Prepregnancy physiology and subsequent preterm preeclampsia.

BACKGROUND: Preeclampsia is a common pregnancy complication with debated etiology. OBJECTIVE: To evaluate the contribution of prepregnancy physiology, biochemistry, and anthropometrics to the subsequent development of preterm preeclampsia. STUDY DESIGN: One hundred twenty-four participants were recruited through open recruitment and targeted mailings. Participants included 81 nulliparous women and 43 with a history of preterm preeclampsia. We characterized cardiovascular function, metabolic profile, and body composition in 100 nonpregnant women who went on to subsequent pregnancy. Measures included plasma volume, baseline cardiovascular function and cardiovascular response to volume challenge, body composition, and circulating biochemical measures. Pregnancy outcome was obtained through chart review. Prepregnancy metrics for women who developed preterm preeclampsia were compared with measurements for those who did not, with adjustment for a history of prior preterm preeclampsia. Logistic regression modeling was used to identify the strongest prepregnancy factors associated with preterm preeclampsia. RESULTS: Pregnancy outcomes included 11 women with preterm preeclampsia, 7 women with term preeclampsia, 20 women with other hypertension affecting their pregnancy, and 62 with uncomplicated pregnancies. We observed no difference in maternal age, study cycle day, lean body mass, uterine hemodynamics, or flow-mediated dilation across groups. Women with preterm preeclampsia had greater android fat content 3215±1143 vs 1918±1510 g (P=.002), faster supine pulse, 77±7 vs 67±10 beats per minute (P=.001), higher supine diastolic blood pressure 82±6 vs 68±6 mmHg (P<.001), increased cardiac output 5.6±1.1 vs 4.6±1 L/min (P=.002), faster aortic-popliteal pulse wave velocity 4.5±0.7 vs 3.8±0.5 m/sec (P<.001), and exaggerated cardiac output response to volume challenge 20±9 vs 9±12 L/min (P=.002) compared to those with other pregnancy outcomes. Women who developed preterm preeclampsia also had reduced renal vascular resistance index 0.86±0.08 vs 0.97±0.12 (P=.005) compared with other pregnancy outcomes when assessed prior to pregnancy. Women with subsequent preterm preeclampsia had higher serum c-reactive protein 10.7±12.5 vs 4.1±5.8 mg/mL (P=.003) and greater insulin resistance, as assessed by Homeostatic Model Assessment for Insulin Resistance calculation 2.2±1.1 vs 1.2±0.9 (P<.001). CONCLUSION: Prepregnancy physiology is linked to subsequent preterm preeclampsia. The same factors associated with metabolic syndrome are more prominent in patients who develop preterm preeclampsia than those who do not, including increased vessel stiffness, low vascular compliance, high cardiac output, reduced renal vascular resistance index, insulin resistance, and increased android fat, all consistent with subclinical features of the metabolic syndrome.

Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels.

During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.

Subclinical Metabolic and Cardiovascular Factors and Brain White Matter Microstructural Integrity in Young Women.

Women who have experienced pregnancy complications, specifically preeclampsia and gestational diabetes, have well documented increased risks of cardiovascular, metabolic, and neurological disease later in life. This study examined how specific cardiovascular and metabolic risk factors for preeclampsia assessed in a non-pregnant state were associated with brain white matter microstructural integrity. This study examined sixty-two healthy women (mean age 31 ± 5 years) who received metabolic and cardiovascular assessments as well as multiple modality MRI imaging. Participants were either nulliparous (n = 31) or had a history of preterm preeclampsia (n = 31). Imaging included acquisition Diffusion Tensor Imaging (DTI) to assess white matter integrity within the brain. We hypothesized that healthy, young, non-pregnant women with cardiovascular and metabolic profiles suggesting elevated risk would have decreased white matter integrity, represented by lower Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) estimates in the posterior cortical areas of the brain. We observed increased white matter degradation (lower FA and increased MD) in posterior and occipital tracts, commissural fibers, and subcortical structures in women with increased adiposity, worse measures of cardiovascular and metabolic function, including greater insulin resistance (HOMA-IR), hyperlipidemia, elevated blood pressure, and increased arterial stiffness. The relationships detected between subclinical cardiovascular and metabolic phenotypes and increased white matter disruption at a young age, outside of pregnancy, are indicative that adverse changes are detectable long before cognitive clinical presentation. This may suggest that many of the long-term cardiovascular and metabolic risks of aging are influenced by physiologic aging trajectories rather than damage caused by pregnancy complications.

Care plan for individuals at risk for preeclampsia: shared approach to education, strategies for prevention, surveillance, and follow-up.

Preeclampsia is a multisystemic disorder of pregnancy that affects 250,000 pregnant individuals in the United States and approximately 10 million worldwide per annum. Preeclampsia is associated with substantial immediate morbidity and mortality but also long-term morbidity for both mother and offspring. It is now clearly established that a low dose of aspirin given daily, beginning early in pregnancy modestly reduces the occurrence of preeclampsia. Low-dose aspirin seems safe, but because there is a paucity of information about long-term effects on the infant, it is not recommended for all pregnant individuals. Thus, several expert groups have identified clinical factors that indicate sufficient risk to recommend low-dose aspirin preventive therapy. These risk factors may be complemented by biochemical and/or biophysical tests that either indicate increased probability of preeclampsia in individuals with clinical risk factors, or more importantly, identify increased likelihood in those without other evident risk. In addition, the opportunity exists to provide this population with additional care that may prevent or mitigate the short- and long-term effects of preeclampsia. Patient and provider education, increased surveillance, behavioral modification, and other approaches to improve outcomes in these individuals can improve the chance of a healthy outcome. We assembled a group with diverse, relevant expertise (clinicians, investigators, advocates, and public and private stakeholders) to develop a care plan in which providers and pregnant individuals at risk can work together to reduce the risk of preeclampsia and associated morbidities. The plan is for care of individuals at moderate to high risk for developing preeclampsia, sufficient to receive low-dose aspirin therapy, as identified by clinical and/or laboratory findings. The recommendations are presented using the GRADE methodology with the quality of evidence upon which each is based. In addition, printable appendices with concise summaries of the care plan's recommendations for patients and healthcare providers are provided. We believe that this shared approach to care will facilitate prevention of preeclampsia and its attendant short- and long-term morbidity in patients identified as at risk for development of this disorder.

Corrigendum: Preeclampsia and its relationship to pathological brain aging.

[This corrects the article DOI: 10.3389/fphys.2022.979547.].

Preeclampsia and its relationship to pathological brain aging.

The development of preeclampsia during pregnancy may have long-term effects on brain aging in women. Associations between preeclampsia and vascular dementia have been established, however the connection between preeclampsia and Alzheimer's disease has not been as thoroughly explored. Both preeclampsia and Alzheimer's disease have been associated with misfolded amyloid beta proteins and inflammation; due to these similarities, in this minireview, we examined the potential links between a history of preeclampsia and the development of dementia. We also discussed how hypertensive disorders of pregnancy may relate to both normal brain aging and dementia to highlight the need for additional research regarding the long-term cognitive effects of preeclampsia on the brain.

Randomized Controlled Trial Examining the Efficacy of Adding Financial Incentives to Best practices for Smoking Cessation Among pregnant and Newly postpartum Women.

We report results from a single-blinded randomized controlled trial examining financial incentives for smoking cessation among 249 pregnant and newly postpartum women. Participants included 169 women assigned to best practices (BP) or BP plus financial incentives (BP + FI) for smoking cessation available through 12-weeks postpartum. A third condition included 80 never-smokers (NS) sociodemographically-matched to women who smoked. Trial setting was Burlington, Vermont, USA, January, 2014 through January, 2020. Outcomes included 7-day point-prevalence abstinence antepartum and postpartum, and birth and other infant outcomes during 1st year of life. Reliability and external validity of results were assessed using pooled results from the current and four prior controlled trials coupled with data on maternal-smoking status and birth outcomes for all 2019 singleton live births in Vermont. Compared to BP, BP + FI significantly increased abstinence early- (AOR = 9.97; 95%CI, 3.32-29.93) and late-pregnancy (primary outcome, AOR = 5.61; 95%CI, 2.37-13.28) and through 12-weeks postpartum (AOR = 2.46; CI,1.05-5.75) although not 24- (AOR = 1.31; CI,0.54-3.17) or 48-weeks postpartum (AOR = 1.33; CI,0.55-3.25). There was a significant effect of trial condition on small-for-gestational-age (SGA) deliveries (χ2 [2] = 9.01, P = .01), with percent SGA deliveries (+SEM) greatest in BP, intermediate in BP + FI, and lowest in NS (17.65 + 4.13, 10.81 + 3.61, and 2.53 + 1.77, respectively). Reliability analyses supported the efficacy of financial incentives for increasing abstinence antepartum and postpartum and decreasing SGA deliveries; external-validity analyses supported relationships between antepartum cessation and SGA risk. Adding financial incentives to Best Practice increases smoking cessation among antepartum and postpartum women and improves other maternal-infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210832.

Placental Maternal Vascular Malperfusion is Associated with Prepregnancy and Early Pregnancy Maternal Cardiovascular and Thrombotic Profiles.

Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation potential in healthy young women. Sixty-three healthy young women were recruited and assessed prior to pregnancy on cycle day 9 ± 4, at gestational age 90 ± 6 of early pregnancy, and gestational age 216 ± 5 of late pregnancy. Women were assessed for plasma volume, blood pressure, response to volume loading, cardiac output, and uterine hemodynamics. Platelet-poor plasma was collected to assess thrombin generation on a subset of 33 women at all time points. Following delivery, placentas were collected and analyzed for evidence of MVM. Thrombin generation (TG) was evaluated in the presence of tissue factor (TF) with and without recombinant soluble thrombomodulin (TM). For each, we compared TG lagtime, peak level, and endogenous thrombin potential (ETP). Comparisons were made between dichotomized presence and absence of each individual feature of MVM and cardiovascular and coagulation features. Mean ± standard deviation are presented. Women were 31 ± 4 years of age, body mass index of 24 ± 5 kg/m2, 86% white race, and 80% nulliparous. MVM occurred in 70% of placentas, with infarcts and agglutination (44%), decidual arteriopathy (40%), accelerated villous maturation (32%), placental hypoplasia (29%), and distal villous hypoplasia (17%) documented. Decidual arteriopathy and distal villous hypoplasia were associated with prepregnancy maternal physiology, including decreased plasma volume and subclinical cardiovascular variations. All assessed MVM characteristics had identifiable early pregnancy physiologic characteristics consistent with altered cardiovascular function and decreased uterine response to pregnancy when compared with women who did and did not develop MVM. Accelerated villous maturation was the only MVM feature to differ by thrombin generation parameters in early pregnancy. Thrombin generation potential and blood pressure were elevated in late pregnancy in women who developed decidual arteriopathy. Prepregnancy health status and adaptation to pregnancy play important roles in pregnancy outcomes. Both cardiovascular health and thrombin generation potential may influence early placentation. Longitudinal assessment of subclinical maternal factors may allow for better understanding of the etiologies of MVM lesions, as well as allow for identification of a timeline of the origins of placental pathologies.

Cardiovascular profiles associated with white matter hyperintensities in healthy young women.

Women who experience hypertension in pregnancy have increased risk of both chronic hypertension and dementia. High blood pressure is associated with increased evidence of white matter hyperintensities (WMH) in brain imaging. WMH are disruptions of the white matter of the brain that occur with demyelination and axonal degeneration, are associated with vascular disease, occur more frequently in people with hypertension, and are associated with cognitive impairment. We evaluated the relationship between WMH and subclinical cardiovascular function in healthy young nulliparous women and women with a history of early-onset preeclampsia. Sixty-two reproductive-aged women were assessed during the follicular phase of the menstrual cycle after a 3-day sodium/potassium-controlled diet. Half of participants had a history of early-onset preeclampsia, and half were nulliparous. Blood was drawn to assess inflammatory markers. Cardiovascular assessments included tonometric blood pressure monitoring, volume loading to assess vascular compliance, echocardiography to assess cardiac ejection time, brachial pulse wave velocity of the brachial artery, assessing cardiovascular stiffness, and brachial artery flow mediated vasodilation to assess endothelial mediated dilatory response. T2 fluid-attenuated inversion recovery (FLAIR) MRI imaging was obtained. Two raters, blinded to cardiovascular assessments and pregnancy history, reviewed MRI scans for evidence of WMH using the Fazekas rating scale. WMHs were detected in 17 women; 45 had normal white matter structure. Participants with Fazekas score>0 had exaggerated response to volume loading compared to women with a Fazekas score of 0 and longer cardiac ejection times. Fazekas scores >0 had lower brachial flow-mediated vasodilation and increased white blood count compared to those with no evidence of WMH. Women with WMH had reduced cardiovascular compliance, and a trend towards decreased endothelial responsiveness compared to those without WMH. These data demonstrated that the relationship between cardiovascular and brain health was detectable in young, healthy, reproductive-aged women, and may play a role in later development of clinical disease. These findings may help identify women who are at risk for cognitive decline and pathological aging.

Association of pre-pregnancy subclinical insulin resistance with cardiac dysfunction in healthy nulliparous women.

OBJECTIVES: To investigate the association between pre-pregnancy subclinical insulin resistance and cardiovascular dysfunction in healthy nulliparous women, and with hypertension in subsequent pregnancy. STUDY DESIGN: Secondary analysis of a single center prospective observational study conducted November 2011-June 2014. Healthy nulliparous women underwent detailed cardiovascular and metabolic assessment. Insulin resistance was determined by homeostasis model assessment (HOMA-IR). Associations of HOMA-IR with metabolic and cardiovascular measurements were assessed with Spearman correlations. Charts were reviewed in women who conceived singleton pregnancies. MAIN OUTCOME MEASURES: Metabolic measurements included serum glucose, insulin, creatinine, CRP, and lipids. HOMA-IR was calculated using fasting serum insulin and glucose. Indices of cardiovascular stiffness were determined from pulse wave velocity and response to volume challenge. Pregnancy outcomes included delivery mode and gestational age, birthweight, and hypertension. RESULTS: HOMA-IR was positively associated with BMI (r = 0.462, p < 0.001), body fat percentile (r = 0.463, p < 0.001), CRP (r = 0.364, p = 0.003), and negatively associated with serum HDL (r = -0.38, p = 0.002) and creatinine (r = -0.242, p = 0.049). HOMA-IR was positively associated with blood pressure (r = 0.347, p = 0.004), resting heart rate (r = 0.433, p = <0.001), response to volume challenge (r = 0.325, p < 0.01). Increased HOMA-IR was associated with a faster cardiac ejection time in response to volume challenge (r = -0.415, p < 0.001), which is a marker of decreased cardiac compliance to volume increase, or cardiac stiffness. CONCLUSION: HOMA-IR is associated with pre-pregnancy cardiac stiffness. Cholesterol was not associated with cardiovascular dysfunction. A non-significant trend was observed between HOMA-IR and hypertension in subsequent pregnancy.

Measures of adiposity correlate with renal filtration in young nulliparous women: An observational cohort study.

OBJECTIVE: Renal hyperfiltration, which has been documented in severe obesity and obesity-associated hypertension, can occur with hypertensive disorders of pregnancy. Identification of prepregnancy risk factors for unrecognized renal hyperfiltration could inform screening and intervention strategies to protect against pregnancy complications. In young, healthy, nulliparous women, associations between associations between measures of adiposity, insulin resistance, and renal vascular resistance were thus evaluated. METHODS: This is a secondary analysis of a prospective observational trial characterizing associations of prepregnancy and late-pregnancy maternal physiology. Seventy-nine nulligravid women aged 18-42 years without major medical conditions were assessed for percent android body fat using dual-energy X-ray absorption. Renal cortical vessel blood flow resistance index (CVRI) was determined using Doppler ultrasonography. Creatinine clearance was calculated from 24-hour urine collection. RESULTS: Renal CVRI inversely correlates with body mass index (r = -0.23, p = 0.047), percent android fat (r = -0.30, p = 0.008), and supine pulse (r = -0.44, p < 0.001). Creatinine clearance is positively associated with BMI and HOMA-IR.In regression modeling, supine pulse (r2 = 0.22, p < 0.001) and cardiac index (r2 = 0.05, p = 0.045) predict renal CVRI, whereas HOMA-IR (r2 = 0.11, p = 0.008) and cardiac output (r2 = 0.06, p = 0.039) predict creatinine clearance. Measures of adiposity are not independently predictive of either measure. CONCLUSIONS: In healthy young women, measures of adiposity and insulin resistance correlate positively with renal filtration. Preclinical manifestations of renal hyperfiltration may have implications for pregnancy outcomes.

Subclinical cardiac stiffness is associated with arterial stiffness in healthy young nulligravid women: Potential links to preeclampsia.

OBJECTIVES: Preeclampsia is an independent risk factor for subsequent cardiovascular disease and diastolic dysfunction and has been linked to arterial stiffness. We hypothesized that arterial stiffness would be associated with echocardiographic markers of diastolic dysfunction in healthy nulligravid women. STUDY DESIGN: 31 healthy nulligravid women underwent assessment of peripheral arterial stiffness via aorto-femoral pulse wave velocity, popliteal distensibility and ß stiffness measures as well as hemodynamic response to volume challenge. 22 underwent cardiac assessment via conventional and stress echocardiography with a focus on diastolic function utilizing tissue/pulse wave Doppler imaging and 3D speckle tracking. Bivariate associations between variables were evaluated using correlation coefficients (Pearson r) and Student's t-tests. RESULTS: No participants had echocardiographic values meeting criteria for overt diastolic dysfunction. Baseline global circumferential strain was significantly correlated with distensibility and ß stiffness (n = 18, r = -0.61, p = 0.007, n = 18, r = 0.56, p = 0.01). Peak deceleration time was correlated with ßstiffness (n = 9; r = 0.80, p = 0.01). Pulse wave velocity was not significantly correlated with cardiac measures (p > 0.05). Family history of a first or second degree relative with myocardial infarction or hypertension was associated with decreased popliteal artery distensibility (p = 0.02 and p = 0.03, respectively). CONCLUSIONS: In healthy nulligravid women there is evidence that markers of decreased left ventricular relaxation are associated with increased peripheral vascular stiffness as is a family history of myocardial infarction or hypertension. These findings raise the possibility that the diastolic dysfunction and arterial stiffness observed in the setting of preeclampsia are driven by underlying properties present prior to pregnancy and contribute to lifetime cardiovascular risk.

Combined financial incentives and behavioral weight management to enhance adherence with gestational weight gain guidelines: a randomized controlled trial.

BACKGROUND: Excessive gestational weight gain, particularly among overweight and obese women, is associated with adverse perinatal outcomes. Current interventions to limit gestational weight gain have achieved only modest success. OBJECTIVE: We sought to improve adherence to gestational weight gain guidelines with a dual intervention of financial incentives and antenatal behavioral weight management. STUDY DESIGN: This was a prospective randomized controlled trial at a single academic medical center in which women were assigned randomly to the intervention group or standard care. The primary outcome was adherence to gestational weight gain guidelines. Secondary outcomes included total gestational weight gain, mode of delivery, birthweight, neonatal intensive care unit admission, and development of gestational diabetes mellitus and hypertensive disorders of pregnancy. RESULTS: A total of 136 women were assigned randomly, with data available for analysis of 124 women. Gestational weight gain within the Institutes of Medicine guidelines was similar (30% vs 29%) in the intervention and standard care groups, respectively. There were no statistically significant differences in total gestational weight gain or perinatal outcomes. There was a nonstatistically significant decrease in macrosomia in the intervention compared with standard care condition. CONCLUSION: A combined financial incentive and behavioral weight management intervention did not improve adherence to gestational weight gain guidelines. Modifications to the intervention may achieve improved results.

Associations of maternal obesity and smoking status with perinatal outcomes.

Maternal obesity and smoking are associated with adverse perinatal outcomes. These prevalent conditions contribute to health disparities. In this study, we examine whether maternal BMI moderates the impact of smoking cessation on short-term perinatal outcomes. This is a secondary analysis of assessments conducted from several prospective clinical trials examining the efficacy of incentives to promote smoking cessation during pregnancy. Participants were randomly assigned to receive financial incentives contingent upon smoking abstinence or a control condition. Pregnancy outcomes were abstracted from the medical record. ANCOVA and multiple logistic regression were used for statistical analysis. Among 388 women, there was a significant interaction between maternal pre-pregnancy BMI and smoking status on gestational age at delivery (p = .03) and admission to the NICU (p = .04). Among underweight/normal weight gravidas, smoking resulted in earlier deliveries and a greater likelihood of NICU admission than in those who abstained. Among overweight/obese gravidas, there was no effect of smoking on gestational age at delivery and infants of smokers were less likely to be admitted to the NICU. Maternal obesity and smoking have significant individual effects on perinatal outcome. Maternal overweight/obesity appears to moderate the effect of smoking on gestational age at delivery and on NICU admissions.

Effect of Pregnancy Interval on Second Pregnancy Blood Pressure Following Prior Preeclampsia.

OBJECTIVE: Preeclampsia generally occurs in first pregnancies and tends not to recur when the interpregnancy interval (IPI) is short. We hypothesized that, in women experiencing preeclampsia in their first pregnancy, the difference in mean arterial pressure (MAP) across pregnancy between their index and subsequent pregnancy would be inversely associated with the length of time between pregnancies and that the interval between pregnancies will be directly associated with the likelihood of preeclampsia recurrence. METHODS: This was a retrospective chart review evaluating 171 women diagnosed with preeclampsia during their first pregnancy who had a subsequent pregnancy at our institution. Blood pressures were collected from each pregnancy, marking the recurrence of hypertensive disorders, including preeclampsia. Antepartum MAP was compared between pregnancies, examining differences as a function of IPI. RESULTS: There was a significant association of IPI with the reduction in MAP between pregnancies across trimesters ( P = .04), but this reduction became smaller over time. The MAP during the third trimester decreased significantly between pregnancies across all patient groups (IPI <24 months: -5.7 mm Hg, P < .0001; IPI 24-48 months: -4.5 mm Hg, P < .0001; IPI >48 months -3.4 mm Hg, P = .03). The recurrence rate of preeclampsia did not vary significantly with IPI ( P = .21). CONCLUSION: The IPI influences the MAP of the second pregnancy in women with prior preeclampsia. Shorter IPI is associated with a greater reduction in MAP when compared to the longer IPI. Although there was a trend toward higher preeclampsia recurrence with longer IPI, this trend did not reach statistical significance.

Association of Antenatal Steroid Exposure With Survival Among Infants Receiving Postnatal Life Support at 22 to 25 Weeks' Gestation.

Importance: Although evidence of antenatal steroids (ANS) efficacy at 22 to 25 weeks' gestation is limited, increasingly these infants are treated with postnatal life support. Objectives: To estimate the proportion of infants receiving postnatal life support at 22 to 25 weeks' gestation who had exposure to ANS, and to examine if the provision of ANS was associated with a higher rate of survival to hospital discharge and survival without major morbidities. Design, Setting, and Participants: This multicenter observational cohort study consisted of 33 472 eligible infants liveborn at 431 US Vermont Oxford Network member hospitals between January 1, 2012, and December 31, 2016. We excluded infants with recognized syndromes or major congenital anomalies. Of the eligible infants, 29 932 received postnatal life support and were included in the analyses. Data analysis was conducted from July 2017 to July 2018. Exposure: Antenatal steroids administered to the mother at any time prior to delivery. Main Outcomes and Measures: Survival to hospital discharge, major morbidities among survivors, and the composite of survival to discharge without major morbidities. Results: Among 29 932 infants who received postnatal life support, 51.9% were male, with a mean (SD) gestational age of 24.12 (0.86) weeks and mean (SD) birth weight of 668 (140) g; 26 090 (87.2%) had ANS exposure and 3842 (12.8%) had no ANS exposure. Survival to hospital discharge was higher for infants with ANS exposure (18 717 of 25 892 [72.3%]) compared with infants without ANS exposure (1981 of 3820 [51.9%]); the adjusted risk ratio for 22 weeks was 2.11 (95% CI, 1.68-2.65), for 23 weeks was 1.54 (95% CI, 1.40-1.70), for 24 weeks was 1.18 (95% CI, 1.12-1.25), and for 25 weeks was 1.11 (95% CI, 1.07-1.14). Survival to hospital discharge without major morbidities was higher for infants with ANS exposure (3777 of 25 833 [14.6%]) compared with infants without ANS exposure (347 of 3806 [9.1%]); the adjusted risk ratio for 22 through 25 weeks was 1.67 (95% CI, 1.49-1.87). Conclusions and Relevance: Concordant receipt of ANS and postnatal life support was associated with significantly higher survival and survival without major morbidities at 22 through 25 weeks' gestation compared with life support alone. Although statistically higher with ANS, survival without major morbidities remains low at 22 and 23 weeks. There is an opportunity to reevaluate national obstetric guidelines, allowing for shared decision making at the edge of viability with concordant obstetrical and neonatal treatment plans.

The Independent Contribution of Uterine Blood Flow to Birth Weight and Body Composition in Smoking Mothers.

OBJECTIVE: This study aims to evaluate the relationship of maternal smoking to uterine artery hemodynamics and examine independent contributions to birth weight and fetal body composition. STUDY DESIGN: Women were enrolled in a prospective randomized controlled study targeting smoking abstinence. Uterine artery Doppler ultrasound was performed and volumetric blood flow was calculated. Third trimester ultrasound estimates of fetal body composition were performed and birth weight was recorded. RESULTS: Uterine artery volumetric flow and resistance index (RI) were significantly correlated with birth weight adjusted for gestational age (R = 0.35, p = 0.002; R = - 0.27, p = 0.02). Volumetric flow was significantly associated with fetal fat mass (R = 0.30, p = 0.018). Smoking status did not have significant effects on lean body mass (t [61] = 0.60, p = 0.55), fat mass (t [61] = 1.67, p = 0.10), or volumetric flow (t = 0.86, df = 87, p = 0.39). Stepwise regression identified volumetric flow (ß = 0.81, 95% confidence interval [CI]: 0.35-1.27, p < 0.001), maternal prepregnancy body mass index (ß = 16.04, 95% CI: 2.57-29.50, p = 0.02), and fetal sex (ß = 346.28, 95% CI: -532.64 to 159.91, p < 0.001, where male = 0 and female = 1) as independent contributors to birth weight adjusted for gestational age. CONCLUSION: No direct relationship of smoking to uterine artery hemodynamics was demonstrated. Volumetric flow was an independent contributor to birth weight and was associated with fetal fat deposition, while smoking was not independently associated with either outcome.

Maternal Hypertension and Mortality in Small for Gestational Age 22- to 29-Week Infants.

Infants born before 30 weeks gestational age (GA) to mothers with hypertension (HTN) experience lower rates of mortality and serious morbidities when corrected for maternal and infant characteristics. Growth restriction and maternal HTN are often associated. We sought to determine if small for gestational age (SGA) infants have similarly decreased mortality risk when born to mothers with HTN. We identified 6897 singleton SGA, 22 + 0 to 29 + 6 weeks GA infants born between 2008 and 2011, cared for at 578 North American centers in the Vermont Oxford Network. Chromosomal abnormalities and birth defects were excluded. Mortality rates prior to discharge were compared between 4317 HTN and 2580 comparison infants. Logistic regression was used to adjust for birth weight, infant sex, maternal race, inborn/outborn, antenatal steroid exposure, prenatal care, and GA. Small for gestational age HTN infants were older (mean: 26.9 [1.9] vs 26.6 [2.2] weeks; P < .001) and larger (HTN = 584 [159] g vs 562 [156] g; P < .001) than comparison infants. Death prior to discharge occurred in 29% of HTN and 43% of comparison infants. Univariate analyses revealed lower mortality for HTN infants (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.48-0.60). After adjustment, mortality remained lower when compared to non-HTN infants (OR = 0.60, 95% CI: 0.52-0.69). Extremely preterm SGA infants face high rates of mortality. Although maternal HTN is associated with SGA, SGA infants born to mothers with HTN have decreased risk of mortality compared to non-HTN SGA infants, prior to and after adjustment for antenatal and maternal characteristics. This may reflect detrimental physiologic effects associated with alternative mechanisms for fetal growth restriction and is important for parental counseling.

Embryo cryopreservation and preeclampsia risk.

OBJECTIVE: To determine whether assisted reproductive technology (ART) cycles involving cryopreserved-warmed embryos are associated with the development of preeclampsia. DESIGN: Retrospective cohort study. SETTING: IVF clinics and hospitals. PATIENT(S): A total of 15,937 births from ART: 9,417 singleton and 6,520 twin. INTERVENTION(S): We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data, considering resident singleton and twin births from autologous or donor eggs from 2005-2010. MAIN OUTCOME MEASURE(S): We compared the frequency of preeclampsia diagnosis for cryopreserved-warmed versus fresh ET and used multivariable logistic regression to adjust for confounders. RESULT(S): Among pregnancies conceived with autologous eggs resulting in singletons, preeclampsia was greater after cryopreserved-warmed versus fresh ET (7.51% vs. 4.29%, adjusted odds ratio = 2.17 [95% CI 1.67-2.82]). Preeclampsia without and with severe features, preeclampsia with preterm delivery, and chronic hypertension with superimposed preeclampsia were more frequent after cryopreserved-warmed versus fresh ET (3.99% vs. 2.55%; 2.95% vs. 1.41%; 2.76 vs. 1.48%; and 0.95% vs. 0.43%, respectively). Among pregnancies from autologous eggs resulting in twins, the frequency of preeclampsia with severe features (9.26% vs. 5.70%) and preeclampsia with preterm delivery (14.81% vs. 11.74%) was higher after cryopreserved versus fresh transfers. Among donor egg pregnancies, rates of preeclampsia did not differ significantly between cryopreserved-warmed and fresh ET (10.78% vs. 12.13% for singletons and 28.0% vs. 25.15% for twins). CONCLUSION(S): Among ART pregnancies conceived using autologous eggs resulting in live births, those involving transfer of cryopreserved-warmed embryos, as compared with fresh ETs, had increased risk for preeclampsia with severe features and preeclampsia with preterm delivery.

Examination of Prepregnancy and Pregnancy Urinary Protein Levels in Healthy Nulliparous Women.

During pregnancy, abnormal proteinuria is defined as urine protein excretion greater than 300 mg/24 h. Although widely accepted, this definition is not based on clinical outcomes. Our study aimed to longitudinally examine proteinuria in healthy women prior to, and in late pregnancy and to compare inpatient and outpatient 24-hour urine collections. Nulliparous women planning to conceive were recruited and completed a 24-hour urinary collection. Those who subsequently conceived completed a second 24-hour urinary collection in late pregnancy. In the first 5 years of the study, urinary collections were completed during an inpatient admission; all collections during the latter part of the study were performed as outpatients. Urine protein was measured using the VITROS UPRO Slide kit. Wilcoxon signed rank tests were used for paired comparisons of prepregnancy and late pregnancy proteinuria and Wilcoxon rank sum tests were used to compare inpatient and outpatient collections. Among 134 women completing a prepregnancy collection, median urinary protein excretion was 188 mg/24 h (IQR 103-280). Sixty-five women subsequently conceived and completed a late pregnancy collection. In healthy women, urinary protein increased to 254 mg/24 h during pregnancy (IQR 166-396). Forty-five percent of women exceeded the defined normal threshold of proteinuria in 24 hours in the absence of disease. Inpatient collections resulted in higher levels of urinary protein than outpatient at both time points. Our data suggest that significant proteinuria is present in healthy nonpregnant women. Even in the absence of disease, proteinuria increases during pregnancy. Outpatient collections may underestimate proteinuria, especially in late pregnancy.