Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence.

BACKGROUND: The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. OBJECTIVE: This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. STUDY DESIGN: In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. RESULTS: Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi; 95% confidence interval, -467 to -98; P<.01), a smaller stem villous area (-4.3 mm2; 95% confidence interval, -7.3 to -1.2; P<.01), and fewer stem villous vessels (-4967 stem villous vessels; 95% confidence interval, -8501 to -1433; P<.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (-873 terminal villi; 95% confidence interval, -1501 to -246; P<.01), the villous area (-1.5 mm2; 95% confidence interval, -2.7 to -0.4; P<.01), the number of blood vessels (-5165 terminal villous vessels; 95% confidence interval, -8201 to -2128; P<.01), and the vascular area (-0.6 mm2; 95% confidence interval, -1.1 to -0.1; P=.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. CONCLUSION: Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

The Impact of Social Vulnerability on Substance Use Detection Practices in Pregnancy.

This study aimed to synthesize current literature regarding the impact of social vulnerability on pregnancy-related substance use detection in the United States and highlight disparities in substance use detection practices. Clinicaltrials.gov, Google Scholar, PubMed (includes MEDLINE), and Cochrane Library databases were searched using the following Medical Subject Headings (MeSH): (["pregnancy" or "prenatal"] AND ["substance use screening" or "urine toxicology testing" or "toxicology testing" or "urine drug screening" or "CRAFFT" or "4P's" or "4P's Plus" or "NIDA Quick Screen" or "DAST-10" or "SURP-P" or "WIDUS"], AND ("bias" or "disparities" or "social vulnerability"]). The search included systematic reviews, prospective and retrospective studies, randomized controlled trials, case studies, and qualitative and quantitative research from January 2014 through November 2023. Selected literature was limited to studies published in English, which included a study population of either pregnant individuals or pregnancy health care providers in the United States, and that were focused on inequities in pregnancy substance use detection. Using Covidence, three authors screened abstracts, and two screened full articles for inclusion. The included studies were evaluated for quality of evidence using the mixed methods appraisal tool. The search yielded 4,188 manuscripts; 37 were eligible for full review. A total of 18 manuscripts were included based on the relevancy of the topic. The most common social vulnerability domain identified was minority status (17/18), followed by socioeconomic status (11/18), household characteristics (8/18), and housing type (1/18). Social vulnerability plays a role in substance use detection among pregnant individuals. Most notably, race and ethnicity, age, and public insurance lead to increased rates of detection, though most individual factors need to be studied in greater depth. This study was registered with PROSPERO (PROSPERO ID CRD42022352598), the International Prospective Register of Systematic Reviews. KEY POINTS: · Socially vulnerable pregnant individuals are more likely to receive substance use screening or urine toxicology testing.. · Race, ethnicity, age, and insurance influence substance use detection disparities.. · More research is needed to understand how other characteristics influence disparities in substance use detection..

Notes from the field: rapidly growing nontuberculous Mycobacterium wound infections among medical tourists undergoing cosmetic surgeries in the Dominican Republic--multiple states, March 2013-February 2014.

In August 2013, the Maryland Department of Health and Mental Hygiene (MDHMH) was notified of two persons with rapidly growing nontuberculous mycobacterial (RG-NTM) surgical-site infections. Both patients had undergone surgical procedures as medical tourists at the same private surgical clinic (clinic A) in the Dominican Republic the previous month. Within 7 days of returning to the United States, both sought care for symptoms that included surgical wound abscesses, clear fluid drainage, pain, and fever. Initial antibiotic therapy was ineffective. Material collected from both patients' wounds grew Mycobacterium abscessus exhibiting a high degree of antibiotic resistance characteristic of this organism.

Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated sudden cardiac death--United States.

On December 13, 2013, MMWR published a report describing three cases of sudden cardiac death associated with Lyme carditis. State public health departments and CDC conducted a follow-up investigation to determine 1) whether carditis was disproportionately common among certain demographic groups of patients diagnosed with Lyme disease, 2) the frequency of death among patients diagnosed with Lyme disease and Lyme carditis, and 3) whether any additional deaths potentially attributable to Lyme carditis could be identified. Lyme disease cases are reported to CDC through the Nationally Notifiable Disease Surveillance System; reporting of clinical features, including Lyme carditis, is optional. For surveillance purposes, Lyme carditis is defined as acute second-degree or third-degree atrioventricular conduction block accompanying a diagnosis of Lyme disease. During 2001-2010, a total of 256,373 Lyme disease case reports were submitted to CDC, of which 174,385 (68%) included clinical information. Among these, 1,876 (1.1%) were identified as cases of Lyme carditis. Median age of patients with Lyme carditis was 43 years (range = 1-99 years); 1,209 (65%) of the patients were male, which is disproportionately larger than the male proportion among patients with other clinical manifestations (p<0.001). Of cases with this information available, 69% were diagnosed during the months of June-August, and 42% patients had an accompanying erythema migrans, a characteristic rash. Relative to patients aged 55-59 years, carditis was more common among men aged 20-39 years, women aged 25-29 years, and persons aged ≥75 years.

Preconception Counseling: Identifying Ways to Improve Services.

Objective The aim of this retrospective study was to evaluate the maternal conditions for which preconception services are provided and the routine services and recommendations offered through the Maternal Fetal Medicine group at the University of Colorado (CU). The study sought to determine how services and recommendations differ by maternal condition, demographics, and reproductive health history. Materials and Methods Charts of patients who received preconception counseling through the CU MFM department during 2018 were reviewed to evaluate maternal conditions and the type of counseling patients received. Patients were grouped by their referral reason and subsequently by counseling recommendations to either proceed with immediate conception, defer immediate conception pending completion of further recommendations or to not conceive. Results Of the fifty-nine patients referred to preconception counseling, 52% ( n = 31) of the women were referred for maternal disease, 40% ( n = 24) for infertility, 32% ( n = 19) for previous poor obstetric outcomes, 30% ( n = 18) for advanced maternal age and finally, 15% ( n = 9) for gynecologic anatomic abnormalities. Conclusion During the initial evaluation, 58% ( n = 34) of patients were determined to have no concern for immediate conception while 7% ( n = 4) were ultimately advised to not conceive. Using this data, we identified areas of preconception counseling that standardization will improve by ensuring patients receive comparable services and advice.

Adverse perinatal outcomes in pregnancies affected by severe COVID-19 infection.

BACKGROUND: Severe COVID-19 infection in pregnancy has been associated with an increase in adverse perinatal outcomes, although studies differ regarding which outcomes are affected. Increased characterization of obstetrical and neonatal outcomes is needed, including details on indications for preterm delivery and additional neonatal adverse outcomes. OBJECTIVE: This study aimed to determine whether there is a higher rate of adverse perinatal outcomes with severe-to-critical COVID-19 infection compared with nonsevere COVID-19 diagnosed during pregnancy. STUDY DESIGN: This was a retrospective observational cohort study that compared rates of adverse perinatal outcomes between patients with severe-to-critical and those with nonsevere (asymptomatic, mild, or moderate) COVID-19 infection. Patients had singleton pregnancies and a positive laboratory polymerase chain reaction result for COVID-19. Primary outcomes included hypertensive disorders of pregnancy, cesarean delivery, fetal growth restriction, preterm birth, and neonatal intensive care unit admission. Additional neonatal outcomes analyzed included need for cardiopulmonary resuscitation, low birthweight (<2500 g), 1- or 5-minute Apgar score <7, need for supplemental oxygen, need for intubation, intraventricular hemorrhage, sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, blood transfusion, necrotizing enterocolitis, hypoxic-ischemic encephalopathy, birth trauma, or neonatal death. Appropriate bivariate analyses were used to compare groups. Logistic regression was used to examine primary outcomes while adjusting for confounders. RESULTS: A total of 441 participants were identified and confirmed via detailed chart review to be pregnant with a singleton pregnancy while diagnosed with COVID-19. Of these, 44 (10%) met National Institutes of Health criteria for severe-to-critical COVID-19 infection. The median gestational age at the time of maternal COVID-19 diagnosis was 36.4 weeks (interquartile range, 29.6-38.6). Severe-to-critical COVID-19 infection had a higher risk of a composite adverse neonatal outcome (36.4% vs 21.4%; P=.03). There was a high incidence of hypertensive disorders of pregnancy overall (20.6%), but this outcome was not higher in the severe-to-critical vs nonsevere group. There were no maternal deaths. There was a low incidence of neonatal COVID-19 test positivity among those tested (1.8%). When adjusting for presence of heart disease and gestational age at COVID-19 diagnosis, severe-to-critical COVID-19 was strongly associated with fetal growth restriction (adjusted odds ratio, 2.73; confidence interval, 1.03-7.25) and neonatal intensive care unit admission (adjusted odds ratio, 3.50; confidence interval, 1.56-7.87). Preterm delivery was more common but was no longer significant after adjustment (adjusted odds ratio, 2.23; confidence interval, 0.99-5.05). CONCLUSION: Severe-to-critical COVID-19 infection during pregnancy is associated with higher rates of adverse neonatal outcomes and strongly associated with neonatal intensive care unit admission and fetal growth restriction compared with nonsevere disease. There is a high rate of hypertensive disorders of pregnancy overall in all those affected by COVID-19, regardless of severity. Pregnant persons should be counseled on these risks to encourage vaccination, and those with infection during pregnancy should be monitored for fetal growth disorders.

Upper respiratory infection during pregnancy and neurodevelopmental outcomes among offspring.

OBJECTIVE: Maternal infection during pregnancy is associated with psychiatric disorders among offspring. The aim of this study was to investigate associations between upper respiratory infection (URI) in pregnancy and measures of cognitive and behavioral outcomes in child offspring. MATERIALS AND METHODS: A longitudinal study of 534 mother-child pairs with information regarding prenatal exposures collected through an interview conducted on average one year after delivery and subsequent participation in a childhood cognitive and psychosocial assessment between the ages 5-12years. Childhood cognition was measured using the Peabody Picture Vocabulary Test (PPVT-III) and the Beery-Buktenica Test of Visual Motor Integration-Fifth Edition (VMI-5) and behavioral function measured using the Child Behavior Checklist (CBCL) and teacher-report using the Teacher Report Form (TRF). Adjusted mean differences (adjMD) in outcome measures were calculated between mothers reporting the presence or absence of a URI during pregnancy. RESULTS: URI during pregnancy was not associated with the two measures of cognition given to offspring, but was associated with modest increases in total behavioral problems reported by mothers (adjMD: 3.72; CI: 1.91-5.54) and teachers (adjMD: 2.74; CI: 0.97-4.50). We observed differences in CBCL and TRF scores based on timing of URI: infections in mid-pregnancy (lunar months 4-5) were associated with poorer scores than were infections in early pregnancy (lunar months 2-3). CONCLUSIONS: In general, URI in pregnancy was not associated with decrements in childhood cognition, but may be associated with behavior problems.