Discrete glucose profiles identified using continuous glucose monitoring data and their association with adverse pregnancy outcomes.

BACKGROUND: Continuous glucose monitoring has facilitated the evaluation of dynamic changes in glucose throughout the day and their effect on fetal growth abnormalities in pregnancy. However, studies of multiple continuous glucose monitoring metrics combined and their association with other adverse pregnancy outcomes are limited. OBJECTIVE: This study aimed to (1) use machine learning techniques to identify discrete glucose profiles based on weekly continuous glucose monitoring metrics in pregnant individuals with pregestational diabetes mellitus and (2) investigate their association with adverse pregnancy outcomes. STUDY DESIGN: This study analyzed data from a retrospective cohort study of pregnant patients with type 1 or 2 diabetes mellitus who used Dexcom G6 continuous glucose monitoring and delivered a nonanomalous, singleton pregnancy at a tertiary center between 2019 and 2023. Continuous glucose monitoring data were collapsed into 39 weekly glycemic measures related to centrality, spread, excursions, and circadian cycle patterns. Principal component analysis and k-means clustering were used to identify 4 discrete groups, and patients were assigned to the group that best represented their continuous glucose monitoring patterns during pregnancy. Finally, the association between glucose profile groups and outcomes (preterm birth, cesarean delivery, preeclampsia, large-for-gestational-age neonate, neonatal hypoglycemia, and neonatal intensive care unit admission) was estimated using multivariate logistic regression adjusted for diabetes mellitus type, maternal age, insurance, continuous glucose monitoring use before pregnancy, and parity. RESULTS: Of 177 included patients, 90 (50.8%) had type 1 diabetes mellitus, and 85 (48.3%) had type 2 diabetes mellitus. This study identified 4 glucose profiles: (1) well controlled; (2) suboptimally controlled with high variability, fasting hypoglycemia, and daytime hyperglycemia; (3) suboptimally controlled with minimal circadian variation; and (4) poorly controlled with peak hyperglycemia overnight. Compared with the well-controlled profile, the suboptimally controlled profile with high variability had higher odds of a large-for-gestational-age neonate (adjusted odds ratio, 3.34; 95% confidence interval, 1.15-9.89). The suboptimally controlled with minimal circadian variation profile had higher odds of preterm birth (adjusted odds ratio, 2.59; 95% confidence interval, 1.10-6.24), cesarean delivery (adjusted odds ratio, 2.76; 95% confidence interval, 1.09-7.46), and neonatal intensive care unit admission (adjusted odds ratio, 4.08; 95% confidence interval, 1.58-11.40). The poorly controlled profile with peak hyperglycemia overnight had higher odds of preeclampsia (adjusted odds ratio, 2.54; 95% confidence interval, 1.02-6.52), large-for-gestational-age neonate (adjusted odds ratio, 3.72; 95% confidence interval, 1.37-10.4), neonatal hypoglycemia (adjusted odds ratio, 3.53; 95% confidence interval, 1.37-9.71), and neonatal intensive care unit admission (adjusted odds ratio, 3.15; 95% confidence interval, 1.20-9.09). CONCLUSION: Discrete glucose profiles of pregnant individuals with pregestational diabetes mellitus were identified through joint consideration of multiple continuous glucose monitoring metrics. Prolonged exposure to maternal hyperglycemia may be associated with a higher risk of adverse pregnancy outcomes than suboptimal glycemic control characterized by high glucose variability and intermittent hyperglycemia.

Clinical Trials That Have Changed Obstetric Practice: The Chronic Hypertension and Pregnancy (CHAP) Trial.

We describe the evolution of treatment recommendations for chronic hypertension (CHTN) in pregnancy, the CHTN and pregnancy (CHAP) trial, and its impact on obstetric practice. The US multicenter CHAP trial showed that antihypertensive treatment for mild CHTN in pregnancy [blood pressures (BP)<160/105 mm Hg] to goal<140/90 mm Hg, primarily with labetalol or nifedipine compared with no treatment unless BP were severe reduced the composite risk of superimposed severe preeclampsia, indicated preterm birth <35 weeks, placental abruption, and fetal/neonatal death. As a result of this trial, professional societies in the United States recommended treatment of patients with CHTN in pregnancy to BP goal<140/90 mm Hg.

Predicting Spontaneous Labor beyond 39 Weeks among Low-Risk Expectantly Managed Pregnant Patients.

OBJECTIVES: The aim of the study was to identify the characteristics associated with spontaneous labor onset in pregnant patients undergoing expectant management at greater than 39 weeks' gestation and delineate perinatal outcomes associated with spontaneous labor compared with labor induction. STUDY DESIGN: This was a retrospective cohort study of singleton pregnancies at ≥390/7 weeks' gestation delivered at a single center in 2013. The exclusion criteria were elective induction, cesarean delivery or presence of a medical indication for delivery at 39 weeks, more than one prior cesarean delivery, and fetal anomaly or demise. We evaluated prenatally available maternal characteristics as potential predictors of the primary outcome-spontaneous labor onset. Multivariable logistic regression was used to generate two parsimonious models: one with and one without third trimester cervical dilation. We also performed sensitivity analysis by parity and timing of cervical examination, and compared the mode of delivery and other secondary outcomes between patients who went into spontaneous labor and those who did not. RESULTS: Of 707 eligible patients, 536 (75.8%) attained spontaneous labor and 171 (24.2%) did not. In the first model, maternal body mass index (BMI), parity, and substance use were identified as the most predictive factors. Overall, the model did not predict spontaneous labor (area under the curve [AUC]: 0.65; 95% confidence interval [CI]: 0.61-0.70) with high accuracy. The addition of third trimester cervical dilation in the second model did not significantly improve labor prediction (AUC: 0.66; 95% CI: 0.61-0.70; p = 0.76). These results did not differ by timing of cervical examination or parity. Patients admitted in spontaneous labor had lower odds of cesarean delivery (odds ratio [OR]: 0.33; 95% CI: 0.21-0.53) and neonatal intensive care unit (NICU) admission (OR: 0.38; 95% CI: 0.15-0.94). Other perinatal outcomes were similar between the groups. CONCLUSION: Maternal characteristics did not predict spontaneous labor onset at ≥39 weeks' gestation with high accuracy. Patients should be counseled on the challenges of labor prediction regardless of parity and cervical examination, outcomes if spontaneous labor does not occur, and benefits of labor induction. KEY POINTS: · Majority of patients will attain spontaneous labor at ≥39 weeks.. · Maternal characteristics do not predict labor at ≥39 weeks.. · Spontaneous labor has associated lower perinatal risks.. · A shared decision model should be utilized in counseling patients who may choose expectant management..

Respiratory Viral Infections and Infection Prevention Practices Among Women With Acute Respiratory Illness During Delivery Hospitalizations During the 2019-2020 Influenza Season.

BACKGROUND: We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices. METHODS: Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. RESULTS: Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. CONCLUSIONS: Peripartum respiratory infections may be underrecognized.

Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.

Recurrent Severe Maternal Morbidity in an Obstetric Population With a High Comorbidity Burden.

OBJECTIVE: To evaluate the risk of severe maternal morbidity (SMM) in subsequent pregnancies in patients who experienced SMM in a previous pregnancy compared with those who did not. METHODS: We conducted a retrospective cohort study of patients with two or more deliveries at 23 or more weeks of gestation at a single Southeastern U.S. tertiary care center between 2015 and 2018. The primary exposure was SMM including transfusion (transfusion SMM) in a previous pregnancy, as defined by the Centers for Disease Control and Prevention, using International Classification of Diseases, Ninth or Tenth Revision codes. The primary outcome was transfusion SMM in any subsequent pregnancy in the study time frame. Generalized estimating equation models were used to estimate the relative risk (RR) and associated 95% CIs of transfusion SMM in patients with transfusion SMM in a prior pregnancy compared with patients without transfusion SMM in a previous pregnancy. Severe maternal morbidity without transfusion (nontransfusion SMM) and cross-analysis to determine risk of a different type of SMM after a history of SMM were analyzed similarly. RESULTS: Of 852 included patients, transfusion SMM and nontransfusion SMM occurred in 90 (10.6%) and 18 (2.1%), respectively, in the first captured pregnancy and in 79 (9.3%) and 9 (1.1%), respectively, in subsequent pregnancies. Anemia (34.6-40.0%), obesity (33.4-40.4%), substance use disorder (14.2-14.6%), and preeclampsia (12.0-11.4%) were the most prevalent morbidities at first captured and subsequent pregnancies, respectively. There was a 16-fold higher risk of transfusion SMM in a subsequent pregnancy after experiencing transfusion SMM in the first captured pregnancy (57.8% vs 3.5%, RR 16.3 95% CI, 10.8-24.6). Nontransfusion SMM was similarly higher in patients with nontransfusion SMM in their first captured pregnancy compared with those without (16.7% vs 0.7%, RR 23.2 95% CI, 6.3-85.4). Additionally, patients who experienced transfusion SMM in their first captured pregnancies were at sixfold higher risk of developing nontransfusion SMM in a subsequent pregnancy (RR 6.2, 95% CI, 1.7-22.6). However, in cross-analysis of patients who experienced nontransfusion SMM, the risk of transfusion SMM in a subsequent pregnancy was not statistically significant. CONCLUSION: The risks of SMM in subsequent pregnancies after previous SMM are extremely high and are higher than previous estimates. Future studies should estimate the contributions of comorbidities and other structural determinants including social vulnerability to help design interventions to reduce subsequent pregnancy risks.

Association of Continuous Glucose Monitoring Metrics With Pregnancy Outcomes in Patients With Preexisting Diabetes.

OBJECTIVE: Continuous glucose monitoring (CGM) improves maternal glycemic control and neonatal outcomes in type 1 diabetes pregnancies compared with self-monitoring of blood glucose. However, CGM targets for pregnancy are based on expert opinion. We aimed to evaluate the association between CGM metrics and perinatal outcomes and identify evidence-based targets to reduce morbidity. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of pregnant patients with type 1 or 2 diabetes who used real-time CGM and delivered at a U.S. tertiary center (2018-2021). Multiple gestations, fetal anomalies, and early pregnancy loss were excluded. Exposures included time in range (TIR; 65-140 mg/dL), time above range (TAR), time below range (TBR), glucose variability, average glucose, and glucose management indicator. The primary outcome was a composite of fetal or neonatal mortality, large or small for gestational age at birth, neonatal intensive care unit admission, hypoglycemia, shoulder dystocia or birth trauma, and hyperbilirubinemia. Logistic regression estimated the association between CGM metrics and outcomes, and optimal TIR was calculated. RESULTS: Of 117 patients, 16 (13.7%) used CGM before pregnancy and 68 (58.1%) had type 1 diabetes. Overall, 98 patients (83.8%) developed the composite neonatal outcome. All CGM metrics, except TBR, were associated with neonatal morbidity. For each 5 percentage-point increase in TIR, there was 28% reduced odds of neonatal morbidity (odds ratio 0.72, 95% CI 0.58-0.89). The statistically optimal TIR was 66-71%. CONCLUSIONS: Nearly all CGM metrics were associated with adverse neonatal morbidity and mortality and may aid management of preexisting diabetes in pregnancy. Our findings support the American Diabetes Association recommendation of 70% TIR.

Physiologic blood pressure patterns in pregnancies with mild chronic hypertension.

OBJECTIVES: To assess physiologic blood pressure (BP) changes throughout pregnancy in patients with mild chronic hypertension (CHTN) who do and do not develop preeclampsia (PEC), compared to patients with normal BP. STUDY DESIGN: Retrospective cohort of singleton gestations with CHTN at a single tertiary center from 2000 to 2014 and a randomly selected cohort of patients without CHTN and normal pregnancy outcomes (NML) in the same time period with BP measurements available <12 weeks gestational age. MAIN OUTCOME MEASURES: The primary outcome was gestational age (GA) at nadir of systolic and diastolic BP. Secondary outcomes included perinatal death, umbilical cord pH, maternal and neonatal length of stay, GA at delivery, and mode of delivery. Quadratic mixed models were used to estimate SBP and DBP throughout gestation. RESULTS: Of 367 pregnancies with CHTN, 268 (73%) had CHTN without PEC and 99 (27%) had CHTN with PEC; 198 NML pregnancies were used as a comparison group. The median GA nadir for patients in the NML, CHTN without PEC, and CHTN with PEC for SBP were 20, 24, and 21, respectively. For DBP, the median GA nadir were 22, 24, and 21 for patients in the NML, CHTN without PEC, and CHTN with PEC cohorts, respectively. Adverse secondary outcomes were more frequent in patients with CHTN who developed PEC. CONCLUSIONS: BP trajectories in pregnancy are different between patients with CHTN with PEC, CHTN without PEC, and patients with normal BP. These findings may be useful in assessing patients' risks for developing preeclampsia during pregnancy.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Timing of Adjunctive Azithromycin for Unscheduled Cesarean Delivery and Postdelivery Infection.

OBJECTIVE: To estimate the association between timing of administration of adjunctive azithromycin for prophylaxis at unscheduled cesarean delivery and maternal infection and neonatal morbidity. METHODS: We conducted a secondary analysis of a randomized trial of adjunctive azithromycin prophylaxis in patients with singleton gestations who were undergoing unscheduled cesarean delivery. The primary exposure was the timing of initiation of the study drug (after skin incision or 0-30 minutes, more than 30-60 minutes, or more than 60 minutes before skin incision). The primary outcome was a composite of endometritis, wound infection, and other maternal infections occurring up to 6 weeks after cesarean delivery. Secondary outcomes included composite neonatal morbidity, neonatal intensive care unit admission for longer than 72 hours, and neonatal sepsis. The association of azithromycin with outcomes was compared within each antibiotic timing group and presented as risk ratios (RRs) with 95% CIs. A Breslow-Day homogeneity test was applied to assess differences in association by antibiotic timing. RESULTS: Of 2,013 participants, antibiotics were initiated after skin incision (median 3 minutes, range 0-229 minutes) in 269 (13.4%), 0-30 minutes before skin incision in 1,378 (68.5%), more than 30-60 minutes before skin incision in 270 (13.4%), and more than 60 minutes before skin incision (median 85 minutes, range 61-218 minutes) in 96 (4.8%). The RRs (95% CIs) of the infectious composite outcome for azithromycin compared with placebo were significantly lower for groups that initiated azithromycin after skin incision or within 1 hour before skin incision (after skin incision: RR 0.31, 95% CI 0.13-0.76; 0-30 minutes before: RR 0.62, 95% CI 0.44-0.89; more than 30-60 minutes before: 0.31, 95% CI 0.13-0.66). Risks were not significantly different in patients who received azithromycin more than 60 minutes before skin incision (RR 0.59, 95% CI 0.10-3.36). Results were similar when endometritis and wound infections were analyzed separately. Neonatal outcomes were not significantly different for azithromycin compared with placebo across all timing groups. CONCLUSION: Adjunctive azithromycin administration up to 60 minutes before or at a median of 3 minutes after skin incision was associated with reduced risks of maternal composite postoperative infection in unscheduled cesarean deliveries. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01235546.

Delivery timing for the opioid-exposed infant.

BACKGROUND: The prevalence of opioid use disorder and medication-assisted treatment in pregnancy is increasing. Compared with term infants, preterm infants have a lower incidence of neonatal opioid withdrawal syndrome. It is unknown whether early term delivery compared with full or late-term delivery decreases the risk of neonatal opioid withdrawal syndrome. OBJECTIVE: This study aimed to compare the neonatal outcomes among opioid-exposed infants born in the early, full, and late-term periods. STUDY DESIGN: This was a retrospective cohort study of opioid-exposed pregnancies delivering at a single center from 2010 to 2017 at ≥37 weeks gestation. Participants with multiple gestations or fetal anomalies were excluded. Maternal opioid exposure was defined as prescription (including medication-assisted treatment) or nonprescription opioid use or a positive urine drug screen in pregnancy for opiates. The primary outcome was a neonatal composite of respiratory distress syndrome, neonatal sepsis, neonatal seizures, hypoxic ischemic encephalopathy, jaundice requiring treatment, 5-minute Apgar <5, neonatal intensive care unit admission, neonatal opioid withdrawal syndrome, or neonatal death. The secondary outcomes included individual components of the primary outcome, birthweight, need for and length of neonatal opioid withdrawal syndrome treatment, length of hospital admission, and maximum Finnegan scores. Early (37-<39), full (39-<41), and late (41-<42 weeks) term groups were defined by the American College of Obstetricians and Gynecologists. RESULTS: Of 399 infants, 136 (34.1%), 229 (57.4%), and 34 (8.5%) were born in the early, full, and late-term periods, respectively. Two hundred and seventy patients (67.7%) received medication-assisted treatment for opioid use disorder, and the baseline characteristics were similar in all the groups except for history of intranasal heroin use, positive urine toxicology screen for heroin or any opiates, and delivery indication (P<.05). The primary composite outcome occurred in 313 (78.4%) neonates, and 296 (74.2%) neonates had neonatal opioid withdrawal syndrome. More than half (219 [54.9%]) of opioid-exposed neonates were admitted to the neonatal intensive care unit, and 160 (40.1%) required pharmacologic neonatal opioid withdrawal syndrome treatment for a mean duration of almost 3 weeks (19.0±16.1 days). There were no significant differences in the primary composite outcome, incidence of neonatal opioid withdrawal syndrome, or other secondary outcomes (except birthweight) between neonates born in the early, full, or late-term periods. CONCLUSION: Although neonatal morbidity was frequent among opioid-exposed neonates, the incidence and severity of neonatal opioid withdrawal syndrome or other neonatal outcomes were not different between neonates delivered in the early, full, and late-term periods, suggesting that opioid-exposed infants may not benefit from early term delivery.