Differential expression of cord blood neurotrophins in gestational diabetes: the impact of fetal growth abnormalities

Objective: Gestational diabetes mellitus (GDM) may induce fetal macrosomia or growth restriction and is associated with later offspring neurodevelopmental disorders. We aimed to determine whether neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-4 (NT-4) are differentially expressed in cord blood samples at birth in large-for-gestational-age (LGA), intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) offspring of diabetic mothers, as compared to AGA controls from non-diabetic mothers.

Methods: BDNF, NGF and NT-4 concentrations were prospectively determined in 80?cord blood samples from LGA (n?=?15), IUGR (n?=?12) and AGA (n?=?33) diabetic, as well as from AGA normal (controls, n?=?20) singleton full-term pregnancies.

Results: Fetal BDNF concentrations considerably decreased in GDM, as compared with normal pregnancies [(b?=??2.836, 95%CI ?5.067 to (?0.604), p?=?0.013)] and were higher in females (b?=?2.298, 95%CI 0.357–4.238, p?=?0.021). Cord blood NGF concentrations were lower in IUGR than AGA infants (p?=?0.038).

Conclusions: BDNF is down-regulated in the fetus exposed to GDM, independently of the fetal growth pattern, probably representing a candidate mechanism underlying the association between maternal diabetes and later psychopathology. IUGR fetuses born to diabetic mothers present with NGF deficiency, which may contribute to their long-term neurodevelopmental sequelae. Gender-dependent differences in fetal BDNF may partly explain the higher prevalence of adverse neurodevelopmental outcomes following brain insults in male infants.     

Perinatal sclerostin concentrations in abnormal fetal growth: the impact of gestational diabetes

Objective: To prospectively evaluate maternal and cord blood concentrations of sclerostin – an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism – in pregnancies with normal and abnormal fetal growth.

Methods: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80?cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n?=?30), large-for-gestational-age (LGA, n?=?30), and appropriate-for-gestational-age (AGA, n?=?20) singleton full-term pregnancies. Fourteen out of 30 mothers with LGA offspring presented with gestational diabetes mellitus (GDM).

Results: Maternal and fetal sclerostin concentrations did not differ among LGA, IUGR, and AGA groups. Fetal concentrations were higher than maternal. In LGA group, maternal concentrations were elevated in cases of GDM (b?=?13.009, 95%CI 1.425–24.593, p?=?.029). In a combined group and the IUGR group, maternal concentrations were elevated in older mothers (b?=?0.788, 95%CI 0.190–1.385, p?=?.010, and b?=?0.740, 95%CI 0.042–1.438, p?=?.039, respectively).

Conclusions: Maternal and fetal sclerostin concentrations may not be differentially regulated in pregnancies complicated by abnormal fetal growth. Circulating maternal levels are higher in cases of GDM, probably implying reduced bone formation. Sclerostin up-regulation with aging may be one of the molecular pathways responsible for the observed age-related decline in bone synthesis, leading to accelerated bone loss in humans.     

Clinical factors that enhance morbidity and mortality in intrauterine growth restricted foetuses delivered between 23 and 30 weeks of gestation

Objective.?To find clinical factors that are associated with poor outcome (death and brain damage) in premature intrauterine growth restricted (IUGR) infants.

Methods.?A retrospective study was performed to compare the incidence of poor outcome between 45 IUGR and 203 appropriate-for-gestational-age (AGA) infants born before 30 weeks of gestation. Foetal tests included foetal heart rate monitoring, Doppler flow, amniotic fluid, and head circumference. Growth for gestational age was categorised as 10th through 3rd, third through first, and below first percentiles.

Results.?In infants below 25 weeks of gestation, the incidence of poor outcome was not different between IUGR and AGA. In infants between 25 and 30 weeks of gestation, the incidence of poor outcome was significantly increased in IUGR compared with AGA (12/40, 30% versus 11/136, 8.1%, p?<?0.01). Univariate analysis showed that abnormality in foetal heart rate monitoring [odds ratio (OR) 8.3, 95% confidence interval (CI) 1.58–43.6], head circumference (OR 7.0, 95%CI 1.42–34.4), and Doppler flow (OR 10.9, 95%CI 1.83–64.6) was significantly associated with poor outcome in IUGR infants. However, no foetal tests were significantly associated with poor outcome after adjusting for the 3-grade birthweight percentiles.

Conclusions.?Immaturity outweighs clinical problem associated with IUGR in infants below 25 weeks of gestation. Between 25 and 30 weeks of gestation, there was a growth threshold below third percentile where foetal tests were not significant predictors of poor outcome, but that was primarily determined by birthweight.     

Cord blood netrin-1 and -4 concentrations in term pregnancies with normal,restricted and increased fetal growth

Abstract

Objective: To determine levels of the possible angioregulatory molecules netrin-1 and -4, in intrauterine-growth-restricted (IUGR), large for gestational age (LGA) (both groups characterized by altered angiogenic mechanisms) and appropriate-for-gestational-age (AGA) pregnancies.

Methods: Cord blood (UC) netrin-1 and -4 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA infants and their mothers (MS).

Results: Netrin-1 and -4 concentrations did not differ in all groups. UC netrin-4 increased with gestational age (b?=?0.075, 95% CI 0.029–0.121, p?=?0.002). In the IUGR group, MS netrin-4 decreased as birth-weight centiles increased [b?=??0.058, 95% CI ?0.112 to ?0.004, p?=?0.036]. In the LGA group, MS netrin-1 decreased with advanced gestational age [b?=??0.063, 95% CI ?0.105 to ?0.022, p?=?0.004]. In all cases, MS netrin-1 positively correlated with MS netrin-4 (r?=?0.299, p?=?0.007), while UC netrin-1 negatively correlated with UC netrin-4 (r?=??0.239, p?=?0.033).

Conclusions: Increased UC netrin-4 levels with advancing gestational age may reflect its effect on fetal development. Decreased maternal netrin-1 levels in the LGA group possibly represent a negative feedback mechanism against increased angiogenesis. Increased maternal netrin-4 levels in IUGR neonates may reflect in utero hypoxia, while the negative correlations between fetal netrin-1 and -4 levels may exert the dynamic balance between their angio- and anti-angiogenic properties.     

The insulin-like growth factor 2 receptor gene Gly1619Arg polymorphism and idiopathic recurrent spontaneous abortion

Abstract

Objective.?The insulin-like growth factor 2 (IGF2) and its receptor (IGF2R) are important regulators of placental function and fetal growth. Our aim was to investigate the association between IGF2R gene Gly1619Arg G>A polymorphism and recurrent spontaneous abortion (RSA).

Methods.?Polymerase chain reaction and restriction fragment length polymorphism methods were performed to identify the genotypes in 149 couples with a history of at least three consecutive spontaneous abortions and 149 age-matched, unrelated, and fertile couples.

Results.?There were no statistically significant differences in genotype or allele frequency among the couples with RSA and healthy controls.

Conclusions.?We found no evidence that the IGF2R Gly1619Arg variation is associated with RSA.     

Implication of the myokine irisin in maternal energy homeostasis in pregnancies with abnormal fetal growth

Objective: To prospectively investigate maternal concentrations of the myokine irisin in large for gestational age (LGA) and intrauterine growth restricted (IUGR) versus appropriate for gestational age (AGA) normal pregnancies and associate them with various perinatal parameters.

Methods: Plasma irisin and insulin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assay (IRMA), respectively, in a cohort of 80 mothers delivering LGA (n?=?30), IUGR (n?=?30) and AGA (n?=?20) singleton full-term infants.

Results: Maternal irisin concentrations were similar among LGA, IUGR and AGA groups and did not correlate with respective insulin ones or maternal body mass index. In a combined group, maternal irisin concentrations decreased with advancing gestational age (p?<?0.001) and were lower in multi-, compared to nulliparous women (p?=?0.004). In the IUGR group, maternal irisin concentrations were higher in cases of smoking (p?=?0.006).

Conclusions: Irisin may not be differentially regulated in insulin resistance-associated pregnancy disorders resulting in fetal macrosomia and IUGR. Maternal irisin down-regulation with advancing gestation could possibly contribute to the observed maternal fat accumulation and progressive insulin resistance towards term. Similarly, lower maternal irisin concentrations in multiparous women may reflect the documented positive association between parity and fat deposition. Irisin up-regulation in cases of smoking may indicate the need for enhanced oxygen consumption to maintain energy production under conditions of hypoxia.     

Serum fetuin-A/alpha2-HS-glycoprotein in human pregnancies with normal and restricted fetal growth

Objective. To investigate circulating concentrations of human fetuin-A (important fetal glycoprotein, involved in vascular pathology and bone metabolism) in mothers, fetuses and neonates from intrauterine-growth-restricted (IUGR, associated with low bone mass at birth and metabolic syndrome in adult life) and appropriate-for-gestational-age (AGA) pregnancies.

Methods. Serum fetuin-A concentrations were prospectively measured in 40 mothers, the doubly-clamped umbilical cords (representing fetal state) and their 20 IUGR and 20 AGA full-term neonates on postnatal day 1 (N1) and 4 (N4).

Results. No significant differences in fetuin-A concentrations were observed between groups, or between maternal, fetal and neonatal samples in both groups. In the AGA group, maternal fetuin-A concentrations positively correlated with fetal and N1 ones (r = 0.599, p = 0.005 and r = 0.469, p = 0.037, respectively). In the IUGR group, maternal fetuin-A concentrations positively correlated with N4 ones (r = 0.541, p = 0.014).

Conclusion. Serum fetuin-A concentrations do not differ between IUGR cases and AGA controls. Maternal and fetal fetuin-A concentrations are similar and positively correlated, indicating the likelihood of passive transplacental transfer of this substance.     

The effect of intrauterine growth on leukocyte telomere length at birth

Abstract

Objective: Telomeres are specialized nucleoprotein structures located at the ends of chromosomes, which play a crucial role in genomic stability. Telomere shortening has been proposed as a biomarker for the onset of age-related diseases. This study aimed to determine whether restricted or increased intrauterine growth affects leukocyte telomere length (LTL) at birth.

Materials and methods: One hundred sixty-five (n?=?165) full-term neonates participated in the study. Fetuses were classified as intrauterine growth restriction (IUGR, n?=?21), large-for-gestational-age (LGA, n?=?15), or appropriate-for-gestational-age (AGA, n?=?129), based on customized birth-weight standards. Mixed arteriovenous cord blood samples were collected for isolation of leukocyte DNA. The LTL was measured using multiplex monochrome quantitative real-time PCR and telomeric restriction fragments through Southern blot analysis (terminal restriction fragment [TRF]).

Results: Despite differences among groups in birth weight, length and head circumference, LTL did not differ among AGA (6.78?±?0.58), IUGR (10.54?±?1.80), and LGA (11.95?±?2.42) neonates (p?=?.098). Cord blood IGF-1 and IGFBP-3 concentrations were higher in the LGA group. LTL positively correlated with birth length (r?=?0.176, p?=?.032).

Conclusions: Intrauterine growth does not seem to affect LTL at birth. Further studies, comprising a larger sample size of IUGR, LGA, and AGA neonates, are required to determine whether growth at birth influences LTL.     

Relationship between Doppler findings and fetal brain apparent diffusion coefficient in early-onset intra-uterine growth restriction*

Objective: The aim of the study is to assess the relationship between uteroplacental Doppler sonography findings and cerebral diffusion measured by diffusion-weighted magnetic resonance imaging (DWI) in fetuses with early-onset intrauterine growth restriction (IUGR).

Materials and methods: The study included 54 pregnant women with fetal IUGR and 15 healthy controls (n: 15). Fetuses with IUGR were classified into four groups based on Doppler findings: group 1 (n?=?12), umbilical artery (UA) pulsatility index (PI)?>?95pc; group 2 (n?=?11), UA PI >95?pc and middle cerebral artery PI?n?=?21), absent end-diastolic (A-EDF) in UA; group 4 (n?=?10), reversed EDF in UA. After Doppler evaluation, DWI was performed in all patients within hours. The groups were compared with respect to apparent diffusion coefficient (ADC) levels.

Findings: In cases with fetal IUGR, significant decreases were detected in ADC values of periatrial white matter (PAWM) (p?=?.01), frontal white matter (FWM) (p?=?.038), thalamus (p?=?.004), and basal ganglia (p?=?.013) compared to controls. In Doppler subgroup analysis adjusted for gestational age, ADC values of FWM, thalami, and pons were significantly lower in group 4 than control group (p?=?.02, p?=?.02, and p?=?.037, respectively). In PAWM, ADC values were significantly lower in group 4 than control and Group 1 (p?=?.004). No significant differences with regard to ADC values in basal ganglia, cerebellum was found between Doppler groups and control.

Conclusions: In fetuses with IUGR, ADC values as measured by DWI decreases. The critical Doppler finding that is associated with reduced diffusion in some brain areas (FWM, PAWM, thalami, pons) is reverse end-diastolic flow in umbilical artery. Further prospective studies with larger sample size are needed to introduce cerebral ADC values in the management of IUGR     

Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction

Objective.?To verify whether adrenomedullin (AM) and nitric oxide (NO) concentrations are changed in the maternal and fetal circulation in pregnancies complicated by intrauterine growth restriction (IUGR) compared to normal pregnancies, and to determine any relationship between them.

Methods.?Forty-six small for gestational age (SGA) and 34 appropriate for gestational age (AGA) infants were included in the study. Umbilical and maternal venous AM and NO concentrations were determined.

Results.?Umbilical NO concentrations in SGA infants (mean ± SD; 176.2 ± 75.8 μmol/L) were significantly greater than in AGA infants (143.4 ± 39.2 μmol/L) (p = 0.015). However, umbilical AM concentrations were similar in SGA and AGA infants with 14.2 ± 4.4 pmol/mL and 14.5 ± 6.2 pmol/mL, respectively (p > 0.05). There was no relationship between NO and AM levels in umbilical blood (r = 0.09, p = 0.40). No difference was found between either AM or NO levels in the maternal plasma of the two groups.

Conclusions.?We suggest that NO is increased in the fetoplacental circulation in SGA infants probably as a response to decreased blood flow, whereas AM is not. Additionally, increased NO in the fetoplacental circulation was found to be independent from AM secretion.     

Adropin concentrations in term pregnancies with normal,restricted and increased fetal growth

Objective: To determine levels of adropin (implicated in insulin resistance and endothelial dysfunction) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies.

Methods: Cord-blood (UC) adropin and insulin concentrations were measured in 30 IUGR, 30 LGA and 20 AGA full-term infants and their mothers (MS).

Results: No significant differences in adropin concentrations were observed between the three groups. In the IUGR group MS adropin was significantly decreased when neonates had higher birth weights [b?= ?0.003, 95% CI??0.006 to 0.0, p?=?0.043]. In all groups, MS adropin levels were positively correlated with UC ones (r?=?0.282, p?=?0.011) and were significantly increased in female neonates [b?=?0.977, 95% CI 0.122–1.832, p?=?0.026]. In the LGA group, MS insulin was negatively correlated with UC adropin (r?= ?0.362 p?=?0.049).

Conclusions: Increased maternal adropin levels in severe IUGR cases might represent a regulatory feedback mechanism against endothelial placental dysfunction. The positive correlation between maternal and umbilical cord adropin levels implies its transplacental transfer. Increased maternal adropin levels in female neonates could be attributed to interaction of adropin with fetal estrogens through vascular endothelial growth factor (VEGF). The negative correlation between maternal insulin and fetal adropin levels in the LGA group is probably attributed to their respective insulin resistance.     

Associations between neural injury markers of intrauterine growth-restricted infants and neurodevelopment at 2 years of age

Objectives: The aim of this study was to evaluate the relationships between brain injury biomarkers in intrauterine growth-restricted (IUGR) infants (S100B and neuron-specific enolase (NSE)) and neurodevelopment at 2 years of age.

Methods: This prospective case-control study was a cooperative effort among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler variables were measured for each infant. Maternal venous blood and fetal umbilical arterial blood samples were collected at the time of delivery and neural injury markers S100B and NSE concentrations were measured. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III).

Results: Fifty six pregnancies were included. Thirty-one infants were classified as IUGR and 25 as non-IUGR. Neurodevelopmental evaluation at 2 years of age indicated that there were no between-group differences for any of the tests. For all patients in both groups, we found statistically significant inverse relationships between the concentrations of NSE in the cord blood and the results of the cognitive test (r?=??271, p?=?.042), fine motor subtest (r?=??280, p?=?.036), and social-emotional test (r?=??349, p?=?.015). We also found statistically significant differences between the concentrations of S100B in the cord blood and the results of the cognitive test (r?=??306, p?=?.022) and expressive communication subtest (r?=??304, p?=?.023). For the IUGR group, we found a significant inverse relationship between the concentrations of S100B in the maternal serum and the results of adaptive behavior test (p?p?=?.025) and social-emotional test (r?=??489, p?=?.021). The difference between the concentration of S100B in the cord blood and the language composite score was also statistically significant (p?=?.038).

Conclusions: At 2 years of age, the concentrations of NSE and S100B were higher in the non-IUGR and IUGR groups with the worst scores for some areas of neurodevelopmental evaluation. The value of these biomarkers for prognostic neurodevelopmental use requires further investigation for both non-IUGR and IUGR infants.     

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy

Objective.?To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET).

Methods.?Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P?<?0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET.

Results.?There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET.

Conclusions.?Maternal IGF-2 has a significant positive correlation with PET.     

Plasma copeptin may not be a sensitive marker of perinatal stress in healthy full-term growth-restricted fetuses

Objective: Intrauterine-growth-restriction-(IUGR) is associated with chronic fetal stress, as well as a phase of enhanced fetal/early postnatal insulin sensitivity, followed by a later emergence of insulin resistance. We aimed to prospectively investigate concentrations of copeptin, a sensitive marker of stress and insulin resistance, in IUGR versus appropriate-for-gestational-age-(AGA) fetuses.

Methods: Cord blood copeptin concentrations were determined by ELISA in well-defined, non-distressed at birth, asymmetric IUGR (n?=?30) and AGA (n?=?20) full-term pregnancies. Doppler studies were indicative of placental insufficiency.

Results: Cord blood copeptin concentrations were similar in IUGR cases and AGA controls, after controlling for delivery mode. Copeptin concentrations were markedly elevated in vaginally delivered fetuses (p?=?0.001). No association was recorded between fetal copeptin concentrations and maternal age, parity, gestational age, or fetal gender.

Conclusions: Cord blood copeptin concentrations are probably not affected by IUGR at term, in the absence of fetal distress, possibly due to a balance between copeptin up-regulation by chronic fetal stress, on one hand, and copeptin down-regulation in the presence of increased insulin sensitivity, on the other hand; thus, copeptin may not be a sensitive marker of chronic perinatal stress in healthy asymmetric IUGR infants. Cord blood copeptin seems to primarily reflect perinatal stress associated with delivery mode.     

Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction

Objective: We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR.

Methods: During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression.

Results: There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2^α: 0.92; p?α: 0.72; p?=?0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2^α: ?1.49; p?Conclusion: We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.     

Transmembrane G protein-coupled receptor 30 gene polymorphisms and uterine adenomyosis in Korean women

Abstract

To compare the genetic distributions of 14G protein-coupled receptor 30 (GPR30) single-nucleotide polymorphisms (SNPs) between women with and without uterine adenomyosis. The study population comprised 69 Korean women. Uterine tissues from the adenomyosis and non-adenomyosis groups were used for DNA extraction. Pre-designed PCR/Sanger or Sequencing Primer and TaqMan^® SNP Genotyping Assays were used for the SNP genotyping of the GPR30 gene. Immunohistochemical staining was performed to confirm the GPR30 expression. Differences in genotype and allele frequencies between the two groups were calculated using Fisher’s exact test. The rs3802141 CT genotype was more common in the control group (p?=?.02), and the rs4266553?CC genotype was more common in the adenomyosis group (p?=?.02). The C allele of the SNP rs4266553 was more common in the adenomyosis group (p?=?.02). GPR30 expression was confirmed in 69 individuals in both groups. GPR30 gene polymorphism is presumed to affect the risk of adenomyosis with limited sample size. Further large-scale study is needed to explain the genetic influence of GPR30 gene polymorphism.     

Cord blood intestinal fatty acid-binding protein (I-FABP) in full-term intrauterine growth restricted pregnancies

Objective: To prospectively investigate cord blood concentrations of intestinal fatty acid-binding protein-[I-FABP, a useful marker in the early detection of necrotizing enterocolitis-(NEC)] in full-term intrauterine-growth-restricted-(IUGR, associated with NEC, regardless of gestational age) and appropriate-for-gestational-age-(AGA) pregnancies. We also aimed to determine cord blood I-FABP concentrations in IUGR cases with abnormal versus normal antenatal Doppler results and investigate a possible association with feeding intolerance or NEC.Methods: I-FABP concentrations were determined by ELISA in 154 mixed arteriovenous cord blood samples from IUGR (n = 50) and AGA (n = 104) singleton full-term infants.Results: Cord blood I-FABP concentrations did not differ between IUGR and AGA groups, as well as between IUGR infants with normal versus abnormal(however, lacking absent/ reversed end-diastolic umbilical artery flow) antenatal Doppler results. No infant presented with feeding intolerance or NEC. Customized centiles were lower in IUGR infants with abnormal versus normal antenatal Doppler results (p < 0.001). Conclusions: Full-term IUGR infants present with normal cord blood I-FABP concentrations and do not seem to be at higher risk for developing feeding intolerance or NEC, including those with compromised fetal perfusion.     

Assessment of interleukin-6, interleukin-8 and interleukin-18 count in the serum of IUGR newborns

Abstract

Aim: Aim of this study was to assess concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations in serum of newborns with weight appropriate for gestational age (AGA).

Materials: Research was conducted at the Lodz Medical University Clinic of Neonatology during 2010–2011. Surveyed group consisted of 50 hypotrophic full-term infants of single pregnancies (average weight: 2329?±?287?g); control group, enclosing 50 infants AGA (average weight: 3544?±?2161?g). Both groups received average Apgar score of 9 points. Concentrations of analysed cytokines were marked between 4–6 hours after birth. The enzyme-linked immunosorbent assay (ELISA) test was used to determine interleukins concentrations. Study was prospective. Statistics on the data were conducted with the Kolmogorov–Smirnov test. Significance level: p?<?0.05.

Results: Concentrations of IL-6 and IL-18 were elevated in the IUGR group in a statistically significant manner in comparison to the control group.

Conclusions: An elevated level of IL-6 and IL-18 in the IUGR group, comparing to control group, signifies the existence of inflammation in the process of developing IUGR, therefore, screening tests estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in predicting the occurrence of IUGR and help preventing it.     

The potential role of the lectin pathway of complement in the host defence of full-term intrauterine growth restricted neonates at birth

Objective: To prospectively investigate the potential role of the lectin pathway of complement in intrauterine-growth-restriction (IUGR, associated with impaired immunocompetence and increased risk for neonatal infections), by determining cord blood concentrations of mannose-binding lectin (MBL), H-ficolin and L-ficolin (important mediators of neonatal innate immunity) in IUGR and appropriate for gestational age (AGA) pregnancies. Furthermore, we aimed to describe correlations among cord blood MBL, H- and L-ficolin concentrations and with several demographic parameters of the infants at birth. Methods: Serum MBL, H- and L-ficolin concentrations were determined by ELISA in 154 mixed arteriovenous cord blood samples from IUGR (n?=?50) and AGA (n?=?104) singleton full-term infants. Results: Cord blood MBL concentrations were significantly lower in IUGR cases than AGA controls (p?=?0.029). No differences in cord blood H- and L-ficolin concentrations were observed between groups. In the IUGR group, cord blood MBL concentrations negatively correlated with respective L-ficolin ones (r?=??0.442, p?=?0.001). Conclusions: The relatively decreased MBL expression in IUGR fetuses at term could possibly contribute to IUGR-associated neonatal immunodeficiency, predisposing to increased susceptibility to infections. The negative correlation between MBL and L-ficolin concentrations in the IUGR group might suggest an underlying immune variation and needs to be further investigated.     

IGF2/ApaI polymorphism associated with birth weight in children of the region of Petrolina–PE,Brazil

Insulin-like growth factor 2 (IGF2) gene has an important role in fetal growth. It was investigated association of the IGF2/ApaI polymorphism with low birth weight and normal birth weight (as control) in children attended in Hospital Dom Malan Petrolina, PE-Brazil. The genotype frequencies did not differ statistically between low birth weight (AA = 16.22%, AG = 43.24%, GG = 40.54%) and control (AA = 20% AG = 35%, GG= 45% groups) and the allele frequencies were not significantly different (p > 0.05).The observed genotype frequencies in both groups did not deviate significantly from Hardy–Weinberg equilibrium. Then, no significant correlation was found for this polymorphism in the population studied.