Patisiran exposure in early pregnancy: a case report.

We describe here the first case of exposure to patisiran treatment, a small interfering RNA molecule, during early pregnancy of a 36-year-old woman with symptomatic hereditary transthyretin-related amyloidosis. There were no major complications during pregnancy and delivery, except for a postpartum hemorrhage due to uterine atony. Vitamin A levels had to be closely monitored during pregnancy, and vitamin A substitution adapted accordingly. There was no sign of minor or major congenital abnormalities of the baby. One month after delivery, the patient showed slight clinical and electrophysiological signs of neuropathy progression due to patisiran treatment withdrawal. Patisiran infusions were resumed 3 months after delivery. Due to the unknown teratogenic potential of patisiran, the risk of neuropathy worsening associated with withholding treatment must of course be weighed against a potential teratogenic risk of treatment during pregnancy. Vitamin A levels need to be closely assessed, and substitution must be adapted accordingly, to avoid embryofetal adverse outcome due to vitamin A deficiency or toxicity.

[Pregnancy and bariatric surgery : from pre-conception to postpartum]. / Grossesse et chirurgie bariatrique : du préconceptionnel au postpartum.

Bariatric surgery is regularly offered to women of childbearing age. Pregnancy after such surgery should be planned and requires special attention. Some complications associated with obesity during pregnancy are reduced after bariatric surgery, but reduced dietary intake and malabsorption can cause nutritional deficiencies, that need to be carefully screened for and supplemented. Dietary management is recommended, and any unusual abdominal pain should be referred to a bariatric surgeon. We offer a summary of recommendations for appropriate follow-up of these pregnancies.

La chirurgie bariatrique est régulièrement proposée à des femmes en âge de procréer. Une grossesse après une telle chirurgie devrait être planifiée et demande une attention particulière. Certaines complications liées à l'obésité durant la grossesse sont réduites après une chirurgie bariatrique mais une diminution des apports alimentaires et la malabsorption peuvent engendrer des carences nutritionnelles qui doivent être attentivement dépistées et supplémentées. Une prise en charge diététique est recommandée et toute douleur abdominale inhabituelle doit faire demander l'avis d'un chirurgien bariatrique. Nous proposons une synthèse des recommandations pour un suivi adéquat de ces grossesses.

[Hematological workup in cases of recurrent early miscarriages: what evidences?] / Bilan hématologique en cas de fausses couches précoces à répétition : quelles évidences ?

Recurrent miscarriages have a major psychological and somatic impact, as well as a significant economic burden. An etiological work-up should be offered after two or three miscarriages, the threshold varying from one scientific society to another. However, the proposed biological work-up must be justified by scientific evidence. A simple blood count, basic coagulation tests including fibrinogen assay and anti-phospholipid antibodies testing should be performed initially. Hereditary thrombophilia testing should only be carried out if there is a history of maternal thrombosis. In the event of an abnormality, management should be multidisciplinary, and the prescription of medication should follow recommended guidelines. Prophylactic treatment is not justified in the absence of a known etiology.

Les fausses couches précoces (FCP) à répétition ont un impact psychologique et somatique important, ainsi qu'un poids économique non négligeable. Un bilan étiologique devrait être proposé à partir de deux ou trois fausses couches, le seuil variant selon les sociétés savantes. Cependant, le bilan biologique doit être justifié par des évidences scientifiques. Une formule sanguine simple, des tests de coagulation de base avec le dosage du fibrinogène et une recherche d'anticorps anti-phospholipides devraient être réalisés en première intention. Une recherche de thrombophilie héréditaire ne devrait être effectuée qu'en cas d'antécédent thrombotique maternel. En cas d'anomalie, la prise en charge doit être multidisciplinaire et la prescription de médicaments doit suivre les recommandations. Un traitement prophylactique n'est pas justifié en l'absence d'étiologie retrouvée.

What do mothers think about their antenatal classes? A mixed-method study in Switzerland.

PROBLEM: Research so far has evaluated the effect of antenatal classes, but few studies have investigated its usefulness from the perspective of mothers after birth. BACKGROUND: Antenatal classes evolved from pain management to a mother-centred approach, including birth plans and parenting education. Evaluating the perception of the usefulness of these classes is important to meet mother's needs. However, so far, research on the mothers' perception of the usefulness of these classes is sparse, particularly when measured after childbirth. Given that antenatal classes are considered as adult education, it is necessary to carry out this evaluation after mothers have had an opportunity to apply some of the competences they acquired during the antenatal classes during their childbirth. AIM: This study investigated mothers' satisfaction and perceived usefulness of antenatal classes provided within a university hospital in Switzerland, as assessed in the postpartum period. METHODS: Primiparous mothers who gave birth at a Swiss university hospital from January 2018 to September 2020 were contacted. Those who had attended the hospital's antenatal classes were invited to complete a questionnaire consisting of a quantitative and qualitative part about usefulness and satisfaction about antenatal classes. Quantitative data were analysed using both descriptive and inferential statistics. Qualitative data were analysed using thematic analysis. FINDINGS: Among the 259 mothers who answered, 61% (n = 158) were globally satisfied with the antenatal classes and 56.2% (n = 145) found the sessions useful in general. However, looking at the utility score of each theme, none of them achieved a score of usefulness above 44%. The timing of some of these sessions was questioned. Some mothers regretted the lack of accurate information, especially on labour complications and postnatal care. DISCUSSION: Antenatal classes were valued for their peer support. However, in their salutogenic vision of empowerment, they did not address the complications of childbirth, even though this was what some mothers needed. Furthermore, these classes could also be more oriented towards the postpartum period, as requested by some mothers. CONCLUSION: Revising antenatal classes to fit mothers' needs could lead to greater satisfaction and thus a better impact on the well-being of mothers and their families.

Pregnancy after kidney transplantation: an observational study on maternal, graft and offspring outcomes in view of current literature.

Introduction: Pregnancy after kidney transplantation (KTx) is considered to have a high risk of non-negligible complications for the mother, the allograft, and the offspring. With an increased incidence of these pregnancies over the past decades, transplant nephrologists and specialized obstetricians face increasing challenges, with scarce literature regarding long-term outcomes. Methods: We retrospectively collected data from all women with at least one live birth pregnancy after KTx who were followed at our tertiary hospital between 2000 and 2021 to study maternal, graft and fetal outcomes. Results: Ten patients underwent 14 live birth pregnancies after KTx. Preponderant maternal complications were stage 1 acute kidney injury (43%), urinary tract infections (UTI, 43%), progression of proteinuria without diagnostic criteria for preeclampsia (29%), and preeclampsia (14%). Median baseline serum creatinine at conception was 126.5 µmol/L [median estimated glomerular filtration rate (eGFR) 49 mL/min/1.73m2], and eGFR tended to be lower than baseline at follow-ups. Overall, there was no increase in preexisting or occurrence of de novo donor-specific antibodies. No graft loss was documented within the 2-year follow-up. There were nine premature births (64%), with a median gestational age of 35.7 weeks. The median birth weight, height, and head circumference were 2,560 g, 45.5 cm, and 32.1 cm, respectively. These measurements tended to improve over time, reaching a higher percentile than at birth, especially in terms of height, but on average remained under the 50th percentile curve. Discussion: Overall, pregnancies after KTx came with a range of risks for the mother, with a high prevalence of cesarean sections, emergency deliveries, UTI, and preeclampsia, and for the child, with a high proportion of prematurity, lower measurements at birth, and a tendency to stay under the 50th percentile in growth charts. The short- and long-term impact on the allograft seemed reassuring; however, there was a trend toward lower eGFR after pregnancy. With these data, we emphasize the need for a careful examination of individual risks via specialized pre-conception consultations and regular monitoring by a transplant nephrologist and a specialist in maternal-fetal medicine during pregnancy. More data about the long-term development of children are required to fully apprehend the impact of KTx on offspring.

Early noninvasive prenatal paternity testing by targeted fetal DNA analysis.

Today the challenge in paternity testing is to provide an accurate noninvasive assay that can be performed early during pregnancy. This requires the use of novel analytical methods capable of detecting the low fraction of circulating fetal DNA in maternal blood. We previously showed that forensic compound markers such as deletion/insertion polymorphisms-short tandem repeats (DIP-STR) can efficiently resolve complex mixed biological evidence including the target analysis of paternally inherited fetal alleles. In this study, we describe for the first time the validation of this type of markers in the first trimester of pregnancies, in addition to defining the statistical framework to evaluate paternity. To do so, we studied 47 DIP-STRs in 87 cases, with blood samples collected throughout gestation starting from the seven weeks of amenorrhea. Fetal DNA detection in the first trimester shows a false negative rate as low as 6%. The combined paternity index (CPI) results indicate that seven markers with fully informative genotypes are sufficient to determine the paternity. This study demonstrates that DIP-STR markers can be used from early pregnancy and that a small set of markers (about 40) is sufficient to address the question of paternity. The novel method offers substantial improvements over similar approaches in terms of reduced number of markers, lower costs and increased accuracy.

[Pregnancy and chronic renal failure: what is new in 2023?] / Grossesse et insuffisance rénale chronique : quelle prise en charge en 2023 ?

Chronic renal failure (CRF) during pregnancy increases the risk of fetomaternal complications such as preeclampsia, premature delivery and, above all, a deterioration of renal function. A multidisciplinary preconceptional assessment is necessary in this complex clinical situation. Progress in neonatal resuscitation and a better understanding of the pathophysiological mechanisms of autoimmune nephropathy have improved the prognosis of these high-risk pregnancies. This article provides an overview of the issues related to the follow-up of pregnant women with renal disease. It summarizes the glomerular and hemodynamic physiological changes during pregnancy, the fetal and maternal risk, and the adaptation of antihypertensive and immunosuppressive drug treatments.

La présence d'une insuffisance rénale chronique (IRC) lors d'une grossesse augmente le risque de complications fœto-maternelles, comme une prééclampsie, un accouchement prématuré et surtout une péjoration de la fonction rénale. Un bilan préconceptionnel multidisciplinaire permet d'optimiser une situation clinique complexe. Les progrès de la réanimation néonatale et une meilleure compréhension des mécanismes physiopathologiques des néphropathies auto-immunes permettent une amélioration du pronostic de ces grossesses à risque. Cet article donne une vue d'ensemble des problématiques liées au suivi des femmes enceintes souffrant d'une maladie rénale. Il résume les modifications physiologiques glomérulaires et hémodynamiques durant la grossesse, le risque fœto-maternel ainsi que l'adaptation des traitements médicamenteux antihypertenseurs et immunosuppresseurs.

Safety and efficacy of a suction cervical stabilizer for intrauterine contraceptive device insertion: Results from a randomized, controlled study.

OBJECTIVES: To compare patient-reported pain, bleeding, and device safety between intrauterine contraceptive device (IUD) insertion procedures employing a suction cervical stabilizer or single-tooth tenaculum. STUDY DESIGN: This was a randomized, prospective, single-blinded study conducted at two centers, enrolling women aged 18 years or older, eligible for IUD insertion. The primary end point measure was patient-reported pain, measured on a 100-mm Visual Analogue Scale. Safety was assessed on the amount of bleeding, adverse events, and serious adverse events. RESULTS: One hundred women were randomized, 48 to the investigational device and 52 to control. There were no statistically significant differences between the groups in factors potentially associated with pain on IUD insertion. IUD insertion was successful in 94% of all subjects. Subjects in the investigational device group reported pain scores ≥14 points lower than in the control group at cervix grasping (14.9 vs 31.3; p < 0.001) and traction (17.0 vs 35.9; p < 0.001), and smaller differences in pain scores at the IUD insertion (31.5 vs 44.9; p = 0.021) and cervix-release (20.6 vs 30.9; p = 0.049) steps. Nulliparous women experienced the greatest pain differences to control. Mean blood loss was 0.336 (range 0.022-2.189) grams in the investigational device group and 1.336 (range 0.201-11.936) grams in the control group, respectively (p = 0.03 for the comparison). One adverse event (bruising and minor bleeding) in the investigational device group was considered causally related to the study device. CONCLUSIONS: The suction cervical stabilizer had a reassuring safety profile and its use was associated with significant reductions in pain during the IUD insertion procedure compared with standard single-tooth tenaculum use, particularly among nulliparous women. IMPLICATIONS: Pain can be an important barrier to greater use of IUD devices among prescribers and users, particularly nulliparous women. The suction cervical stabilizer may provide an appealing alternative to currently available tenacula, filling an important unmet need.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

[Trial of labour after c-section in 2022: a narrative review of the literature]. / Accouchement vaginal après une césarienne en 2022 : revue narrative de la littérature.

One in three women in Switzerland gives birth by c-section. This high incidence of c-section frequently exposes obstetricians and midwives to the management of women and their deliveries with a scarred uterus. The decision of couples is multifactorial, but the information that will be delivered by their gynaecologist will necessarily influence the delivery route choice. We propose to review the international recommendations and the literature on the subject, to provide the couple and the attending physician with elements of reflection to guide the choice of delivery route or to monitor adequately when attempting vaginal delivery after a caesarean section.

En Suisse, une femme sur trois donne naissance à son enfant par césarienne. Cette forte incidence de la césarienne expose régulièrement les obstétriciens et les sages-femmes à la gestion de femmes et de leur accouchement avec un utérus cicatriciel. La décision des couples est multifactorielle, mais l'information qui sera délivrée par leur gynécologue va nettement influencer le choix de la voie d'accouchement. Nous proposons ici de passer en revue les recommandations internationales et la littérature sur le sujet, afin de procurer les éléments de réflexion au couple et au médecin traitant afin de guider le choix de la voie d'accouchement et de monitorer adéquatement au cours d'une tentative d'accouchement par voie basse.

[Access to donor human milk in Switzerland and CHUV's first human milk bank in Romandy : issues and perspectives]. / Pédiatrie - Accès au lait de donneuses en Suisse et création de la première banque de lait maternel romande au CHUV : enjeux et perspectives.

Mother's own milk (MOM) is ideal for infant growth and health. When MOM is unavailable, donor human milk (DHM), rather than infant formula, is recommended for at-risk, preterm or sick neonates (NN), in view of its protective effects. Human milk banks (HMB) collect, secure, process and distribute DHM. In Switzerland, there is insufficient and unequal access to DHM in the absence of a national policy framework. With the support of the State of Vaud, the CHUV and the Interregional Blood Transfusion of the Swiss Red Cross will open the first HMB in Romandy in 2022. This HMB offers an innovative system in Switzerland, based on complementary expertise, in order to guarantee the quality and safety of DHM and to support the promotion of breastfeeding and human milk donation.

Le lait maternel (LM) est idéal pour la croissance et la santé des nourrissons. En l'absence de LM, le lait de donneuses (LD) est préférable au lait artificiel pour les nouveau-nés (NN) à risques, prématurés ou présentant certaines pathologies, au vu de ses effets protecteurs. Les banques de lait (BL) collectent, sécurisent, traitent et distribuent le LD. Il existe en Suisse une insuffisance et une inégalité d'accès au LD, faute de cadre national. Avec le soutien de l'État de Vaud, le CHUV et la Transfusion interrégionale de la Croix-Rouge suisse ouvriront en 2022 la première BL romande. Cette BL propose un système novateur en Suisse, fondé sur une complémentarité d'expertises, afin d'optimiser la qualité et la sécurité du LD et de soutenir la promotion de l'allaitement et du don.

Safety and Efficacy of an Atraumatic Uterine Cervical Traction Device: A Pilot Study.

Introduction: Alignment of the uterine cervix with the vaginal canal is often required during insertion of an intrauterine contraceptive device (IUD). Currently available instruments are traumatic tenacula, which can cause pain and bleeding and represent an obstacle for certain patients to pursue their medical follow-up. A novel investigational cervical vacuum tenaculum, enables atraumatic traction of the cervix using a semi-circular suction pad, designed to conform to the anatomical shape of the external cervical os. Suction is generated by manually pulling out a sliding tube in a vacuum chamber. Methods: We performed a single arm non-comparative pilot study to assess the safety and efficacy of the cervical vacuum tenaculum in 13 women receiving an IUD. Data on procedural efficacy, safety, patient-reported pain scores at specific time points during IUD insertion procedure and patient satisfaction were collected prospectively. Results: Insertion of IUD was successful with use of the study device in 7 of the 13 enrolled patients (54%). No bleeding or only limited ecchymosis were caused by the device. No adverse events were reported. Participants reported very little pain (mean Visual Analog Scale <10) when applying the device. Participants who achieved IUD insertion with the device reported strong overall satisfaction with the procedure. Conclusions: The suction-based atraumatic tenaculum can be used to manipulate the cervix during IUD insertion with satisfactory efficacy and safety. The results of this pilot study support further studies of this device in larger populations comparing with standard single-tooth tenaculum. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04441333.

Carbetocin versus Oxytocin for the Prevention of Postpartum Hemorrhage in Cesarean Deliveries: A Retrospective Study of Two Consecutive Periods.

Objective The aim of the study is to investigate whether carbetocin prevents postpartum hemorrhage (PPH) more effectively than oxytocin Methods This historical retrospective single-center cohort study compares women who underwent cesarean deliveries during two periods. During period A, oxytocin was used as a 10-unit bolus immediately after delivery, with 20 units thereafter infused for 24 hours. During period B, carbetocin in a single 100-µg injection replaced this protocol. The main outcome was PPH, defined as a decline in hemoglobin of more than 2 g/dL after the cesarean. The analysis was performed on the overall population and then stratified by the timing of the cesareans (before or during labor). A logistic regression analysis was performed. Results This study included 1,796 women, 52% of whom had a cesarean before labor; 15% had a PPH. The crude PPH rate was lower in period B than in period A (13 vs. 17%, respectively, odds ratio 0.75, 95% confidence interval [CI]: 0.58-0.98). The difference was no longer significant in the multivariate analysis (adjusted odds ratio: 0.81, 95% CI 0.61-1.06). Results were similar when stratified by the timing of the cesareans (before or during labor). Conclusion Carbetocin is not superior to oxytocin in preventing PPH. However, it does provide the advantage of requiring a single injection.

[Perinatal care for extremely preterm labor between 23 and 26 weeks : management in CHUV]. / Menace sévère d'accouchement entre 23 et 26 SA†: algorithme de prise en charge obstétrico-néonatale au CHUV.

Management of patients at high risk of extreme premature birth between 23 and 26 weeks should be performed by an experienced multidisciplinary team. In order to optimize guidance for couples with regard to this complex decision, we developed joint guidelines between obstetricians and neonatologists, in order to standardize practices and insure individualized care plans. Fetal outcome is not solely associated with gestational age but is multifactorial, and this should be considered when counseling parents. Thus, enhancement of fetal lung maturation, a major prognostic factor, should be promptly acted upon when delivery is anticipated. Antenatal corticosteroids should not be withheld while awaiting the parents' ultimate decision on neonatal care.

La prise en charge des patientes à haut risque d'accouchement prématuré entre 23 et 26 semaines d'aménorrhée (SA) doit être faite par une équipe périnatale expérimentée. Afin d'améliorer la prise en charge des couples dans cette situation particulièrement difficile, nous avons élaboré un protocole commun entre obstétriciens et néonatologues. Cette réflexion vise à uniformiser les pratiques au sein du CHUV et à assurer aux couples des soins personnalisés. Le pronostic fœtal ne dépend pas uniquement de l'âge gestationnel mais d'un ensemble de facteurs dont il est important de tenir compte dans la discussion avec les parents. Ainsi la corticothérapie, facteur pronostique majeur, doit être réalisée le plus rapidement possible en cas de menace sévère. L'injection ne doit pas être différée par la réflexion des couples sur les soins néonataux.

Evaluation of the implementation of a protocol for the restrictive use of oxytocin during spontaneous labor.

INTRODUCTION: Use of oxytocin is associated with uterine hyperstimulation and postpartum hemorrhage with a dose-dependent effect. We aimed to evaluate the effect of the implementation of a protocol for the restrictive use of oxytocin during spontaneous labor on obstetric and neonatal outcomes. MATERIAL AND METHODS: We performed an observational before-and-after study among 2174 women in spontaneous labor with a term singleton cephalic fetus. Obstetric and neonatal outcomes were compared according to the period, before (period A) and after (period B) the implementation of a protocol for the restrictive use of oxytocin. RESULTS: 1235 women were included in period A and 939 in period B. Compared to period A, the use of oxytocin during period B was significantly lower (45.5 vs. 35.1%, p<0.001) in both nulliparous (61.2 vs 54.6%, p=0.04) and multiparous women (34.0 vs. 21.1%, p<0.001). Labor was significantly longer in period B, both in nulliparous (6.7 vs. 7.9 h, p<0.01) and multiparous women (4.1 vs. 4.5 h, p<0.01). A lower frequency of uterine hyperstimulation (6.6 vs. 2.7%, p=0.01) was observed in period B. The odds of instrumental and cesarean delivery were not different between the periods (respectively adjusted odds ratio (AOR), 95% confidence interval (CI), 1.1(0.8-1.4); 1.2(0.8-1.8)) including for nulliparous women (respectively, 1.3(0.9-1.7); 1.3(0.8-1.9)). DISCUSSION: Reducing the use of oxytocin during spontaneous labor through the implementation of a protocol may reduce the iatrogenic effects without increasing the risk of caesarean section but this implies longer duration of labor.

[Preconception care in patients with diabetes]. / Prise en charge préconceptionnelle chez une patiente avec un diabète préexistant.

In patients with diabetes, pregnancy is associated with high maternal and fetal risks, especially in unplanned pregnancies. Current evidence confirms that timely family planning and interdisciplinary care and management starting at the preconceptional period can optimize metabolic control and significantly reduce these risks. The purpose of this article is to summarize the different aspects to consider as well as provide tools to use when preparing patients with diabetes for a pregnancy.

Chez les patientes diabétiques, la grossesse est associée à des hauts risques materno-fœtaux, notamment lorsqu'elle n'est pas planifiée. L'évidence actuelle confirme que la planification familiale opportune ainsi qu'une prise en charge interdisciplinaire depuis la période préconceptionnelle permettent d'optimiser le contrôle métabolique et de diminuer ces risques de façon significative. Le but de cet article est de résumer les différents aspects à considérer ainsi que de fournir des outils à utiliser lors de la préparation des patientes avec un diabète à une grossesse.

Impact of Roux-en-Y gastric bypass and sleeve gastrectomy on fetal growth and relationship with maternal nutritional status.

BACKGROUND: There is a lack of evidence on whether sleeve gastrectomy (SG), which induces fewer nutritional deficiencies than Roux-en-Y gastric bypass (RYGB), also affects fetal growth (FG). OBJECTIVES: To compare neonatal outcomes after RYGB and SG and to assess the impact of maternal nutritional alterations on FG after both procedures. SETTING: University Hospital, France. METHODS: Women with singleton pregnancies who had at least 1 nutritional evaluation in our institution between 2004 and 2017 were included. FG was assessed with birth weight (BW) and BW-Z score (adjusted for sex and term), and maternal nutritional deficiencies were defined according to standard and pregnancy-specific norms. RESULTS: During the study period 123 pregnancies were included, 77 after RYGB and 46 after SG. Weight loss was higher after RYGB than after SG (45.6 ± 12.4 versus 39.5 ± 13.7 kg, P = .02), but mean weight before pregnancy and weight gain during pregnancy were similar. Mean BW (3026 ± 677 versus 3162 ± 712 g), mean BW Z-score and incidence of small for gestational age (24% versus 19%) were not significantly different after RYGB and SG. Mean number of nutritional deficiencies during the second trimester was similar (2.2 ± 1.5 versus 2.1 ± 1.2 with specific norms), but the affected parameters differed between procedures. Urinary urea (R = .285, P = .04) was positively correlated to BW Z-score after both procedures. In contrast, serum iron parameters were negatively associated to BW Z-score. CONCLUSION: FG restriction occurs after both SG and RYGB. FG after bariatric surgery is positively associated with protein supply and negatively correlated with maternal iron status.

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.