Influencia de la malnutrición fetal en el crecimiento y desarrollo craneofacial

Introducción: La malnutrición fetal incide de forma negativa en el crecimiento y la maduración, afectando las estructuras craneofaciales en el feto. Objetivo: Determinar los efectos de la malnutrición fetal por defecto en el crecimiento y desarrollo craneofacial en niños. Métodos: Se realizó un estudio analítico de casos y controles, en el área de salud José Martí del municipio Camagüey, desde enero de 2018 hasta diciembre de 2020. El universo estuvo constituido por niños de 6-11 años de edad, pertenecientes al área salud y la muestra quedó conformada por 40 niños, 20 en el grupo de estudio y 20 controles. El grupo de estudio se conformó por niños que presentaron bajo peso al nacer por defecto y tuvieron alteraciones en el crecimiento del complejo craneofacial y el grupo control por niños que no presentaron alteraciones en el crecimiento del complejo craneofacial y que al nacimiento se encontraban normopeso. A todos los niños se les efectuaron mediciones antropométricas craneofaciales. Resultados: La medida de la circunferencia cefálica al nacer en los controles masculinos superó en 0,78 cm al sexo femenino y entre los malnutridos por defecto, los masculinos lograron 1,57 cm más que los femeninos. En el diámetro bicigomático hubo una fuerte asociación estadística y el riesgo relativo indicó que la incidencia del bajo peso al nacer fue mayor que en los controles (p <0,05). Conclusiones: Los niños con bajo peso al nacer presentan menor crecimiento y desarrollo craneofacial según las variables antropométricas.

Introduction: Fetal malnutrition impacts in a negative way the growth and development, thus affecting the craniofacial structures of the fetus. Objective: To determine the effects of fetal malnutrition by defect on craniofacial growth and development in children. Methods: An analytical case and control study was carried out in Jose Martí health area of Camagüey, from January 2018 to December 2020. A sample of 40 was selected from the totality of the children between 6 and 11 years old who belong to the referred health area, to be divided into 20 cases and the same number in the control group. The study group was composed of those low birth weight who present craniofacial abnormalities while control group included the children without craniofacial abnormalities and normal weight at birth. Anthropometric craniofacial measurements were performed on all the sample. Results: The head circumference at birth in male children of control group was 0.78 cm higher than that on female sex. Among those low birth weight, male children exhibited 1.57 cm higher than females. Regarding the bizygomatic diameter there was a strong statistic association and the relative risk indicated a higher incidence on the study group compared to the control group (p <0.05). Conclusions: Low birth weight children show lower craniofacial growth and development, with higher impact on females according to anthropometric variables.

Hyperemesis gravidarum severity, enteral tube feeding and cardiometabolic markers in offspring cord blood.

This study aimed to investigate the association between hyperemesis gravidarum (HG) severity and early enteral tube feeding on cardiometabolic markers in offspring cord blood. We included women admitted for HG, who participated in the MOTHER randomised controlled trial (RCT) and observational cohort. The MOTHER RCT showed that early enteral tube feeding in addition to standard care did not affect symptoms/birth outcomes. Among RCT and cohort participants, we assessed how HG severity affected lipid, c-peptide, glucose and free thyroxine cord blood levels. HG severity measures were severity of vomiting at inclusion and 3 weeks after inclusion, pregnancy weight gain and 24-h energy intake at inclusion, readmissions and duration of hospital admissions. Cord blood measures were also compared between RCT participants allocated to enteral tube feeding and those receiving standard care. Between 2013-2016, 215 women were included: 115 RCT and 100 cohort participants. Eighty-one cord blood samples were available. Univariable not multivariable regression analysis showed that lower maternal weight gain was associated with higher cord blood glucose levels (ß: -0·08, 95% CI -0·16, -0·00). Lower maternal weight gain was associated with higher Apo-B cord blood levels in multivariable regression analysis (ß: -0·01, 95% CI -0·02, -0·01). No associations were found between other HG severity measures or allocation to enteral tube feeding and cord blood cardiometabolic markers. In conclusion, while lower maternal weight gain was associated with higher Apo-B cord blood levels, no other HG severity measures were linked with cord blood cardiometabolic markers, nor were these markers affected by enteral tube feeding.

Maternal low-protein diet on the last week of pregnancy contributes to insulin resistance and ß-cell dysfunction in the mouse offspring.

Maternal low-protein diet (LP) throughout gestation affects pancreatic ß-cell fraction of the offspring at birth, thus increasing their susceptibility to metabolic dysfunction and type 2 diabetes in adulthood. The present study sought to strictly examine the effects of LP during the last week of gestation (LP12.5) alone as a developmental window for ß-cell programming and metabolic dysfunction in adulthood. Islet morphology analysis revealed normal ß-cell fraction in LP12.5 newborns. Normal glucose tolerance was observed in 6- to 8-wk-old male and female LP12.5 offspring. However, male LP12.5 offspring displayed glucose intolerance and reduced insulin sensitivity associated with ß-cell dysfunction with aging. High-fat diet exposure of metabolically normal 12-wk-old male LP12.5 induced glucose intolerance due to increased body weight, insulin resistance, and insufficient ß-cell mass adaptation despite higher insulin secretion. Assessment of epigenetic mechanisms through microRNAs (miRs) by a real-time PCR-based microarray in islets revealed elevation in miRs that regulate insulin secretion (miRs 342, 143), insulin resistance (miR143), and obesity (miR219). In the islets, overexpression of miR143 reduced insulin secretion in response to glucose. In contrast to the model of LP exposure throughout pregnancy, islet protein levels of mTOR and pancreatic and duodenal homeobox 1 were normal in LP12.5 islets. Collectively, these data suggest that LP diet during the last week of pregnancy is critical and sufficient to induce specific and distinct developmental programming effects of tissues that control glucose homeostasis, thus causing permanent changes in specific set of microRNAs that may contribute to the overall vulnerability of the offspring to obesity, insulin resistance, and type 2 diabetes.

Evaluation of the INTERGROWTH-21st project newborn standard for neonatal phenotypes and neonatal morbidity and mortality.

INTRODUCTION: The use of local references or standard for neonatal studies still requires their validation through indicators of morbidity and mortality. OBJECTIVE: evaluate the performance of the INTERGROWTH-21st Project (IG-21) standard and a commonly used Argentinian reference (Urquia) by examining the differences in the frequency of growth phenotypes, and the associated neonatal morbidity and mortality. METHODS: Retrospective cohort study of all singleton live-births from Sarda Maternity Hospital (Buenos Aires, Argentina) between 33 and 42 gestational age, using information obtained from a Perinatal Surveillance System (Agustina) dataset between 1996-2001 (n = 25948). Phenotypes small- and large-for-gestational age, stunting and waisting and a composite of neonatal morbidity/mortality (CNMM) were contrasted between the IG-21 standard and Urquia reference. RESULTS: the Urquia 3rd centile value was lower than IG-21 before 37 weeks, but then it surpassed IG-21 until term. Among Sarda , 2.3%, 5.9% and 8.9 were <3rd, <10th and >97th centile, respectively, under the IG-21 standard, while 3.7%, 10.1% and 8.4% were <3rd, <10th and >97th centile, respectively, under the Urquia reference. Stunting and waisting were 16.1% and 0.9%, respectively under IG-21. The IG-21 detection rates of CNMM showed that 28.5%, 19.6% and 8.5% occurred among weight<3rd,<10th and >97th centile, respectively, while 21.8%, 14.2% and 8.0%  occurred among <3rd, <10th and >97th centile under the Urquia criteria. Newborn weight <3rd,<10th and >97th  centile under IG-21 showed higher neonatal CNMM risk compared with Urquia reference. CONCLUSIONS: The IG-21 standard identified a higher risk of neonatal morbidity and mortality than the Urquia reference.

Introducción: El uso de referencias locales o estándares para estudios neonatales aún requiere su validación a través de indicadores de morbilidad y mortalidad. Objetivo: Comparar la capacidad predictiva del estándar INTERGROWTH-21st (IG-21st) y una referencia argentina (Urquia) mediante los fenotipos de crecimiento fetal y morbi-mortalidad neonatales. Métodos: Estudio de cohorte retrospectivo de recién nacidos vivos entre 33 y 42 semanas del Hospital Materno-Infantil Ramón Sarda (Buenos Aires, Argentina), entre 1996-2001 (n = 25948). Los fenotipos pequeños (PEG) y grandes para la edad gestacional, acortado y emaciado y un índice compuesto de morbilidad / mortalidad neonatal (CNMM) se contrastaron entre IG-21st y la referencia Urquia. Resultados: El 3er percentil del peso al nacer de Urquia fue menor que el de IG-21st antes de las 37 semanas; 2.3%, 5.9% y 8.9 de los RN fueron <3o, <10° y > 97° percentil, respectivamente, bajo el estándar IG-21st, mientras que 3,7%, 10,1% y 8,4% fueron <3 °, <10 ° y> 97 ° percentil, respectivamente, bajo la referencia Urquia. Acortados fueron 16.1% y emaciados 0.9%, bajo IG-21st. CNMM bajo IG-21st fueron 28.5%, 19.6% y 8.5% en peso<3o, <10º y >97º percentil, respectivamente, mientras que 21.8%, 14.2% y 8.0% ocurrieron en peso< 3°, <10° y > 97° percentil bajo Urquia. Acortados fueron 17.3% y emaciados 18.3%. Los RN <3er°, <10° y > 97° percentil bajo IG-21st mostraron mayor riesgo de CNMM en comparación con la referencia Urquia. Conclusiones: El estándar IG-21st identificó mayor riesgo de morbilidad y mortalidad que la referencia Urquia.

Adequação do peso ao nascer para idade gestacional de acordo com a curva INTERGROWTH-21 st e fatores associados ao pequeno para idade gestacional / Adequacy of birth weight for gestational age according to INTERGROWTH-21st curve and factors associated with the small for gestational age

Resumo Introdução Apesar do conhecimento sobre a etiologia multifatorial do crescimento intrauterino restrito, há escassez de estudos nacionais. Objetivo Estimar a adequação do peso ao nascer para idade gestacional e investigar fatores associados ao recém-nascido pequeno para idade gestacional (RN-PIG), com destaque para tabagismo e pré-natal. Método Estudo seccional em maternidades públicas no Rio de Janeiro e em Niterói, em 2011, com 1.771 nascidos vivos. Foram realizadas entrevistas com puérperas e consultas em prontuários. Estimaram-se prevalências e intervalos de confiança (IC95%) de recém-nascido pequeno para idade gestacional (RN-PIG), recém-nascido adequado para idade gestacional (RN-AIG) e recém-nascido grande para idade gestacional (RN-GIG), usando a curva INTERGROWTH-21st , segundo características maternas, da gestação e do recém-nascido. Utilizou-se regressão de Poisson, com o desfecho sendo nascer PIG. Resultados As prevalências foram de 9,3% para PIG e de 15,9% para GIG. Cor parda (RP = 1,4), baixa escolaridade (RP = 1,3), inadequação de pré-natal (RP = 1,3), tabagismo (redução/cessação: RP = 1,7; continuidade: RP = 2,4) e hipertensão arterial (RP = 1,3) foram associados ao PIG na análise univariada (p < 0,20), e apenas tabagismo manteve-se associado no modelo final (redução/cessação: RP = 1,7 e continuidade: RP = 2,3; p < 0,05). Conclusão A prevalência de PIG mostrou um efeito dose-resposta com o tabagismo. Estratégias populacionais antitabaco devem intensificar a prevenção direcionada às mulheres em idade fértil e, particularmente, às gestantes, com ações específicas para estímulo à cessação no pré-natal.

Abstract Background There are few national studies despite the knowledge about the multifactorial etiology of restricted intrauterine growth. Objective To estimate the adequacy of birth weight for gestational age and investigate factors associated with the newborns small for the gestational age (NB-SGA). Method This is a cross-sectional study in public maternity hospitals in Rio de Janeiro and Niterói, RJ, in 2011 (1,771 live births). Data sources was through interviews with the mothers and medical records. The prevalence of NB-SGA, adequate (NB-AGA) and large (NB-LGA) for gestational age newborn were estimated (INTERGROWTH21st) according to maternal, gestational and newborn characteristics. Poisson regression was used (outcome SGA). Results The prevalence rates were: 9.3% SGA and 15.9% LGA. Brown skin color (prevalence rate - PR = 1.4), low scholarship (RP=1.3), prenatal inadequacy (RP = 1.3), smoking (reduction/cessation: RP = 1.7, continuity: RP = 2.4) and arterial hypertension (RP = 1.3) were associated with SGA in the univariate analysis (p<0.20) and only smoking remained in the final model (reduction/cessation: RP = 1.7 and continuity: RP = 2.3, p<0.05). Conclusion SGA prevalence showed dose-response relationship with smoking. Population-based anti-smoking strategies should be intensified for women of childbearing age, and particularly for pregnant women, promoting prenatal care smoking-cessation practices.

The association between fetal-stage exposure to the China famine and risk of diabetes mellitus in adulthood: results from the China health and retirement longitudinal study.

BACKGROUND: The associations of famine exposure with diabetes risk in adulthood are still unclear. This study aimed to explore the association between famine exposure in early life and risk of diabetes in adulthood. METHODS: A total of 4138 subjects were selected from the data of the China Health and Retirement Longitudinal Study (CHARLS) 2011-2012. Diabetes was diagnosed as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated haemoglobin (HbA1C) > 6.5%, or self-reported diabetes. Birthdates of subjects were used to categorize famine exposure groups. The association of fetal-stage famine exposure with diabetes risk in adults was assessed using logistics regression model. RESULTS: The prevalence of diabetes in the non-exposed, fetal-stage exposed, infant-stage exposed, and preschool-stage exposed groups were 9.0, 13.6, 12.7 and 10.8%, respectively. Compared with the age-balanced control group, the fetal-stage exposed group was associated with the elevated risk of diabetes in later life after adjusting for covariates (OR = 1.37; 95%CI: 1.09-1.72; P = 0.008). Stratified analysis showed that the association between prenatal famine exposure and diabetes risk in adulthood was comparable between severely affected areas and less severely affected areas (P for interaction =0.153). CONCLUSIONS: Famine exposure in fetal stages was associated with the elevated diabetes risk in adults, which could be the critical periods for relative intervention.

Bajo peso al nacer, una problemática actual / Low birth weight, a current problem

RESUMEN Fundamento: el bajo peso al nacer con cifras inferiores a 2 500 gramos de peso, es una de las causas más importantes de morbilidad y mortalidad infantil y perinatal. Objetivo: caracterizar el bajo peso al nacer. Desarrollo: el bajo peso al nacer es uno de los aspectos más importantes que influyen en que un recién nacido experimente un crecimiento y desarrollo satisfactorio. (1) Para la Organización Mundial de la Salud, la incidencia de bajo peso al nacer es un indicador de gran utilidad para vigilar el progreso de las naciones hacia el logro de la meta de Salud para todos. Conclusiones: la sepsis vaginal, la anemia y la hipertensión figuran como las enfermedades o estados maternos asociados al embarazo que más se relacionan con el bajo peso al nacer.

ABSTRACT Background: low birth weight (newborn with figures below 2500 g of weight) is one of the most important causes of infant and perinatal morbidity and mortality. Objective: to characterize low birth weight. Development: birth weight is undoubtedly one of the most important aspects that influence a newborn to experience a satisfactory growth and development.1 For the World Health Organization, the incidence of low birth weight is a very useful indicator to monitor the progress of nations towards achieving the goal of Health for all. Conclusions: vaginal sepsis, anemia and hypertension are the diseases or maternal states associated with pregnancy that are most related with low birth weight.

What is fetal programming?: a lifetime health is under the control of in utero health.

The "Barker hypothesis" postulates that a number of organ structures and associated functions undergo programming during embryonic and fetal life, which determines the set point of physiological and metabolic responses that carry into adulthood. Hence, any stimulus or insult at a critical period of embryonic and fetal development can result in developmental adaptations that produce permanent structural, physiological and metabolic changes, thereby predisposing an individual to cardiovascular, metabolic and endocrine disease in adult life. This article will provide evidence linking these diseases to fetal undernutrition and an overview of previous studies in this area as well as current advances in understanding the mechanism and the role of the placenta in fetal programming.

What is fetal programming?: a lifetime health is under the control of in utero health

The “Barker hypothesis” postulates that a number of organ structures and associated functions undergo programming during embryonic and fetal life, which determines the set point of physiological and metabolic responses that carry into adulthood. Hence, any stimulus or insult at a critical period of embryonic and fetal development can result in developmental adaptations that produce permanent structural, physiological and metabolic changes, thereby predisposing an individual to cardiovascular, metabolic and endocrine disease in adult life. This article will provide evidence linking these diseases to fetal undernutrition and an overview of previous studies in this area as well as current advances in understanding the mechanism and the role of the placenta in fetal programming.

[Complications due to malnutrition and intrauterine growth restriction in preterm newborns]. / Complicaciones por desnutrición y restricción del crecimiento intrauterino en niños prematuros.

BACKGROUND: To analyze neonatal complications in preterm infants with or without previous diagnosis of intrauterine growth restriction (IUGR) and malnutrition at birth. METHODS: We integrated four preterm cohorts: IUGR and malnourished at birth (n = 24), IUGR without malnutrition (n = 22), without IUGR and malnourished (n = 43), and with proper weight without IUGR (n = 224). Nutritional status was determined by weighted index adjusted for weeks of gestation and fetal ultrasound IUGR. Apgar, type of resuscitation, neonatal morbidities, and hospital days of stay were analyzed at birth. RESULTS: Malnutrition was observed more frequently in infants with preeclamptic or eclamptic mothers, or in multiple pregnancies. There were no differences in birth conditions between groups. There were more complications in cohorts of infants with IUGR, but even more if they had malnutrition as well. Infants with IUGR adjusted for gestational age had more days of hospital stay, without differences regarding their nutritional status. CONCLUSIONS: In preterm infants, important growth impairments at birth (malnutrition) after being diagnosed with IUGR increase the likelihood of neonatal complications.

OBJETIVO: analizar las complicaciones en recién nacidos pretérmino con o sin diagnóstico previo de restricción del crecimiento intrauterino (RCIU) y con o sin desnutrición al nacimiento. MÉTODOS: se integraron cuatro cohortes retrospectivas de pretérminos: RCIU y desnutrición al nacer (n = 24), RCIU sin desnutrición (n = 22), sin RCIU y desnutrición (n = 43), y con peso adecuado sin RCIU (n = 224). El estado nutricional se determinó por índice ponderal ajustado por las semanas de gestación y RCIU por ultrasonido fetal. Se analizó el Apgar al nacimiento, el tipo de reanimación, las morbilidades neonatales y los días de hospitalización. RESULTADOS: la desnutrición neonatal se observó más en madres con preeclampsia o con embarazos múltiples. No hubo diferencias en las condiciones al nacimiento entre los grupos. Hubo más complicaciones en las cohortes de neonatos con RCIU, pero aún más si además tuvieron desnutrición. Los neonatos con RCIU ajustado por la edad gestacional estuvieron más días hospitalizados, sin haber diferencias con respecto a su estado de nutrición. CONCLUSIONES: en neonatos de pretérmino, el mayor deterioro del crecimiento al nacer (desnutrición) después de ser diagnosticado con RCIU incrementa la probabilidad de presentar complicaciones neonatales.

A developmental perspective on the origins of obesity and metabolic syndrome

Metabolic syndrome comprises central obesity, dyslipidemia, hypertension, glucose intolerance, and insulin resistance. Children sometimes develop metabolic syndrome, and it is strongly associated with the same syndrome in adulthood. Recently, there is evidence that obesity and metabolic syndrome originate from fetal life. Possible explanations of fetal and developmental origin of metabolic syndrome are the thrifty genotype and thrifty phenotype hypothesis, which together confer insulin resistance on developing fetus. Poor nutrition in utero as well as extrauterine growth restriction of preterm infants are important triggers of this hypothesis. Like metabolic syndrome in adulthood, the high levels of inflammatory cytokines and adipokines are certainly characteristic in pediatric patients. Increased fat mass was also observed in these patients, although their birth weight was lower than average. The mitochondrial genome is responsible for the inheritance of obesity from the maternal line. This can be a key as to why the phenotypes of obesity and metabolic syndrome start in fetal life with an association with poor maternal nutrition. In such circumstances, catch-up growth with an over-nutrition strategy can aggravate those features, suggesting that rapid catch-up growth in early infancy should not be encouraged.

Impact of prenatal protein-calorie malnutrition on the odontogenesis of wistar rats / Impacto da desnutrição protéico-calórica pré-natal sobre a odontogênese de ratos wistar

Objetivo: Este trabalho teve por objetivo determinar alterações na odontogênese decorrentes da desnutrição protéico-calórica pré e pós-natal. Foram selecionados 12 ratos Wistar adultos, 8 fêmeas e 4 machos. As fêmeas foram divididas em dois grupos, sendo que um deles recebeu dieta normoprotéica (G1) e o outro recebeu dieta hipoprotéica (G2). Material e Métodos: Após o nascimento das ninhadas, foram separados aleatoriamente 24 filhotes de cada grupo. Os animais foram sacrificados, 12 aos 5 dias de vida e 12 aos 8, e suas mandíbulas submetidas à preparação histológica para a obtenção de cortes dos germes dentários. Foram selecionadas 48 lâminas que apresentavam os germes adequadamente cortados (24 de cada grupo), as quais foram analisadas em microscópio e medidas por um examinador calibrado utilizando-se o software Image Pro Plus for Windows, versão 6.0. As diferenças entre as médias foram verificadas mediante o teste não paramétrico de Mann Whitney. Resultados: Os resultados obtidos demonstram que, aos 5 dias, as diferenças de espessura de esmalte e dentina foram estatisticamente significantes entre G1 (84,08 ± 28,9 e 141,51 ± 33,2; p = 0,026) e G2 (47,26 ± 43,8 e 91,19 ± 54,7; p = 0,006). Aos 8 dias de vida não foram identificadas diferenças significativas entre os grupos. Conclusão: Os resultados demonstraram indícios de impacto da desnutrição sobre a espessura dos tecidos dentários. Sugere-se o aprofundamento desta linha de investigação com delineamentos mais complexos.

Objective: This study aimed to determine changes in odontogenesis arising from prenatal and postnatal protein-calorie malnutrition. Material and Methods: Twelve adult Wistar rats were selected; 8 females and 4 males. The females were divided into two groups, one of which received a normoproteic diet (NG) and the other received a hypoproteic diet (HG). After the birth of the litters, 24 pups were randomly separated from each group. The animals were sacrificed, 12 at five-days old and 12 at eight-days old, and their jaws were subjected to histological preparation to obtain cuts of tooth germs. Forty-eight slides were selected that presented the germs properly cut (24 from each group), which were analyzed by microscopy and measured by a calibrated examiner. The differences between means were verified by the nonparametric Mann-Whitney test. Results: The results showed that at 5 days the differences in thickness of enamel and dentin were statistically significant between NG (84.08 ± 28.9 and 141.51 ± 33.2; p = 0.026) and HG (47.26 ± 43.8 and 91.19 ± 54.7; p = 0.006). At 8 days of life there were no significant differences between the groups. Conclusion: The results showed evidence of the impact of malnutrition on the thickness of dental tissues. It is suggested that further work should be carried out in this line of research with more complex designs.