Reference values for biochemical tests during pregnancy: analysis of the PRECAREbio Cohort and correlation with precarious status.

OBJECTIVE: To establish normal current values of various biochemical parameters during pregnancy in the northern area of Paris (France) in a subgroup from the PreCARE cohort and to study their changes according to the term of pregnancy, and to determine the influence of maternal precarity. DESIGN: The PreCAREbio cohort of pregnant women was defined in the PreCARE study, a multicenter cohort study. SETTING: Participants completed detailed questionnaires at enrolment and immediately postpartum. Data were collected prospectively. 26 biochemical parameters were longitudinally assessed. POPULATION: All women registered to deliver or who delivered at one of the four participating university hospitals in Paris between October 2010 and November 2011 were eligible for study inclusion (n=10,419). METHODS: We studied 26 biochemical markers during pregnancy and the influence of maternal social deprivation. MAIN OUTCOME MEASURES: Baseline values for 26 biochemical markers and their changes according to the term of pregnancy, and the influence of maternal social deprivation on these biochemical markers. RESULTS: 386 patients with 1733 blood samples recruited in one of the four centers in the PreCARE cohort were included. Baseline concentrations (median, 2.5th and 97.5th percentile) for each marker and did not differ at the different time points. Mean concentrations of each biochemical marker did not differ between socially deprived women and non-socially deprived women. CONCLUSIONS: We have established normal values for 26 biochemical parameters during pregnancy. We have also shown no difference in these values between socially deprived and non- socially deprived women.

Impact of variants of SARS-CoV-2 on obstetrical and neonatal outcomes.

BACKGROUND: SARS-CoV-2 can lead to several types of complications during pregnancy. Variant surges are associated with different severities of disease. Few studies have compared the clinical consequences of specific variants on obstetrical and neonatal outcomes. Our goal was to evaluate and compare disease severity in pregnant women and obstetrical or neonatal complications between variants of SARS-CoV-2 that have circulated in France over a two-year period (2020-2022). METHOD: This retrospective cohort study included all pregnant women with a confirmed SARS-CoV-2 infection (positive naso-pharyngeal RT-PCR test) from March 12, 2020 to January 31, 2022, in three tertiary maternal referral obstetric units in the Paris metropolitan area, France. We collected clinical and laboratory data for mothers and newborns from patients' medical records. Variant identification was either available following sequencing or extrapolated from epidemiological data. RESULTS: There were 234/501 (47%) Wild Type (WT), 127/501 (25%) Alpha, 98/501 (20%) Delta, and 42/501 (8%) Omicron. No significative difference was found regarding two composite adverse outcomes. There were significantly more hospitalizations for severe pneumopathy in Delta variant than WT, Alpha and Omicron respectively (63% vs 26%, 35% and 6%, p<0.001), more frequent oxygen administration (23% vs 12%, 10% and 5%, p = 0,001) and more symptomatic patients at the time of testing with Delta and WT (75% and 71%) versus Alpha and Omicron variants (55% and 66% respectively, p<0.01). Stillbirth tended to be associated with variants (p = 0.06): WT 1/231 (<1%) vs 4/126 (3%), 3/94 (3%), and 1/35 (3%) in Alpha, Delta and Omicron cases respectively. No other difference was found. CONCLUSION: Although the Delta variant was associated with more severe disease in pregnant women, we found no difference regarding neonatal and obstetrical outcomes. Neonatal and obstetrical specific severity may be due to mechanisms other than maternal ventilatory and general infection.

[SARS-Cov-2 vaccine's acceptance among pregnant women-A cross-sectional survey]. / Acceptabilité du vaccin-Sars CoV-2 chez les femmes enceintes, une enquête transversale par questionnaire.

OBJECTIVE: SARS-CoV-2 is more likely to cause severe cases in pregnant women. They were part of the priority groups since April 2021 to benefit from SARS-CoV-2 vaccination before its extent to general population. This contribution aims to evaluate, in the postpartum period, the achievement of COVID-19 vaccination and factors associated in women during their pregnancy. MATERIAL AND METHOD: Multicenter cross-sectional survey study conducted from September to December 2021 with online self-questionnaire. All postpartum patients hospitalized in one of the 6 participating maternity hospitals were invited to answer. The questionnaire asked patients about their demographic characteristics, vaccination modalities, vaccine tolerance, and their general perception of vaccination. RESULTS: Of the 371 women who responded, the vaccination rate was 65.7% (IC95% [60.8-70.4]), whom 98.8% entirely during pregnancy. Associated factors with vaccination during pregnancy were older age, higher socio-professional category, and prior information provided by health professionals. Factors that appear to motivate vaccination were personal protection and protection of the newborn. Finally, main factors negatively influencing the vaccination process were the fear of vaccine side effects and the negative perception of vaccines in general. DISCUSSION: Acceptability and information about the vaccine by health professionals is in constant improvement. Information campaigns should be continued to improve the acceptability of vaccination, in light of the accumulating data.

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.

[Infection with SARS-CoV-2 in pregnancy. Update of Information and proposed care. CNGOF]. / Infection par le SARS-CoV-2 chez les femmes enceintes. Actualisation de l'état des connaissances et de la proposition de prise en charge. CNGOF.

OBJECTIVES: The coronavirus SARS-CoV-2 identified late 2019 in China had spread across all continents. In the majority of cases, patients have mild symptoms (fever, cough, myalgia, headache, some digestive disorders) or are asymptomatic, however it can cause serious lung diseases and lead to death. On September 2020, over 28 million people have been infected with over 920,000 deaths. METHODS: In view of the evolution of the epidemic the French National College of Obstetricians and Gynecologists has decided to update the recommendations previously issued. To do this, the same group of experts was called upon to carry out a review of the literature and take into account the opinions of the General Directorate of Health (DGS), the "Haute Autorité de Santé" (HAS) and the "Haut Conseil de santé Publique" (HCSP). RESULTS: The data on consequences during pregnancy have accumulated. The symptoms in pregnant women appear to be similar to those of the general population, but an increased risk of respiratory distress exists in pregnant women especially in the third trimester. A case of intrauterine maternal-fetal transmission has been clearly identified. Induced prematurity and cases of respiratory distress in newborns of infected mothers have been described. CONCLUSION: In light of the new data, we propose updated recommendations. These proposals may continue to evolve in view of the pandemic and of advances in studies in pregnant women.

[SARS-CoV-2 infection during pregnancy. Information and proposal of management care. CNGOF]. / Infection par le SARS-CoV-2 chez les femmes enceintes : état des connaissances et proposition de prise en charge par CNGOF.

A new coronavirus (SARS-CoV-2) highlighted at the end of 2019 in China is spreading across all continents. Most often at the origin of a mild infectious syndrome, associating mild symptoms (fever, cough, myalgia, headache and possible digestive disorders) to different degrees, SARS-Covid-2 can cause serious pulmonary pathologies and sometimes death. Data on the consequences during pregnancy are limited. The first Chinese data published seem to show that the symptoms in pregnant women are the same as those of the general population. There are no cases of intrauterine maternal-fetal transmission, but cases of newborns infected early suggest that there could be vertical perpartum or neonatal transmission. Induced prematurity and cases of respiratory distress in newborns of infected mothers have been described. Pregnancy is known as a period at higher risk for the consequences of respiratory infections, as for influenza, so it seems important to screen for Covid-19 in the presence of symptoms and to monitor closely pregnant women. In this context of the SARS-Covid-2 epidemic, the societies of gynecology-obstetrics, infectious diseases and neonatalogy have proposed a French protocol for the management of possible and proven cases of SARS-Covid-2 in pregnant women. These proposals may evolve on a daily basis with the advancement of the epidemic and knowledge in pregnant women. Subsequently, an in-depth analysis of cases in pregnant women will be necessary in order to improve knowledge on the subject.

Maternity staff immunization coverage against pertussis and maternal vaccination practices: Results of a 2017 cross-sectional survey in five public maternity hospitals.

OBJECTIVES: To conduct an audit of vaccination practices against pertussis in maternity wards to assess immunization practices targeting women, knowledge and awareness among health professionals and their involvement in the vaccination process, and to estimate their vaccine coverage. MATERIALS AND METHODS: 2017 cross-sectional descriptive survey using a data collection sheet of immunization practices targeting women and an anonymous questionnaire for health professionals whose vaccine coverage had been documented by the occupational health service. RESULTS: Five public maternity wards participated: one had a vaccination policy for women; 426 of 822 health professionals completed the questionnaire, 76% (from 50% of all residents to 83% of nurses) declared their vaccination status as up to date. Staff files in occupational health services showed that 69% of 822 health professionals received at least one vaccine booster during adulthood (57% less than 10 years before the survey); documented vaccination coverage rates ranged from 75% for residents to 91% for senior physicians. Occupational physicians and family physicians respectively performed 41% and 34% of vaccinations. While knowledge regarding vaccines was good, only 47% of health professionals declared prescribing them and 18% declared administering the anti-pertussis vaccine "often" or "very often". CONCLUSIONS: Updated data is needed to confirm the reported increase as participating centers are not representative of all birth centers. The active role of health professionals in vaccination-based pertussis prevention needs to be reinforced.

A randomised controlled trial of amnioexchange for fetal gastroschisis.

OBJECTIVE: Morbidity in fetuses affected by gastroschisis is mainly the result of bowel ischaemic and inflammatory processes. Experimental studies on animal models show that clearing amniotic fluid from the digestive secretions by amnioexchange procedures reduces the inflammatory process. We evaluated the benefit of the amnioexchange procedure for fetal gastroschisis in humans. DESIGN: Prospective, interventional, randomised study. SETTING: Eight referral centres for fetal medicine. POPULATION: Pregnant women carrying a fetus with gastroschisis. METHODS: We compared, in utero, amnioexchange with a sham procedure. The protocol included, in both arms, steroid injections at 30 weeks of gestation and the use of postnatal minimal enteral feeding. MAIN OUTCOME MEASURES: The primary outcome was a composite variable based on the duration of ventilation and parenteral nutrition. Secondary outcomes were the effectiveness and safety of the amnioexchange procedure, including the rate of perinatal death, time to full enteral feeding, primary closure, and late feeding disorders. RESULTS: Sixty-four patients were randomised. There was no difference in the composite criteria between the amnioexchange and control groups. Based on an intention-to-treat analysis, there were no significant between-group differences in pregnancy outcome or complications. When studying the relationship between digestive compounds and amniotic fluid inflammatory markers, a clear correlation was found between bile acid and both ferritin and interleukin 1ß (IL1ß). CONCLUSIONS: In humans, amnioexchange, as described in our protocol, is not an option for fetal care; however, we provide supplementary proof of the involvement of inflammation in the pathogenicity of gastroschisis and suggest that future research should aim at reducing inflammation. ClinicalTrials.gov: NCT00127946. TWEETABLE ABSTRACT: A prospective, interventional, randomised study shows no benefit of amnioexchange for fetal gastroschisis in humans.

Association between inadequate antenatal care utilisation and severe perinatal and maternal morbidity: an analysis in the PreCARE cohort.

OBJECTIVE: Because the effectiveness of antenatal care in reducing pregnancy complications is still discussed despite widespread recommendations of its use, we sought to assess the association between utilisation of recommended antenatal care and severe maternal (SMM) and perinatal morbidity (SPM). DESIGN: Prospective cohort study. SETTING: Four maternity units around Paris in 2010-2012. SAMPLE: 9117 women with singleton pregnancies. METHODS: Logistic regression models adjusted for maternal social, demographic and medical characteristics. MAIN OUTCOME MEASURES: Antenatal care utilisation was assessed by: (1) initiation of care after 14 weeks, (2) < 50% of recommended visits made, according to gestational age, (3) absence of the first, second or third trimester ultrasounds, (4) two modified Adequacy of Prenatal Care Utilisation indexes, combining these components. The two main outcomes were composite variables of SMM and SPM. RESULTS: According to the modified Adequacy of Prenatal Care Utilisation index, 34.6% of women had inadequate antenatal care utilisation; the incidence of severe maternal morbidity (SMM) was 2.9% and severe perinatal morbidity (SPM) 5.5%. A percentage of recommended visits below 50% (2.6% of women) was associated with SMM [adjusted odds ratio (OR) 2.40 (1.38-4.17)] and SPM [aOR 2.27 (1.43-3.59)]. Late initiation of care (17.0% of women) was not associated with SMM or SPM. Failure to undergo the recommended ultrasounds (16, 17 and 22% of women) was associated with SPM. Inadequate antenatal care utilisation according to the index was associated with SPM [aOR 1.37 (1.05-1.80)]. CONCLUSION: Inadequate antenatal care utilisation is associated with SMM and SPM, to degrees that vary with the component of care and the outcome considered. TWEETABLE ABSTRACT: Inadequate antenatal care utilisation is associated with severe maternal and perinatal morbidity.

[Perinatal care for extremely preterm infants. Considerations of the "risks in pregnancy" department]. / Prise en charge de la prématurité extrême. Réflexions du département hospitalo-universitaire (DHU) « risques et grossesse ¼.

Decisions regarding whether to initiate or forgo intensive care for extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients and must be taken into account. After a short review of these factors, we present the thoughts and proposals of the Risks and Pregnancy department. The proposals are to limit emergency decisions, to better take into account other factors than gestational age and prenatal predicted fetal weight in assessing the prognosis, to introduce multidisciplinary consultation in the evaluation and proposals that will be discussed with the parents, and to separate prenatal steroid therapy from decision-making regarding whether or not to administer intensive care.

[Fertility-sparing management of endometrial cancer and atypical hyperplasia]. / Traitement conservateur des hyperplasies atypiques et cancers de l'endomètre et préservation de la fertilité.

The fertility sparing management of endometrial cancer and atypical hyperplasia concern women in childbearing age with stage 1, grade 1, endometrioid adenocarcinoma confined to endometrium or atypical hyperplasia (simple or complex). These pathologies affecting more frequently postmenopausal women, the number of people involved is relatively low. The main risk factor is hyperestrogenism and these patients often present a history of infertility with a desire for pregnancy. The recommendations for this conservative management are scarce and unclear. The national observatory in the gynecology and obstetrics department of Bichat hospital gives expert advice to help doctors and patients concerned. We present a type of conservative management based on the expertise of the national observatory. Rigorous pre-therapeutic assessment must first be made to avoid missing a more advanced lesion. Hormone therapy is then started to obtain complete remission. In case of remission, fast achieving pregnancy is advised, and the use of assisted reproductive therapy is possible if necessary. Monitoring by hysteroscopy and histological examination is essential during the treatment. Hysterectomy is the last time the conservative management. It is motivated by the risk of recurrence and progression. The probability of remission after conservative treatment is estimated at 78.0 % at 12 months, the probability of recurrence at 29.2 % at 24 months, and the risk of progression at 15 % (stage 1A with myometrial invasion or more on the hysterectomy specimen). In terms of fertility, 32 % of women get at least one pregnancy.

French prenatal Vitamin D recommended supplementation: Enough or not?

OBJECTIVE: To determine the impact of current recommended vitamin D prenatal supplementation on blood cord 25(OH)D level in a French cohort and to determine population at risk of higher needs. DESIGN AND SETTING: An observational prospective study was conducted in teaching hospital including two large groups of newborns, one born after summer and another after winter period. PATIENTS AND METHODS: Three hundred and ninety-nine mother/newborns pairs were enrolled and blood cord results were available for 225 newborns in the post-summer group and 174 newborns in the post-winter group. Maternal supplementation during pregnancy was recorded from medical notes and questionnaires. RESULTS: 25(OH)D level were generally low with mean at 50.9±24.7nM. Vitamin D supplementation was prescribed in only 37.6% over all the study period. Studying general population, 25(OH)D was significantly higher in the supplemented group, but current recommended supplementation failed to cover the needs for most subgroups of newborns. After winter, 25(OH)D cord blood level was in deficiency range for 40.7% of the general population and in the pigmented mothers group the deficiency rates even rose up to 61.9%. DISCUSSION AND CONCLUSION: Vitamin D cord level is low in north of France as in other industrial countries. Despite national guidelines on vitamin D supplementation, the rates are currently insufficient. Beside, although the recommended 100,000IU single dose helps to limit deficiency in newborns, it fails to cover infant's needs for optimal status. Actually, benefit of this substitution is for children below the 10th percentile weight. A new recommendation with higher rate of vitamin D for all pregnant women after specific studies seems to be indicated.

[Zika virus infection during pregnancy]. / Infection par le virus Zika chez la femme enceinte.

A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman.

[An update on adenomyosis and implantation]. / Adénomyose et implantation : mise au point.

Adenomyosis is an enigmatic disease whose impact on implantation and fertility outcome is still controversial. A negative effect on IVF outcome was already observed, but it is mainly explained by an increase in early spontaneous miscarriages. We reviewed scientific data in order to bring relevant information about adenomyosis and endometrial receptivity for patient counselling and to precise if screening of adenomyosis is indicated before IVF treatment.

Ulipristal acetate for uterine fibroid-related symptoms.

Uterine fibroids are the most common benign uterine tumors in women of reproductive age. Although most women are asymptomatic (80%), fibroids, according to their type and location, can cause several symptoms and impact quality of life. To date, no medical treatment is able to eliminate fibroids. Ulipristal acetate (UPA) is an orally active synthetic selective progesterone receptor modulator (SPRM) characterized by a tissue-specific progesterone antagonist effect that reduces the proliferation of leiomyoma cells and induces apoptosis. It was licensed in Europe for preoperative fibroid treatment in 2012. Its pharmacological and pharmacodynamic characteristics, its efficacy and good tolerance make UPA a new important tool in the management of uterine fibroids.

Can rectal endoscopic sonography be used to predict infiltration depth in patients with deep infiltrating endometriosis of the rectum?

OBJECTIVES: To evaluate the diagnostic accuracy of rectal endoscopic sonography (RES) in the prediction of the infiltration depth of rectal endometriosis and to ascertain whether RES could be used to choose between segmental bowel resection and a more conservative approach, such as shaving or discoid resection. METHODS: In this retrospective study, 38 consecutive patients with symptomatic deep infiltrating endometriosis of the rectum who underwent laparoscopic colorectal resection were included. RES results for infiltration depth of rectal endometriosis were compared with results of pathological examination. The sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), positive and negative likelihood ratios (LRs) and test accuracy were calculated for the presence of infiltration of the muscularis layers and submucosal/mucosal layers, as demonstrated by RES and confirmed by histopathological analysis. RESULTS: For the detection of muscularis layer infiltration by endometriosis, the PPV of RES was 100%, whereas for the detection of submucosal/mucosal layer involvement, the sensitivity was 89%, specificity was 26%, PPV was 55%, NPV was 71%, test accuracy was 58% and positive and negative LRs were 1.21 and 0.40, respectively. CONCLUSIONS: RES is a valuable tool for detecting rectal endometriosis as endometriotic infiltration of the muscularis layer can be predicted accurately. However, RES is less accurate in detecting submucosal/mucosal layer involvement and cannot, therefore, be used to choose between bowel resection and a more conservative approach.

[Primary biliary cirrhosis and pregnancy]. / Cirrhose biliaire primitive et grossesse.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, asymptomatic during a protracted time, characterized by changes in the small-sized bile ducts near portal spaces. The etiology of PBC is undefined, but immunologic and environmental disturbances may contribute to the disease. Infertility is often associated with PBC and cirrhosis, but pregnancy may well occur in women with PBC and without cirrhosis or in some others with compensated cirrhosis. A pluridisciplinary approach including gastroenterologists and obstetricians is recommended. The patient must be closely monitored throughout her pregnancy with maternal and routine antenatal care. Medical treatment requires ursodeoxycholic acid (UDCA). In non-cirrhotic UDCA-treated women with PBC, pregnancy often follows a normal course with vaginal delivery. In cirrhotic patients, UDCA must be continued during pregnancy, esophageal and gastric varices must be evaluated before pregnancy, and endoscopic ligature is recommended for treating large varices. Additionally, beta-blocker therapy may be associated, especially when variceal rupture occurred previously. Elective cesarean section is recommended in patients with large esophageal or gastric varices because of the potentially increased risk of variceal bleeding during maternal expulsive efforts in case of vaginal delivery.

Acute pancreatitis during pregnancy: a review.

This article aims to draw together recent thinking on pregnancy and acute pancreatitis (AP), with a particular emphasis on pregnancy complications, birth outcomes and management of AP during pregnancy contingent on the etiology. AP during pregnancy is a rare but severe disease with a high maternal-fetal mortality, which has recently decreased thanks to earlier diagnosis and some maternal and neonatal intensive care improvement. AP usually occurs during the third trimester or the early postpartum period. The most common causes of AP are gallstones (65 to 100%), alcohol abuse and hypertriglyceridemia. Although the diagnostic criteria for AP are not specific for pregnant patients, Ranson and Balthazar criteria are used to evaluate the severity and treat AP during pregnancy. The fetal risks from AP during pregnancy are threatened preterm labor, prematurity and in utero fetal death. In cases of acute biliary pancreatitis during pregnancy, a consensual strategy could be adopted according to the gestational age, and taking in consideration the high risk of recurrence of AP (70%) with conservative treatment and the specific risks of each treatment. This could include: conservative treatment in first trimester and laparoscopic cholecystectomy in second trimester. During the third trimester, conservative treatment or endoscopic retrograde cholangiopancreatography with biliary endoscopic sphincterotomy, and laparoscopic cholecystectomy in early postpartum period are recommended. A multidisciplinary approach, including gastroenterologists and obstetricians, seems to be the key in making the best choice for the management of AP during pregnancy.