For thirty years, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network has had significant impact on clinical practice in obstetrics. The MFMU Network has conducted 50 randomized clinical trials and observational studies designed to improve pregnancy outcomes for mothers and children. Each center has a designated clinical research nurse coordinator who coordinates the day-to-day operations of each trial and leads a research team that is responsible for recruitment, and retention, of participants. Some of the lessons learned by the nurse coordinators over the past 30 years are described with examples from recent studies. Best practices that we have amassed from our experience are also described.
Objective Insulin resistance (IR) increases during pregnancy which can lead to hyperinsulinemia, gestational diabetes mellitus (GDM), and neonatal hypoglycemia (NH), especially in obese women. Glucose tolerance testing (GTT) is used clinically to evaluate IR in pregnancy. Quantose IR score index is a novel blood screen of IR validated in nonpregnant individuals. The score is generated using an algorithm that combines insulin and three biomarkers of fatty acid pathways (α-hydroxybutyrate, oleic acid, linoleoyl-glycerophospocholine). Our objective was to determine the validity of Quantose IR test (Metabolan Inc. Morrisville, NC) in assessing IR in pregnant obese women, as compared with the homeostatic model assessment of insulin resistance (HOMA-IR), and its ability to predict GDM and NH.
Study Design Women between 100/7 and 136/7 weeks of gestation with a pre-pregnancy or early pregnancy body mass index more than 30 kg/m2, and no pregestational diabetes, were included. Fasting blood samples were collected at 100/7 to 136/7 (T1) and 240/7 to 280/7 (T2) weeks. Quantose IR and HOMA-IR were calculated. All women underwent an early (T1; indicated for women with obesity) and a T2 glucose tolerance tests. GDM was diagnosed using the two-step approach, and NH was defined as a neonatal glucose less than 40 mg/dL in the first 24 hours of life. Linear regression and receiver operating characteristic curves were used for analysis.
Results The trial enrolled 100 patients. Ten subjects (10%) were diagnosed with GDM in the second trimester and none in the first trimester. At T1, Quantose IR (R2 = 0.48), but not 1-hour glucose tolerance test (R2 = 0.07), correlated with HOMA-IR. Similar correlations were observed at T2. The 1-hour glucose tolerance test followed by HOMA-IR and Quantose IR (area under the curve [AUC]: 0.82, 0.68, and 0.62, respectively) were predictors of GDM. Quantose IR (AUC: 0.74) and 1-hour glucose tolerance test (AUC: 0.72) at T1 and T2 (AUC: 0.75; AUC: 0.93; respectively) were best predictors of NH. The best cut offs, sensitivities, and specificities for prediction of NH were determined.
Conclusion Similar to nonpregnant individuals, Quantose IR appears to be a valid measure of IR in obese pregnant women. First trimester Quantose IR is a predictor of GDM diagnosed in the second trimester and NH. Given that it requires a single blood draw and no glucose challenge, it may be a useful test to evaluate and monitor IR in pregnancy. Our findings may be used as pilot data to explore the potential use of Quantose IR in pregnancy further.
Key Points
ImportanceA short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting.ObjectiveTo determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix.Design, Setting, and ParticipantsWe performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded.InterventionsParticipants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians.Main Outcome and MeasuresThe primary outcome was delivery or fetal death prior to 37 weeks.ResultsA total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32).Conclusions and RelevanceCervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality.Trial RegistrationClinicalTrials.gov Identifier: NCT02901626
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