Magnesium sulfate and risk of hypoxic-ischemic encephalopathy in a high-risk cohort.

BACKGROUND: Hypoxic-ischemic encephalopathy contributes to morbidity and mortality among neonates ≥36 weeks of gestation. Evidence of preventative antenatal treatment is limited. Magnesium sulfate has neuroprotective properties among preterm fetuses. Hypertensive disorders of pregnancy are a risk factor for hypoxic-ischemic encephalopathy, and magnesium sulfate is recommended for maternal seizure prophylaxis among patients with preeclampsia with severe features. OBJECTIVE: (1) Determine trends in the incidence of hypertensive disorders of pregnancy, antenatal magnesium sulfate, and hypoxic-ischemic encephalopathy; (2) evaluate the association between hypertensive disorders of pregnancy and hypoxic-ischemic encephalopathy; and (3) evaluate if, among patients with hypertensive disorders of pregnancy, the odds of hypoxic-ischemic encephalopathy is mitigated by receipt of antenatal magnesium sulfate. STUDY DESIGN: We analyzed a prospective cohort of live births ≥36 weeks of gestation between 2012 and 2018 within the California Perinatal Quality Care Collaborative registry, linked with the California Department of Health Care Access and Information files. We used Cochran-Armitage tests to assess trends in hypertensive disorders, encephalopathy diagnoses, and magnesium sulfate utilization and compared demographic factors between patients with or without hypertensive disorders of pregnancy or treatment with magnesium sulfate. Hierarchical logistic regression models were built to explore if hypertensive disorders of pregnancy were associated with any severity and moderate/severe hypoxic-ischemic encephalopathy. Separate hierarchical logistic regression models were built among those with hypertensive disorders of pregnancy to evaluate the association of magnesium sulfate with hypoxic-ischemic encephalopathy. RESULTS: Among 44,314 unique infants, the diagnosis of hypoxic-ischemic encephalopathy, maternal hypertensive disorders of pregnancy, and the use of magnesium sulfate increased over time. Compared with patients with hypertensive disorders of pregnancy alone, patients with hypertensive disorders treated with magnesium sulfate represented a high-risk population. They were more likely to be publicly insured, born between 36 and 38 weeks of gestation, be small for gestational age, have lower Apgar scores, require a higher level of resuscitation at delivery, have prolonged rupture of membranes, experience preterm labor and fetal distress, and undergo operative delivery (all P<.002). Hypertensive disorders of pregnancy were associated with hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.13-1.40]; P<.001) and specifically moderate/severe hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.11-1.42]; P<.001). Among patients with hypertensive disorders of pregnancy, treatment with magnesium sulfate was associated with 29% reduction in the odds of neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.71 [95% confidence interval, 0.52-0.97]; P=.03) and a 37% reduction in the odds of moderate/severe neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.63 [95% confidence interval, 0.42-0.94]; P=.03). CONCLUSION: Hypertensive disorders of pregnancy are associated with hypoxic-ischemic encephalopathy and, specifically, moderate/severe disease. Among people with hypertensive disorders, receipt of antenatal magnesium sulfate is associated with a significant reduction in the odds of hypoxic-ischemic encephalopathy and moderate/severe disease in a neonatal cohort admitted to neonatal intensive care unit at ≥36 weeks of gestation. The findings of this observational study cannot prove causality and are intended to generate hypotheses for future clinical trials on magnesium sulfate in term infants.

Validity of ICD-10 diagnosis codes for placenta accreta spectrum disorders.

BACKGROUND: The 10th revision of the International Classification of Diseases, Clinical Modification (ICD-10) includes diagnosis codes for placenta accreta spectrum for the first time. These codes could enable valuable research and surveillance of placenta accreta spectrum, a life-threatening pregnancy complication that is increasing in incidence. OBJECTIVE: We sought to evaluate the validity of placenta accreta spectrum diagnosis codes that were introduced in ICD-10 and assess contributing factors to incorrect code assignments. METHODS: We calculated sensitivity, specificity, positive predictive value and negative predictive value of the ICD-10 placenta accreta spectrum code assignments after reviewing medical records from October 2015 to March 2020 at a quaternary obstetric centre. Histopathologic diagnosis was considered the gold standard. RESULTS: Among 22,345 patients, 104 (0.46%) had an ICD-10 code for placenta accreta spectrum and 51 (0.23%) had a histopathologic diagnosis. ICD-10 codes had a sensitivity of 0.71 (95% CI 0.56, 0.83), specificity of 0.98 (95% CI 0.93, 1.00), positive predictive value of 0.61 (95% CI 0.48, 0.72) and negative predictive value of 1.00 (95% CI 0.96, 1.00). The sensitivities of the ICD-10 codes for placenta accreta spectrum subtypes- accreta, increta and percreta-were 0.55 (95% CI 0.31, 0.78), 0.33 (95% CI 0.12, 0.62) and 0.56 (95% CI 0.31, 0.78), respectively. Cases with incorrect code assignment were less morbid than cases with correct code assignment, with a lower incidence of hysterectomy at delivery (17% vs 100%), blood transfusion (26% vs 75%) and admission to the intensive care unit (0% vs 53%). Primary reasons for code misassignment included code assigned to cases of occult placenta accreta (35%) or to cases with clinical evidence of placental adherence without histopatholic diagnostic (35%) features. CONCLUSION: These findings from a quaternary obstetric centre suggest that ICD-10 codes may be useful for research and surveillance of placenta accreta spectrum, but researchers should be aware of likely substantial false positive cases.

Associations between anxiety, sleep, and blood pressure parameters in pregnancy: a prospective pilot cohort study.

BACKGROUND: The potential effect modification of sleep on the relationship between anxiety and elevated blood pressure (BP) in pregnancy is understudied. We evaluated the relationship between anxiety, insomnia, and short sleep duration, as well as any interaction effects between these variables, on BP during pregnancy. METHODS: This was a prospective pilot cohort of pregnant people between 23 to 36 weeks' gestation at a single institution between 2021 and 2022. Standardized questionnaires were used to measure clinical insomnia and anxiety. Objective sleep duration was measured using a wrist-worn actigraphy device. Primary outcomes were systolic (SBP), diastolic (DBP), and mean (MAP) non-invasive BP measurements. Separate sequential multivariable linear regression models fit with generalized estimating equations (GEE) were used to separately assess associations between anxiety (independent variable) and each BP parameter (dependent variables), after adjusting for potential confounders (Model 1). Additional analyses were conducted adding insomnia and the interaction between anxiety and insomnia as independent variables (Model 2), and adding short sleep duration and the interaction between anxiety and short sleep duration as independent variables (Model 3), to evaluate any moderating effects on BP parameters. RESULTS: Among the 60 participants who completed the study, 15 (25%) screened positive for anxiety, 11 (18%) had subjective insomnia, and 34 (59%) had objective short sleep duration. In Model 1, increased anxiety was not associated with increases in any BP parameters. When subjective insomnia was included in Model 2, increased DBP and MAP was significantly associated with anxiety (DBP: ß 6.1, p = 0.01, MAP: ß 6.2 p < 0.01). When short sleep was included in Model 3, all BP parameters were significantly associated with anxiety (SBP: ß 9.6, p = 0.01, DBP: ß 8.1, p < 0.001, and MAP: ß 8.8, p < 0.001). No moderating effects were detected between insomnia and anxiety (p interactions: SBP 0.80, DBP 0.60, MAP 0.32) or between short sleep duration and anxiety (p interactions: SBP 0.12, DBP 0.24, MAP 0.13) on BP. CONCLUSIONS: When including either subjective insomnia or objective short sleep duration, pregnant people with anxiety had 5.1-9.6 mmHg higher SBP, 6.1-8.1 mmHg higher DBP, and 6.2-8.8 mmHg higher MAP than people without anxiety.

Trends and Disparities in Severe Maternal Morbidity Indicator Categories during Childbirth Hospitalization in California from 1997 to 2017.

OBJECTIVE: Severe maternal morbidity (SMM) is increasing and characterized by substantial racial and ethnic disparities. Analyzing trends and disparities across time by etiologic or organ system groups instead of an aggregated index may inform specific, actionable pathways to equitable care. We explored trends and racial and ethnic disparities in seven SMM categories at childbirth hospitalization. STUDY DESIGN: We analyzed California birth cohort data on all live and stillbirths ≥ 20 weeks' gestation from 1997 to 2017 (n = 10,580,096) using the Centers for Disease Control and Prevention's SMM index. Cases were categorized into seven nonmutually exclusive indicator categories (cardiac, renal, respiratory, hemorrhage, sepsis, other obstetric, and other medical SMM). We compared prevalence and trends in SMM indicator categories overall and by racial and ethnic group using logistic and linear regression. RESULTS: SMM occurred in 1.16% of births and nontransfusion SMM in 0.54%. Hemorrhage SMM occurred most frequently (27 per 10,000 births), followed by other obstetric (11), respiratory (7), and sepsis, cardiac, and renal SMM (5). Hemorrhage, renal, respiratory, and sepsis SMM increased over time for all racial and ethnic groups. The largest disparities were for Black individuals, including over 3-fold increased odds of other medical SMM. Renal and sepsis morbidity had the largest relative increases over time (717 and 544%). Sepsis and hemorrhage SMM had the largest absolute changes over time (17 per 10,000 increase). Disparities increased over time for respiratory SMM among Black, U.S.-born Hispanic, and non-U.S.-born Hispanic individuals and for sepsis SMM among Asian or Pacific Islander individuals. Disparities decreased over time for sepsis SMM among Black individuals yet remained substantial. CONCLUSION: Our research further supports the critical need to address SMM and disparities as a significant public health priority in the United States and suggests that examining SMM subgroups may reveal helpful nuance for understanding trends, disparities, and potential needs for intervention. KEY POINTS: · By SMM subgroup, trends and racial and ethnic disparities varied yet Black individuals consistently had highest rates.. · Hemorrhage, renal, respiratory, and sepsis SMM significantly increased over time.. · Disparities increased for respiratory SMM among Black, U.S.-born Hispanic and non-U.S.-born Hispanic individuals and for sepsis SMM among Asian or Pacific Islander individuals..

A Novel Fetal Magnetic Resonance Imaging Lung Volume Nomogram Stratified by Estimated Fetal Weight.

INTRODUCTION: Fetal magnetic resonance imaging (MRI) lung volume nomograms are increasingly used to prognosticate neonatal outcomes in fetuses with suspected pulmonary hypoplasia. However, pregnancies complicated by fetal anomalies associated with pulmonary hypoplasia may also be complicated by fetal growth restriction (FGR). If a small lung volume is suspected in such cases, it is often unclear whether the lungs are "small" because of underlying lung pathology, or small fetal size. Existing MRI lung volume nomograms have mostly been stratified by gestational age (GA), rather than estimated fetal weight (EFW). Therefore, we aimed to develop a novel fetal lung volume nomogram stratified by EFW. METHODS: Consecutive fetal MRIs performed at a quaternary medical center from 2019 to 2021 were analyzed. MRIs performed due to fetal lung anomalies and cases with FGR were excluded. All MRIs were performed without IV contrast on GE 3 or 1.5 Tesla scanners (GE Healthcare). Images were reviewed by three experienced fetal radiologists. Freehand ROI in square centimeter was drawn around the contours of the lungs on consecutive slices from the apex to the base. The volume of the right, left and total lungs were calculated in mL. Lung volumes were plotted by both EFW and GA. RESULTS: Among 301 MRI studies performed during the study period, 170 cases met inclusion criteria and were analyzed. MRIs were performed between 19- and 38-week gestation, and a sonographic EFW was obtained within a mean of 2.9 days (SD ± 5.5 days, range 0-14 days) of each MRI. Nomograms stratified by both EFW and GA were created using 200 g. and weekly intervals respectively. A formula using EFW to predict total lung volume was calculated: LV = 0.07497804 EFW0.88276 (R2 = 0.87). CONCLUSIONS: We developed a novel fetal lung volume nomogram stratified by EFW. If validated, this nomogram may assist clinicians predict outcomes in cases of fetal pulmonary hypoplasia with concomitant FGR.

Validation of ICD-10-CM Diagnosis Codes for Gestational Age at Birth.

BACKGROUND: The International Classification of Diseases , 10th Revision, Clinical Modification (ICD-10-CM) introduced diagnosis codes for week of gestation. Our objective was to assess the validity of these codes among live births, which could have major utility in perinatal research and quality improvement. METHODS: We used linked birth certificate and patient discharge data from births in California during 2016-2019 (N = 1,843,992). We identified gestational age using Z3A.xx ICD-10-CM diagnosis codes in birthing patient discharge data and compared it with the gold standard of obstetric estimate, as recorded on the birth certificate. We further assessed sensitivity and specificity of gestational age categories (≥37 weeks, <37 weeks, <32 weeks, <28 weeks), given these categories are frequently of interest, and evaluated differences in validity of preterm birth (<37 weeks' gestation) by patient characteristics. RESULTS: One-million seven-hundred seventy-thousand one-hundred three patients had a gestational age recorded in patient discharge and birth certificate data. When comparing gestational age in patient discharge data with birth certificate data, the concordance correlation coefficient was 0.96 (95% confidence interval [CI] = 0.96, 0.96) and the mean difference between the two measurements was 0.047 weeks (95% CI = 0.046, 0.047 weeks). Ninety-five percent of the differences between the two measurements were between -1.00 week and +1.09 weeks. Sensitivity and specificity were 0.94 to 1.00 for all gestational age categories and were 0.94 to 1.00 for preterm birth across sociodemographic groups. CONCLUSIONS: We found week-specific gestational age at delivery ICD-10-CM diagnosis codes in patient discharge data to have high validity when compared with the best obstetric estimate on the birth certificate.

Early Postpartum Hospital Encounters among Patients with Genitourinary and Wound Infections during Hospitalization for Birth.

OBJECTIVES: This study aimed to assess the associations between genitourinary and wound infections during the birth hospitalization and early postpartum hospital encounters, and to evaluate clinical risk factors for early postpartum hospital encounters among patients with genitourinary and wound infections during the birth hospitalization. STUDY DESIGN: We conducted a population-based cohort study of births in California during 2016 to 2018 and postpartum hospital encounters. We identified genitourinary and wound infections using diagnosis codes. Our main outcome was early postpartum hospital encounter, defined as a readmission or emergency department (ED) visit within 3 days after discharge from the birth hospitalization. We evaluated the association of genitourinary and wound infections (overall and subtypes) with early postpartum hospital encounter using logistic regression, adjusting for sociodemographic factors and comorbidities and stratified by mode of birth. We then evaluated factors associated with early postpartum hospital encounter among patients with genitourinary and wound infections. RESULTS: Among 1,217,803 birth hospitalizations, 5.5% were complicated by genitourinary and wound infections. Genitourinary or wound infection was associated with an early postpartum hospital encounter among patients with both vaginal births (2.2%; adjusted risk ratio [aRR[: 1.26; 95% confidence interval [CI]: 1.17-1.36) and cesarean births (3.2%; aRR: 1.23; 95% CI: 1.15-1.32). Patients with a cesarean birth and a major puerperal infection or wound infection had the highest risk of an early postpartum hospital encounter (6.4 and 4.3%, respectively). Among patients with genitourinary and wound infections during the birth hospitalization, factors associated with an early postpartum hospital encounter included severe maternal morbidity, major mental health condition, prolonged postpartum hospital stay, and, among cesarean births, postpartum hemorrhage (p-value < 0.05). CONCLUSION: Genitourinary and wound infections during hospitalization for birth may increase risk of a readmission or ED visit within the first few days after discharge, particularly among patients who have a cesarean birth and a major puerperal infection or wound infection. KEY POINTS: · In all, 5.5% of patients giving birth had a genitourinary or wound infection (GWI).. · A total of 2.7% of GWI patients had a hospital encounter within 3 days of discharge after birth.. · Major puerperal infection and wound infection had the highest risk of an early hospital encounter.. · Among GWI patients, several birth complications were associated with an early hospital encounter..

Vaginal Progesterone Is Associated with Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: The frequency of intrahepatic cholestasis of pregnancy (ICP) peaks during the third trimester of pregnancy when plasma progesterone levels are the highest. Furthermore, twin pregnancies are characterized by higher progesterone levels than singletons and have a higher frequency of cholestasis. Therefore, we hypothesized that exogenous progestogens administered for reducing the risk of spontaneous preterm birth may increase the risk of cholestasis. Utilizing the large IBM MarketScan Commercial Claims and Encounters Database, we investigated the frequency of cholestasis in patients treated with vaginal progesterone or intramuscular 17α-hydroxyprogesterone caproate for the prevention of preterm birth. STUDY DESIGN: We identified 1,776,092 live-born singleton pregnancies between 2010 and 2014. We confirmed second and third trimester administration of progestogens by cross-referencing the dates of progesterone prescriptions with the dates of scheduled pregnancy events such as nuchal translucency scan, fetal anatomy scan, glucose challenge test, and Tdap vaccination. We excluded pregnancies with missing data regarding timing of scheduled pregnancy events or progesterone treatment prescribed only during the first trimester. Cholestasis of pregnancy was identified based on prescriptions for ursodeoxycholic acid. We used multivariable logistic regression to estimate adjusted (for maternal age) odds ratios for cholestasis in patients treated with vaginal progesterone, and in patients treated with 17α-hydroxyprogesterone caproate compared with those not treated with any type of progestogen (the reference group). RESULTS: The final cohort consisted of 870,599 pregnancies. Among patients treated with vaginal progesterone during the second and third trimester, the frequency of cholestasis was significantly higher than the reference group (0.75 vs. 0.23%, adjusted odds ratio [aOR]: 3.16, 95% confidence interval [CI]: 2.23-4.49). In contrast, there was no significant association between 17α-hydroxyprogesterone caproate and cholestasis (0.27%, aOR: 1.12, 95% CI: 0.58-2.16) CONCLUSION: Using a robust dataset, we observed that vaginal progesterone but not intramuscular 17α-hydroxyprogesterone caproate was associated with an increased risk for ICP. KEY POINTS: · Previous studies have been underpowered to detect potential association between progesterone and ICP.. · Vaginal progesterone was significantly associated with ICP.. · Intramuscular 17α-hydroxyprogesterone was not associated with ICP..

Sexual and/or gender minority disparities in obstetrical and birth outcomes.

BACKGROUND: Many sexual and/or gender minority individuals build families through pregnancy and childbirth, but it is unknown whether they experience different clinical outcomes than those who are not sexual and/or gender minority individuals. OBJECTIVE: To evaluate obstetrical and birth outcomes comparing couples who are likely sexual and/or gender minority patients compared with those who are not likely to be sexual and/or gender minority patients. STUDY DESIGN: We performed a population-based cohort study of live birth hospitalizations during 2016 to 2019 linked to birth certificates in California. California changed its birth certificate in 2016 to include gender-neutral fields such as "parent giving birth" and "parent not giving birth," with options for each role to specify "mother," "father," or "parent." We classified birthing patients in mother-mother partnerships and those who identified as a father in any partnership as likely sexual and/or gender minority and classified birthing patients in mother-father partnerships as likely not sexual and/or gender minority. We used multivariable modified Poisson regression models to estimate the risk ratios for associations between likely sexual and/or gender minority parental structures and outcomes. The models were adjusted for sociodemographic factors, comorbidities, and multifetal gestation selected by causal diagrams. We replicated the analyses after excluding multifetal gestations. RESULTS: In the final birthing patient sample, 1,483,119 were mothers with father partners, 2572 were mothers with mother partners, and 498 were fathers with any partner. Compared with birthing patients in mother-father partnerships, birthing patients in mother-mother partnerships experienced significantly higher rates of multifetal gestation (adjusted risk ratio, 3.9; 95% confidence interval, 3.4-4.4), labor induction (adjusted risk ratio, 1.2; 95% confidence interval, 1.1-1.3), postpartum hemorrhage (adjusted risk ratio, 1.4; 95% confidence interval, 1.3-1.6), severe morbidity (adjusted risk ratio, 1.4; 95% confidence interval, 1.2-1.8), and nontransfusion severe morbidity (adjusted risk ratio, 1.4; 95% confidence interval, 1.1-1.9). Severe morbidity was identified following the Centers for Disease Control and Prevention "severe maternal morbidity" index. Gestational diabetes mellitus, hypertensive disorders of pregnancy, cesarean delivery, preterm birth (<37 weeks' gestation), low birthweight (<2500 g), and low Apgar score (<7 at 5 minutes) did not significantly differ in the multivariable analyses. No outcomes significantly differed between father birthing patients in any partnership and birthing patients in mother-father partnerships in either crude or multivariable analyses, though the risk of multifetal gestation was nonsignificantly higher (adjusted risk ratio, 1.5; 95% confidence interval, 0.9-2.7). The adjusted risk ratios for the outcomes were similar after restriction to singleton gestations. CONCLUSION: Birthing mothers with mother partners experienced disparities in several obstetrical and birth outcomes independent of sociodemographic factors, comorbidities, and multifetal gestation. Birthing fathers in any partnership were not at a significantly elevated risk of any adverse obstetrical or birth outcome considered in this study.

Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress.

BACKGROUND: Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress. METHODS: In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis. RESULTS: A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03). CONCLUSIONS: In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

"Ignored and Invisible": Perspectives from Black Women, Clinicians, and Community-Based Organizations for Reducing Preterm Birth.

OBJECTIVES: The preterm birth rate for Black women in the U.S. is consistently higher than other racial groups. The crisis of preterm birth and adverse birth outcomes among Black people is a historical, systematic confluence of racism, stressors, and an unsupportive and hostile healthcare system. To inform the development of preterm birth risk reduction interventions, this study aimed to collect and synthesize the experiences of Black women who gave birth preterm along with clinicians and community-based organizations who serve them. METHODS: A qualitative study design was employed whereby nine focus groups and 17 key informant interviews that included Black women, clinicians, and representatives from community-based organizations were facilitated in Los Angeles County from March 2019 to March 2020. Participants were recruited through the organizations and the focus groups took place virtually and in person. The process of thematic analysis was employed to analyze the focus group and interview transcripts. RESULTS: Five overarching themes emerged from the data. Black women experience chronic and pregnancy-related stress, and have lasting trauma from adverse maternal health experiences. These issues are exacerbated by racism and cultural incongruence within healthcare and social services systems. Black women have relied on self-education and self-advocacy to endure the barriers related to racism, mistreatment, and their experiences with preterm birth. CONCLUSIONS FOR PRACTICE: Healthcare and social service providers must offer more holistic care that prioritizes, rather than ignores, the racial components of health, placing increased importance on implementing inclusive and culturally-appropriate patient education, attentiveness to patient needs, respectful care, and support for Black women.

Integrating oral immunotherapy into clinical practice.

In 2020, the first food allergy treatment, an oral immunotherapy (OIT) product for peanut allergy, was approved by the Food and Drug Administration, and a peanut epicutaneous immunotherapy patch was under review. As food allergy therapies become available and widespread, allergy offices will need to adjust practices to be able to offer their patients these new treatments. OIT is an intensive therapy that requires commitment from patients and their families, and open communication with the practice is paramount. OIT may not be the right therapy for every patient, and although identifying good candidates is still an area rich for research opportunity, experience from cohorts and clinical trials provides some insight. It is important to understand the scope of practice for each member of the OIT team based on state regulations for a particular location. Staffing and space will likely dictate how many patients at an individual office could be on active OIT at one time. Emergency medications, supplies, and protocols must be in place. Screening, scheduling, visit procedures, monitoring, home dosing, dose modifications, safety precautions, adverse reactions, and maintenance will be addressed in this article. Finally, adjunct therapies under investigation will be reviewed.

Karyotype of first clinical miscarriage and prognosis of subsequent pregnancy outcome.

RESEARCH QUESTION: Is the karyotype of the first clinical miscarriage in an infertile patient predictive of the outcome of the subsequent pregnancy? DESIGN: Retrospective cohort study of infertile patients undergoing manual vacuum aspiration with chromosome testing at the time of the first (index) clinical miscarriage with a genetic diagnosis and a subsequent pregnancy. Patients treated at two academic-affiliated fertility centres from 1999 to 2018 were included; those using preimplantation genetic testing for aneuploidy were excluded. Main outcome was live birth in the subsequent pregnancy. RESULTS: One hundred patients with euploid clinical miscarriage and 151 patients with aneuploid clinical miscarriage in the index pregnancy were included. Patients with euploid clinical miscarriage in the index pregnancy had a live birth rate of 63% in the subsequent pregnancy compared with 68% among patients with aneuploid clinical miscarriage (adjusted odds ratio [aOR] 0.75, 95% CI 0.47-1.39, P = 0.45, logistic regression model adjusting for age, parity, body mass index and mode of conception). In a multinomial logistic regression model with three outcomes (live birth, clinical miscarriage or biochemical miscarriage), euploid clinical miscarriage for the index pregnancy was associated with similar odds of clinical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage for the index pregnancy (32% versus 24%, respectively, aOR 1.49, 95% CI 0.83-2.70, P = 0.19). Euploid clinical miscarriage for the index pregnancy was not associated with likelihood of biochemical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage (5% versus 8%, respectively, aOR 0.46, 95% CI 0.14-1.55, P = 0.21). CONCLUSION: Prognosis after a first clinical miscarriage among infertile patients is equally favourable among patients with euploid and aneuploid karyotype, and independent of the karyotype of the pregnancy loss.

Birth hospital and racial and ethnic differences in severe maternal morbidity in the state of California.

BACKGROUND: Birth hospital has recently emerged as a potential key contributor to disparities in severe maternal morbidity, but investigations on its contribution to racial and ethnic differences remain limited. OBJECTIVE: We leveraged statewide data from California to examine whether birth hospital explained racial and ethnic differences in severe maternal morbidity. STUDY DESIGN: This cohort study used data on all births at ≥20 weeks gestation in California (2007-2012). Severe maternal morbidity during birth hospitalization was measured using the Centers for Disease Control and Prevention index of having at least 1 of the 21 diagnoses and procedures (eg, eclampsia, blood transfusion, hysterectomy). Mixed-effects logistic regression models (ie, women nested within hospitals) were used to compare racial and ethnic differences in severe maternal morbidity before and after adjustment for maternal sociodemographic and pregnancy-related factors, comorbidities, and hospital characteristics. We also estimated the risk-standardized severe maternal morbidity rates for each hospital (N=245) and the percentage reduction in severe maternal morbidity if each group of racially and ethnically minoritized women gave birth at the same distribution of hospitals as non-Hispanic white women. RESULTS: Of the 3,020,525 women who gave birth, 39,192 (1.3%) had severe maternal morbidity (2.1% Black; 1.3% US-born Hispanic; 1.3% foreign-born Hispanic; 1.3% Asian and Pacific Islander; 1.1% white; 1.6% American Indian and Alaska Native, and Mixed-race referred to as Other). Risk-standardized rates of severe maternal morbidity ranged from 0.3 to 4.0 per 100 births across hospitals. After adjusting for covariates, the odds of severe maternal morbidity were greater among nonwhite women than white women in a given hospital (Black: odds ratio, 1.25; 95% confidence interval, 1.19-1.31); US-born Hispanic: odds ratio, 1.25; 95% confidence interval, 1.20-1.29; foreign-born Hispanic: odds ratio, 1.17; 95% confidence interval, 1.11-1.24; Asian and Pacific Islander: odds ratio, 1.26; 95% confidence interval, 1.21-1.32; Other: odds ratio, 1.31; 95% confidence interval, 1.15-1.50). Among the studied hospital factors, only teaching status was associated with severe maternal morbidity in fully adjusted models. Although 33% of white women delivered in hospitals with the highest tertile of severe maternal morbidity rates compared with 53% of Black women, birth hospital only accounted for 7.8% of the differences in severe maternal morbidity comparing Black and white women and accounted for 16.1% to 24.2% of the differences for all other racial and ethnic groups. CONCLUSION: In California, excess odds of severe maternal morbidity among racially and ethnically minoritized women were not fully explained by birth hospital. Structural causes of racial and ethnic disparities in severe maternal morbidity may vary by region, which warrants further examination to inform effective policies.

Management of acute food protein-induced enterocolitis syndrome emergencies at home and in a medical facility.

OBJECTIVE: Acute food protein-induced enterocolitis syndrome (FPIES) is characterized by delayed repetitive vomiting after ingestion of a trigger food, and severe reactions may lead to dehydration, hypotension, and shock. We provide recommendations on management of FPIES emergencies in a medical facility and at home. DATA SOURCES: This review summarizes the literature on clinical context, pathophysiology, presentation, and treatment of FPIES emergencies. STUDY SELECTIONS: We referred to the 2017 International Consensus Guidelines for the Diagnosis and Management of FPIES and performed a literature search identifying relevant recent primary articles and review articles on clinical management. RESULTS: Management of FPIES emergencies in a medical facility is based on severity of symptoms and involves rehydration, ondansetron, and corticosteroids. A proactive approach for reactions occurring at home involves prescribing oral ondansetron and providing an individualized treatment plan based on the evolution of symptoms and severity of past reactions. A better understanding of the pathophysiology of FPIES and randomized trials on ondansedron and cocorticosteroid use could lead to more targeted treatments. CONCLUSION: Children with FPIES are at risk for severe symptoms constituting a medical emergency. Management of FPIES emergencies is largely supportive, with treatment tailored to the symptoms, severity of the patient's condition, location of reaction, and reaction history.

Association of Maternal Comorbidity With Severe Maternal Morbidity: A Cohort Study of California Mothers Delivering Between 1997 and 2014.

BACKGROUND: Rates of maternal mortality and severe maternal morbidity (SMM) are higher in the United States than in other high-resource countries and are increasing further. OBJECTIVE: To examine the association of maternal comorbid conditions, age, body mass index, and previous cesarean birth with occurrence of SMM. DESIGN: Population-based cohort study using linked delivery hospitalization discharge data and vital records. SETTING: California, 1997 to 2014. PATIENTS: All 9 179 472 mothers delivering in California during 1997 to 2014. MEASUREMENTS: SMM rate, total and without transfusion-only cases; 2019 maternal comorbidity index. RESULTS: Total SMM increased by 160% during this time, and SMM excluding transfusion-only cases increased by 53%. Medical comorbid conditions were associated with an increasing portion of SMM occurrences. Medical comorbid conditions increased over the study period by 111%, and obstetric comorbid conditions increased by 30% to 40%. Identified medical comorbid conditions had high relative risks ranging from 1.3 to 14.3 for total SMM and even higher relative risks for nontransfusion SMM (to 32.4). The obstetric comorbidity index that is most often used may be undervaluing the degree of association with SMM. LIMITATIONS: Hospital discharge diagnosis files and birth certificate records can have misclassifications and may not include all relevant clinical data or social determinants. The period for analysis ended in 2014 to avoid the transition to the International Classification of Diseases, 10th Revision, Clinical Modification, and therefore missed more recent years. CONCLUSION: Obstetric and, particularly, medical comorbid conditions are increasing among women who develop SMM. The maternal comorbidity index is a promising tool for patient risk assessment and case-mix adjustment, but refinement of factor weights may be indicated. PRIMARY FUNDING SOURCE: National Institutes of Health.

Pre-pregnancy Obesity and the Risk of Peripartum Cardiomyopathy.

OBJECTIVE: The aim of this study is to evaluate the contribution of pre-pregnancy obesity and overweight to peripartum cardiomyopathy. STUDY DESIGN: This population-based study used linked birth record and maternal hospital discharge data from live births in California during 2007 to 2012 (n = 2,548,380). All women who had a diagnosis of peripartum cardiomyopathy during the childbirth hospitalization or who were diagnosed with peripartum cardiomyopathy during a postpartum hospital readmission within 5 months of birth were identified as cases. Pre-pregnancy body mass index (BMI, kg/m2) was classified as normal weight (18.5-24.9), overweight (25.0-29.9), obesity class 1 (30.0-34.9), obesity class 2 (35.0-39.9), and obesity class 3 (≥40). Because of small numbers, we excluded women with underweight BMI, and in some analyses, we combined obesity classes into one group. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) expressing associations between BMI and peripartum cardiomyopathy, adjusted for maternal age, race/ethnicity, education, health care payer, parity, plurality, and comorbidities. RESULTS: The overall prevalence of peripartum cardiomyopathy during hospital admissions was 1.3 per 10,000 live births (n = 320). Unadjusted ORs were 1.32 (95% CI: 1.01-1.74) for women with overweight BMI and 2.03 (95% CI: 1.57-2.62) for women with obesity, compared with women with normal pre-pregnancy BMI. Adjusted ORs were 1.26 (95% CI: 0.95-1.66) for overweight women and 1.38 (95% CI: 1.04-1.84) for women with obesity. The ORs suggested a dose-response relationship with increasing levels of obesity, but the 95% CIs for the specific classes of obesity included 1.00. CONCLUSION: Pre-pregnancy obesity was associated with an increased risk of peripartum cardiomyopathy. These findings underscore the importance of BMI during pregnancy. There is a need to recognize the increased risk of peripartum cardiomyopathy in women with high BMI, especially in the late postpartum period. KEY POINTS: · Pre-pregnancy obesity affects maternal health.. · Effects may extend to peripartum cardiomyopathy.. · The risk includes peripartum cardiomyopathy that emerges postpartum..

Risk of severe maternal morbidity in relation to prepregnancy body mass index: Roles of maternal co-morbidities and caesarean birth.

BACKGROUND: An association between prepregnancy body mass index (BMI) and severe maternal morbidity (SMM) has been reported, but evidence has been mixed and potential explanations have not been examined. OBJECTIVE: To evaluate the association between prepregnancy BMI and SMM in a large, diverse birth cohort and assess potential mediation by obesity-related co-morbidities and caesarean birth. METHODS: This cohort study used linked birth certificate and hospitalisation discharge records from Californian births during 2007-2012. We assessed associations between prepregnancy BMI and SMM, and used inverse probability weighting for multiple mediators to estimate relative and absolute natural direct and indirect effects accounting for mediation by co-morbidities (hypertensive conditions, diabetes, asthma) and caesarean birth. RESULTS: Among 2 650 182 births, the prevalence of SMM was 1.42%. Adjusted risk ratios for the total association between prepregnancy BMI category and SMM were 1.12 (95% confidence interval [CI] 1.07, 1.18) for underweight, 1.02 (95% CI 0.99, 1.04) for overweight, 1.04 (95% CI 1.00, 1.07) for obesity class 1, 1.14 (95% CI 1.09, 1.20) for obesity class 2, and 1.28 (95% CI 1.22, 1.36) for obesity class 3 compared to women with normal weight. After accounting for mediation by co-morbidity and caesarean birth, the risk ratios were 1.19 (95% CI 1.14, 1.26) for underweight, 0.91 (95% CI 0.89, 0.94) for overweight, 0.86 (95% CI 0.84, 0.89) for obesity class 1, 0.88 (95% CI 0.84, 0.92) for obesity class 2, and 0.89 (95% CI 0.83, 0.95) for obesity class 3. CONCLUSIONS: Co-morbidities and caesarean birth explained an association between high prepregnancy BMI and SMM. These findings suggest that promotion of healthy prepregnancy weight, along with management of co-morbidities and support of vaginal birth in pregnant women with high BMI, could reduce the risk of SMM. However, these mediators did not reduce the elevated risk of SMM observed in women with low BMI.

Invited Commentary: The Causal Association Between Obesity and Stillbirth-Strengths and Limitations of the Consecutive-Pregnancies Approach.

There has been a resurgence in analyses of consecutive pregnancies (or similarly, sibling designs) in perinatal and pediatric epidemiology. These approaches have attractive qualities for estimating associations with complex multifactorial exposures like obesity. In an article appearing in this issue of the Journal, Yu et al. (Am J Epidemiol. 2019;188(7):1328-1336) apply a consecutive-pregnancies approach to characterize the risk of stillbirth among women who develop obesity between pregnancies ("incident obesity"). Working within a causal framework and using parametric and nonparametric estimation techniques, the authors find an increase in stillbirth risk associated with incident obesity. Risk differences varied between 0.4 per 1,000 births (95% confidence interval (CI): 0.1, 0.7) and 6.9 per 1,000 births (95% CI: 3.7, 10.0), and risk ratios ranged from 1.12 (95% CI: 1.02, 1.23) to 2.99 (95% CI: 2.19, 4.08). The strengths of this approach include starting from a clearly defined causal estimand and exploring the sensitivity of parameter estimates to model selection. In this commentary, we put these findings in the broader context of research on obesity and birth outcomes and highlight concerns regarding the generalizability of results derived from within-family designs. We conclude that while causal inference is an important goal, in some instances focusing on formulation of a causal question drives results away from broad applicability.

The contribution of maternal characteristics and cesarean delivery to an increasing trend of severe maternal morbidity.

BACKGROUND: Severe maternal morbidity - life-threatening childbirth complications - has more than doubled in the United States over the past 15 years, affecting more than 50,000 women (1.4% of deliveries) annually. During this time period, maternal age, obesity, comorbidities, and cesarean delivery also increased and may be related to the rise in severe maternal morbidity. We sought to evaluate: (1) the association of advanced maternal age, pre-pregnancy obesity, pre-pregnancy comorbidities, and cesarean delivery with severe maternal morbidity, and (2) whether changes in the prevalence of these risk factors affected the trend of severe maternal morbidity. METHODS: This population-based cohort study used linked birth record and patient discharge data from live births in California during 2007-2014 (n = 3,556,206). We used multivariable logistic regression models to assess the association of advanced maternal age (≥35 years), pre-pregnancy obesity (body mass index ≥30 kg/m2), pre-pregnancy comorbidity (index of 12 conditions), and cesarean delivery with severe maternal morbidity prevalence and trends. Severe maternal morbidity was identified by an index of 18 diagnosis and procedure indicators. We estimated odds ratios, predicted prevalence, and population attributable risk percentages. RESULTS: The prevalence of severe maternal morbidity increased by 65% during 2007-2014. Advanced maternal age, pre-pregnancy obesity, and pre-pregnancy comorbidity also increased during this period, but cesarean delivery did not. None of these risk factors affected the increasing trend of severe maternal morbidity. However, the pre-pregnancy risk factors together were estimated to contribute to 13% (95% confidence interval: 12, 14%) of severe maternal morbidity cases in the study population overall, and cesarean delivery was estimated to contribute to 37% (95% confidence interval: 36, 38%) of cases. CONCLUSIONS: Pre-pregnancy health and cesarean delivery are important risk factors for severe maternal morbidity but do not explain an increasing trend of severe maternal morbidity in California during 2007-2014. Investigation of other potential contributors is needed in order to identify ways to reverse the trend of severe maternal morbidity.