Jean Bouyer

Background: Prescribed contraception is used worldwide by over 400 million women of reproductive age. Monitoring contraceptive use is a major public health issue that usually relies on population-based surveys. However, these surveys are conducted on average every 6 years and do not allow close follow-up of contraceptive use. Moreover, their sample size is often too limited for the study of specific population subgroups such as people with low income. Health administrative data could be an innovative and less costly source to study contraceptive use. Objective: We aimed to explore the potential of health administrative data to study prescribed contraceptive use and compare these data with observations based on survey data. Methods: We selected all women aged 15-49 years, covered by French health insurance and living in France, in the health administrative database, which covers 98% of the resident population (n=14,788,124), and in the last French population–based representative survey, the Health Barometer Survey, conducted in 2016 (n=4285). In health administrative data, contraceptive use was recorded with detailed information on the product delivered, whereas in the survey, it was self-declared by the women. In both sources, the prevalence of contraceptive use was estimated globally for all prescribed contraceptives and by type of contraceptive: oral contraceptives, intrauterine devices (IUDs), and implants. Prevalences were analyzed by age. Results: There were more low-income women in health administrative data than in the population-based survey (1,576,066/14,770,256, 11% vs 188/4285, 7%, respectively; P<.001). In health administrative data, 47.6% (7034,710/14,770,256; 95% CI 47.6%-47.7%) of women aged 15-49 years used a prescribed contraceptive versus 50.5% (2297/4285; 95% CI 49.1%-52.0%) in the population-based survey. Considering prevalences by the type of contraceptive in health administrative data versus survey data, they were 26.9% (95% CI 26.9%-26.9%) versus 27.7% (95% CI 26.4%-29.0%) for oral contraceptives, 17.7% (95% CI 17.7%-17.8%) versus 19.6% (95% CI 18.5%-20.8%) for IUDs, and 3% (95% CI 3.0%-3.0%) versus 3.2% (95% CI 2.7%-3.7%) for implants. In both sources, the same overall tendency in prevalence was observed for these 3 contraceptives. Implants remained little used at all ages, oral contraceptives were highly used among young women, whereas IUD use was low among young women. Conclusions: Compared with survey data, health administrative data exhibited the same overall tendencies for oral contraceptives, IUDs, and implants. One of the main strengths of health administrative data is the high quality of information on contraceptive use and the large number of observations, allowing studies of subgroups of population. Health administrative data therefore appear as a promising new source to monitor contraception in a population-based approach. They could open new perspectives for research and be a valuable new asset to guide public policies on reproductive and sexual health.

Background: Access to IVF/ICSI is facilitated when the financial barrier is removed. In a national context where in vitro fertilisation (IVF)/intracytoplasmic sperm Injection (ICSI) treatment is cost-free, how many women do not access IVF/ICSI and what are the factors associated with non-access? Methods: Using French national health insurance databases, the cohort included 20,240 women aged 18–43 years living in France who underwent unsuccessful treatment (no pregnancy) with clomiphene citrate (CC) and/or gonadotropins with treatment started between January and August 2016. The outcome measure was non-access to IVF/ICSI during the 24-month following start of infertility care. Factors associated with non-access to IVF/ICSI were explored using mixed effects logistic regression. Results: In the cohort, 65.4% of women did not access IVF/ICSI. In multivariable analysis, non-access to IVF/ICSI was higher in younger women (18–25 years: (OR 2.17, 95% CI: 1.85–2.54) and in older women (40–43 years: (OR=3.60, 95% CI: 3.25–3.98)). Non-access was higher among women below the poverty line (OR=3.76, 95% CI: 3.34–4.23) and showed a significant upward trend with increasing deprivation of place of residence. Distance to the nearest fertility centre was not significantly associated with non-access to IVF/ICSI. Conclusions: In a national context of cost-free ART treatment, a large proportion of women did not access treatment, with a strong social gradient that raises important issues. We need to understand the underlying social mechanisms to develop an efficient and equitable health policy regarding infertility care.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Prescribed contraception is used worldwide by over 400 million women of reproductive age. Monitoring contraceptive use is a major public health issue that usually relies on population-based surveys. However, these surveys are conducted on average every 6 years and do not allow close follow-up of contraceptive use. Moreover, their sample size is often too limited for the study of specific population subgroups such as people with low income. Health administrative data could be an innovative and less costly source to study contraceptive use. Objective: We aimed to explore the potential of health administrative data to study prescribed contraceptive use and compare these data with observations based on survey data. Methods: We selected all women aged 15-49 years, covered by French health insurance and living in France, in the health administrative database, which covers 98% of the resident population (n=14,788,124), and in the last French population–based representative survey, the Health Barometer Survey, conducted in 2016 (n=4285). In health administrative data, contraceptive use was recorded with detailed information on the product delivered, whereas in the survey, it was self-declared by the women. In both sources, the prevalence of contraceptive use was estimated globally for all prescribed contraceptives and by type of contraceptive: oral contraceptives, intrauterine devices (IUDs), and implants. Prevalences were analyzed by age. Results: There were more low-income women in health administrative data than in the population-based survey (1,576,066/14,770,256, 11% vs 188/4285, 7%, respectively; P<.001). In health administrative data, 47.6% (7034,710/14,770,256; 95% CI 47.6%-47.7%) of women aged 15-49 years used a prescribed contraceptive versus 50.5% (2297/4285; 95% CI 49.1%-52.0%) in the population-based survey. Considering prevalences by the type of contraceptive in health administrative data versus survey data, they were 26.9% (95% CI 26.9%-26.9%) versus 27.7% (95% CI 26.4%-29.0%) for oral contraceptives, 17.7% (95% CI 17.7%-17.8%) versus 19.6% (95% CI 18.5%-20.8%) for IUDs, and 3% (95% CI 3.0%-3.0%) versus 3.2% (95% CI 2.7%-3.7%) for implants. In both sources, the same overall tendency in prevalence was observed for these 3 contraceptives. Implants remained little used at all ages, oral contraceptives were highly used among young women, whereas IUD use was low among young women. Conclusions: Compared with survey data, health administrative data exhibited the same overall tendencies for oral contraceptives, IUDs, and implants. One of the main strengths of health administrative data is the high quality of information on contraceptive use and the large number of observations, allowing studies of subgroups of population. Health administrative data therefore appear as a promising new source to monitor contraception in a population-based approach. They could open new perspectives for research and be a valuable new asset to guide public policies on reproductive and sexual health.

Background: To assess changes in the number and profile of in utero transfer requests during the first lockdown. Methods: An observational, retrospective, cohort study. All pregnant women, from the Paris area (France), for whom a request for in utero transfer to the transfer unit was made during the first lockdown in France (from 17 March to 10 May 2020) or during a mirror period (years 2016 to 2019) were included. We compared the numbers and proportions of various indications for in utero transfer, the rates of in utero transfer acceptance and the proportion of outborn deliveries. Results: 206 transfer requests were made during the lockdown versus 227, 236, 204 and 228 in 2016, 2017, 2018 and 2019, respectively. The relative proportion of requests for threatened preterm births and for fetal growth restriction decreased from 45% in the mirror period to 37% and from 8 to 3%, respectively. The transfer acceptance rates and outborn deliveries did not differ between time periods. Conclusions: Although a reduction in in utero transfer requests was observed for certain indications, the first lockdown was not associated with a decrease in acceptance rates nor in an increase in outborn births of pregnancies with a high risk of prematurity in the Paris area.

Objective: The magnitude and direction of effects on pregnancy outcomes of the lockdown imposed during COVID-19 have been uncertain and debated. Therefore, we aimed to quantify delivery and perinatal outcomes during the first nationwide lockdown due to the COVID-19 pandemic compared with the same durations of time for the pre- and post-lockdown periods. Study design: This was a retrospective cohort study of six university hospital maternity units distributed across France, each of which serves as the obstetric care referral unit within its respective perinatal network. Maternal and perinatal outcomes were compared between the lockdown period and same-duration (i.e., 55-day) periods before and after the 2020 lockdown (pre-lockdown: 22 January–16 March; lockdown: 17 March–10 May; post-lockdown: 11 May–4 July). We compared the overall rates of Caesarean delivery (CD), pre-labor CD, labor induction, operative vaginal delivery, severe postpartum hemorrhage (≥1 L), severe perineal tear, maternal transfusion, and neonatal mortality and morbidity (1- and 5-min Apgar scores < 7), hypoxia and anoxia (umbilical arterial pH < 7.20 or <7.10, respectively), and admission to a neonatal intensive care unit before discharge. Adjusted odds ratios were estimated using logistic regression, controlling for region of birth, maternal age category, multiparity, multiple pregnancies, diabetes, and hypertensive disorders. Results: The study sample consisted of 11,929 women who delivered consecutively at one of the six maternity units studied (4093 pre-lockdown, 3829 during lockdown, and 4007 post-lockdown) and their 12,179 neonates (4169 pre-lockdown, 3905 during lockdown, and 4105 post-lockdown). The maternal and obstetric characteristics of the women delivering during the lockdown period were alike those delivering pre- and post-lockdown on maternal age, parity, body mass index, rate of complication by hypertensive disorders or insulin-treated diabetes, and gestational age at delivery. Overall CD rates were similar during the three periods (23.6%, 24.8%, and 24.3% pre-lockdown, lockdown, and post-lockdown, respectively) and no outcome differed significantly during lockdown compared to pre- and post-lockdown. These findings were consistent across maternity units. Conclusion: The maternal and perinatal outcomes are reassuring regarding the performance of the health-care system during the COVID-19 lockdown studied. Such information is crucial, because additional COVID-19-related lockdowns might still be needed. They are also instructive regarding potential future pandemics.

Background: Pregnancies in women over 35 years of age are becoming more frequent. The majority of studies point to an age of 35 as a provider of obstetric and neonatal complications. But several confounding factors are not taken into account and this results in contradictory results.Methods: The objective was to quantify the strength of the association between maternal age and obstetric and neonatal morbidity. This observational study was based on systematic records of 9 years of pregnancies managed in the Obstetrics and Gynaecology Department of Antoine Béclère Hospital, Clamart, France. In all, 24,674 pregnancies were managed at Antoine Béclère Hospital between April 1, 2007 and December 31, 2015, including 23,291 singleton pregnancies. Maternal age was the age at the beginning of pregnancy, taken as a quantitative variable. The main outcome measure was a composite “unfavourable” pregnancy outcome that included miscarriage, induced abortion, in utero foetal death, stillborn or newborn infant weighing under 500 g or delivered before 24 weeks of gestational age. Obstetric and neonatal morbidity comprised hospitalisation during pregnancy for more than 1 day, pre-eclampsia, gestational diabetes requiring hospitalisation, caesarean delivery, preterm birth, small-for-gestational age, and newborn transfer to the paediatric unit or neonatal intensive care unit.Results: Analyses were conducted among singleton pregnancies (n = 23,291) and were adjusted for obesity, assisted reproductive technology and geographical origin of the mother. Unfavourable pregnancy outcome rate tripled with age, from 5% among women aged 25 to 34 to 16% among those over 45. Women over 40 were twice as likely to be hospitalised as those aged 25 to 34. The caesarean section rate reached more than 40% among women over 40 and more than 60% in women over 45. The rate of newborn transfer to paediatric intensive care or a neonatal intensive care unit was doubled in women over 40 and small-for-gestational age was more frequent with age, reaching 34% in women over 45.Conclusions: The risk of maternal-foetal complications increases steadily with age and is particularly high after 35 years and closer monitoring appears to be necessary. These results provide additional evidence and information for public health decision-makers.

Introduction Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED). Methods Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority. Results A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756–2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France. Discussion Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.

WHO has recommended using Robson’s Ten Group Classification System (TGCS) to monitor and analyze CD rates. Its failure to take some maternal and organizational factors into account, however, could limit the interpretation of CD rate comparisons, because it may contribute to variations in hospital CD rates. To study the contribution of maternal socioeconomic and clinical characteristics and hospital organizational factors to the variation in CD rates when using Robson’s ten-group classification system for CD rate comparisons. This prospective, observational, population-based study included all deliveries at a gestational age > 24 weeks at the 10 hospitals of the French MYPA perinatal network in the Paris area. CD rates were calculated for each TGCS group in each hospital. Interhospital variations in these rates were investigated with hierarchical logistic regression models to quantify the variation explained by differences in patient and hospital characteristics when the TGCS is considered. Variations in CD rates between hospitals were estimated with median odds ratios (MOR) to express interhospital variance on the standard odds ratio scale. The percentage of variation explained by TGCS and maternal and hospital characteristics was also calculated. The global CD rate was 24.0% (interhospital range: 17–32%). CD rates within each TGCS group differed significantly between hospitals (P40 years), severe preeclampsia, and two organizational factors: hospital status (private maternities) and the deliveries per staff member per 24 hours. The MOR in the empty model was 1.27 and did not change after taking the TGCS into account. Adding maternal characteristics and hospital organizational factors lowered the MOR to 1.14 and reduced the variation between hospital CD rates by 70%. Maternal characteristics and hospital factors are needed to address variation in CD rates among the TGCS groups. Therefore, comparisons of these rates that do not consider these factors should be interpreted carefully.

In pregnant women with gestational diabetes, glyburide can be an alternative to insulin despite concerns about its transplacental transfer. However, transplacental transfer of glyburide is poorly quantified and the relationship between cord blood glyburide concentration and hypoglycemia has not been studied. Our objective was to quantify the transplacental transfer of glyburide at delivery and to study the association between the cord blood glyburide concentration and the risk of neonatal hypoglycemia in patients with gestational diabetes treated with glyburide. INDAO was a multicenter, noninferiority, randomized trial conducted between May 2012 and November 2016 in 914 women with singleton pregnancies and gestational diabetes. An ancillary study was conducted in the 87 patients of the Bicêtre University Hospital Center. The sample consisted of 46 patients with utilizable assays at delivery. The relationships between glyburide concentration and the time since the last intake of glyburide and between fetal glyburide concentration and neonatal hypoglycemia were modeled with linear or logistic regressions using fractional polynomials. There was placental transfer of glyburide at a fetal to maternal ratio of 62% (95% CI [50; 74]). Umbilical cord blood glyburide concentration decreased steeply after the last maternal glyburide intake. After 24 hours, the mean umbilical cord blood concentration was less than 5 ng/mL. Neonatal hypoglycemia risk was increased with an odds ratio of hypoglycemia equal to 3.70 [1.40–9.77] for each 10 ng/mL increase in the cord blood glyburide concentration. However, no newborns were admitted to the NICU because of clinical signs of hypoglycemia or for treatment of hypoglycemia. Considering that neonatal glyburide exposure may be limited by stopping treatment a sufficient time before labor, there may still be a place for glyburide in the management of gestational diabetes.