Association Between Intrapartum Nitrous Oxide for Labor Analgesia and Short-Term Neonatal Outcomes.

OBJECTIVE: To evaluate the association between intrapartum nitrous oxide use and adverse short-term neonatal outcomes. METHODS: This was a retrospective cohort study of individuals with singleton gestations at 35 or more weeks who attempted labor and delivered at an academic hospital between June 1, 2015, and February 28, 2020. Data were extracted from the electronic medical record using billing and diagnostic codes. Patients were classified based on whether they received no intrapartum analgesia or received nitrous oxide only. Those who received other analgesia types were excluded. The primary outcome was neonatal intensive care unit (NICU) admission. Secondary outcomes included Apgar score less than 7 at 1 minute and 5 minutes, respiratory composite outcome (including meconium aspiration syndrome, neonatal bronchopulmonary disorders, neonatal transient tachypnea, and other neonatal respiratory distress that required NICU admission), hypoglycemia, and hyperbilirubinemia. Univariable and multivariable analyses were used to estimate the association between nitrous oxide exposure intrapartum and the selected outcomes. RESULTS: Of 6,047 included, 4,153 (68.7%) received no analgesia, and 1,894 (31.3%) received nitrous oxide only. In comparison with individuals who received no analgesia, those who received nitrous oxide were more likely to be nulliparous, be of Black racial identity, have noncommercial insurance, and be less likely to deliver by intrapartum cesarean. The reception of nitrous oxide, compared with the reception of no analgesia, was associated with a lower likelihood of NICU admission (6.4% vs 8.1%; adjusted odds ratio [aOR] 0.77, 95% CI, 0.62-0.96) and an increased likelihood of neonatal hyperbilirubinemia (aOR 1.23, 95% CI, 1.08-1.41). Inhaled nitrous oxide exposure, in comparison with the reception of no analgesia, was not associated with the other secondary outcomes, including Apgar score less than 7 at 1 minute (odds ratio [OR] 0.74, 95% CI, 0.50-1.10) or 5 minutes (OR 0.91, 95% CI, 0.32-2.60), respiratory composite outcome (OR 0.91, 95% CI, 0.70-1.17), and hypoglycemia (OR 0.82, 95% CI, 0.64-1.05). CONCLUSION: In this single-center retrospective cohort of low-risk patients, intrapartum inhaled nitrous oxide, compared with the reception of no analgesia, was associated with a decreased risk for NICU admission but with an increased risk for hyperbilirubinemia; other outcomes did not differ. These findings may be used to counsel patients when considering nitrous oxide for labor analgesia.

Co-existing chronic hypertension and hypertensive disorders of pregnancy and associated adverse pregnancy outcomes.

OBJECTIVE: Chronic hypertension (CHTN) causes vascular damage and resistance in the pregnant person and malperfusion in the placenta which may worsen the endothelial dysfunction of hypertensive disorders of pregnancy (HDP). These conditions frequently co-exist. A cumulative effect has been inconsistently demonstrated in prior studies, and it is unclear how co-existing hypertensive conditions affect pregnancy outcomes. We sought to examine maternal and neonatal outcomes in pregnancies affected by co-existing CHTN and HDP and compare these outcomes to those of pregnancies which were unaffected or affected by either condition alone. METHODS: This is a retrospective cohort study of singleton deliveries at a single institution 1 October 2013 to 1 October 2021. Data were extracted from the electronic medical record using standardized definitions and billing and diagnosis codes. Pregnant people with no evidence of hypertensive condition were compared to those with CHTN only, HDP only, and co-existing CHTN and HDP. Demographics, baseline clinical data, and use of aspirin or antihypertensive medications were assessed. Maternal outcomes included cesarean delivery, critical range blood pressure, intensive care unit (ICU) admission, and death. Neonatal outcomes included preterm birth <37 weeks' gestation, small for gestational age (SGA) birthweight, ICU admission, and a morbidity composite. Bivariate tests of association were performed using Chi-square test. Crude and adjusted odds ratios (aORs) were calculated using logistic regression for three maternal and four neonatal outcomes. Descriptive statistics and multivariable analyses were performed. RESULTS: Of 40,840 eligible people, 1451 (3.6%) had CHTN only; 5213 (12.8%) had HDP only; and 1890 (4.6%) had co-existing CHTN and HDP. Though odds of adverse maternal and neonatal outcomes were significantly increased for all hypertensive groups relative to the unaffected referent group, co-existing CHTN and HDP had the highest odds of cesarean delivery (aOR 1.60; 95% confidence interval (CI) 1.45-1.77), critical blood pressure (OR 41.54; 95% CI 35.96-47.99), maternal ICU admission or death (aOR 3.52; 95% CI 2.65-4.67), preterm birth (aOR 2.76; 95% CI 2.41-3.16), and SGA birthweight (aOR 1.61; 95% CI 1.39-1.87). CONCLUSIONS: Hypertensive disorders of pregnancy in the setting of CHTN are associated with the highest odds of serious consequences on the pregnant person and neonate independent of maternal comorbidities and prematurity. Antihypertensive medication use lowers the odds of some adverse outcomes. Patients should be informed of heightened risks, but optimal management remains unclear.

The association between a low 50-gram, 1-hour glucose challenge test value and neonatal morbidity.

OBJECTIVE: To evaluate the association between a low 50-gram, 1-hour glucose challenge test (GCT) value and adverse maternal and neonatal outcomes among patients receiving care at a single center tertiary care academic hospital. METHODS: We performed a retrospective cohort study of pregnant patients with a documented result of a 50-gram, 1-hour GCT performed ≥24 weeks 0 days gestation at a single tertiary care academic hospital from 2013-2021. Patients with a low GCT value, defined as cohort specific ≤10th percentile (<82 mg/dL), were compared to patients with a GCT value ≥82 mg/dL who were not diagnosed with gestational diabetes (GDM) to examine adverse maternal and neonatal outcomes. Additionally, these comparisons were repeated across patients with low GCT (<82 mg/dL), those with a GCT ≥82 mg/dL without diagnosis of GDM (heretofore referred to as normal glycemic screening) and patients diagnosed with GDM. Our primary outcome was a composite neonatal morbidity variable, inclusive of stillbirth, neonatal death, neonatal hypoglycemia with neonatal intensive care unit (NICU) admission, neonatal hyperbilirubinemia with NICU admission, respiratory distress with NICU admission, and/or small for gestational age (SGA). Multivariable logistic regression modeling was used to examine the association of low GCT value and the composite neonatal morbidity outcome, compared to those with the normal glycemic screening. RESULTS: Of 36,342 eligible patients, 3,789 (10.4%) had a low GCT value of <82 mg/dL, 30,729 (84.6%) had a GCT value ≥82 mg/dL and were not diagnosed with GDM, and 1,824 (5.0%) had a diagnosis of GDM. Patients with a low GCT value were significantly less likely to be diagnosed with hypertensive disorder of pregnancy (HDP) (12.4% vs 16.3%, p < .01), undergo cesarean delivery (22.8% vs 29.9%, p < .01), or experience postpartum hemorrhage (7.8% vs 9.4%, p < .01) as compared to patients with normal glycemic screening. Compared to newborns whose mothers had normal glycemic screening, newborns of mothers with a low GCT value were significantly more likely to experience the composite morbidity outcome (OR 1.17; 95% CI 1.08-1.27); this persisted after adjusting for potential confounders (aOR 1.18; 95% CI 1.09-1.29). CONCLUSION: A low maternal GCT value after 24 weeks gestation is significantly associated with an increased risk of morbidity in the newborn, driven by higher rates of SGA. Patients with a low GCT value may have underlying maternal hypoglycemia or other glycemic dysregulation affecting fetal development and may benefit from enhanced antenatal surveillance.

Fetal growth restriction and small for gestational age as predictors of neonatal morbidity: which growth nomogram to use?

BACKGROUND: Fetal growth nomograms were developed to screen for fetal growth restriction and guide clinical care to improve perinatal outcomes; however, existing literature remains inconclusive regarding which nomogram is the gold standard. OBJECTIVE: This study aimed to compare the ability of 4 commonly used nomograms (Hadlock, International Fetal and Newborn Growth Consortium for the 21st Century, Eunice Kennedy Shriver National Institute of Child Health and Human Development-unified standard, and World Health Organization fetal growth charts) and 1 institution-specific reference to predict small for gestational age and poor neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of all nonanomalous singleton pregnancies undergoing ultrasound at ≥20 weeks of gestation between 2013 and 2020 and delivering at a single academic center. Using random selection methods, the study sample was restricted to 1 pregnancy per patient and 1 ultrasound per pregnancy completed at ≥22 weeks of gestation. Fetal biometry data were used to calculate estimated fetal weight and percentiles according to the aforementioned 5 nomograms. Maternal and neonatal data were extracted from electronic medical records. Logistic regression was used to estimate the association between estimated fetal weight of <10th and <3rd percentiles compared with estimated fetal weight of 10th to 90th percentile as the reference group for small for gestational age and the neonatal composite outcomes (perinatal mortality, hypoxic-ischemic encephalopathy or seizures, respiratory morbidity, intraventricular hemorrhage, necrotizing enterocolitis, hyperbilirubinemia or hypoglycemia requiring neonatal intensive care unit admission, and retinopathy of prematurity). Receiver operating characteristic curve contrast estimation (primary analysis) and test characteristics were calculated for all nomograms and the prediction of small for gestational age and the neonatal composite outcomes. We restricted the sample to ultrasounds performed within 28 days of delivery; moreover, similar analyses were completed to assess the prediction of small for gestational age and neonatal composite outcomes. RESULTS: Among 10,045 participants, the proportion of fetuses classified as <10th percentile varied across nomograms from 4.9% to 9.7%. Fetuses with an estimated fetal weight of <10th percentile had an increased risk of small for gestational age (odds ratio, 9.9 [95% confidence interval, 8.5-11.5] to 12.8 [95% confidence interval, 10.9-15.0]). In addition, the estimated fetal weight of <10th and <3rd percentile was associated with increased risk of the neonatal composite outcome (odds ratio, 2.4 [95% confidence interval, 2.0-2.8] to 3.5 [95% confidence interval, 2.9-4.3] and 5.7 [95% confidence interval, 4.5-7.2] to 8.8 [95% confidence interval, 6.6-11.8], respectively). The prediction of small for gestational age with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 6.3 to 8.5 and an area under the curve of 0.62 to 0.67. Similarly, the prediction of the neonatal composite outcome with an estimated fetal weight of <10th percentile had a positive likelihood ratio of 2.1 to 3.1 and an area under the curve of 0.55 to 0.57. When analyses were restricted to ultrasound within 4 weeks of delivery, among fetuses with an estimated fetal weight of <10th percentile, the risk of small for gestational age increased across all nomograms (odds ratio, 16.7 [95% confidence interval, 12.6-22.3] to 25.1 [95% confidence interval, 17.0-37.0]), and prediction improved (positive likelihood ratio, 8.3-15.0; area under the curve, 0.69-0.75). Similarly, the risk of neonatal composite outcome increased (odds ratio, 3.2 [95% confidence interval, 2.4-4.2] to 5.2 [95% confidence interval, 3.8-7.2]), and prediction marginally improved (positive likelihood ratio, 2.4-4.1; area under the curve, 0.60-0.62). Importantly, the risk of both being small for gestational age and having the neonatal composite outcome further increased (odds ratio, 21.4 [95% confidence interval, 13.6-33.6] to 28.7 (95% confidence interval, 18.6-44.3]), and the prediction of concurrent small for gestational age and neonatal composite outcome greatly improved (positive likelihood ratio, 6.0-10.0; area under the curve, 0.80-0.83). CONCLUSION: In this large cohort, Hadlock, recent fetal growth nomograms, and a local population-derived fetal growth reference performed comparably in the prediction of small for gestational age and neonatal composite outcomes.

Pregnant Patients with a Documented History of Penicillin Allergy and Associated Maternal and Neonatal Outcomes at a Tertiary Care Center.

OBJECTIVE: Pregnant individuals are likely to need antibiotics during the peripartum period. For pregnant individuals who report a history of penicillin allergy, non-ß-lactam antibiotics are often administered. Compared with first-line ß-lactam antibiotics, alternative antibiotics can be less effective, more toxic, and more costly. It remains unclear if being labeled with a penicillin allergy is associated with adverse maternal and neonatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study of all pregnant patients who delivered a viable singleton between 24 and 42 weeks of gestation at a large academic hospital from 2013 to 2021. We compared patients who had a documented penicillin allergy history in their electronic medical record versus those who did not and examined whether there were significant differences in maternal outcomes and neonatal outcomes. Bivariable and multivariable analyses were performed. RESULTS: Of 41,943 eligible deliveries included in the analysis, 4,705 (11.2%) patients had a penicillin allergy history documented in their electronic medical record and 37,238 (88.8%) did not. Even after adjusting for potential confounders, patients with a documented penicillin allergy had a higher risk of postpartum endometritis (adjusted odds ratio [aOR]: 1.46; 95% confidence interval [CI]: 1.01-2.11) and a higher risk of their neonates having a postnatal hospital stay lasting more than 72 hours (aOR: 1.10; 95% CI: 1.02-1.18). There were no significant differences seen in the other maternal and neonatal outcomes in both bivariable and multivariable analyses. CONCLUSION: Pregnant patients who are labeled as having a penicillin allergy are more likely to have postpartum endometritis, and neonates born to mothers who are labeled as having a penicillin allergy are more likely to have a postnatal hospital stay lasting more than 72 hours. There were no other significant differences seen in pregnant patients and their newborns whether they were labeled as having a penicillin allergy history or not. However, pregnant individuals with a penicillin allergy documented in their medical record were significantly more likely to receive alternative non-ß lactam antibiotics, and may have benefitted from having more details of their allergy history available as well as proper allergy verification with testing. KEY POINTS: · It is unclear whether pregnant individuals labeled with penicillin allergies have worse obstetric outcomes.. · These individuals were significantly more likely to have endometritis and their newborns hospitalized for >72 hours.. · They were significantly more likely to receive alternative non-ß lactam antibiotics than those without documented allergies..

Low-Dose Aspirin during Pregnancy and Postpartum Bleeding.

OBJECTIVE: This study aimed to investigate whether aspirin 81 mg daily for preeclampsia prevention is associated with increased risk of postpartum blood loss at the time of delivery. STUDY DESIGN: This is a retrospective cohort study performed at a tertiary hospital from January 2018 to April 2021. Data were extracted from the electronic medical record. Patients prescribed low-dose aspirin (LDA) were compared with patients who were not. The primary outcome was a composite of postpartum blood loss, defined as: estimated blood loss (EBL) >1,000 mL, documentation of International Classification of Diseases-9/-10 codes for postpartum hemorrhage (PPH), or red blood cell (RBC) transfusion. Bivariate analysis, and unadjusted and adjusted logistic regression modeling were performed. RESULTS: Among 16,980 deliveries, 1,922 (11.3%) were prescribed LDA. Patients prescribed LDA were more likely to be >35 years old, nulliparous, obese, taking other anticoagulants, or have diagnoses of diabetes, systemic lupus erythematosus, fibroids, or hypertensive disease of pregnancy. After adjusting for potential confounders, the significant association between LDA use and the composite did not persist (adjusted odds ratio [aOR]: 1.1, 95% confidence interval [CI]: 1.0-1.3) nor did the association between EBL > 1,000 mL (aOR: 1.0, 95% CI: 0.9-1.3) and RBC transfusion (aOR: 1.3, 95% CI: 0.9-1.7). The association between LDA and PPH remained significant (aOR: 1.3, 95% CI: 1.1-1.6). Patients who discontinued LDA <7 days prior to delivery had an increased risk of the postpartum blood loss composite compared discontinuation ≥7 days (15.0 vs. 9.3%; p = 0.03). CONCLUSION: There may be an association between LDA use and increased risk of postpartum bleeding. This suggests that use of LDA outside the recommended guidelines should be cautioned and further investigation is needed to determine its ideal dosing and timing of discontinuation. KEY POINTS: · There may be an association with LDA and an increased risk of postpartum bleeding.. · Patients who discontinued LDA less than 7 days prior to delivery had an increased rate of postpartum bleeding.. · Additional research is need to determine optimal LDA dose and timing of discontinuation..

Intravenous iron for treatment of iron deficiency anemia during pregnancy and associated maternal outcomes.

BACKGROUND: More than 40% of pregnant patients worldwide are anemic, with at least half resulting from iron deficiency anemia (IDA). Anemia in pregnancy is linked with adverse maternal and neonatal outcomes. Treatment for IDA is iron supplementation; however, the optimal route of administration remains unclear. We sought to investigate whether patients with IDA who received intravenous iron (IVI) had decreased odds of maternal morbidity compared to patients who did not. METHODS: This is a retrospective cohort study of pregnant patients with presumed IDA with term deliveries at a tertiary hospital from 2013-2021. Data were extracted from the hospital's electronic medical record using standardized definitions and billing codes. Patients who received antepartum IVI were compared to patients who did not. The primary outcome was a maternal morbidity composite inclusive of receipt of blood transfusion, hysterectomy, admission to the intensive care unit or death. Bivariate analyses and multivariable logistic regression modelling were performed adjusting for potential confounders. RESULTS: Of 45,345 pregnancies, 5054 (11.1%) met eligibility criteria. Of these, 944 (18.7%) patients received IVI while 4110 (81.3%) did not. Patients who received IVI had higher risk baseline characteristics. They experienced a greater increase in hematocrit from pregnancy nadir to delivery admission (4.5% vs. 3.3%, p < .01). Despite this, patients who received IVI had higher odds of the maternal morbidity composite (OR 1.47, 95%CI 1.11-1.95). This finding persisted after adjusting for potential confounders, although the strength of the association became attenuated (aOR 1.37, 95%CI 1.02-1.85). Odds of the morbidity composite were not elevated among patients who received a full IVI treatment course (OR 1.2, 95% CI 0.83-1.90). DISCUSSION: Odds of the maternal morbidity composite were increased among patients who received IVI despite greater increases in hematocrit. The effect was attenuated after adjusting for potential confounders and was not significant among patients who completed a full treatment course.

The Uptake of Telemedicine in Obstetric Care During the Early Acute Phase of the Coronavirus 2019 Pandemic.

Introduction: The early acute phase of the coronavirus disease 2019 pandemic created rapid adaptation in health care delivery. Methods: Using electronic medical record data from two different institutions located in two different states, we examined how telemedicine was integrated into obstetric care. Results: With no telemedicine use prior, both institutions rapidly incorporated telemedicine into prenatal care (PNC). There were significant patient-level and institutional-level differences in telemedicine use. Telemedicine users initiated PNC earlier and had more total visits, earlier timing of ultrasounds, and earlier diabetes screening during pregnancy compared with nonusers. There were no significant differences in delivery mode or stillbirth associated with telemedicine use at either institution. Conclusions: Rapid adoption of obstetric telemedicine maintained adequate prenatal care provision during the early pandemic, but implementation varied across institutions.

Changes in prenatal testing during the COVID-19 pandemic.

Objective: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare delivery, including prenatal care. The study objective was to assess if timing of routine prenatal testing changed during the COVID-19 pandemic. Methods: Retrospective observational cohort study using claims data from a regional insurer (Highmark) and electronic health record data from two academic health systems (Penn Medicine and Yale New Haven) to compare prenatal testing timing in the pre-pandemic (03/10/2018-12/31/2018 and 03/10/2019-12/31/2019) and early COVID-19 pandemic (03/10/2020-12/31/2020) periods. Primary outcomes were second trimester fetal anatomy ultrasounds and gestational diabetes (GDM) testing. A secondary analysis examined first trimester ultrasounds. Results: The three datasets included 31,474 pregnant patients. Mean gestational age for second trimester anatomy ultrasounds increased from the pre-pandemic to COVID-19 period (Highmark 19.4 vs. 19.6 weeks; Penn: 20.1 vs. 20.4 weeks; Yale: 18.8 vs. 19.2 weeks, all p < 0.001). There was a detectable decrease in the proportion of patients who completed the anatomy survey <20 weeks' gestation across datasets, which did not persist at <23 weeks' gestation. There were no consistent changes in timing of GDM screening. There were significant reductions in the proportion of patients with first trimester ultrasounds in the academic institutions (Penn: 57.7% vs. 40.6% and Yale: 78.7% vs. 65.5%, both p < 0.001) but not Highmark. Findings were similar with multivariable adjustment. Conclusion: While some prenatal testing happened later in pregnancy during the pandemic, pregnant patients continued to receive appropriately timed testing. Despite disruptions in care delivery, prenatal screening remained a priority for patients and providers during the COVID-19 pandemic.

Maternal Subjective Expectations about the Technology of Skill Formation Predict Investments in Children One Year Later.

A growing literature reports significant socio-economic gaps in investments in the human capital of young children. Because the returns to these investments may be huge, parenting programs attempt to improve children's environments by increasing parental expectations about the importance of investments for their children's human capital formation. We contribute to this literature by investigating the relevance of maternal subjective expectations (MSE) about the technology of skill formation in predicting investments in the human capital of children. We develop and implement a framework to elicit and analyze MSE data. We launch a longitudinal study with 822 participants, all of whom were women in the second trimester of their first pregnancy at the date of enrollment. In the first wave of the study, during pregnancy, we elicited the woman's MSE. In the second wave, approximately one year later, we measured maternal investments using the Home Observation for the Measurement of the Environment (HOME) Inventory. The vast majority of study participants believe that the Cobb-Douglas technology of skill formation describes the process of child development accurately. We observed substantial heterogeneity in MSE about the impact of human capital at birth and investments in child development at age two. Family income explains part of this heterogeneity in MSE. The higher the family income, the higher the MSE about the impact of investment in child development. We find that a one-standard-deviation of MSE measured at pregnancy is associated with 11% of a standard deviation in investments measured when the child is approximately nine months old.

Changes in preterm birth during the COVID-19 pandemic by duration of exposure and race and ethnicity.

OBJECTIVE: We aimed to determine whether coronavirus-disease-2019 (COVID-19) pandemic exposure duration was associated with PTB and if the pandemic modified racial disparities. STUDY DESIGN: We analyzed Philadelphia births and replicated in New Haven. Compared to matched months in two prior years, we analyzed overall PTB, specific PTB phenotypes, and stillbirth. RESULTS: Overall, PTB was similar between periods with the following exceptions. Compared to pre-pandemic, early pregnancy (<14 weeks') pandemic exposure was associated with lower risk of PTB < 28 weeks' (aRR 0.60 [0.30-1.10]) and later exposure with higher risk (aRR 1.77 [0.78-3.97]) (interaction p = 0.04). PTB < 32 weeks' among White patients decreased during the pandemic, resulting in non-significant widening of the Black-White disparity from aRR 2.51 (95%CI: 1.53-4.16) to aRR 4.07 (95%CI: 1.56-12.01) (interaction P = 0.41). No findings replicated in New Haven. CONCLUSION: We detected no overall pandemic effects on PTB, but potential indirect benefits for some patients which could widen disparities remains possible.

Does Antenatal Progesterone Administration Modify the Risk of Neonatal Intraventricular Hemorrhage?

OBJECTIVE: Progesterone administration has been associated with improved neurological outcomes following traumatic brain injury in adults. However, studies examining the effect of progesterone on the risk of neonatal intraventricular hemorrhage (IVH) are inconsistent. We sought to determine if maternal administration of intramuscular 17-α-hydroxyprogesterone caproate (17-OHPC) is associated with decreased rates of IVH in infants born before 32-weeks gestation. STUDY DESIGN: This is a retrospective study of liveborn singleton deliveries between 20- and 32-weeks gestation at two large academic medical centers from January 1, 2012 to August 30, 2020. Data were extracted from hospital electronic medical record data warehouses using standardized definitions and billing and diagnosis codes. We evaluated receipt of 17-OHPC in the antepartum period and diagnosis of IVH (grade I-IV, per Volpe classification) during the neonatal delivery hospitalization encounter. Bivariate and multivariate analyses were performed to examine the association between 17-OHPC and neonatal IVH adjusting for potential confounders. Odds ratio (ORs) and 95% confidence intervals (CIs) were presented. RESULTS: Among 749 neonates born between 20- and 32-week gestation, 140 (18.7%) of their mothers had received antenatal 17-OHPC and 148 (19.8%) were diagnosed with IVH after birth. No significant association was observed between maternal 17-OHPC and neonatal IVH in unadjusted (OR 1.14, 95% CI 0.72-1.78) or adjusted analyses (adjusted odds ratio 1.14, 95% CI 0.71-1.84). Independent of exposure to 17-OHPC, as expected, infants born <28-weeks gestation or those with very low birthweight (<1,500 g) were at an increased risk of IVH (OR 2.32, 95% CI 1.55-3.48 and OR 2.19, 95% CI 1.09-4.38, respectively). CONCLUSION: Antenatal maternal 17-OHPC administration was not associated with the risk of neonatal IVH. Further research may be warranted to determine whether timing, route of delivery, and duration of progesterone therapy impact rates of neonatal IVH. KEY POINTS: · This study aimed to compare the frequency of intraventricular hemorrhage in preterm neonates exposed to antenatal 17-α-hydroxyprogesterone caproate to those not exposed.. · In neonates born at <32-weeks gestation, maternal use of progesterone is not associated with the risk of intraventricular hemorrhage.. · In contrast to preclinical and adult data, this study suggests that progesterone exposure is not associated with the prevention of neonatal brain injury..

Postpartum Length of Stay and Hospital Readmission Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic.

OBJECTIVE: To compare postpartum hospitalization length of stay (LOS) and hospital readmission among obstetric patients before (March 2017-February 2020; prepandemic) and during the coronavirus disease 2019 (COVID-19) pandemic (March 2020-February 2021). METHODS: We conducted a retrospective cohort study, using Epic Systems' Cosmos research platform, of obstetric patients who delivered between March 1, 2017, and February 28, 2021, at 20-44 weeks of gestation and were discharged within 7 days of delivery. The primary outcome was short postpartum hospitalization LOS (less than two midnights for vaginal births and less than three midnights for cesarean births) and secondary outcome was hospital readmission within 6 weeks of postpartum hospitalization discharge. Analyses compared outcomes before and during the pandemic using standardized differences and Bayesian logistic mixed-effects models, among all births and stratified by mode of delivery. RESULTS: Of the 994,268 obstetric patients in the study cohort, 742,113 (74.6%) delivered prepandemic and 252,155 (25.4%) delivered during the COVID-19 pandemic. During the COVID-19 pandemic, the percentage of short postpartum hospitalizations increased among all births (28.7-44.5%), vaginal births (25.4-39.5%), and cesarean births (35.3-55.1%), which was consistent with the adjusted analysis (all births: adjusted odds ratio [aOR] 2.35, 99% credible interval 2.32-2.39; vaginal births: aOR 2.14, 99% credible interval 2.11-2.18; cesarean births aOR 2.90, 99% credible interval 2.83-2.98). Although short postpartum hospitalizations were more common during the COVID-19 pandemic, there was no change in readmission in the unadjusted (1.4% vs 1.6%, standardized difference=0.009) or adjusted (aOR 1.02, 99% credible interval 0.97-1.08) analyses for all births or when stratified by mode of delivery. CONCLUSION: Short postpartum hospitalization LOS was significantly more common during the COVID-19 pandemic for obstetric patients with no change in hospital readmissions within 6 weeks of postpartum hospitalization discharge. The COVID-19 pandemic created a natural experiment, suggesting shorter postpartum hospitalization may be reasonable for patients who are self-identified or health care professional-identified as appropriate for discharge.

Birth Hospital Length of Stay and Rehospitalization During COVID-19.

OBJECTIVES: To determine if birth hospitalization length of stay (LOS) and infant rehospitalization changed during the coronavirus disease 2019 (COVID-19) era among healthy, term infants. METHODS: Retrospective cohort study using Epic's Cosmos data from 35 health systems of term infants discharged ≤5 days of birth. Short birth hospitalization LOS (vaginal birth <2 midnights; cesarean birth <3 midnights) and, secondarily, infant rehospitalization ≤7 days after birth hospitalization discharge were compared between the COVID-19 (March 1 to August 31, 2020) and prepandemic eras (March 1 to August 31, 2017, 2018, 2019). Mixed-effects models were used to estimate adjusted odds ratios (aORs) comparing the eras. RESULTS: Among 202 385 infants (57 110 from the COVID-19 era), short birth hospitalization LOS increased from 28.5% to 43.0% for all births (vaginal: 25.6% to 39.3%, cesarean: 40.1% to 61.0%) during the pandemic and persisted after multivariable adjustment (all: aOR 2.30, 95% confidence interval [CI] 2.25-2.36; vaginal: aOR 2.12, 95% CI 2.06-2.18; cesarean: aOR 3.01, 95% CI 2.87-3.15). Despite shorter LOS, infant rehospitalizations decreased slightly during the pandemic (1.2% to 1.1%); results were similar in adjusted analysis (all: aOR 0.83, 95% CI 0.76-0.92; vaginal: aOR 0.82, 95% CI 0.74-0.91; cesarean: aOR 0.87, 95% CI 0.69-1.10). There was no change in the proportion of rehospitalization diagnoses between eras. CONCLUSIONS: Short infant LOS was 51% more common in the COVID-19 era, yet infant rehospitalization within a week did not increase. This natural experiment suggests shorter birth hospitalization LOS among family- and clinician-selected, healthy term infants may be safe with respect to infant rehospitalization, although examination of additional outcomes is needed.

Coronavirus Disease 2019 (COVID-19) Pandemic and Pregnancy Outcomes in a U.S. Population.

OBJECTIVE: To examine whether the coronavirus disease 2019 (COVID-19) pandemic altered risk of adverse pregnancy-related outcomes and whether there were differences by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status among pregnant women. METHODS: In this retrospective cohort study using Epic's Cosmos research platform, women who delivered during the pandemic (March-December 2020) were compared with those who delivered prepandemic (matched months 2017-2019). Within the pandemic epoch, those who tested positive for SARS-CoV-2 infection were compared with those with negative test results or no SARS-CoV-2 diagnosis. Comparisons were performed using standardized differences, with a value greater than 0.1 indicating meaningful differences between groups. RESULTS: Among 838,489 women (225,225 who delivered during the pandemic), baseline characteristics were similar between epochs. There were no significant differences in adverse pregnancy outcomes between epochs (standardized difference<0.10). In the pandemic epoch, 108,067 (48.0%) women had SARS-CoV-2 testing available; of those, 7,432 (6.9%) had positive test results. Compared with women classified as negative for SARS-CoV-2 infection, those who tested positive for SARS-CoV-2 infection were less likely to be non-Hispanic White or Asian or to reside in the Midwest and more likely to be Hispanic, have public insurance, be obese, and reside in the South or in high social vulnerability ZIP codes. There were no significant differences in the frequency of preterm birth (8.5% vs 7.6%, standardized difference=0.032), stillbirth (0.4% vs 0.4%, standardized difference=-0.002), small for gestational age (6.4% vs 6.5%, standardized difference=-0.002), large for gestational age (7.7% vs 7.7%, standardized difference=-0.001), hypertensive disorders of pregnancy (16.3% vs 15.8%, standardized difference=0.014), placental abruption (0.5% vs 0.4%, standardized difference=0.007), cesarean birth (31.2% vs 29.4%, standardized difference=0.039), or postpartum hemorrhage (3.4% vs 3.1%, standardized difference=0.019) between those who tested positive for SARS-CoV-2 infection and those classified as testing negative. CONCLUSION: In a geographically diverse U.S. cohort, the frequency of adverse pregnancy-related outcomes did not differ between those delivering before compared with during the pandemic, nor between those classified as positive compared with negative for SARS-CoV-2 infection during pregnancy.

Factors associated with appropriate treatment of acute-onset severe obstetrical hypertension.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends that pregnant patients receive expeditious treatment with first-line antihypertensive agents within 1 hour of confirmed severe hypertension to reduce the risk for maternal stroke. However, it is unknown how often this guideline is followed and what factors influence a patient's likelihood of receiving guideline-concordant care. OBJECTIVE: We aimed to identify factors associated with receiving guideline-concordant treatment for an obstetrical hypertensive emergency. STUDY DESIGN: We present a case-control study of all pregnant and postpartum patients who had persistent severe hypertension (≥2 systolic blood pressures ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg, or both within 1 hour of each other) during their delivery hospitalization at a tertiary hospital from October 1, 2013, to August 31, 2020. Data were extracted from the hospital electronic medical records using standard definitions and billing and diagnosis codes. We defined receipt of the recommended treatment as administration of a first-line antihypertensive agent (intravenous labetalol, intravenous hydralazine, or immediate-release oral nifedipine) within 60 minutes of the first or second severe-range blood pressure measurement during their delivery hospitalization. Delayed treatment was defined as the administration of a first-line agent >60 minutes after the second elevated blood pressure measurement. Patients were considered untreated if a first-line agent was never administered. Maternal sociodemographic, clinical and pregnancy factors, and time and day of the week of the hypertensive emergency were compared among patients who received the recommended treatment, those who received delayed treatment, and those who were untreated. Bivariate analyses were performed, and multinomial and multivariable logistic regression models were used to adjust for potential confounders. RESULTS: Of the 39,918 deliveries in the cohort, 1987 (5.0%) were complicated by severe, persistent obstetrical hypertension. Of these patients, 532 (26.8%) received the recommended treatment, 356 (17.9%) received delayed treatment, and 1099 (55.3%) did not receive any first-line antihypertensive therapy. The multinomial regression models that were used to compare these 3 groups indicated that patients who received the recommended treatment were more likely to be Black (adjusted odds ratio, 1.85; 95% confidence interval, 1.36-2.51), Hispanic (adjusted odds ratio, 1.77; 95% confidence interval, 1.28-2.52), or pregnant and at <37 weeks of gestation (adjusted odds ratio, 6.65; 95% confidence interval, 5.08-8.72). Treatment was less likely if the severe obstetrical hypertension emergency occurred overnight (7:00 PM to 6:59 AM) (adjusted odds ratio, 0.79; 95% confidence interval, 0.64-0.97) or during the postpartum period (adjusted odds ratio, 0.66; 95% confidence interval, 0.51-0.86). CONCLUSION: Approximately half of obstetrical patients with at least 2 documented severely elevated blood pressure measurements did not receive the recommended antihypertensive treatment. Of those who did receive treatment, about 40% had delayed treatment. Black and Hispanic race and preterm gestation were associated with an increased likelihood of receiving the recommended treatment when compared with White race and term pregnancies. Patients whose severe obstetrical hypertension emergency occurred overnight and those who were postpartum were less likely to receive any first-line antihypertensive treatment. Overall, patients without sociodemographic and clinical risk factors for severe obstetrical hypertension or other pregnancy complications were less likely to be treated. However, treatment improved significantly over time with the implementation of targeted quality measures and specific institutional policies based on the American College of Obstetricians and Gynecologists' latest severe obstetrical hypertension management guidelines.

Predictors of Initiation of Medication for Opioid Use Disorder and Retention in Treatment Among U.S. Pregnant Women, 2013-2017.

OBJECTIVE: To describe trends and factors associated with medication administration for opioid use disorder (OUD) and retention in treatment among pregnant women with OUD. METHODS: This is a retrospective, nationwide, cross-sectional analysis of treatment episodes for primary OUD among pregnant women from 2013 to 2017. The primary outcome was initiation of methadone, buprenorphine, or naltrexone. Secondary outcomes were retention in treatment defined as length of treatment episode lasting six months or greater, and completion of treatment. Descriptive statistics and logistic regression were applied to describe trends in, and identify factors associated with the outcomes. RESULTS: There were 42,239 treatment episodes for primary OUD among pregnant women who reported using heroin (65.0%, 27,459), synthetic opioid (33.2%, 14,034), or nonprescribed methadone (1.8%, 746) between 2013 and 2017. Medications for OUD were administered in 47.4% (20,013) of episodes. Retention in treatment occurred in 16.6% of episodes without medications for OUD, and 37.8% of episodes with medications for OUD (P=.01). The rate of medication administration for OUD increased from 41.0% in 2013 to 52.0% in 2017; however, retention rates declined from 39.0% to 33.0% among treatment episodes with medication for OUD. History of at least one prior treatment episode was associated with both administration of medications for OUD and retention in treatment. CONCLUSION: In spite of current guidelines, most treatment episodes for OUD during pregnancy did not involve administration of medications for OUD. Although administration of medications for OUD has improved over time, retention in treatment is lagging. These findings highlight gaps in the U.S. addiction care system.

Cytokine profiling: variation in immune modulation with preterm birth vs. uncomplicated term birth identifies pivotal signals in pathogenesis of preterm birth.

OBJECTIVES: To assess deviations in longitudinally measured cytokines with preterm birth (PTB). METHODS: Prospective longitudinal study targeting 80 subjects. Phlebotomy specimens for broad panel of cytokine analysis were obtained at three time (T) intervals: first trimester (T1: 8-14 weeks' gestation), second trimester (T2: 18-22 weeks' gestation), and third trimester (T3: 28-32 weeks' gestation). Important demographics and outcomes were tracked. Data were stratified and the target groups were analyzed as follows: "Uncomplicated" (delivered ≥37 weeks) or "Preterm Birth" (<37 weeks). Generalized Linear Modeling determined rate of change T1-T3 by outcome. RESULTS: Complete data replete with phlebotomy at all three visits were obtained on 80 women. Birth outcomes were as follows: 11 Uncomplicated Term Birth (UTB), 28 PTB, 4 low birth weight (LBW), 16 OB complications (OBC), 11 current infections (IFN), and 10 mixed complications (MC=2 or more of the above). 28 PTB were compared to 11 uncomplicated term deliveries. In both groups, T helper type 1 (TH1) cytokine (IL-1ß), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over gestation, but rates of change in IL-1ß, IL-6, and IL-10 were significantly different. Stratification of women by smoking status additionally demonstrated significant variance in immune status over the course of pregnancy. CONCLUSIONS: Women delivering PTB demonstrated significant differences in cytokine trajectory over pregnancy; these data further validate key role played by immune regulation in directing pregnancy outcome. Likewise, smoking impacts longitudinal trajectory of cytokines over pregnancy.