Publications by authors named "François Goffinet"

225 Publications

Frequency and determinants of misuse of augmentation of labor in France: A population-based study.

PLoS One 2021 9;16(2):e0246729. Epub 2021 Feb 9.

INSERM UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Center for Epidemiology and Statistics, FHU PREMA, Université de Paris, Paris, France.

Introduction: While use of augmentation of labor (AL) is appropriate for labor dystocia, it is frequently used inadequately and unnecessarily. The objective was to assess at a national level, the frequency and determinants of misuse of augmentation of labor (AL).

Material And Methods: Women of the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. "Misuse of AL" was defined by artificial rupture of the membranes (ROM) and/or oxytocin within one hour of admission and/or duration between ROM and oxytocin of less than one hour. Women, labor and maternity unit's characteristics were compared between the "misuse of AL" and "no misuse of AL" groups by bivariate analysis. To identify the determinants of misuse of AL, a multivariable multilevel logistic regression was performed taking into account the data's hierarchical structure (first level: women, second level: maternity units).

Results: Among the 7196 women included, 1524 (21.2%) had a misuse of AL. The determinants of misuse of AL were middle school educational level (reference high school), aOR = 1.21; 95%CI[1.01-1.45], gestational age at delivery ≥41weeks (reference 39-40 weeks), aOR = 1.19; 95%CI[1.00-1.42], cervical dilation ≥6cm at admission (reference <3cm), aOR = 1.39; 95%CI[1.10-1.76], epidural analgesia aOR = 1.63; 95%CI[1.35-1.96], delivery in a private hospital (reference public teaching hospital), aOR = 2.25; 95%CI[1.57-3.23]; and maternity units with <1000 deliveries/year and 1000-1999 deliveries/year (reference ≥3000 deliveries/year), respectively aOR = 1.52; 95%CI[1.11-2.08] and aOR = 1.42; 95%CI[1.05-1.92]. Less than 3% of the variance was explained by women characteristics, and 24.17% by the maternity units' characteristics.

Conclusions: In France, one spontaneous laboring woman among five is subject to misuse of AL. The misuse is mostly explained by maternity unit's characteristics. The determinants identified in this study can be used to implement targeted actions in small and private maternity units.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246729PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872232PMC
February 2021

Streptococcus pyogenes infects human endometrium by limiting the innate immune response.

J Clin Invest 2021 02;131(4)

Université de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.

Group A Streptococcus (GAS), a Gram-positive human-specific pathogen, yields 517,000 deaths annually worldwide, including 163,000 due to invasive infections and among them puerperal fever. Before efficient prophylactic measures were introduced, the mortality rate for mothers during childbirth was approximately 10%; puerperal fever still accounts for over 75,000 maternal deaths annually. Yet, little is known regarding the factors and mechanisms of GAS invasion and establishment in postpartum infection. We characterized the early steps of infection in an ex vivo infection model of the human decidua, the puerperal fever portal of entry. Coordinate analysis of GAS behavior and the immune response led us to demonstrate that (a) GAS growth was stimulated by tissue products; (b) GAS invaded tissue and killed approximately 50% of host cells within 2 hours, and these processes required SpeB protease and streptolysin O (SLO) activities, respectively; and (c) GAS impaired the tissue immune response. Immune impairment occurred both at the RNA level, with only partial induction of the innate immune response, and protein level, in an SLO- and SpeB-dependent manner. Our study indicates that efficient GAS invasion of the decidua and the restricted host immune response favored its propensity to develop rapid invasive infections in a gynecological-obstetrical context.
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http://dx.doi.org/10.1172/JCI130746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880408PMC
February 2021

Fetal heart rate nadir during bradycardia and umbilical artery acidemia at birth.

Acta Obstet Gynecol Scand 2020 Dec 14. Epub 2020 Dec 14.

Department of Obstetrics and Gynecology of Port Royal, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris Descartes University, Paris, France.

Introduction: Fetal bradycardia due to sentinel events such as placental abruption, cord prolapse or uterine rupture is associated with an increased risk of acidemia at birth. In the absence of a sentinel event, data regarding neonatal prognosis are scarce, and it seems plausible that the depth of bradycardia might be associated with an increased risk of acidosis at birth. The objective was to determine whether the depth of bradycardia is associated with a higher risk of umbilical artery acidemia at birth in term singleton pregnancies requiring cesarean delivery during labor.

Material And Methods: A retrospective comparative study of all cesarean deliveries for bradycardia in an academic tertiary center in the 6-year period of 2013-2018, among term singleton pregnancies. Bradycardia associated with a sentinel event such as placental abruption, cord prolapse or uterine rupture, were excluded. The nadir of the bradycardia was defined as the lowest fetal heart rate baseline lasting at least 3 minutes during bradycardia. Women who delivered an infant with an umbilical pH at birth <7.00 (acidosis group) were compared with women who delivered an infant with an umbilical pH at birth ≥7.00 (non-acidosis group).

Results: Among 111 eligible cases, 32 women in the acidosis group were compared with 79 in the non-acidosis group. The median nadir of the bradycardia was lower in the acidosis than in the non-acidosis group (60 bpm, interquartile range [56-65] vs 70 [60-76], P < .01). A bradycardia nadir <60 bpm emerged as the optimal threshold for predicting acidemia and was more frequently observed in the acidosis than in the non-acidosis group (10 [31%] vs 10 [13%], P = .02). In the multivariable analysis, a nadir <60 bpm was independently associated with an umbilical artery pH <7.00 (adjusted OR 3.16, 95% CI 1.10-9.04).

Conclusions: A bradycardia nadir <60 bpm was associated with a tripled risk of umbilical artery acidemia at birth.
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http://dx.doi.org/10.1111/aogs.14061DOI Listing
December 2020

SARS-COV-2 IgG antibody response in pregnant women at delivery.

J Gynecol Obstet Hum Reprod 2020 Dec 10;50(7):102041. Epub 2020 Dec 10.

Université Paris-Saclay, 94804 Villejuif, France; Laboratoire de Virologie, AP-HP, Hôpital Paul-Brousse, F-94804 Villejuif, France.

Background: The prevalence of COVID-19 infection during pregnancy is not known. COVIPREG is a prospective French multicenter study to assess the seroprevalence at the time of delivery and the maternal and neonatal impact of COVID-19 infection during pregnancy. In order to study factors associated with poor outcomes after COVID-19 Infection during pregnancy and adapt the sample size of the study, a preliminary assessment of the prevalence of SARS-CoV-2 IgG was planned after 500 inclusions in a one perinatal center of Paris area.

Objectives: To assess the prevalence of SARS-CoV-2 IgG antibody response in pregnant women at the time of delivery during the COVID-19 pandemia.

Study Design: A prospective observational study at Cochin hospital (Level III maternity). Patients admitted for delivery were offered to participate to the study. Each patient participating to the study was tested for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA.

Results: Among the 529 patients included in the COVIPREG study between April 29 and June 26, 529 were assessed for SARS-CoV-2 IgG antibody response and 25 had a positive test, ie 4.7 % with a confidence interval at 95 % [3.0 %-6.9 %]).

Conclusions: Four months after the beginning of the infection in Paris, the seroprevalence of SARS-CoV-2 IgG in pregnant women at the time of delivery is low. Studies evaluating the impact of COVID-19 infection during pregnancy should take this information in account in order to adapt the sample size.
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http://dx.doi.org/10.1016/j.jogoh.2020.102041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831450PMC
December 2020

Contemporary duration of spontaneous labor and association with maternal characteristics: A French national population-based study.

Birth 2021 Mar 4;48(1):86-95. Epub 2020 Dec 4.

INSERM, UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Center for Epidemiology and Statistics Sorbonne Paris Cité, FHU PREMA, Université de Paris, Paris, France.

Background: The objective of this study was to describe labor duration of women managed with current obstetric practices in a French national population-based cohort and to assess the association of age and BMI on this duration.

Methods: All women in the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. Duration of labor was defined as time between admission to the labor ward and birth. Duration of total labor and first and second stage of labor were described. Then, duration of labor was estimated according to maternal age and BMI, using Kaplan-Meier's method and compared with the log-rank test after stratification on parity. Intrapartum cesarean birth was considered as a censoring event. Multivariable modeling was performed using Cox's proportional hazard's method.

Results: Data of 3120 nulliparous and 4385 multiparous women were analyzed. Median labor duration was 6.1 hours ([5th; 95th percentile]) [1.4; 12.6] and 3.1 hours [0.3; 8.5] in nulliparous and multiparous women. Multivariable Cox analysis showed no independent association of maternal age and duration of labor. Nulliparous obese women had significantly lower odds of having a shorter labor than women with a BMI < 25 kg/m , HR: 0.75; 95% CI [0.64-0.88], but BMI was not associated with labor duration in multiparous women.

Conclusions: Our study provides important information for both women and care practitioners on what to expect when entering the labor ward. There appears to be little association between maternal characteristics and labor duration, with the exception of BMI in nulliparous women.
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http://dx.doi.org/10.1111/birt.12518DOI Listing
March 2021

Impact of history of myomectomy on preterm birth risk in women with a leiomyomatous uterus: a propensity score analysis.

BMC Pregnancy Childbirth 2020 Nov 23;20(1):720. Epub 2020 Nov 23.

Maternité Port Royal, AP-HP, Hôpital Cochin, FHU PREMA, F-75014, Paris, France.

Background: To evaluate if women with a history of myomectomy have a modified preterm birth risk compared to women with myomas during pregnancy.

Methods: Retrospective cohort study including all women with a history of myomectomy (operated group) or uterine myomas during pregnancy (unoperated group) who delivered in a tertiary center between January, 2011 and December, 2017. The operated group included women who had a myomectomy history with or without myomas during the ongoing pregnancy. The unoperated group included women with uterine myoma(s) seen on at least one ultrasound during pregnancy without history of myomectomy. The primary outcome was preterm birth < 37 weeks, and the secondary outcome spontaneous preterm birth < 37 weeks. To control for confounding factors, a propensity score approach was used. Two sensitivity analysis were performed, one repeating the analysis using the propensity score after excluding operated women with persistent myomas and one using a classical multivariable logistic regression model.

Results: The cohort included 576 women: 283 operated women and 293 unoperated women. The rate of preterm birth was similar in the two groups: 12.6% in the unoperated group and 12.0% in the operated group (p = 0.82). No difference in preterm birth risk was shown between unoperated and operated women in the cohort matched on the propensity score: OR 0.86; 95%CI [0.47-1.59]. These results were consistent for spontaneous preterm birth (OR 1.61; 95%CI [0.61-4.23]) and for the sensitivity analyses.

Conclusion: In women with a leiomyomatous uterus, a history of myomectomy is not associated with a reduced preterm birth risk.
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http://dx.doi.org/10.1186/s12884-020-03413-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686718PMC
November 2020

Preeclampsia before 26 weeks of gestation: Obstetrical prognosis for the subsequent pregnancy.

J Gynecol Obstet Hum Reprod 2021 Mar 19;50(3):102000. Epub 2020 Nov 19.

Department of Obstetrics Gynecology and Reproductive Medicine, University Paris Est Créteil, Centre Hospitalier Inter-Communal de Créteil, 94000, CRETEIL, France.

Introduction: Gestational age at delivery seems to be a risk factor of recurrence of preeclampsia. The objective of this study was to analyze adverse pregnancy outcomes and recurrence of preeclampsia during the subsequent pregnancy in women with a history of pre-eclampsia delivered before 26 weeks of gestation.

Material And Method: We performed a retrospective study in two French tertiary care hospitals between 2000 and 2018. Patients with a history of pre-eclampsia delivered before 26 weeks of gestation were analyzed. Information on the immediate subsequent pregnancy was collected. Adverse composite outcome was defined as recurrent preeclampsia, HELLP syndrome, placental abruption, fetal growth restriction <3rd percentile or <10 percentile with Doppler abnormalities, maternal death and fetal death.

Results: Among the 107 patients who met the criteria, 48 were analyzed for a subsequent pregnancy. Seventeen women (35.4 %) developed an adverse composite outcome, occurring for 15 women (31.2 %) before 34 weeks. Ten women (20.8 %) developed a recurrent preeclampsia occurring for 5 women (10.4 %) before 34 weeks. We related 3 HELLP syndromes, 1 placental abruption, 9 fetal growth restrictions, 3 fetal deaths and no maternal death. Compared to baseline normotensive women, chronic hypertension was significantly associated with an increased risk of adverse composite outcome (19.3 vs 58.8 %, p-value 0.014).

Conclusion: In our population, preeclampsia with delivery before 26 weeks is associated with 35.4 % of adverse composite outcomes and 20.8 % of recurrent preeclampsia during the immediate subsequent pregnancy. These results justify the importance of an ongoing monitoring of these patients during subsequent pregnancy.
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http://dx.doi.org/10.1016/j.jogoh.2020.102000DOI Listing
March 2021

Induction of labour with unfavourable local conditions for suspected fetal growth restriction after 36 weeks of gestation: Factors associated with the risk of caesarean.

J Gynecol Obstet Hum Reprod 2020 Nov 17;50(7):101996. Epub 2020 Nov 17.

Department of Obstetrics and Gynecology, Port-Royal Maternity, Groupe Hospitalier Cochin-Broca-Hôtel Dieu, Assistance Publique des Hôpitaux de Paris, Paris, France.

Introduction: Induction of labour in women with an unfavourable cervix is associated with a risk of caesarean delivery. When a diagnosis of fetal growth restriction (FGR) is also involved, the risk of intrapartum fetal acidosis increases. The main objective was to identify prognostic factors for the risk of caesarean delivery after induction for suspected FGR after 36 weeks of gestation with an unripe cervix.

Material And Methods: This was a retrospective, single-centre (Port Royal, Paris, France) study of women with a singleton fetus in cephalic presentation, with labour induced at or after 36 weeks for suspected FGR diagnosed during second or third trimester of pregnancy with an unripe cervix (Bishop score under 6) who gave birth between 1 January 2015 and 31 December 2019. A multivariable analysis was performed to identify the factors related to an increased risk of caesarean section.

Results: Of the 146 women included, 56 (38.4 %) had caesarean deliveries. After adjustment, the factors significantly associated with the risk of caesarean were maternal age greater than 39 years (ORa = 4.33 [1.22-17.2], reference: 25-39 years), nulliparity (ORa = 3.49 [1.25-11.2]), and an abnormal fetal umbilical artery Doppler velocimetry (ORa = 3.50 [1.47-8.70]). The risk of poor neonatal condition did not differ significantly between women with vaginal and caesarean deliveries (2.3 % vs 7.3 %, P = 0.21).

Conclusion: When FGR is suspected at 36 weeks of gestation and later, induction of labour is a reasonable option, even if the cervix is unripe, as the risk of caesarean delivery appears acceptable and neonatal status is good and similar with both modes of delivery.
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http://dx.doi.org/10.1016/j.jogoh.2020.101996DOI Listing
November 2020

Fetal scalp blood sampling: Do pH and lactates provide the same information?

J Gynecol Obstet Hum Reprod 2021 Apr 31;50(4):101964. Epub 2020 Oct 31.

Maternity of Port-Royal, AP-HP. APHP., Paris University Center, FHU PREMA, Paris, France; Paris University, INSERM U1153, Obstetrical Perinatal and Pediatric Epidemiology Research Team (EPOPé), Center of Research on Epidemiology and Statisctics Sorbonne Paris Cité (CRESS), Paris, France.

Objective: Assess the discordance between scalp pH and lactates performed from the same sample during labor.

Method: This single-center retrospective study included all women with a singleton fetus who had at least one fetal blood sample taken during labor. Some of them had up to seven samples. Scalp pH was the reference parameter for obstetric decision-making. The correlation between the pH and lactates was studied using Pearson coefficient. By categorizing the values as normal, pre-acidosis and acidosis, we were able to estimate agreement with Cohen's kappa coefficient. The frequency of discordance in the categorization and the factors related to it were studied with univariate and multivariable analyses. Cases of severe acidosis at birth (cord pH < 7.00) and cases with acidosis scalp lactates but normal scalp pH were analyzed.

Results: We analyzed 480 samples from 268 fetuses among the 2644 deliveries during the study periode. Fetal blood sampling represented 10 % of deliveries. The scalp pH and lactates results were strongly correlated (r=-0.83), but their agreement was only fair (K = 0.36). In 29.4 % of cases, pH and lactates were discordant. Factors related to discordance were meconium-stained fluid, sampling at full dilation and multiple sampling. Six infants (2.2 %) had severe acidosis at birth. Cases' analyses did not allow to conclude severe acidosis could have been avoided using scalp lactates for obstetric decision-making.

Conclusion: For more than a quarter of the samples, results were discordant between scalp pH and lactates, especially when cervix was full dilated and when the amniotic fluid was meconium-stained. A randomized controlled trial comparing the relevance of each parameter according to the obstetrical situation would be necessary.
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http://dx.doi.org/10.1016/j.jogoh.2020.101964DOI Listing
April 2021

Reducing neonatal morbidity by discontinuing oxytocin during the active phase of first stage of labor: a multicenter randomized controlled trial STOPOXY.

BMC Pregnancy Childbirth 2020 Oct 20;20(1):640. Epub 2020 Oct 20.

Université de Paris, INSERM UMR 1153, Equipe EPOPé, 123 boulevard Port Royal, 75014, Paris, France.

Background: Oxytocin is effective in reducing labor duration, but can be associated with fetal and maternal complications such as neonatal acidosis and post-partum hemorrhage. When comparing discontinuing oxytocin in the active phase with continuing oxytocin infusion, previous studies were underpowered to show a reduction in neonatal morbidity. Thus, we aim at evaluating the impact of discontinuing oxytocin during the active phase of the first stage of labor on the neonatal morbidity rate.

Methods: STOPOXY is a multicenter, randomized, open-label, controlled trial conducted in 20 maternity units in France. The first participant was recruited January 17th 2020. The trial includes women with a live term (≥37 weeks) singleton, in cephalic presentation, receiving oxytocin before 4 cm, after an induced or spontaneous labor. Women aged < 18 years, with a lack of social security coverage, a scarred uterus, a multiple pregnancy, a fetal congenital malformation, a growth retardation <3rd percentile or an abnormal fetal heart rate at randomization are excluded. Women are randomized before 6 cm when oxytocin is either continued or discontinued. Randomization is stratified by center and parity. The primary outcome, neonatal morbidity is assessed using a composite variable defined by an umbilical arterial pH at birth < 7.10 and/or a base excess > 10 mmol/L and/or umbilical arterial lactates> 7 mmol/L and/or a 5 min Apgar score < 7 and/or admission in neonatal intensive care unit. The primary outcome will be compared between the two groups using a chi-square test with a p-value of 0.05. Secondary outcomes include neonatal complications, duration of active phase, mode of delivery, fetal and maternal complications during labor and delivery, including cesarean delivery rate and postpartum hemorrhage, and birth experience. We aim at including 2475 women based on a reduction in neonatal morbidity from 8% in the control group to 5% in the experimental group, with a power of 80% and an alpha risk of 5%.

Discussion: Discontinuing oxytocin during the active phase of labor could improve both child health, by reducing moderate to severe neonatal morbidity, and maternal health by reducing cesarean delivery and postpartum hemorrhage rates.

Trial Registration: Clinical trials NCT03991091 , registered June 19th, 2019.
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http://dx.doi.org/10.1186/s12884-020-03331-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576841PMC
October 2020

Risk of small for gestational age is reduced after frozen compared with fresh embryo transfer in endometriosis.

Reprod Biomed Online 2021 Jan 18;42(1):133-141. Epub 2020 Aug 18.

Service de Gynécologie et Médecine de la Reproduction, AP-HP, Centre-Université de Paris, Paris, France; Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité, Paris 75679, France.

Research Question: What are the perinatal outcomes and especially the risk of small for gestational age (SGA) babies born after frozen versus fresh embryo transfer in mothers affected by endometriosis undergoing treatment with assisted reproductive technology (ART)?

Design: A cohort study conducted between November 2012 and October 2017, in which infertile women with endometriosis undergoing ART and achieving singleton pregnancies that lasted beyond 12 weeks of gestation were included. Pregnancies obtained after a frozen embryo transfer (FET) were compared with those obtained after a fresh embryo transfer. A total of 339 pregnant women were included: 112 patients in the fresh embryo transfer group and 227 in the FET group. The main outcome was the rate of SGA. Secondary analyses were performed for adverse pregnancy outcomes and perinatal complications.

Results: Of the included women, 109/112 (97.3%) and 222/227 (97.8%) delivered a live child after at least 24 weeks of gestation in the fresh and in the frozen embryo transfer groups, respectively (P = 0.53). The risk of SGA decreased after a FET compared with a fresh embryo transfer (odds ratio [OR] 0.49 [0.25-0.98], P = 0.04) after multivariable analysis. The mean birthweight and the gestational age at delivery were not significantly different between the two study groups. Other pregnancy and perinatal complications were not statistically different between the two study populations.

Conclusions: The present study of endometriosis-affected women found a significantly lower risk of SGA in patients undergoing frozen, mainly blastocyst, embryo transfer compared with patients undergoing fresh, mainly cleavage stage, embryo transfer.
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http://dx.doi.org/10.1016/j.rbmo.2020.08.009DOI Listing
January 2021

The cause of birth is associated with neonatal prognosis in late preterm singletons.

J Gynecol Obstet Hum Reprod 2020 Sep 22:101920. Epub 2020 Sep 22.

Université de Paris, INSERM U1153, Equipe de recherche en Epidémiologie Obstétricale, Périnatale et Pédiatrique (EPOPé), Centre de Recherche Epidémiologie et Biostatistique Sorbonne Paris Cité (CRESS), Paris, France; Sorbonne Université, AP-HP, Department of Gynaecology and Obstetrics, Trousseau Hospital, Paris, France.

Introduction: Recent studies have shown that the cause of very preterm births may be related to neonatal morbidity and mortality. Even though these risks are lower among late preterm births, this group accounts for the vast majority of all preterm births. The objective of this study was to evaluate the relation of neonatal morbidity and mortality to the cause of late preterm birth.

Materials And Methods: This retrospective observational cohort study included all women who gave birth to liveborn singletons from 34 to 36 weeks+6 days of gestation in a French level III maternity hospital in the 5-year period 2013-2017. The causes of preterm delivery were divided into 6 mutually exclusive groups. The main outcome was a composite neonatal morbidity criterion, defined by at least one among the following criteria: neonatal respiratory distress, neurological complications, neonatal sepsis, severe necrotizing enterocolitis, and neonatal hypoglycemia. We analyzed the association between cause of preterm delivery and neonatal morbidity after adjustment for gestational age and antenatal corticosteroid therapy. The reference group was preterm labor, defined by spontaneous preterm labor with intact membranes.

Results: During the study period, there were a total of 27 110 births, including 1114 singleton births at 34 to 36 weeks of gestation + 6 days (4.1%). Among the 968 late preterm births included, the risk of neonatal morbidity in the group with preterm premature rupture of membranes (PPROM) was similar to that in the preterm labor (reference) group: adjusted odds ratio (aOR) 1.2 (95% CI, 0.8-1.8). All the other causes of late preterm birth were associated with a higher risk of neonatal morbidity than the reference group: aOR 2.0 [95% CI, 1.1-3.5] for hypertensive disorders without suspected fetal growth restriction (FGR) (9.1% of cases), aOR 2.4 [95% CI, 1.4-4.2] for hypertensive disorders with suspected FGR (8.9%), aOR 4.2 [95% CI, 2.2-8.0] for suspected FGR without hypertensive disorders (5.8%), and aOR 4.4 [95% CI, 2.2-8.8] for vaginal bleeding related to abnormal placental insertion (4.7%).

Conclusion: Among infants born from 34 to 36 weeks + 6 days of gestation, PPROM and preterm labor had similar risks of neonatal morbidity, while the other causes were associated with a risk of neonatal morbidity at least twice that with preterm labor.
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http://dx.doi.org/10.1016/j.jogoh.2020.101920DOI Listing
September 2020

Persistence of group B Streptococcus vaginal colonization and prevalence of hypervirulent CC-17 clone correlate with the country of birth: a prospective 3-month follow-up cohort study.

Eur J Clin Microbiol Infect Dis 2021 Jan 18;40(1):133-140. Epub 2020 Aug 18.

Department of Bacteriology, University Hospitals Paris Centre Cochin Port Royal, French National Reference Centre for Streptococci, AP-HP, Paris, France.

To identify factors associated with vaginal colonization and persistence by group B Streptococcus (GBS) and by the hypervirulent neonatal CC-17 clone in late pregnancy and after delivery, a multicentre prospective observational cohort with 3-month follow-up was established in two university hospitals, Paris area, France. Pregnant women were recruited when antenatal screening for GBS vaginal colonization at 34-38 weeks of gestational age was positive. Vaginal samples were analysed by conventional culture methods at antenatal screening, delivery, and 21 and 60 days following delivery. Identification of the hypervirulent neonatal GBS CC-17 was performed. Colonization was defined as persistent when all vaginal samples were positive for GBS. A total of 754 women were included. GBS vaginal colonization was persistent in 63% of the cases (95% CI 59%-67%). Persistent colonization was more likely in women born in Sub-Saharan Africa compared with women born in France (OR = 1.88, 95% CI 1.05-3.52), and GBS CC-17 was overrepresented in women born in Sub-Saharan Africa (OR = 2.09, 95% CI 1.20-3.57). Women born in Sub-Saharan Africa are at higher risk for GBS vaginal persistence than women born in France. This observation correlates with an increased prevalence of the hypervirulent GBS CC-17 in the former group, which likely reflect variations linked to ethnicity and vaginal community-state types and might account for the increased susceptibility of black neonates to GBS infections.
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http://dx.doi.org/10.1007/s10096-020-04011-6DOI Listing
January 2021

Increased risk of severe maternal morbidity in women with twin pregnancies resulting from oocyte donation.

Hum Reprod 2020 08;35(8):1922-1932

Centre for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Université de Paris, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRA, Paris, France.

Study Question: Is there a difference in the risk of serious maternal complications during pregnancy and the postpartum in twin pregnancies according to mode of conception: natural conception, non-IVF fertility treatment, IVF, ICSI or oocyte donation?

Summary Answer: Women with twin pregnancies after medically assisted reproduction (MAR) had an overall risk of serious maternal complications 30% higher compared with women with natural twin pregnancies, and this association varied according to the MAR procedure; the risk was increased by 50% with IVF using autologous oocytes and by 270% with oocyte donation.

What Is Known Already: IVF has been reported as a risk factor for serious maternal complications in several concordant studies of singleton pregnancies. For twin pregnancies, this association is less well documented with imprecise categorisation of the mode of conception, and results are contradictory.

Study Design, Size, Duration: This is a secondary analysis of the national, observational, prospective, population-based cohort study of twin pregnancies (JUmeaux Mode d'Accouchement), which took place in France from 10 February 2014 through 1 March 2015. All French maternity units performing more than 1500 annual deliveries were invited to participate, regardless of their academic, public or private status or level of care. Of the 191 eligible units, 176 (92%) participated.

Participants/materials, Setting, Methods: Women with a twin pregnancy who gave birth at or after 22 weeks of gestation were eligible (N = 8823 women included). We excluded women whose mode of conception was unknown (n = 75). Serious maternal complications were regrouped within the recently emerged concept of severe acute maternal morbidity (SAMM), as a binary composite outcome. The exposure of interest was the mode of conception, studied in five classes: natural conception (reference group), non-IVF fertility treatment including insemination and ovarian stimulation, IVF with autologous oocyte, ICSI with autologous oocyte and oocyte donation. To assess the association between the mode of conception and SAMM, we used multivariate logistic regression to adjust for confounders. Structural equation modelling (SEM) was used to explore the contribution to this association of potential intermediate factors, i.e. factors possibly caused by the mode of conception and responsible for SAMM: non-severe pre-eclampsia, placenta praevia and planned mode of delivery.

Main Results And The Role Of Chance: Among the 8748 women of the study population, 5890 (67.3%) conceived naturally, 854 (9.8%) had non-IVF fertility treatment, 1307 (14.9%) had IVF with autologous oocytes, 368 (4.2%) had ICSI with autologous oocytes and 329 (3.8%) used oocyte donation. Overall, 538 (6.1%) developed SAMM. Women with twin pregnancy after any type of MAR had a higher risk of SAMM than those with a natural twin pregnancy, after adjustment for confounders (7.9% (227/2858) compared to 5.3% (311/5890), adjusted odds ratio (aOR) 1.3, 95% CI 1.1-1.6). This association varied according to the MAR procedure. The risk of SAMM was higher among women with IVF using either autologous oocytes (8.3%; 108/1307) or oocyte donation (14.0%; 46/329) compared with the reference group (respectively aOR 1.5, 95% CI 1.1-1.9 and aOR 2.7, 95% CI 1.8-4.1) and higher after oocyte donation compared with autologous oocytes (aOR 1.7, 95% CI 1.1-2.6). Conversely, the risk of SAMM for women with non-IVF fertility treatment (6.2%; 53/854) and with ICSI using autologous oocytes (5.4%; 20/368) did not differ from that of the reference group (5.3%; 311/5890) (respectively aOR 1.1, 95% CI 0.8-1.5 and aOR 0.9, 95% CI 0.6-1.5). The tested intermediate factors poorly explained these increased risks.

Limitations, Reasons For Caution: Beyond the confounders and intermediate factors considered in our analysis, specific causes of infertility and specific aspects of infertility treatments may explain the differences in the risk of SAMM by mode of conception. However, these data were not available.

Wider Implications Of The Findings: Our study showed an increased risk of SAMM in women with twin pregnancies after MAR, notably after IVF using autologous oocytes and particularly after oocyte donation. To avoid unnecessary exposure to the high-risk combination of MAR and multiple pregnancies, transfer of a single embryo should be encouraged whenever possible. Knowledge of these differential risks may inform discussions between clinicians and women about the mode of conception and help to optimise obstetric care for women in subgroups at higher risk.

Study Funding/competing Interest(s): This work was supported by a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique, AOM2012). There are no competing interests.

Trial Registration Number: Not applicable.
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http://dx.doi.org/10.1093/humrep/deaa108DOI Listing
August 2020

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

J Pediatr 2020 07;222:71-78.e6

Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Statistics Sorbonne Paris Cité, INSERM U1153, Paris, France; Paris Descartes University, France; Department of Obstetrics and Gynecology, Hôpital Armand Trousseau, Sorbonne University, Assistance Publique-Hôpitaux de Paris, Paris, France.

Objective: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth.

Study Design: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 24 to 31 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period.

Results: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2."

Conclusions: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.
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http://dx.doi.org/10.1016/j.jpeds.2020.03.021DOI Listing
July 2020

Planned delivery route and outcomes of cephalic singletons born spontaneously at 24-31 weeks' gestation: The EPIPAGE-2 cohort study.

Acta Obstet Gynecol Scand 2020 12 13;99(12):1682-1690. Epub 2020 Jul 13.

Pôle Femme Mère Nouveau-né, CHU Lille, Jeanne de Flandre Hospital, University of Lille, Lille, France.

Introduction: The objective of this study was to investigate the association between planned mode of delivery and neonatal outcomes with spontaneous very preterm birth among singletons in cephalic presentation.

Material And Methods: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national, prospective, population-based cohort study of preterm infants. For this study, we included women with a singleton cephalic pregnancy and spontaneous preterm labor or preterm premature rupture of membranes at 24-31 weeks' gestation. The main exposure was the planned mode of delivery (ie planned vaginal delivery or planned cesarean delivery at the initiation of labor). The primary outcome was survival at discharge and secondary outcome survival at discharge without severe morbidity. Propensity scores were used to minimize indication bias in estimating the association.

Results: The study population consisted of 1008 women: 206 (20.4%) had planned cesarean delivery and 802 (79.6%) planned vaginal delivery. In all, 723 (90.2%) finally had a vaginal delivery. Overall, 187 (92.0%) and 681 (87.0%) neonates in the planned cesarean delivery and planned vaginal delivery groups were discharged alive, and 156 (77.6%) and 590 (76.3%) were discharged alive without severe morbidity. After matching on propensity score, planned cesarean delivery was not associated with survival (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 0.48-2.28) or survival without severe morbidity (aOR 0.64, 95% CI 0.36-1.16).

Conclusions: Planned cesarean delivery for cephalic presentation at 24-31 weeks' gestation after preterm labor or preterm premature rupture of membranes does not improve neonatal outcomes.
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http://dx.doi.org/10.1111/aogs.13939DOI Listing
December 2020

Internal Version Compared With Pushing for Delivery of Cephalic Second Twins.

Obstet Gynecol 2020 06;135(6):1435-1443

Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service de Gynécologie Obstétrique, Université de Paris, INSERM, U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Research Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Assistance Publique-Hôpitaux de Paris, Maternité Port-Royal, DHU risques et grossesse, Clinical Research Unit of Paris Descartes Necker Cochin, APHP, Maternité Notre Dame de Bon Secours, Groupe Hospitalier Saint-Joseph, and Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Gynécologie Obstétrique, Paris, Université Paris Sud, Le Kremlin Bicêtre, CHRU de Lille, Maternité Jeanne de Flandre, and Université de Lille 2, Lille, Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Service de Gynécologie Obstétrique, and Université Pierre et Marie Curie, Paris, Centre Hospitalier Intercommunal de Poissy, Service de Gynécologie Obstétrique, Poissy, Université de Versailles Saint-Quentin-en-Yvelines, Versailles, CHU de Strasbourg, Hôpital Hautepierre, and Université de Strasbourg, Strasbourg, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Gynécologie Obstétrique, Le Kremlin Bicêtre, CHU de Bordeaux, Service de Gynécologie Obstétrique, and Université de Bordeaux, Bordeaux, CHU de Toulouse, Service de Gynécologie Obstétrique, and Université Toulouse III Paul Sabatier, Toulouse, and CHU de Nantes, Service de Gynécologie Obstétrique, CIC Mère enfant, INRA, UMR 1280 Physiologie des adaptations nutritionnelles, and Université de Nantes, Nantes, France.

Objective: To assess neonatal morbidity and mortality according to whether cephalic second twins were born after internal version followed by total breech extraction or after instructions to push. We hypothesized that interval version would result in shorter intertwin delivery intervals and lower cesarean delivery rates for the second twin and therefore better neonatal outcomes.

Methods: These planned analyses of the JUMODA (JUmeaux MODe d'Accouchement) cohort, a national prospective population-based study of twin deliveries, examined births of cephalic second twins after vaginal birth of the first twin at or after 32 weeks of gestation. The internal version group of second twins born in breech presentation after obstetric maneuvers was compared with the pushing group, comprising those born in cephalic presentation. The primary outcome was a composite of neonatal morbidity and mortality. Multivariate modified Poisson regression models were used to control for potential confounders.

Results: Of 2,256 cephalic second twins, 487 (21.6%) were born in breech presentation after internal version and total breech extraction and 1,769 (78.4%) in cephalic presentation after pushing. Composite neonatal morbidity and mortality was not lower in the internal version (17/487 [3.5%]) compared with the pushing group (38/1,769 [2.1%]; adjusted relative risk [aRR] 1.73 [95% CI 0.98-3.05]), although median [quartile 1-quartile 3] intertwin delivery intervals were shorter (5 [4-8] vs 8 [5-12] minutes, P<.001) and the cesarean delivery rate for the second twin lower (5/487 [1.0%] vs 66/1,769 [3.7%], P=.002). Subgroup analyses showed no difference between groups at or after 37 weeks of gestation but higher composite neonatal morbidity and mortality after internal version before 37 weeks (14/215 [6.5%] vs 26/841 [3.1%]; aRR 2.18 [95% CI 1.15-4.13]). Secondary analyses according to center expertise in the overall population and stratified by gestational age yielded concordant results.

Conclusion: Although our sample size precluded a robust assessment for small differences in outcomes between groups, internal version followed by total breech extraction of cephalic second twins was not associated with better neonatal outcomes than pushing.
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http://dx.doi.org/10.1097/AOG.0000000000003862DOI Listing
June 2020

Are there specific factors associated with prenatally undiagnosed foetal macrosomia?

J Gynecol Obstet Hum Reprod 2020 Oct 11;49(8):101802. Epub 2020 May 11.

Port-Royal Maternity Unit, Department of Obstetrics Paris, Cochin Broca Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Objective: Fetal macrosomia is known to increase maternal and neonatal complications, but 20%-50% of the macrosomic fetuses are prenatally undiagnosed. Our objective was to identify specific factors associated with undiagnosed fetal macrosomia in women without diabetes.

Methods: Retrospective case-control study in a tertiary maternity unit between January 1st and December 31st, 2016. Inclusion of all women delivering after 37 weeks of a single live-born macrosomic infant, i.e., with a birth weight ≥ 90th percentile for gestational age (GA). Women with pre-existing or gestational diabetes were excluded. To identify specific factors associated with undiagnosed foetal macrosomia, we compared risk factors for macrosomia, maternal characteristics, father's body mass index (BMI) and prenatal follow up between two groups depending on whether macrosomia was prenatally diagnosed or not.

Results: Among 428 macrosomic newborns, 224 (52.3 %) were prenatally undiagnosed. Known risk factors for macrosomia, maternal characteristics (such as low socio-economic level, low education level) and father's BMI were similar between the two groups. The prenatal follow up was comparable between the two groups. Ultrasound estimated foetal weight during the 3rd trimester was lower in the undiagnosed macrosomic foetuses compared to diagnosed macrosomic foetuses (2130±279 vs 2445±333, p<0.001).

Conclusions: No specific factor of undiagnosed macrosomia was identified, and women with prenatally undiagnosed fetal macrosomia had the same risk factors than women with diagnosed macrosomia. Our study suggests that our groups have different growth curves. This hypothesis has yet to be studied.
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http://dx.doi.org/10.1016/j.jogoh.2020.101802DOI Listing
October 2020

Adrenalectomy during pregnancy: A 15-year experience at a tertiary referral center.

Surgery 2020 Aug 17;168(2):335-339. Epub 2020 May 17.

Department of Digestive, Hepato-biliary and Endocrine Surgery, Referral Center for Rare Adrenal Diseases, Cochin Hospital, APHP, Paris, France; Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, France; INSERM Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Institut Cochin, Paris, France.

Background: Adrenal lesions diagnosed during pregnancy remain rare, and their management is challenging because of maternal physiologic modifications, restricted imaging investigations, and contraindications to several treatments. Surgical issues of adrenalectomy during pregnancy and consequences on perinatal outcomes are poorly described. We therefore aimed to report maternal and fetal outcomes after adrenalectomy during pregnancy.

Methods: All pregnant women who underwent adrenalectomy over a 15-year inclusion period were identified from a prospectively maintained database. Surgical management and maternal and fetal outcomes were reviewed.

Results: From January 2003 to July 2018, a total of 12 women underwent adrenalectomy at a median gestation of 20 weeks. Of these women, 11 had hyper-secreting lesions, including 8 with cortisol oversecretion, and 11 had benign lesions, including cortisol-secreting adenoma (n = 5), pheochromocytoma (n = 2), primary pigmented, nodular adrenal disease (n = 1), severe Cushing's disease (n = 2), and hematoma (n = 1). A total of 3 patients with severe Cushing's disease (n = 2) and primary pigmented, nodular adrenal disease (n = 1) required bilateral adrenalectomy. One patient presented with a malignant adrenal Ewing sarcoma. Adrenalectomy during pregnancy was performed by the lateral laparoscopic transabdominal laparoscopic route in 9 patients. Postoperative morbidity occurred in 3 women. Maternal mortality was nil, but preterm birth occurred in 7 cases and intrauterine growth retardation was observed in 3 cases. Finally, among the 12 women, 10 had a child in good health.

Conclusion: During pregnancy, a lateral laparoscopic transabdominal approach is a feasible procedure. Maternal outcome is acceptable but fetal outcome is determined by the underlying disease, with a worse outcome when the adrenalectomy is indicated for malignant lesions or Cushing's syndrome.
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http://dx.doi.org/10.1016/j.surg.2020.03.019DOI Listing
August 2020

Maternal Betamethasone for Prevention of Respiratory Distress Syndrome in Neonates: Population Pharmacokinetic and Pharmacodynamic Approach.

Clin Pharmacol Ther 2020 Nov 4;108(5):1026-1035. Epub 2020 Jun 4.

Pediatric and Perinatal Drug Evaluation and Pharmacology, Université de Paris, Paris, France.

Despite antenatal corticosteroids therapy, respiratory distress syndrome (RDS) is still a leading cause of neonatal morbidity and mortality in premature newborns. To date, the relationship between in utero fetal drug exposure and occurrence of RDS remains poorly evaluated. This study aims to describe the pharmacokinetics of betamethasone in pregnant women and to evaluate the transplacental drug transfer and administration scheme for the prevention of RDS. Pregnant women > 27 weeks' gestation and who received at least a single dose of betamethasone for prevention of RDS were enrolled. Maternal, cord blood, and amniotic fluid betamethasone time-courses were analyzed using the Monolix software. A total of 220 maternal blood, 56 cord blood, and 26 amniotic fluid samples were described by a two-compartment model with two effect compartments linked by rate transfer constants. Apparent clearances and volumes of distribution parameters were allometrically scaled for a 70 kg third trimester pregnant woman. The impact of a twin pregnancy was found to increase maternal clearance by 28%. Using a fetal-to-mother exposure ratio, the median (95% confidence interval (CI)) transplacental transfer of betamethasone was estimated to 35% (95% CI 0.11-0.67). After adjustment for gestational age and twin pregnancy, RDS was found to be associated to the time spent in utero below quantifiable concentrations (i.e., < 1 ng/mL): odds ratio of 1.10 (95% CI 1.01-1.19) per day increase (P < 0.05). Trying to take into account both efficacy and safety, we simulated different dosing schemes in order to maintain a maximum of fetuses above 1 ng/mL without exceeding the total standard dose.
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http://dx.doi.org/10.1002/cpt.1887DOI Listing
November 2020

First Twin in Breech Presentation and Neonatal Mortality and Morbidity According to Planned Mode of Delivery.

Obstet Gynecol 2020 05;135(5):1015-1023

Université de Paris, Epidemiology and Statistics Research Center/CRESS, INSERM, INRA, the Department of Obstetrics and Gynecology, Robert Debré Hospital, APHP, and Port-Royal maternity unit, Cochin Hospital, APHP, Paris, the Department of Gynecology-Obstetric and Reproductive Medicine, Hôpital La Conception/Hôpital Nord, AP-HM, and Aix Marseille Univ, UM 63, CNRS 7278, IRD 198, INSERM 1095, Marseille, Inserm, UMR1027, Equipe SPHERE, the Université de Toulouse III, UMR1027, and CHU Toulouse, Pôle de gynécologie obstétrique, Hôpital Paule de Viguier, Toulouse, the Obstetrical Care Unit, Hôpital Couple Enfant, Grenoble University Hospital, CS 10217, 38043, Grenoble, the Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, and the Department of Obstetrics and Gynecology, CHU de Rouen, Université de Rouen, Rouen, France.

Objective: To compare neonatal mortality and morbidity of first twins according to the planned mode of delivery when the first twin is in breech presentation, in a country where planned vaginal delivery is an option.

Methods: This is a planned secondary analysis of the JUMODA (JUmeaux MODe d'Accouchement) cohort, a national prospective population-based study of twin deliveries conducted in 176 French hospitals. We analyzed pregnancies with first twins in breech presentation and applied the inclusion criteria of the Twin Birth Study (except the criterion for first-twin presentation): both fetuses alive, with a birth weight between 1,500 g and 4,000 g, at or after 32 0/7 weeks of gestation. The primary outcome was a composite of neonatal mortality and morbidity. We used multivariate Poisson regression models to control for potential confounders and propensity score analyses, that is, matching and inverse probability of treatment weighting to control for indication bias.

Results: Among the 1,467 women with a breech-presenting first twin included in this analysis, 1,169 (79.7%) had planned cesarean and 298 (20.3%) planned vaginal births, of whom 185 (62.1%) delivered both twins vaginally. The neonatal mortality and severe morbidity rate for first twins was 1.7% (5/298) in the planned vaginal and 1.9% (22/1,169) in the planned cesarean delivery groups (crude relative risk [RR] 0.90, 95% CI 0.34-2.34). Planned vaginal delivery was not associated with higher neonatal mortality and morbidity than planned cesarean delivery, regardless of the statistical method used: adjusted RR 0.71, 95% CI 0.27-1.86; RR 0.61, 95% CI 0.20-1.83 after matching for propensity score; RR 0.63, 95% CI 0.23-1.74 with inverse probability of treatment weighting. Analyses of neonatal mortality and morbidity of second twins yielded similar results.

Conclusion: Although our sample size precluded a robust assessment for small differences in outcomes between planned cesarean and planned vaginal delivery in twin pregnancies in which the first twin was in breech presentation, in our cohort planned vaginal delivery was not associated with higher neonatal mortality and morbidity for either twin.
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http://dx.doi.org/10.1097/AOG.0000000000003785DOI Listing
May 2020

Severe maternal morbidity by mode of delivery in women with twin pregnancy and planned vaginal delivery.

Sci Rep 2020 03 18;10(1):4944. Epub 2020 Mar 18.

Université de Paris, Epidemiology and Statistics research Center/CRESS, INSERM, INRA, F-75004, Paris, France.

Planned vaginal delivery in twin pregnancies has three potential outcomes: vaginal or cesarean delivery of both twins, or cesarean for the second twin. Our objective was to assess the association between delivery mode and severe acute maternal morbidity (SAMM) in women with twin pregnancies and planned vaginal deliveries. We limited this planned secondary analysis of the JUMODA cohort, a national prospective population-based study of twin deliveries, to women with planned vaginal delivery at or after 24 weeks of gestation who gave birth to two live fetuses at hospital. The association between delivery mode and SAMM was estimated from multivariate Poisson regression models. Of 5,055 women with planned vaginal delivery, 4,007 (79.3%) delivered both twins vaginally, 134 (2.6%) had cesarean for the second twin and 914 (18.1%) cesarean for both twins. Compared to vaginal delivery of both twins, the risk of SAMM was significantly higher after cesarean for the second twin (9.0% versus 4.5%; aRR 2.22, 95% CI 1.27-3.88) and for both twins (9.4% versus 4.5%, aRR 1.56, 95% CI 1.16-2.10). In twin pregnancies with planned vaginal delivery, cesarean deliveries for the second twin and for both twins are associated with higher risks of SAMM than vaginal delivery.
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http://dx.doi.org/10.1038/s41598-020-61720-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080743PMC
March 2020

Risk factors and high-risk subgroups of severe acute maternal morbidity in twin pregnancy: A population-based study.

PLoS One 2020 28;15(2):e0229612. Epub 2020 Feb 28.

Université de Paris, Epidemiology and Statistics Research Center/CRESS, INSERM, INRA, Paris, France.

Objective: To determine risk factors of severe acute maternal morbidity in women with twin pregnancies and identify subgroups at high risk.

Methods: In a prospective, population-based study of twin deliveries, the JUMODA cohort, all women with twin pregnancies at or after 22 weeks of gestation were recruited in 176 French hospitals. Severe acute maternal morbidity was a composite criterion. We determined its risk factors by multilevel multivariate Poisson regression modeling and identified high-risk subgroups by classification and regression tree (CART) analysis, in two steps: first considering only characteristics known at the beginning of pregnancy and then adding factors arising during its course.

Results: Among the 8,823 women with twin pregnancies, 542 (6.1%, 95% confidence interval (CI) 5.6-6.6) developed severe acute maternal morbidity. Risk factors for severe maternal morbidity identified at the beginning of pregnancy were maternal birth in sub-Saharan Africa (adjusted relative risk (aRR) 1.6, 95% CI 1.1-2.3), preexisting insulin-treated diabetes (aRR 2.2, 95% CI 1.1-4.4), nulliparity (aRR 1.6, 95% CI 1.3-2.0), IVF with autologous oocytes (aRR, 1.3, 95% CI, 1.0-1.6), and oocyte donation (aRR 2.0, 95% CI 1.4-2.8); CART analysis identified nulliparous women with oocyte donation as the subgroup at highest risk (SAMM rate: 14.7%, 95% CI, 10.3-19.1). At the end of pregnancy, additional risk factors identified were placenta praevia (aRR 3.5, 95% CI 2.3-5.3), non-severe preeclampsia (aRR 2.5, 95% CI 1.9-3.2), and macrosomia for either twin (aRR 1.7, 95% CI 1.3-2.1); CART analysis identified women with both oocyte donation and non-severe preeclampsia (SAMM rate: 28.9%, 95% CI, 19.9-37.9) and sub-Saharan nulliparous women with non-severe preeclampsia (SAMM rate: 26.9%, 95% CI, 9.9-43.9) as the two subgroups at highest risk.

Conclusion: In woman with twin pregnancy, rates of severe acute maternal morbidity vary between subgroups from 4.6% to 14.7% and from 3.8% to 28.9% at the beginning and at the end of pregnancy respectively, depending on the combined presence of risk factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229612PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048407PMC
May 2020

Intrathoracic Migration of Abdominal Viscera in Pregnancy.

Ann Thorac Surg 2020 06 20;109(6):e461. Epub 2020 Feb 20.

Department of Thoracic Surgery, Paris Centre University Hospitals, Assistance Publique-Hôpitaux de Paris, Paris, France.

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http://dx.doi.org/10.1016/j.athoracsur.2019.12.083DOI Listing
June 2020

Causes of fever in pregnant women with acute undifferentiated fever: a prospective multicentric study.

Eur J Clin Microbiol Infect Dis 2020 May 18;39(5):999-1002. Epub 2020 Jan 18.

Institut Pasteur, Biology of Infection Unit, Paris, France.

The etiologies of undifferentiated fever in pregnant women have not been studied thoroughly. Because of its non-specific presentation but severe prognosis, listeriosis is often suspected in this setting, but in most cases not confirmed. We studied the causes of undifferentiated fever in pregnant women who received preemptive listeriosis treatment. We conducted from November 1, 2011, to June 30, 2013, a prospective multicentric observational cohort study of pregnant women referred to obstetrical wards with undifferentiated fever and who received listeriosis preemptive treatment. Clinical and biological features, treatment, outcome, and final diagnosis were collected. We enrolled 103 febrile pregnant women. A cause was identified in 77/103 (75%): viral infection in 52/103 (50%, influenza in 21 (20%)), bacterial infection in 22 (21%, including 16 pyelonephritis (16%) and 3 pneumonias (3%)), and TORCH infection in 3 (3%, varicella, toxoplasmosis, and cytomegalovirus primo-infections, n=1, each). Viral infections collected during influenza outbreaks (December-March) accounted for 43/57 (75%) cases. Two fetal losses were reported in the context of febrile pneumonia. Final diagnoses required adapting medical care in 46/77 (60%) of cases, for bacterial, influenza, or TORCH infections. A large array of benign to potentially severe infections manifests as acute undifferentiated fever in pregnant women, requiring careful repeated evaluation.
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http://dx.doi.org/10.1007/s10096-019-03809-3DOI Listing
May 2020

Association of Oxytocin Use and Artificial Rupture of Membranes With Cesarean Delivery in France.

Obstet Gynecol 2020 02;135(2):436-443

Port-Royal Maternity Unit, Department of Obstetrics, Cochin Broca Hôtel-Dieu Hospital, Assistance Publique-Hôpitaux de Paris, and INSERM UMR 1153, Obstetrical, Perinatal and Paediatric Epidemiology Research Team (Epopé), Centre for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), DHU Risks in Pregnancy, Paris Descartes University, Paris, France.

Objective: To evaluate whether the decrease in the frequency of oxytocin administration and artificial rupture of membranes observed between the 2010 and 2016 French Perinatal Surveys was associated with a change in the frequency of cesarean delivery or cesarean delivery indications among women who entered labor spontaneously.

Methods: This cross-sectional study included women who participated in the 2010 and 2016 French National surveys who had singleton pregnancies and who gave birth at at least 37 weeks of gestation after spontaneous labor to a liveborn neonate in cephalic presentation. To test whether the observed decrease of oxytocin administration and artificial rupture of membranes between the two study years was explained by the women's individual characteristics and maternity units' organizational characteristics change, multivariable analyses were performed. The same strategy was applied for the change in intrapartum cesarean delivery rates between the 2 years. These analyses were repeated in nulliparous, low obstetric risk women, multiparous low obstetric risk women, and women with a previous cesarean delivery. The cesarean delivery indications were compared in 2010 and 2016.

Results: Oxytocin administration decreased significantly from 58.3% in 2010 to 45.2% in 2016 (adjusted odds ratio [aOR] 0.51; 95% CI 0.47-0.55), as did artificial rupture of membranes, from 52.4% to 42.6% (aOR 0.66; 95% CI 0.62-0.71). The intrapartum cesarean delivery rate remained stable-6.9% compared with 6.6% (aOR 0.93; 95% CI 0.82-1.06). The same patterns were observed in low risk groups and women with a previous cesarean delivery. The cesarean delivery indications were similar in both years.

Conclusion: The significant decrease in oxytocin administration and artificial rupture of membranes in 2016 compared with 2010 was not accompanied by an increase in the intrapartum cesarean delivery rate for women in France who entered labor spontaneously. These results support the recent international guidelines.
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http://dx.doi.org/10.1097/AOG.0000000000003618DOI Listing
February 2020

Intensity of perinatal care for extremely preterm babies and outcomes at a higher gestational age: evidence from the EPIPAGE-2 cohort study.

BMC Pediatr 2020 01 7;20(1). Epub 2020 Jan 7.

Université de Paris, Epidemiology and Statistics Research Center/CRESS, INSERM (U1153 - Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé)), INRA, Hôpital Tenon, Bâtiment Recherche, Rue de la Chine, Paris, 75020, France.

Background: Perinatal decision-making affects outcomes for extremely preterm babies (22-26 weeks' gestational age (GA)): more active units have improved survival without increased morbidity. We hypothesised such units may gain skills and expertise meaning babies at higher gestational ages have better outcomes than if they were born elsewhere. We examined mortality and morbidity outcomes at age two for babies born at 27-28 weeks' GA in relation to the intensity of perinatal care provided to extremely preterm babies.

Methods: Fetuses from the 2011 French national prospective EPIPAGE-2 cohort, alive at maternal admission to a level 3 hospital and delivered at 27-28 weeks' GA, were included. Morbidity-free survival (survival without sensorimotor (blindness, deafness or cerebral palsy) disability) and overall survival at age two were examined. Sensorimotor disability and Ages and Stages Questionnaire (ASQ) result below threshold among survivors were secondary outcomes. Perinatal care intensity level was based on birth hospital, grouped using the ratio of 24-25 weeks' GA babies admitted to neonatal intensive care to fetuses of the same gestation alive at maternal admission. Sensitivity analyses used ratios based upon antenatal steroids, Caesarean section, and newborn resuscitation. Multiple imputation was used for missing data; hierarchical logistic regression accounted for births nested within centres.

Results: 633 of 747 fetuses (84.7%) born at 27-28 weeks' GA survived to age two. There were no differences in survival or morbidity-free survival: respectively, fully adjusted odds ratios were 0.96 (95% CI: 0.54 to 1.71) and 1.09 (95% CI: 0.59 to 2.01) in medium and 1.12 (95% CI: 0.63 to 2.00) and 1.16 (95% CI: 0.62 to 2.16) in high compared to low-intensity hospitals. Among survivors, there were no differences in sensorimotor disability or ASQ below threshold. Sensitivity analyses were consistent with the main results.

Conclusions: No difference was seen in survival or morbidity-free survival at two years of age among fetuses alive at maternal hospital admission born at 27-28 weeks' GA, or in sensorimotor disability or presence of an ASQ below threshold among survivors. There is no evidence for an impact of intensity of perinatal care for extremely preterm babies on births at a higher gestational age.
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http://dx.doi.org/10.1186/s12887-019-1856-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945524PMC
January 2020

Staffing needs for unscheduled activity in obstetrics and gynecology.

Eur J Obstet Gynecol Reprod Biol 2020 Feb 29;245:19-25. Epub 2019 Nov 29.

Société Française d'Anesthésie Réanimation (SFAR), France; Club d'Anesthésie Réanimation en Obstétrique (CARO), France; Pole Anesthésie Réanimation, Maternité Jeanne de Flandre, Centre Hospitalier Régional Universitaire de Lille, France.

Introduction: To determine a minimum threshold of medical staffing needs (obstetricians-gynecologists, anesthesiologists-resuscitation specialists, nurse-anesthetists, pediatricians, and midwives) to ensure the safety and quality of care for unscheduled obstetrics-gynecology activity.

Materials And Methods: Face to face meetings of French healthcare professionals involved in perinatal care in different types of practices (academic hospital, community hospital or private practice) who belong to French perinatal societies: French National College of Gynecologists-Obstetricians (CNGOF), the French Society of Anesthesia and Resuscitation Specialists (SFAR), the French Society of Neonatology (SFN), the French Society of Perinatal Medicine (SFMP), the National College of French Midwives (CNSF), and the French Federation of Perinatal Care Networks (FFRSP).

Results: Different minimum thresholds for each category of care provider were proposed according to the number of births/year in the facility. These minimum thresholds can be modulated upwards as a function of the level of care (Level 1, 2 or 3 for perinatal centers), existence of an emergency department, and responsibilities as a referral center for maternal-fetal and/or surgical care. For example, an obstetrics-gynecology department handling 3000-4500 births per year without serving as a referral center must have an obstetrician-gynecologist, an anesthesiologist-resuscitation specialist, a nurse-anesthetist, and a pediatrician onsite specifically to provide care for unscheduled obstetrics-gynecology needs and a second obstetrician-gynecologist available within a time compatible with security requirements 24/7; the number of midwives always present (24/7) onsite and dedicated to unscheduled care is 5.1 for 3000 births and 7.2 for 4500 births. A maternity unit's occupancy rate must not exceed 85 %.

Conclusion: The minimum thresholds proposed here are intended to improve the safety and quality of care of women who require unscheduled care in obstetrics-gynecology or during the perinatal period.
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http://dx.doi.org/10.1016/j.ejogrb.2019.11.020DOI Listing
February 2020

Delayed-interval delivery of twins in 13 pregnancies.

J Gynecol Obstet Hum Reprod 2020 Feb 3;49(2):101660. Epub 2019 Dec 3.

Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Department of Obstetrics and Gynecology, Colombes, France; Université de Paris, Paris, France; DHU Risques et Grossesse, Paris, France; Inserm IAME U1137, F-75018, Paris, France. Electronic address:

Background: Delayed interval delivery is a rare practice aiming at prolonging gestation for the second twin in case of pre-viable birth of twin one. Our objective was to identify factors related to successful delayed delivery of the second twin, among cases in which the interval after delivery of the first twin was above 24h.

Method: A descriptive, retrospective and multicenter study of all delayed interval deliveries in dichorionic twins in 4 perinatal centers in Paris over a 14-year period.

Results: In 13 cases of delayed interval delivery, delivery of twin 1 was at a median of 18 weeks' gestation (range 14WG+2days to 24WG), and none survived. Delivery of the second twin occurred at a median of 25 weeks' gestation +3 days, 51 days after twin 1 (range 13-138 days). Seven of the 13s twins (54 %) survived. There were 5 cases of chorioamnionitis and 1 case of maternal disseminated intravascular coagulation. Poor outcome was not significantly associated with the gestational age, presentation for PPROM or inflammatory markers (C-reactive protein and white blood cell count) at the time of delivery of twin 1.

Conclusion: Delayed-interval delivery of the second twin may prolong pregnancy and lead the second twin child to a viable term of birth; but carries a risk of maternal complications.
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February 2020

Association between planned mode of delivery and severe maternal morbidity in women with breech presentations: A secondary analysis of the PREMODA prospective general population study.

J Gynecol Obstet Hum Reprod 2020 Feb 4;49(2):101662. Epub 2019 Dec 4.

INSERM U1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Research Center for Epidemiology and Biostatistics Sorbonne Paris Cité (CRESS), Université de Paris, F-75014, France; Port-Royal Maternity Unit, Cochin Hospital, APHP, Paris, France.

Background: Neonatal morbidity among fetuses in breech presentation is not associated with planned mode of delivery in France. Data about consequences to these mothers are sparse.

Methods: The prospective PREMODA study took place in France and Belgium (2001-2002) in 138 maternity units and included all women with a singleton fetus in breech presentation ≥ 37 weeks of gestation (n=8105). We excluded women with more than one previous cesarean delivery, an in utero fetal death, or for whom cesarean delivery or induction of labor was planned due to maternal disease. The composite variable "severe acute maternal morbidity" (SAMM) grouped severe events. Associations between planned modes of delivery and SAMM were estimated from multivariable Poisson regression models adjusted for potential confounders. A control group with fetuses in cephalic presentation enabled us to compare maternal complications by fetal presentation.

Results: Among the 7564 women included in the analysis, 5098 (67.4%) had a planned cesarean and 2466 (32.6%) a planned vaginal delivery; their SAMM rates did not differ: 48/8098 (0.9%) versus 17/2466 (0.7%), respectively, with an adjusted risk ratio (aRR) of 1.60, 95% confidence interval (95% CI) 0.81-3.15. The SAMM rate was significantly higher in the planned vaginal breech group than in the planned vaginal cephalic group: 17/2466 (0.7%) versus 39/10156 (0.4%) (aRR 2.10, 95% CI 1.18-3.74).

Conclusion: In women with a fetus in breech presentation at term, the short-term risk of severe maternal morbidity did not differ significantly according to planned mode of delivery.
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http://dx.doi.org/10.1016/j.jogoh.2019.101662DOI Listing
February 2020