Thalita Frutuoso Lobo

Fetal growth restriction: current knowledge

BackgroundFetal growth restriction (FGR) is a condition that affects 5–10% of pregnancies and is the second most common cause of perinatal mortality. This review presents the most recent knowledge on FGR and focuses on the etiology, classification, prediction, diagnosis, and management of the condition, as well as on its neurological complications.MethodsThe Pubmed, SCOPUS, and Embase databases were searched using the term “fetal growth restriction”.ResultsFetal growth restriction (FGR) may be classified as early or late depending on the time of diagnosis. Early FGR (<32 weeks) is associated with substantial alterations in placental implantation with elevated hypoxia, which requires cardiovascular adaptation. Perinatal morbidity and mortality rates are high. Late FGR (≥32 weeks) presents with slight deficiencies in placentation, which leads to mild hypoxia and requires little cardiovascular adaptation. Perinatal morbidity and mortality rates are lower. The diagnosis of FGR may be clinical; however, an arterial and venous Doppler ultrasound examination is essential for diagnosis and follow-up. There are currently no treatments to control FGR; the time at which pregnancy is interrupted is of vital importance for protecting both the mother and fetus.ConclusionEarly diagnosis of FGR is very important, because it enables the identification of the etiology of the condition and adequate monitoring of the fetal status, thereby minimizing risks of premature birth and intrauterine hypoxia.

Resistin concentration and gestational diabetes: a systematic review of the literature

Gestational diabetes (GD) exposes mothers and infants to the risk of immediate and later adverse outcomes. Increased insulin resistance is a common feature of GD and obesity. Because of its critical role in regulating insulin sensitivity, resistin has been implicated in the physiopathology of GD. The aim of this study was to review the existing literature on the relationship between circulating maternal resistin levels and GD. Three electronic databases (MEDLINE, EMBASE, and LILACS) were searched for pertinent studies published from 2001 to 2012, without language restrictions. Eleven studies, with a total of 639 participants between 23 and 41 weeks of gestation, were included. The number of GD patients per study ranged from 11 to 81, with varying degrees of disease severity and several different GD diagnostic criteria. Mean concentrations of resistin varied widely both in control women (0.05-22.21 ng/ml) and in GD patients (0.05-62.38 ng/ml). We performed a meta-analysis including a total of 10 studies, and also subgroup analyses according to gestational age at sample collection (up to 32 and >33 weeks). The pooled absolute mean difference (WMD) in resistin levels was slightly lower in GD patients than in controls, but this did not reach statistical significance (WMD=-0.02, 95% CI -0.07 to 0.04). According to the data from the 11 studies analyzed, there was no association between circulating resistin levels and GD. However, this result should be interpreted with caution owing to the large heterogeneity amongst the existing published studies.

Impaired Treg and NK cells profile in overweight women with gestational diabetes mellitus

Maternal obesity is frequently associated with gestational diabetes mellitus (GDM), and immunological mechanisms seem to be involved in the physiopathology of these conditions. The aim of this study was to characterize the profile of immune cells in peripheral blood of overweight women with GDM.

In response to Manuscript AJRI 01-18-016 entitled “Regulatory T cells, natural killer cells and obesity in patients with gestational diabetes mellitus”-Kawada T

We thank Dr. Kawada1 for his interest in our new publication.2 Dr. Kawada mentions a recently published review on this topic by Bonamachi and Lee,3 but according to these authors, there are few studies investigating the role of natural killer (NK) cells on the development of obesityinduced inflammation and insulin resistance (IR). We evaluated subsets of regulatory T (Treg) and NK cells in peripheral blood of overweight women with Gestational Diabetes Mellitus (GDM). As we mentioned in our article, there are a few other studies on GDM that evaluated similar cellular subpopulations but using different markers.4-6 The Bonamachi and Lee3 review presented interesting results on NK cells and other cell populations (innate lymphoid cells and invariant NKT cells) but mostly in experimental studies and do not mention any studies involving pregnant women nor patients with GDM. Dr. Kawada states that CD4Treg and other T lymphocytes subpopulations “play an important role in the regulation of obesityinduced inflammation in visceral adipose tissue,” thus “subclinical glucose intolerance had already been recognized in obese subjects.” In addition, Dr. Kawada points out that CD8T cells increase with obesity in blood and adipose tissue and their inhibition could be related to the prevention of metabolic disorders. Although some investigators reported these findings, the profile of immune cells in peripheral blood in obese individuals with or without metabolic disorders remains controversial.7 Different studies have reported the existence of Tcells subsets and NK cells not in all obese (body index mass—BMI >30 kg/m2) patients, but only in those with morbid obesity (BMI >40 kg/m2) and metabolic alterations.7-10 van der Weerd et al8 reported increased numbers of CD4T lymphocytes with predominance of Treg (T CD4+ CD25+ FoxP3+) subset, but normal number of CD8T cells in peripheral blood of adults with morbid obesity without metabolic alterations. On the other hand, Sen et al9 found a significant decrease in circulating CD8T cells in healthy obese pregnant women, but no difference in CD4T population. According to Han et al,10 obesity did not affect the immune response of young adults; however, these individuals had a lower number of CD8T lymphocytes in their peripheral blood. We evaluated subsets of Treg and NK cells defined by specific cell markers in overweight pregnant women with and without GDM, and we found significant differences that seem to be related with the development of IR and inflammation. Our patients were mostly overweight (BMI ≥25 kg/m2) but not obese, and had mild, wellcontrolled GDM (only with diet); we recognize that is a limitation of our study and may explain why we did not find more significant changes. In addition, Dr. Kawada reported some data on the expression of perforin, granzyme, and granulysin on CD8T lymphocytes of peripheral blood and adipose tissue. We detected increased percentages of circulating NK cells with cytotoxic profile, but we did not investigate lymphocytes in adipose tissue, nor did we assess the expression of these toxins; therefore, we cannot speculate about its relation with overweight and GDM. Finally, we agree with Dr. Kawada that the effect of impaired Treg and NK cell profile on GDM should be confirmed in a prospective study. We recommend that this future study should include more participants with higher BMIs and a group of women with more severe forms of GDM who require insulin for their treatment.

Monocyte profile in peripheral blood of gestational diabetes mellitus patients

HighlightsIncreased percentage of CD14+ cells in gestational diabetes.Reduced frequency of CD14+CD16+ monocytes in gestational diabetes.Lower percentage of circulating monocytes that express TLR4 in gestational diabetes.Higher serum levels of soluble CD14+ in gestational diabetes. Objective Gestational diabetes Mellitus has been considered an inflammatory disease involving different cells and mediators in its development. The role of innate immune cells in GDM physiopathology remains unclear, therefore this study was conducted to assess monocyte profile in GDM patients. Design This was a case‐control study including 20 glucose‐tolerant pregnant women (controls) and 18 GDM patients. Methods Flow cytometry was used to assess peripheral blood monocytes subsets (classical, intermediate, non‐classical), the expression of TLR4 and CCR2 chemokine receptor (CD192) and cytokines (TNFA, IL6, IL10) secretion by monocytes subsets. In addition, sCD14 serum levels were evaluated by ELISA. Results We observed increased percentage of CD14+ cells, decreased frequency of intermediate monocytes (CD14+CD16+), and lower percentage of circulating monocytes (classical, intermediate and non‐classical) that express TLR4 in the diabetic group compared to controls. Soluble CD14+ serum levels were higher in GDM patients compared to controls. There were no differences in the expression of the CCR2 chemokine receptor and cytokines (TNFA, IL6 and IL10) secretion between the studied groups. Conclusions Our results demonstrated that GDM patients present impaired monocyte profile in the peripheral blood, suggesting that these cells are involved in GDM physiopathology.

Lipid Fingerprinting in Mild versus Severe Forms of Gestational Diabetes Mellitus

The blood serum lipid profile of women with Gestational Diabetes Mellitus (GDM) is still under study. There are no data on the serum lipid profile of GDM patients with more severe (insulin treated) compared to milder forms (diet treated) GDM. The aim of our study was to analyze the blood serum lipid profile of patients with milder versus more severe forms of GDM and to compare these findings with those of healthy pregnant women. This cross-sectional analytical study included 30 insulin-treated GDM, 30 diet-only GDM and 30 healthy pregnant women. Serum lipid was extracted from the 90 participants and their lipid profiles were analyzed by lipid fingerprinting using liquid-chromatography-mass spectrometry. A total of 143 parent ions were differentially represented in each of the three groups, belonging to the following classes: Glycerophospholipids, Sterol Lipids, Sphingolipids, Prenol Lipids, Fatty Acyls and Glycerolipids. There were significant differences in the lipid profiles of healthy pregnant women compared to GDM patients and also between milder versus more severe forms of GDM. There are marked differences in lipid fingerprinting between healthy pregnant women compared to those with GDM in the third trimester. Moreover, the lipid profile of women with more severe forms of GDM differs considerably from that of women with milder forms of GDM. These findings may be useful to help clarify the pathogenesis of milder and more severe forms of GDM.