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OBJECTIVE: To estimate the association between maternal metformin use for the treatment of early gestational or pre-existing type 2 diabetes and preterm preeclampsia. METHODS: This is a planned secondary analysis of the MOMPOD study (Medical Optimization of Management of Overt Type 2 Diabetes in Pregnancy), a randomized trial comparing the effect of adding metformin with insulin treatment on composite neonatal outcome in singleton pregnancies with early gestational or type 2 diabetes. Participants were randomized at 11-23 weeks of gestation to 1,000 mg metformin twice daily or placebo until delivery. A subset of participants had maternal blood collected at 24-30 weeks of gestation, and serum soluble endoglin, apolipoprotein B, vascular cell adhesion molecule-1, soluble fms-like tyrosine kinase 1, placental growth factor, high-sensitivity C-reactive protein, adiponectin, and vascular endothelial growth factor levels were measured. Our primary outcome was preterm preeclampsia, defined as preeclampsia requiring delivery before 37 weeks of gestation. Secondary outcomes included preterm preeclampsia requiring delivery before 34 weeks of gestation and differences in serum biomarkers. Multivariable regression analysis was used to estimate the associations between metformin use and primary or secondary study outcomes. RESULTS: Of 831 participants, 119 (14.3%) developed preeclampsia requiring delivery before 37 weeks of gestation: 57 of 416 (13.7%) in the placebo group and 62 of 415 (14.9%) in the metformin group. Thirty-seven (4.4%) developed preeclampsia requiring delivery before 34 weeks of gestation: 15 (3.6%) receiving placebo and 22 (5.3%) receiving metformin. Compared with placebo, metformin was not associated with a significant difference in the occurrence of preeclampsia before 37 weeks of gestation (adjusted odds ratio [aOR] 1.04, 95% CI, 0.70-1.56) or before 34 weeks (aOR 1.43, 95% CI, 0.73-2.81). Similarly, there was no association between maternal metformin use and serum biomarker levels. CONCLUSION: Among parturients with early gestational or pre-existing type 2 diabetes, the addition of metformin to insulin was not associated with lower odds of preterm preeclampsia or with serum biomarkers associated with cardiovascular disease risk.
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Previable and periviable preterm prelabor rupture of membranes are challenging obstetrical complications to manage given the substantial risk of maternal morbidity and mortality, with no guarantee of fetal benefit. The following are the Society for Maternal-Fetal Medicine recommendations for the management of previable and periviable preterm prelabor rupture of membranes before the period when a trial of neonatal resuscitation and intensive care would be considered appropriate by the healthcare team and desired by the patient: (1) we recommend that pregnant patients with previable and periviable preterm prelabor rupture of membranes receive individualized counseling about the maternal and fetal risks and benefits of both abortion care and expectant management to guide an informed decision; all patients with previable and periviable preterm prelabor rupture of membranes should be offered abortion care, and expectant management can also be offered in the absence of contraindications (GRADE 1C); (2) we recommend antibiotics for pregnant individuals who choose expectant management after preterm prelabor rupture of membranes at ≥24 0/7 weeks of gestation (GRADE 1B); (3) antibiotics can be considered after preterm prelabor rupture of membranes at 20 0/7 to 23 6/7 weeks of gestation (GRADE 2C); (4) administration of antenatal corticosteroids and magnesium sulfate is not recommended until the time when a trial of neonatal resuscitation and intensive care would be considered appropriate by the healthcare team and desired by the patient (GRADE 1B); (5) serial amnioinfusions and amniopatch are considered investigational and should be used only in a clinical trial setting; they are not recommended for routine care of previable and periviable preterm prelabor rupture of membranes (GRADE 1B); (6) cerclage management after previable or periviable preterm prelabor rupture of membranes is similar to cerclage management after preterm prelabor rupture of membranes at later gestational ages; it is reasonable to either remove the cerclage or leave it in situ after discussing the risks and benefits and incorporating shared decision-making (GRADE 2C); and (7) in subsequent pregnancies after a history of previable or periviable preterm prelabor rupture of membranes, we recommend following guidelines for management of pregnant persons with a previous spontaneous preterm birth (GRADE 1C).
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Rotura Prematura de Membranas Fetales , Humanos , Embarazo , Rotura Prematura de Membranas Fetales/terapia , Femenino , Espera Vigilante , Antibacterianos/uso terapéutico , Sulfato de Magnesio/uso terapéutico , Aborto Inducido/métodos , Edad Gestacional , Viabilidad Fetal , Recién Nacido , Cerclaje CervicalRESUMEN
Continuous glucose monitoring (CGM) has the potential to revolutionize diabetes management during pregnancy by providing detailed and real-time data to patients and clinicians, overcoming many of the limitations of self-monitoring of blood glucose. Although there are limited data on the role of CGM to improve pregnancy outcomes in patients with type 2 diabetes or gestational diabetes, CGM has been shown to reduce pregnancy complications in patients with type 1 diabetes. Despite the limited data in some populations, given its ease of use and recent U.S. Food and Drug Administration approval with expanding insurance coverage, CGM has gained widespread popularity among pregnant patients with all types of diabetes. It is critical for obstetric clinicians to understand how CGM can be successfully integrated into clinical practice. We present a practical, step-wise approach to CGM data interpretation that can be incorporated into diabetes management during pregnancy and common CGM pitfalls and solutions. Although technology will continue to advance with newer-generation CGM devices and diabetes technology such as automated insulin delivery (not covered here), these key principles form a basic foundation for understanding CGM technology and its utility for pregnant people.
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Importance: In 2016, our institution adopted a pregnancy-related venous thromboembolism (VTE) prophylaxis protocol based on American College of Obstetricians and Gynecologists guidelines that recommended postpartum heparin-based chemoprophylaxis (enoxaparin) based on a risk-stratified algorithm. In response to increased wound hematomas without significant reduction in VTE using this protocol, a more selective risk-stratified approach was adopted in 2021. Objective: To evaluate outcomes of the more selective risk-stratified approach to heparin-based obstetric thromboprophylaxis (enoxaparin) protocol. Design, Setting, and Participants: Retrospective observational study of 17â¯489 patients who delivered at a single tertiary care center in the southeast US between January 1, 2016, and December 31, 2018 (original protocol), and between December 1, 2021, and May 31, 2023 (more selective protocol). Patients receiving outpatient anticoagulation for active VTE or high VTE risk during pregnancy were excluded. Exposure: Standard risk-stratified and more selective postpartum VTE chemoprophylaxis protocols. Main Outcomes and Measures: The primary outcome was clinical diagnosis of wound hematoma up to 6 weeks pos tpartum. The secondary outcome was new diagnosis of VTE up to 6 weeks post partum. We compared baseline characteristics and outcomes between groups and estimated adjusted odds ratios with 95% CIs of primary and secondary outcomes using the original protocol group as reference. Results: Of 17â¯489 patients included in the analysis, 12â¯430 (71%) were in the original protocol group and 5029 (29%) were in the more selective group. Rates of chemoprophylaxis decreased from 16% (original protocol) to 8% (more selective protocol). Patients in the more selective group were more likely to be older, be married, and have obesity or other comorbidities (hypertension, diabetes, cardiac disease). Compared with the original protocol, the more selective protocol was associated with a decrease in any wound hematoma (0.7% vs 0.3%; adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.67), specifically due to a lower rate of superficial wound hematomas (0.6% vs 0.3%; aOR, 0.43; 95% CI, 0.24-0.75). There was no significant increase in VTE or individual types of VTE (0.1% vs 0.1%; aOR, 0.40; 95% CI, 0.12-1.36). Conclusions and Relevance: A more selective risk-stratified approach to an enoxaparin thromboprophylaxis protocol for VTE was associated with decreased rates of wound hematomas without increased rates of postpartum VTE.
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Anticoagulantes , Enoxaparina , Hematoma , Tromboembolia Venosa , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Tromboembolia Venosa/prevención & control , Adulto , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Enoxaparina/uso terapéutico , Medición de Riesgo , Hematoma/prevención & control , Protocolos Clínicos , Complicaciones Cardiovasculares del Embarazo/prevención & control , Guías de Práctica Clínica como AsuntoRESUMEN
OBJECTIVE: To evaluate the association between continuous glucose monitoring in pregnant people with type 2 diabetes and perinatal outcomes. METHODS: This was a retrospective cohort study of pregnant people with type 2 diabetes who received prenatal care and delivered singleton, nonanomalous neonates at a single academic tertiary care center from November 1, 2019, to February 28, 2023. The primary outcome was a composite of neonatal morbidity, including hypoglycemia, hyperbilirubinemia, shoulder dystocia, large for gestational age at birth, preterm birth, neonatal intensive care unit (NICU) admission, or perinatal death. Demographics and outcomes were compared by type of monitoring (continuous glucose monitoring vs intermittent self-monitoring of blood glucose), and multivariable logistic regression estimated the association between continuous glucose monitoring use and perinatal outcomes. RESULTS: Of 360 pregnant people who met the inclusion criteria, 82 (22.7%) used continuous glucose monitoring. The mean gestational age at continuous glucose monitoring initiation was 21.3±6.4 weeks. The use of continuous glucose monitoring was associated with lower odds of the primary composite neonatal morbidity (65.9% continuous glucose monitoring vs 77.0% self-monitoring of blood glucose, adjusted odds ratio [aOR] 0.48, 95% CI, 0.24-0.94). Continuous glucose monitoring use was also associated with lower odds of preterm birth (13.4% vs 25.2%, aOR 0.48, 95% CI, 0.25-0.93) and NICU admission (33.8% vs 47.6%, aOR 0.36, 95% CI, 0.16-0.81). CONCLUSION: In pregnant people with type 2 diabetes, continuous glucose monitoring use was associated with less neonatal morbidity, fewer preterm births, and fewer NICU admissions.
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OBJECTIVE: Studies have suggested an association between prenatal care (PNC) and preterm birth (PTB). We evaluated trends in PTB and association of PNC and PTB. STUDY DESIGN: This was a retrospective cohort study of singleton, viable nonanomalous deliveries from 1991 to 2018. PNC utilization was defined by World Health Organization using number of visits: adequate (≥8), suboptimal (5-7), and inadequate (<5). Primary outcome was PTB. Tests of trend were used to assess changes in PTB over time. Baseline characteristics and outcomes were compared. Logistic regression estimated the association of PNC and PTB. We evaluated for effect modification by year of birth. RESULTS: Of 92,294 patients, 14,057 (15%) had PTB. Inadequate and suboptimal PNC were associated with higher odds of PTB compared to adequate PNC (adjusted odds ratios = [aOR 6.21], 95% confidence interval [CI]: 5.84-6.60; aOR = 3.57, 95% CI: 3.36-3.79). Inadequate PNC was associated with higher odds of PTB over time (effect modification p < 0.0001). Inadequate PNC was associated with 5.4 times higher odds of PTB in 1998, 7.0 times in 2008, and 9.1 times in 2018. CONCLUSION: Despite an increase in adequate PNC, there was a rise in PTB associated with inadequate and suboptimal PNC. PNC utilization was a stronger risk factor in recent years with higher PTB in patients who attended more than five PNC visits. KEY POINTS: · PNC utilization is associated with the risk of PTB.. · Despite an increase in PNC utilization, PTB rates have increased.. · There is an even stronger association between PNC utilization and PTB over time..
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Nacimiento Prematuro , Atención Prenatal , Humanos , Femenino , Nacimiento Prematuro/epidemiología , Embarazo , Estudios Retrospectivos , Atención Prenatal/estadística & datos numéricos , Adulto , Modelos Logísticos , Recién Nacido , Adulto Joven , Aceptación de la Atención de Salud/estadística & datos numéricos , Factores de Riesgo , Oportunidad RelativaRESUMEN
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.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Cesárea , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglucemia , Preeclampsia , Resultado del Embarazo , Embarazo en Diabéticas , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Embarazo en Diabéticas/sangre , Diabetes Mellitus Tipo 1/sangre , Hipoglucemia/epidemiología , Glucemia/metabolismo , Glucemia/análisis , Nacimiento Prematuro/epidemiología , Cesárea/estadística & datos numéricos , Preeclampsia/epidemiología , Recién Nacido , Diabetes Mellitus Tipo 2/sangre , Macrosomía Fetal/epidemiología , Aprendizaje Automático , Unidades de Cuidado Intensivo Neonatal , Estudios de Cohortes , Cuidado Intensivo Neonatal , Monitoreo Continuo de GlucosaRESUMEN
INTRODUCTION: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown. METHODS AND ANALYSIS: The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis. ETHICS AND DISSEMINATION: The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT05124808.
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Diabetes Gestacional , Hipoglucemia , Femenino , Humanos , Recién Nacido , Embarazo , Diabetes Gestacional/tratamiento farmacológico , Macrosomía Fetal , Estudios Multicéntricos como Asunto , Obesidad/complicaciones , Sobrepeso/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Pragmáticos como AsuntoRESUMEN
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.
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Diabetes Mellitus Tipo 1 , Resultado del Embarazo , Embarazo , Recién Nacido , Femenino , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucemia , Automonitorización de la Glucosa Sanguínea , Estudios Retrospectivos , Monitoreo Continuo de Glucosa , GlucosaRESUMEN
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.
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Complicaciones del Embarazo , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Factores de Riesgo , Complicaciones del Embarazo/epidemiología , Comorbilidad , MorbilidadRESUMEN
We aimed to evaluate physiologic treatment of severe hypertension. This was a retrospective cohort study of pregnant and postpartum patients with severe hypertension (systolic blood pressure [BP] 160 mm Hg or higher or diastolic BP 110 mm Hg or higher) treated with intravenous labetalol or hydralazine at a single tertiary care center between 2013 and 2018. Patients were classified as having physiologic treatment if they had hyperdynamic physiology (pulse pressure 65 mm Hg or higher) and received labetalol or had vasoconstrictive physiology (diastolic BP 100 mm Hg or higher) and received hydralazine. The primary outcome was number of antihypertensive doses to achieve nonsevere BP. Of 1,120 patients included in the analysis, 653 had physiologic treatment and 467 had nonphysiologic treatment, with 16 (1.4%) excluded for inability to classify physiology. Physiologic treatment was associated with fewer antihypertensive doses (1.4±0.9 doses vs 1.6±1.4 doses; adjusted ß -0.28, 95% CI, -0.42 to -0.14) and lower odds of medication conversion (2.5% vs 4.7%; adjusted odds ratio 0.48, 95% CI, 0.24-0.93) but no difference in time to nonsevere BP (31 minutes [interquartile range 16-66 minutes] vs 34 minutes [interquartile range 15-76 minutes]; adjusted hazard ratio 1.0, 95% CI, 0.9-1.2). Physiologic treatment of severe hypertension warrants further evaluation.
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Hipertensión , Labetalol , Femenino , Humanos , Embarazo , Antihipertensivos , Presión Sanguínea , Hidralazina/efectos adversos , Hipertensión/tratamiento farmacológico , Nifedipino/uso terapéutico , Periodo Posparto , Estudios Retrospectivos , Hipertensión Inducida en el EmbarazoRESUMEN
Neonates born at the cusp of viability are at particularly high risk of severe morbidity and mortality. With advances in medicine and technology, the ability to resuscitate smaller, more premature neonates has become possible, and survival as early as 21 weeks of gestation has been reported. Although administration of antenatal corticosteroids has been shown to reduce the risk of morbidity and mortality at later gestational ages, neonates born before 24 weeks of gestation have not been included in randomized clinical trials. Changing clinical practices surrounding neonatal resuscitation with intervention offered after birth at earlier gestational ages has prompted re-evaluation of the use of antenatal corticosteroids at these very early gestational ages. Recent observational data demonstrate that antenatal corticosteroids administered before deliveries at or after 22 weeks of gestation are associated with lower risks of neonatal mortality, although survival with severe morbidity remains high. Future research is needed to determine the efficacy of antenatal corticosteroids for deliveries before 22 weeks of gestation and should evaluate the timing of corticosteroid administration. Furthermore, efforts should be made to include diverse populations and clinically meaningful long-term outcomes. At this time, the decision surrounding antenatal corticosteroids for threatened periviable deliveries should incorporate multidisciplinary counseling with the goal of achieving concordant prenatal and postnatal management aligned with the patient's desires.
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Nacimiento Prematuro , Atención Prenatal , Recién Nacido , Embarazo , Humanos , Femenino , Lactante , Resucitación , Corticoesteroides/uso terapéutico , Edad Gestacional , Mortalidad Infantil , Nacimiento Prematuro/prevención & controlRESUMEN
OBJECTIVE: Elective induction of labor versus expectant management at 39 weeks gestation in low-risk nulliparous patients was shown in the ARRIVE randomized trial of over 6000 patients to decrease risks of cesarean delivery without significant change in the composite perinatal outcome. We aimed to pragmatically analyze the effect of offering elective induction of labor (eIOL) to all low-risk patients. METHODS: Retrospective cohort study of low-risk nulliparous and multiparous patients delivering live, non-anomalous singletons at a single center at greater than or equal to 39 0/7 weeks gestational age. Those with prior or planned cesarean delivery, ruptured membranes, medical comorbidities, or contraindications to vaginal delivery were excluded. Patients were categorized as before (pre-eIOL; 1/2012-3/2014) or after (post-eIOL; 3/2019-12/2021) an institution-wide policy offering eIOL at 39 0/7 weeks. Births occurring April 2014 to December 2018 were allocated to a separate cohort (during-eIOL) given increased exposure to eIOL as our center recruited participants for the ARRIVE trial. The primary outcome was cesarean birth. Secondary outcomes included select maternal (e.g. chorioamnionitis, operative delivery, postpartum hemorrhage) and neonatal morbidities (e.g. birthweight, small- and large-for gestational age, hypoglycemia). Characteristics and outcomes were compared between the pre and during-eIOL, and pre and post-eIOL groups; adjusted OR (95% CI) were calculated using multivariable regression. Subgroup analysis by parity was planned. RESULTS: Of 10,758 patients analyzed, 2521 (23.4%) were pre-eIOL, 5410 (50.3%) during-eIOL, and 2827 (26.3%) post-eIOL. Groups differed with respect to labor type, age, race/ethnicity, marital and payor status, and gestational age at care entry. Post-eIOL was associated with lower odds of cesarean compared to pre-eIOL (aOR 0.83 [95% CI 0.72-0.96]), which was even lower among those specifically undergoing labor induction (aOR 0.58 [0.48-0.70]. During-eIOL was also associated with lower odds of cesarean compared to pre-eIOL (aOR 0.79 [0.69-0.90]). Both during and post-eIOL groups were associated with higher odds of chorioamnionitis, operative delivery, and hemorrhage compared to pre-eIOL. However, only among post-eIOL were there fewer neonates weighing ≥4000 g, large-for-gestational age infants, and neonatal hypoglycemia compared to pre-IOL. CONCLUSION: An institutional policy offering eIOL at 39 0/7 to low-risk patients was associated with a lower cesarean birth rate, lower birthweights and lower neonatal hypoglycemia, and an increased risk of chorioamnionitis and hemorrhage.
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Corioamnionitis , Hipoglucemia , Enfermedades del Recién Nacido , Hemorragia Posparto , Femenino , Humanos , Recién Nacido , Embarazo , Corioamnionitis/etiología , Edad Gestacional , Hipoglucemia/etiología , Enfermedades del Recién Nacido/etiología , Trabajo de Parto Inducido/métodos , Política Organizacional , Hemorragia Posparto/etiología , Estudios Retrospectivos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Hipoglucemiantes , Insulina , Metformina , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Gestacional/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Enfermedades del Recién Nacido/inducido químicamente , Enfermedades del Recién Nacido/etiología , Enfermedades del Recién Nacido/prevención & control , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina/uso terapéutico , Insulina Regular Humana/uso terapéutico , Metformina/administración & dosificación , Metformina/efectos adversos , Metformina/uso terapéutico , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Adolescente , Adulto Joven , Persona de Mediana EdadRESUMEN
BACKGROUND: Leptin resistance occurs with obesity, but it is unknown if individuals at risk for obesity develop leptin resistance prior to obesity. OBJECTIVE: Investigate whether leptin resistance is independent of weight status in children at risk for obesity due to intrauterine exposure to maternal obesity or gestational diabetes mellitus (GDM). METHODS: Mother-child dyads (N = 179) were grouped by maternal pregnancy weight and GDM status: (1) normal weight, no GDM; (2) overweight/obesity, no GDM; (3) overweight/obesity with GDM. Children (4-10 years) were further stratified by current body mass index (BMI) <85th or ≥85th percentile. Leptin resistance of children and mothers was calculated as fasting leptin/fat mass index. Two-way ANOVA was used to assess whether leptin concentrations and leptin resistance differed by current weight status or in utero exposure group, after adjusting for race, sex and Tanner stage. RESULTS: Children with a BMI ≥85th percentile had more leptin resistance than those with a BMI <85th percentile (p < 0.001), but leptin resistance did not differ by in utero exposure. Similarly, leptin resistance in women was associated with weight status and not prior GDM. CONCLUSIONS: Results suggest that leptin concentrations are associated with obesity but not risk for obesity based on in utero exposure to maternal obesity or GDM.
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Diabetes Gestacional , Obesidad Materna , Femenino , Humanos , Embarazo , Peso al Nacer , Índice de Masa Corporal , Diabetes Gestacional/epidemiología , Leptina , Obesidad/epidemiología , Obesidad/complicaciones , Obesidad Materna/complicaciones , Sobrepeso/complicaciones , Factores de Riesgo , Preescolar , NiñoRESUMEN
We examined associations between mild or asymptomatic prenatal SARS-CoV-2 infection and preterm live birth in a prospective cohort study. During August 2020-October 2021, pregnant persons were followed with systematic surveillance for RT-PCR or serologically confirmed SARS-CoV-2 infection until pregnancy end. The association between prenatal SARS-CoV-2 infection and preterm birth was assessed using Cox proportional-hazards regression. Among 954 pregnant persons with a live birth, 185 (19%) had prenatal SARS-CoV-2 infection and 123 (13%) had preterm birth. The adjusted hazard ratio for the association between SARS-CoV-2 infection and preterm birth was 1.28 (95% confidence interval 0.82-1.99, p = 0.28), although results did not reach statistical significance.
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COVID-19 , Nacimiento Prematuro , Recién Nacido , Femenino , Embarazo , Humanos , COVID-19/epidemiología , Nacimiento Vivo , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , SARS-CoV-2 , VitaminasRESUMEN
Background: Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. Methods: In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Results: Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Conclusions: Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.
RESUMEN
OBJECTIVE: This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers. STUDY DESIGN: Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic ß-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy. RESULTS: Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: -0.24, 95% confidence interval: -0.44, -0.03). There were no differences between gestational hypertension and no HDP. CONCLUSION: In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum. KEY POINTS: · Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.. · Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.. · Longitudinal studies with postpartum interventions after preeclampsia are needed..