small for gestational age and compare it with children appropriate for gestational age. Methods Observational, analytical, case-control and non-paired study, nested in a cohort with the outcome of phonological disorder. We assessed 36 children according to the predetermined sample calculation, 24 (66.7%) without phonological disorders and 12 (33.3%) with phonological disorders. Of these, 24 (66.7%) children were classified as small for gestational age (SGA) and 12 (33%) as appropriate for gestational age (AGA). Phonological aspects of oral language were assessed by the ABFW children's language test (2004). The results were subjected to descriptive analysis and, in order to assess the existence of an association among categorical variables, we used Fisher's exact test for association. Results The SGA group revealed a significantly higher number of phonological processes that change the syllable structure when compared to the AGA group. We noted that the phonological processes present and unexpected for age in the SGA population were: fricative plosivation, liquid simplification, palatal posteriorization and frontalization, plosive and fricative deafening, in addition to simplifying the consonant cluster and simplifying the final consonant, which were the most frequent in both groups. Conclusion Although no association was found between phonological disorders and SGA children, we have noted a greater use of productive phonological processes in this group.

Diseases during pregnancy in a large unselected South American sample / Prevalência de doenças durante a gravidez em uma grande amostra sul-americana não selecionada

ABSTRACT Objective: Our aim was to describe the prevalence of diseases during pregnancy and the association between fetal exposure to the most frequent maternal diseases and the risk of preterm (PTB) and/or small for gestational age (SGA) newborns in an unselected sample of women who gave birth in South American countries. Methods: We conducted a descriptive, cross-sectional study including 56,232 mothers of non-malformed infants born between 2002 and 2016, using data from the Latin American Collaborative Study of Congenital Malformations (ECLAMC). Diseases with higher- than-expected PTB/SGA frequencies were identified. Odds ratios of confounding variables for diseases and birth outcomes were calculated with a multivariable logistic regression. Results: Of the 14 most reported diseases, hypertension, genitourinary infection, epilepsy, hypothyroidism, diabetes, and HIV/AIDS showed higher PTB and/or SGA frequencies. Advanced and low maternal age, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with PTB, while advanced maternal age, primigravidity, previous fetal loss, low socioeconomic level, and African-American ancestry were associated with SGA. After adjusting for the associated variables, the identified illnesses maintained their association with PTB and all, except epilepsy, with SGA. Conclusion: The description of an unselected population of mothers allowed identifying the most frequent diseases occurring during gestation and their impact on pregnancy outcomes. Six diseases were associated with PTB and two with SGA newborns. To the best of our knowledge, there are no similar reports about women not intentionally selected by specific diseases during pregnancy in South American populations.

RESUMO Objetivo: Descrever a prevalência de doenças durante a gravidez e a associação entre a exposição fetal às doenças maternas mais prevalentes e o risco de recém-nascidos prematuros (PP) e/ou pequenos para a idade gestacional (PIG) em uma amostra não selecionada de mulheres que deram à luz em países da América do Sul. Métodos: Estudo descritivo transversal que incluiu 56.232 mães de crianças não malformadas nascidas entre 2002 e 2016, utilizando dados do Estudo Colaborativo Latino-americano de Malformações Congênitas (ECLAMC). Foram identificadas as doenças com maior número de casos observado/esperado de PP/PIG. O esperado foi obtido dos controles sem doenças. Odds ratios para variáveis de confusão de doença e eventos ao nascimento foram calculadas usando regressão logística multivariada. Resultados: Das 14 doenças mais referidas, hipertensão, infecção geniturinária, epilepsia, hipotireoidismo, diabetes e HIV/AIDS apresentaram maiores frequências de PP e/ou PIG. Idade materna nos dois extremos, perda fetal prévia, baixo nível socioeconômico e ascendência afro-americana foram associados a PP, enquanto idade materna avançada, primigravidez, perda fetal prévia, baixo nível socioeconômico e ascendência afro-americana foram associados a PIG. Após ajuste para as variáveis associadas, as doenças identificadas mantiveram associação com PP e todas, exceto epilepsia, com PIG. Conclusão: A descrição de uma população não selecionada de gestantes possibilitou identificar as doenças mais frequentes e seu impacto nos resultados adversos na gravidez. Seis doenças foram associadas a PP e duas a recém-nascidos PIG. Até onde sabemos, não há relatos semelhantes sobre mulheres não selecionadas intencionalmente por doenças específicas durante a gravidez em populações sul-americanas.

Variables maternas metabólicas y mixtas, su relación con la restricción del crecimiento uterino / Metabolic and mixed maternal variables,theirrelationship with uterine growth restriction

RESUMEN Fundamento: la restricción del crecimiento intrauterino constituye uno de los principales desafíos de la obstetricia moderna, en países en vías de desarrollo. Los individuos que fueron víctimas de restricción del crecimiento intrauterino son biológicamente diferentes, lo que incluye una mayor susceptibilidad a padecer enfermedades crónicas en la adultez. Objetivo: identificar variables maternas metabólicas y mixtas presumiblemente relacionadas con las restricciones del crecimiento intrauterino. Métodos: se realizó estudio analítico transversal engestantes del policlínico Chiqui Gómez Lubiándel municipio Santa Clara, que terminaron su embarazo entre septiembre de 2013 y octubre de 2018, y cuyos recién nacidos presentaron restricción del crecimiento intrauterino. La muestra se clasificó en pequeños y adecuados, según condición trófica al nacimiento. En cada grupo se estudió relación con variables maternas metabólicas y mixtas presumiblemente vinculadas con el fenómeno de restricción. Resultados: las madres de niños restringidos mantuvieron valores normales de variables metabólicas a la captación, pero mostraron alteración de las variables mixtas. Conclusiones: la restricción del crecimiento intrauterino pudiera estar relacionado con la alteración de las variables mixtas observadas en sus madres.

ABSTRACT Background: intrauterine growth restriction is one of the main challenges of modern obstetrics, mainly in developing countries. Individuals who were victims of intrauterine growth restriction are biologically different, which includes a greater susceptibility to suffering from chronic diseases in adulthood. Objective: to identify maternal, metabolic and mixed variables presumably related to intrauterine growth restrictions. Methods: a transverse analytic study of pregnant women, who ended their pregnancy between September 2013 and October 2018 and whose newborns had intrauterine growth restriction was carried out in the Chiqui Gómez Lubián polyclinic of the municipality of Santa Clara. The sample was classified as small and adequate, according to trophic condition at birth. In each group, a relationship with metabolic and mixed variables, presumably related to the intrauterine restriction phenomenon, was studied. Results: mothers of restricted children maintained normal values ​​of metabolic variables upon uptake, but showed alteration of mixed variables. Conclusions: intrauterine growth restriction could be related to the alteration of the mixed variables observed in their mothers.