Can hydrogen sulfide prevent preeclampsia and fetal growth restriction?

The exact aetiology of preeclampsia is unknown, but there is a good association with an imbalance in angiogenic growth factors and abnormal placentation [1]. Hydrogen sulphide (H2S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), is pro-angiogenic vasodilator [2] and [3]. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension. Plasma levels of H2S were significantly decreased in preeclamptic women (p < 0.01), which was associated with reduced CSE message and protein expression in human placenta as determined by real-time PCR and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine (PAG) in first trimester (8–12 weeks gestation) human placental explants had reduced placenta growth factor (PlGF) production as assessed by ELISA and inhibited trophoblast invasion in vitro. Endothelial CSE knockdown by siRNA transfection increased the endogenous release of soluble fms-Like tyrosine kinase-1 (sFlt-1) and soluble endoglin, (sEng) from human umbilical vein endothelial cells while adenoviral-mediated CSE overexpression inhibited their release. Administration of PAG to pregnant mice induced hypertension, liver damage, and promoted abnormal labyrinth vascularisation in the placenta and decreased fetal growth. Finally, a slow releasing, H2S-generating compound, GYY4137, inhibited circulating sFlt-1 and sEng levels and restored fetal growth that was compromised by PAG-treatment demonstrating that the effect of CSE inhibitor was due to inhibition of H2S production. These results imply that endogenous H2S is required for healthy placental vasculature and a decrease in of CSE/H2S activity may contribute to the pathogenesis of preeclampsia. References [1] S. Ahmad, A. Ahmed, Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia, Circ Res., 95 (2004), pp. 884–891. [2] G. Yang, et al., H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase, Science, 322 (2008), pp. 587–590. [3] A. Papapetropoulos, et al., Hydrogen sulfide is an endogenous stimulator of angiogenesis, Proc Natl Acad Sci USA, 106 (2009), pp. 21972–21977.

The impact of statin use on fetal development:a meta-analysis

INTRODUCTION: Statin use inadvertently during pregnancy and proposed use of statins for the treatment of preeclampsia, led us to question the evidence behind their current contraindicated status. Several studies have evaluated the relationship between statin use in pregnancy with fetal outcome but their results have not been quantitatively assessed by meta-analysis. Our objective was to undertake a systematic review of all published clinical evidence to assess the effects of statin use in pregnancy on subsequent fetal wellbeing. METHODS: A comprehensive search strategy was performed of all electronic databases and the Merck reporting database for studies published from 1966 to 2014. Two reviewers independently screened citations and undertook study quality assessment and data extraction. We obtained summary estimates of adverse fetal events that were classified as potentially fatal, clinically significant morbidity or minor adverse event. We identified 602 titles and reviewed 30 articles for inclusion and exclusion criteria. Meta-analysis was performed on seven studies (3 cohort, 3 case-series and 1 case-control). RESULTS: Of the 922 cases of statin exposure in pregnancy, 27 exposures were associated with lethal or clinically significant fetal morbidity and 10 with minor adverse events. Statin exposure was limited to the first trimester in all but two cases. The pooled rate of lethal or clinically significant fetal abnormalities in pregnant women exposed to statins was 0.01 (95% CI 0.00-0.04), less than the European rate of 0.026 (95% CI 2.54- 2.57)EUROCAT. The rate of fetal abnormality for simvastatin was 0.03 (95% CI 0.00-0.08), atorvostatin 0.11 (95% CI 0.00-0.52), pravastatin 0.01 (95% CI 0.00-0.2) and lovastatin use 0.04 (95% CI 0.00-0.28). Systems based anomalies were also calculated, congenital heart disease was 0.8 (95% CI 0.02-0.12) compared with the background rate of 0.79 (95% CI 0.78- 0.80). CONCLUSIONS: The published data suggests that statins may not be teratogenic when given inadvertently during pregnancy and prospective studies such as The StAmP Trial may provide more data

THE EFFECT OF PREECLAMPSIA ON RENAL FUNCTION: CROSS-SECTIONAL STUDIES OF POSTPARTUM PREECLAMPTICS AND WOMEN WHO WERE DESTINED TO DEVELOP PREECLAMPSIA

Preeclampsia (PE) is a pregnancy complication that is new-onset of hypertension and proteinuria after 20 weeks of gestation. However, subclinical renal dysfunction may be apparent earlier in gestation prior to the clinical presentation of PE. Although the maternal syndrome of PE resolves early postpartum, women with a history of PE are at higher risk of renal dysfunction later in life. Mineral metabolism, such as phosphate balance is heavily dependent on renal function, yet, phosphate handling in women with a history of PE is largely unknown. To investigate whether women with a history of PE would exhibit changes in phosphate metabolism compared to healthy parous women, phosphate loading test was used. Women with or without a history of PE, who were 6 months to 5 years postpartum, were recruited for this study. Blood and urine samples were collected before and after the oral dosing of 500mg phosphate solution. Biochemical markers of phosphate metabolism and renal function were evaluated. In order to assess the difference in renal function alteration between first trimester women who were or were not destined to develop PE, plasma cystatin C concentration was analysed. After phosphate loading, women with a history of PE had significantly elevated serum phosphate at both 1- and 2-hour, while controls had higher urine phosphate:urine creatinine excretion ratio at 1-hour than women with a history of PE. Women with a history of PE had no changes in intact parathyroid hormone (iPTH) concentration throughout the study period, whereas controls had elevated iPTH at 1-hour from baseline. In terms of renal function in the first trimester, there was no difference in plasma cystatin C concentration between women who were or were not destined to develop PE. The elevation of serum phosphate in women with a history of PE could be due to the delay in phosphate excretion. Prolong elevation of serum phosphate can have serious consequences later in life. Thus, oral phosphate challenge may serve as a useful method of early screening for altered phosphate metabolism and renal function.

THE EFFECT OF PREECLAMPSIA ON RENAL FUNCTION: CROSS-SECTIONAL STUDIES OF POSTPARTUM PREECLAMPTICS AND WOMEN WHO WERE DESTINED TO DEVELOP PREECLAMPSIA

Preeclampsia (PE) is a pregnancy complication that is new-onset of hypertension and proteinuria after 20 weeks of gestation. However, subclinical renal dysfunction may be apparent earlier in gestation prior to the clinical presentation of PE. Although the maternal syndrome of PE resolves early postpartum, women with a history of PE are at higher risk of renal dysfunction later in life. Mineral metabolism, such as phosphate balance is heavily dependent on renal function, yet, phosphate handling in women with a history of PE is largely unknown. To investigate whether women with a history of PE would exhibit changes in phosphate metabolism compared to healthy parous women, phosphate loading test was used. Women with or without a history of PE, who were 6 months to 5 years postpartum, were recruited for this study. Blood and urine samples were collected before and after the oral dosing of 500mg phosphate solution. Biochemical markers of phosphate metabolism and renal function were evaluated. In order to assess the difference in renal function alteration between first trimester women who were or were not destined to develop PE, plasma cystatin C concentration was analysed. After phosphate loading, women with a history of PE had significantly elevated serum phosphate at both 1- and 2-hour, while controls had higher urine phosphate:urine creatinine excretion ratio at 1-hour than women with a history of PE. Women with a history of PE had no changes in intact parathyroid hormone (iPTH) concentration throughout the study period, whereas controls had elevated iPTH at 1-hour from baseline. In terms of renal function in the first trimester, there was no difference in plasma cystatin C concentration between women who were or were not destined to develop PE. The elevation of serum phosphate in women with a history of PE could be due to the delay in phosphate excretion. Prolong elevation of serum phosphate can have serious consequences later in life. Thus, oral phosphate challenge may serve as a useful method of early screening for altered phosphate metabolism and renal function.

The changing epidemiology of Ebstein's anomaly and its relationship with maternal mental health conditions: a European registry-based study

OBJECTIVES: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy.

DESIGN: We carried out a descriptive epidemiological analysis of population-based data.

SETTING: We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country.

RESULTS: In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p<0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal β-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n=3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n=11) compared with cardiac controls.

CONCLUSIONS: The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.

Monoamniotic twins discordant for body stalk anomaly

Body stalk anomaly is a rare malformation. This anomaly in monozygotic twins is extremely unusual. We describe a case of monoamniotic pregnancy discordant for body stalk anomaly diagnosed at 11 weeks. Ultrasound showed a fetus with a large anterior abdominal wall defect, anomaly of the spine and no evidence of lower extremities and other with a normal morphology. As far as our concern, only three monoamniotic pregnancies discordant for this malformation were reported. Our case represents the fourth reported monoamniotic pregnancy discordant for body stalk anomaly with diagnosis made by ultrasound and the second diagnosed in the first trimester.

Sociodemographic factors influencing adherence to antenatal iron supplementation recommendations among pregnant women in Malawi: Analysis of data from the 2010 Malawi Demographic and Health Survey

Background and Aim: Maternal morbidity and mortality statistics remain unacceptably high in Malawi. Prominent among the risk factors in the country is anaemia in pregnancy, which generally results from nutritional inadequacy (particularly iron deficiency) and malaria, among other factors. This warrants concerted efforts to increase iron intake among reproductive-age women. This study, among women in Malawi, examined factors determining intake of supplemental iron for at least 90 days during pregnancy. Methods: A weighted sample of 10,750 women (46.7%), from the 23,020 respondents of the 2010 Malawi Demographic and Health Survey (MDHS), were utilized for the study. Univariate, bivariate, and regression techniques were employed. While univariate analysis revealed the percent distributions of all variables, bivariate analysis was used to examine the relationships between individual independent variables and adherence to iron supplementation. Chi-square tests of independence were conducted for categorical variables, with the significance level set at P < 0.05. Two binary logistic regression models were used to evaluate the net effect of independent variables on iron supplementation adherence. Results: Thirty-seven percent of the women adhered to the iron supplementation recommendations during pregnancy. Multivariate analysis indicated that younger age, urban residence, higher education, higher wealth status, and attending antenatal care during the first trimester were significantly associated with increased odds of taking iron supplementation for 90 days or more during pregnancy (P < 0.01). Conclusions: The results indicate low adherence to the World Health Organization’s iron supplementation recommendations among pregnant women in Malawi, and this contributes to negative health outcomes for both mothers and children. Focusing on education interventions that target populations with low rates of iron supplement intake, including campaigns to increase the number of women who attend antenatal care clinics in the first trimester, are recommended to increase adherence to iron supplementation recommendations.

Epidemiological features of patients with nonsyndromic cleft lip and/or palate in Western Parana

Aim:To describe the clinical, demographic and environmental features associated with NSCL/P (nonsyndromic cleft lip and/or palate) patients born in western Parana state, Brazil. Methods: This cross-sectional, observational, retrospective study included 188 patients attended at the Association of Carriers of Cleft Lip and Palate - APOFILAB, Cascavel-Parana, between 2012 and 2014. Information on demographic characteristics, medical and dental histories and life style factors were obtained from records and personal interviews. Results: Among the 188 patients, cleft lip and palate (CLP) was the most frequent subtype (55.8%), followed by cleft lip only (CLO, 25.0%) and cleft palate only (CPO, 19.2%). Caucasian males were the most affected, although no differences among types of cleft were observed. The otorhinolaryngologic and respiratory alterations were the most frequent systemic alterations in NSCL/P patients, and more than 80% of the NSCL/P mothers reported no vitamin supplements during the first trimester of pregnancy. Conclusions: This study revealed that the prevalence of nonsyndromic oral cleft types in this cohort was quite similar to previously reported prevalence rates. Systemic alterations were identified among 23.4% of the patients and patients with CLP were the most affected. History of maternal exposition to environmental factors related to nonsyndromic oral clefts was frequent and most mothers reported no vitamin supplements during the pregnancy. This study highlights the importance of identifying systemic alterations and risk factors associated with NSCL/P in the Brazilian population for planning comprehensive strategies and integrated actions for the development of preventive programs and treatment.

A cross sectional study of leptospirosis and fetal death in Yucatan, Mexico

Introduction: Leptospirosis is a zoonotic disease affecting mainly to low income human population. Acute leptospiral infection during pregnancy has been associated with spontaneous abortion and fetal death during the first trimester and the abortion may occur as consequence of systemic failure. Objective: To estimate the frequency of Leptospira interrogans infection in women with spontaneous abortion in the state of Yucatan, Mexico. Methods: A cross sectional study on women with spontaneous abortion was conducted. Serum samples were tested for Leptospirosis by the microaglutination test, to estimate the frequency of the infecting serovar. The indirect ELISA IgM was used to detect recent infection by L. interrogans. DNA was extracted from paraffin-embedded tissue of placenta for PCR detection of L. interrogans. Results: Overall frequency of infection with L. interrogans in the 81 women with abortion was 13.6%. Five of the 12 serovars evaluated were found and included. Two of the 11 women with abortion and positive to microaglutination test were also positive to the ELISA IgM test. None samples were positive for PCR Leptospira diagnosis. Conclusion: two women could be associated with spontaneous abortion due to leptospirosis, because they showed antibodies against L. interrogans in the microaglutination test and ELISA IgM assays. Differences between regions were found with respect to the prevalences of lesptospirosis.

Anomalies immunitaires chez les enfants exposés au VIH mais non infectés.

La thérapie antirétrovirale prévient la transmission mère-enfant du VIH dans plus de 98% des cas lorsqu’administrée pendant la grossesse, le travail et au nouveau-né. L’accessibilité à la thérapie antirétrovirale dans près de 70% des 1,5 millions cas de grossesses VIH+ dans le monde mène à la naissance de plus d’un million d’enfants exposés non infectés chaque année. Le nombre d’enfants exposés non infectés est à la hausse ainsi que les préoccupations concernant leur santé. En effet, plusieurs groupes ont signalé une augmentation de la morbidité et de la mortalité chez les enfants exposés non infectés. L’analyse des données rétrospectives de 705 enfants exposés non infectés de la cohorte mère-enfant du CMIS a révélé qu’à 2 mois d’âge, les enfants nés de mères ayant une charge virale supérieure à 1,000 copies d’ARN / ml avaient une fréquence de lymphocytes B significativement plus élevés par rapport aux enfants exposés non infectés nés de mères ayant une charge virale indétectable. L’objectif de cette étude est de caractériser ces anomalies. Les lymphocytes, provenant du sang de cordon ombilical et de sang veineux obtenu à 6 et 12 mois d’âge, ont été phénotypés par cytométrie en flux à l’aide des marqueurs CD3 / CD10 / CD14 / CD16 / CD19 / CD20 / CD21 / CD27 / IgM pour les lymphocytes B et CD4 / CD8 / CD3 / CCR7 / CD45RA pour les lymphocytes T. De plus, afin d’étudier les capacités fonctionnelles des lymphocytes B CD19+, la réponse antigène-spécifique au vaccin antitétanique a été mesurée par marquage avec des tétramères fluorescents de fragment C du toxoïde tétanique. Nos travaux ont mis en évidence des différences statistiquement significatives entre les enfants exposés non-infectés (ENI) nés de mères avec une charge virale détectable comparativement à ceux nés de mères avec une charge virale indétectable. À la naissance, les enfants ENI nés de mères avec une charge virale détectable avaient significativement moins de lymphocytes B totaux, plus de lymphocytes B mémoires classiques, activés, plasmablastes et lymphocytes T CD8+ mémoires centrales. À 6 mois, ils avaient significativement plus de lymphocytes B naïfs et significativement moins de lymphocytes T CD8+ effecteurs mémoires. À 12 mois d’âge, ils avaient significativement plus de lymphocytes B et T CD8+ totaux; significativement moins de lymphocytes T CD4+ totaux et leurs lymphocytes T affichaient un profil significativement plus activé (plus de cellules mémoires). L’analyse de la réponse antigène-spécifique a révélé une fréquence plus élevé de lymphocytes B mémoires IgM+ suggérant que les enfants nés de mères avec une virémie détectable ont plus de mal à établir une mémoire immunitaire efficace face au vaccin antitétanique. Nos données suggèrent qu’il y a exposition durant le premier trimestre de grossesse à la virémie maternelle et que cette exposition impacte le système immunitaire en développement du fœtus. Les mécanismes sous-jacents causant ces anomalies doivent encore être élucidés et l’épuisement du compartiment T à la naissance et à 6 mois reste à être investigué. Dans un pays industrialisé où l’accès aux soins est facilité, ces anomalies ont des conséquences modérées mais dans des pays à faible et moyen revenu, les conséquences peuvent être beaucoup plus tragiques voir fatales.

Anomalies immunitaires chez les enfants exposés au VIH mais non infectés

La thérapie antirétrovirale prévient la transmission mère-enfant du VIH dans plus de 98% des cas lorsqu’administrée pendant la grossesse, le travail et au nouveau-né. L’accessibilité à la thérapie antirétrovirale dans près de 70% des 1,5 millions cas de grossesses VIH+ dans le monde mène à la naissance de plus d’un million d’enfants exposés non infectés chaque année. Le nombre d’enfants exposés non infectés est à la hausse ainsi que les préoccupations concernant leur santé. En effet, plusieurs groupes ont signalé une augmentation de la morbidité et de la mortalité chez les enfants exposés non infectés. L’analyse des données rétrospectives de 705 enfants exposés non infectés de la cohorte mère-enfant du CMIS a révélé qu’à 2 mois d’âge, les enfants nés de mères ayant une charge virale supérieure à 1,000 copies d’ARN / ml avaient une fréquence de lymphocytes B significativement plus élevés par rapport aux enfants exposés non infectés nés de mères ayant une charge virale indétectable. L’objectif de cette étude est de caractériser ces anomalies. Les lymphocytes, provenant du sang de cordon ombilical et de sang veineux obtenu à 6 et 12 mois d’âge, ont été phénotypés par cytométrie en flux à l’aide des marqueurs CD3 / CD10 / CD14 / CD16 / CD19 / CD20 / CD21 / CD27 / IgM pour les lymphocytes B et CD4 / CD8 / CD3 / CCR7 / CD45RA pour les lymphocytes T. De plus, afin d’étudier les capacités fonctionnelles des lymphocytes B CD19+, la réponse antigène-spécifique au vaccin antitétanique a été mesurée par marquage avec des tétramères fluorescents de fragment C du toxoïde tétanique. Nos travaux ont mis en évidence des différences statistiquement significatives entre les enfants exposés non-infectés (ENI) nés de mères avec une charge virale détectable comparativement à ceux nés de mères avec une charge virale indétectable. À la naissance, les enfants ENI nés de mères avec une charge virale détectable avaient significativement moins de lymphocytes B totaux, plus de lymphocytes B mémoires classiques, activés, plasmablastes et lymphocytes T CD8+ mémoires centrales. À 6 mois, ils avaient significativement plus de lymphocytes B naïfs et significativement moins de lymphocytes T CD8+ effecteurs mémoires. À 12 mois d’âge, ils avaient significativement plus de lymphocytes B et T CD8+ totaux; significativement moins de lymphocytes T CD4+ totaux et leurs lymphocytes T affichaient un profil significativement plus activé (plus de cellules mémoires). L’analyse de la réponse antigène-spécifique a révélé une fréquence plus élevé de lymphocytes B mémoires IgM+ suggérant que les enfants nés de mères avec une virémie détectable ont plus de mal à établir une mémoire immunitaire efficace face au vaccin antitétanique. Nos données suggèrent qu’il y a exposition durant le premier trimestre de grossesse à la virémie maternelle et que cette exposition impacte le système immunitaire en développement du fœtus. Les mécanismes sous-jacents causant ces anomalies doivent encore être élucidés et l’épuisement du compartiment T à la naissance et à 6 mois reste à être investigué. Dans un pays industrialisé où l’accès aux soins est facilité, ces anomalies ont des conséquences modérées mais dans des pays à faible et moyen revenu, les conséquences peuvent être beaucoup plus tragiques voir fatales.

Array-CGH testing in spontaneous abortions with normal karyotypes

In about 50% of first trimester spontaneous abortion the cause remains undetermined after standard cytogenetic investigation. We evaluated the usefulness of array-CGH in diagnosing chromosome abnormalities in products of conception from first trimester spontaneous abortions. Cell culture was carried out in short- and long-term cultures of 54 specimens and cytogenetic analysis was successful in 49 of them. Cytogenetic abnormalities (numerical and structural) were detected in 22 (44.89%) specimens. Subsequent, array-CGH based on large insert clones spaced at ~1 Mb intervals over the whole genome was used in 17 cases with normal G-banding karyotype. This revealed chromosome aneuplodies in three additional cases, giving a final total of 51% cases in which an abnormal karyotype was detected. In keeping with other recently published works, this study shows that array-CGH detects abnormalities in a further ~10% of spontaneous abortion specimens considered to be normal using standard cytogenetic methods. As such, array-CGH technique may present a suitable complementary test to cytogenetic analysis in cases with a normal karyotype.

Atividade física durante a gestação e desfechos fetais: um estudo de casos e controles

OBJETIVO: Analisar a relação entre atividade física durante o segundo trimestre de gestação e baixo peso ao nascer, prematuridade e restrição de crescimento intra-uterino. MÉTODOS: Estudo de caso-controle realizado no município de São Paulo, em 2005. Foram estudados 273 recém-nascidos de baixo peso e 546 controles. Dentre os casos foram selecionadas duas sub-amostras: 117 nascimentos pré-termo e 132 com restrição de crescimento intra-uterino (n=132) e seus respectivos controles. As informações foram obtidas mediante entrevistas com as puérperas e transcrição de dados dos prontuários. Foram realizadas análises de regressão logística múltipla condicional e hierarquizada. RESULTADOS: Foi identificado como fator de proteção para baixo peso ao nascer a realização de atividades leves por mais de sete horas diárias (ORaj:0,61; IC 95 por cento :0,39;0,94), para a qual identificou-se relação do tipo dose-resposta (p de tendência=0,026), e tendência similar na análise da restrição de crescimento intra-uterino (ORaj:0,51; IC 95 por cento :0,26;0,97). A realização de atividades domésticas associou-se como fator protetor tanto contra o baixo peso ao nascer quanto à prematuridade (p de tendência=0,013 e 0,035, respectivamente). Foi detectado efeito de proteção contra prematuridade para a caminhada no lazer. CONCLUSÕES: Atividades físicas leves, como caminhadas, durante o segundo trimestre de gestação exercem efeito protetor independente sobre o baixo peso ao nascer, a prematuridade e a restrição de crescimento intrauterino

Prematurity prevention: the role of progesterone

Purpose of review This review summarizes the evidence of the effectiveness of progesterone on the rate of preterm birth and evaluates the most recent studies. Recent findings The incidence of preterm delivery is about 7-11% of all pregnant women and preterm birth is one of the most important causes of neonatal morbidity and mortality. Interventions to reduce such complications have been attempted for several years. Most efforts so far have been tertiary interventions, such as treatment with antenatal corticosteroids, tocolytic agents, and antibiotics. Some of these measures have reduced perinatal morbidity and mortality, but the incidence of preterm birth is increasing. Recently, researches have suggested prophylactic progesterone could reduce the preterm birth rate in a select group presenting previous preterm birth and a short cervical length by transvaginal scan at mid-trimester pregnancy. Summary This review intends to define the current indication for administration of progesterone for pregnant women. On the basis of current knowledge, progesterone should be offered to women with a documented history of a previous spontaneous birth at less than 37 weeks and for those found to have a short cervical length of 15 mm or less. Studies are needed to evaluate progesterone efficacy on other risk factors.

Placental Volumes Measured by 3-Dimensional Ultrasonography in Normal Pregnancies From 12 to 40 Weeks` Gestation

Objective. The purpose of this study was to construct nomograms of placental volumes according to gestational age and estimated fetal weight. Methods. From March to November 2007, placental volumes were prospectively measured by ultrasonography in 295 normal pregnancies from 12 to 40 weeks` gestation and correlated with gestational age and estimated fetal weight. Inclusion criteria were healthy women, singleton pregnancies with normal fetal morphologic characteristics on ultrasonography, and confirmed gestational age by first-trimester ultrasonography. Results. The mean placental volume ranged from 83 cm(3) at 12 weeks to 427.7 cm(3) at 40 weeks. Linear regression yielded the following formula for the expected placental volumes (ePV) according to gestational age (GA): ePV` (cm(3)) = -64.68 + 12.31 x GA (r = 0.572; P < .001). Placental volumes also varied according to estimated fetal weight (EFW), and the following mathematical equation was also obtained by linear regression: ePV = 94.19 + 0.09 x EFW (r = 0.505; P < 0.001). Conclusions. Nomograms of placental volumes according to gestational age and estimated fetal weight were constructed, generating reference values.