Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study.

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.

General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial.

BACKGROUND: In 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment. METHODS: A secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders. RESULTS: Of 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010). CONCLUSIONS: General anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.

Gestational weight gain and preterm birth: disparities in adolescent pregnancies.

OBJECTIVE: To examine racial differences in the association between gestational weight gain and preterm birth subtypes among adolescents. STUDY DESIGN: We conducted a retrospective cohort study of 211 403 adolescents using 2012 United States natality data. The outcome was preterm birth and the primary exposure was gestational weight gain. Multinomial logistic regression analyses were used to estimate adjusted odds ratios, stratified by race and body mass index (BMI). RESULTS: Black and White mothers who gained below the recommendations had increased risks for spontaneous preterm birth in all BMI categories, except obese. All Hispanic mothers who gained below the recommendations had increased risks of spontaneous preterm birth. White normal and overweight mothers and Black, Hispanic and Other normal weight mothers who exceeded the recommendations had decreased risks of spontaneous preterm birth. CONCLUSION: The effect of gestational weight gain on spontaneous and medically indicated preterm birth is modified by race and BMI.

Predicting failure of glyburide therapy in gestational diabetes.

OBJECTIVE: We sought to develop a prediction model to identify women with gestational diabetes (GDM) who require insulin to achieve glycemic control. STUDY DESIGN: Retrospective cohort of all singletons with GDM treated with glyburide from 2007 to 2013. Glyburide failure was defined as reaching glyburide 20 mg day(-1) and receiving insulin. Glyburide success was defined as any glyburide dose without insulin and >70% of visits with glycemic control. Multivariable logistic regression analysis was performed to create a prediction model. RESULT: Of the 360 women, 63 (17.5%) qualified as glyburide failure and 157 (43.6%) as glyburide success. The final prediction model for glyburide failure included prior GDM, GDM diagnosis ⩽26 weeks, 1-h glucose challenge test ⩾228 mg dl(-1), 3-h glucose tolerance test 1-h value ⩾221 mg dl(-1), ⩾7 postprandial blood sugars >120 mg dl(-1) in the week glyburide started and ⩾1 blood sugar >200 mg dl(-1). The model accurately classified 81% of subjects. CONCLUSION: Women with GDM who will require insulin can be identified at the initiation of pharmacological therapy.

Timing of elective delivery in gastroschisis: a decision and cost-effectiveness analysis.

OBJECTIVE: To determine the most cost-effective timing of delivery in pregnancies complicated by gastroschisis, using a decision-analytic model. METHODS: We created a decision-analytic model to compare planned delivery at 35, 36, 37, 38 and 39 weeks' gestation. Outcomes considered were stillbirth, death within 1 year of birth and respiratory distress syndrome (RDS). Probability estimates of events (stillbirth, complex gastroschisis and RDS for each gestational age at delivery and risk of death with simple and complex gastroschisis), utilities and costs assigned to the outcomes were obtained from the published literature. Cost analysis was assessed from a societal perspective, using a willingness-to-pay threshold of $100,000 per surviving infant. Outcomes and costs were considered throughout 1 year of postnatal life. Multiway sensitivity analysis was performed to address uncertainties in baseline assumptions. RESULTS: In the base-case analysis, delivery at 38 weeks' gestation was the most cost-effective strategy. Planned delivery at 35 weeks was associated with the fewest stillbirths and deaths within 1 year of delivery, owing largely to a lower ongoing risk of stillbirth. In Monte Carlo simulation when every variable was varied over its entire range, delivery at 38 weeks was cost-effective compared to delivery at 39 weeks in 76% of trials and delivery at 37 weeks was cost-effective in 69% of trials. Delivery at 38 weeks resulted in three additional cases of RDS for every 100 stillbirths or deaths within 1 year that were prevented. CONCLUSIONS: For pregnancies complicated by gastroschisis, the most cost-effective timing of delivery is at 38 weeks. Few additional cases of RDS are caused for every one stillbirth or death within 1 year that was prevented with delivery at 37-38 weeks compared with at 39 weeks.

Gestational weight gain in insulin-resistant pregnancies.

OBJECTIVE: To examine the Institute of Medicine (IOM) guidelines for gestational weight gain (GWG) in insulin-resistant pregnancy. STUDY DESIGN: Secondary analysis of a prospective cohort of 435 women with type 2 or gestational diabetes from 2006 to 2010. The exposure was categorized as GWG less than, within or greater than the IOM recommendations for body mass index. The maternal outcome was a composite of preeclampsia, eclampsia, third- to fourth-degree laceration, readmission or wound infection. The neonatal outcome was a composite of preterm delivery, level 3 nursery admission, oxygen requirement >6 h, shoulder dystocia, 5-min Apgar3, umbilical cord arterial pH<7.1 or base excess <-12. Secondary outcomes were cesarean delivery (CD), macrosomia and small for gestational age (SGA). RESULT: Incidence of the maternal outcome did not differ with GWG (P=0.15). Women gaining more than recommended had an increased risk of CD (relative risk (RR) 1.31, 95% confidence interval (CI) 1.01 to 1.69) and the neonatal outcome (RR 1.40, 95% CI 1.01 to 1.95) compared with women gaining within the IOM recommendations. Women gaining less than recommended had an increased risk of SGA (RR 3.29, 95% CI 1.09 to 9.91) without a decrease in the risk of the maternal outcome (RR 0.93, 95% CI 0.49 to 1.78) or CD (RR 0.74, 95% CI 0.40 to 1.37) compared with women gaining within the IOM recommendations. CONCLUSION: Women with insulin resistance should be advised to gain within the current IOM guidelines.

Customized growth charts for twin gestations to optimize identification of small-for-gestational age fetuses at risk of intrauterine fetal death.

OBJECTIVE: Customized growth charts developed for singleton pregnancies have been shown to be more effective than population-based ones at identifying small-for-gestational age (SGA) fetuses at risk for intrauterine fetal death (IUFD). We sought to compare the association between SGA and IUFD in twins using customized growth charts designed for twin gestations compared to those designed for singletons. METHODS: This was a retrospective cohort study using a database including singleton and twin pregnancies undergoing ultrasound examination between 16 and 20 weeks' gestation. After excluding preterm births < 34 weeks, congenital anomalies and stillbirths, we identified 51, 150 singleton births. Coefficients for significant physiological and pathological variables affecting birth weight for singletons were derived using backward stepwise multiple regression. The same process was repeated for twin births (1608 pairs), also adjusting for chorionicity. Customized growth charts for each pregnancy were derived using these two regression models for optimal birth weight at term and a proportionality equation. The association between SGA < 10(th) percentile, defined using the twin and singleton-customized charts, and IUFD were compared. Statistical analysis, including calculation of adjusted odds ratios (OR) for IUFD and screening accuracy using each chart, was performed. RESULTS: The derived coefficients for optimal birth weight for twins were different from those for singletons, with lower constants and root mean square error (3422 and 288.9, respectively, in twins vs 3543 and 416 in singletons). Among 3786 twin infants, IUFD was seen in 123 (3.2%). The numbers of fetuses identified as SGA were 575 (15.2%) and 504 (13.3%) by the singleton and twin charts, respectively. Fetuses classified as SGA by the twin-specific customized charts were at a significantly increased risk for IUFD (adjusted OR, 2.3 (95% CI, 1.4-3.5)), whereas those classified as SGA by the singleton-customized charts were not (adjusted OR, 1.2 (95% CI, 0.7-2.0)). CONCLUSION: Customized charts designed specifically for twins are more effective at identifying twin pregnancies at risk for IUFD than are those derived using singleton birth data.

First-trimester growth discordance and adverse pregnancy outcome in dichorionic twins.

OBJECTIVE: To evaluate the association between first-trimester growth discordance and adverse pregnancy outcome in dichorionic twin pregnancies. METHODS: This was a retrospective cohort study of consecutive women with dichorionic twin pregnancies undergoing an ultrasound scan at our institution between 7 and 14 weeks' gestation. Study groups were defined by the presence or absence of ≥ 11% crown-rump length (CRL) discordance. Pregnancies were excluded if one twin was dead on initial ultrasound or if a termination was performed. The primary outcome was loss of one or both fetuses before 20 weeks. Secondary outcomes included fetal anomaly, fetal demise after 20 weeks (stillbirth), small-for-gestational-age (SGA) at birth, admission to the neonatal intensive care unit (NICU) and preterm delivery before 34 weeks. RESULTS: Of 805 dichorionic twin pregnancies undergoing first-trimester ultrasound, 610 met the inclusion criteria. Eighty-six had ≥ 11% CRL discordance and, of these, nine (10.5%) had a fetal loss at < 20 weeks (risk ratio (RR) 7.8 (95% CI, 3.0-20.5)). In the surviving pregnancies, an increased risk of fetal anomalies was seen (27.3 vs 17.4%, RR 1.6 (95% CI, 1.1-2.4)). In surviving pregnancies unaffected by anomalies, no increased risk of stillbirth, SGA, NICU admission or delivery before 34 weeks was noted in the discordant group. A post-hoc power analysis demonstrated 80% power to detect a five-fold increase in the risk of stillbirth and 90% power to detect a two-fold increase in other outcomes. CONCLUSION: Dichorionic pregnancies in which a CRL discordance of at least 11% is noted are at increased risk for fetal anomalies and fetal loss prior to 20 weeks' gestation. However, patients can be reassured that, in the absence of structural anomalies, CRL discordance does not appear to be associated with other adverse outcomes in continuing pregnancies, although the power to detect small increases in the risk of stillbirth may have been limited by the sample size.