Circulating Tissue Inhibitor of Metalloproteinase-4 levels are not a Predictor of Preeclampsia in the period between 20 and 25 Weeks of Gestation / Níveis circulantes de inibidor tecidual da metaloproteinase tipo-4 não são um preditor de preeclampsia no período entre 20 e 25 semanas de gestação

Abstract Objective To evaluate whether the circulating level of tissue inhibitor of metalloproteinase- 4 (TIMP-4) in the period between 20 and 25 weeks of gestation is a predictor of preeclampsia. Methods We have performed a case-control study, nested in a prospective study cohort in Ribeirão Preto, in the state of São Paulo, Brazil. Of the 1,400 pregnant women evaluated between 20 and 25 weeks of gestation, 460 delivered in hospitals outside of our institution. Of the 940 pregnant women who completed the protocol, 30 developed preeclampsia. Healthy pregnant women (controls, n = 90) were randomly selected from the remaining 910 participants. From blood samples collected between 20 and 25 weeks of gestation, we performed a screening of 55 angiogenesis-related proteins in 4 cases and 4 controls. The protein TIMP-4 was the most differentially expressed between cases and controls. Therefore, wemeasured this protein in all cases (n = 30) and controls selected (n = 90). Results There were no differences in the plasma TIMP-4 levels of cases compared with controls (1,144 263 versus 1,160 362 pg/mL, respectively; p > 0.05). Conclusion Plasma TIMP-4 levels were not altered at 20 to 25 weeks of gestation, before the manifestation of clinical symptoms; therefore, they are not good predictors of the development of preeclampsia.

Resumo Objetivo Avaliar se o nível de inibidor tecidual de metaloproteinases tipo-4 (TIMP-4, na sigla em inglês) circulante no período entre 20 e 25 semanas de gestação é um preditor de preeclâmpsia. Métodos Foi realizado um estudo caso-controle aninhado em uma coorte de estudo prospectivo em Ribeirão Preto, São Paulo, Brasil. De 1.400 mulheres grávidas avaliadas entre 20 e 25 semanas de gestação, 460 tiveram parto em hospitais fora da nossa instituição. Das 940 gestantes que completaram o protocolo, 30 desenvolveram preeclâmpsia. Gestantes saudáveis (controles, n = 90) foram selecionadas aleatoriamente das 910 participantes restantes. A partir de amostras de sangue coletadas entre 20 e 25 semanas de gestação, foi realizada uma triagem de 55 proteínas relacionadas à angiogênese em 4 casos e 4 controles. A proteína TIMP-4 foi a mais diferentemente expressa entre os casos e os controles; portanto, medimos esta proteína em todos os casos (n = 30) e controles selecionados (n = 90). Resultados Não houve diferenças nos níveis plasmáticos de TIMP-4 nos casos em comparação com os controles (1.144 263 versus 1.160 362 pg/mL, respectivamente; p > 0,05). Conclusão Os níveis plasmáticos de TIMP-4 não foramalterados no período entre 20 e 25 semanas de gestação antes da manifestação dos sintomas clínicos; portanto, não são um bom preditor do desenvolvimento da preeclâmpsia.

Incorporación del estudio de ADN fetal en sangre materna al cribado de cromosomopatías / Incorporation of the study of fetal DNA in maternal blood to the screening of chromosomal diseases

OBJETIVO: Evaluar la efectividad del cribado combinado de primer trimestre para la detección prenatal de aneuploidías tras 6 años de implantación en nuestro servicio y su repercusión en la disminución de pruebas diagnósticas invasivas. Se propone establecer un protocolo para incorporar el estudio de ADN fetal en sangre materna a partir de las revisiones bibliográficas publicadas. MÉTODO: Se evaluó el riesgo de anomalía cromosómica fetal en 3177 gestaciones mediante cribado combinado de primer trimestre entre enero de 2011 y diciembre de 2014. Se revisaron las amniocentesis realizadas desde que se instauró el cribado combinado en 2008 comparándolas con las de los 5 años anteriores. RESULTADOS: La tasa de detección del cribado para trisomía 21 fue del 94,4% y la tasa de falsos positivos de 6,4%. En el año 2005 estábamos realizando 194 amniocentesis, tras 6 años de implantación del cribado, en el año 2013 se realizaron 35 amniocentesis lo que implica una disminución del 70%. CONCLUSIONES: El cribado combinado de primer trimestre ha demostrado una mayor tasa de detección para trisomía 21 que el cribado de segundo trimestre y/o la edad materna, además de que ha llevado a una importante reducción en el número de pruebas invasivas. En los próximos años la incorporación del estudio de ADN fetal mejorará la detección de aneuploidías, con una drástica disminución de las pruebas invasivas por lo que se hace necesario la implantación de nuevos protocolos.

AIMS: To evaluate the effectiveness of first trimester combined screening in the prenatal detection of aneuploidy after 6 years of implantation in our service and its impact in reducing invasive diagnostic tests. It is proposed to establish a protocol to incorporate the study of fetal DNA in maternal blood from published literature reviews. METHODS: The risk of fetal chromosomal anomalies was assessed in 3177 pregnancies with first trimester combined screening between January 2009 and December 2014. The amniocenteses performed were checked against those of the previous 5 years. RESULTS: The detection rate of screening for trisomy 21 was 94.4% and the false-positive rate was 6.4%. In 2005 there were 194 amniocenteses. In 2013, 5 years after the introduction of screening, 68 amniocenteses were performed, representing a 70% reduction in invasive procedures. CONCLUSIONS: First trimester combined screening has shown a higher detection rate for trisomy 21 that the second trimester screening and/or maternal age, and has substantially reduced the use of invasive prenatal diagnostics procedures. In the coming years, the incorporation of the study of fetal DNA improve the detection of aneuploidys with a drastic reduction of invasive tests so that, the implementation of new protocols is necessary.

Niveles de ácido úrico sérico y riesgo de desarrollar preeclampsia

Si bien se conoce que existe una asociación entre los niveles elevados de ácido úrico y la preeclampsia, el debate sobre su aplicación clínica aún está abierto. Nuestro objetivo fue estudiar la utilidad del dosaje periódico del ácido úrico sérico durante el embarazo para identificar gestantes con mayor riesgo de desarrollar preeclampsia. Realizamos un estudio retrospectivo en gestantes primíparas: 79 normotensas y 79 con preeclampsia atendidas en el Hospital Nacional Posadas durante el año 2010. Se analizaron los niveles séricos de ácido úrico, creatinina y urea, y los datos de proteinuria de las historias clínicas de las mujeres embarazadas. Los niveles de ácido úrico fueron similares en ambos grupos durante la primera mitad de la gestación. Sin embargo, a partir de la semana 20, el ácido úrico se incrementó 1.5 veces en gestantes preeclámpticas, sin cambios en la uremia y creatininemia, descartándose así el compromiso renal. Además, encontramos que niveles más altos de ácido úrico se correlacionaban con bajo peso del recién nacido. También vimos que las gestantes con antecedentes familiares de hipertensión eran más propensas a desarrollar esta condición. Por otro lado, no observamos una relación directa ni con el sexo fetal ni con el tiempo de aparición de los síntomas clínicos. Estos hallazgos sugieren que los cambios en las concentraciones de ácido úrico se deberían a alteraciones en los estadios iniciales de la preeclampsia. Por ello, la monitorización de los niveles del mismo durante el embarazo podría contribuir al abordaje precoz de este desorden gestacional.

It is well known that preeclampsia is associated to high uric acid levels, but the clinical assessment of this relationship is still under consideration. Our research was to evaluate if periodic doses of uric acid during pregnancy might help to identify a high risk group prior to the onset of preeclampsia. We conducted a retrospective investigation in 79 primary gestates with normal blood pressure and 79 women with preeclampsia who were assisted at Hospital Nacional Posadas during 2010. Serum uric acid levels, creatininemia, uremia, and proteinuria data from the clinical records of the pregnant women were considered. Uric acid levels were similar in both groups during the first half of gestation. However, as of the 20th week, uric acid increased 1.5-times in preeclamptic women with no changes in creatinine and urea, confirming that these patients had no renal complications. Furthermore, we noted that higher levels of uric acid correlated with low birth weight. We also observed that pregnant women with a family history of hypertension were more likely to develop this condition. Moreover, we did not find a direct relationship with the fetal sex or the appearance of clinical symptoms. The analytical evidence suggests that changes in uric acid concentrations may be due to metabolic alterations at the initial stages of preeclampsia. Therefore, we propose that monitoring levels of uric acid during pregnancy might contribute to the early control of this condition.

Comparison of the prevalence of anemia in the first, second and third trimester of pregnancy in a medical and educational center in Shiraz

The high rate of anemia in pregnancy is associated with complications of pregnancy and delivery; therefore, to assess the level of hemoglobin [Hb] in women who are at risk can prevent these complications. In this descriptive study, 108 pregnant women referred to a medical and educational center in Shiraz in 2006. They were enrolled in three different occasions: first trimester [10-14 weeks], second trimester [25-30 weeks], and third trimester [37-40 weeks]. The correlation of blood hemoglobin concentration with the risk of severe nausea, vomiting, and iron supplementation in pregnant women was estimated. Statistical analysis was done with SPSS 11.5 and Pearson correlation. The mean age of the participants is 25.74 +/- 5.66. In the first trimester of pregnancy 71.9% had normal hemoglobin level and 28.1% higher than normal with no case being anemic. In the second and third trimester of pregnancy, 29.2% of the subjects were anemic. The level of hemoglobin had positive correlation with the total amount of iron intake in the second trimester [p= 0.001 and r= 0.44], also in the third trimester [p< 0.001 and r= 0.46] and the whole pregnancy [p< 0.001 and r= 0.38]. This study indicated that despite regular intake of iron,%29.2 of the subjects had anemia. These findings emphasize the importance of treating these groups of patients and measuring levels of hemoglobin in each trimester together with reviewing other risk factors which are effective on anemia

[Relationship between human chorionic gonadotrapin [HCG] level in second trimester pregnancy and preeclampsia]

Many researches have shown a relationship between levels of beta HCG in pregnancy and preeclampsia, which can be used as a method for early diagnosis. The aim of this study was to determine relationship between levels of HCG in second trimester of pregnancy and preeclampsia. This study was conducted as a Nested case control study. Blood samples were taken from 1200 pregnant women who were in their second trimester of pregnancy and were admitted for prenatal care in Arak prenatal clinics. After isolation of serums, blood samples were stored in-20°C until delivery time. Finally serum HCG levels, blood pressure, proteinurea, edema, seizure and neonate statue were analyzed in 50 preeclamptic women [case group] and were compared with 50 normotensive women [control group]. All women were complicated with mild preeclampsia. The mean of the beta HCG in preeclamptic women was 43.08 +/- 32.56 Iu/ml and means of HCG in normotensive women was 27.48 +/- 25.97 mu/ml [P<0.05], the mean of systolic blood pressure in case and control groups were 144.09 +/- 11.30 mmHg and 110.26 +/- 8.13 mmHg, respectively [P<0.001]. The mean of diastolic blood pressure in preeclamptic women was higher than normotensive women [90.45 +/- 4.34 mm/hg and 70 +/- 9.80 mm/hg] [P<0.001]. Our data showed a significant relationship between mean levels of HCG preeclampsia in second trimester. Therefore, screening of high risk group with HCG hormone and careful prenatal care should be considered during pregnancy

Lipid profile changes in second trimester of pregnancy.

The present study was carried out in the department of physiology, Mymensingh Medical College, Mymensingh, Bangladesh during the period of July 2006 to June 2007. The aim of the study was to investigate the changes in serum total cholesterol, triacylglycerol, HDL-cholesterol and LDL-cholesterol during the 2nd trimester of normal pregnancy. The serum concentrations of total cholesterol, triacylglycerol, HDL-cholesterol and LDL-cholesterol were measured in 50 cases during the second trimester of pregnancy and in a control group of 100 cases of non pregnant women, which was matched on reproductive age. Data were analyzed by computer with SPSS program using unpaired 't' test. The result showed that the pregnant women had significantly higher concentrations of serum total cholesterol, triacylglycerol and LDL cholesterol (p<0.001). But in case of HDL-cholesterol the mean concentration was slightly higher than control group though not statistically significant (p<0.079). Higher concentration of lipids and lipoproteins in second trimester of pregnancy may be a purely physiological response to pregnancy or it may be indicative of pathology in some women. These results warrant a follow up study to investigate whether the hyperlipidaemic response to pregnancy is variable and if so, whether it can predict future hyperlipidaemia in later life.

Proteína S libre en embarazadas normales: comparación entre dos métodos / Free protein S (PS) in normal pregnancy: A comparison between two analytical methods

Background: Pregnancy is a physiological hypercoagulable state with an increased incidence of thromboembolic phenomena. There is an increase in the concentrations of most clotting factors, a decrease in concentration of some of the natural anticoagulants and reduced fibrinolytic activity. Changes in PS levels have also been reported. Aim: To establish referral range values of functional PS and free PS antigen, during the second (2nd T) and third trimester (3rd T) of normal gestation. Patients and methods: Forty one normal pregnant women were included in our study, 20 during the 2nd T (22-24 weeks) and 21 during the 3rd T (29-38 weeks). Functional PS was measured by a clot based test and free PS antigen by ELISA. Results: Free PS Antigen was 65.8±18.3% during the 2nd T and 62.3±16.5% during the 3rd T. The figures for normal controls were 106±6.5%. Functional PS was 43.8±13.3 and 25.9±14.6% during the 2nd T and 3rd T, respectively. The figures for normal controls were 97±24% (p <0.001 compared with pregnant women). Free PS antigen did not change from the 2nd to the 3rd T (p=NS), however functional PS fell significantly from the 2nd to the 3rd T (p <0.001) and was significantly lower than free PS antigen in both trimesters (p <0.001). Conclusions: Pregnancy is associated to a decrease in PS. This abnormality is more pronounced for functional PS than free PS antigen and functional PS falls progressively during pregnancy. These assays should not be used to screen for PS deficiency during pregnancy because they could lead to a misdiagnosis.

Adverse pregnancy outcomes after a false-positive second trimester serum screen for Down syndrome in Thai pregnant women.

OBJECTIVE: To determine whether a false-positive second trimester serum screen for Down syndrome in Thai pregnant women is predictive of adverse pregnancy outcomes. MATERIAL AND METHOD: The relationship between adverse pregnancy outcomes in women and a false-positive screening for Down syndrome was investigated in a case-control study. The Double-marker maternal serum screening for Down syndrome (alpha-fetoprotein and free beta-hCG) was performed on Thai pregnant women between 14 and 21 weeks 'gestation at Charoenkrung Pracharuk Hospital from March 1998 to August 2002. The pregnancy outcomes of 165 women having false positive serum screening (risk ratio at least 1.270; study group) were compared to the outcomes of 165 control patients having negative serum screening results (control group). The outcome indices analyzed were preterm delivery, low birth weight newborn, small-for-gestational age newborn, preeclampsia, placenta previa, and fetal death. RESULTS: The incidence of adverse pregnancy outcomes was 18.2% in the study group and 15.2% in the control group (odds ratio = 1.244; 95% confidence interval = 0.696, 2.225; p = 0.46). Women in the study group delivered at a significantly lower birth weight of newborns than women in the control group did (3088.1 +/- 543.9 versus 3229.1 +/- 454.6 g, respectively; p = 0.011). No significant differences in adverse outcomes was discovered after the comparisons between the study group and the control group. preterm delivery 11 of 165 (6.6%) versus 5 of 165 (3%), p = 0.124; low birth weight newborn 11 of 165 (6.6%) versus 6 of 165 (3.6%), p = 0.213; small for gestational age newborn 4 of 165 (2.4%) versus 0 of 165 (0%), p = 0.123; preeclampsia 16 of 165 (9.7%) versus 12 of 165 (7.3%), p = 0.429; placenta previa 4 of 165 (2.4%) versus 4 of 165 (2.4%), p=1; fetal death 1 of 165 (0.6%) versus 0 of 165 (0%), p=1. CONCLUSION: The present findings revealed no apparent increase in the adverse pregnancy outcomes analyzed in women with false positive Down syndrome screening test.

Maternal serum alpha fetoprotein among pregnant females in Alexandria

Maternal serum alpha fetoprotein [MSAFP] was introduced as a screening test for congenital malformations especially neural tube defects [NTDs] two decades ago. However, many factors were known to affect its level. From these are racial differences and maternal weight. The aim of the present work is to illustrate the normal distribution of MSAFP among working pregnant women in Alexandria in gestational age 16- 18 weeks, to identify some of its determinants, and to determine the specificity and sensitivity of MSAFP for the detection of congenital anomalies and adverse pregnancy outcome. A sample of 608 pregnant working women who were 16-18 week gestation was recruited for the study from the antenatal clinic affiliated to Gamal Abdel Nasser Health Insurance Hospital in Alexandria. The enrolled women were interviewed using a structured questionnaire and a blood sample was collected from each of them to measure the level of MSAFP. At the expected time of delivery, Gamal Abd el Nasser Health Insurance Hospital was visited to collect data about the outcome of pregnancy of the enrolled women. The median of MSAFP level for deliveries with no congenital anomalies were 25.5, 33.5, and 53.2 IU/ml, at gestational weeks 16, 17 and 18 respectively. The significant variables related positively to MSAFP level included abortion or stillbirth, congenital anomalies in the index pregnancy, gestational age, bleeding during pregnancy, gestational diabetes, twin pregnancy, consanguinity between maternal parents, history of congenital or genetic diseases in maternal family, and caesarian section deliveries. Fatigue score was negatively correlated to MSAFP level. Using MSAFP multiples of median [MOM], 42.9% of abortions and stillbirths, 57.1% of twin pregnancies, 31. 25% of preterm deliveries and 27.3% of low birth weight had levels of 3 MOM or more. One fourth of the congenital anomalies were below 0.5 MOM and 41.7% were at or above 3 MOM. The sensitivity of MSAFP test for the detection of NTDs [cutoff point 2.5+ MOM] or Down syndrome [cutoff point <0.5 MOM] among the study sample was 100% [Cl: 19.8-100%]. Specificity for NTDs was 92.7% [Cl: 90.3-94.6%], while the specificity for Down syndrome was 89.1% [86.3-91.4%]. The sensitivity for adverse pregnancy outcome [cutoff point <0.5 or 2.5+ MOM] was 41.6, and the specificity was 85.8%.In conclusion, the cutoff points of MSAFP of the study sample are different from those for other populations. Different factors affect the level of MSAFP including adverse pregnancy outcomes. It is recommended to introduce antenatal screening for congenital anomalies as a routine screening test during pregnancy using levels adapted from the local population for cutoff point determination

clinical utility of serum lipids in early pregnancy and risk of pre-eclampsia

This study was carried out on 393 women to evaluate the clinical utility of the measurements of serum lipids in the first and late second trimester of pregnancy and the risk of development of preeclampsia in a prospectively followed group of healthy pregnant women aged 36 years and older. Criteria for eligibility were diastolic blood pressure at recruitment below 85 mmHg, no history of cardiovascular disease or diabetes, a viable singleton pregnancy not beyond 11 weeks and maternal age 36 years or older at 20 weeks of gestation. Serum total cholesterol and high density lipoprotein cholesterol were measured by an automated enzymatic method. Uterine artery flow velocity waveforms were recorded using continuous Doppler ultrasound. Pregnancy outcome was also assessed. In conclusion, the data suggested a relation between serum lipids in early pregnancy and the development of preeclampsia

Effects of first and second trimester vaginal bleeding on pregnancy outcome

The effects of vaginal bleeding during first and second trimester on pregnancy outcomes was assessed in a hospital-based population of 268 non-diabetic women. The group of non-bleeders comprised 173 females whereas, there were 71 females with first and 24 with second trimester bleeding. Fetal loss [abortion] occurred in 34% of first trimester and 25% of second trimester bleeders. Low birth weight and preterm delivery were significantly associated with second trimester haemorrhage. The results suggest that first and second trimester vaginal bleeding correlates with adverse infant outcomes

Elevación inexplicada de niveles plasmáticos maternos de alfa fetoproteína en el segundo trimestre del embarazo: resultados perinatales / Unexplained elevation of maternal plasmatic levels of alpha fetoprotein in the second trimester of pregnancy: perinatal results

El objetivo del trabajo fue determinar la relación entre eventos perinatales adversos y valores inexplicadamente elevados de alfa fetoproteínas en el plasma materno de embarazadas en el segundo trimestre de la gestación. Entre enero de 1985 y noviembre de 1991, se estudiaron 16.093 embarazadas que dieron a luz en el Queen Mothers Hospital, Glasgow, Escocia. El grupo con valores elevados de AFP (n=606) estuvo asociado con elevados riesgos de parto prematuro (radio de riesgo/95 por ciento intervalo confianza) (3,7/2,6-5,2), pequeño para la edad gestacional (4,5/3,3-6-1), muerte intaruterina (3,9/1,7-9-4), desprendimiento placentario (3,2/1,5-6,7). Los riesgos se incrementarom proporcionalmente a la elevación de AFP. De este trabajo se desprende que una elevación inexplicada de AFP en el segundo trimestre del embarazo se asocia a riesgo elevados de eventos perinatales adversos, demostrando que la AFP puede usarse como un marcador no específico de alto riesgo obstétrico

Plasma levels of estradiol & progesterone at different gestational ages in Indian women.

Plasma levels of estradiol and progesterone were determined at different gestational ages in Indian pregnant women from the low socio-economic group. The levels of estradiol and progesterone progressively increased with gestation and reached maximum values (14.35 +/- 1.092 and 145.9 +/- 7.69 ng/ml, respectively) by term. Though the estradiol values were comparable to those reported in literature, the term values of progesterone were found to be lower (145.9 +/- 7.69 ng/ml) than those reported from Western countries (160 +/- 7.5 ng/ml) at 34-38 wk of gestation. These low progesterone values may have physiological implication in placental function.