Perinatal substance use disorder: Examining the impact on adverse pregnancy outcomes.

Objective: Substance use disorder is a growing concern in the USA, especially among pregnant women. This study was undertaken to assess the impact of substance use disorder on adverse pregnancy outcomes using a nationwide sample of inpatient pregnancy hospitalizations in the USA, and to elucidate the influence on each type of adverse pregnancy outcome. Study design: A cross-sectional analysis of inpatient pregnancy hospitalizations in the USA from the Healthcare Cost and Utilization Project National Inpatient Sample from 2016 to 2020 was conducted. International Classification of Diseases - 10th revision and diagnosis-related group codes were used to identify inpatient pregnancy-related delivery hospitalizations with a substance use disorder and/or adverse pregnancy outcomes. Propensity score matching and multiple logistic regression analyses were undertaken to predict the likelihood of adverse pregnancy outcomes among pregnancy hospitalizations with and without substance use disorder. Subgroup analyses were performed to estimate the impact of substance use disorder on each adverse pregnancy outcome. Results: From 3,238,558 hospitalizations, the prevalence of adverse pregnancy outcomes was substantially higher among pregnancy hospitalizations with substance use disorder (35.6 %) compared with pregnancy hospitalizations without substance use disorder (25.1 %, p < 0.001). After matching and model adjustment for sociodemographic covariates, substance use disorder was identified as an independent predictor of adverse pregnancy outcomes [adjusted odds ratio (aOR) 1.47, 95 % confidence interval (CI) 1.45-1.49]. In subgroup analyses based on type of adverse pregnancy outcome, the greatest exposure risks were fetal growth restriction (aOR 1.96, 95 % CI 1.91-2.01), antepartum hemorrhage (aOR 1.79, 95 % CI 1.73-1.85) and preterm birth (aOR 1.65, 95 % CI 1.62-1.68). Conclusion: Patients with substance use disorder are at higher risk of adverse pregnancy outcomes, particularly fetal growth restriction, antepartum hemorrhage and preterm birth.

Racial and Ethnic Disparities Among Pregnancies with Substance Use Disorder: Impact on Perinatal Outcomes.

Objective: To examine racial/ethnic disparities in severe maternal morbidity (SMM) and adverse pregnancy outcomes (APOs) among pregnant patients with substance use disorder (SUD) compared to individuals without SUD. Materials and Methods: We conducted a cross-sectional analysis of inpatient hospitalizations of pregnant people from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) from 2016 to 2019. ICD-10 codes were used to identify the frequency of SMM and/or APO between those with and without SUD by race/ethnicity. Multilevel logistic regression analyses were performed to identify the effect of race/ethnicity as an independent predictor and as an effect modifier of SMM and APO in patients with SUD. Results: From 2,508,259 hospitalizations, SUD was identified in 6.7% admissions with the highest rate in White patients (8.2%) followed by Black (7.7%) and Hispanic (2.2%) patients. Rate of SMM and APO were increased in patients with SUD in all racial/ethnic groups compared to those without SUD, increasing by 1% and 10%, respectively. Among all patients, Black race was an independent predictor of SMM (adjusted odds ratio [aOR] 2.09; 95% confidence interval [CI]: 2.05-2.13) and APO (aOR 1.58; 95% CI: 1.56-1.59). Hispanic ethnicity was also an independent risk factor for predicting SMM (aOR 1.40; 95% CI: 1.37-1.43). Among Hispanic patients, SUD was associated with an ∼90% increased likelihood of SMM and APO. Conclusion: Although higher rates of SMM and APO are seen among hospitalizations of pregnant people with SUD, racial/ethnic disparities also exist among this population. This warrants further attention and presents an opportunity for intervention and for addressing the root causes of racial and ethnic disparities.

Reproductive decision making in women with medical comorbidities: a qualitative study.

BACKGROUND: A growing number of reproductive-age women in the U.S. have chronic medical conditions, increasing their risk of perinatal morbidity and mortality. Still, they experience unintended pregnancies at similar rates to low-risk mothers. We have limited understanding of how these individuals consider decisions about pregnancy and contraceptive use. The purpose of this study was to understand factors that influence reproductive decision-making among pregnant women with chronic medical conditions. METHODS: We conducted 28 semi-structured interviews with pregnant women with pre-existing medical conditions admitted to a tertiary maternal hospital to examine factors influencing reproductive decision making. Maternal demographic characteristics, medical history, and pregnancy outcome data were obtained through participant surveys and abstraction from electronic health records. Interview transcripts were coded and analyzed using Dedoose® with both deductive and inductive content analysis. RESULTS: Out of 33 eligible participants, 30 consented to participate and 28 completed interviews. The majority of participants identified as black, Christian, made less than $23,000 yearly, and had a variety of preexisting medical conditions. Overarching themes included: 1) Perceived risks-benefits of pregnancy, 2) Perceived risks-benefits of birth control, 3) Determinants of contraceptive utilization, and 4) Perceived reproductive self-agency. Contraception was viewed as acceptable, but with concerning physical and psychological side effects. Although some considered pregnancy as a health threat, more experienced pregnancy as positive and empowering. Few planned their pregnancies. CONCLUSIONS: Preexisting health conditions did not significantly influence reproductive decision-making. Barriers to birth control use were generally based in patient value-systems instead of external factors. Interventions to improve uptake and use of birth control in this cohort should focus on improving care for chronic health conditions and influencing patient knowledge and attitudes toward contraception.

Risk of adverse perinatal outcomes in pregnancies with "small" fetuses not meeting Delphi consensus criteria for fetal growth restriction.

BACKGROUND: Previous research endeavors examining the association between clinical characteristics, sonographic indices, and the risk of adverse perinatal outcomes in pregnancies complicated by fetal growth restriction have been hampered by a lack of agreement regarding its definition. In 2016, a consensus definition was reached by an international panel of experts via the Delphi procedure, but as it currently stands, this has not been endorsed by all professional organizations. OBJECTIVE: This study aimed to assess whether an independent association exists between estimated fetal weight and/or abdominal circumference of <10th percentile and adverse perinatal outcomes when consensus criteria for growth restriction are not met. STUDY DESIGN: Data were derived from a passive prospective cohort of singleton nonanomalous pregnancies at a single academic tertiary care institution (2010-2022) that fell into 3 groups: (1) consecutive fetuses that met the Delphi criteria for fetal growth restriction, (2) small-for-gestational-age fetuses that failed to meet the consensus criteria, and (3) fetuses with birthweights of 20th to 80th percentile randomly selected as an appropriately grown (appropriate-for-gestational-age) comparator group. This nested case-control study used 1:1 propensity score matching to adjust for confounders among the 3 groups: fetal growth restriction cases, small-for-gestational-age cases, and controls. Our primary outcome was a composite: perinatal demise, 5-minute Apgar score of <7, cord pH of ≤7.10, or base excess of ≥12. Pregnancy characteristics with a P value of <.2 on univariate analyses were considered for incorporation into a multivariable model along with fetal growth restriction and small-for-gestational-age to evaluate which outcomes were independently predictive of adverse perinatal outcomes. RESULTS: Overall, 2866 pregnancies met the inclusion criteria. After propensity score matching, there were 2186 matched pairs, including 511 (23%), 1093 (50%), and 582 (27%) patients in the small-for-gestational-age, appropriate-for-gestational-age, and fetal growth restriction groups, respectively. Moreover, 210 pregnancies (10%) were complicated by adverse perinatal outcomes. None of the pregnancies with small-for-gestational-age OR appropriate-for-gestational-age fetuses resulted in perinatal demise. Twenty-three of 511 patients (5%) in the small-for-gestational-age group had adverse outcomes based on 5-minute Apgar scores and/or cord gas results compared with 77 of 1093 patients (7%) in the appropriate-for-gestational-age group (odds ratio, 0.62; 95% confidence interval, 0.39-1.00). Furthermore, 110 of 582 patients (19%) with fetal growth restriction that met the consensus criteria had adverse outcomes (odds ratio, 3.08; 95% confidence interval, 2.25-4.20), including 34 patients with perinatal demise or death before discharge. Factors independently associated with increased odds of adverse outcomes included chronic hypertension, hypertensive disorders of pregnancy, and early-onset fetal growth restriction. Small-for-gestational age was not associated with the primary outcome after adjustment for 6 other factors included in a model predicting adverse perinatal outcomes. The bias-corrected bootstrapped area under the receiver operating characteristic curve for the model was 0.72 (95% confidence interval, 0.66-0.74). The bias-corrected bootstrapped area under the receiver operating characteristic curve for a 7-factor model predicting adverse perinatal outcomes was 0.72 (95% confidence interval, 0.66-0.74). CONCLUSION: This study found no evidence that fetuses with an estimated fetal weight and/or abdominal circumference of 3rd to 9th percentile that fail to meet the consensus criteria for fetal growth restriction (based on Doppler waveforms and/or growth velocity of ≥32 weeks) are at increased risk of adverse outcomes. Although the growth of these fetuses should be monitored closely to rule out evolving growth restriction, most cases are healthy constitutionally small fetuses. The management of these fetuses in the same manner as those with suspected pathologic growth restriction may result in unnecessary antenatal testing and increase the risk of iatrogenic complications resulting from preterm or early term delivery of small fetuses that are at relatively low risk of adverse perinatal outcomes.

Appalachian Women's perspectives on preterm birth and transvaginal ultrasound cervical length screening: Implications for addressing disparities in preterm birth.

PURPOSE: Preterm birth (PTB), a pressing issue for US maternal-child health, disproportionately impacts women in Appalachia. Transvaginal ultrasound (TVU) cervical length (CL) screening is the most accurate PTB risk predictor but remains underutilized. This study characterizes the knowledge, attitudes and beliefs of patients with prior PTB concerning PTB prevention efforts and TVU CL screening. METHODS: Participants were recruited from community-based health centers in Appalachian Kentucky. Semi-structured interviews and likert-scale surveys were conducted with 22 pregnant women with a history of spontaneous PTB. Methods for data collection were guided by the Consolidated Framework for Implementation Research (CFIR). RESULTS: Most participants reported that TVU was uncomfortable, but none refused it. Most women were able to articulate the benefits of TVU, but several had concerns about its safety in pregnancy. Participants suggested that pregnant women receive more PTB education and self-advocate. They urged providers to take patient concerns seriously, and better educate patients on PTB risks and TVU safety. DISCUSSION: Our study contributes crucial insights about the experience of a vulnerable population as it pertains to PTB prevention and the uptake of TVU CL screening. Our findings emphasize the need for increased efforts to better educate patients on the impact of prematurity and the safety and benefits of TVU CL screening as an evidence-based strategy for PTB prevention.

Correlation of placental MR imaging signs and pathologic diagnosis of placenta accreta spectrum: Retrospective single center case series.

INTRODUCTION: Alongside initial screening obstetric US, use of placental MRI has been increasing in the last few decades to aid with antenatal diagnosis and delivery planning in Placenta Accreta Spectrum (PAS). The aim of this study was to determine if the MRI pathophysiological sign subcategories described in the current literature can predict the severity of pathologic diagnosis. METHODS: Institutional imaging records were reviewed for placental MRIs performed for suspicion of PAS in the last decade. Electronic health records were searched for patient history and pathology. The 59 MRI studies were reviewed using the 11 MRI signs described by the SAR and ESUR joint consensus statement. Further breakdown of the signs was divided by underlying pathophysiologic subcategories including gross morphologic, interface and tissue architecture signs. RESULTS: Pathologic diagnosis yielded 34 cases: accreta 4/34, incerta 14/34, percreta 10/34 and normal 6/34. Of the accreta cases all of them demonstrated at least two interface and half of the cases had tissue architecture signs, 13/14 increta cases demonstrated interface signs and 12/14 demonstrated tissue architecture signs, 9/10 percreta cases had two interface and at least six demonstrated three tissue architecture signs. Statistical analysis showed significant difference between pathologic diagnosis and the number of positive interface signs with p = 0.02. DISCUSSION: Interface signs were the most objective and sensitive MRI subcategory. Statistical analysis determined there was a significant difference between PAS diagnosis and number of interface signs present. This subcategory has the most overlap with classic US signs which are traditionally used before MRI referral.

Preterm Birth Prevention in Appalachia: Restructuring Prenatal Care to Address Rural Health Disparities and Establish Perinatal Health Equity.

Purpose: This perspective piece reflects off previously published qualitative work to explore (1) themes surrounding equitable prenatal care in Appalachia and (2) strategies to restructure care delivery in a population with disparate rates of preterm birth (PTB). Methods: This study reflects in-depth interviews with 22 Appalachian women who experienced PTB and 14 obstetric providers. Results: Our findings underscore the need for greater cultural humility in prenatal care, heightened awareness of social determinants of health, and strategic planning to establish equity in birth outcomes. Conclusion: Prenatal care must undergo a paradigm shift to include a comprehensive discussion of cultural humility, social disparities, and health equity.

Preterm Birth Prevention in Appalachian Kentucky: Understanding Barriers and Facilitators Related to Transvaginal Ultrasound Cervical Length Surveillance Among Prenatal Care Providers.

Background: Appalachian Kentucky has higher-than-average rates of preterm birth (PTB)-a health disparity associated with increased maternal and fetal/neonatal morbidity and neonatal mortality. Transvaginal ultrasound (TVU) cervical length measurement is the best predictor of PTB risk, but is underutilized in Appalachia. This study explores prenatal care providers' TVU-related knowledge and practices, and identifies barriers and facilitators, which impact the adoption of this evidence-based technology. Materials and Methods: This study recruited providers from three Appalachian Kentucky health care sites. Prenatal care providers took part in semistructured interviews and completed brief survey scales. Questions focused on PTB knowledge, TVU-related barriers, and suggestions for clinician and/or patient-focused interventions. Transcripts were coded using a multistage process based in grounded theory. Descriptive statistics were calculated. Results: Eleven physicians, one nurse practitioner, one physician assistant, and one midwife completed interviews. Average participant age was 44 years with 17 years in practice; 43% of providers were female. Practitioners described the sociodemographic characteristics, health behaviors (e.g., smoking, opioid abuse), and comorbid conditions (e.g., obesity, hypertension, and diabetes) endemic in Appalachia that heightened their patients' PTB risk. TVU use was reported as important by all respondents, but not all were satisfied with their level of training. The most commonly identified barriers to TVU were patient access to transportation and social support. Participants stressed a need for changing community perceptions regarding consequences of PTB. Conclusions: Providers identified multiple TVU-related barriers and facilitators. These data will inform the design of a multifaceted dissemination and implementation strategy targeting PTB prevention in Appalachia.

Care-by-parent model as a tool for reduction of neonatal opioid withdrawal syndrome in neonates exposed to buprenorphine maintenance therapy in-utero.

Objective: To determine if a structured care-by-parent (CBP) protocol is associated with a reduction in diagnosis of treatment-requiring Neonatal Opioid Withdrawal Syndrome (NOWS).Study design: We performed a pilot retrospective, case control study of pregnant women enrolled in a comprehensive prenatal care program for opioid-dependent patients during which they received buprenorphine for Medication Assisted Treatment (MAT) for Opioid Use Disorder (OUD). Patients who participated in the CBP program actively roomed-in with their infants even after maternal hospital discharge while infants continued to be monitored for development of treatment-requiring NOWS. The primary outcome was the rate of treatment-requiring NOWS in the CBP grouping.Results: Thirty-two (32) cases that were enrolled in the CBP model were compared with 32 matched controls that were not enrolled in this model. There was a significant reduction in the rate of treatment-requiring NOWS among cases compared to the controls (OR = 0.10; p = .001). Neonates undergoing CBP had a decreased length of stay and lower Finnegan scores compared to those who did not undergo CBPConclusion: Among infants born to mothers with OUD in pregnancy, CBP significantly reduces the rate of treatment-requiring NOWS.

Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History.

CONTEXT: After completion of puberty a subset of men experience functional hypogonadotropic hypogonadism (FHH) secondary to excessive exercise or weight loss. This phenomenon is akin to hypothalamic amenorrhea (HA) in women, yet little is known about FHH in men. OBJECTIVE: To investigate the neuroendocrine mechanisms, genetics, and natural history underlying FHH. DESIGN: Retrospective study in an academic medical center. PARTICIPANTS: Healthy postpubertal men presenting with symptoms of hypogonadism in the setting of excessive exercise (>10 hours/week) or weight loss (>10% of body weight). Healthy age-matched men served as controls. INTERVENTIONS: Clinical assessment, biochemical and neuroendocrine profiling, body composition, semen analysis, and genetic evaluation of genes known to cause isolated GnRH deficiency. MAIN OUTCOME MEASURES: Reproductive hormone levels, endogenous GnRH-induced LH pulse patterns, and rare genetic variants. RESULTS: Ten men with FHH were compared with 18 age-matched controls. Patients had significantly lower body mass index, testosterone, LH, and mean LH pulse amplitudes yet normal LH pulse frequency, serum FSH, and sperm counts. Some patients exhibited nocturnal, sleep-entrained LH pulses characteristic of early puberty, and one FHH subject showed a completely apulsatile LH secretion. After decreased exercise and weight gain, five men with men had normalized serum testosterone levels, and symptoms resolved. Rare missense variants in NSMF (n = 1) and CHD7 (n = 1) were identified in two men with FHH. CONCLUSIONS: FHH is a rare, reversible form of male GnRH deficiency. LH pulse patterns in male FHH are similar to those observed in women with HA. This study expands the spectrum of GnRH deficiency disorders in men.

Smoking during pregnancy increases chemerin expression in neonatal tissue.

NEW FINDINGS: What is the central question of this study? Is chemerin, an adipokine implicated in obesity, increased in neonates following in utero cigarette smoke exposure. What is the main finding and its importance? Chemerin mRNA expression was increased and chemerin DNA methylation was decreased in babies born to mothers who smoked during pregnancy. These data provide a potential mechanism that may be mediating the increased obesity risk in individuals that are born to mothers who smoked during pregnancy. ABSTRACT: It has been shown that in utero tobacco exposure increases offspring risk for obesity, but the mechanisms responsible for this increased risk are not well understood. Chemerin is an adipokine that regulates adipocyte differentiation. This chemokine is elevated in obese individuals and with smoke exposure, but its levels have not been measured in neonates exposed to cigarette smoke in utero. We examined chemerin gene expression [n = 31 non-smoker (NS) and 15 smoker (S)] and DNA methylation (n = 28 NS and n = 11 S) in skin collected from babies born to mothers who smoked during pregnancy as compared to non-smoking controls. Quality RNA and DNA were isolated from foreskin tissue following circumcision, and chemerin gene expression and DNA methylation were assessed. Further, in a second cohort, we utilized primary dermal foreskin fibroblasts as a functional measure of adipogenesis in living cells (n = 11 NS and n = 8 S). Cells were stimulated with an adipogenic cocktail, mRNA was isolated from cells after 14 days, and chemerin gene expression assessed via real-time PCR. Chemerin mRNA was elevated in both whole tissue (NS: 2409.20 ± 555.28 counts and S: 2966.72 ± 636.84 counts; P < 0.01) and primary fibroblasts (NS: 1.12 ± 0.55 2 Δ Δ C T and S: 2.13 ± 1.34 2 Δ Δ C T ; P = 0.04) collected from infants born to smoking mothers. Chemerin DNA methylation was reduced in whole tissue of offspring born to smokers (NS: 4.18 ± 1.28 and S: 3.07 ± 1.31%; P = 0.02), which may contribute to the increased gene expression. Neonates born to mothers who smoke during pregnancy exhibit distinct changes in chemerin gene expression in response to in utero tobacco smoke exposure which are regulated in part by epigenetic alterations.

Previous cesarean delivery associated with subsequent preterm birth in the United States.

OBJECTIVE: To examine the relationship between previous cesarean delivery and subsequent preterm birth in the second pregnancy among women in the United States with registered birth records. STUDY DESIGN: We conducted a retrospective cohort study utilizing United States birth certificate data to generate the study population, which consisted of women delivering a singleton infant in their second live birth (n = 1,076,517) in the year 2016. Preterm birth and previous cesarean delivery measures were derived from United States birth certificates. Covariates included maternal age, race/ethnicity, education, marital status, payer source for delivery, pre-pregnancy body mass index, previous preterm birth, interpregnancy interval, and factors in the second pregnancy such as hypertensive disorders, diabetes, and cigarette use, trimester prenatal care began, weight gain during pregnancy, and presence of congenital anomalies. Women who experienced a cesarean delivery in the first pregnancy were compared to those who did not. RESULTS: When controlling for all covariates, women who had a cesarean delivery in their first pregnancy were 14% more likely to have a preterm birth in their second pregnancy (OR = 1.137, 95% CI = 1.117-1.158) compared to women who had not previously experienced a cesarean delivery. When risk was analyzed by sub categories of preterm birth based on gestational age, a differential association was noted, with a 10% increased risk of delivering before 34 weeks, a 1% increased risk for delivery between 34-36 weeks and no increased risk for delivery after 36 weeks compared to delivery at 39-40 weeks. CONCLUSION: This small, but statistically significant association between previous cesarean section and subsequent preterm birth suggests that efforts to reduce the number of index cesarean sections may contribute to reducing the overall preterm birth rate in the United States.

Comparison of Serum and Cervical Cytokine Levels throughout Pregnancy between Preterm and Term Births.

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births. Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1ß, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study ( N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester). Results For the CVF values of IL-6, IL-8, IL-10, TNF-α, and CRP, and serum MMP-8, those who delivered preterm had significantly higher values than the full-term group regardless of trimester. For the serum values of IL-1ß, IL-6, and TNF-α, those delivering preterm had significantly lower values than those delivering full-term regardless of trimester. For IL-1ß in CVF, the cytokine was significantly higher in the PTB group for second and third trimesters only, relative to the full-term group. Conclusion For each CVF cytokine that differed by birth status, values were higher for PTB than term, averaged over trimester. Numerous cytokine profiles varied across trimesters in women delivering term versus preterm in both CVF and serum.

Buprenorphine for Medication-Assisted Treatment of Opioid Use Disorder in Pregnancy: Relationship to Neonatal Opioid Withdrawal Syndrome.

Objective To examine the relationship between antepartum buprenorphine dose for medication-assisted treatment (MAT) of opioid use disorder (OUD) and incident neonatal opioid withdrawal syndrome (NOWS). Study Design We performed a prospective cohort study of pregnant women with a singleton gestation diagnosed with OUD and receiving buprenorphine for MAT at a tertiary care academic institution from July 2015 to January 2017. We divided the study cohort into two groups-pregnancies with versus without NOWS. Substance abuse patterns in pregnancy, maternal, and neonatal clinical outcomes were compared. Results The incidence of NOWS was 31.11% ( n = 28/90) in our study cohort. Pregnancies with NOWS had a significantly higher rate of benzodiazepine positive urine tests and number of positive urine drug screen (UDS) results for illicit opioids. The group without NOWS had significantly higher number of patients with an appropriate UDS result at delivery through postpartum. Rates of neonatal intensive care unit (NICU) admission, length of NICU stay, and maximum Finnegan score were significantly higher in the group with NOWS. Neither the initial (10.6 ± 5.2 versus 10.3 ± 4.8 mg, p = 0.80) nor the final buprenorphine doses (13.3 ± 5.1 versus 13.0 ± 4.6 mg, p = 0.81) were significantly different between study groups. Conclusion The occurrence of NOWS was not related to buprenorphine dose used for MAT.

Maternal smoking during pregnancy is associated with mitochondrial DNA methylation.

Maternal smoking during pregnancy (MSDP) has detrimental effects on fetal development and on the health of the offspring into adulthood. Energy homeostasis through ATP production via the mitochondria (mt) plays a key role during pregnancy. This study aimed to determine if MSDP resulted in differences in DNA methylation to the placental mitochondrial chromosome at the transcription and replication control region, the D-Loop, and if these differences were also present in an alternate neonatal tissue (foreskin) in an independent birth cohort. We investigated mtDNA methylation by bisulfite-pyrosequencing in two sections of the D-Loop control region and in long interspersed nuclear element-1 (LINE-1) genomic sequences in placenta from 96 mother-newborn pairs that were enrolled in a Rhode Island birth cohort along with foreskin samples from 62 infants from a Kentucky birth cohort. In both placenta and foreskin, mtDNA methylation in the light chain D-Loop region 1 was positively associated with MSDP in placenta (difference+2.73%) (P=0.001) and foreskin (difference+1.22%) (P=0.08). Additionally, in foreskin, a second segment of the D-Loop-heavy chain region 1 showed a small but significant change in methylation with MSDP (+0.4%, P=0.04). No methylation changes were noted in either tissue at the LINE-1 repetitive element. We identified a similar pattern of epigenetic effect to mitochondria arising in cells from different primordial lineages and in different populations, associated with MSDP. These robust and consistent results build evidence that MSDP may impact mt D-Loop methylation, as one mechanism through which this exposure affects newborn health.

Type of high-school credentials and older age ADL and IADL limitations: is the GED credential equivalent to a diploma?

PURPOSE: Educational attainment is a robust predictor of disability in elderly Americans: older adults with high-school (HS) diplomas have substantially lower disability than individuals who did not complete HS. General Educational Development (GED) diplomas now comprise almost 20% of new HS credentials issued annually in the United States but it is unknown whether the apparent health advantages of HS diplomas extend to GED credentials. This study examines whether adults older than 50 years with GEDs have higher odds of incident instrumental or basic activities of daily living (IADLs) limitations compared with HS degree holders. METHODS: We compared odds of incident IADL limitations by HS credential type using discrete-time survival models among 9,426 Health and Retirement Study participants followed from 1998 through 2008. RESULTS: HS degree holders had lower odds of incident IADLs than GED holders (OR = 0.72, 95% CI = 0.58, 0.90 and OR = 0.69, 95% CI = 0.56, 0.86 for ADLs and IADLs, respectively). There was no significant difference in odds of incident IADL limitations between GED holders and respondents without HS credentials (OR = 0.89, 95% CI = 0.71, 1.11 for ADLs; OR = 0.88, 95% CI = 0.70, 1.12 for IADLs). IMPLICATIONS: Although GEDs are widely accepted as equivalent to high school diplomas, they are not associated with comparable health advantages for physical limitations in older age.

Trendelenburg position in gynecologic robotic-assisted surgery.

OBJECTIVE: To estimate the necessity of routine patient positioning in steep Trendelenburg in robotic-assisted gynecologic surgery performed for benign indications. DESIGN: Descriptive study (Canadian Task Force classification II-2). SETTING: University-affiliated community hospital. PATIENTS: Twenty women undergoing robotic-assisted gynecologic surgery for benign indications. INTERVENTION: Robotic-assisted total hysterectomy, supracervical hysterectomy, myomectomy, and sacrocolpopexy. MEASUREMENTS AND MAIN RESULTS: Demographic data and perioperative variables were recorded including age, body mass index, procedure type, console time, perioperative complications, estimated blood loss, hospital length of stay, and degree of Trendelenburg position. The degree of Trendelenburg position was measured at the end of each procedure using an electronic level. The surgeons were blinded to the degree of Trendelenburg used. All procedures were performed successfully without conversion to laparotomy. All patients were discharged to home within 24 hours. No perioperative complications were noted. The mean (SD; 95% CI) Trendelenburg position used in this cohort was 16.4 (4.1; 14.4-18.3) degrees. Patient body mass index was 28.5 (5.3; 26.1-31.1). Median console time was 87.5 (27-112) minutes. CONCLUSION: Robotic-assisted benign gynecologic surgery can be effectively performed without use of the steep Trendelenburg position. The practice of routine adherence to steep Trendelenburg positioning in benign gynecologic robotic surgery should be questioned.

A pilot study on the use of serum glyoxalase as a supplemental biomarker to predict malignant cases of the prostate in the PSA range of 4-20 ng/ml.

BACKGROUND & OBJECTIVES: Serum prostate specific antigen (PSA) though most commonly used for diagnosis of prostate cancer lacks specificity. This study was aimed at exploring the use of serum glyoxalase as a supplemental biomarker to differentiate between malignant vs non-malignant diseases of the prostate in patients with PSA in the range of 4-20 ng/ml. METHODS: Serum glyoxalase and PSA were measured in 92 men (30 control, 31 cases of benign prostate hyperplasia (BPH) and 31 cases of adenocarcinoma of prostate). Of the latter group, 11 cases of prostate cancer in the PSA range of 4-20 ng/ml were included for studying the diagnostic utility of combination of both serum PSA and glyoxalase. RESULTS: In prostate cancer cases with PSA in the range of 4-20 ng/ml, the glyoxalase was found to be 233.3 ± 98.6 µmol/min while for the non-malignant group it was 103.1 ± 19.7 µmol/min. A cut-off of 19.2 ng/ml PSA showed sensitivity of 9 per cent, specificity of 96.7 per cent, positive predictive value (PPV) of 50 per cent and negative predictive value (NPV) of 75 per cent. A serum glyoxalase cut-off of 141 µmol/min showed sensitivity of 81.8 per cent, specificity of 100 per cent, PPV of 100 per cent and NPV of 93.9 per cent. Further, ROC analysis showed a significant difference in the area under curve (AUC) for glyoxalase as compared to serum PSA (0.92 vs 0.57; P<0.001). INTERPRETATION & CONCLUSIONS: Serum glyoxalase appears to be predictive of prostate cancer in the PSA range of 4-20 ng/ml. Studies with larger number of participants would be required to confirm this finding.