Investigation of health inequities in maternal and neonatal outcomes of patients with placenta accreta spectrum: a multicenter study.

BACKGROUND: Placenta accreta spectrum (PAS) is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in outcomes of patients with PAS. OBJECTIVE: To investigate health inequities in maternal and neonatal outcomes of pregnancies with PAS. STUDY DESIGN: This multicentered retrospective cohort study included patients with histopathological diagnosis of PAS at four regional perinatal centers between 1/1/2013 - 6/30/2022. Maternal race and/or ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. Primary outcome was a composite adverse maternal outcome: transfusion of 4+ units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury or mortality. Secondary outcomes were composite adverse neonatal outcome (APGAR < 7 at 1-minute, morbidity, or mortality), gestational age at PAS diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race/ethnicity with maternal and neonatal outcomes. RESULTS: 408 pregnancies with PAS were included. In 218 patients (53%), the diagnosis of PAS was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, BMI, income and parity, there was no difference in composite adverse maternal outcome among racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team and cesarean hysterectomy were similar between groups. CONCLUSION: In our multicenter PAS cohort, race and/or ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis and planned multi-disciplinary care. We hypothesize that comparable incidence of individual risk factors for perinatal morbidity as well as geographic proximity reduce potential inequities that may exist in the larger population.

SARS-CoV-2 infection, inflammation and birth outcomes in a prospective NYC pregnancy cohort.

Associations between antenatal SARS-CoV-2 infection and pregnancy outcomes have been conflicting and the role of the immune system is currently unclear. This prospective cohort study investigated the interaction of antenatal SARS-CoV-2 infection, changes in cytokine and HS-CRP levels, birthweight and gestational age at birth. 2352 pregnant participants from New York City (2020-2022) were included. Plasma levels of interleukin (IL)-1ß, IL-6, IL-17A and high-sensitivity C-reactive protein (HS-CRP) were quantified in blood specimens obtained across pregnancy. Quantile and linear regression models were conducted to 1) assess the impact of antenatal SARS-CoV-2 infection, overall and by timing of detection of SARS-CoV-2 positivity (< 20 weeks versus ≥ 20 weeks), on birthweight and gestational age at delivery; 2) examine the relationship between SARS-CoV-2 infection and maternal immune changes during pregnancy. All models were adjusted for maternal demographic and obstetric factors and pandemic timing. Birthweight models were additionally adjusted for gestational age at delivery and fetal sex. Immune marker models were also adjusted for gestational age at specimen collection and multiplex assay batch. 371 (15.8%) participants were infected with SARS-CoV-2 during pregnancy, of which 98 (26.4%) were infected at < 20 weeks gestation. Neither SARS-CoV-2 infection in general nor in early or late pregnancy was associated with lower birthweight nor earlier gestational age at delivery. Further, we did not observe cytokine or HS-CRP changes in response to SARS-CoV-2 infection and thus found no evidence to support a potential association between immune dysregulation and the diversity in pregnancy outcomes following infection.

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes.

INTRODUCTION: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. METHODS: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. RESULTS: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DISCUSSION: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.

The influence of structural racism, pandemic stress, and SARS-CoV-2 infection during pregnancy with adverse birth outcomes.

BACKGROUND: Structural racism and pandemic-related stress from the COVID-19 pandemic may increase the risk of adverse birth outcomes. OBJECTIVE: Our objective was to examine associations between neighborhood measures of structural racism and pandemic stress with 3 outcomes: SARS-CoV-2 infection, preterm birth, and delivering small-for-gestational-age newborns. Our secondary objective was to investigate the joint association of SARS-CoV-2 infection during pregnancy and neighborhood measures with preterm birth and delivering small-for-gestational-age newborns. STUDY DESIGN: We analyzed data of 967 patients from a prospective cohort of pregnant persons in New York City, comprising 367 White (38%), 169 Black (17%), 293 Latina (30%), and 87 Asian persons (9%), 41 persons of other race or ethnicity (4%), and 10 of unknown race or ethnicity (1%). We evaluated structural racism (social/built structural disadvantage, racial-economic segregation) and pandemic-related stress (community COVID-19 mortality, community unemployment rate increase) in quartiles by zone improvement plan code. SARS-CoV-2 serologic enzyme-linked immunosorbent assay was performed on blood samples from pregnant persons. We obtained data on preterm birth and small-for-gestational-age newborns from an electronic medical record database. We used log-binomial regression with robust standard error for clustering by zone improvement plan code to estimate associations of each neighborhood measure separately with 3 outcomes: SARS-CoV-2 infection, preterm birth, and small-for-gestational-age newborns. Covariates included maternal age, parity, insurance status, and body mass index. Models with preterm birth and small-for-gestational-age newborns as the dependent variables additionally adjusted for SARS-CoV-2 infection. RESULTS: A total of 193 (20%) persons were SARS-CoV-2-seropositive, and the overall risks of preterm birth and small-for-gestational-age newborns were 8.4% and 9.8%, respectively. Among birthing persons in neighborhoods in the highest quartile of structural disadvantage (n=190), 94% were non-White, 50% had public insurance, 41% were obese, 32% were seropositive, 11% delivered preterm, and 12% delivered a small-for-gestational-age infant. Among birthing persons in neighborhoods in the lowest quartile of structural disadvantage (n=360), 39% were non-White, 17% had public insurance, 15% were obese, 9% were seropositive, 6% delivered preterm, and 10% delivered a small-for-gestational-age infant. In adjusted analyses, structural racism measures and community unemployment were associated with both SARS-CoV-2 infection and preterm birth, but not small-for-gestational-age infants. High vs low structural disadvantage was associated with an adjusted relative risk of 2.6 for infection (95% confidence interval, 1.7-3.9) and 1.7 for preterm birth (95% confidence interval, 1.0-2.9); high vs low racial-economic segregation was associated with adjusted relative risk of 1.9 (95% confidence interval, 1.3-2.8) for infection and 2.0 (95% confidence interval, 1.3-3.2) for preterm birth; high vs low community unemployment increase was associated with adjusted relative risk of 1.7 (95% confidence interval, 1.2-1.5) for infection and 1.6 (95% confidence interval, 1.0-2.8) for preterm birth. COVID-19 mortality rate was associated with SARS-CoV-2 infection but not preterm birth or small-for-gestational-age infants. SARS-CoV-2 infection was not independently associated with birth outcomes. We found no interaction between SARS-CoV-2 infection and neighborhood measures on preterm birth or small-for-gestational-age infants. CONCLUSION: Neighborhood measures of structural racism were associated with both SARS-CoV-2 infection and preterm birth, but these associations were independent and did not have a synergistic effect. Community unemployment rate increases were also associated with an increased risk of preterm birth independently of SARS-CoV-2 infection. Mitigating these factors might reduce the impact of the pandemic on pregnant people.

SARS-CoV-2 during pregnancy and associated outcomes: Results from an ongoing prospective cohort.

BACKGROUND: The COVID-19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Questions remain about how SARS-CoV-2 impacts pregnant individuals and their children. OBJECTIVE: To expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. METHODS: The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT-PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. RESULTS: The SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS-CoV-2 RT-PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. CONCLUSION: Seropositivity for SARS-CoV-2 without RT-PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

Sentinel bowel loop as a marker for primary segmental intestinal volvulus in extreme low birth weight neonates.

Primary segmental intestinal volvulus is a rare condition that may affect neonates. This condition occurs when a loop of bowel torses around the axis of its mesentery without any other abnormality or malrotation. In the earlier stages, the diagnosis can be challenging due to the lack of specific clinical and radiographic signs. Prompt surgical management is critical as a delay in diagnosis may result in bowel loss or death. We present a series of three cases of extremely low birth weight infants with primary segmental volvulus. A sentinel bowel loop was critical in guiding each patient's surgical management as there were no other clinical markers concerning a pending intra-abdominal catastrophe. This case series suggests that a sentinel bowel loop may be a radiographic marker for primary segmental intestinal volvulus in extremely low birth weight infants.

Decreased placental folate transporter expression and activity in first and second trimester in obese mothers.

Obese women have an approximately twofold higher risk to deliver an infant with neural tube defects (NTDs) despite folate supplementation. Placental transfer of folate is mediated by folate receptor alpha (FR-α), proton coupled folate transporter (PCFT), and reduced folate carrier (RFC). Decreased placental transport may contribute to NTDs in obese women. Serum folate levels were measured and placental tissue was collected from 13 women with normal BMI (21.9±1.9) and 11 obese women (BMI 33.1±2.8) undergoing elective termination at 8-22 weeks of gestation. The syncytiotrophoblast microvillous plasma membranes (MVM) were isolated using homogenization, magnesium precipitation, and differential centrifugation. MVM expression of FR-α, PCFT and RFC was determined by western blot. Folate transport capacity was assessed using radiolabeled methyl-tetrahydrofolate and rapid filtration techniques. Differences in expression and transport capacity were adjusted for gestational age and maternal age in multivariable regression models. P<.05 was considered statistically significant. Serum folate levels were not significantly different between groups. Placental MVM folate transporter expression did not change with gestational age. MVM RFC (-19%) and FR-α (-17%) expression was significantly reduced in placentas from obese women (P<.05). MVM folate transporter activity was reduced by-52% (P<.05) in obese women. These differences remained after adjustment for gestational age. There was no difference in mTOR signaling between groups. In conclusion, RFC and FR alpha expression and transporter activity in the placental MVM are significantly reduced in obese women in early pregnancy. These results may explain the higher incidence of NTDs in infants of obese women with adequate serum folate.

Leveraging Technology to Improve Diabetes Care in Pregnancy.

Pregnant women with diabetes are at higher risk of adverse outcomes. Prevention of such outcomes depends on strict glycemic control, which is difficult to achieve and maintain. A variety of technologies exist to aid in diabetes management for nonpregnant patients. However, adapting such tools to meet the demands of pregnancy presents multiple challenges. This article reviews the key attributes digital technologies must offer to best support diabetes management during pregnancy, as well as some digital tools developed specifically to meet this need. Despite the opportunities digital health tools present to improve the care of people with diabetes, in the absence of robust data and large research studies, the ability to apply such technologies to diabetes in pregnancy will remain imperfect.

Management of lower vaginal agenesis in a patient with unicornuate uterus.

BACKGROUND: Absence of the lower vagina occurs from abnormal development of the sinovaginal bulbs and vaginal plate. CASE: We present a case of an adolescent girl, with a history of VACTERL and VATER status post flap vaginoplasty at 8 m of age and correction of vaginal-urethral fistula, with primary amenorrhea and cyclic pelvic pain. MRI showed a right hematocolpos. On exam the obstructed vagina was deviated to the right. Given prior urologic and rectal surgery, and laterality of unicornuate system, intra-operative ultrasonography (US) was performed. A needle was used to enter the inferior aspect of the obstructed vagina. A pull-through vaginoplasty was performed. SUMMARY AND CONCLUSION: Vaginal pull-through is the standard treatment for lower vaginal agenesis. In a unicornuate system, the use of intra-operative US is helpful to determine the appropriate angle of dissection.

The selective estrogen receptor modulator DT56a (Femarelle) does not affect platelet reactivity in normal or thrombophilic postmenopausal women.

OBJECTIVE: The purpose of this study was to assess the effect of DT56a (Femarelle), a selective estrogen receptor modulator, on platelet function in normal and thrombophilic women being treated for severe menopausal symptoms. METHODS: The Platelet Function Analyzer-100 (PFA-100) was used to asses platelet reactivity at baseline and after 8 weeks of treatment with Femarelle (644 mg/d in divided doses) in 25 symptomatic postmenopausal women with normal clotting times and seven symptomatic women with shortened clotting times (<61 s). The PFA-100 measure of closure time is considered equal to clotting time in assessing clotting function and platelet adhesion, aggregation, and blood coagulation factors. Closure times were measured after 3 and 8 weeks in all participants and at 1 year in the women with shortened clotting times. The nonparametric Wilcoxon signed rank test was used to assess the changes between baseline and each of the three subsequent measurements. RESULTS: Pretreatment study of all seven women with shortened closure times confirmed abnormalities associated with thrombophilia: four women were heterozygous for the factor V Leiden gene mutation, one was heterozygous for the prothrombin gene mutation, one was found to have protein S deficiency, and one had increased anticardiolipin antibodies. All participants reported improved symptoms during the treatment period. No significant change in closure times was found in the normally clotting participants after 3 or 8 weeks of Femarelle therapy (P > 0.26). No significant change in closure time was seen in the seven thrombophilic women after 3 or 8 weeks or 1 year of Femarelle treatment (P > 0.26). The regression curve for measures over time was not significant (P = 0.26). CONCLUSIONS: Femarelle, whose active ingredient is DT56a, did not adversely affect platelet reactivity as measured by PFA closure times in symptomatic thrombophilic postmenopausal women or normal controls. Femarelle, a novel selective estrogen receptor modulator that inhibits menopausal symptoms without thrombogenicity, may offer a new clinical choice for therapy of symptomatic postmenopausal women.

Assessment of osteoarthritis in hips with femoroacetabular impingement using delayed gadolinium enhanced MRI of cartilage.

PURPOSE: To determine the feasibility of assessing early osteoarthritis (OA) in hips with femoroacetabular impingement (FAI) using delayed Gadolinium enhanced MRI of Cartilage (dGEMRIC). MATERIALS AND METHODS: Thirty-seven hips in 30 patients who had a dGEMRIC scan and radiographic evidence of FAI were identified. Clinical symptoms were assessed. Radiographic measurements were performed to determine acetabular and femoral morphology. The severity of radiographic OA was determined using Tönnis grade and minimum joint space width (JSW). On MRI, the alpha angle was measured on the sagittal oblique slices. Correlations between dGEMRIC index, patient symptoms, morphologic measurements, radiographic OA, and age were determined. RESULTS: Significant correlations were observed between dGEMRIC index, pain (P < 0.05), and alpha angle (P < 0.05). The correlation of dGEMRIC with alpha angle suggests that hips with more femoral deformity show signs of early OA. CONCLUSION: The results of osteoplasty for FAI depend on the amount of pre-existing OA in the joint. dGEMRIC may be a useful technique for diagnosis and staging of early osteoarthritis in hips with impingement.

Radiographic and patient factors associated with pre-radiographic osteoarthritis in hip dysplasia.

BACKGROUND: Hip dysplasia leads to abnormal loading of articular cartilage, which results in osteoarthritis. The purpose of this study was to investigate the anatomic and demographic factors associated with the early onset of osteoarthritis in dysplastic hips by utilizing the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) index as a marker of the disease. METHODS: Ninety-six symptomatic dysplastic hips in seventy-four patients were assessed with standard radiographs and a dGEMRIC scan. The lateral center-edge angle of Wiberg, the acetabular index of Tönnis, and the break in the Shenton line were measured on a standing anteroposterior radiograph. Anterior undercoverage was assessed by measuring the anterior center-edge angle on a Lequesne false-profile view. A labral tear was considered to be present when contrast agent was seen through the entire thickness of the labrum on magnetic resonance arthrography. Osteoarthritis was defined as a dGEMRIC value of <390 msec (two standard deviations below the dGEMRIC index in normal hips). RESULTS: The mean dGEMRIC index (and standard deviation) for this cohort (473 +/- 104 msec) was significantly lower than that of a morphologically normal hip (570 +/- 90 msec). The anterior center-edge angle, the joint space width, and the presence of a labral tear were all found to be associated with osteoarthritis in the univariate analysis. Multivariate analysis identified age, the anterior center-edge angle, and the presence of a labral tear as independent factors associated with osteoarthritis. A second model was fitted with omission of the anterior center-edge angle because the lateral and anterior center-edge angles were highly correlated and the lateral center-edge angle is a more common clinical measure. This model identified age, the lateral center-edge angle, and the presence of a labral tear as significant independent factors associated with osteoarthritis. CONCLUSIONS: As has been demonstrated in previous studies of the hip, this investigation showed osteoarthritis to be associated with increasing age and the severity of dysplasia, as demonstrated both by the Wiberg lateral center-edge angle and the Lequesne anterior center-edge angle. Additionally, we identified a labral tear as being a risk factor for osteoarthritis.

Measuring surgeons' treatment preferences and satisfaction with nerve reconstruction techniques for children with unique brachial plexus birth palsies.

BACKGROUND: This study surveyed microsurgeons on treatments chosen for infants with brachial plexus birth palsies who have had failure of antigravity biceps and/or triceps function due to nerve surgery or natural history. METHODS: Questionnaires were sent to surgeons participating in a prospective multicenter brachial plexus birth palsy study. With a response rate of 82 percent, the sample comprised 22 surgeons with extensive experience in treating brachial plexus birth palsy. The survey gathered collective information on two unique clinical groups: (1) infants with no antigravity biceps function but intact antigravity deltoid and radial nerve function and (2) infants with no antigravity radial nerve function (wrist and digital extension, triceps) but intact antigravity biceps and deltoid function. Analysis of data and age-based trends was performed using the Fisher's exact test. RESULTS: With failure of biceps recovery, surgeons preferred microsurgery for children 6 to 18 months old and tendon transfers for children older than 18 months. Both procedures were preferred over observation alone (p < 0.001). With regard to microsurgery techniques, with increasing age, surgeons used nerve transfers more than resected neuroma and grafting. With tendon transfers, regional transfers were performed more than 90 percent of the time at all ages. For patients with no antigravity radial nerve function, most cases at all ages were managed by observation rather than microsurgery or tendon transfers (p < 0.001). CONCLUSIONS: The authors' data indicate a general consensus in treatment choices for the two cases of microsurgical failure in infants with brachial plexus birth palsies as well as in satisfaction among experienced surgeons in using these treatments.