Adipokine levels in overweight women with early-onset gestational diabetes mellitus.

PURPOSE: The study of adipokines in overweight women with early-onset (diagnosed before 20 weeks) gestational diabetes mellitus (GDM) could help to understand the ethiopathological mechanisms of this disorder. Our aim was to assess adipokine levels in overweight pregnant women with early-onset GDM compared to patients with standard-onset (diagnosed at 24-28 weeks) GDM and to glucose-tolerant women at the same gestational ages. METHODS: This nested case-control study included 133 overweight pregnant women: 33 with early-onset (diagnosed < 20 weeks) GDM; 40 with standard-onset (diagnosed ≥ 24 weeks) GDM and 60 glucose-tolerant (normal oral glucose tolerance tests < 20 and ≥ 24 weeks). Adiponectin, leptin, resistin, visfatin and ghrelin serum levels were measured by ELISA. RESULTS: Adiponectin serum levels were significantly lower in early-onset GDM women than in standard-onset GDM patients or controls matched for gestational age. Leptin serum levels were significantly higher in women with early-onset GDM than in controls. Women with early-onset GDM had lower adiponectin/leptin ratio than those with standard-onset GDM. There were no significant differences in resistin, ghrelin and visfatin serum levels among the participants. CONCLUSIONS: Our results suggest that, compared to overweight glucose-tolerant women and patients with standard-onset GDM, overweight women with early-onset GDM have unbalanced adipokine levels, suggesting that they have a more inflammatory profile.

Quality of oxytocin available in low- and middle-income countries: a systematic review of the literature.

BACKGROUND: Oxytocin is the drug of choice for preventing and treating postpartum haemorrhage, an important cause of maternal death. Oxytocin is widely available in low and middle-income countries (LMIC) but there are concerns about its quality. OBJECTIVE: To identify, critically appraise and synthesise the findings of studies on the quality of oxytocin available in LMIC. SEARCH STRATEGY: We searched seven electronic databases, without language restriction. SELECTION CRITERIA: Studies reporting results of tests to assess quality of oxytocin samples from LMIC. DATA COLLECTION AND ANALYSIS: Study selection, data extraction and quality assessment were performed in duplicate. Results are presented descriptively. MAIN RESULTS: The search identified 2611 unique citations; eight studies, assessing 559 samples from 15 different countries were included. Most samples were collected from facility level settings (n = 509) and from the private sector (n = 321). The median prevalence of oxytocin samples that failed quality tests was 45.6% (range 0-80%), mostly due to insufficient amounts of active pharmacological ingredient. Over one-third of the samples (n = 204) had low (<90%) oxytocin content indicating substandard medicine; two samples had no active ingredient, suggesting possible counterfeit drugs. The proportion of low fails was higher in samples collected in Africa than in Asia or Latin America (57.5% versus 22.3% versus 0%, respectively, P < 0.0001), in private than in public sectors (34.0% versus 25.3%, P = 0.032) and in facilities than in central distributors (37.9% versus 22.0%, P = 0.030). CONCLUSION: There is a high prevalence of poor-quality oxytocin samples in LMIC countries, mainly due to inadequate amounts of active ingredient. TWEETABLE ABSTRACT: Systematic review points to problems with quality of oxytocin samples from low- and middle-income countries.

Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: A systematic review of the literature.

BACKGROUND: Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear. This review was conducted to assess the knowledge on placental aging related biochemical changes leading to placental dysfunction in PTB and/or preterm premature rupture of membranes (pPROM). METHODS: We performed a systematic review of studies published over the last 50 years in two electronic databases (Pubmed and Embase) on placental aging and PTB or pPROM. RESULTS: The search yielded 554 citations, 30 relevant studies were selected for full-text review and three were included in the review. Only one study reported oxidative stress-related aging and degenerative changes in human placental membranes and telomere length reduction in fetal cells as part of PTB and/or pPROM mechanisms. Similarly, two animal studies reported findings of decidual senescence and referred to PTB mechanisms. CONCLUSION: Placental and fetal membrane oxidative damage and telomere reduction are linked to premature aging in PTB and pPROM but the risk factors and biomolecular pathways causing this phenomenon are not established in the literature. However, no biomarkers or clinical indicators of premature aging as a pathology of PTB and pPROM have been reported. We document major knowledge gaps and propose several areas for future research to improve our understanding of premature aging linked to placental dysfunction.

Googling caesarean section: a survey on the quality of the information available on the Internet.

OBJECTIVE: To examine the quality and completeness of information on caesarean section in web pages used by laypersons in Brazil, a country with very high rates of caesarean delivery. DESIGN: Cross-sectional study. SETTING: Brazil. SAMPLE: A total of 176 Internet websites. METHODS: The term 'caesarean delivery' and 25 synonyms were entered into the most popular search engines in Brazil. The first three pages of hits were downloaded and assessed by two independent investigators using the DISCERN instrument and a content checklist. MAIN OUTCOME MEASURES: Quality and completeness of information on caesarean section. RESULTS: A total of 3900 web pages were retrieved and 176 fulfilled the selection criteria. The overall average DISCERN score was 43.6 (±8.9 SD), of a maximum score of 75; 30% of the pages were of poor or very poor quality and 47% were of moderate quality. Most pages scored low, especially in questions related to reliability of the information. The most frequently covered topics were: indications for caesarean section (80% of websites), which did not reflect clinical practice; short-term maternal risks (80%); and potential benefits of caesarean section (56%), including maternal and doctor convenience. Less than half of the websites mentioned perinatal risks and less than one-third mentioned long-term maternal risks associated with caesarean section, such as uterine rupture (17%) or placenta praevia/accreta (12%) in future pregnancies. CONCLUSIONS: The quality and completeness of web-based resources in Portuguese about caesarean section were poor to moderate. Pending improvement of these resources, obstetricians should warn pregnant women about these facts and encourage them to discuss what they have read on the Internet about caesarean section. TWEETABLE ABSTRACT: The quality and completeness of information about caesareans is poor in 176 websites used by Brazilians.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial.

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

What do popular Spanish women's magazines say about caesarean section? A 21-year survey.

OBJECTIVES: Caesarean section (CS) rates are increasing worldwide and maternal request is cited as one of the main reasons for this trend. Women's preferences for route of delivery are influenced by popular media, including magazines. We assessed the information on CS presented in Spanish women's magazines. DESIGN: Systematic review. SETTING: Women's magazines printed from 1989 to 2009 with the largest national distribution. SAMPLE: Articles with any information on CS. METHODS: Articles were selected, read and abstracted in duplicate. Sources of information, scientific accuracy, comprehensiveness and women's testimonials were objectively extracted using a content analysis form designed for this study. MAIN OUTCOME MEASURES: Accuracy, comprehensiveness and sources of information. RESULTS: Most (67%) of the 1223 selected articles presented exclusively personal opinion/birth stories, 12% reported the potential benefits of CS, 26% mentioned the short-term and 10% mentioned the long-term maternal risks, and 6% highlighted the perinatal risks of CS. The most frequent short-term risks were the increased time for maternal recovery (n = 86), frustration/feelings of failure (n = 83) and increased post-surgical pain (n = 71). The most frequently cited long-term risks were uterine rupture (n = 57) and the need for another CS in any subsequent pregnancy (n = 42). Less than 5% of the selected articles reported that CS could increase the risks of infection (n = 53), haemorrhage (n = 31) or placenta praevia/accreta in future pregnancies (n = 6). The sources of information were not reported by 68% of the articles. CONCLUSIONS: The portrayal of CS in Spanish women's magazines is not sufficiently comprehensive and does not provide adequate important information to help the readership to understand the real benefits and risks of this route of delivery.

Does motherhood affect the quality of life of adolescents?

STUDY OBJECTIVE: Assess the quality of life (QOL) of female adolescents with children compared to those without children. DESIGN: Cross-sectional. SETTING: Public university-affiliated family planning clinic, São Paulo, Brazil. PARTICIPANTS: 91 female adolescents (16-19 years) of low socio-economic status with and without children. INTERVENTIONS: The Portuguese version of the WHOQOL-BREF questionnaire was used. OUTCOME MEASURES: Mean scores of the 4 main domains were compared between adolescents with and without children. RESULTS: Both mothers (N = 40) and nonmothers (N = 51) had low mean scores (<75%) in most of the QOL domains. Compared to adolescents without children, adolescent mothers scored significantly lower in the physical (52.1 vs 59.4, P = .0137) and social (66.9 vs 77.3, P = .0182) domains. CONCLUSION: Adolescent mothers have a significantly lower quality of life in the physical and in the social relationships domains than nonmothers.

Premature rupture of membranes before 28 weeks managed expectantly: maternal and perinatal outcomes in a developing country.

This study aimed to assess outcomes of expectant management for early preterm premature rupture of membranes (PPROM). This retrospective cohort involved 66 women with PPROM <28 weeks managed in a single hospital (1999-2006). Main outcomes were chorioamnionitis, severe maternal morbidity (maternal sepsis, haemorrhage/blood transfusion, hysterectomy or admission to intensive care unit), maternal mortality, low birth weight, preterm birth, neonatal infection and perinatal mortality. Mean gestational ages at PPROM and delivery were 21.7 ± 4.2 and 28.4 ± 5.9 weeks, respectively. Chorioamnionitis was diagnosed in 47%; no cases of severe maternal morbidity or mortality occurred. Stillbirth rate was 25.7% and >80% of infants were delivered before 34 weeks. Neonatal infection was diagnosed in 42.9% of the 49 live-births. Overall survival rate was 57.6%. Expectant management of PPROM <28 weeks resulted in high rates of chorioamnionitis and preterm deliveries but in over half of the cases, a live infant was discharged home.

PP115. Relationship between angiogenic factors and preeclampsia: Preliminary results.

INTRODUCTION: The pathogenesis of preeclampsia (PE) is complex and involves many mechanisms, including impaired placental angiogenesis. Endoglin (Eng) promotes angiogenesis, but in its soluble form (sEng) it is antiangiogenic and adiponectin has pro-angiogenic and anti-inflammatory effects on the endothelium. The combined analysis of these factors seems to better reflect maternal vascular damage. OBJECTIVES: We aimed to evaluate adiponectin and soluble endoglin levels, to analyze adiponectin (+45) gene polymorphism and its relation with adiponectin serum levels in patients with PE. METHODS: This case-control study included 24 PE patients and 20 healthy pregnant women (C: control). Adiponectin and sEng serum levels were determined by ELISA. Polymorphism genotyping was obtained by PCR-RFLP. Data were analyzed by Mann-Whitney, Chi-square or Fisher's exact tests and significance was set at p<0.05. RESULTS: There were no differences in adiponectin levels between the groups (C×PE: 6772.4ng/mL×7763.2ng/mL, p=0.99), but women with PE had significantly higher sEng levels (23.45 ng/mL×3.35ng/mL, p<0.0001). Moreover, the ratio adiponectin/sEng was significantly lower in PE than in C women (325.02×2119.4, p<0.0001). There was no association between PE and the analyzed polymorphism, neither between adiponectin genotype/phenotype. CONCLUSION: Our findings confirm an association between PE and altered sEng levels. In addition, these results suggest that angiogenic mediators when analyzed together, can better reflect their involvement in the pathophysiology of PE. Financial support: FAPESP (09/54729-6 and 10/08082-8).

Evaluation of placental volume at 7-10+6 weeks of pregnancy by 3D-sonography.

The aim of the study was to establish normative data for placental volume (PV) at 7-10+6 weeks of gestation using three-dimensional ultrasound (3DUS). The cross-sectional study involved 70 healthy pregnancies between 7 and 11 weeks. The VOCAL (Virtual Organ Computer-aided Analysis) method with a 30 degrees rotation angle and six planes was used for volumetric calculations. Regression models were constructed to assess the correlation between PV and crown-rump length (CRL) adjusted by the determination coefficient (R2). The method proposed by Royston and Wright was used to establish the 2.5th; 10th; 50th; 90th and 97.5th percentiles (percentile=mean+KxSD). The intraclass correlation coefficient (ICC), Bland-Altman graphs and Student's paired t-tests were used to assess intra- and interobserver variability. PV ranged from 1.7 to 42.6 cm3, with a mean of 13.6cm3 (+/-9.4cm3). There was a strong correlation between PV and CRL; the exponential equation was the model that best expressed the correlation between them (R2=0.76). For CRL between 9 and 40 mm, the mean PV increased 10.5 times, while CRL increased only 4.4 times. Inter- and intraobserver correlation were excellent (ICC=0.979 and 0.971, respectively). Bland-Altman graphs indicated a good reproducibility with a mean intraobserver and interobserver difference of 0.2 cm3 (95% CI: -0.7-1.2cm3) and -0.2cm3 (95% CI: -1.3-0.9cm3), respectively. Reference limits were generated for first trimester PV assessed by 3DUS using the VOCAL method. There is a strong correlation between PV and CRL. Placental volume obtained through this method was highly reproducible.

Safety of ultrasonography in pregnancy: WHO systematic review of the literature and meta-analysis.

OBJECTIVE: In the context of the planned International Society of Ultrasound in Obstetrics and Gynecology-World Health Organization multicenter study for the development of fetal growth standards for international application, we conducted a systematic review and meta-analysis to evaluate the safety of human exposure to ultrasonography in pregnancy. METHODS: A systematic search of electronic databases, reference lists and unpublished literature was conducted for trials and observational studies that assessed short- and long-term effects of exposure to ultrasonography, involving women and their fetuses exposed to ultrasonography, using B-mode or Doppler sonography during any period of pregnancy, for any number of times. The outcome measures were: (1) adverse maternal outcome; (2) adverse perinatal outcome; (3) abnormal childhood growth and neurological development; (4) non-right handedness; (5) childhood malignancy; and (6) intellectual performance and mental disease. RESULTS: The electronic search identified 6716 citations, and 19 were identified from secondary sources. A total of 61 publications reporting data from 41 different studies were included: 16 controlled trials, 13 cohort and 12 case-control studies. Ultrasonography in pregnancy was not associated with adverse maternal or perinatal outcome, impaired physical or neurological development, increased risk for malignancy in childhood, subnormal intellectual performance or mental diseases. According to the available clinical trials, there was a weak association between exposure to ultrasonography and non-right handedness in boys (odds ratio 1.26; 95% CI, 1.03-1.54). CONCLUSION: According to the available evidence, exposure to diagnostic ultrasonography during pregnancy appears to be safe.

Prediction of acidemia at birth by Doppler assessment of fetal cerebral transverse sinus in pregnancies with placental insufficiency.

OBJECTIVES: To evaluate the prediction of acidemia at birth using cerebral transverse sinus (CTS) Doppler velocimetry and to determine the best parameter and cut-off values for its prediction in pregnancies complicated with placental insufficiency. METHODS: This was a prospective cross-sectional study involving 69 pregnant women (26-40 weeks' gestation) with placental insufficiency managed in two Brazilian hospitals. Doppler assessment of the CTS was carried out in the last 24 h before delivery, and the peak ventricular systolic (S-wave) and diastolic (D-wave) velocities as well as the atrial systolic velocity (A-wave) were recorded and the pulsatility index for veins (PIV) was calculated. At birth, arterial and venous umbilical cord blood samples were collected to determine acid-base and pH status. A receiver-operating characteristics (ROC) curve was constructed for each Doppler parameter with birth acidemia as the dependent variable. Sensitivity, specificity, positive and negative predictive values, accuracy and false-positive and false-negative rates were calculated for the parameters considered to be good predictors of acidemia. RESULTS: The S, D and A peak velocities and the S/A ratio were not good predictors of acidemia at birth. The PIV and the (S - A)/S ratio were good predictors of acidemia (area under the ROC curve = 0.698 (P = 0.009) and 0.654 (P = 0.009), respectively). The cut-off values were PIV = 0.855 and (S - A)/S = 0.703). CONCLUSIONS: The PIV and the (S - A)/S ratio of the CTS were good predictors of acidemia at birth in this high-risk population with placental insufficiency.

Prepregnancy BMI and the risk of gestational diabetes: a systematic review of the literature with meta-analysis.

The objective of this study is to assess and quantify the risk for gestational diabetes mellitus (GDM) according to prepregnancy maternal body mass index (BMI). The design is a systematic review of observational studies published in the last 30 years. Four electronic databases were searched for publications (1977-2007). BMI was elected as the only measure of obesity, and all diagnostic criteria for GDM were accepted. Studies with selective screening for GDM were excluded. There were no language restrictions. The methodological quality of primary studies was assessed. Some 1745 citations were screened, and 70 studies (two unpublished) involving 671 945 women were included (59 cohorts and 11 case-controls). Most studies were of high or medium quality. Compared with women with a normal BMI, the unadjusted pooled odds ratio (OR) of an underweight woman developing GDM was 0.75 (95% confidence interval [CI] 0.69 to 0.82). The OR for overweight, moderately obese and morbidly obese women were 1.97 (95% CI 1.77 to 2.19), 3.01 (95% CI 2.34 to 3.87) and 5.55 (95% CI 4.27 to 7.21) respectively. For every 1 kg m(-2) increase in BMI, the prevalence of GDM increased by 0.92% (95% CI 0.73 to 1.10). The risk of GDM is positively associated with prepregnancy BMI. This information is important when counselling women planning a pregnancy.

The cross-sectional area of umbilical cord components in normal pregnancy.

OBJECTIVE: To determine the normal cross-sectional areas of the umbilical vein, umbilical artery, and Wharton jelly in healthy pregnancies, and correlate the obtained values with fetal anthropometric parameters. METHODS: A cross-sectional study was performed with 312 women between the 24th and 39th weeks of a normal pregnancy. The cross-sectional areas of umbilical cord vessels were measured at the junction of the cord and fetal abdomen, and the values were subtracted from the total cord cross-sectional area to assess the cross-sectional area of the Wharton jelly. The anthropometric parameters analyzed were biparietal diameter, head circumference, femur length, and estimated fetal weight, and the Spearman correlation was used to assess the correlation between the cross-sectional areas of umbilical cord components and fetal anthropometric parameters. A polynomial regression analysis was performed to identify the curves that best adjusted to mean and standard deviation according to gestational age. RESULTS: A statistically significant correlation was observed between the cross-sectional areas of cord components and fetal anthropometric parameters (P<0.001) as well as gestational age (P<0.001). CONCLUSIONS: Reference measurements of the cross-sectional areas of umbilical cord components are important tools in the assessment of fetal growth.

Chromosomal and cardiac anomalies in fetuses with intracardiac echogenic foci.

OBJECTIVE: To evaluate the prevalence of intracardiac echogenic foci (ICEF) and the association between ICEF and chromosomal and cardiac anomalies in Brazilian women. METHODS: In a cross-sectional observational study, 373 of the 23,360 genetic sonograms performed at a private maternal-fetal medicine clinic over 5 years showed intracardiac echogenic foci (ICEF). These 373 sonograms were reviewed for chromosomal and cardiac anomalies and associations were analyzed using the chi(2) test or the Fisher exact test. P<0.05 was considered significant. RESULTS: The prevalence of ICEF was 1.7%. Cardiac anomalies were detected in 10 sonograms (2.7%) and chromosomal anomalies in 14 (3.7%). There were cardiac defects in 6 (1.7%) of the 359 euploid fetuses with isolated ICEF. Of the 373 women who had fetuses with ICEF, 295 were younger than 35 years and 78 were 35 years or older. There were 6 fetuses (2.1%) with aneuploidy in the younger group and 8 (10.3%) in the older group. CONCLUSION: The prevalence of ICEF was 1.7%, and there was an association between cardiac and chromosomal anomalies. Women carrying fetuses with ICEF should be offered fetal echocardiography and karyotyping.

Venous-arterial Doppler ratios in the prediction of acidemia at birth in pregnancies with placental insufficiency.

OBJECTIVES: Investigate the prediction of birth acidemia in pregnancies with placental insufficiency using two newly created venous-arterial Doppler ratios: pulsatility index (PI) of the ductus venosus (DV) over PI of the middle cerebral artery (MCA) and PI of the DV over PI of the umbilical artery and establish cut-off values for this prediction. METHODS: This was a prospective cross-sectional study involving 47 patients with placental insufficiency managed in two Brazilian hospitals. All pregnancies were singleton, over 26 weeks of age and without structural or chromosome anomalies. A ROC curve was calculated for the venous-arterial ratios (independent variable) and acidemia (dependent variable). RESULTS: The DV/AU PI ratio was not a good predictor of acidemia at birth. The DV/MCA PI ratio was related to fetal acidemia (area under the ROC curve 0.785, p = 0.004). The cut-off value was 0.582, sensibility 66.7%, specificity 77.1% and accuracy 74.5%. CONCLUSIONS: The DV/MCA PI ratio is adequate for the diagnosis of acidemia at birth in pregnancies with placental insufficiency. The cut-off value was 0.582.