Rosiane Mattar

Associations between cytokine gene polymorphisms and recurrent pregnancy loss

Since certain cytokines may play a role in unexplained recurrent pregnancy loss (RPL) and also some cytokine gene polymorphisms may affect the level of cytokine production, the aim of the present study was to investigate the relationship between RPL and polymorphisms of the genes coding for TNF-alpha (-308 G-->A), IL-10 (-1082 G-->A), IL-6 (-174 G-->C), and IFN-gamma (+874 A-->T). Genotyping was performed in 48 RPL women and 108 ethnically matched healthy individuals. In addition, we performed a meta-analysis encompassing the present results and those from studies on the association of TNF-alpha, IL-10 and IFN-gamma polymorphisms with RPL published in the literature until December 2001. The results showed: (1) no evidence of association with IL-6 gene polymorphisms; (2) significant associations, revealed by the meta-analysis, with the high cytokine production genotypes of IFN-gamma (+874 T/T: odds ratio (OR)=1.92, P=0.04) and IL-10 (-1082 G/G: OR=1.75, P=0.03), and a trend for association with the high TNF-alpha production genotypes -308 A/A and A/G (OR=1.61; P=0.18). We believe that the associations of these genotypes with RPL are interesting not only as risk factors but also because they represent another piece of evidence that these cytokines might be important in the pathogenesis of RPL.

Cytokine genotyping in preeclampsia.

Problem  Considering that cytokines are involved in preeclampsia (PE) pathogenesis and that cytokine gene polymorphism may affect cytokine production, our purpose was to investigate the association of PE with tumor necrosis factor (TNF)‐α (−308), transforming growth factor‐β1 (+10; 25), interleukin (IL)‐10 (−1082), IL‐6 (−174), and interferon‐γ (+874) polymorphisms.

Aspectos epidemiológicos da depressão pós-parto em amostra brasileira

Introduction: Psychiatric symptoms are frequent in the postpartum period, a moment marked by hormonal alterations and changes in social character, family organization and women’s identity. The Edinburgh Postnatal Depression Scale (EPDS) is a selfreporting instrument to track depression after pregnancy, unfortunately not always properly supported by health care professionals. This study aimed at verifying the prevalence of postpartum depression in women receiving care at basic health units. Methods: Cross-sectional study including 292 women in the postpartum period (from day 31 to 180) who answered the EPDS questionnaire. Cut-off point < 12 for EPDS depression was used. Results: A total of 115 women (39.4%) had scores < 12 in EPDS, classified as depressive; 177 (60.6%) had scores < 12 and were not considered depressive. Women with lower education, higher number of pregnancies, higher parity, higher number of live children and shortest relationship time had more depression. Conclusion: High frequency of postpartum depression is associated with social factors, which shows the importance of health care professionals in early detection of depression, with the aid of instruments such as EPDS, due to its efficacy and practicability.INTRODUCTION: Psychiatric symptoms are frequent in the postpartum period, a moment marked by hormonal alterations and changes in social character, family organization and womens identity. The Edinburgh Postnatal Depression Scale (EPDS) is a self-reporting instrument to track depression after pregnancy, unfortunately not always properly supported by health care professionals. This study aimed at verifying the prevalence of postpartum depression in women receiving care at basic health units. METHODS: Cross-sectional study including 292 women in the postpartum period (from day 31 to 180) who answered the EPDS questionnaire. Cut-off point < 12 for EPDS depression was used. RESULTS: A total of 115 women (39.4%) had scores < 12 in EPDS, classified as depressive; 177 (60.6%) had scores < 12 and were not considered depressive. Women with lower education, higher number of pregnancies, higher parity, higher number of live children and shortest relationship time had more depression. CONCLUSION: High frequency of postpartum depression is associated with social factors, which shows the importance of health care professionals in early detection of depression, with the aid of instruments such as EPDS, due to its efficacy and practicability.

Adverse pregnancy outcomes in women with diabetes

Pregnancy affects both the maternal and fetal metabolism and even in nondiabetic women exerts a diabetogenic effect. Among pregnant women, 2 to 17.8% develop gestational diabetes. Pregnancy can also occur in women with preexisting diabetes, that can predispose the fetus to many alterations in organogenesis, growth restriction and the mother to some diabetes-related complications like retinopathy and nephropathy or accelerate the course of these complications if they are already present. Women with gestational diabetes generally start their treatment with diet and lifestyle modification; when these changes fail in keeping an optimal glycemic control, then insulin therapy must be considered. Women with type 2 diabetes in use of oral hypoglycemic agents are advised to change to insulin therapy. Those with preexisting type 1 diabetes must start an intensive glycemic control, preferably before conception. All these procedures are performed aiming to keep glycemic levels normal or near-normal as possible to avoid the occurrence of adverse perinatal outcomes to the mother and to the fetus. The aim of this review is to reinforce the need to improve the knowledge on reproductive health of women with diabetes during gestation and to understand what are the reasons for them failing to attend for prepregnancy care programs, and to understand the underlying mechanisms of adverse fetal and maternal outcomes, which in turn may lead to strategies for its prevention.

Inflammatory cytokine gene polymorphisms and spontaneous preterm birth

The objective was to search for an association between spontaneous preterm birth (sPTB) and single and/or combined polymorphisms in genes TNFA -308 G>A, IL10 -1082 G>A, IL10 -819 C>T, IL10 -592 C>A, IL6 -174 G>C, and IFNG +874 A>T. Genotyping was performed on 410 Brazilian ethnically matched women managed at two hospitals (two independent case-control sets). One set consisted of 122 cases and 101 controls, and the other set comprised 82 cases and 105 controls. We compared genotype and genotype-combination frequencies between cases and controls using Fishers exact or the chi(2) tests and confirmed results using logistic regression. Among the six SNPs studied, we found no independent association between any single SNP and sPTB risk. The multi-locus analysis revealed a significant association between sPTB and the TNFA(GG)/IL6(GG)/IFNG(AA) genotype combination (p=0.002), confirmed by logistic regression. Our data suggest that the combination of TNF-alpha, IFN-gamma, and IL-6 maternal gene polymorphisms might contribute to susceptibility to sPTB. This finding could be investigated as a possible genetic marker for the risk of spontaneous preterm birth.

Genetic Polymorphisms and Recurrent Spontaneous Abortions: An Overview of Current Knowledge

The relevance of gene polymorphisms in the development of unexplained recurrent spontaneous abortion is still unclear. Cytokines, angiogenic mediators, and hormones are involved in all stages of reproduction and pregnancy outcome. Impaired production and/or unbalanced ratios of these mediators have been implicated in the pathogenesis of unexplained recurrent spontaneous abortion. Functional polymorphism influence gene activity and therefore can interfere with the expression of mediators. Several studies have been carried out to evaluate the relationship between cytokines, angiogenic mediators, and hormones gene polymorphisms and unexplained recurrent spontaneous abortion. The results of these studies are mostly contradictory, and few significant associations have been identified. Up to present time, the evidence is insufficient to support the evaluation of cytokines, angiogenic mediators, and hormones gene polymorphism in routine workup in all cases of recurrent pregnancy loss, and these tests are not included in any of the major obstetric guidelines.

Cytokine gene polymorphisms in preeclampsia and eclampsia

The clinical spectrum of preeclampsia (PE) ranges from mild hypertension to severe vasospasm associated with convulsions and multiple organ damage. The biological factors that determine the progression of PE to eclampsia (E) are unknown. Endothelial cell activation seems related to an impaired maternal immune response. The production of cytokines, IL-10 and TGF-β1, is apparently suppressed, and altered IL-2/IL-10 and TNF-α/IL-10 ratios have been reported in preeclamptic cases. The relationship between PE and cytokine gene polymorphism has been studied, but there are few studies that include eclamptic patients. This study aimed at investigating whether polymorphisms in genes, TNF-α promoter (−308 G>A), IL6 promoter (−174 G>C), IFN-γ intron 1 (+874 A>T), IL10 promoters (−1082 A>G), (−819 C>T) and (−592 C>A) and TGF-β1 codon 10 (+869 T>C) and codon 25 (+915 G>C) are associated with E and/or PE. Genotyping was carried out in 266 Mulatto women from the northeastern region of Brazil who were referred to a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls. The χ2 or Fishers exact tests were used to compare genotype frequencies. Among the six single-nucleotide polymorphisms (SNPs) studied, we found no difference in genotype frequencies between the groups. There was a higher frequency of IFN-γ (+874 A) in eclamptic patients in comparison with that in controls. (70.3 vs. 57.8%, respectively; P=0.02). There were no other significant differences in allelic frequencies between eclamptic, preeclamptic and control groups We found no independent association between any single SNP and PE or E risk in this population of Mulatto women from the northeastern region of Brazil.

Cytokine Levels in Gestational Diabetes Mellitus: a Systematic Review of the Literature

Gestational diabetes mellitus (GDM) is an inflammatory condition that involves unbalanced cytokine production. We carried out a systematic review on the relationship between GDM and maternal circulating levels of cytokines in the 2nd/3rd trimesters.

Sleep disorders in pregnancy

CONTEXT The precise function of sleep in animals and human beings is still unknown, and any sort of physical, social or psychological variation may change the normal sleep-wake cycle. PURPOSE This research aims is to determine the sleep disorders (SD) for each of the three trimesters of the pregnancy comparing them to the pre-pregnancy state (PG). METHOD SD were investigated in three hundred pregnant women 11- to 40-years-old through with a brief clinical interview based on directed questions. One hundred pregnant women were considered for each trimester. RESULTS The rate of pregnant women with insomnia increased by 23% in the 2nd trimester (p< 0.005); the rate for excessive daytime sleepiness (EDS) by 15% in the 1st trimester (p<0.003), 55% in the 2nd trimester (p<0.001) and by 14% in the 3rd trimester (p<0.002); the rate for mild sleepiness increased by 33% in the 2nd trimester (p<0.002) and by 48% in the 3rd trimester (p<0.001); the rate for specific awakenings increased by 63% in the 1st trimester, by 80% in the 2nd trimester and by 84% in the 3rd trimester (p<0.001). CONCLUSION SD were more frequent during pregnancy comparatively to PG state, mostly at the expenses of EDS and specific awakenings.

Gestação na adolescência precoce e tardia: há diferença nos riscos obstétricos?

OBJETIVOS: descrever aspectos da assistencia e resultados obstetricos da gravidez em adolescentes atendidas em um centro de atendimento terciario do Ceara e comparar os resultados maternos e perinatais entre adolescentes precoces e tardias. METODOS: em estudo transversal, analitico, avaliaram-se 2.058 casos, sendo 322 (15,6%) de adolescentes precoces e 1.736 (84,4%) tardias, atendidas no ano de 2000. Foram analisados as intercorrencias clinicas no pre-natal, tipo de parto, indicacoes de cesarea, idade gestacional no parto, peso do recem-nascido ao nascimento, adequacao do peso a idade gestacional, indices de Apgar no primeiro e quinto minuto de vida, presenca de malformacoes e obito neonatal. Utilizaram-se o teste exato de Fisher e o c2 na comparacao entre os dois grupos. Calculou-se tambem a razao de prevalencia. RESULTADOS: do total de partos ocorridos no periodo, 25,9% eram de adolescentes e a media de idade destas foi de 17,2 anos. Constatou-se que 88% frequentaram o pre-natal, sendo 60% com numero insuficiente de consultas. As intercorrencias clinicas mais frequentes foram a pre-eclâmpsia (14,7%), a anemia (12,9%) e a infeccao do trato urinario (6,4%), sem diferenca de frequencia entre os grupos. Ocorreram 31,3% de nascimentos por cesarea, sendo a pre-eclâmpsia a principal indicacao nas duas faixas etarias (25 e 23%, respectivamente). A frequencia de Apgar menor que 7 no primeiro minuto foi de 19,9% no grupo das adolescentes precoces e 14,2% entre as tardias (x²=6,96, p=0,008). Nao houve diferenca quanto a frequencia de prematuridade (20,2 vs 16,1%), recem-nascido pequeno para idade gestacional (12,4 vs 10,4%), baixos escores de Apgar de quinto minuto (5,3 vs 3,3%), malformacoes congenitas (3,1 vs 2,7%) e morte neonatal (1,6 vs 3,1%). CONCLUSOES: as gestantes adolescentes precoces e tardias apresentaram evolucao da gestacao e desempenho obstetrico semelhantes, exceto pela diferenca nos escores de Apgar no primeiro minuto.