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.

Permissive Intrapartum Glucose Control: An Equivalence Randomized Control Trial (PERMIT).

BACKGROUND: There is limited high quality data to determine 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 first neonatal heel stick glucose within two 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 (two-tailed, α= 0.05, ß= 0.1), 96 total participants were required. We calculated adjusted relative risk (aRR) and 95% confidence intervals (CI) in an intention-to-treat analysis. A Bayesian analysis was preplanned to estimate the probability of equivalence with a neutral informative prior. RESULTS: Of 511 deliveries with diabetes assessed for eligibility (10/2022 - 6/2023), 280 (54.8%) met eligibility criteria, and 96 (34.3%) agreed and were randomized. In the usual care group, 17% required an insulin drip compared to 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% CI -8.87,7.43). Bayesian analysis indicated 98% posterior probability of mean difference not being greater than ±10 mg/dL. The rate of neonatal hypoglycemia was 25% in the usual care group and 29% in permissive group (adjusted relative risk 1.14, 95% CI 0.60, 2.17). There was no difference in other neonatal or maternal outcomes. CONCLUSION: In this randomized control trial, while 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.

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..

Emerging concepts since the Chronic Hypertension and Pregnancy trial.

The recent publication of the Chronic Hypertension and Pregnancy (CHAP) trial has already changed the management of pregnant people with mild chronic hypertension. However, similar to any new intervention or change in management, we have encountered confusion regarding the management and implementation of the "Treatment for mild chronic hypertension during pregnancy" trial findings. In this clinical opinion, we addressed the aspects relating to the implementation that cannot be gleaned from the manuscript but were part of the trial conduct. Furthermore, we discussed several clinical questions that may affect the management of a patient with chronic hypertension following the "Treatment for mild chronic hypertension during pregnancy" trial and provided suggestions based on our experience and opinion.

Oral combined hydrochlorothiazide and lisinopril vs nifedipine for postpartum hypertension: a comparative-effectiveness pilot randomized controlled trial.

BACKGROUND: Angiotensin-converting enzyme inhibitors and diuretics may be underutilized for postpartum hypertension because of their teratogenicity during pregnancy. OBJECTIVE: We evaluated whether combined oral hydrochlorothiazide and lisinopril therapy produced superior short-term blood pressure control when compared with nifedipine among postpartum individuals with hypertension requiring pharmacologic treatment. STUDY DESIGN: We performed a pilot randomized controlled trial (October 2021 to June 2022) that included individuals with chronic hypertension or hypertensive disorders of pregnancy with 2 systolic blood pressure measurements ≥150 mm Hg and/or diastolic blood pressure measurements ≥100 mm Hg within 72 hours after delivery. Participants were randomized to receive either combined hydrochlorothiazide and lisinopril therapy or nifedipine therapy after stratifying the participants by diagnosis (chronic hypertension vs hypertensive disorders of pregnancy). The primary outcome was stage 2 hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) determined using a home blood pressure monitor on days 7 to 10 after delivery or at readmission to the hospital for blood pressure control. The secondary outcomes included severe maternal morbidity (any of the following: intensive care unit admission; hemolysis, elevated liver enzymes, low platelet count syndrome; eclampsia; stroke; cardiomyopathy; or maternal death), need for intravenous medications after randomization, hospital length of stay, blood pressure during first clinic visit, medication compliance, and adverse events. A pilot trial with 70 individuals was planned given the limited available data on combined hydrochlorothiazide and lisinopril therapy use in postpartum care. We calculated relative risks and 95% credible intervals in an intention-to-treat analysis. Finally, we conducted a preplanned Bayesian analysis to estimate the probability of benefit or harm with a neutral informative prior. RESULTS: Of 111 eligible individuals, 70 (63%) agreed and were randomized (31 in the hydrochlorothiazide and lisinopril group and 36 in the nifedipine group; 3 withdrew consent after randomization), and the characteristics were similar at baseline between the groups. The primary outcome was unavailable for 9 (12.8%) participants. The primary outcome occurred in 27% of participants in the hydrochlorothiazide and lisinopril group and in 43% of the participants in the nifedipine group (posterior adjusted relative risk, 0.74; 95% credible interval, 0.40-1.31). Bayesian analysis indicated an 85% posterior probability of a reduction in the primary outcome with combined hydrochlorothiazide and lisinopril therapy relative to nifedipine treatment. No differences were noted in the secondary outcomes or adverse medication events. CONCLUSION: The results of the pilot trial suggest a high probability that combined hydrochlorothiazide and lisinopril therapy produces superior short-term BP control when compared with nifedipine. These findings should be confirmed in a larger trial.

Continuous glucose monitoring in individuals undergoing gestational diabetes screening.

BACKGROUND: Among guidelines on gestational diabetes mellitus, there is an incongruity about the threshold of maternal hyperglycemia to diagnose gestational diabetes mellitus. OBJECTIVE: This study aimed to ascertain the association between continuous glucose monitoring metrics and adverse outcomes among individuals undergoing gestational diabetes mellitus screening. STUDY DESIGN: This was a prospective study (from June 2020 to January 2022) of individuals who underwent 2-step gestational diabetes mellitus screening at ≤30 weeks of gestation. The participants wore a blinded continuous glucose monitoring device (Dexcom G6 Pro; Dexcom, Inc, San Diego, CA) for 10 days starting when they took the 50-g glucose challenge test. The primary outcome was a composite of adverse neonatal outcomes (large for gestational age, shoulder dystocia or neonatal injury, respiratory distress, need for intravenous glucose treatment for hypoglycemia, or fetal or neonatal death). The secondary neonatal outcomes included preterm birth, neonatal intensive care unit admission, hypoglycemia, mechanical ventilation or continuous positive airway pressure, hyperbilirubinemia, and hospital length of stay. The secondary maternal outcomes included weight gain during pregnancy, hypertensive disorders of pregnancy, induction of labor, cesarean delivery, and postpartum complications. Time within the target range (63-140 mg/dL), time above the target range (>140 mg/dL) expressed as a percentage of all continuous glucose monitoring readings, and mean glucose level were analyzed. The Youden index was used to choose the threshold of ≥10% for the time above the target range and association with adverse outcomes. RESULTS: Of 136 participants recruited, data were available from 92 individuals (67.6%). The 2-step method diagnosed gestational diabetes mellitus in 2 individuals (2.2%). Continuous glucose monitoring indicated that 17 individuals (18.5%) had time above the target range of ≥10%. Individuals with time above the target range of ≥10% had a significantly higher likelihood of composite adverse neonatal outcomes than individuals with time above the target range of <10% (63% vs 18%; P=.001). Furthermore, compared with neonates born to individuals with time above the target range of <10%, neonates born to individuals with time above the target range of ≥10% had an increased likelihood for hypoglycemia (14.5% vs 47%; P=.009) and had a longer length of stay (2 vs 4 days; P=.03). No difference in maternal outcomes was noted between the groups. CONCLUSION: In this prospective study of individuals undergoing gestational diabetes mellitus screening, a cutoff of the time above the target range of ≥10% using continuous glucose monitoring was associated with a higher rate of neonatal adverse outcomes. A randomized trial of continuous glucose monitoring vs 2-step screening for gestational diabetes mellitus to lower the rate of adverse outcomes is underway (identification number: NCT05430204).

Factors associated with exclusive formula feeding among individuals with low-risk pregnancies in the United States.

BACKGROUND: Better understanding of the factors associated with formula feeding during the hospital stay can help in identifying potential lactation problems and promote early intervention. Our aim was to ascertain factors associated with exclusive formula feeding in newborns of low-risk pregnancies. METHODS: A population-based, retrospective study using the United States vital statistics datasets (2014-2018) evaluating low-risk pregnancies with a nonanomalous singleton delivery from 37 to 41 weeks. People with hypertensive disorders, or diabetes, were excluded. Primary outcome was newborn feeding (breast vs exclusive formula feeding) during hospital stay. Adjusted relative risks (aRRs) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 19 623 195 live births during the study period, 11 605 242 (59.1%) met inclusion criteria and among them, 1 929 526 (16.6%) were formula fed. Factors associated with formula feeding included: age < 20 years (aRR 1.31 [95% CI 1.31-1.32]), non-Hispanic Black (1.42, 1.41-1.42), high school education (1.69, 1.69-1.70) or less than high school education (1.94, 1.93, 1.95), Medicaid insurance (1.52, 1.51, 1.52), body mass index (BMI) < 18.5 (1.10, 1.09-1.10), BMI 25-29.9 (1.09, 1.09-1.09), BMI 30-34.9 (1.19, 1.19-1.20), BMI 35-39.9 (1.31, 1.30-1.31), BMI ≥ 40 (1.43, 1.42-1.44), multiparity (1.29, 1.29-1.30), lack of prenatal care (1.49, 1.48-1.50), smoking (1.75, 1.74-1.75), and gestational age (ranged from 37 weeks [1.44, 1.43-1.45] to 40 weeks [1.11, 1.11-1.12]). CONCLUSIONS: Using a large cohort of low-risk pregnancies, we identified several modifiable factors associated with newborn feeding (eg, prepregnancy BMI, access to prenatal care, and smoking cessation). Improving the breast feeding initiation rate should be a priority in our current practice to ensure equitable care for all neonates.

Time in Range and Pregnancy Outcomes in People with Diabetes Using Continuous Glucose Monitoring.

OBJECTIVE: The international consensus on continuous glucose monitoring (CGM) recommends time in range (TIR) target of >70% for pregnant people. Our aim was to compare outcomes between pregnant people with TIR ≤ versus >70%. STUDY DESIGN: This study was a retrospective study of all people using CGM during pregnancy from January 2017 to May 2021 at a tertiary care center. All people with pregestational diabetes who used CGM and delivered at our center were included in the analysis. Primary neonatal outcome included any of the following: large for gestational age, neonatal intensive care unit (NICU) admission, need for intravenous (IV) glucose, or respiratory distress syndrome (RDS). Maternal outcomes included hypertensive disorders of pregnancy and delivery outcomes. Logistic regression was used to estimate unadjusted and adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Of 78 people managed with CGM, 65 (80%) met inclusion criteria. While 33 people (50.1%) had TIR ≤70%, 32 (49.2%) had TIR >70%. People with TIR ≤70% were more likely to be younger, have a lower body mass index, and have type 1 diabetes than those with TIR >70%. After multivariable regression, there was no difference in the composite neonatal outcome between the groups (aOR: 0.56, 95% CI: 0.16-1.92). However, neonates of people with TIR ≤70% were more likely to be admitted to the NICU (p = 0.035), to receive IV glucose (p = 0.005), to have RDS (p = 0.012), and had a longer hospital stay (p = 0.012) compared with people with TIR >70%. Furthermore, people with TIR ≤70% were more likely to develop hypertensive disorders (p = 0.04) than those with TIR >70%. CONCLUSION: In this cohort, the target of TIR >70% was reached in about one out of two people with diabetes using CGM, which correlated with a reduction in neonatal and maternal complications. KEY POINTS: · Among people with diabetes, 50% reached the recommended time in range using CGM.. · Time in range >70% was associated with reducing the rate of some neonatal complications.. · Time in range ≤70% was associated with increased risk for adverse maternal outcomes..

The Role of Cerclage in Subsequent Pregnancy following Previable Prelabor Rupture of Membranes.

OBJECTIVE: This study aimed to ascertain the outcomes associated with a cervical cerclage among individuals with a history of previable prelabor rupture of membranes (PROM). STUDY DESIGN: This study was a retrospective cohort study conducted at a single tertiary center between 2011 and 2021. We included individuals with a history of previable (before 24 weeks) PROM and the subsequent viable pregnancy. Women with multifetal gestation, preterm birth (PTB) or cerclage in previous gestation, or abdominal cerclage after trachelectomy were excluded. Primary outcome was PTB rate (delivery <37 weeks). Recurrence of preterm PROM and adverse composite maternal and neonatal outcomes (CMO and CNO) were evaluated as secondary outcomes. CMO included any of the following: suspected chorioamnionitis, endometritis, red blood cell transfusion, uterine rupture, unplanned hysterectomy, or death. CNO included any of the following: previable PTB (<24 weeks of gestation), bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, mechanical ventilation, seizures, hypoxic ischemic encephalopathy, or death. RESULTS: During the study period, 118 individuals had a history of previable PROM and a documented subsequent pregnancy, out of which 74 (62.7%) met inclusion criteria. Nineteen (25.7%) of eligible individuals underwent a cerclage for prior previable PROM and were compared with controls (n = 55, 74.3%). Women who underwent a cerclage had higher rates of PTB < 37 weeks (63.2 vs. 10.9%, p < 0.001; odds ratio [OR]: 14.00, 95% confidence interval [CI]: 3.97-49.35) and < 34 weeks (21.1 vs. 3.6%, p = 0.03; OR: 7.07, 95% CI: 1.18-42.39) compared with those without cerclage. Furthermore, recurrent preterm PROM and previable PTB rates were higher among patients who underwent cerclage. The survival curve further indicated that individuals with cerclage delivered earlier. CMO and CNO rates were similar in those with and without cerclage. CONCLUSION: Cerclage placement in individuals with prior previable PROM was associated with higher rates of recurrent preterm PROM and PTB. KEY POINTS: · The management of individuals in a subsequent pregnancy following previable PROM is a conundrum.. · Cerclage following previable PROM is associated with higher rates of recurrent preterm PROM and PTB.. · Composite maternal and neonatal outcome rates were similar in those with and without cerclage..

Racial and Ethnic Disparities among Pregnancies with Chronic Hypertension and Adverse Outcomes.

OBJECTIVE: We aimed to ascertain whether the risk of adverse pregnancy outcomes in the United States among individuals with chronic hypertension differed by maternal race and ethnicity and to assess the temporal trend. STUDY DESIGN: Population-based retrospective study using the U.S. Vital Statistics datasets evaluated pregnancies with chronic hypertension, singleton live births that delivered at 24 to 41 weeks. The coprimary outcomes were a composite maternal adverse outcome (preeclampsia, primary cesarean delivery, intensive care unit admission, blood transfusion, uterine rupture, or unplanned hysterectomy) and a composite neonatal adverse outcome (preterm birth, small for gestational age, Apgar's score <5 at 5 minutes, assisted ventilation> 6 hours, seizure, or death). Multivariable Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs). RESULTS: Between 2014 and 2019, the rate of chronic hypertension in pregnancy increased from 1.6 to 2.2%. After multivariable adjustment, an increased risk for the composite maternal adverse outcome was found in Black (aRR = 1.10, 95% CI = 1.09-1.11), Hispanic (aRR = 1.04, 95% CI = 1.02-1.05), and Asian/Pacific Islander (aRR = 1.07, 95% CI = 1.05-1.10), compared with White individuals. Compared with White individuals, the risk of the composite neonatal adverse outcome was higher in Black (aRR = 1.39, 95% CI = 1.37-1.41), Hispanic (aRR = 1.15, 95% CI = 1.13-1.16), Asian/Pacific Islander (aRR = 1.34, 95% CI = 1.31-1.37), and American Indian (aRR = 1.12, 95% CI = 1.07-1.17). The racial and ethnic disparity remained unchanged during the study period. CONCLUSION: We found a racial and ethnic disparity with maternal and neonatal adverse outcomes in pregnancies with chronic hypertension that remained unchanged throughout the study period. KEY POINTS: · Between 2014 and 2019, the rate of chronic hypertension in pregnancy increased.. · Among people with chronic hypertension, there are racial and ethnic disparities in adverse outcomes.. · Black, Hispanic, and Asian/Pacific Islander have a higher risk of the adverse neonatal outcomes..

Continuous Glucose Monitoring and Time in Range: Association with Adverse Outcomes among People with Type 2 or Gestational Diabetes Mellitus.

OBJECTIVE: Continuous glucose monitoring (CGM) has become available for women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) during pregnancy. The recommended time in range (TIR, blood glucose 70-140 mg/dL) and its correlation with adverse pregnancy outcomes in this group is unknown. Our aim was to compare maternal and neonatal outcomes in pregnant people with T2DM or GDM with average CGM TIR values >70 versus ≤ 70%. STUDY DESIGN: We conducted a retrospective cohort study of all individuals using CGM during pregnancy from January 2017 to June 2022. Individuals with type 1 diabetes mellitus, or those missing CGM or delivery data were excluded. Primary composite neonatal outcome included any of the following: large for gestational age, NICU admission, need for intravenous glucose, respiratory support, or neonatal death. Secondary outcomes included other maternal and neonatal outcomes. Regression models were used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: During the study period, 141 individuals with diabetes utilized CGM during pregnancy, with 65 (46%) meeting inclusion criteria. Of the study population, 28 (43%) had TIR ≤70% and 37 (57%) had TIR > 70%. Compared with those with TIR > 70%, the primary composite outcome occurred more frequently in neonates of individuals TIR ≤70% (71.4 vs. 37.8%, aOR: 4.8, 95% CI: 1.6, 15.7). Furthermore, individuals with TIR ≤70% were more likely to have hypertensive disorders (42.9 vs. 16.2%, OR: 3.9, 95% CI: 1.3, 13.0), preterm delivery (54 vs. 27%, OR: 3.1, 95% CI: 1.1, 9.1): , and cesarean delivery (96.4 vs. 51.4%, OR: 4.6, 95% CI: 2.2, 15.1) compared with those with TIR >70%. CONCLUSION: Among people with T2DM or GDM who utilized CGM during pregnancy, 4 out 10 individuals had TIR ≤70% and, compared with those with TIR > 70%, they had a higher likelihood of adverse neonatal and maternal outcomes. KEY POINTS: · Time in range can be utilized as a metric for pregnant patients using continuous glucose monitor.. · Time in range >70% is achievable by 6 out of 10 patients.. · Time in range below goal is associated with adverse neonatal and maternal outcomes..

Does Prediction of Neonatal Mortality by the Observed/Expected Lung-To-Head Ratio Change during Pregnancy in Fetuses with Left Congenital Diaphragmatic Hernia?

INTRODUCTION: The aim of this study was to evaluate prediction of neonatal mortality in fetuses with isolated left congenital diaphragmatic hernia (CDH) when the observed/expected lung-to-head ratio (O/E LHR) was estimated at two different gestational time points during pregnancy. METHODS: Forty-four (44) fetuses with isolated left CDH were included. O/E LHR was estimated at the time of referral (first scan) and before delivery (last scan). The main outcome was neonatal death due to respiratory complications. RESULTS: There were 10/44 (22.7%) perinatal deaths. The areas under (AU) the ROC curves were: first scan, 0.76, best O/E LHR cut-off 35.5% with 76% sensitivity and 70% specificity; last scan, AU-ROC 0.79, best O/E LHR cut-off 35.2%, with 79.0% sensitivity and 80% specificity. Considering an O/E LHR cut-off ≤35% to define high-risk fetuses at any examination, prediction for perinatal mortality showed: 80% sensitivity, 73.5% specificity, 47.1% positive and 92.6% negative predictive values, and 3.02 (95% CI 1.59-5.73) positive and 0.27 (95% CI 0.08-0.96) negative likelihood ratios. Prediction was similar in the two evaluations as 16/21 (76.2%) of fetuses considered at risk had an O/E LHR ≤35% in the two examinations; in the remaining 5 cases, two were identified only in the first and three only in the last scan. CONCLUSION: The O/E LHR is a good predictor of perinatal death in fetuses with left isolated CDH. Approximately 80% of fetuses at risk of perinatal death can be identified with an O/E LHR ≤35%, and 90% of them will have similar O/E LHR values at the first and at the last ultrasound examinations prior to delivery. In general, 88.6% of all CDH fetuses have a similar severity classification based on the O/E LHR at the first diagnostic ultrasound or at the ultrasound examination prior to delivery.

Eclampsia in the 21st century.

The reported incidence of eclampsia is 1.6 to 10 per 10,000 deliveries in developed countries, whereas it is 50 to 151 per 10,000 deliveries in developing countries. In addition, low-resource countries have substantially higher rates of maternal and perinatal mortalities and morbidities. This disparity in incidence and pregnancy outcomes may be related to universal access to prenatal care, early detection of preeclampsia, timely delivery, and availability of healthcare resources in developed countries compared to developing countries. Because of its infrequency in developed countries, many obstetrical providers and maternity units have minimal to no experience in the acute management of eclampsia and its complications. Therefore, clear protocols for prevention of eclampsia in those with severe preeclampsia and acute treatment of eclamptic seizures at all levels of healthcare are required for better maternal and neonatal outcomes. Eclamptic seizure will occur in 2% of women with preeclampsia with severe features who are not receiving magnesium sulfate and in <0.6% in those receiving magnesium sulfate. The pathogenesis of an eclamptic seizure is not well understood; however, the blood-brain barrier disruption with the passage of fluid, ions, and plasma protein into the brain parenchyma remains the leading theory. New data suggest that blood-brain barrier permeability may increase by circulating factors found in preeclamptic women plasma, such as vascular endothelial growth factor and placental growth factor. The management of an eclamptic seizure will include supportive care to prevent serious maternal injury, magnesium sulfate for prevention of recurrent seizures, and promoting delivery. Although routine imagining following an eclamptic seizure is not recommended, the classic finding is referred to as the posterior reversible encephalopathy syndrome. Most patients with posterior reversible encephalopathy syndrome will show complete resolution of the imaging finding within 1 to 2 weeks, but routine imaging follow-up is unnecessary unless there are findings of intracranial hemorrhage, infraction, or ongoing neurologic deficit. Eclampsia is associated with increased risk of maternal mortality and morbidity, such as placental abruption, disseminated intravascular coagulation, pulmonary edema, aspiration pneumonia, cardiopulmonary arrest, and acute renal failure. Furthermore, a history of eclamptic seizures may be related to long-term cardiovascular risk and cognitive difficulties related to memory and concentration years after the index pregnancy. Finally, limited data suggest that placental growth factor levels in women with preeclampsia are superior to clinical markers in prediction of adverse pregnancy outcomes. This data may be extrapolated to the prediction of eclampsia in future studies. This summary of available evidence provides data and expert opinion on possible pathogenesis of eclampsia, imaging findings, differential diagnosis, and stepwise approach regarding the management of eclampsia before delivery and after delivery as well as current recommendations for the prevention of eclamptic seizures in women with preeclampsia.

Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance.

Qualitative and quantitative measurement of urine protein excretion is one of the most common tests performed during pregnancy. For more than 100 years, proteinuria was necessary for the diagnosis of preeclampsia, but recent guidelines recommend that proteinuria is sufficient but not necessary for the diagnosis. Still, in clinical practice, most patients with gestational hypertension will be diagnosed as having preeclampsia based on the presence of proteinuria. Although the reference standard for measuring urinary protein excretion is a 24-hour urine collection, spot urine protein-to-creatinine ratio is a reasonable "rule-out" test for proteinuria. Urine dipstick screening for proteinuria does not provide any clinical benefit and should not be used to diagnose proteinuria. The classic cutoff cited to define proteinuria during pregnancy is a value of >300 mg/24 hours or a urine protein-to-creatinine ratio of at least 0.3. Using this cutoff, the rate of isolated proteinuria in pregnancy may reach 8%, whereas preeclampsia occurs among 3% to 8% of pregnancies. Although this threshold is widely accepted, its origin is not based on evidence on adverse pregnancy outcomes but rather on expert opinion and results of small studies. After reviewing the available data, the most important factor that influences maternal and neonatal outcome is the severity of blood pressures and presence of end organ damage, rather than the excess protein excretion. Because the management of gestational hypertension and preeclampsia without severe features is almost identical in frequency of surveillance and timing of delivery, the separation into 2 disorders is unnecessary. If the management of women with gestational hypertension with a positive assessment of proteinuria will not change, we believe that urine assessment for proteinuria is unnecessary in women who develop new-onset blood pressure at or after 20 weeks' gestation. Furthermore, we do not recommend repeated measurement of proteinuria for women with preeclampsia, the amount of proteinuria does not seem to be related to poor maternal and neonatal outcomes, and monitoring proteinuria may lead to unindicated preterm deliveries and related neonatal complications. Our current diagnosis of preeclampsia in women with chronic kidney disease may be based on a change in protein excretion, a baseline protein excretion evaluation is critical in certain conditions such as chronic hypertension, diabetes, and autoimmune or other renal disorders. The current definition of superimposed preeclampsia possesses a diagnostic dilemma, and it is unclear whether a change in the baseline proteinuria reflects another systemic disease such as preeclampsia or whether women with chronic disease such as chronic hypertension or diabetes will experience a different "normal" pattern of protein excretion during pregnancy. Finally, limited data are available regarding angiogenic and other biomarkers in women with chronic kidney disease as a potential aid in distinguishing the worsening of baseline chronic kidney disease and chronic hypertension from superimposed preeclampsia.

Hypertension in pregnancy and adverse outcomes among low-risk nulliparous women expectantly managed at or after 39 weeks: a secondary analysis of a randomised controlled trial.

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy (HDP) among low-risk nulliparous women expectantly managed at or after 39 weeks of gestation are associated with adverse outcomes. DESIGN: Secondary analysis of a randomised trial. SETTING: Multicentre, USA. POPULATION: Individuals in the expectantly managed group who delivered on or after 39 weeks. METHODS: Multivariable analysis to estimate adjusted relative risks (aRR) for binomial outcomes, adjusted odds ratios (aOR) for multinomial outcomes and 95% CI. MAIN OUTCOME MEASURES: Composite adverse maternal outcome including placental abruption, pulmonary oedema, postpartum haemorrhage, postpartum infection, venous thromboembolism or intensive care unit admission. Secondary outcomes included a composite of perinatal death or severe neonatal complications, mode of delivery, small and large for gestational age and neonatal intermediate or intensive unit length of stay. RESULTS: Of the 3044 women randomised to expectant management in the original trial, 2718 (89.3%) were eligible for this analysis, of whom 373 (13.7%) developed HDP. Compared with participants who remained normotensive, those who developed HDP were more likely to experience the maternal composite (12% versus 6%, aRR 1.84, 95% CI 1.33-2.54) and caesarean delivery (29% versus 23%, aOR 1.32, 95% CI 1.01-1.71). Differences between the two groups were not significantly different for the adverse perinatal composite (7% versus 5%, aRR 1.38, 95% CI 0.92-2.07) or for other secondary outcomes. CONCLUSION: Almost 14% of low-risk nulliparous individuals expectantly managed at 39 weeks developed HDP, and were more likely to experience adverse maternal outcomes compared with those who did not develop HDP. TWEETABLE ABSTRACT: Almost 14% of low-risk nulliparous individuals expectantly managed at 39 weeks developed hypertensive disorders of pregnancy, and were more likely to experience adverse maternal outcomes compared with those who did not develop hypertensive disorders.

Maternal Education Level Among People with Diabetes and Associated Adverse Outcomes.

OBJECTIVE: The aim of the study is to determine the relation between education and adverse outcomes in individuals with pregestational or gestational diabetes. STUDY DESIGN: This population-based cohort study, using the U.S. vital statistics datasets, evaluated individuals with pregestational or gestational diabetes who delivered between 2016 and 2019. The primary outcome was composite neonatal adverse outcome including any of the following: large for gestational age (LGA), Apgar's score 6 hours, neonatal seizure, or neonatal death. The secondary outcome was composite maternal adverse outcomes including any of the following: admission to intensive care unit, transfusion, uterine rupture, or unplanned hysterectomy. Multivariable analysis was used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CIs). RESULTS: Of 15,390,962 live births in the United States, 858,934 (5.6%) were eligible for this analysis. Compared with individuals with a college education and above, the risk of composite neonatal adverse outcome was higher in individuals with some college (aRR = 1.08, 95% CI = 1.07-1.09), high school (aRR = 1.06, 95% CI = 1.04-1.07), and less than high school (aRR = 1.05, 95% CI = 1.03-1.07) education. The components of composite neonatal adverse outcome that differed significantly between the groups were LGA, Apgar's score 6 hours. Infant death differed when stratified by education level. An increased risk of composite maternal adverse outcome was also found with a lower level of education. CONCLUSION: Among individuals with diabetes, lower education was associated with a modestly higher risk of adverse neonatal and maternal outcomes. KEY POINTS: · Education levels were associated with adverse outcomes among individuals with diabetes.. · Lower education is associated with multiple neonatal complications, including infant death.. · Individuals with varying levels of education are at higher risk for adverse maternal outcomes..

Leaving the Placenta In Situ in Placenta Accreta Spectrum Disorders: A Single-Center Case Series.

OBJECTIVE: The most common treatment for placenta accreta spectrum (PAS) disorders is planned primary cesarean hysterectomy. However, other management strategies may improve outcomes and/or allow fertility preservation. The objective of this study was to describe the course and outcomes of patients with PAS managed by leaving the placenta in situ. STUDY DESIGN: This is a series of 11 patients with PAS managed by leaving the placenta in situ at a single academic center in the United States from 2015 to 2022. The approach described involves delivery of the fetus via cesarean, no attempt at placental removal, closure of the hysterotomy, prophylactic intravenous antibiotics for up to 1 week, and close outpatient follow-up until the uterus is empty. RESULTS: The uterus was successfully preserved in six (55%), minimally invasive hysterectomy was performed in four (36%), and abdominal hysterectomy was performed in 1 (9%). During cesarean delivery, the median estimated blood loss was 650mL (range: 200-1,000mL). The majority of patients had no vaginal discharge for several weeks after delivery, followed by brown or bloody discharge, and intermittent mild-to-moderate cramping. The median time to resolution of PAS was 18 weeks in patients with successful uterine preservation (range: 5-25 weeks). Indications for hysterectomy included hemorrhage (n=1), coagulopathy (n=1), endomyometritis (n=2), and pain (n=1), and these occurred at a median of 5 weeks postpartum (range: 1-25 weeks). Four patients had subsequent pregnancies of whom three were live births at or near term and one was a spontaneous abortion at 19 weeks. CONCLUSION: Leaving the placenta in situ may be an appropriate management strategy for some carefully selected and counseled patients with PAS. KEY POINTS: · Overall, 55% had uterine preservation (6/11).. · Minimally invasive approach in 80% of hysterectomies (4/5).. · Of patients, 67% with uterine preservation had subsequent pregnancies (4/6)..

Planned versus Unplanned Delivery for Placenta Accreta Spectrum.

OBJECTIVE: Women with placenta accreta spectrum (PAS) having an unplanned delivery may have worse outcome compared with women with a planned delivery. The primary objective of this study was to compare severe maternal morbidity among women with PAS who had a planned scheduled delivery versus an unplanned delivery. Secondary objective was to compare neonatal outcomes. STUDY DESIGN: Retrospective cohort study at two tertiary centers (January 2009 to June 2019) of all women who underwent a hysterectomy with a histologic proven PAS. Primary outcome was severe maternal morbidity which defined as any of the following: transfusion of ≥4 RBC units or ureter/bowel injury. Neonatal outcome was a composite neonatal morbidity defined as any of the following: Apgar score's < 5 at 5 minutes, mechanical ventilation, or respiratory distress syndrome. Maternal demographic, clinical, and sonographic characteristics were compared between the two groups (planned vs. unplanned). Descriptive statistics were used as appropriate, and a statistical significance was established if p-value was < 0.05. RESULTS: Of 109 women who underwent cesarean hysterectomy for PAS, 41 (37.6%) had an unplanned delivery. There was no significant difference in the number of previous cesarean deliveries or ultrasound findings between the two groups. Women with an unplanned delivery were more likely to bleed during pregnancy than those that had a planned delivery (p = 0.04). Women with unplanned delivery had lower gestational age at delivery (30.3 vs. 33.8 weeks, p = 0.001) had a 75% higher rate of the primary outcome (63 vs. 36%, p = 0.007) and had a higher rate of intensive care unit admissions (39 vs. 17.7%, p = 0.01) compared with women with a planned delivery. The neonatal morbidity did not differ between the two groups. CONCLUSION: Since unplanned cesarean hysterectomy among women with PAS occurs in 40% and is associated with significantly higher morbidity, interventions are needed to mitigate the rate of adverse outcomes. KEY POINTS: · Only 60% of women with PAS reached planned delivery at 34 weeks.. · PAS unplanned delivery is associated with high morbidity.. · Some women with PAS may need a scheduled earlier delivery..

Detemir vs neutral protamine Hagedorn insulin for diabetes mellitus in pregnancy: a comparative effectiveness, randomized controlled trial.

BACKGROUND: Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn. OBJECTIVE: We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at <20 weeks' gestation). STUDY DESIGN: We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks' gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of <7, lowest glucose level, need for intravenous glucose, respiratory distress syndrome, need for mechanical ventilation or continuous positive airway pressure, neonatal jaundice requiring therapy, brachial plexus injury, and hospital length of stay. The secondary maternal outcomes included hypoglycemic events, hospital admission for glucose control, hypertensive disorder of pregnancy, maternal weight gain, cesarean delivery, and postpartum complications. We used the Bayesian statistics to estimate a sample size of 108 to have >75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890). RESULTS: There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks' gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61-1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29-1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54-1.16). CONCLUSION: In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn.

Fetal esophageal imaging: Early pregnancy as a window of opportunity.

OBJECTIVE: To describe the sonographic appearance of the fetal esophagus during early pregnancy and evaluate the feasibility of imaging the entire esophageal length. In addition, we present a case of disrupted esophageal continuity, subsequently diagnosed with esophageal atresia (EA). METHODS: A prospective observational study of 145 patients. During the early second trimester anomaly scan performed at 12-17 weeks' gestation the entire esophagus was captured in a single sonographic image at the midsagittal plane (one shot technique). Postnatal follow-up of esophageal patency included review of medical records and telephone interviews. RESULTS: Complete visualization of the esophagus (neck to diaphragm) was possible in 144 cases. In 88% of cases the esophagus was demonstrated by transvaginal approach. The time required to obtain the desired view of the esophagus, once the fetus was in an optimal position, was on average 13 s (range: 5-30 s). In one case at 15 weeks' gestation, the cervical segment of the esophagus was demonstrated while the lower thoracic segment was not identified. Subsequently EA was diagnosed. CONCLUSIONS: It is feasible to demonstrate the entire esophagus during early second trimester anomaly scan. An early second trimester anomaly scan may serve as a window of opportunity for EA screening.