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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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Pharmacoepidemiological studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a non-linear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose-response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose-response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).
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This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.
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Anticonvulsivantes , Epilepsia , Trastornos del Neurodesarrollo , Complicaciones del Embarazo , Efectos Tardíos de la Exposición Prenatal , Femenino , Humanos , Recién Nacido , Embarazo , Anomalías Inducidas por Medicamentos/prevención & control , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Trastornos del Neurodesarrollo/prevención & control , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/inducido químicamente , Complicaciones del Embarazo/tratamiento farmacológico , Teratogénesis/efectos de los fármacosRESUMEN
Both endocannabinoid (EC) and endogenous opioid systems are involved in nociceptive processing and may work together synergistically based on preclinical models. This study evaluated the interactive effects of preoperative beta-endorphin (BE) concentrations (a key analgesic endogenous opioid) in cerebrospinal fluid (CSF) and ECs (CSF and plasma 2-arachidonoylglycerol and plasma anandamide) on postoperative opioid use and pain intensity in a prospective cohort of n = 112 pregnant patients undergoing scheduled cesarean delivery. Maternal blood and CSF samples were collected preoperatively for BE and EC assays. Patients completed measures of outpatient opioid use (number of tablets used and days of use) and average pain intensity at 2 weeks postoperatively. Results of general linear model analyses controlling for maternal age, body mass index at time of delivery, and race revealed significant multiplicative interactions between EC and BE concentrations on number of opioid tablets used (based on pill count), days of opioid use, and total milligram morphine equivalents used in the 2-week follow-up period. Elevated preoperative plasma and CSF 2-arachidonoylglycerol predicted reduced outpatient opioid analgesic use, particularly for patients low in CSF BE. Similar analyses for pain intensity at 2-week follow-up indicated a significant interaction (P < .02) characterized by higher preoperative BE concentrations being associated with lower subsequent pain only for individuals with low preoperative plasma anandamide concentrations. Further exploration of interactions between EC and endogenous opioid inhibitory systems as they influence responses to opioid analgesics in other clinical pain populations may help guide the development of precision pain management approaches. PERSPECTIVE: In the postoperative setting of patients undergoing cesarean delivery, elevated ECs were linked to reduced outpatient opioid analgesic use in individuals who had low endogenous opioid concentrations in CSF. Further exploration of interactions between these 2 inhibitory systems as they impact responses to pain management interventions appears warranted.
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Analgésicos Opioides , Ácidos Araquidónicos , Cesárea , Endocannabinoides , Glicéridos , Dolor Postoperatorio , Alcamidas Poliinsaturadas , Humanos , Femenino , Endocannabinoides/sangre , Endocannabinoides/líquido cefalorraquídeo , Embarazo , Adulto , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/líquido cefalorraquídeo , Dolor Postoperatorio/sangre , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/líquido cefalorraquídeo , Analgésicos Opioides/farmacología , Glicéridos/sangre , Glicéridos/líquido cefalorraquídeo , Alcamidas Poliinsaturadas/sangre , Alcamidas Poliinsaturadas/líquido cefalorraquídeo , Ácidos Araquidónicos/sangre , Ácidos Araquidónicos/líquido cefalorraquídeo , betaendorfina/sangre , betaendorfina/líquido cefalorraquídeo , Estudios Prospectivos , Adulto JovenRESUMEN
Importance: Opioid exposure during pregnancy has been associated with preterm birth, but prior studies have not differentiated between spontaneous and indicated preterm birth or fully investigated these associations as functions of opioid dose. Objective: To determine whether prescription opioid use during pregnancy is associated with spontaneous preterm birth and whether the association is dose-dependent. Design, Setting, and Participants: This case-control study examined a retrospective cohort of pregnant patients enrolled in Tennessee Medicaid. Enrollment files were linked to health care encounters, hospital discharge information, birth certificate data, and prescription fills. Eligible participants were pregnant people ages 15 to 44 years without opioid use disorder who experienced birth of a single fetus at 24 weeks gestation or greater between 2007 and 2019 with linked birth certificate data. Cases of spontaneous preterm birth were matched with up to 10 controls based on pregnancy start date, race, ethnicity, age at delivery within 2 years, and history of prior preterm birth. Cases and matched controls were continuously enrolled in TennCare for at least 90 days prior to the index date (case delivery date). Exposure: Total opioid MME filled during the 60 days prior to the index date. Main Outcomes and Measures: The primary outcome was spontaneous preterm birth determined by a validated algorithm using birth certificate data. Conditional logistic regression was used to estimate the association between spontaneous preterm birth and total opioid morphine milligram equivalents (MME) dispensed, adjusting for parity, prepregnancy body mass index, education level, tobacco use, hepatitis infections, and pain indications. Results: A total of 25â¯391 cases (median [IQR] age, 23 [20-28] years; 127 Asian [0.5%], 9820 Black [38.7%], 664 Hispanic [2.6%]; 14â¯748 non-Hispanic White [58.1%]) with spontaneous preterm birth were identified and matched with 225â¯696 controls (median [IQR] age, 23 [20-27] years; 229 Asian [0.1%], 89â¯819 Black [39.8%], 3590 Hispanic [1.6%]; 132â¯002 non-Hispanic White [58.5%]) (251â¯087 patients total), with 18â¯702 patients (7.4%) filling an opioid prescription in the 60 days prior to the index date. Each doubling of nonzero opioid MME was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure (adjusted odds ratio, 1.04; 95% CI, 1.01-1.08). Conclusions and Relevance: In this case-control study, a positive association was found between total prescription opioid dose dispensed and the odds of spontaneous preterm birth. These findings support guidance to minimize opioid exposure during pregnancy and prescribe the lowest dose necessary.
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Endrín/análogos & derivados , Trastornos Relacionados con Opioides , Nacimiento Prematuro , Recién Nacido , Estados Unidos , Femenino , Embarazo , Humanos , Adulto Joven , Adulto , Analgésicos Opioides/efectos adversos , Nacimiento Prematuro/epidemiología , Estudios de Casos y Controles , Estudios Retrospectivos , Trastornos Relacionados con Opioides/epidemiologíaRESUMEN
BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by widespread vascular inflammation. It occurs frequently in pregnancy, often without known risk factors, and has high rates of maternal and fetal morbidity and mortality. Identification of biomarkers that predict preeclampsia and its cardiovascular sequelae before clinical onset, or even before pregnancy, is a critical unmet need for the prevention of adverse pregnancy outcomes. METHODS: We explored differences in cardiovascular proteomics (Olink Explore 384) in 256 diverse pregnant persons across 2 centers (26% Hispanic, 21% Black). RESULTS: We identified significant differences in plasma abundance of markers associated with angiogenesis, blood pressure, cell adhesion, inflammation, and metabolism between individuals delivering with preeclampsia and controls, some of which have not been widely described previously and are not represented in the preeclampsia placental transcriptome. While we observed a broadly similar pattern in early (<34 weeks) versus late (≥34 weeks) preeclampsia, several proteins related to hemodynamic stress, hemostasis, and immune response appeared to be more highly dysregulated in early preeclampsia relative to late preeclampsia. CONCLUSIONS: These results demonstrate the value of performing targeted proteomics using a panel of cardiovascular biomarkers to identify biomarkers relevant to preeclampsia pathophysiology and highlight the need for larger multiomic studies to define modifiable pathways of surveillance and intervention upstream to preeclampsia diagnosis.
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Enfermedades Cardiovasculares , Preeclampsia , Embarazo , Femenino , Humanos , Preeclampsia/diagnóstico , Placenta , Resultado del Embarazo , Biomarcadores , Inflamación/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/complicaciones , Factor de Crecimiento PlacentarioRESUMEN
Background: Prior laboratory work indicates that lower endogenous opioid function is associated with greater analgesic and subjective responses to opioid analgesics. We evaluated whether lower preoperative cerebrospinal uid (CSF) levels of the analgesic endogenous opioid ß-Endorphin (BE) were associated with increased opioid use after cesarean delivery (CD). Methods: We enrolled 136 pregnant women without opioid use or chronic pain who were undergoing CD under regional anesthesia. Preoperatively, participants completed validated pain measures and biospecimens were collected to assess BE levels in plasma and CSF. Postoperatively, pain measures at 48 hours and 2 weeks postpartum were assessed. We evaluated the association between CSF BE levels and total opioid use (in morphine milligram equivalents; MMEs) using linear regression controlling for confounding factors (primary analysis). In secondary analyses, we examined: 1) associations between plasma BE levels and total opioid use, and 2) associations between CSF and plasma BE levels and secondary outcomes (inpatient versus outpatient opioid use, pain intensity). Results: Participants completed surveys with 100% response rate. The majority were non-Hispanic white (65%), college educated (58%), had private insurance (71%), and had a prior cesarean delivery (69%). Psychiatric diagnoses (depression or anxiety) were common, both currently (22%) and in the past (26%).The median total opioid use across the inpatient and 2-week postpartum follow-up period was 89.1 milligram morphine equivalents (IQR 25-138). Preoperative cerebrospinal uid ß-Endorphin levels were not associated with total opioid use (beta = -0.05, SE 0.45, p = 0.64). Similar findings were noted for plasma ß-Endorphin levels. cerebrospinal uid ß-Endorphin levels were only weakly correlated with plasma ß-Endorphin levels (r = 0.30, p < .01). Preoperative cerebrospinal uid and plasma ß-Endorphin levels were both positively associated with postpartum pain measures (cerebrospinal uid: at 48 hours, beta = 0.19, SE 0.16, p < 0.05; Plasma: at 48-hours, beta = 0.02, SE 0.03, p = 0.02, and at 2-weeks, beta = 0.27, SE 0.03, p < 0.01). Conclusions: Lower preoperative cerebrospinal uid levels of ß-Endorphin are not associated with increased opioid analgesic use after scheduled cesarean delivery. It is possible that unassessed variability in baseline opioid receptor sensitivity may have confounded ability to test associations between ß-Endorphin levels and opioid use outcomes.
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Importance: The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS). Objective: To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD. Design, Setting, and Participants: The study team conducted a retrospective cohort study of 390â¯075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023. Exposure: Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed). Main Outcome and Measures: The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death. Results: Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375â¯718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65). Conclusions and Relevance: Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.
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Síndrome de Abstinencia Neonatal , Trastornos Relacionados con Opioides , Lactante , Recién Nacido , Embarazo , Femenino , Masculino , Humanos , Adulto Joven , Adulto , Estudios Retrospectivos , Mortalidad Infantil , Trastornos Relacionados con Opioides/epidemiología , Madres , Síndrome de Abstinencia Neonatal/epidemiología , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Analgésicos Opioides/efectos adversosRESUMEN
Abstract. BACKGROUND: Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics. METHODS: Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report. RESULTS: After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed. CONCLUSIONS: There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.
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BACKGROUND: Suboptimal treatment of postpartum pain is associated with persistent pain and postpartum depression. Multimodal analgesia can achieve superior pain relief and decreased opioid consumption after surgery. There is limited and conflicting data on abdominal support devices to reduce postoperative pain and opioid use after cesarean delivery. OBJECTIVE: This study aimed to examine whether the use of a panniculus elevation device decreases opioid use and improves postoperative pain after cesarean delivery. STUDY DESIGN: This was an unblinded prospective trial in which eligible, consenting patients aged ≥18 years were randomized to the panniculus elevation device group or no device group within 36 hours after cesarean delivery. The device studied adheres to the abdomen and lifts the panniculus. Moreover, it can be repositioned during use. Patients with a vertical skin incision or chronic opioid use disorder were excluded. Participants were surveyed 10 and 14 days after delivery about opioid use and pain satisfaction. The primary outcome was total morphine milligram equivalents used after delivery. The secondary outcomes were inpatient and outpatient opioid use, subjective pain scores, and Patient-Reported Outcomes Measurement Information System pain interference scores. An a priori subgroup analysis was performed on participants with obesity who may uniquely benefit from panniculus elevation. RESULTS: Of 538 patients screened for inclusion from April 2021 to July 2022, 484 were eligible, and 278 were consented and randomized. Moreover, 56 participants (20%) were lost to follow-up, leaving 222 (118 in the device group vs 104 in the control group) for analysis. Follow-up frequency was similar between groups (P=.09). Demographic and clinical characteristics were similar between groups. There was no statistically significant difference in total opioid use, other opioid use measures, or pain satisfaction outcomes. Median device use was 5 days (interquartile range, 3-9), and 64% of participants randomized to device use stated that they would use it again. Here, similar trends were observed among participants with obesity (n=152). CONCLUSION: The use of a panniculus elevation device did not significantly reduce total opioid use after cesarean delivery in patients.
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Analgésicos Opioides , Dolor Postoperatorio , Embarazo , Femenino , Humanos , Adolescente , Adulto , Analgésicos Opioides/efectos adversos , Estudios Prospectivos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Cesárea/efectos adversosRESUMEN
OBJECTIVE: Our study examines the association between social vulnerability index (SVI) and pharmacotherapy initiation for gestational diabetes mellitus (GDM). METHODS: We studied a retrospective cohort of pregnant patients with GDM, enrolled in Tennessee Medicaid, who gave birth between 2007 and 2019. Enrollment files were linked to birth and death certificates, state hospitalization registries, and pharmacy claims. SVI, measured at the community level and determined by residential census tract, ranged from 0 to 100 (low to high vulnerability). Multivariable logistic regression assessed the association between SVI and the odds of initiating the most common pharmacotherapies for GDM-insulin, glyburide, or metformin-and adjusted for relevant covariates. SVI was modeled with restricted cubic splines to account for nonlinear associations, using the median Tennessee SVI as a reference. Secondary analysis assessed associations with the SVI subthemes. RESULTS: Among 33,291 patients with GDM, 21.7% (7,209) initiated pharmacotherapy during pregnancy. Patients from areas with higher SVI were more likely to be non-Hispanic Black with higher body mass index, whereas those with lower SVI were more likely to be nulliparous. Multivariable modeling demonstrated a complex nonlinear association between SVI and GDM pharmacotherapy initiation, relative to the reference. Higher SVI was associated with elevated odds of GDM pharmacotherapy initiation (e.g., odds ratio 1.11 [95% confidence interval 1.02-1.22] for SVI 80) and low to medium SVI had variable nonsignificant associations with GDM pharmacotherapy initiation, relative to the reference (lower odds of initiation for values 25-50, higher odds of initiation for values < 25). Secondary analysis demonstrated a nonlinear association between subtheme 3 and the odds of GDM pharmacotherapy initiation. CONCLUSION: Social vulnerability is associated with initiation of pharmacotherapy for GDM, highlighting the possible role of social determinants of health in achieving glycemic control.
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Diabetes Gestacional , Embarazo , Femenino , Humanos , Diabetes Gestacional/tratamiento farmacológico , Estudios Retrospectivos , Vulnerabilidad Social , Medicaid , Gliburida/uso terapéuticoRESUMEN
Systemic lupus erythematosus (SLE) is a chronic, multisystem, inflammatory autoimmune disease characterized by relapses (commonly called "flares") and remission. Many organs may be involved, and although the manifestations are highly variable, the kidneys, joints, and skin are commonly affected. Immunologic abnormalities, including the production of antinuclear antibodies, are also characteristic of the disease. Maternal morbidity and mortality are substantially increased in patients with systemic lupus erythematosus, and an initial diagnosis of systemic lupus erythematosus during pregnancy is associated with increased morbidity. Common complications of systemic lupus erythematosus include nephritis, hematologic complications such as thrombocytopenia, and a variety of neurologic abnormalities. The purpose of this document is to examine potential pregnancy complications and to provide recommendations on treatment and management of systemic lupus erythematosus during pregnancy. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend low-dose aspirin beginning at 12 weeks of gestation until delivery in patients with systemic lupus erythematosus to decrease the occurrence of preeclampsia (GRADE 1B); (2) we recommend that all patients with systemic lupus erythematosus, other than those with quiescent disease, either continue or initiate hydroxychloroquine (HCQ) in pregnancy (GRADE 1B); (3) we suggest that for all other patients with quiescent disease activity who are not taking HCQ or other medications, it is reasonable to engage in shared decision-making regarding whether to initiate new therapy with this medication in consultation with the patient's rheumatologist (GRADE 2B); (4) we recommend that prolonged use (>48 hours) of nonsteroidal antiinflammatory drugs (NSAIDs) generally be avoided during pregnancy (GRADE 1A); (5) we recommend that COX-2 inhibitors and full-dose aspirin be avoided during pregnancy (GRADE 1B); (6) we recommend discontinuing methotrexate 1-3 months and mycophenolate mofetil/mycophenolic acid at least 6 weeks before attempting pregnancy (GRADE 1A); (7) we suggest the decision to initiate, continue, or discontinue biologics in pregnancy be made in collaboration with a rheumatologist and be individualized to the patient (GRADE 2C); (8) we suggest treatment with a combination of prophylactic unfractionated or low-molecular-weight heparin and low-dose aspirin for patients without a previous thrombotic event who meet obstetrical criteria for antiphospholipid syndrome (APS) (GRADE 2B); (9) we recommend therapeutic unfractionated or low-molecular-weight heparin for patients with a history of thrombosis and antiphospholipid (aPL) antibodies (GRADE 1B); (10) we suggest treatment with low-dose aspirin alone in patients with systemic lupus erythematosus and antiphospholipid antibodies without clinical events meeting criteria for antiphospholipid syndrome (GRADE 2C); (11) we recommend that steroids not be routinely used for the treatment of fetal heart block due to anti-Sjögren's-syndrome-related antigen A or B (anti-SSA/SSB) antibodies given their unproven benefit and the known risks for both the pregnant patient and fetus (GRADE 1C); (12) we recommend that serial fetal echocardiograms for assessment of the PR interval not be routinely performed in patients with anti-SSA/SSB antibodies outside of a clinical trial setting (GRADE 1B); (13) we recommend that patients with systemic lupus erythematosus undergo prepregnancy counseling with both maternal-fetal medicine and rheumatology specialists that includes a discussion regarding maternal and fetal risks (GRADE 1C); (14) we recommend that pregnancy be generally discouraged in patients with severe maternal risk, including patients with active nephritis; severe pulmonary, cardiac, renal, or neurologic disease; recent stroke; or pulmonary hypertension (GRADE 1C); (15) we recommend antenatal testing and serial growth scans in pregnant patients with systemic lupus erythematosus because of the increased risk of fetal growth restriction (FGR) and stillbirth (GRADE 1B); and (16) we recommend adherence to the Centers for Disease Control and Prevention medical eligibility criteria for contraceptive use in patients with systemic lupus erythematosus (GRADE 1B).
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Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Nefritis , Complicaciones del Embarazo , Embarazo , Humanos , Femenino , Síndrome Antifosfolípido/complicaciones , Perinatología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Complicaciones del Embarazo/terapia , Complicaciones del Embarazo/tratamiento farmacológico , Anticuerpos Antifosfolípidos , Hidroxicloroquina/uso terapéutico , Aspirina/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Nefritis/complicaciones , Nefritis/tratamiento farmacológico , Derivación y ConsultaAsunto(s)
Analgésicos Opioides , Obstetricia , Embarazo , Femenino , Humanos , Tennessee , Pautas de la Práctica en Medicina , CesáreaRESUMEN
The prevalence of pregnant people with opioid use disorder (OUD), including those receiving medications for opioid use disorder (MOUD), is increasing. Challenges associated with pain management in people with OUD include tolerance, opioid-induced hyperalgesia, and risk for return to use. Yet, there are few evidence-based recommendations for pain management in the setting of pregnancy and the postpartum period, and many peripartum pain management studies exclude people with OUD. This scoping review summarized the available literature on peridelivery pain management in people with OUD, methodologies used, and identified specific areas of knowledge gaps. PubMed and Embase were comprehensively searched for publications in all languages on peripartum pain management among people with OUD, both treated with MOUD and untreated. Potential articles were screened by title, abstract, and full text. Data abstracted were descriptively analyzed to map available evidence and identify areas of limited or no evidence. A total of 994 publications were imported for screening on title, abstracts, and full text, yielding 84 publications identified for full review: 32 (38.1%) review articles, 14 (16.7%) retrospective studies, and 8 (9.5%) case reports. There were 5 randomized controlled trials. Most studies (64%) were published in perinatology (32; 38.1%) journals or anesthesiology (22; 26.2%) journals. Specific areas lacking trial or systematic review evidence include: (1) methods to optimize psychological and psychosocial comorbidities relevant to acute pain management around delivery; (2) alternative nonopioid and nonpharmacologic analgesia methods; (3) whether or not to use opioids for severe breakthrough pain and how best to prescribe and monitor its use after discharge; (4) monitoring for respiratory depression and sedation with coadministration of other analgesics; (5) optimal neuraxial analgesia dosing and adjuncts; and (6) benefits of abdominal wall blocks after cesarean delivery. No publications discussed naloxone coprescribing in the labor and delivery setting. We observed an increasing number of publications on peripartum pain management in pregnant people with OUD. However, existing published works are low on the pyramid of evidence (reviews, opinions, and retrospective studies), with a paucity of original research articles (<6%). Opinions are conflicting on the utility and disutility of various analgesic interventions. Studies generating high-quality evidence on this topic are needed to inform care for pregnant people with OUD. Specific research areas are identified, including utility and disutility of short-term opioid use for postpartum pain management, role of continuous wound infiltration and truncal nerve blocks, nonpharmacologic analgesia options, and the best methods to support psychosocial aspects of pain management.
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Anestesia Obstétrica , Trastornos Relacionados con Opioides , Embarazo , Femenino , Humanos , Manejo del Dolor/efectos adversos , Manejo del Dolor/métodos , Analgésicos Opioides , Perinatología , Estudios Retrospectivos , Trastornos Relacionados con Opioides/diagnóstico , Analgésicos/uso terapéutico , NaloxonaRESUMEN
OBJECTIVE: Current evidence is conflicting on whether early screening and treatment for gestational diabetes mellitus improve pregnancy outcomes. Thus, this systematic review and meta-analysis of randomized controlled trials aimed to assess the rate of adverse pregnancy outcomes among participants with early screening and treatment for gestational diabetes mellitus vs those with routine care. DATA SOURCES: A systematic review of the literature was conducted using MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the Central Register of Controlled Trials, and SciELO from inception to November 2021. STUDY ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they described randomized controlled trials comparing early screening with routine care for gestational diabetes mellitus to assess the effects of early screening and treatment on pregnancy outcomes. METHODS: All randomized controlled trials comparing early vs standard screening of gestational diabetes mellitus assessing the effect of early screening (defined as a screening at <20 weeks of gestation) vs routine screening (defined as a screening at ≥20 weeks of gestation) on pregnancy outcomes were included. The primary outcome was defined as large for gestational age, as defined by the trial. The secondary maternal and neonatal outcomes were also evaluated. Subgroup analyses were performed on the basis of screening strategy and methods. RESULTS: After exclusion, 8 randomized clinical trials (1920 participants) of early screening and treatment vs standard care were included. There were a total of 746 participants with early gestational diabetes mellitus. The risk of large for gestational age at birth did not differ between early screening and treatment for gestational diabetes mellitus and routine care among all included trials (8.1 vs 9.0%; relative risk, 0.94; 95% confidence interval, 0.73-1.22). Trials with a protocol of universal screening of participants at their first prenatal visit (>80% screened with HbA1c) and receiving early treatment if the screening test returned positive had a lower risk of large for gestational age (2.3 vs 9.1%; relative risk, 0.29; 95% confidence interval, 0.09-0.90) than those who had routine screening and care. CONCLUSION: Overall, early screening and treatment of gestational diabetes mellitus did not reduce the risk of large for gestational age at birth. However, trials that screened all participants at their first visit and treated early, most for an HbA1c of 5.7% to 6.4%, had a reduced risk of large for gestational age at birth compared with routine care, suggesting a possible benefit of screening all pregnant patients. However, future well-designed trials are needed to confirm these findings.
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OBJECTIVE: Opioids are commonly prescribed to women for acute pain following childbirth. Postpartum prescription opioid exposure is associated with adverse opioid-related morbidities but the association with all-cause mortality is not well studied. This study aimed to examine the association between postpartum opioid prescription fills and the 1-year risk of all-cause mortality among women with live births. METHODS: In a retrospective cohort study of live births among women enrolled in Tennessee Medicaid (TennCare) between 2007 and 2015, we compared women who filled two or more postpartum outpatient opioid prescriptions (up to 41 days of postdelivery discharge) to women who filled one or fewer opioid prescription. Women were followed from day 42 postdelivery discharge through 365 days of follow-up or date of death. Deaths were identified using linked death certificates (2007-2016). We used Cox's proportional hazard regression and inverse probability of treatment weights to compare time to death between exposure groups while adjusting for relevant confounders. We also examined effect modification by delivery route, race, opioid use disorder, use of benzodiazepines, and mental health condition diagnosis. RESULTS: Among 264,135 eligible births, 216,762 (82.1%) had one or fewer maternal postpartum opioid fills and 47,373 (17.9%) had two or more fills. There were 182 deaths during follow-up. The mortality rate was higher in women with two or more fills (120.5 per 100,000 person-years) than in those with one or fewer (57.7 per 100,000 person-years). The risk of maternal death remained higher in participants exposed to two or more opioid fills after accounting for relevant covariates using inverse probability of treatment weighting (adjusted hazard ratio: 1.46 [95% confidence interval: 1.01, 2.09]). Findings from stratified analyses were consistent with main findings. CONCLUSION: Filling two or more opioid prescriptions during the postpartum period was associated with a significant increase in 1-year risk of death among new mothers. KEY POINTS: · Opioid prescribing in the postpartum period is common.. · Prior studies show that >1 postnatal opioid fill is associated with adverse opioid-related events.. · > 1 opioid fill within 42 days of delivery was associated with an increase in 1-year risk of death..
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OBJECTIVE: To develop and validate a prediction model for postdischarge opioid use in patients undergoing cesarean birth. METHODS: We conducted a prospective cohort study of patients undergoing cesarean birth. Patients were enrolled postoperatively, and they completed pain and opioid use questionnaires 14 days after cesarean birth. Clinical data were abstracted from the electronic health record (EHR). Participants were prescribed 30 tablets of hydrocodone 5 mg-acetaminophen 325 mg at discharge and were queried about postdischarge opioid use. The primary outcome was total morphine milligram equivalents used. We constructed three proportional odds predictive models of postdischarge opioid use: a full model with 34 predictors available before hospital discharge, an EHR model that excluded questionnaire data, and a reduced model. The reduced model used forward selection to sequentially add predictors until 90% of the full model performance was achieved. Predictors were ranked a priori based on data from the literature and prior research. Predictive accuracy was estimated using discrimination (concordance index). RESULTS: Between 2019 and 2020, 459 participants were enrolled and 279 filled the standardized study prescription. Of the 398 with outcome measurements, participants used a median of eight tablets (interquartile range 1-18 tablets) after discharge, 23.5% used no opioids, and 23.0% used all opioids. Each of the models demonstrated high accuracy predicting postdischarge opioid use (concordance index range 0.74-0.76 for all models). We selected the reduced model as our final model given its similar model performance with the fewest number of predictors, all obtained from the EHR (inpatient opioid use, tobacco use, and depression or anxiety). CONCLUSION: A model with three predictors readily found in the EHR-inpatient opioid use, tobacco use, and depression or anxiety-accurately estimated postdischarge opioid use. This represents an opportunity for individualizing opioid prescriptions after cesarean birth.