Amélie Tétu

Bacteriology of Amniotic Fluid in Women With Suspected Cervical Insufficiency

OBJECTIVE To determine the prevalence of mid-trimester microbial invasion of the amniotic cavity (MIAC) in women with suspected cervical insufficiency. METHODS A prospective observational cohort study was performed in women with suspected cervical insufficiency and visible fetal membranes who were undergoing amniocentesis to rule out MIAC between 16 and 26 weeks of gestation. Women with preterm premature rupture of membranes, regular uterine contractions, or who had a cervical cerclage were excluded. Gram staining of amniotic fluid, glucose and lactate dehydrogenase (LDH) levels in amniotic fluid, and aerobic and anaerobic amniotic fluid cultures were performed, along with polymerase chain reaction (PCR) for the detection of Ureaplasma and Mycoplasma species. RESULTS Fifteen women with a mean gestational age of 22.6 +/- 2.3 weeks were included in the study. The diagnosis of MIAC was confirmed in 47% (7/15), of whom 20% (3/15) were infected with more than one bacterial strain and 33% (5/15) with Ureaplasma species. According to receiver-operator curve analyses, amniotic fluid levels of glucose were associated with MIAC (P = 0.02), but not amniotic fluid LDH (P = 0.25). CONCLUSION MIAC is present in approximately one half of women with suspected cervical insufficiency and visible fetal membranes at speculum examination.

The Proximal Gata4 Promoter Directs Reporter Gene Expression to Sertoli Cells During Mouse Gonadal Development

Abstract The GATA4 transcription factor is an important developmental determinant for many organs, such as the heart, gut, and testis. Despite this pivotal role, our understanding of the transcriptional mechanisms that control the proper spatiotemporal expression of the GATA4 gene remains limited. We have generated transgenic mice expressing a green fluorescent protein (GFP) marker under the control of rat Gata4 5′ flanking sequences. Several GATA4-expressing organs displayed GFP fluorescence, including the heart, intestine, and pancreas. In the gonads, while GATA4 is expressed in pregranulosa, granulosa, and theca ovarian cells, and Sertoli, Leydig, and peritubular testicular cells, the first 5 kb of Gata4 regulatory sequences immediately upstream of exon 1 were sufficient to direct GFP reporter expression only in testis and, specifically, in Sertoli cells. Onset of GFP expression occurred after Sertoli cell commitment and was maintained in these cells throughout development to adulthood. In vitro studies revealed that the first 118 bp of the Gata4 promoter is sufficient for full basal activity in several GATA4-expressing cell lines. Promoter mutagenesis and DNA-binding experiments identified two GC-box motifs and, particularly, one E-box element within this −118-bp region that are crucial for its activity. Further analysis revealed that members of the USF family of transcription factors, especially USF2, bind to and activate the Gata4 promoter via this critical E-box motif.

The origin of Fusobacterium nucleatum involved in intra-amniotic infection and preterm birth

Objective. To evaluate the potential oral origin of Fusobacterium nucleatum found in amniotic fluid of women at high risk of preterm birth. Methods. A transversal study nested into a cohort study of women with preterm labor and/or preterm premature rupture of membranes was undergone. Women with the presence of F. nucleatum in the amniotic fluid and their respective partners were invited to be examined for their periodontal health after delivery, and samples of saliva and subgingival plaque were collected. For each couple, specific PCR detection of Fusobacterium species was performed on each oral sample, and the DNA sequences were compared with the one obtained from amniotic fluid. Results. Three women, all in preterm labor with intact membranes, were included. Intra-amniotic sludge was observed in all of them. A strain of F. nucleatum with 100% sequence identity with the strain detected in the amniotic fluid was found in the oral samples of one of them and of two partners. Conclusion. This study suggests that intra-amniotic F. nucleatum could originate from the patients or the partners oral microflora.

Maternal Characteristics for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes (GOS) Study

OBJECTIVE Low-dose aspirin started in early pregnancy significantly reduces the risk of preeclampsia (PE) in high-risk women, especially preterm PE. This study aimed to evaluate the influence of maternal characteristics on the risk of PE in nulliparous women. METHODS The Great Obstetrical Syndromes (GOS) study recruited nulliparous women with singleton pregnancies at 11 to 13 weeks. The following maternal characteristics were collected: age, BMI, ethnicity, chronic diseases, smoking, and assisted reproductive technologies. Relative weight analyses were conducted, and predictive multivariate proportional hazard models were constructed. Receiver operating characteristic curve analyses with their area under the curve (AUC) were used to evaluate the value of each factor for the prediction of PE and preterm PE. The study also evaluated the SOGC guidelines for identification of women at high risk of PE. RESULTS Of 4739 participants, 232 (4.9%) developed PE, including 30 (0.6%) with preterm PE. In univariate analyses, only BMI was significantly associated with the risk of PE (AUC 0.60; 95% CI 0.55-0.65) and preterm PE (AUC 0.64; 95% CI 054-0.73). Adding other maternal characteristics to BMI had a non-significant and marginal impact on the discriminative ability to the models for PE (AUC 0.62; 95% CI 0.58-0.66) and preterm PE (AUC 0.65; 95% CI 0.56-0.74). At a false-positive rate of 10%, maternal characteristics could have predicted 23% of PE and 19% of preterm PE. The SOGC guidelines were not discriminant for PE (detecting 96% of PE and 93% of preterm PE with a 94% false-positive rate). CONCLUSION In nulliparous women, BMI is the most discriminant maternal characteristic for the prediction of PE. Maternal characteristics should not be used alone to identify nulliparous women at high risk of PE.

Comparison of first‐tier cell‐free DNA screening for common aneuploidies with conventional publically funded screening

This study evaluates the impact of offering cell‐free DNA (cfDNA) screening as a first‐tier test for trisomies 21 and 18.

First Trimester Screening for Fetal Aneuploidies Using Placental Growth Factor: The Great Obstetrical Syndrome (GOS) Study

OBJECTIVE This study sought to estimate the ability of first trimester maternal serum placental growth factor (PlGF) to identify fetal aneuploidies. METHODS A prospective cohort study of singleton pregnancy at 11 to 13 weeks was conducted. Maternal serum PlGF concentration was measured using BRAHMS PlGF plus KRYPTOR automated assays (Thermo Scientific BRAHMS, Hennigsdorf, Germany). PlGF and nuchal translucency were log-transformed and reported as multiples of the median (MoM) adjusted for crown-rump length. Detection rates were calculated using receiver-operator characteristic curves. RESULTS The study observed 21 cases of fetal aneuploidies (0.4%) out of 4765 participants. Trisomy 21 (13 cases; 0.85 MoM; interquartile range [IQR] 0.80-0.93), trisomy 18 (two cases; 0.77 MoM; IQR 0.66-0.87) and trisomy 13 (two cases; 0.68 MoM; IQR 0.61-0.75) were associated with low PlGF concentrations. The low PlGF values observed in the cases of monosomy X (two cases; 0.85 MoM; IQR 0.82-0.88, P = 0.05), triploidy (0.78 MoM, P = 0.11), and 47,XX,i(22)(p10) (0.18 MoM, P = 0.08) were not statistically different from the controls. A model including maternal age, nuchal translucency, and PlGF could have identified all (95% CI 83%-100%) cases of trisomy 21 and six of the other fetal aneuploidies (75%) at a false-positive rate of 9%. CONCLUSION Low first trimester PlGF is associated with an increased risk of fetal aneuploidy. PlGF combined with first trimester ultrasound (nuchal translucency, uterine artery Doppler, and early fetal anatomy) could identify not only women at high risk for preeclampsia, but also fetuses at high risk of aneuploidy for optimal further testing (non-invasive testing for common aneuploidy screening or chorionic villus sampling for full screening and diagnosis).

First-Trimester Placental Growth Factor for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes Cohort Study

Background: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. Subjects and Methods: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11–13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). Results: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57–0.65) and preterm PE (AUC = 0.73, 95% CI 0.64–0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62–0.71; AUC for preterm PE 0.81, 95% CI 0.72–0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. Conclusion: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.