Makarios Eleftheriades

Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases.

This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5‐Mb resolution.

Prenatal detection of full monosomy 21 in a fetus with increased nuchal translucency: Molecular cytogenetic analysis and review of the literature

Full monosomy 21 is an extremely rare chromosomal disorder. A 38‐year‐old woman attended a first trimester scan. Ultrasound (U/S) imaging of the fetus at 12u2003weeks of gestation showed features of increased nuchal translucency measurement (12u2003mm). Chorionic villi sampling (CVS) was performed after genetic counseling. At 16u2003weeks of gestation the fetus showed U/S characteristics of severe intrauterine growth restriction, generalized edema and hydrothorax. Cytogenetic examination was performed using quantitative fluorescent polymerase chain reaction analysis, standard Giesma banding and fluorescent in situ hybridization analysis. Non‐mosaic full monosomy 21 was detected and the parents opted to terminate the pregnancy. Microsatellite analysis demonstrated maternal origin of the single chromosome. This case represents one of the few cases of prenatally diagnosed full monosomy 21 confirmed only by CVS, in which the parental origin of the single chromosome was determined.

Maternal serum levels of neutrophil gelatinase‐associated lipocalin (NGAL), matrix metalloproteinase‐9 (MMP‐9) and their complex MMP‐9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study

The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase‐associated lipocalin (NGAL), matrix metalloproteinase‐9 (MMP‐9), and MMP‐9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA).

Prenatal detection of TAR syndrome in a fetus with compound inheritance of an RBM8A SNP and a 334‑kb deletion: A case report

Thrombocytopenia‑absent radius syndrome (TAR) is a rare genetic disorder that is characterized by the absence of the radius bone in each forearm and a markedly reduced platelet count that results in life‑threatening bleeding episodes (thrombocytopenia). Tar syndrome has been associated with a deletion of a segment of 1q21.1 cytoband. The 1q21.1 deletion syndrome phenotype includes Tar and other features such as mental retardation, autism and microcephaly. This study describes a case of a prenatally diagnosed fetus with compound inheritance of a small (334xa0kb) deletion, as detected by array‑comparative genomic hybridization, and a 5 untranslated region (UTR) low‑frequency allele (rs139428292) in genexa0RBM8A as detected by Sanger sequencing. The study describes the first case of prenatal analysis of TAR syndrome in a fetus with compound inheritance of a 334‑kbxa0deletion in the 1q21.1xa0region and a low‑frequency 5 UTRxa0single nucleotide polymorphism, and provides confirmation of the causal nature of the RBM8Axa0gene in the diagnosis of TAR syndrome.

Assessment of body composition in Wistar rat offspring by DXA in relation to prenatal and postnatal nutritional manipulation

Background:This experimental study aims to investigate the impact of combinations of prenatal and postnatal food manipulation on body composition in rat offspring.Methods:On day 12 of gestation, 100 timed pregnant rats were randomized into two nutritional groups: standard laboratory and 50% starved. Pups born to starved mothers were subdivided, based on birthweight (BiW), into fetal growth restricted (FGR) and non-FGR. Pups were born on day 21, cross-fostered, then left undisturbed lactating until the 26th postnatal day when they underwent dual-energy X-ray absorptiometry (DXA) examination.Results:Prenatally control-fed animals had a significantly greater body weight at 26 d postnatally than the prenatally starved groups, irrespective of their postnatal diet (P < 0.001). Postnatal control diet was associated with significantly increased abdominal and total fat in non-FGR compared to FGR rats (P < 0.001). non-FGR/CONTROL rats showed higher values of abdominal fat than prenatally starved animals that were starved postnatally irrespective of their birth weight (P < 0.001). Postnatal control diet significantly increased total bone mineral content (BMC), head BMC, head area, abdominal BMC in non-FGR compared to FGR rats (P < 0.001).Conclusion:Interaction between prenatal and postnatal nutrition affects growth, abdominal adiposity, and bone accrual in Wistar rats’ offspring at 26 d of life.

Protein expression in the brain of rat offspring in relation to prenatal caloric restriction

Abstract Objective: Intrauterine growth restriction (IUGR) has been associated with decreased supply of crucial substrates to the fetus and affects its growth and development by temporarily or permanently modifying gene expression and function. However, not all neonates born by calorie restricted mothers are IUGR and there are no reports regarding their brain protein expression vis-à-vis that of their IUGR siblings. Here, we investigated the expression of key proteins that regulate growth and development of the brain in non-IUGR newborn pups versus IUGR siblings and control pups. Methods: Rat brain proteins were isolated from each group upon delivery and separated by two-dimensional gel electrophoresis (2-DE). Results: 14-3-3 Protein, calreticulin, elongation factor, alpha-enolase, fascin, heat-shock protein HSP90 and pyruvate kinase isozymes were significantly increased (pu2009<u20090.05) in samples obtained from IUGR newborn pups compared to non-IUGR. Conversely, collapsin response mediator proteins, heat-shock70 and peroxiredoxin2 were decreased in IUGR group compared to non-IUGR. Conclusions: In our experimental study, IUGR pups showed an altered proteomic profile compared to their non-IUGR siblings and non-IUGR controls. Thus, not all offspring of calorie-restricted mothers become IUGR with the accompanying alterations in the expression of proteins. The differentially expressed proteins could modulate alterations in the energy balance, plasticity and maturation of the brain.

Metabolic profiles of adult Wistar rats in relation to prenatal and postnatal nutritional manipulation: The role of birthweight

OBJECTIVEnThis experimental study aimed to prospectively investigate the impact of combinations of prenatal and postnatal food manipulations on the metabolic profile of adult offspring.nnnDESIGNnOn day 12 of gestation, 67 timed pregnant rats were randomized into three nutritional groups, control: standard laboratory food; starved: 50% food restricted, FR; fat-fed: fat-rich diet, FF. Seven hundred and seventy-four (774) pups were born on day 21 and culled to 8 (4 males, 4 females) per litter to normalize rearing. Rats born to starved mothers were later subdivided, based on birthweight (BiW), into fetal growth restricted (FGR) and non-FGR. The pups were then weaned to the diet of their fostered mother until one year old. Thus, 12 groups were studied: 1.nnnCONTROL/CONTROLn14 rats, 2.nnnCONTROL/FRn12 rats, 3.nnnCONTROL/FFn15 rats, 4.nnnFGR/CONTROLn16 rats, 5.nnnFGR/FRn10 rats, 6.nnnFGR/FFn15 rats, 7. non-nnnFGR/CONTROLn10 rats, 8. non-nnnFGR/FRn17 rats, 9. non-nnnFGR/FFn10 rats, 10.nnnFF/CONTROLn15 rats, 11.nnnFF/FRn14 rats, and 12.nnnFF/FFn13 rats. During sacrifice, body weight (BW) and liver weight (LW) were measured (expressed in grams) and concentrations of serum glucose, triglycerides, HDL and NEFA were determined.nnnRESULTSnPostnatal food restriction, compared to control diet significantly reduced BW (p=0.004, p=0.036, p<0.001, p=0.008) and LW (p<0.001) in all study groups. Postnatal control diet significantly increased BW in non-FGR compared to FGR rats (p=0.027). No significant differences were detected in biochemical parameters (excluding NEFA) between FGR and non-FGR, regardless of the postnatal diet.nnnCONCLUSIONSnInteraction between prenatal and postnatal nutrition produces distinct metabolic profiles. Apart from BiW, prenatal diet had an important impact on the metabolic profile of the adult offspring, implying that intrauterine events should be considered in the estimation of the metabolic risk of an individual, independently of BiW.

Adipokines and Anthropometry: Childhood and Adolescent Obesity or Adipocytokines and Anthropometry in Childhood and Adolescence

Adipose tissue is no longer considered an inert tissue simply devoted to energy storage, but it has emerged as an active organ in regulating a variety of physiological processes. Adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, are proteins secreted by the adipocytes and released into the circulation, participating in the regulation of insulin sensitivity, food intake, inflammation, immunity, and vascular sclerosis. The prevalence of obesity is dramatically increasing worldwide in both children and adults and, along with the increase of obesity, is a parallel increase in the prevalence of comorbid disorders such as hyperlipidemia, arterial hypertension, insulin resistance, and diabetes type 2. In obesity, adipocytes enlarge and macrophages infiltrate adipose tissue, resulting in the large-scale release of several adipokines and in an imbalance between molecules and peptides secreted by the adipose tissue. The proinflammatory cytokines contribute to the “low-grade inflammatory state” of obese individuals, especially those with the Metabolic Syndrome (MetS), a clustering of metabolic abnormalities related to obesity, in both adults and children. Leptin and adiponectin are the two most studied adipokines in neonates, children, and adults and the majority of studies in obese individuals have shown hyperleptinemia and hypoadiponectinemia compared to normal-weight individuals. Furthermore, levels of circulating leptin are negatively associated with insulin sensitivity and conversely, adiponectin improves insulin sensitivity by stimulating glucose uptake and fatty acid oxidation in skeletal muscle. However, anthropometric changes during growth and puberty as well as changes in endocrine and metabolic parameters may contribute to the varied effects of adipokines on insulin sensitivity and the metabolic profile.

Divergence of estimated fetal weight and birth weight in singleton fetuses

Abstract Objective: To evaluate differences in distribution of estimated fetal weight (EFW) and birth weight (BW) of ongoing fetuses and neonates of the same gestational age. Methods: Reference curves for EFW (Hadlock BPD-HC-AC-FL formula, Nu2009=u20091191) and BW (Nu2009=u20091036) in singleton pregnancies from 24+0 to 40+6 gestational weeks were calculated. Multiple pregnancies, fetuses with major or multiple abnormalities or syndromes and iatrogenic preterm deliveries due to preeclampsia or abnormal fetal Doppler were excluded. The standardized residuals for EFW and BW were calculated and compared. Results: EFW and BW can be accurately described by quadratic equations (R2u2009=u20090.944 and 0.807, respectively). The distribution of standardized residuals for BW using the EFW formula was negative from 28+0 to 35+6 weeks. The 50th and 5th centiles of BW were lower than those of EFW throughout prematurity, and they converged at approximately 38 gestational weeks. The 5th centile for BW was 30% lower than the 5th centile for EFW at 27 weeks, 27.5% lower at 30 weeks and 19.4% at 34 weeks. Conclusions: Preterm infants have lower BW distribution compared to the expected EFW of ongoing pregnancies of the same gestational age, supporting the concept of hidden intrauterine morbidity for a proportion of these infants.