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Objective: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. Design: Secondary analysis of a case–control study. Setting: Multicentre study of five geographic catchment areas in the USA. Population: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. Main outcome measures: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. Results: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 μmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 μmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 μmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605–0.663) overall, 0.713 (0.624–0.802) with diabetes and 0.625 (0.595–0.656) with no diabetes. Conclusions: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes. Maternal serum fructosamine levels are higher in women with stillbirth than in women live birth, especially in women with diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Comparison of contingent, step-wise and integrated screening policies. METHODS: Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free beta-human chorionic gonadotrophin (hCG) at 11-13 weeks, and classified positive (>1 in 30), borderline (1 in 30-1500) or negative. Borderline risks were recalculated using alpha-fetoprotein, hCG, unconjugated estriol (uE3) and inhibin at 15-18 weeks, and reclassified as positive (>1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers. RESULTS: There were 86 Down syndrome and 32,269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively. CONCLUSION: As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing. [ABSTRACT FROM AUTHOR]

Pre-eclampsia, one of the most significant health problems in human pregnancy, complicates approximately 6-8% of all gestations and is the leading cause of fetal growth retardation, infant morbidity and mortality, premature birth and maternal death. Recent research implicates free radicals in the pathophysiology of pre-eclampsia. This review covers the biochemistry of nitric oxide (NO) and possible interactions with other free radicals. Studies in the rat show that pregnancy is associated with enhanced production and responsiveness to NO in both reproductive tissues and blood vessels. Rats infused with NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) have been used as an animal model of pre-eclampsia, and the effects of steroid hormones on blood pressure in this model have been tested. Results suggest that pre-eclampsia may be a state of NO deficiency. However, in humans there seem to be contradictions regarding the involvement of NO in maternal adaptation to pregnancy. It is suggested that NO may be one of several systems that act in concert to maintain a symbiotic relationship between mother and fetus. However, the input of each system may be genetically determined. [ABSTRACT FROM AUTHOR]

The hypothesis that the changes in vascular reactivity seen during pregnancy are determined by the gestational age was examined. Experiments were designed to investigate changes in vascular responses with progression of pregnancy. The contractile responses to potassium and phenylephrine (in the presence and absence of N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor) and the relaxant responses to acetylcholine and sodium nitroprusside were measured in isolated aortic rings from pregnant rats at various stages of gestation and from non-pregnant female rats. Potassium-evoked contractile response was higher early in pregnancy and was decreased at term (P < 0.05). The contractile response to phenyllephrine was decreased and the relaxant response to acetylcholine was increased in early pregnancy (P < 0.05). Inhibition of nitric oxide synthase caused an increase in the contractile response to phenylephrine in all the groups, but the attenuation of the response in early pregnancy was maintained (P < 0.05). There was a small decrease in the maximal relaxant response to sodium nitroprusside at term (P < 0.05). It was concluded that the effects of pregnancy on the responses of rat aorta in vitro vary at different stages of gestation. Vascular resistance may be lowered by changes in vascular reactivity in early gestation and by a decrease in the contractile potential of the vasculature during the later stages. [ABSTRACT FROM AUTHOR]

Her title alone won't reveal nearly enough about the on-the-job risks and stressors pregnant patients may face. Pin down the details of workplace activities to tailor counseling about heavy lifting, physical and chemical exposures, air travel, and more. [ABSTRACT FROM AUTHOR]

Objective: It has been shown that the level of soluble fms-like tyrosine kinase-1 (sFlt-1) is elevated in pregnant women who are destined to have preeclampsia, and a role for sFlt-1 in its pathogenesis has been suggested. Our objective was to determine the effect of the over-expression of sFlt-1 on blood pressure and the occurrence of other manifestations of preeclampsia in pregnant mice. Study Design: At day 8 of gestation CD-1 mice were allocated randomly to an injection of an adenovirus carrying sFlt-1 (10(9) plaque-forming units; sFlt-1 group), adenovirus carrying the murine immunoglobulin G2alpha Fc fragment (10(9) plaque-forming units; mFc group used as a control for the virus) or saline solution (100 microL; saline group). At day 10 of gestation, blood pressure catheters were inserted through the left carotid artery into the aortic arch and tunneled to a telemetric transmitter. Blood pressure was monitored continuously in the conscious unrestrained animals until day 18. Blood was collected from the pregnant mice at different gestational times, and plasma sFlt-1 was measured by enzyme-linked immunosorbent assay. Pups and placentae were weighed, and maternal platelet counts were determined at death on day 18. Results: Plasma levels of sFlt-1 increased significantly in the sFlt-1 mice and were significantly higher than the 2 control groups. The mean blood pressure in the sFlt-1 mice was significantly higher on days 17 and 18 of gestation, compared with the mFc and saline solution groups. The time-course of blood pressure rise mirrored that of the sFlt-1 levels. The average pup weight, placental weight, and maternal platelet counts were significantly lower in the sFlt-1 group, compared with the controls. Conclusion: SFlt-1 induces hypertension and fetal growth restriction in pregnant mice, which supports its hypothesized role in the pathogenesis of preeclampsia. This animal model minimizes the need for manipulation or the administration of various compounds to induce the condition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to determine the effect of statins on lipopolysaccharide (LPS)-induced inflammatory response in a mouse model of preterm birth (PTB). STUDY DESIGN: Day 15 CD1 mice were randomly allocated to intraperitoneal LPS injection (100 [mu]g) or control. Mice in the LPS group were pretreated, 16 and 2 hours prior, with pravastatin (10 [mu]g/g), simvastatin (10 [mu]g/g), or vehicle control. Animals were sacrificed 6 hours after LPS. Cytokine messenger ribonucleic acid (mRNA) expression in the uterus and cervix, and concentrations in the maternal serum and amniotic fluid (AF) were determined. RESULTS: Pravastatin reduced interleukin (IL)-1[beta] and IL-6 mRNA expression in the uterus and cervix, respectively, and serum IL-1[beta] and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. Simvastatin reduced IL-1[beta] and IL-6 mRNA expressions in the uterus, IL-6 and tumor necrosis factor alpha (TNF-[alpha]) in the cervix, and IL-1[beta], IL-2, IL-12p70, IL-13, TNF-[alpha], GM-CSF, and interferon-[gamma] concentrations in the serum and IL-6 in AF. CONCLUSION: Statins reduce the LPS-induced inflammatory responses in a mouse model of PTB. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to determine whether perinatal nicotine exposure adversely affects cardiovascular health in adulthood. STUDY DESIGN: C57Bl/6J female mice were randomized to 200 [mu]g/mL nicotine in 2% saccharin or 2% saccharin alone from 2 weeks before breeding until weaning. Offspring weight, vital signs, and carotid artery vascular reactivity were studied. A second cohort was subjected to shaker stress on day 4 of 7 days. Selected mediators of vascular tone were evaluated by molecular studies. Student t or Mann-Whitney U test was performed for statistical analysis (significance: P < .05). RESULTS: Nicotine-exposed compared with control female offspring had significantly elevated mean blood pressure under normal and stress conditions. Nicotine females lacked heart rate elevation after stress. Nicotine males had higher mean heart rate and a blunted contractile response to phenylephrine compared with controls, without an increase in blood pressure. CONCLUSION: Perinatal nicotine exposure has an impact on the developmental programming of future cardiovascular health, with adverse effects more evident in female offspring. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to investigate the mechanisms of action by which pravastatin improves vascular reactivity in a mouse model of preeclampsia induced by overexpression of soluble Fms-like tyrosine kinase-1 (sFlt)-1. STUDY DESIGN: Pregnant CD-1 mice were randomly allocated to tail vein injection with adenovirus carrying sFlt-1 or murine immunoglobulin G2 Fc (control), and thereafter to receive pravastatin (5 mg/kg/d) or water. Mice were sacrificed at gestational day 18. Protein expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-1, and hemeoxygenase-1 were assayed by Western blot in aorta, liver, and kidneys. Serum total cholesterol concentrations were measured. RESULTS: Pravastatin up-regulated eNOS expression in the aorta of sFlt-1 mice by nearly 2-fold (P = .005) to levels similar to control mice. Total cholesterol levels, vascular endothelial growth factor receptor-1, and hemeoxygenase-1 protein expression were similar across groups. CONCLUSION: Pravastatin prevents vascular dysfunction in part by up-regulation of eNOS in the vasculature. Our data support a role for statins in preeclampsia prevention. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to report the frequency of fetal growth restriction (FGR) based on indication for late preterm birth (LPTB). STUDY DESIGN: Singleton live born pregnancies that were delivered from 34-36 weeks 6 days of gestation over a 1-year period at a tertiary care medical center were studied. Indications for delivery were categorized as spontaneous (spontaneous preterm birth or premature rupture of membranes), medically indicated, or elective. A customized birthweight percentile was calculated for each pregnancy; the rate of FGR was compared based on indication for LPTB. RESULTS: There were 482 LPTBs that met all criteria. Customized birthweight percentiles (median; interquartile range) were different among groups (spontaneous, 45.5%; 20.8-73.5%; medically indicated, 26.9%; 4.1-63.6%; elective, 45.9%; 22.2-78.3%; P = .001). The rate of FGR was also different among groups (spontaneous, 13%; medically indicated, 32%; elective, 21%; P = .001). CONCLUSION: With the use of customized birthweight standards, we found that FGR complicated approximately one-third of all cases of medically indicated LPTB. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to test the hypothesis that prepregnancy obesity and soluble fms-like tyrosine kinase-1 (sFlt-1)-induced preeclampsia lead to altered vascular function in the offspring later in life. STUDY DESIGN: CD-1 female mice were placed on a low-fat (LF) or high-fat (HF) diet before mating. On day 8 of pregnancy, the HF mice were injected with adenovirus that carried either sFlt-1 (HF sFlt-1) or murine immunoglobulin G2alpha Fc fragment (HF mFc). LF dams received saline solution. After being weaned, all offspring were placed on a standard diet. At 3 months of age, the carotid artery was isolated for in vitro vascular reactivity studies. RESULTS: Among male offspring, the response to phenylephrine was significantly lower in the HF sFlt-1 group. The response to serotonin in males and to thromboxane in females was lower in the HF sFlt-1 and HF mFc groups. In females, the HF sFlt-1 and LF groups displayed less relaxation to acetylcholine. The response to phenylephrine was significantly lower in females than males in the HF mFc and LF groups. The response to thromboxane was significantly lower in the HF sFlt-1 females, compared with males. CONCLUSION: Prepregnancy obesity and preeclampsia alter fetal programming of adult vascular function. The mechanism is complex and gender specific. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to determine whether fetal programming of adult blood pressure is altered in a previously characterized mouse model of preeclampsia that was induced by sFlt-1. STUDY DESIGN: CD-1 mouse mothers at day 8 of gestation were injected with an adenovirus carrying Flt 1-3 (10(9) plaque-forming units) or with an adenovirus carrying mFc as control (10(9) plaque-forming units). The resulting pups were followed until 6 months of age, at which time blood pressure (BP) was recorded continuously for 6 days. The offspring weight was also recorded from weaning until adulthood. RESULTS: BP was significantly higher in the male offspring that were born to sFlt-1-treated mothers compared with the controls. Male offspring from sFlt-1-treated mothers were significantly smaller from weaning until adulthood. However, there were no significant differences in BP and postweaning weight in female offspring between the 2 groups. CONCLUSION: Our findings highlight the role of the intrauterine environment in the developmental origin of adult disease. [ABSTRACT FROM AUTHOR]

Background: Implications of life-long, perceived discrimination on nutrient intake during the preconception period are unclear., Objective: The objective is to identify associations between perceived discrimination and consumption of specific nutrients associated with risk of adverse pregnancy outcomes., Design: This is a secondary data analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (NuMom2b) cohort. Participants completed a Block Food Frequency Questionnaire assessing diet in the three months prior to pregnancy and a Krieger Experiences of Discrimination Scale assessing personal encounters of discrimination., Participants/setting: Participants were recruited from eight clinical centers across the US between 2010-2013. Each participant completed the Food Frequency and Krieger questionnaires and self-identified as belonging to a minoritized racial or ethnic group for this analysis (n=2457)., Main Outcome Measures: Main outcomes include reported total energy and macronutrient intake, percent of energy from macronutrients, saturated and unsaturated fatty acids (FA), added sugar, sodium, dietary fiber, and Healthy Eating Index-2010 Seafood and Plant Proteins component score., Statistical Analyses Performed: Participants were grouped as reporting fewer (<3) or more (≥3) circumstances of discrimination on the Krieger Scale. Multivariable regression models examined associations between discrimination group and nutrient intake. Variables with non-normal distributions were log transformed. Associations were adjusted for total energy intake. Primary outcomes underwent false discovery rate correction (FDR)., Results: Those reporting three or more circumstances of discrimination had higher reported energy intake (p=0.002) and higher reported intake of total fat, saturated fat, unsaturated fats, protein, added sugar and sodium after FDR (all p<0.05) as compared to those reporting fewer circumstances. After adjustment for total energy intake, reporting three or more circumstances was associated with greater reported intake of saturated fat and n-3 polyunsaturated FA, and lower reported intake of dietary fiber (all p<0.05)., Conclusion: Reporting three or more circumstances of discrimination was associated with higher reported total energy intake. After adjustment for total energy, reporting three or more circumstances of perceived discrimination was associated with less nutritious intake for some (higher saturated fat and lower dietary fiber) but not all (higher eicosapentaenoic and docosahexaenoic acids) nutrients., (Copyright © 2024. Published by Elsevier Inc.)

Background: Perinatal depression has been suggested to adversely impact child neurodevelopment. However, the complexity of the early childhood environment challenges conclusive findings., Objective: To evaluate whether there is an association between perinatal depressive symptoms and child intelligence quotient (IQ) at 5 years of age., Study Design: Secondary analysis of an ancillary study to a multicenter randomized trial of thyroxine therapy for pregnant individuals with subclinical hypothyroidism. Dyads of infants and birthing parent, with completed Center for Epidemiological Studies-Depression (CES-D) screens during pregnancy and postpartum and child neurodevelopment testing completed at five years of age (n=209) were included. CES-D screening was performed at 11-20 weeks, 34-38 weeks, and one-year postpartum. Depressive symptoms were categorized as antenatal (i.e., a positive screen at any point during pregnancy) or postpartum. The primary outcome was child IQ score < 85 at 5 years of age using the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) Full Scale test. Secondary outcomes included other assessments of childhood neurodevelopment. Bivariable analyses and multivariable logistic regressions were utilized., Results: Of the 209 birthing people included, 72 (34%) screened positive for depression during pregnancy and 32 (15%) screened positive one year postpartum. Children born to individuals with a positive antenatal depression screen had a higher odds of IQ < 85 at 5 years of age compared with children born to individuals with a CES-D < 16 (35% vs. 18%, OR 2.4, 95% CI 1.2-4.7). Similar findings were seen for children born to individuals with a positive postpartum depression screen (47% vs. 21%, OR 3.3, 95% CI 1.5-7.3). These associations did not persist in multivariable analyses that controlled for social determinants of health and clinical characteristics (adjusted odd ratio [aOR] 1.4, 95% CI 0.7-3.1; aOR 2.1, 95% CI 0.9-5.1, for antenatal and postpartum depressive symptoms, respectively). Similar findings were observed for other adverse neurodevelopmental outcomes., Conclusions: Having a positive perinatal depression screen was not associated with child cognitive outcomes after controlling for covariates including social determinants of health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Suboptimal prenatal care is linked to increased risk of stillbirth, but this association is not well-understood. The study objective was to evaluate the relationship between prenatal visit adherence and cause of death in stillbirths., Study Design: This is a secondary analysis from the Stillbirth Collaborative Research Network of data with complete cause of death evaluation. Appropriateness of prenatal visit frequency was determined per American College of Obstetricians and Gynecologists/American Academy of Pediatrics (ACOG/AAP) recommendations and the novel Michigan Plan for Appropriately Tailored Healthcare in Pregnancy (MiPATH) guidelines. Multivariate regression controlled for differences between groups., Results: Among 451 stillbirths included, 63.6% and 55.9% were non-adherent to ACOG/AAP and MiPATH recommendations, respectively. Non-adherent parturients according to the Michigan plan were more likely to have a stillbirth due to hypertensive disorders of pregnancy., Conclusion: Non-adherence to prenatal visit guidelines is associated with higher risk of stillbirth due to hypertensive disorders of pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective:  This study aimed to evaluate the safety of peripheral administration of vasopressor agents among patients with circulatory shock., Study Design:  We reviewed the published literature evaluating the use of peripheral norepinephrine in patients with shock and proposed a protocol for use in labor and delivery units., Results:  Peripheral administration of norepinephrine is a safe and potentially lifesaving intervention for patients in labor and delivery with extremely low complication rates., Conclusion:  Adoption of a protocol for peripheral administration of vasopressors in labor and delivery is safe and may prevent life threatening delays in hemodynamic resuscitation., Key Points: · Administering vasopressors through a peripheral line is safe and helps avoid delays in care.. · An established protocol is essential for the safe peripheral administration of vasopressors.. · Understanding continuous blood pressure monitoring is crucial for managing critically ill patients.., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: We examined the association between iron deficiency anemia (IDA) and severe maternal morbidity (SMM) during delivery and up to 1-year postpartum., Methods: In a retrospective cohort study across 3 states, we computed adjusted relative risks (aRR) for SMM comparing individuals with IDA versus those without, using modified Poisson regression models., Results: Among 2459,106 individuals, 10.3 % (n = 252,240) had IDA. Individuals with IDA experienced higher rates of blood transfusion and non-transfusion SMM (329 and 122 per 10,000 deliveries, respectively) than those without IDA (33 and 46 per 10,000 deliveries, respectively). The risk of blood transfusion (aRR: 8.2; 95 % CI 7.9-8.5) and non-transfusion SMM (aRR: 1.9; 95 % CI: 1.8-2.0) were higher among individuals with IDA. The attributable risk per 10,000 deliveries due to IDA for blood transfusion and non-transfusion SMM during delivery were 29.5 (95 % CI: 28.9-30.0) and 5.7 (95 % CI: 5.3-6.2), respectively. Within 1-year postpartum, the relative risk of non-transfusion SMM (aRR:1.3; 95 % CI: 1.2-1.3) was 30 % higher among individuals with IDA., Conclusion: IDA is associated with increased SMM risk. Addressing IDA in pregnant individuals may reduce SMM rates., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Nansi Boghossian reports financial support was provided by National Institute on Minority Health and Health Disparities. Samuel Nyarko reports financial support was provided by National Institute on Minority Health and Health Disparities. Lucy Greenberg reports financial support was provided by National Institute on Minority Health and Health Disparities. Molly Passarella reports financial support was provided by National Institute on Minority Health and Health Disparities. Scott Lorch reports financial support was provided by National Institute on Minority Health and Health Disparities. Ciaran Phibbs reports financial support was provided by National Institute on Minority Health and Health Disparities. George Saade reports financial support was provided by National Institute on Minority Health and Health Disparities. Jeff Buzas reports financial support was provided by National Institute on Minority Health and Health Disparities. None If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Financial Disclosure Brenna Hughes reports an ongoing financial relationship with UpToDate. Rebecca Clifton reports funding from the University of Arkansas for Medical Sciences for DSMB meetings and from the NIH to her institution. Anna Bartholomew reports money paid to her institution by NICHD and George Washington University. Alan Tita reports money paid to his institution from Pfizer. Torri D. Metz received UpToDate royalties for two topics on trial of labor after cesarean. Money was paid to her institution from Pfizer (site PI for phase III respiratory syncytial virus [RSV] vaccine trial and site PI for a COVID-19 vaccination trial in pregnancy). Geeta Swamy reports receiving past funding from GlaxoSmithKline and ongoing funding from Pfizer, Medscape, UpToDate, Moderna, and Sanofi. The other authors did not disclose any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Following the results of the A Randomized Trial of Induction Versus Expectant Management trial, which demonstrated a reduction in cesarean delivery with no increase in adverse perinatal outcomes after elective induction of labor in low-risk nulliparous patients at 39 weeks of gestation compared with expectant management, the use of induction of labor has increased. Current evidence is insufficient to recommend mid- to high-dose regimens over low-dose regimens for routine induction of labor., Objective: This study aimed to evaluate the association between oxytocin regimen and cesarean delivery and an adverse perinatal composite outcome in low-risk nulliparous patients undergoing induction of labor at ≥39 weeks of gestation., Study Design: This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network's A Randomized Trial of Induction Versus Expectant Management randomized trial. Patients who received a mid- to high-dose oxytocin regimen (starting or incremental increase >2 mU/min) were compared with those who received a low-dose oxytocin regimen (starting and incremental increase ≤2 mU/min). The co-primary outcomes for this secondary analysis were (1) cesarean delivery and (2) composite of perinatal death or severe neonatal complications. Multivariate Poisson regression was used to estimate adjusted relative risks and 97.5% confidence intervals for the co-primary endpoints and 95% confidence intervals for binomial outcomes, and multinomial logistic regression was used to estimate adjusted odds ratios and 95% adjusted relative risks for multinomial outcomes., Results: Of 6106 participants enrolled in the primary trial, 2933 underwent induction of labor with oxytocin: 861 in the mid- to high-dose group and 2072 in the low-dose group. The lower frequency of cesarean delivery in the mid- to high-dose group than in the low-dose group (20.3% vs 25.2%, respectively; relative risk, 0.81; 95% confidence interval, 0.69-0.94) was not significant after adjustment (adjusted relative risk, 0.90; 97.5% confidence interval, 0.76-1.07). The composite of perinatal death or severe neonatal complications was more frequent in the mid- to high-dose group than in the low-dose group (6.7% vs 4.3%, respectively; relative risk, 1.55; 95% confidence interval, 1.13-2.14) and remained significant after adjustment (adjusted relative risk, 1.61; 97.5% confidence interval, 1.11-2.35). Most cases in the composite were from the respiratory support (5.2% in the mid- to high-dose group vs 3.1% in the low-dose group) component, with an increase in transient tachypnea in newborns (3.8% in the mid- to high-dose group vs 2.5% in the low-dose group; adjusted relative risk, 1.63; 95% confidence interval, 1.04-2.54). The duration of neonatal respiratory support for 1 day was significantly longer in the mid- to high-dose group than in the low-dose group (3.5% vs 1.4%, respectively; adjusted relative risk, 2.59; 95% confidence interval, 1.52-4.39). However, support beyond 1 day was not different between the 2 groups. Compared with the low-dose group, the mid- to high-dose group had a higher operative vaginal delivery rate (10.0% vs 7.0%, respectively; adjusted relative risk, 1.54; 95% confidence interval, 1.18-2.00) and shorter duration of time from start of oxytocin to delivery (crude median: 12 hours [interquartile range, 8-17] vs 13 hours [interquartile range 9-19], respectively; adjusted median difference: -2 [95% CI, -2 to -1]; P<.001)., Conclusion: The use of mid-to high-dose oxytocin regimens for induction of labor in nulliparas at ≥39 weeks of gestation was not associated with a lower cesarean delivery rate or improved neonatal outcomes compared with the use of low-dose oxytocin regimens. Although the use of mid- to high-dose oxytocin regimens was associated with a shorter duration of labor, there was an increase in self-limited neonatal respiratory support and no difference in cesarean delivery rates. More evidences are needed to define the magnitude of potential maternal and neonatal benefits and risks associated with oxytocin regimens., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The Chronic Hypertension and Pregnancy Study demonstrated that a target blood pressure of <140/90 mm Hg during pregnancy is associated with improved perinatal outcomes. Outside of pregnancy, pharmacologic therapy for patients with diabetes and hypertension is adjusted to a target blood pressure of <130/80 mm Hg. During pregnancy, patients with both diabetes and chronic hypertension may also benefit from tighter control with a target blood pressure <130/80 mm Hg., Objective: We compared perinatal outcomes in patients with hypertension and diabetes who achieved blood pressure <130/80 vs 130 to 139/80 to 89 mm Hg., Study Design: This was a secondary analysis of a multcenter randomized controlled trial. Participants were included in this secondary analysis if they had diabetes diagnosed prior to pregnancy or at <20 weeks of gestation and at least 2 recorded blood pressure measurements prior to delivery. Average systolic and diastolic blood pressure were calculated using ambulatory antenatal blood pressures. The primary composite outcome was preeclampsia with severe features, indicated preterm birth <35 weeks, or placental abruption. Secondary outcomes were components of the primary outcome, cesarean delivery, fetal or neonatal death, neonatal intensive care unit admission, and small for gestational age. Comparisons were made between those with an average systolic blood pressure <130 mm Hg and average diastolic blood pressure <80 mm Hg and those with an average systolic blood pressure 130 to 139 mm Hg or diastolic blood pressure 80 to 89 mm Hg using Student's t test and chi-squared tests. Multivariable log-binomial regression models were used to evaluate risk ratios between blood pressure groups for dichotomous outcomes while accounting for baseline covariates., Results: Of 434 participants included, 150 (34.6%) had an average blood pressure less than 130/80 mm Hg. Participants with an average blood pressure less than 130/80 were more likely to be on antihypertensive medications at the start of pregnancy and more likely to have newly diagnosed diabetes mellitus prior to 20 weeks. Participants with an average blood pressure less than 130/80 mm Hg were less likely to have the primary adverse perinatal outcome (19.3% vs 46.5%, adjusted relative risk 0.43, 95% confidence interval 0.30-0.61, P<.01), with decreased risks specifically of preeclampsia with severe features (adjusted relative risk 0.35, 95% confidence interval 0.23-0.54) and indicated preterm birth prior to 35 weeks (adjusted relative risk 0.44, 95% confidence interval 0.24-0.79). The risk of neonatal intensive care unit admission was lower in the lower blood pressure group (adjusted relative risk 0.74, 95% confidence interval 0.59-0.94). No differences were noted in cesarean delivery (adjusted relative risk 1.04, 95% confidence interval 0.90-1.20), fetal or neonatal death (adjusted relative risk 0.59, 95% confidence interval 0.12-2.92). Small for gestational age less than the 10th percentile was lower in the lower blood pressure group (adjusted relative risk 0.37, 95% confidence interval 0.14-0.96)., Conclusion: In those with chronic hypertension and diabetes prior to 20 weeks, achieving an average goal blood pressure of <130/80 mm Hg may be associated with improved perinatal outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia., Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP., Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates., Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models., Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC)., Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs., Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

Objective: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes., Methods: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported., Results: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38)., Conclusion: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks., Competing Interests: Financial Disclosure: Torri D. Metz reports personal fees from Pfizer for her role as a medical consultant for a SARS-CoV-2 vaccination in pregnancy study, grants from Pfizer for role as a site PI for SARS-CoV-2 vaccination in pregnancy study, and grants from Pfizer for role as a site PI for RSV vaccination in pregnancy study outside the submitted work. Sherri Longo reports that UAB received NIH funding for the CHAP trial and Ochsner was one of the sites participating in the trial. Ochsner received a subaward from UAB for participation in the trial. Ochsner is a subsite to UAB, who is in the MFMU network; therefore, they have participated in trials. They have participated in other studies with UAB, including the CSOAP trial. They have collaborated on studies with Tulane and have subawards. Kelly Gibson reports money was paid to her institution from NHLBI, NICHD, and Materna Medical. Lauren Plante reports receiving payment from Cambridge University Press and Taylor & Francis for textbook royalties. She also received an honorarium speaking fee from Monmouth Medical Center. Sean Esplin received payment from Laborie and Nemo Health. Heather Frey and Wendy Kinzler received payment from UpToDate. Todd Rosen's institution received payment from Materna, Inc. and Myriad, Inc. Mary Norton received payment from Luna Genetics. Daniel Skupski received payment from Organon and Cooper Surgical. Leonardo Pereira's institution received payment for a Johnson & Johnson clinical trial. He received payment from Prehevbrio for serving on the data safety monitoring board for hepatitis vaccine in pregnancy. Namasivayam Ambalavanan received payment from Oak Hill Bio and for serving on the advisory board and holding intellectual property with AlveolusBio and Resbiotic. Alan T. N. Tita's institution received payment from Pfizer. Everett Magann received payment from UpToDate for co-authorship of the Ultrasound Assessment of Amniotic Fluid Volume chapter. Lorraine Dugoff reports that money was paid to her institution from Myriad and Natera. Brenna L. Hughes reports receiving funding from UpToDate and Moderna. Eugene Chang reports money was paid to his institution from Roche Diagnostics and Roche. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)