RESUMEN
Heterozygous mutations in GCK result in a persistent, mildly raised glucose from birth, but it is usually diagnosed in adulthood as maturity-onset diabetes of the young (MODY), where hyperglycemia is often an incidental finding. The hyperglycemia of GCK-MODY is benign and does not require treatment, but is important to be aware of, particularly in females where it has implications for managing pregnancy. We present three cases of neonatal hyperglycemia resulting from a heterozygous mutation in GCK, illustrating its clinical presentation and evolution in early life. In summary, as with adults, neonatal hyperglycemia is an incidental finding, does not require treatment and has no adverse consequences for health. Neonates and their parents should be referred for genetic testing to confirm the diagnosis, avoid a label of diabetes and enable pregnancy counseling for females found to be affected.
Asunto(s)
Diabetes Mellitus Tipo 2/diagnóstico , Glucoquinasa/genética , Hiperglucemia/genética , Diabetes Mellitus Tipo 2/genética , Femenino , Humanos , Lactante , Recién Nacido , Masculino , LinajeRESUMEN
OBJECTIVES: Congenital Hyperinsulinism (CHI) is the most common cause of persistent hypoketotic hypoglycaemia in neonates and infants. It is a genetic disorder with both familial and sporadic forms. CASE PRESENTATION: In this study, we examined two unrelated infants of diabetic mothers (IDMs) presented with HH. DNA sequencing (Sanger and NGS panel) identified pathogenic variants of the Hepatocyte Nuclear Factor 4A (HNF4A) gene in both families. Pathogenic variants of HNF4A gene are reported to cause HH in the newborn period and Maturity Onset Diabetes of the Young (MODY) later in life. The diagnosis of MODY was made in retrospect for the two mothers, thus improving the management of their diabetes. CONCLUSION: Genetic testing for CHI is strongly recommended if neonatal hypoglycemia persists. A family history of MODY or presumed type II diabetes can support that the affected gene is HNF4A.
Asunto(s)
Hiperinsulinismo Congénito/genética , Factor Nuclear 4 del Hepatocito/genética , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/genética , Hipoglucemia/diagnóstico , Hipoglucemia/genética , Adulto , Femenino , Pruebas Genéticas , Variación Genética , Humanos , Recién Nacido , Masculino , Madres , EmbarazoRESUMEN
BACKGROUND: Antenatal corticosteroid therapy recently has been considered for term and near-term infants, in addition to preterm infants, delivered by elective cesarean section, with the aim of preventing an adverse respiratory outcome. OBJECTIVES: The objective of this study was to investigate hormonal and metabolic effects of antenatal betamethasone when administered to term fetuses. METHODS: Cord blood levels of cortisol, C-peptide, insulin-like growth factor I and its binding protein 3, and 5 more analytes including glucose were measured in singleton newborns of over 35 weeks of gestational age. In anticipation of a cesarean delivery, the mother was either treated or not treated with 12 mg of intramuscularly administered antenatal betamethasone approximately 24 hours prior to birth. Babies of comparable gestational age, sex, and nutritional status who were not treated antenatally served as controls. RESULTS: Cord serum cortisol levels of the betamethasone-treated fetuses were suppressed to <10% of that of untreated controls (median levels of 11.6 nmol/L vs. 138.2 nmol/L, respectively), and their C-peptide and glucose levels were significantly higher (2.85 mcg/L vs. 1.19 mcg/L, respectively, p < 0.0001; and 62.5 mg/dL vs. 56.0 mg/dL, respectively, p = 0.01). CONCLUSIONS: Prophylactic betamethasone therapy causes immediate hormonal alterations, which might interfere with the metabolic adaptation of the newborn. This issue deserves thorough investigation.
RESUMEN
OBJECTIVE: The aim of this study was to investigate whether readily available laboratory tests may aid in the identification of growth-restricted neonates. DESIGN: Cord serum levels of 15 chemical analytes, including insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) were measured in newborns ≥36 weeks gestational age (GA). Based on the number of anthropometric indices (out of four) with values ≤25th centile for GA, the babies were allocated into three groups, i.e., Group(25)0, Group(25)1 and Group(25)2 corresponding to neonates with 0, 1 and 2 or more indices, respectively, that were ≤25th centile for GA. Furthermore, two composite variables were developed: A25 (Group(25)0 and Group(25)1) and B25 (Group(25)0 and Group(25)2). The data were evaluated by the Mann-Whitney test and multiple regression analyses. RESULTS: Cord serum triglycerides and total cholesterol levels were significantly higher in Group(25)2 compared to Group(25)0 (p values 0.004 and 0.0009, respectively). The triglycerides almost doubled the power of the variable B25 for predicting IGF-I levels and were found to have a highly significant, negative association with the IGF-I levels (p<0.0001). The IGF-I along with the IGFBP-3 levels explained almost one third of the variation of triglycerides. CONCLUSION: Cord serum triglycerides can assist in the identification of growth-restricted neonates. The novel finding of the association of triglycerides with IGF-I calls for further research as this can illuminate unknown aspects of the fetal lipid metabolism.
Asunto(s)
Sangre Fetal/química , Recién Nacido Pequeño para la Edad Gestacional , Triglicéridos/sangre , Antropometría , Peso al Nacer , Colesterol/sangre , Femenino , Sangre Fetal/metabolismo , Retardo del Crecimiento Fetal , Edad Gestacional , Humanos , Recién Nacido , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismoRESUMEN
BACKGROUND: The identification of growth-restricted neonates is hampered by the lack of an appropriate diagnostic tool. AIM: To determine the value of combining diagnostic markers in detecting growth-restricted neonates. METHODS: A set of anthropometric indices, nutritional status and placental weight were assessed in the study population soon after birth. Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) were assayed in cord blood. Babies having low values (≤25th centile for gestational age) in 0, 1 or more of four anthropometric indices were classified as Group(25)0, Group(25)1 and Group(25)2, respectively. For statistical evaluation the Mann-Whitney test and a multiple regression analysis were performed. RESULTS: One hundred-eighty (180) singleton babies of over 36 weeks of gestational age (GA) were studied. IGF-I, IGFBP-3 levels and placental weight were significantly lower in Group(25)2 than both Group(25)0 (P<0.0001) and Group(25)1 (p<0.0001 to p = 0.03). Group(25)1 and Group(25)0 did not differ significantly regarding IGF-I and IGFBP-3 levels (p values 0.09 and 0.13, respectively). The combination of anthropometric indices enhanced their ability to predict IGF-I, IGFBP-3 levels and placental weight; the nutritional status of the babies added power to all individual models in predicting the three outcome variables. Analogous results were obtained when the 10th (instead of the 25th) centile for GA was used for the anthropometric indices. CONCLUSION: The combination of simple diagnostic markers of growth restriction can define a reference test with enhanced diagnostic potential compared to the potential of the same markers in isolated use.
Asunto(s)
Biomarcadores/sangre , Retardo del Crecimiento Fetal/diagnóstico , Antropometría , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Recién Nacido , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Estado Nutricional , Tamaño de los Órganos , Placenta/patología , EmbarazoRESUMEN
BACKGROUND: The consequences of in utero growth restriction have been attracting scholarly attention for the past two decades. Nevertheless, the diagnosis of growth-restricted neonates is as yet an unresolved issue. Aim of this study is the evaluation of the performance of simple, common indicators of nutritional status, which are used in the identification of growth-restricted neonates. METHODS: In a cohort of 418 consecutively born term and near term neonates, four widely used anthropometric indices of body proportionality and subcutaneous fat accretion were applied, singly and in combination, as diagnostic markers for the detection of growth-restricted babies. The concordance of the indices was assessed in terms of positive and negative percent agreement and of Cohen's kappa. RESULTS: The agreement between the anthropometric indices was overall poor with a highest positive percent agreement of 62.5% and a lowest of 27.9% and the kappa ranging between 0.19 and 0.58. Moreover, 6% to 32% of babies having abnormal values in just one index were apparently well-grown and the median birth weight centile of babies having abnormal values of either of two indices was found to be as high as the 46th centile for gestational age (95%CI 35.5 to 60.4 and 29.8 to 63.9, respectively). On the contrary, the combination of anthropometric indices appeared to have better distinguishing properties among apparently and not apparently well-grown babies. The median birth weight centile of babies having abnormal values in two (or more) indices was the 11th centile for gestational age (95%CI 6.3 to 16.3). CONCLUSIONS: Clinical assessment and anthropometric indices in combination can define a reference standard with better performance compared to the same indices used in isolation. This approach offers an easy-to-use tool for bedside diagnosis of in utero growth restriction.
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Antropometría/métodos , Retardo del Crecimiento Fetal/diagnóstico , Peso al Nacer , Estatura , Distribución de Chi-Cuadrado , Estudios de Cohortes , Femenino , Retardo del Crecimiento Fetal/clasificación , Retardo del Crecimiento Fetal/epidemiología , Edad Gestacional , Grecia/epidemiología , Humanos , Recién Nacido , Masculino , Morbilidad , Tamizaje Neonatal , Evaluación Nutricional , Estado Nutricional , Estudios Prospectivos , Valores de Referencia , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
UNLABELLED: The terms "small for gestational age" and "intrauterine growth restriction" have been used interchangeably to denote an in utero growth-restricted neonate. However, the two terms are not synonymous; not all small babies are growth restricted and not all growth-restricted ones are small. Research evidence, extending back to the middle of the last century, reveals that the number of growth-restricted babies who escape attention is not negligible and that the postnatal outcome of these babies is not uneventful. This paper highlights this issue and further discusses the available diagnostic tools for the identification of in utero-restricted neonates, that is, clinical assessment, anthropometric indices and obstetric ultrasound. Each of these tools has strengths and limitations, but, if combined, each could complement the other and help differentiate well-grown babies from those who are growth restricted. CONCLUSION: Identification of growth-restricted neonates is feasible through the integrated use of diagnostic tools.