Early- and late-onset postpartum depression exhibit distinct associated factors: the IGEDEPP prospective cohort study.

OBJECTIVE: To identify risk factors for early- and late-onset postpartum depression (PPD) among a wide range of variables, including sociodemographic characteristics, childhood trauma, stressful life events during pregnancy and history of personal and family psychiatric disorders, and to assess the contribution of each risk factor. DESIGN: Nested case-control study in a prospective longitudinal cohort study. SETTING: Eight maternity departments in the Paris metropolitan area, France. SAMPLE: A cohort of 3310 women with deliveries between November 2011 and June 2016. METHODS: Cases were women with early- or late-onset PPD. Controls were women without depression during pregnancy or the postpartum period. Logistic regression adjusted on sociodemographic variables was performed for each outcome and a multivariable model was proposed based on a stepwise selection procedure. MAIN OUTCOME MEASURES: Early- and late-onset PPD assessed at 2 months and 1 year postpartum, respectively. RESULTS: Stressful life events during pregnancy have a dose-response relationship with both early- and late-onset PPD. CONCLUSIONS: Early- and late-onset PPD presented distinct patterns of determinants. These results have important consequences in terms of prevention and specific care. TWEETABLE ABSTRACT: Early- and late-onset postpartum depression are associated with stressful life events and psychiatric history.

Risk factors for conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia: A retrospective case-control study.

OBJECTIVES: General anesthesia for cesarean is associated with an increased risk of maternal morbidity compared with neuraxial anesthesia. Reducing the rate of general anesthesia for urgent cesarean in women with epidural analgesia may improve maternal outcomes. Our objective was to identify the rate and factors associated with the conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia. STUDY DESIGN: We performed a retrospective case-control study including singleton-laboring women with epidural analgesia who delivered after 37 gestational weeks by urgent cesarean (Port Royal Maternity unit, 2012-2017). Cases were all women who required conversion from neuraxial analgesia to general anesthesia. Controls were women just before and after each case included. Factors associated with the conversion to general anesthesia were identified using logistic regression analysis. RESULTS: Among 3,300 laboring women with an epidural analgesia who delivered by urgent cesarean during the study period, 113 (3.4%,) had a conversion to general anesthesia. Factors associated with conversion to general anesthesia were a cervical dilation ≥ 5 cm at the time of epidural placement (aOR 2.55, 95%CI 1.05-6.21), asymmetric sensory blockade (aOR 3.39, 95%CI 1.11-10.36), need for ≥2 rescue top-ups (aOR 2.88, 95%CI 1.29-6.44), and category 1 cesarean (aOR 3.61, 95%CI 1.77-7.33). CONCLUSION: Among women with labor epidural analgesia, suboptimal analgesia significantly increased the risk for conversion to general anesthesia for urgent cesarean. Epidural placement without delay during labor, regular checks of epidural analgesia efficiency, and epidural replacement in case of inadequate epidural analgesia may decrease the rate of avoidable general anesthesia for urgent cesarean.

A new individualized prognostic approach to the management of women at risk of extreme preterm birth in France: Effect on neonatal outcome.

INTRODUCTION: After discussion with the parents, periviable infants can receive either active treatment or palliative care. The rate of active treatment in France is lower than in other developed countries, as is the survival rate of infants in this gestational age range. This study's main objective was to assess the effect of a standardized perinatal management protocol (EXPRIM) on the neonatal outcome of children born before 27 weeks of gestation. METHODS: A before-and-after study was conducted in the two level-3 hospitals of the Risks and Pregnancy DHU to compare two 16-month periods. The EXPRIM protocol was based on routine administration of prenatal corticosteroid therapy and a scheduled combined obstetric-pediatric group prenatal prognostic evaluation, not based solely on gestational age. The study included all births between 22 weeks and 26 weeks+6 days of gestation, except in utero deaths diagnosed at admission and medical terminations of pregnancy for fetal malformation, both excluded. The principal endpoint was survival without severe neonatal morbidity. RESULTS: The study included 267 women: 116 (128 newborns) in period 1 and 151 (172 newborns) in period 2. The median gestational age at admission to the maternity unit was 2.5 days younger in period 2, and the number of women admitted at 22-23 weeks doubled in period 2 (59 vs 29, respectively). Overall, the rates of live births, NICU transfer, and survival without severe morbidity were similar during the two periods. More infants were liveborn between 22 and 24 weeks in period 2 (66 vs 43). Of all newborns transferred to the NICU, 26 (29%) survived without severe morbidity in period 1 and 46 (39%) in period 2. After multivariate analysis, survival without severe morbidity did not differ significantly. CONCLUSION: Implementation of the EXPRIM protocol led to active treatment of more mothers and their children at the border of viability, and increased the number of children who survived without severe morbidity even if, overall, there was no statistically significant difference in percentage.

Determinants of a good perinatal outcome in 588 pregnancies in women with type 1 diabetes.

AIM: This study assessed pregnancy outcomes in women with type 1 diabetes (T1D) over the last 15 years and identified modifiable factors associated with good perinatal outcomes. METHODS: Pregnancy outcomes were prospectively assessed in this cohort study of 588 singleton pregnancies (441 women) managed by standardized care from 2000 to 2014. A good perinatal outcome was defined as the uncomplicated delivery of a normally formed, non-macrosomic, full-term infant with no neonatal morbidity. Factors associated with good perinatal outcomes were identified by logistic regression. RESULTS: The rate of severe congenital malformations was 1.5%, and 0.7% for perinatal mortality. The most frequent perinatal complications were macrosomia (41%), preterm delivery (16%) and neonatal hypoglycaemia (11%). Shoulder dystocia occurred in 2.6% of cases, but without sequelae. Perinatal outcomes were good in 254 (44%) pregnancies, and were associated with lower maternal HbA1c values at delivery [adjusted odds ratio (aOR): 2.78, 95% CI: 2.04-3.70, for each 1% (11mmol/mol) absolute decrease], lower gestational weight gains (aOR: 1.06, 95% CI: 1.02-1.10) and absence of preeclampsia (aOR: 2.63, 95% CI: 1.09-6.25). The relationship between HbA1c at delivery and a good perinatal outcome was continuous, with no discrimination threshold. CONCLUSION: In our study, rates of severe congenital malformations and perinatal mortality were similar to those of the general population. Less severe complications, mainly macrosomia and late preterm delivery, persisted. Also, our study identified modifiable risk factors that could be targeted to further improve the prognosis of pregnancy in T1D.

A standardized protocol to achieve normoglycaemia during labour and delivery in women with type 1 diabetes.

AIM: To evaluate a standardized protocol for maintaining near-normoglycaemia during labour and delivery in women with type 1 diabetes. METHODS: Over a nine-year period (1997-2005), 229 pregnancies in 174 women with type 1 diabetes were delivered at one centre. The same regimen was used for the induction of labour (group 1) and in women admitted in spontaneous labour (group 2): 10% dextrose (80ml/h) intravenous was given along with short-acting insulin, starting at 1IU/h intravenous via an infusion pump. Capillary blood glucose (CBG) was determined hourly, and the insulin infusion rate was modified accordingly. RESULTS: Labour was induced in 85 cases (37%) and spontaneous in 23 cases (10%), and an elective C-section was performed in 121 cases (53%). Maternal glycaemia during labour was 6.1+/-1.6 (range: 3.9-9.2)mmol/l in group 1, and 6.9+/-2.0 (range: 4.7-12.0)mmol/l in group 2. Maternal glycaemia at delivery was 5.8+/-1.5 (range: 3.4-9.4) and 6.3+/-1.9 (range: 4.1-11.4)mmol/l in groups 1 and 2, respectively. Women who underwent an elective C-section were not included in the standardized protocol and had higher glycaemia at delivery 7.1+/-2.0 (range: 2.7-13.5)mmol/l. Neonatal hypoglycaemia occurred in 30 infants (13%), and was only associated with preterm delivery. CONCLUSION: Using a standardized simple protocol during labour, maternal glycaemia was maintained within a near-normal range in 80-85% of cases.

[Leptin in pregnancy: facts, questions and future]. / Leptine et grossesse: dogmes, questions et perspectives.

Leptin has been primarily considered as a protein secreted by the adipocyte and a regulator of satiety and energy homeostasis. A role for leptin in pregnancy was later suggested as circulating levels of leptin are high in the pregnant woman and leptin is synthetized within the placenta. Placental leptin production is increased in various obstetrical conditions associated with alterations of fetal growth (diabetes, preeclampsia). Furthermore, umbilical leptin can be viewed as a biomarker of fetal adiposity. Our aim is to review the putative roles of leptin in pregnancy.

[Failure of a conservative treatment of a placenta accreta]. / Echec d'un traitement conservateur d'un placenta accreta.

We report a case of placenta accreta left fully in situ during a cesarean section. Postoperative courses were complicated with a thrombosis of the right external iliac artery after embolization and with a pyometra needing n hysterectomy. We discuss the risks of such conservative treatment of a placenta accreta, compared with classical ablation.

[Primary ovarian abscess. Diagnosis and therapeutic approach]. / Abcès primaire de l'ovaire. Diagnostic et approche thérapeutique.

Primary ovarian abscess is a rare infection. A new case has led us to carry out a literature review in order to optimize the treatment. Exceptionally isolated, primary ovarian abscess usually belongs to the postoperative complications. Nevertheless, its etiopathogenies are numerous. The symptoms are often poor; therefore the diagnosis is difficult to establish. The curative treatment must associate surgery and antibiotherapy. Even if laparoscopic surgery is the first line treatment in many cases, laparotomy remains the choice procedure. Ultrasonographically-guided evacuation has to be further evaluated. Preventive treatment is of major importance.

Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin.

Leptin, a small peptide produced by adipocytes, is implicated in an increasing number of endocrine regulations, including adiposity, satiety, puberty, and fertility. Although the factors involved in controlling maternal and fetal weight gain during pregnancy have not been fully elucidated, leptin has recently emerged as such a potential factor. In our study, we report the presence of high amounts of leptin mRNA and immunoreactive protein in the human placenta, establishing the placental synthesis of this hormone. A large (three- to fivefold) augmentation in leptin mRNA and protein was found in placentas from insulin-treated diabetic women. This finding was associated with increased concentrations of leptin and insulin in venous cord blood without modification of maternal circulating leptin levels. These data provide evidence that the placenta is a site for regulated leptin production in utero. Insulin is likely to play a critical role in this regulation, thus emphasizing the importance of placental leptin signaling in diabetic pregnancy.

[Venous thromboembolism and pregnancy]. / Maladie thrombo-embolique veineuse et grossesse.

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during or early after pregnancy. Prior VTE or family history of VTE, clinical or biological risk factors increased the risk of pregnancy-related VTE. Defining the risk of VTE before or at the beginning of pregnancy is necessary to propose the best prevention. However, the management is not standardized between physicians, centres and countries. Current guidelines for prophylaxis and treatment of VTE are discussed in this review.

Prenatal leptin production: evidence that fetal adipose tissue produces leptin.

In the adult, circulating leptin is highly correlated to adipose tissue mass. Whether such a relationship exists prenatally is unknown, because the actual source of fetal leptin has not been determined. In the present study, we have assessed the placental contribution to fetal and maternal circulating leptin concentrations and determined whether fetal adipose tissue produces leptin. The rate of leptin production in dually perfused human placenta was 0.036 ng/min.g. Ninety-five percent of the leptin released was delivered into the maternal circulation, vs. only 5% on the fetal side. Leptin messenger RNA and protein were detected in adipose tissue biopsies of 20-38 week human fetuses. However, leptin concentration was twice lower in fetal (0.22 +/- 0.11 ng/mg protein, n = 6) than in adult (0.49 +/- 0.12 ng/mg protein, n = 8) adipose tissue. Umbilical leptin levels closely reflected ponderal index at birth over a wide range of birth weights (1.6--4.1 kg). In sharp contrast, maternal and placental leptin concentrations were increased in pregnancies associated with fetal growth retardation. We conclude that umbilical leptin levels are independent of placental leptin production and can be taken as a marker of fat mass in human fetuses. By contrast, placental leptin production makes a substantial contribution to maternal circulating leptin levels during pregnancy.

Unexpected expression of glucose transporter 4 in villous stromal cells of human placenta.

Glucose transporter 4 (GLUT4) protein expression was characterized in human and rodent term placentas. A 50-kDa protein was detected, by immunoblotting, in term human placenta at levels averaging 25% of those found in white adipose tissue. It was also present, albeit at lower levels, in mouse and rat placentas. The specificity of the 50-kDa signal was established by using skeletal muscle and placental tissues obtained from GLUT4-null mice as controls. Indirect immunohistochemistry, performed in human placentas, showed that intravillous stromal cells were conspicuously labeled by GLUT4 and revealed colocalization of GLUT4 transporters with insulin receptors. This study provides the first evidence that the insulin-responsive GLUT4 glucose transporter is present in human and rodent hemochorial placentas. Placental GLUT4 gene and protein levels were not modified in human pregnancy complicated by insulin-dependent diabetes mellitus. The significance of the high level of GLUT4 protein in human placenta remains to be elucidated, because, so far, this organ was not considered to be insulin-sensitive, with regard to glucose transport.

Placental leptin receptor isoforms in normal and pathological pregnancies.

Alternate mRNA splicing of human leptin receptor generates four membrane isoforms with different C-terminal sequences. They differ by the length of their intracellular domain which include specific motifs crucial for the specificity of leptin signalling. As a step towards functional studies, we have characterized leptin receptors in human placenta from normal pregnancies and pregnancies associated with diabetes and pre-eclampsia. Leptin and leptin receptors were visualized by immunohistochemistry of placentas obtained from first and third trimester pregnancies. Antibodies against N and C-terminal epitopes showed signals in the apical membrane of the syncytiotrophoblast in early and term placental villi as well as in JAr and BeWo derived trophoblast cells. In addition, a distinct isoform recognized by its extracellular juxtamembrane epitope was exclusively localized in cytotrophoblast cells and likely stains the soluble receptor. At contrast with the transmembrane receptors, the expression of this isoform is increased in placentas of pre-eclamptic and diabetic women which synthesize more leptin than placenta from uncomplicated pregnancy. These data demonstrate that short and long transmembrane leptin receptors are expressed in the trophoblast and indicate that leptin synthetized within the placenta can act locally through both receptor isoforms. Being also accessible to leptin from maternal origin, these transmembrane receptors may signal differently in pregnancy with normal and increased leptin production. The co-localization of leptin and the soluble receptor isoform suggests that this isoform serves for modulating maternal free leptin levels through modification of leptin binding capacities.

Prenatal diagnosis with repetitive in situ hybridization probes.

We have used chromosome-specific repetitive sequences to detect the most common human aneuploidies prenatally. Together chromosome 21, 13, 18, X, and Y aneuploidy comprises 95% of the chromosome abnormalities that result in a high risk of abnormal phenotypes at birth. The X, Y, and 18 repetitive probes work reliably in multiple tissue types including directly examined and cultured amniocytes, chorionic villus cells, lymphocytes, and cultured fibroblasts. The probe that detects both chromosomes 13 and 21 routinely gives results in each cell type tested except directly studied amniocytes which can be interpreted in seven-ninths of the cases with protocol 1 and all tested samples with protocol 2. Our protocols diagnosed trisomy 21 in a 23-week fetus with low maternal serum AFP and a trisomy 18 in a direct chorionic villus sample 2 working days after the samples were obtained. Trisomy 21 also has been ruled out in a CVS karyotype first thought to be 47,XY, +21. These studies reflect the potential value of in situ hybridization to provide a more rapid, less expensive means to screen most at-risk fetal populations with less effort in first world cytogenetic laboratories, and to provide economical cytogenetic services in less developed countries.

Fetal macrosomia and maternal weight gain during pregnancy.

BACKGROUND: To calculate an adjusted maternal weight gain during pregnancy including infant and placental weights to the actual weight gain and secondarily examine its influence on the occurrence of fetal macrosomia. METHODS: The corrected weight gain was calculated as follows: maternal body weight at the last prenatal visit - (pregravid body weight + birth weight + placental weight) in 259 women (65 with type 1 diabetes, 69 with gestational diabetes mellitus, and 125 controls). RESULTS: Although weight gain was greater in non obese normal glucose tolerant and type 1 diabetic mothers of macrosomic infants, the difference was no longer significant when using corrected maternal weight gain. The correlation between birth weight and maternal weight gain decreased when using this index. CONCLUSION: The corrected weight gain is a better estimate of true accretion of maternal weight. Our results suggest that recommendations for weight gain during pregnancy should take this index into account.

Heterogeneity of fetal growth in type 1 diabetic pregnancy.

OBJECTIVE: To investigate the frequency of macrosomia in an homogeneous cohort of type 1 diabetic mothers and to analyze the influence of maternal factors and glycemic control on the incidence of fetal macrosomia. MATERIAL AND METHODS: Fifty-five consecutive type 1 diabetic first-pregnancies were prospectively studied. Macrosomia was defined by a ponderal index above the 90(th) percentile. Venous cord blood levels of insulin, C peptide and leptin were measured at delivery. The influence of HbA1c levels and other maternal variables on the occurrence of macrosomia and on the ponderal index was assessed using a stepwise regression logistic model. RESULTS: The mean (+/- SD) birth weight was 3482 (+/- 497) g at 37.4 +/- 1.0 weeks gestation. Macrosomia occurred in 29 cases (53.7%). Fetal insulin, C peptide and leptin levels were significantly higher in macrosomic than in non macrosomic infants. Maternal age, duration of diabetes, pregravid body mass index, parity, weight gain during pregnancy, presence of a microangiopathy, nephropathy, smoking habits, gestational hypertension or preeclampsia, and HbA1c levels throughout pregnancy did not differed between mothers of macrosomic and non macrosomic infants. In the stepwise analysis none of these covariates was explanatory of the ponderal index. CONCLUSIONS: The frequency of macrosomia remains very high in infants of type 1 diabetic mothers despite a reasonable degree of glycemic control. The variability of the fetal growth response to mild hyperglycemia prompts for the identification of other factors involved in the modulation of fetal growth.

Recurring episodes of meningitis (Mollaret's meningitis) with one showing an association with herpes simplex virus type 2.

Benign recurrent aseptic (Mollaret's) meningitis is a rare disease of unknown aetiology. We report the case of a 27-year-old woman who experienced three episodes of lymphocytic meningitis. Human Simplex Virus (HSV) type 2 DNA was detected in the CSF by PCR amplification indicating the diagnosis of recurrent HSV type 2 meningitis. Our observation suggests that search of herpes virus DNA by PCR amplification on CSF may be useful in unexplained recurrent meningitis.

The daughters of diethylstilbestrol. Lessons from an error.

Diethylstilbestrol (DES) has been used extensively to prevent pregnancy disorders in Europe but at different levels depending upon the countries. Lessons from the DES story can be learned for research, information for physicians, communication, administration and industry. However, this paper will focus on the incidence of this story in our practice. We will propose guidelines for different conditions: clear cell adenocarcinoma, adenosis, cervical dysplasia, infertility and pregnancy.

[Is there a standard biological screening of gestational diabetes mellitus?]. / Y a-t-il un dépistage biologique de référence du diabète gestationnel?

Universal screening for gestational diabetes mellitus (GDM) is contentious. There is insufficient evidence that universal screening for GDM substantially reduces perinatal complications such as cesarean section and Erb's palsy.However, risk assessment for GDM should be undertaken at the first prenatal visit and selective screening should be performed in high-risk women: diabetes mellitus in first-degree relatives, member of an ethnic group with a high prevalence of diabetes mellitus, body mass index > or 25 kg/m2, personal history of hyperglycemia or GDM, previous poor obstetric outcome. During the first trimester, a fasting glycemia over 1.05 g/l is associated with perinatal complications and should be treated. If fasting glycemia is below this level or unknown, or if glucosuria occurs, they should be re-tested between 24 and 28 weeks of gestation using a 75-g oral glucose load. The actual proposed glucose threshold values for GDM are, respectively, 1.05 and 1.55-1.60 g/l for fasting and 2 h.

[Placental leptin and pregnancy pathologies]. / Leptine placentaire et pathologies de la grossesse.

Leptin, the protein encoded by the Ob gene, is produced by the white adipose tissue and by the placenta during pregnancy. Placental leptin production makes a substantial contribution to maternal circulating levels during pregnancy which rapidly decrease and return to normal after delivery. Leptin has been detected in fetal plasma as early as week 18 of gestation, and umbilical leptin concentrations are closely related to birth weight. This has led to the hypothesis that fetal fat mass mainly determines fetal circulating leptin. Placental leptin production is increased in choriocarcinoma, preeclampsia and type 1 diabetes. Estrogens, hypoxia and insulin have been suggested as positive regulators of placental leptin production. Maternal leptinemia might act as a sensor of energy balance during pregnancy. The presence of both leptin and leptin receptors in the placenta suggests that leptin can act by autocrine or endocrine pathways in the human placenta. The roles of fetal leptin and consequences of increased placental leptin production in pathological pregnancies have yet to be elucidated.