Contraceptive Use Measured in a National Population-Based Approach: Cross-Sectional Study of Administrative Versus Survey Data.

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.

The burden of very early dropout in infertility care: a nationwide population-based cohort study.

STUDY QUESTION: What is the frequency and the associated factors of very early dropout following unsuccessful clomiphene citrate (CC)/gonadotropin treatment in the context of full coverage of treatment cost. SUMMARY ANSWER: Despite free treatment, almost one in four women had a very early dropout following unsuccessful CC/gonadotropin treatment, with patients below the poverty line being more likely to drop out early. WHAT IS KNOWN ALREADY: Success of infertility care is tarnished by very high dropout rates. Infertility care dropout has been considered as resulting principally from financial barriers because of the high cost of treatment. Nearly all previous work addressed dropout following IVF/ICSI. Factors associated with dropout following CC/gonadotropins may be different and also need to be investigated. STUDY DESIGN, SIZE, DURATION: Nationwide population-based cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the French national health insurance and hospital databases, we included in the cohort 27 416 women aged 18-49 years unsuccessfully treated with CC/gonadotropins in 2017. The main outcome was very early dropout, defined as discontinuation of all infertility treatment after unsuccessful treatment for 1-3 months. Very early treatment dropout was analysed by multivariate logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Among women unsuccessfully treated with CC/gonadotropins, 22% dropped out of infertility care within 3 months. In multivariate analysis, higher early dropout following unsuccessful CC/gonadotropin treatment was associated with older and younger ages (≥35 and <25 years), being below the poverty line, being treated with CC prescribed by a general practitioner and lack of infertility tests or monitoring. LIMITATIONS, REASONS FOR CAUTION: This study is based on health administrative data that do not include reasons for dropout and record only a limited amount of information. It is thus not possible to analyse the reason for early dropout. WIDER IMPLICATIONS OF THE FINDINGS: Despite full coverage of all infertility treatment, women under the poverty line have a higher risk of very early dropout following unsuccessful CC/gonadotropin treatment. Better understanding is needed of the non-financial barriers and difficulties faced by these patients. To address disparities in infertility treatment, practitioner training could be reinforced to adapt to patients from different social and cultural backgrounds. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the ANR StimHo project, grant ANR-17-CE36-0011-01 from the French Agence Nationale de la Recherche. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Impact of oxygen tension during in vitro maturation: a sibling-oocyte prospective double-blinded study.

OBJECTIVE: To determine whether oxygen (O2) tension (20% vs. 5%) has an impact on oocyte maturation rates and morphology during in vitro maturation (IVM). DESIGN: A prospective, observational, monocentric, sibling-oocyte study. SETTING: University Hospital. PATIENTS: A total of 143 patients who underwent IVM for fertility preservation purposes from November 2016 to April 2021 were analyzed. Patients were included when ≥2 cumulus-oocyte complexes (COCs) were retrieved. The cohort of COCs obtained for each patient was randomly split into two groups: group 20% O2 and group 5% O2. INTERVENTION: Cumulus-oocyte complexes were incubated for 48 hours either under 5% O2 or 20% O2. After 24 and 48 hours of culture, every oocyte was assessed for maturity and morphology, to estimate oocyte quality. Morphology was evaluated considering six parameters (shape, size, ooplasm, perivitelline space, zona pellucida, and polar body characteristics), giving a total oocyte score ranging from -6 to +6. MAIN OUTCOME MEASURES: Maturation rates and total oocyte scores were compared using paired-sample analysis between group 20% O2 and group 5% O2. RESULTS: Patient median age was 31.4 [28.1-35.2] years-old. The mean serum antimüllerian hormone levels and antral follicle count were 3.2 ± 2.3 ng/mL and 27.2 ± 16.0 follicles, respectively. A mean of 10.7 COCs per cycle were retrieved, leading to 6.1 ± 2.4 metaphase II oocytes vitrified (total maturation rate = 57.3%; 991 metaphase II oocytes/1,728 COCs). A total of 864 COCs were included in each group. Oocyte maturation rates were not different between the two groups (group 20% O2: 56.82% vs. group 5% O2: 57.87%, respectively). Regarding oocyte morphology, the mean total oocyte score was significantly higher in group 5% O2 compared with group 20% O2 (3.44 ± 1.26 vs. 3.16 ± 1.32, P=.014). CONCLUSION: As culture under low O2 tension (5% O2) improves oocyte morphology IVM, our results suggest that culture under hypoxia should be standardized. Additional studies are warranted to assess the impact of O2 tension on oocyte maturation and the benefit of IVM under low O2 tension for embryo culture after utilization of frozen material.

Strong social disparities in access to IVF/ICSI despite free cost of treatment: a French population-based nationwide cohort study.

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.

Low-income women and use of prescribed contraceptives in the context of full health insurance coverage in France, 2019.

OBJECTIVE: Major socioeconomic differences in contraceptive use are observed in high-income countries. Cost is often cited as a main factor to explain these differences but other barriers may also exist. Our aim was to compare prescribed contraceptive use among low-income and non-low-income women in a national context of full health insurance coverage. STUDY DESIGN: In the French national health insurance database, we selected all women (14.8 million) aged 15-49 years living in France in 2019. We compared the prevalence of use of each prescribed contraceptive between low-income and non-low-income women: oral contraceptives, copper intrauterine devices (IUDs), the levonorgestrel intrauterine system (LNG-IUS), and implants. RESULTS: In the study population, 11% had a low income. Fewer low-income women used prescribed contraceptives than non-low-income women (36% vs. 46%, p < 0.001). When using a contraceptive, low-income women used a different method: at 20-24 years old, they used less oral contraceptives (60% vs. 77%, p < 0.001) and more implants (22% vs. 9%, p < 0.001), while at 40-44 years, they used less levonorgestrel intrauterine systems (18% vs. 30%, p < 0.001). CONCLUSIONS: Even in a national context of free access to medical care for low-income women, they use less and different prescribed contraceptives than non-low-income women. These results could reflect barriers other than financial cost to the use of prescribed contraceptives by low-income women. IMPLICATIONS: Financial barriers need to be removed in order to increase contraceptive use. However, this may not be sufficient and further research should explore barriers that low-income women may encounter in accessing and choosing their contraception.

Chronic conditions, subjective wellbeing and risky sexual behaviour among adolescents and young adults.

The purpose of this study is to clarify the relationship between having a chronic condition (CC) and several types of risky sexual behaviour (RSB) among adolescents and young adults. We used data from a multicentre cross-sectional study carried out on 14,431 adolescents from 137 French schools. Logistic regression was used to assess the association between several types of RSB and CCs among the 2680 participants aged 17 years or over who reported sexual intercourse. Survival analysis was conducted to assess the association between CCs and age at first sexual intercourse across the whole sample. Analyses were conducted separately by gender with and without adjustment for the parents' education level, early menarche and subjective wellbeing (relationship with mother and father, depression, perceived health status and liking school). Among boys, having a CC was associated with a higher risk of RSB in both univariate (OR: 1.58 [95% CI: 1.10-2.27]) and multivariate analyses (aOR: 1.62 [95% CI: 1.11-2.38]). Among girls, the association between chronic condition and RSB in univariate analysis was non-significant (OR: 1.30 [95% CI: 0.97-1.76]) and disappeared after adjustment on subjective wellbeing (aOR: 1.08 [95% CI: 0.78-1.49]). There was no association between CC and age at first sexual intercourse.    Conclusion: There were major gender differences. Boys with a CC were more prone to engage in RSB independent of their subjective wellbeing, whereas in girls, subjective wellbeing seemed to mediate the relationship between CC and RSB. Clinicians should be aware of those gender differences in order to deliver preventive strategies regarding sexuality that target both genders. What is Known: • Young people with chronic conditions have a higher likelihood of engaging in risky sexual behaviour. • Engaging in such behaviours can be much more costly, as it can weaken their underlying state of health. What is New: • We found major gender differences. Boys were more prone to engage in risky behaviour independent of their subjective wellbeing, whereas in girls, it seemed to play an important role. • By understanding how risky sexual behaviour differs according to gender, clinicians can deliver prevention messages that target both genders.

Is gestational age at term a risk factor for ongoing pregnancies in nulliparous women: A prospective cohort study.

BACKGROUND: The results of American observational studies and 1 large, randomized trial show that elective induction of labor among nulliparous women can reduce cesarean delivery rates and suggest that gestational age at delivery may be a risk factor for cesarean delivery in pregnancies managed expectantly. However, data on the risk of cesarean delivery at term in ongoing pregnancies are sparse, especially in high-income countries, and further information is needed to explore the external validity of these previous studies. OBJECTIVE: This study aimed to evaluate the risk of cesarean delivery for each gestational week of ongoing pregnancy in nulliparous women with a singleton fetus in the cephalic presentation at term in a French population. STUDY DESIGN: This retrospective study was conducted in a perinatal network of 10 maternity units from January 1, 2016, to December 31, 2017, and included all nulliparous women with a singleton fetus in the cephalic presentation who gave birth at term (≥37 0/7 weeks of gestation). From the start of term (37 completed weeks) and at the start of each subsequent week of completed gestation (each week + 0 days), ongoing pregnancy was defined as that of a woman who was still pregnant and who gave birth at any time after that date. For each week of gestation for these ongoing pregnancies, the cesarean delivery rate was defined as the number of cesarean deliveries performed in each ongoing pregnancy group divided by the number of women in this group. Separate models for each week of gestation, adjusted by maternal characteristics and hospital status, were used to compare the cesarean delivery risk between ongoing pregnancies and those delivered the preceding week. The same methods were applied to subgroups defined according to the mode of labor onset. Odds ratios were calculated after adjusting for maternal age and educational level, presence of severe preeclampsia, and maternity unit status. RESULTS: The study included 11,308 nulliparous women, 2544 (22.5%) of whom had a cesarean delivery. These rates remained stable for ongoing pregnancies at 37 0/7, 38 0/7, and 39 0/7 weeks of gestation; the rates were 22.5% (95% confidence interval, 21.7-23.2), 22.6% (95% confidence interval, 21.8-23.3); and 22.7% (95% confidence interval, 21.9-23.6), respectively. The risk of cesarean delivery started to increase in ongoing pregnancies at 40 0/7 weeks of gestation (24.3%; 95% confidence interval, 23.1-25.4) and especially at 41 0/7 weeks of gestation (30.7%; 95% confidence interval, 28.9-32.5). Similar trends were also shown for all modes of labor onset and in every maternity unit. In univariate and multivariate analyses, ongoing pregnancy at or beyond 40 0/7 weeks of gestation was associated with a higher risk of cesarean delivery than pregnancy delivered the previous week: 24.3% of ongoing pregnancies at 40 0/7 weeks of gestation vs 19.9% of deliveries between 39 0/7 weeks of gestation and 39 6/7 weeks of gestation. The odds ratios were 1.28 (95% confidence interval, 1.15-1.44) or 30.4% of ongoing pregnancies at 41 0/7 weeks of gestation vs 1.73 (95% confidence interval, 1.51-1.96) or 19.6% of deliveries between 40 0/7 weeks of gestation and 40 6/7 weeks of gestation. CONCLUSION: Cesarean delivery rates increased starting at 40 0/7 weeks of gestation in ongoing pregnancies regardless of the mode of labor onset.

Impact of the 1st Wave of the COVID-19 Pandemic and Lockdown on In Utero Transfer Activity in the Paris Area, France.

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.

Risk of hypoglycemia by anthropometric measurements in neonates of mothers with diabetes.

Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. This study aimed to study the association between anthropometric measurements and hypoglycemia in neonates of mothers treated for gestational diabetes. This is a secondary analysis of the INDAO trial study conducted between May 2012 and November 2016 in 13 French tertiary care university hospitals in 890 pregnant women with gestational diabetes treated with either insulin or glyburide. Neonatal anthropometric measurements were birthweight and weight-length ratio (WLR, defined as birth weight/length). Neonatal hypoglycemia was defined as capillary blood glucose below 36 mg/dL (2 mmol/L) or below 45 mg/dL (2.5 mmol/L) associated with clinical signs after 2 h of life. Their relationships were modeled with logistic regressions using fractional polynomials. Extreme categories of birthweight or WLR adjusted for gestational age at birth and sex were defined as Z-score < -1.28 or > 1.28. These categories were compared to Z-score between -1.28 and 1.28 by estimating odds ratios and confidence intervals for neonatal hypoglycemia. Neonatal hypoglycemia occurred in 9.1% of cases. The relationship between birthweight and WLR Z-scores and neonatal risk of hypoglycemia adjusted for maternal treatment was a U-shaped curve. Adjusted odds ratios for the risk of hypoglycemia were 9.6 (95% CI 3.5, 26.8) and 2.3 (95% CI 1.1, 4.9) for WLR Z-score below -1.28 and above 1.28, respectively, compared with WLR Z-score between -1.28 and 1.28.    Conclusion: Birthweight Z-score was associated with the risk of neonatal hypoglycemia in neonates from mothers treated for gestational diabetes. The risk of neonatal hypoglycemia was increased for both extreme birthweight Z-scores, regardless of maternal treatment. Small for gestational age neonates of diabetic mothers require special attention for the risk of neonatal hypoglycemia. What is Known: • Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. Few retrospective studies have assessed the risk for neonatal hypoglycemia among small for gestational age neonates born to diabetic mothers. What is New: • The risk of neonatal hypoglycemia among neonates of diabetic mothers increased for both low and high weight-length ratio, regardless of maternal medicinal treatment, gestational age at birth, and sex of the newborn.

Cesarean section rate changes after audit and feedback with the Ten Group Classification System in a French perinatal network: A retrospective pre-post study.

INTRODUCTION: The rise in the number of cesarean sections (CS) is a major health public problem which concerns nearly all countries. It is suggested that the Ten Group Classification System be adapted to a procedure of audit/feedback cycles, which could have an effect on CS practice. Therefore, we aimed to study changes in CS rates between maternity wards in a perinatal network after implementation of the Ten Group Classification System in an audit with feedback. MATERIAL AND METHODS: This was a retrospective pre-post study of all births from 1 January 2012 to 31 December 2018, in a French perinatal network of 10 maternity wards in the Yvelines district of France. All live births occurring at a gestational age ≥24 weeks in the network were included. During the pre-period (1 January 2012 to 31 December 2014), the audit and feedback provided only overall CS rates. During the post-period (1 January 2015 to 31 December 2018), CS rates for each Robson Ten Group Classification System group were provided. Regression models, adjusted for maternal characteristics and maternity ward, were used to compare CS rates globally and for each group of the system. Variability of CS rates between maternity wards was analyzed using the coefficients of variation. RESULTS: There were 51 082 women who delivered during the pre-period and 63 964 during the post-period. The overall CS rate did not decrease (24.5% during the pre-period vs 25.1% during the post-period). There were no significant differences in CS rates for any group of the Ten Group Classification System after adjustment for maternity, maternal age and sociodemographic characteristics, nor did audit implementation decrease CS rate variability between maternity wards or within groups of the system. CONCLUSIONS: Implementation of an audit-and-feedback cycle using the Ten Group Classification System did not decrease either CS rates or variability between maternity wards.

Impact of COVID-19-Related Lockdown on Delivery and Perinatal Outcomes: A Retrospective Cohort Study.

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.

Impact of maternal age on obstetric and neonatal morbidity: a retrospective cohort study.

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.

Clinical course and cost assessment of infants with a first episode of acute bronchiolitis presenting to the emergency department: Data from the GUERANDE clinical trial.

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.

Variation between hospital caesarean delivery rates when Robson's classification is considered: An observational study from a French perinatal network.

INTRODUCTION: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: The global CD rate was 24.0% (interhospital range: 17-32%). CD rates within each TGCS group differed significantly between hospitals (P<0.001). CD was significantly associated with maternal age (>40 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%. CONCLUSION: 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.

Hypoglycemia and Glycemic Control With Glyburide in Women With Gestational Diabetes and Genetic Variants of Cytochrome P450 2C9 and/or OATP1B3.

Glyburide is mainly metabolized by the cytochrome P450 2C9 (CYP2C9) enzyme and enters the liver via the transporter OATP1B3. The variants OATP1B3*4 (699 G>A; rs7311358) and CYP2C9*2 and *3 are known to have a significant influence on the hepatic uptake and metabolism of glyburide, with lower clearance than in the wild type. In an ancillary study of the INDAO trial, we selected 117 pregnant women with gestational diabetes treated by glyburide and assessed the role of the combined CYP2C9 and OATP1B3 genetic polymorphisms in hypoglycemia and glycemic control. Three groups were constituted: (1) the wild-type genotype group (wild-type allele genotype for both CYP2C9*1 and OATP1B3*1 (699G)), (2) the intermediate group (carriers of CYP2C9*2 allele or OATP1B3*4 (699G>A) heterozygous), and (3) the variant group (carriers of CYP2C9*3 allele and/or OATP1B3*4 (699G>A) homozygous variant). We found that the risk of hypoglycemia was significantly higher in the variant genotype at the second week of treatment: 20.0% (4/20) vs. 8.1% (3/37) in the intermediate group and 4.1% (2/49) in the wild-type genotype group (P = 0.03). The last daily dose of glyburide during pregnancy was lower for patients in the variant genotype group: 4.7 mg (SD 3.5) vs. 8.7 mg (SD 5.7) in the wild-type group and 5.7 mg (SD 3.7) in the intermediate group (P < 0.01). In conclusion, the no-function variants CYP2C9*3 and OATP1B3*4 are associated with a higher risk of hypoglycemia and a lower dose of glyburide in women with gestational diabetes treated with glyburide, which is consistent with the pharmacokinetic roles of both CYP2C9 and OATP1B3.

Glyburide therapy for gestational diabetes: Glycaemic control, maternal hypoglycaemia, and treatment failure.

AIMS: The recommended first-line treatment for women with gestational diabetes mellitus (GDM) in the case of failure of diet is insulin. Recent results suggest that there is a potential role for glyburide therapy and highlight the need for better knowledge of glycaemic control with glyburide. The objective of this study was to describe and quantify in women with GDM the quality of glycaemic control, including the risk of maternal hypoglycaemia and of therapy failure. METHODS: This is a secondary analysis of the French INDAO non-inferiority trial from 2012 to 2016, in which 890 women with GDM randomized to receive glyburide or insulin treatment were compared for perinatal outcomes. Blood glucose concentrations were assessed prospectively during pregnancy. Optimal glycaemic control was defined as less than 20% of blood glucose values exceeding the targets. RESULTS: More than 50% of the women had optimal glycaemic control with glyburide, similar to that with insulin. Around 40% of the women had at least one episode of hypoglycaemia, more than with insulin. However, those hypoglycaemic episodes were mostly moderate and the rate of severe hypoglycaemia decreased significantly during the course of the trial. Failure of glyburide treatment (switch to insulin therapy) occurred in 18% of women and had few predictors. However, when failure occurred, glycaemic control was improved after switching to insulin. CONCLUSIONS: Glyburide is an effective treatment for reaching glycaemic goals during pregnancy in women with GDM. The risk of maternal hypoglycaemia may be minimized by clinical practice experience. These findings could be taken into account in the management of GDM.

Infertility Treatment in France, 2008-2017: A Challenge of Growing Treatment Needs at Older Ages.

Objectives. To measure trends in infertility treatment use between 2008 and 2017 in France using data from the national health insurance system.Methods. Between 2008 and 2017, we observed a representative national sample of nearly 1% of all women aged 20 to 49 years who were affiliated with the main health insurance scheme in France (more than 100 000 women observed each year). We exhaustively recorded all health care reimbursed to these women.Results. Among women aged 20 to 49 years, 1.25% were treated for infertility each year. Logistic regression analysis showed a significant interaction between age and year of treatment use (P < .001). Over the decade, infertility treatment use increased by 23.9% among women aged 34 years or older, whereas among women younger than 34 years there was a nonsignificant variation.Conclusions. Women aged 34 years or older were increasingly treated for infertility between 2008 and 2017.Public Health Implications. Treatment efficiency decreases strongly with a woman's age, presenting a challenge for medical infertility care.

Transplacental transfer of glyburide in women with gestational diabetes and neonatal hypoglycemia risk.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSION: 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.

Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial.

Importance: Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. Objective: To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. Design, Settings, and Participants: The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Interventions: Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. Main Outcomes and Measures: The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. Results: Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19). Conclusion and Relevance: This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01731431.