AN ORGAN-SPECIFIC APPROACH TO THE MANAGEMENT OF GESTATIONAL HYPERTENSION - EVIDENCE VS. TRADITION.

The management of hypertensive disease in pregnancy is currently guided by practice recommendations based largely on observational data from a half century ago and has changed only superficially since that time. These recommendations are both narrowly prescriptive (women without traditional features of severe disease should all be delivered at exactly 37 weeks and 0 days,) and at the same time frustratingly ambiguous (the presence of epigastric pain unresponsive to repeat analgesics precludes expectant management at any gestational age, regardless of laboratory studies.) Guidelines which ignore recent data from the obstetric, pediatric and internal medicine literature too often lead practitioners to be more aggressive than necessary in the delivery of very premature pregnancies, and, conversely, more complacent than patient safety would support in prolonging pregnancy with advanced fetal maturity. We present here an alternative, organ-specific based approach to the management of gestational hypertension which allows and encourages practitioners to formulate a management plan based on a thoughtful and, when possible, evidence- based synthesis of the continuous variables of blood pressure, degree of organ dysfunction and response to treatment, gestational age, and patient balancing of maternal and fetal/neonatal risks. Such clinical care is more complex and nuanced than simply basing life-altering critical management decisions, including timing of delivery, on whether the patient does, or does not have any one of the conditions described by box 4 of the current American College of Obstetricians and Gynecologists practice guidelines. Nonetheless, we believe this approach will not only improve care but will also open the door to useful investigations into prevention and management of the various entities traditionally considered as the same disease process.

Evaluation of fetal growth and birth weight in pregnancies with placenta previa with and without placenta accreta spectrum.

OBJECTIVES: We evaluated fetal growth and birthweight in pregnancies with placenta previa with and without placenta accreta spectrum (PAS). METHODS: We retrospectively studied pregnant patients with placenta previa with or without PAS diagnosed at 20-37 weeks' gestation. Estimated fetal weight (EFW) percentile and fetal growth rate were calculated based on ultrasound at two timepoints: 20-24 and 30-34-weeks' gestation. Fetuses were small (SGA) or large for gestational age (LGA) when EFW or abdominal circumference was <10th or >90th percentile for gestational age, respectively. Fetal growth rate was estimated by subtracting EFW percentiles from the two ultrasounds. Birthweight in grams and percentiles were estimated via Anderson and INTERGROWTH-21 standards adjusted for neonatal sex. EFW percentiles, fetal growth rate, birth weight and birthweight percentiles were compared between patients with placenta previa with and without PAS. RESULTS: We studied 171 patients with and 146 patients without PAS. SGA rates did not differ between groups on first (PAS n=3, no-PAS n=3, p=0.8) or second ultrasound (PAS n=10, no-PAS n=8, p=0.8). LGA rates were similar between groups on first (PAS n=11, no-PAS n=9, p=0.8) and second ultrasound (PAS n=20, no-PAS n=12, p=0.6). The growth rate was higher in fetuses with PAS than placenta previa (1.22 ± 22.3 vs. -4.1 ± 18.1, p=0.07), but not significantly. The birthweight percentile was higher in the PAS than the placenta previa group (74 vs. 67, p=0.01). On multi-linear regression, birthweight percentile remained higher in the PAS group, but not significantly. CONCLUSIONS: Placenta previa with or without PAS is not associated with SGA, LGA or lower birthweight.

Rate of preterm delivery and latency period in asymptomatic patients undergoing cerclage for very short cervix ≤10.0 mm.

BACKGROUND: In asymptomatic women with cervical length ≤10 mm, vaginal progesterone has a limited effect in reducing the rate of preterm delivery. OBJECTIVE: This study aimed to estimate the rate of preterm delivery and mean latency period to delivery in asymptomatic women with no history of preterm delivery and a cervical length of ≤10.0 mm undergoing or not undergoing cerclage and who were not treated with vaginal progesterone. STUDY DESIGN: This was a retrospective analysis of asymptomatic patients with singleton pregnancies and no history of preterm delivery with an incidental finding of a cervical length of ≤10.0 mm measured by transvaginal ultrasound during midtrimester scan. Of note, 56 patients (63.6%) underwent cerclage placement and 32 patients (36.4%) did not, none of them received vaginal progesterone. Patients with evidence of advanced dilation, prolapsing membranes, ruptured membranes, or positive signs of infection were not candidates for cerclage placement and were excluded from the analysis. Differences in the prevalence of preterm delivery, mean gestational age at delivery, and mean latency from very short cervix identification to delivery between the 2 groups were calculated. Associations between cerclage and preterm delivery adjusted for maternal characteristics and fetal weight were estimated. RESULTS: The median gestational ages at the time of cervical length measurement were 20 6/7 weeks (interquartile range, 17 5/7 to 23 3/7) in the cerclage group and 21 5/7 weeks (interquartile range, 17 6/7 to 23 6/7) in the no-cerclage group (P=.02). No difference in cervical length was observed between patients who had a cerclage (5.9±3.1 mm) and those who did not have a cerclage (6.5±3.2 mm) (P=.4). The prevalence of preterm delivery in women with cerclage vs women without cerclage was as follows: PTD at <37 weeks of gestation (31/56 [55.3%] in the cerclage group vs 28/32 [87.5%] in the no-cerclage group; adjusted odds ratio, 0.17; 95% confidence interval, 0.05-0.62; P=.008), PTD at ≤34 weeks of gestation (27/56 [48.2%] in the cerclage group vs 24/32 [75.0%] in the no-cerclage group; adjusted odds ratio, 0.16; 95% confidence interval, 0.05-0.55; P=.02), and PTD at ≤28 weeks of gestation (19/56 [33.9%] in the cerclage group vs 22/32 [68.7%] in the no-cerclage group; adjusted odds ratio, 0.15; 95% confidence interval, 0.05-0.51; P=.002). The median gestational ages at delivery were 32 6/7 weeks (interquartile range, 19 1/7 to 40 1/7) in the cerclage group and 28 1/7 weeks (interquartile range, 20 1/7 to 40 2/7) in the no-cerclage group (P=.001). The median latencies from the time of cervical length measurement to delivery were 84 days (interquartile range, 8-144) in the cerclage group and 43 days (interquartile range, 1-146) in the no-cerclage group (P=.003). CONCLUSION: Among low-risk asymptomatic women with a very short cervix (≤10.0 mm) in the midtrimester of pregnancy, women treated with cerclage have an increased latency to delivery and a lower prevalence of preterm delivery than those treated with expectant management.

Nulliparous with Class III Obesity at Term: Labor Induction or Cesarean Delivery without Labor.

OBJECTIVE: This study aimed to compare maternal and neonatal outcomes between labor induction versus cesarean delivery (CD) without labor among nulliparous individuals with class III obesity (body mass index [BMI] ≥40 kg/m2). STUDY DESIGN: A retrospective cohort study of all nulliparous singleton deliveries at ≥37 weeks with a BMI of ≥40 kg/m2 at delivery between March 2020 and February 2022. We excluded individuals with spontaneous labor, fetal malformations, and stillbirths. The primary outcome was a composite of maternal mortality and morbidity, including infectious and hemorrhagic morbidity. The secondary outcome was a neonatal composite. A subgroup analysis evaluated patients with a BMI of ≥50 kg/m2. Another subgroup analysis compared outcomes between CD without labor and an indicated CD following induction. A multivariable logistic regression was applied. For adjustment, we used possible confounders identified in a univariate analysis. RESULTS: Among 8,623 consecutive deliveries during the study period, 308 (4%) met the inclusion criteria. Among them, 250 (81%) underwent labor induction, and 58 (19%) had a CD without labor. The most common indications for CD without labor were fetal malpresentation (26; 45%), suspected macrosomia (8; 14%), and previous myomectomy (5; 9%). Indicated CD occurred in 140 (56%) of the induced individuals, with the two leading indications being labor arrest (87; 62%) and non-reassuring fetal heart rate tracing (51; 36%). The rates of composite maternal morbidity (adjusted odds ratio [aOR] = 2.14, 95% confidence interval [CI]: 0.64-7.13) and composite neonatal morbidity (aOR = 3.62, 95% CI: 0.42-31.19) did not differ following a CD without labor compared to labor induction. The subgroup analyses did not demonstrate different outcomes between groups. CONCLUSION: Among nulliparous individuals with class III obesity at term who underwent induction, more than 50% had indicated CD; the rate of short-term maternal and neonatal morbidity, however, did not differ between labor induction and CD without labor. KEY POINTS: · The rate of unplanned CD among those who underwent labor induction was relatively high (56.0%).. · Outcomes did not differ between those who underwent CD without labor and those who were induced.. · Outcomes also did not differ between those who underwent CD without labor and those with CD in labor..

Quantifying placenta accreta spectrum severity and its associated blood loss: a novel transvaginal ultrasound scoring system.

BACKGROUND: Hemorrhage associated with placenta accreta spectrum (PAS) is a leading cause of maternal morbidity and mortality. Estimating blood loss in these individuals is a critical component of comprehensive preoperative planning. OBJECTIVE: A semiquantitative score based on transvaginal ultrasound was developed and tested to predict PAS, estimate its severity, and blood loss in individuals with clinical and ultrasound evidence suggesting PAS. STUDY DESIGN: A secondary analysis was conducted of prospectively collected data from a quaternary center of patients with suspected accreta on 2D ultrasound and clinical suspicion. A predetermined scoring system was applied based on three components: (1) uterine wall (score 0: no loss of hypo-translucent uterine wall with overlying placenta in the lower uterine segment; 1: loss of hypo-translucent <3-cm defect; 2: 3-6-cm defect; and 3: >6-cm defect); (2) arterial vascularity at the uterine wall defect (score 0: no vessels observed; 1: 1-2 vessels over the defect; 2: 3-5 vessels; and 3: >5 vessels); and (3) cervical involvement (score 0: normal cervical length without previa; 1: previa with normal cervical length; 2: short cervix with previa, minimal vascularity and small lacunae; 3: short cervix with previa, increased vascularity and large lacunae). Each patient's three domain scores determined a cumulative, final score of 0-9. Patients were managed at the discretion of a multi-disciplinary team and patient's preference among the following options: cesarean delivery with placenta removal, cesarean delivery with placenta in-situ (conservative) with or without delayed hysterectomy, or cesarean hysterectomy. The frequency of different degrees of placental invasion per pathology examination per score unit was registered. Multiple linear regression analysis was performed for association of blood loss according to score adjusted by risk factors for PAS. RESULTS: A total of 73 patients were evaluated. All 11 patients who had a score of 0 had cesarean delivery with placenta removal without evidence of intraoperative PAS, thus resulting in a 100% negative predictive value. The remaining 62 had scores between 1 and 9. Among patients with scores 0-3 (n=20), only one had intraoperative PAS, yielding a negative predictive value of 97%. Higher scores were associated with severe PAS forms (r=0.301, P=.02). Based on the associations between PAS scores, clinical correlation, and blood loss, we divided patients into four categories: Category 0: PAS score 0; Category 1: scores 1-3; Category 2: scores 4-6; and Category 3: scores 7-9. The median blood loss in Category 0=635±352 mL, Category 1=634±599 mL, Category 2=1549±1284 mL, and Category 3=1895±2106 mL (P<.001). On multivariable analysis, Category 2 (ß=0.97, P<.01) and Category 3 (ß=1.26, P<.003) were associated with significantly greater blood loss than Category 0, irrespective of type of surgery. CONCLUSION: The transvaginal ultrasound score separates groups at low risk (Category 0) and at higher risk of PAS (Categories 1-3). Categories 1-3 may provide important clinical information to estimate the risk of severe forms of PAS and of blood loss during surgery. VIDEO ABSTRACT.

Pregnancy Outcomes in Patients With Hepatitis C Virus Infection.

OBJECTIVE: To evaluate the risks of adverse maternal and neonatal outcomes associated with pregnancies complicated by hepatitis C virus (HCV) infection. METHODS: This is a secondary analysis of a multicenter prospective cohort study of HCV infection in pregnancy. Participants were screened for HCV infection with serum antibody tests, and each participant with a positive HCV result (case group) was matched with up to two individuals with negative HCV results (control group) prospectively by gestational age (±2 weeks) at enrollment. Maternal outcomes included gestational diabetes, abruption, preeclampsia or gestational hypertension, cholestasis, and preterm delivery. Neonatal outcomes included hyperbilirubinemia, admission to neonatal intensive care (NICU); small-for-gestational-age (SGA) birth weight; and neonatal infection , defined as sepsis or pneumonia. Models were adjusted for maternal age, body mass index, injection drug use, and maternal medical comorbidities. RESULTS: The 249 individuals in the case group were prospectively matched to 486 individuals in the control group who met eligibility criteria. There were significant differences in demographic characteristics between the groups, including race, socioeconomic markers, education, insurance status, and drug and tobacco use. The frequencies of maternal outcomes of gestational diabetes, preeclampsia, and abruption were similar between the case and control groups. Preterm birth was similar between groups, but neonates born to individuals in the case group were more likely to be admitted to the NICU (45.1% vs 19.0%, adjusted odds ratio [aOR] 2.6, 95% CI, 1.8-3.8) and to have SGA birth weights below the 5th percentile (10.6% vs 3.1%, aOR 2.9, 95% CI, 1.4-6.0). There were no increased odds of hyperbilirubinemia or neonatal infection. CONCLUSION: Despite no increased odds of preterm birth or other adverse maternal outcomes in adjusted analyses, maternal HCV infection was associated with twofold increased odds of NICU admission and nearly threefold increased odds of SGA birth weight below the 5th percentile.

Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy: Pooled Analysis of Data from Two Randomized Controlled Trials.

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

Aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: a comparative effectiveness open-label randomized trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia in women at risk, whereas the NICE guidelines in the United Kingdom recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommended doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared with 81 mg in decreasing the rate of preeclampsia with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12-20 weeks of gestational age with a body mass index ≥30 kg/m2 at the time of enrollment and at least 1 of 3 high-risk factors: history of preeclampsia in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pregestational diabetes or gestational diabetes diagnosed before 20 weeks of gestational age were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin because of other indications, or contraindication to aspirin. The primary outcome was preeclampsia with severe features (preeclampsia or superimposed preeclampsia with severe features; eclampsia; or hemolysis, elevated liver enzymes, low platelet count syndrome). Secondary outcomes included rates of preterm birth because of preeclampsia, small for gestational age, postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Approximately 220/343 (64.1%) individuals were randomized. The primary outcome was available for 209/220 (95%) individuals. Baseline characteristics were similar between groups, with the median gestational age at enrollment being 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment before 16 weeks occurred in 55 of 110 of those assigned to 162 mg and 58 of 110 of those assigned to 81 mg of aspirin. The primary outcome occurred in n of d individuals (35%) in the 162 mg aspirin group and n of d individuals (40%) in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared with 81 mg aspirin dose. Rates of indicated preterm birth because of preeclampsia (21% vs 21%), small for gestational age (6.5% vs 2.9%), abruption (2.8% vs 3.0%), and postpartum hemorrhage (10.0% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was a 78% probability of benefit that 162 mg aspirin compared with 81 mg will decrease the rate of preeclampsia with severe features. With the best estimate of a 12% reduction when using 162 mg of aspirin compared with 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.

Permissive intrapartum glucose control: an equivalence randomized control trial (PERMIT).

BACKGROUND: There is limited high-quality data on the best practices for maternal blood glucose management during labor. OBJECTIVE: We compared permissive care (target maternal blood glucose 70-180 mg/dL) to usual care (blood glucose 70-110 mg/dL) among laboring individuals with diabetes. STUDY DESIGN: This was a two-site equivalence randomized control trial for individuals with diabetes (pregestational or gestational) at ≥34 weeks in labor. Individuals were randomly allocated to usual care or permissive care. Maternal blood glucose was evaluated by capillary blood glucose monitoring in latent and active labor every 4 and 2 hours. Insulin drip was initiated if maternal blood glucose exceeded the upper bounds of the allocated target. The primary outcome was the first neonatal heel stick glucose within 2 hours of birth before feeding. We assumed a mean first neonatal blood glucose of 50±10 mg/dL. To ensure that the use of permissive care did not increase or decrease the first neonatal blood glucose >10 mg/dL (2-tailed: a=0.05, b=0.1), 96 total participants were required. We calculated adjusted relative risk and 95% confidence intervals in an intention-to-treat analysis. A preplanned Bayesian analysis was used to estimate the probability of equivalence with a neutral informative prior. RESULTS: Of deliveries with diabetes assessed for eligibility (from October 2022 to June 2023), 280 of 511 (54.8%) met eligibility criteria, and 96 of 280 (34.3%) agreed and were randomized. In the usual care group, 17% required an insulin drip compared with none in permissive care. There was equivalence in the primary outcome between usual and permissive care (57.9 vs 57.1 mg/dL; adjusted mean difference, -0.72 [95% confidence interval, -8.87 to 7.43]). Bayesian analysis indicated a 98% posterior probability of the mean difference not being >10 mg/dL. The rate of neonatal hypoglycemia was 25% in the usual care group and 29% in the permissive group (adjusted relative risk, 1.14; 95% confidence interval, 0.60-2.17). There was no difference in other neonatal or maternal outcomes. CONCLUSION: In this randomized control trial, although almost 1 in 6 individuals with diabetes required an insulin drip with usual intrapartum maternal blood glucose care, permissive care was associated with equivalent neonatal blood glucose.

Expectant management of preeclampsia with severe features diagnosed at less than 24 weeks.

BACKGROUND: The recent American College of Obstetricians and Gynecologists Practice Bulletin offers no guidance on the management of preeclampsia with severe features at <24 weeks of gestation. Historically, immediate delivery was recommended because of poor perinatal outcomes and high maternal morbidity. Recently, advances in neonatal resuscitation have led to increased survival at periviable gestational ages. OBJECTIVE: This study aimed to report perinatal and maternal outcomes after expectant management of preeclampsia with severe features at <24 weeks of gestation. STUDY DESIGN: This was a retrospective case series of preeclampsia with severe features at <24 weeks of gestation at a level 4 center between 2017 and 2023. Individuals requiring delivery within 24 hours of diagnosis were excluded. Perinatal and maternal outcomes were analyzed. Categorical variables from our database were compared with previously published data using chi-square tests. RESULTS: A total of 41 individuals were diagnosed with preeclampsia with severe features at <24 weeks of gestation. After the exclusion of delivery within 24 hours, 30 individuals (73%) were evaluated. The median gestational age at diagnosis was 22 weeks (interquartile range, 22-23). Moreover, 16% of individuals had assisted reproductive technology, 27% of individuals had chronic hypertension, 13% of individuals had pregestational diabetes mellitus, 30% of individuals had previous preeclampsia, and 73% of individuals had a body mass index of >30 kg/m2. The median latency periods at 22 and 23 weeks of gestation were 7 days (interquartile range, 4-23) and 8 days (interquartile range, 4-13). In preeclampsia with severe features, neonatal survival rates were 44% (95% confidence interval, 3%-85%) at 22 weeks of gestation and 29% (95% confidence interval, 1%-56%) at 23 weeks of gestation. There were 2 cases of acute kidney injury (7%) and 2 cases of pericardial or pleural effusions (7%). Overall perinatal survival at <24 weeks of gestation was 30% in our current study vs 7% in previous reports (P=.02). CONCLUSION: For cases of expectant management of preeclampsia with severe features at <24 weeks of gestation, our findings showed an increased perinatal survival rate with decreased maternal morbidity compared with previously published data. This information may be used when counseling on expectant management of preeclampsia with severe features at <24 weeks of gestation.

Trends and Outcomes among Pregnancy and Nonpregnancy-Related Hospitalizations with Diabetic Ketoacidosis.

OBJECTIVE: The study's primary objective was to evaluate adverse outcomes among reproductive-age hospitalizations with diabetic ketoacidosis (DKA), comparing those that are pregnancy-related versus nonpregnancy-related and evaluating temporal trends. STUDY DESIGN: We conducted a retrospective cross-sectional study using the National Inpatient Sample to identify hospitalizations with DKA among reproductive-age women (15-49 years) in the United States (2016-2020). DKA in pregnancy hospitalizations was compared with DKA in nonpregnant hospitalizations. Adverse outcomes evaluated included mechanical ventilation, coma, seizures, renal failure, prolonged hospital stay, and in-hospital death. Multivariable Poisson regression models with robust error variance were used to estimate adjusted relative risk (aRR) and 95% confidence interval (CI). Annual percent change (APC) was used to calculate the change in DKA rate over time. RESULTS: Among 35,210,711 hospitalizations of reproductive-age women, 447,600 (1.2%) were hospitalized with DKA, and among them, 13,390 (3%) hospitalizations were pregnancy-related. The rate of nonpregnancy-related DKA hospitalizations increased over time (APC = 3.8%, 95% CI = 1.5-6.1). After multivariable adjustment, compared with pregnancy-related hospitalizations with DKA, the rates of mechanical ventilation (aRR = 1.56, 95% CI = 1.18-2.06), seizures (aRR = 2.26, 95% CI = 1.72-2.97), renal failure (aRR = 2.26, 95% CI = 2.05-2.50), coma (aRR = 2.53, 95% CI = 1.68-3.83), and in-hospital death (aRR = 2.38, 95% CI = 1.06-5.36) were higher among nonpregnancy-related hospitalizations with DKA. CONCLUSION: A nationally representative sample of hospitalizations indicates that over the 5-year period, the rate of nonpregnancy-related DKA hospitalizations increased among reproductive age women, and a higher risk of adverse outcomes was observed when compared with pregnancy-related DKA hospitalizations. KEY POINTS: · Over 5 years, the rate of pregnancy-related DKA hospitalizations was stable.. · Over 5 years, the rate of nonpregnancy-related DKA hospitalizations increased.. · There is a higher risk of adverse outcomes with DKA outside of pregnancy..

Factors Associated with Refractory Severe Hypertension in Patients with Preeclampsia.

OBJECTIVE: This study aimed to identify factors associated with refractory severe hypertension that does not resolve after an initial dose of antihypertensive medication in patients with preeclampsia. STUDY DESIGN: This was a retrospective study of all pregnant and postpartum individuals with a diagnosis of preeclampsia, superimposed preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, or eclampsia who delivered at 22 weeks or greater at a single academic institution from 2010 to 2020. Inclusion criteria were patients with preeclampsia who developed severe hypertension (systolic pressure ≥160 mm Hg or diastolic pressure ≥110 mm Hg) and received antihypertensive medications for acute severe hypertension. We defined refractory severe hypertension as a systolic blood pressure of ≥160 mm Hg or a diastolic blood pressure of ≥110 mm Hg that did not improve after receiving the initial treatment. To evaluate for factors associated with refractory severe hypertension, we developed multivariable modified Poisson regression using all variables with p-value <0.1 on bivariable analysis and calculated adjusted relative risks (aRRs) with 95% confidence intervals (95% CIs). RESULTS: Of 850, 386 (45.4%) had refractory severe hypertension and 464 (54.6%) responded to the initial antihypertensive medications. Factors associated with refractory severe hypertension included higher body mass index (BMI), chronic hypertension, and higher systolic pressure. Every 5 kg/m2 increase in BMI was associated with a 7% increased risk of refractory severe hypertension (aRR = 1.07; 95% CI: 1.02-1.12). Every 10 mm Hg increase in systolic blood pressure was associated with a 10% increased risk of refractory severe hypertension (aRR = 1.10; 95% CI: 1.04-1.17). Chronic hypertension was associated with a 25% increased risk of refractory severe hypertension (aRR = 1.25; 95% CI: 1.01-1.56) in the diastolic pressure model. CONCLUSION: Refractory severe hypertension was associated with elevated BMI, chronic hypertension, and higher systolic blood pressure. KEY POINTS: · Risk factors for refractory severe hypertension are not well-known.. · Almost half of the patients had refractory severe hypertension.. · Higher BMI, chronic hypertension, and higher systolic pressure were the risk factors.. · These patients would require closer follow-up and prompt response to vital signs..

Risk of Postpartum Hemorrhage in Hypertensive Disorders of Pregnancy: Stratified by Severity.

OBJECTIVE: We aimed to determine the composite maternal hemorrhagic outcome (CMHO) among individuals with and without hypertensive disorders of pregnancy (HDP), stratified by disease severity. Additionally, we investigated the composite neonatal adverse outcome (CNAO) among individuals with HDP who had postpartum hemorrhage (PPH) versus did not have PPH. STUDY DESIGN: Our retrospective cohort study included all singletons who delivered at a Level IV center over two consecutive years. The primary outcome was the rate of CMHO, defined as blood loss ≥1,000 mL, use of uterotonics, mechanical tamponade, surgical techniques for atony, transfusion, venous thromboembolism, intensive care unit admission, hysterectomy, or maternal death. A subgroup analysis was performed to investigate the primary outcome stratified by (1) chronic hypertension, (2) gestational hypertension and preeclampsia without severe features, and (3) preeclampsia with severe features. A multivariable regression analysis was performed to investigate the association of HDP with and without PPH on a CNAO which included APGAR <7 at 5 minutes, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, seizures, neonatal sepsis, meconium aspiration syndrome, ventilation >6 hours, hypoxic-ischemic encephalopathy, or neonatal death. RESULTS: Of 8,357 singletons, 2,827 (34%) had HDP. Preterm delivery <37 weeks, induction of labor, prolonged oxytocin use, and magnesium sulfate usage were more common in those with versus without HDP (p < 0.001). CMHO was higher among individuals with HDP than those without HDP (26 vs. 19%; adjusted relative risk [aRR] = 1.11, 95% CI: 1.01-1.22). In the subgroup analysis, only individuals with preeclampsia with severe features were associated with higher CMHO (n = 802; aRR = 1.52, 95% CI: 1.32-1.75). There was a higher likelihood of CNAO in individuals with both HDP and PPH compared to those with HDP without PPH (aRR = 1.49, 95% CI: 1.06-2.09). CONCLUSION: CMHO was higher among those with HDP. After stratification, only those with preeclampsia with severe features had an increased risk of CMHO. Among individuals with HDP, those who also had a PPH had worse neonatal outcomes than those without hemorrhage. KEY POINTS: · Individuals with HDP had an 11% higher likelihood of CMHO.. · After stratification, increased CMHO was limited to those with preeclampsia with severe features.. · There was a higher likelihood of CNAO in those with both HDP and PPH compared to HDP without PPH..

Indicated vs universal third-trimester ultrasound examination in low-risk pregnancies: a pre-post-intervention study.

BACKGROUND: In low-risk pregnancies, a third-trimester ultrasound examination is indicated if fundal height measurement and gestational age discrepancy are observed. Despite potential improvement in the detection of ultrasound abnormality, prior trials to date on universal third-trimester ultrasound examination in low-risk pregnancies, compared with indicated ultrasound examination, have not demonstrated improvement in neonatal or maternal adverse outcomes. OBJECTIVE: The primary objective was to determine if universal third-trimester ultrasound examination in low-risk pregnancies could attenuate composite neonatal adverse outcomes. The secondary objectives were to compare changes in composite maternal adverse outcomes and detection of abnormalities of fetal growth (fetal growth restriction or large for gestational age) or amniotic fluid (oligohydramnios or polyhydramnios). STUDY DESIGN: Our pre-post intervention study at 9 locations included low-risk pregnancies, those without indication for ultrasound examination in the third trimester. Compared with indicated ultrasound in the preimplementation period, in the postimplementation period, all patients were scheduled for ultrasound examination at 36.0-37.6 weeks. In both periods, clinicians intervened on the basis of abnormalities identified. Composite neonatal adverse outcomes included any of: Apgar score ≤5 at 5 minutes, cord pH <7.00, birth trauma (bone fracture or brachial plexus palsy), intubation for >24 hours, hypoxic-ischemic encephalopathy, seizure, sepsis (bacteremia proven with blood culture), meconium aspiration syndrome, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, necrotizing enterocolitis, stillbirth after 36 weeks, or neonatal death within 28 days of birth. Composite maternal adverse outcomes included any of the following: chorioamnionitis, wound infection, estimated blood loss >1000 mL, blood transfusion, deep venous thrombus or pulmonary embolism, admission to intensive care unit, or death. Using Bayesian statistics, we calculated a sample size of 600 individuals in each arm to detect >75% probability of any reduction in primary outcome (80% power; 50% hypothesized risk reduction). RESULTS: During the preintervention phase, 747 individuals were identified during the initial ultrasound examination, and among them, 568 (76.0%) met the inclusion criteria at 36.0-37.6 weeks; during the postintervention period, the corresponding numbers were 770 and 661 (85.8%). The rate of identified abnormalities of fetal growth or amniotic fluid increased from between the pre-post intervention period (7.1% vs 22.2%; P<.0001; number needed to diagnose, 7; 95% confidence interval, 5-9). The primary outcome occurred in 15 of 568 (2.6%) individuals in the preintervention and 12 of 661 (1.8%) in the postintervention group (83% probability of risk reduction; posterior relative risk, 0.69 [95% credible interval, 0.34-1.42]). The composite maternal adverse outcomes occurred in 8.6% in the preintervention and 6.5% in the postintervention group (90% probability of risk; posterior relative risk, 0.74 [95% credible interval, 0.49-1.15]). The number needed to treat to reduce composite neonatal adverse outcomes was 121 (95% confidence interval, 40-200). In addition, the number to reduce composite maternal adverse outcomes was 46 (95% confidence interval, 19-74), whereas the number to prevent cesarean delivery was 18 (95% confidence interval, 9-31). CONCLUSION: Among low-risk pregnancies, compared with routine care with indicated ultrasound examination, implementation of a universal third-trimester ultrasound examination at 36.0-37.6 weeks attenuated composite neonatal and maternal adverse outcomes.

Implementing a Bundle for Evidence-based Cesarean Delivery May Not Be As Beneficial as Expected: A Multi-center, Pre- and Post- Study.

BACKGROUND: Standardization of procedures improves outcomes. Though systematic reviews have summarized the evidence-based steps (EBS) of cesarean delivery (CD), their bundled implementation has not been investigated. OBJECTIVE: In this pre- and post-implementation trial, we sought to ascertain if bundled EBS of CD, compared to surgeon's preference, improves outcomes. STUDY DESIGN: A StaRI (Standards for Reporting Implementation Studies) compliant, multi-center pre- and post-implementation trial at 4 teaching hospitals was conducted. The pre-implementation period consisted of CD done based on the physicians' preferences for 3 months; educational intervention (e.g., didactics, badge cards, posters, video) occurred at the 4th month. CDs in post-implementation period employed the bundled EBS. A pre-planned 10% randomized audit of both groups assessed adherence and uptake of EBS. The primary outcome was a composite maternal morbidity (CMM), which included estimated blood loss > 1,000 mL, blood transfusion, endometritis, post-partum fever, wound complications, sepsis, thrombosis, ICU admission, hysterectomy, or death. The secondary outcome was a composite neonatal morbidity (CNM) and some of its components were 5-min Apgar score < 7, positive pressure oxygen use, hypoglycemia, or sepsis. A priori Bayesian sample size calculation indicated 700 CD in each group was needed to demonstrate 20% relative reduction (from 15% to 12%) of CMM with 75% certainty. Bayesian logistic regression with neutral priors was used to calculate likelihood of net-improvement in adjusted relative risk (aRR) with 95% credible intervals (CrI). RESULTS: A total of 1,425 consecutive CD (721 in pre- and 704 in post-implementation group) were examined. Audited data indicated that the baseline EBS utilization rate during the pre-implementation period was 79%; after the implementation bundled EBS of CD the audited adherence was 89%-an uptake of 10.0% of the EBS. In four aspects, the maternal characteristics differed significantly in the pre- and post-implementation periods: race/ethnicity, hypertensive disorder, and the relative contribution of the 4 centers to the cohorts and the gestational age at delivery, but the indications for CD and whether its duration was < versus > 60 min did not. The rates of CMM in the pre- and post-implementation groups were 26% and 22%, respectively (aRR, 0.88; 95% CrI, 0.73-1.04), with a 94 % Bayesian probability of a reduction in CMM. The CNM occurred in 37% of the pre- and in 41% of the post-implementation group (aRR, 1.12; 95% CrI 0.98-1.39), with a 95% Bayesian probability of worsening in CNM. When CMM were segregated by preterm (<37 wks) and term (> 37 weeks) CD, the improvement in maternal outcomes persisted; when CNM were segregated by gestational age subgroupsthe potential for worsening neonatal outcomes persisted as well. CONCLUSIONS: Standardization of the evidence-based bundled steps of cesarean delivery resulted in a modest reduction of the composite maternal outcome; however, a paradoxical increase in neonatal composite morbidity was noted. Although individual evidence-based steps may be of value, while awaiting additional intervention trials a formal bundling of such steps is currently not recommended.

Equivalence of single and standard doses of antenatal corticosteroids for late preterm neonatal outcomes: insights from a secondary analysis.

BACKGROUND: The recent paradigm shift of treating individuals at risk of late preterm birth with antenatal corticosteroids warrants an assessment of the effect of single dosage. OBJECTIVE: To compare outcomes of neonates born in the late preterm period (34.0-36.6 weeks) after a single dose of antenatal corticosteroids vs placebo. STUDY DESIGN: We performed a secondary analysis of the Antenatal Late Preterm Steroids trial. All individuals enrolled in the parent trial who received only a single dose of either antenatal corticosteroids or placebo and delivered within 24 hours were included. Primary outcome was a composite of respiratory support at 72 hours, including continuous positive airway pressure or high-flow nasal cannula ≥2 hours, oxygen with an inspired fraction of ≥30% for ≥4 hours, or mechanical ventilation. RESULTS: Of the 2831 individuals in the parent trial, 1083 (38.3%) met inclusion criteria; of them, 539 (49.8%) received a single dose of antenatal corticosteroids and 544 (50.2%) a single placebo dose. The placebo and antenatal corticosteroids groups had similar demographic and clinical characteristics. There was no difference in the rate of the primary respiratory outcome (adjusted risk ratio, 1.12; 95% confidence interval, 0.85-1.47) or in the rate of respiratory distress syndrome (adjusted risk ratio, 1.47; 95% confidence interval, 0.95-2.26) between those who received a single antenatal corticosteroids dose and placebo. An exploratory stratification by randomization-to-delivery intervals of 12-hour increments also showed no association with lower primary respiratory outcome rates. CONCLUSION: In individuals with late preterm birth pregnancies who received antenatal corticosteroids and delivered before a second dose, there were no differences in neonatal respiratory morbidities compared with placebo. However, this study is not powered to detect treatment efficacy.