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The aim of this study was to explore factors contributing to compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS) during the severe acute respiratory syndrome coronavirus-2 pandemic in pediatric subspecialists. The Compassion Fatigue and Satisfaction Self-Test (CFST) and a questionnaire of personal/professional characteristics were distributed electronically to pediatric subspecialists. There were no significant differences in pre- and early-pandemic CF, BO, and CS scores. Nearly 40% of respondents felt their contributions to the pandemic were not valued by their institutions. Higher CF scores were significantly associated with: higher BO score; “I have put myself at increased risk through my work”; working in one’s specialty >50% of time; distress about mental health and/or future uncertainty. Higher BO scores were significantly associated with: higher CF score; “Self-care is not a priority”; emotional depletion. Higher CS scores were significantly associated with: “My institution values my contribution to the COVID-19 crisis”; workplace debriefs; pet therapy. The pandemic has only increased the need for physicians to receive social/emotional support from their institution and to feel their workplace contributions are valued. Successful pre-pandemic workplace interventions may not adequately support physicians during the pandemic. Further study is needed to identify supports that best counter the pandemic’s unprecedented challenges.

Objective To identify the prevalence of renal insufficiency (RI) in children with a history of prematurity and acute kidney injury (AKI). Study design This prospective cohort study evaluated renal function in children born preterm at 5-9 years of age. Univariable analyses compared perinatal and follow-up data from subjects with and without AKI history, and with and without current RI. Regression analyses were attempted to model RI as a function of AKI and other clinical risk factors. Results Fifteen of 43 (35%) participants had previously undiagnosed RI. Only children with no AKI history or neonatal stage 1 AKI presented for follow-up. Children born preterm with a history of stage 1 AKI had higher serum creatinine (sCr) at follow-up, but were not more likely to have RI compared to children without stage 1 AKI history (RI prevalence 30% and 36% in AKI and non-AKI group, respectively). Conclusion The high prevalence of RI in this preterm cohort at middle childhood follow-up highlights the need for routine kidney health assessments in this population. Large multicenter studies are needed to further characterize the impact of premature birth and mild AKI on renal function throughout childhood.

Introduction Although pediatric surgeons have lower rates of burnout compared to other surgical subspecialists, they still struggle with work-home conflict, depersonalization, and emotional exhaustion. Prior surveys have measured career satisfaction and burnout, but none have identified factors that contribute to physician well-being or provided potential solutions. Methods Members of the American Pediatric Surgical Association were surveyed regarding sources of distress and institutional practices intended to promote well-being. Responses were analyzed using content analysis. Results There was a 31.5% response rate to the survey. The most frequently cited sources of distress were administrative issues (45.2%), work/life balance (42.3%), personal issues (18.8%), and relationships with coworkers (17.9%). In open-ended questions, other sources of distress included poor leadership, loss of autonomy, lack of support and mentorship, and patient complications. Successful wellness strategies included relief from clinical burden, substantive wellness programming, surgeon inclusion in administrative decision making, support after adverse events, appropriate compensation and benefits, and opportunities for career development in research, teaching, and clinical care. Conclusion Pediatric surgeons are affected by multiple sources of distress. Interventions that ameliorate stress in pediatric surgeons were identified and should be considered by local institutions and national organizations to promote well-being. Level of evidence n/a

Objectives The objectives of this study were to establish days between birth and death for neonates over a 14-year period, determine if days between birth and death have changed over time across gestational age cohorts, and identify diagnoses which may put infants at high risk of prolonged hospitalization leading to death. Study Design This was a single-site, retrospective chart review of inborn infants who died prior to hospital discharge. Results Two hundred and thirty-nine patients born between 1/1/2006 and 12/31/2020 met inclusion criteria. Days until death ranged from 0 to 300 with a median of 6 days (interquartile range = 23). Median days until death increased over time, with a statistically significant increase between epoch 1 and epoch 2 (p = 0.016) but not between epoch 2 and epoch 3 (p = 0.618). Extremely premature infants died earlier than more mature infants (p Conclusions Our findings demonstrate an increase in time to death for newborns who did not survive to hospital discharge over a 14-year period. This trend suggests that the dynamics informing Meadows' assertion that “doomed infants die early” may be shifting, with some seriously ill infants who die before hospital discharge surviving longer than previously described. More research is needed to understand how best to care for babies who will not survive to discharge and to explore when supports such as palliative care consultation may be beneficial. Key Points As per W. Meadow, “Doomed infants die early”

The Baby Doe Regulations (BDR) regulate provision of life-sustaining treatment to seriously ill neonates. In 2020, the Trump administration expanded upon these through the Executive Order on Protecting Vulnerable Newborn and Infant Children (EO-PVNIC). Neonatologists were surveyed in 1988 to determine their opinions on the regulations. We sought to compare views of neonatologists from 1988 and 2021 in relation to three hypothetical cases and about the impact of the BDR and to evaluate perceptions of the EO-PVNIC.We modified and distributed the 1988 survey to members of the American Academy of Pediatrics Section on Neonatal Perinatal Medicine. We used Chi-squared tests to compare responses in 1988 to responses in 2021.We received 445 survey responses. Neonatologists today felt less compelled to provide aggressive care to the hypothetical patients, felt less constrained by the regulations, and were more likely to report that parental wishes would impact their actions.There have been shifts in neonatologists' perceptions of the Baby Doe Regulations toward less aggressive medical treatment for seriously ill neonates and more shared decision-making. Further research is required to identify how practices have been impacted over these decades.Neonatologists in the 1980s largely objected to the Baby Doe regulations, fearing the regulations would restrict their ability to provide optimal care to seriously ill neonates. Though still in place, current perceptions of these and newer regulations are unknown. Perspectives on the Baby Doe regulations have changed since their enactment and with the addition of newer, more restrictive regulations. Neonatologists today may favor less aggressive management in the face of poor prognosis. Neonatologists may also favor more shared decision-making now as compared to the past.

Background While institution-sponsored wellness programs may be effective, little is known about their availability and utilization in pediatric subspecialists, and about programs physicians wish were available. Methods A survey of perceptions about, and availability and utilization of institutional wellness activities, was distributed electronically to pediatric subspecialists nationally. Bivariate analyses were performed using χ2 tests or independent t tests. Multivariable logistic regression models for categories of institution-sponsored programming as a function of potential predictors of program utilization were performed. Qualitative content analysis was performed for free-text survey answers. Results Approximately 60% of respondents participated in institution-sponsored wellness opportunities. Debriefs, Schwartz Center Rounds, mental health services, and team building events were the most available institution-sponsored wellness activities, whereas debriefs, team building, Schwartz Center Rounds, and pet therapy were most frequently utilized. Respondents desired greater social/emotional support, improved leadership, enhanced organizational support, and modifications to the physical work environment, with no significant differences across subspecialties for "wish list" items. Conclusions Physician wellness requires more than a "one-size-fits-all" initiative. Our data highlight the importance of encouraging and normalizing self-care practices, and of listening to what physicians articulate about their needs. Pre-implementation needs assessment allows a "bottom-up" approach where physician voices can be heard.

The aim of this study was to explore factors contributing to compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS) during the severe acute respiratory syndrome coronavirus-2 pandemic in pediatric subspecialists.The Compassion Fatigue and Satisfaction Self-Test (CFST) and a questionnaire of personal/professional characteristics were distributed electronically to pediatric subspecialists.There were no significant differences in pre- and early-pandemic CF, BO, and CS scores. Nearly 40% of respondents felt their contributions to the pandemic were not valued by their institutions. Higher CF scores were significantly associated with: higher BO score; "I have put myself at increased risk through my work"; working in one's specialty50% of time; distress about mental health and/or future uncertainty. Higher BO scores were significantly associated with: higher CF score; "Self-care is not a priority"; emotional depletion. Higher CS scores were significantly associated with: "My institution values my contribution to the COVID-19 crisis"; workplace debriefs; pet therapy.The pandemic has only increased the need for physicians to receive social/emotional support from their institution and to feel their workplace contributions are valued. Successful pre-pandemic workplace interventions may not adequately support physicians during the pandemic. Further study is needed to identify supports that best counter the pandemic's unprecedented challenges.The sentiment "My institution has valued my contribution to the Covid-19 crisis" was the only significant factor associated with lower BO scores and was also associated with higher CS scores in pediatric subspecialists. This study is the first comparison of pre- and early-pandemic CF, BO, and CS scores in a national cohort of pediatric subspecialists. When considering interventions to promote CS and mitigate CF and BO for pediatric subspecialists during and after the pandemic, institutional leadership must offer wellness programming focused on social/emotional supports and prioritize a culture that explicitly recognizes and values every physician's contributions.

Background/Purpose To determine the prevalence of compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS) and identify potential predictors of these phenomena in pediatric surgeons. Methods The Compassion Fatigue and Satisfaction Self-Test and a survey of personal/professional characteristics were distributed electronically to American Pediatric Surgical Association members. Linear regression models for CF, BO, and CS as a function of potential risk factors were constructed. Results The analyzeable study response rate was 25.7%. The prevalence of CF, BO, and CS was 22%, 24% and 22, respectively, which were similar to prevalences previously identified in pediatric subspecialists. Higher CF scores were significantly associated with: higher BO scores; solo practice; compensation; ≥5 operating days/week; current distress about a ‘clinical situation’; mental health-care for work-related distress; and history of childhood surgery. Lower CF scores were significantly associated with ‘talking with a life partner’ about work-related distress. Higher BO scores were significantly associated with: higher CF scores; current distress about ‘coworkers’; and ‘keeping lawsuits confidential’. Lower BO scores were significantly associated with higher CS scores. Conclusions CF, BO, and CS are distinct but highly related entities. Pediatric surgeons experience these phenomena at similar rates to other pediatric subspecialists. Establishing local channels for physician peer support may be particularly impactful.

Background Failure to recover after a medical error is a major contributor to burnout. The degree to which pediatric surgeons experience errors and the barriers and facilitators to successful recovery are largely unknown. Methods We conducted a survey of American Pediatric Surgical Association (APSA) members to measure frequency of personal experience with medical errors resulting in significant patient harm, describe coping mechanisms, and explore surgeon satisfaction with institutional support in the wake of an error. Results We found that 80% of respondents have personally experienced a medical error resulting in significant patient harm or death, and that only about one-quarter were satisfied with the support provided by their institution. Only 11% of surgeons would prefer not to be contacted after an adverse event, and most would want to be contacted by their partners. Barriers to providing and receiving support included lack of knowledge, “shame and blame” culture, and lack of trust in the institution as an ally. Conclusions Pediatric surgeons routinely experience intense and stressful clinical scenarios and face challenging paths to recovery after adverse events. Institutions and national societies can play a critical role in creating infrastructure to help surgeons recover, in order to prevent burnout and promote well-being.

ObjectiveCompassion fatigue (CF) is secondary traumatic distress experienced by providers from contact with patients' suffering. Burnout (BO) is job-related distress resulting from uncontrollable workplace factors that manifest in career dissatisfaction. Compassion satisfaction (CS) is emotional fulfillment derived from caring for others. The literature on BO in healthcare providers is extensive, whereas CF and CS have not been comprehensively studied. Because of ongoing exposure to patient and family distress, pediatric palliative care (PPC) providers may be at particular risk for CF. We conducted a cross-sectional pilot study of CF, BO, and CS among PPC providers across the United States.MethodThe Compassion Fatigue and Satisfaction Self-Test for Helpers and a questionnaire of professional and personal characteristics were distributed electronically and anonymously to PPC physicians and nurses. Logistic and linear regression models for CF, BO, and CS as a function of potential risk factors were constructed.ResultsThe survey response rate was 39%, primarily consisting of female, Caucasian providers. The prevalence of CF, BO, and CS was 18%, 12%, and 25%, respectively. Distress about a “clinical situation,” physical exhaustion, and personal loss were identified as significant determinants of CF. Distress about “coworkers,” emotional depletion, social isolation, and “recent involvement in a clinical situation in which life-prolonging activities were not introduced” were significant determinants of BO. Physical exhaustion, personal history of trauma, “recent involvement in a clinical situation in which life-prolonging activities were not introduced,” and not discussing distressing issues were significant predictors of lower CS scores.Significance of resultsCF and BO directly influence the well-being and professional performance of PPC providers. To provide effective compassionate care to patients, PPC providers must be attentive to predictors of these phenomena. Further work is needed to explore additional causes of CF, BO, and CS in PPC providers as well as potential interventions.

Compassion fatigue (CF) is distress experienced by caregivers from ongoing contact with patients who are suffering. Burnout (BO) is occupational stress directly related to dissonance between job demands and available resources. Compassion satisfaction (CS) is professional fulfillment experienced through helping others. CF in physicians is not well studied. Neonatologists may be at particular risk for CF by virtue of recurrent exposure to distress in patients and their families. The objectives of this study were to determine the prevalence of CF, BO and CS, and to identify potential predictors for these phenomena in neonatologists. A modified Compassion Fatigue and Satisfaction Self-Test and a questionnaire of professional details and personal characteristics were distributed electronically to neonatologists nationally. Multivariable logistic and linear regression models for CF, BO and CS as a function of potential predictors were constructed. The survey response rate was 47%. The prevalence of CF, BO and CS was 15.7, 20.8 and 21.9%, respectively. Female gender, emotional depletion, distress from ‘a clinical situation’, ‘co-workers’, ‘personal health issues’ and ‘not talking about distressing issues’ were each significant determinants of CF. Emotional depletion, distress from the ‘physical work environment’ and ‘co-workers’, and ‘not talking about distressing issues’ were significant determinants of BO. Self-identification as Hispanic; ‘not currently feeling distressed’; talking about distressing issues; and utilization of pediatric palliative care services were significant determinants of higher CS. CF and BO may impact emotional well-being and professional performance of neonatologists. Enhancement of CS is a potential target for intervention.

To determine the prevalence of compassion fatigue, burnout, and compassion satisfaction and identify potential personal and professional predictors of these phenomena in pediatric critical care providers.Cross-sectional, online survey.Pediatric critical care practices in the United States.Pediatric critical care fellows and attending physicians.None.A modified Compassion Fatigue and Satisfaction Self-Test for Helpers and a questionnaire of personal and professional characteristics were distributed electronically to pediatric critical care physicians nationally. Prevalence of these phenomena was calculated. Hierarchical linear regression models for compassion fatigue, burnout, and compassion satisfaction as a function of potential risk factors were constructed. The survey response rate was 35.7%. The prevalence of compassion fatigue, burnout, and compassion satisfaction was 25.7%, 23.2%, 16.8%, respectively. Burnout score, emotional depletion, and distress about a patient and/or the physical work environment were each significant determinants of higher Compassion Fatigue scores. Preparing for didactics, Compassion Fatigue score, distress about administrative issues and/or coworkers, and "self-care is not a priority" were each significant determinants of higher burnout scores, whereas female sex, Compassion Satisfaction score, and distress about the physical work environment were each significant determinants of lower burnout scores. Prayer/meditation, talking with colleagues, senior faculty level, and student and/or chaplain involvement when delivering bad news were each significant predictors of higher Compassion Satisfaction scores, whereas female sex, burnout score, emotional depletion, and distress about coworkers were each significant predictors of lower Compassion Satisfaction scores.In our population, chronic exposure to distress in patients and families puts pediatric critical care physicians at risk for compassion fatigue and low compassion satisfaction. Awareness of compassion fatigue, burnout, and compassion satisfaction and their predictors may benefit providers both personally and professionally by allowing them to proactively manage their distress.

Objectives The objective was to determine the prevalence of compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS) and identify potential personal and professional predictors of these phenomena in pediatric emergency medicine (PEM) physicians. Methods A modified Compassion Fatigue and Satisfaction Self-Test for Helpers and a questionnaire of personal and professional characteristics were distributed electronically to PEM physicians nationally. The prevalence of these phenomena was calculated. Hierarchical linear regression models for CF, BO, and CS as a function of potential risk factors were constructed. Results The final analyzable survey rate represented 22.7% of the physicians invited to participate. The prevalences of CF, BO, and CS were 16.4, 21.5, and 18.5%, respectively. BO score, distress about a "clinical situation," "physical work environment," and engaging in prayer/meditation were each significant determinants of higher CF scores, whereas "socializing with family/friends" was significantly associated with lower CF scores. CF score, emotional depletion, and distress due to "coworkers" were each significant determinants of higher BO scores, whereas CS score and "talking with a family member" as a means of self-care were significantly associated with lower BO scores. Socializing with family/friends and >20 years as PEM provider were each significant determinants of higher CS scores, whereas BO score, emotional depletion, distress about the physical work environment and "administrative issues," 10% to 24% of time spent caring for pediatric patients, and "talking with life partner" about work-related distress were each significant determinants of lower CS scores. We acknowledge that the generalizability of our findings is limited by the sample size and by the fact that participants were largely female, Caucasian, and junior faculty and worked in academic medical centers. Conclusions PEM physicians are at risk for developing CF, BO, and low CS. Proactive awareness of these phenomena and their predictors may allow providers to better manage the unique challenges and emotional stressors of the pediatric ED to enhance personal well-being and professional performance.

To determine risk factors for acute kidney injury (AKI) in preterm infants as a function of time of onset. In this 5 1/2-year, single-center, retrospective study, incidence and timing of AKI was determined using modified Acute Kidney Injury Network criteria. Characteristics of newborns with and without AKI were compared by chi square and t-tests. Logistic regression was used to examine risk factors for AKI as a function of time of onset and potential confounders. AKI occurred in 30.3% of 357 neonates; 72.2% was stage 1. Gestational ages (GA), initial Cr, maternal magnesium and volume resuscitation were associated with early AKI (days 0 to 1). Volume resuscitation, umbilical arterial line and receipt of non-steroidal anti-inflammatory drug (NSAID) for patent ductus arteriosus were associated with intermediate AKI (days 2 to 5). GA, steroids for early hypotension, necrotizing enterocolitis and sepsis were associated with late AKI (⩾day 6). Stage 1 AKI is a common morbidity in our population. Risk factors for AKI in our population differed with time of onset.

To examine the relationship between maternal and neonatal creatinine (Cr) in preterm infants in the context of antenatal and intrapartum maternal and neonatal factors. In this 5½-year, single-center, retrospective study, paired maternal and neonatal Cr were compared by t-test. Linear regression for correlated outcomes employing generalized estimating equations was used to examine neonatal Cr as a function of antenatal maternal Cr and potential confounders. A total of 157 neonates of 124 mothers met study criteria. Neonatal Cr values in the first 24 h of life were significantly higher than antenatal maternal values. Linear regression modeling showed that maternal Cr, neonatal lactate, hypoxic–ischemic villous changes on placental pathology and multiple gestation were each significant determinants of the first neonatal Cr. No neonatal Cr was less than its paired maternal value. Maternal Cr, neonatal lactate, hypoxic–ischemic villous changes in the placenta and multiple gestation were each significantly associated with neonatal Cr.

To examine the relationship between blood urea nitrogen (BUN) during the first 3 weeks of life and protein intake and creatinine (Cr) and to quantify the effect of protein intake on postnatal growth in preterm infants.This is a 4-year, single-center, retrospective cohort study. We used multivariable linear regression models to examine the relationships between mean weekly BUN and protein intake adjusted for mean weekly Cr and potential confounders. We used additional regression models to examine the effect of protein intake on growth during this period.Overall, 249 infants met study criteria. As protein intake increased over the first 3 weeks of life, both BUN and Cr decreased significantly. Linear regression models showed protein intake and Cr were each significantly associated with mean BUN for each study week.Protein intake and Cr were each significantly associated with BUN. Significant amelioration of growth failure was seen with higher protein intake.

Background: Self-limited respiratory distress is a common neonatal respiratory morbidity for which effective treatments are lacking. Supportive care with non-invasive respiratory support is the norm. Animal models suggest that intrapartum exposure to group B Streptococcus (GBS) may cause mild pulmonary hypertension in the neonate, resulting in self-resolving respiratory distress. Treatments for pulmonary hypertension are currently not provided to neonates with self-limited respiratory distress empirically. Objectives: This study examines the hypothesis that the incidence and severity of self-limited respiratory distress are altered by intrapartum exposure to GBS and antibiotic prophylaxis (IAP) in a human population. Methods: This is a 10-year single-center cohort study of retrospective data of late preterm and term neonates diagnosed with self-limited respiratory distress. Multiple logistic models were fitted to examine associations between exposure to GBS and IAP, and markers of self-limited respiratory distress severity. Additional linear regression models were fitted to examine the association between exposure to GBS and IAP, and duration of respiratory support for self-limited respiratory distress. Finally, crude and gestational age-adjusted incidence of self-limited respiratory distress among GBS-exposed and -unexposed infants, as well as the odds of self-limited respiratory distress based on GBS exposure were calculated. Results: 584 neonates met study criteria. Neither GBS exposure nor IAP exposure was associated with severity of self-limited respiratory distress in multiple models. Crude and adjusted incidence of self-limited respiratory distress among neonates did not differ by GBS exposure history. Conclusions: Although animal studies indicate that GBS-mediated pulmonary hypertension may contribute to self-limited respiratory distress, neither exposure to GBS nor IAP was associated with an increased severity or incidence of self-limited respiratory distress in our human study population. Treatments for pulmonary hypertension are unlikely to speed symptom resolution for patients with self-limited respiratory distress.

Background: Initiation of empiric antibiotic treatment for possible early-onset sepsis is recommended for late preterm and term neonates with respiratory distress. There is no evidence base to this approach. Objectives: To determine the incidence of adverse infectious events in neonates with transient tachypnea of the newborn (TTN) managed with a risk-factor-based restrictive antibiotic use policy. Methods: This is a single institution retrospective cohort study of neonates with primary diagnosis of TTN between 2004 and 2010. The relationship between antibiotic exposure and infectious outcomes during the neonatal hospitalization was evaluated. An infectious outcome was defined as pneumonia, bacteremia, clinical sepsis, or death. Analysis included t test, χ2 test, and analysis of variance as appropriate. Results: 745 neonates with TTN met inclusion criteria. None of the 494 antibiotic-naive infants, and 212 of the 251 antibiotic-exposed infants had identifiable risk factors for sepsis. No infectious outcomes occurred in infants who did not receive antibiotics. Eight neonates with TTN received full antibiotic treatment for early-onset sepsis. Each was appropriately identified for early receipt of antibiotics based on historical or clinical risk factors for early-onset sepsis. Conclusions: This study suggests that empiric postnatal antibiotic treatment may not be warranted for late preterm and term infants with TTN in the absence of specific infectious risk factors.

Objective: To determine whether an association exists between antenatal antibiotic exposure and incidence of necrotizing enterocolitis (NEC) in low birth weight infants. Study Design: A retrospective case-control study was performed on all infants with a diagnosis of NEC born at our institition between 1988 and 2006. Medical histories of all infants with a diagnosis of NEC ≤Bell's stage IIA and matched controls without NEC were reviewed. Maternal and neonatal characteristics were compared using the Mantel-Haenszel chi-square procedure, and logistic regression models were constructed to account for confounding. Result: Clinical data for 97 matched pairs were analyzed. The adjusted odds ratio (OR) for antenatal exposure to ampicillin was significantly greater for infants who developed NEC (OR 2.3, 95% confidence interval 1.1, 4.8, P=0.003) than for control infants. Conclusion: Infants who developed NEC were more likely to have a history of in utero exposure to ampicillin in the immediate antepartum period than infants who did not develop NEC. © 2012 Nature America, Inc. All rights reserved.

Based on anecdotal observations, there is concern that severe preeclampsia leads to greater morbidity and mortality for mothers and neonates of twin pregnancies than for mothers and neonates of singleton pregnancies. Because few studies have been done, this study compared maternal disease characteristics and maternal/neonatal clinical outcomes of twin and singleton pregnancies complicated by severe preeclampsia.An historical cohort study of patients hospitalized at the Mount Sinai Hospital in New York City, NY, USA, from 2006 to 2010, compared 63 twin and 339 singleton pregnancies complicated by severe preeclampsia via chart review. Women were analyzed in two groups: hospitalized ≤34 weeks gestational age (GA) and hospitalized34 weeks GA. Univariable analysis (using Chi-square test, Fisher's Exact test, Student's t-test, or Wilcoxon Rank-Sum test, as appropriate) then multivariable analysis (using multivariable linear regression or multivariable logistic regression, as appropriate) compared maternal disease characteristics and maternal/neonatal clinical outcomes in twin and singleton pregnancies.Women with twins were older [mean age 34.9 years (standard deviation (SD) 7.9 years) vs. 29.4 years (SD 7.4 years), P-value.001] and women with singletons had a higher prevalence of chronic hypertension (21% vs. 8%, P=.02) and higher prevalence of history of preeclampsia (13% vs. 2%, P=.006). Women with twins were admitted for severe preeclampsia at an earlier gestational age (GA) [median twin 34.9 weeks GA (interquartile range, IQR, 32.7, 36.1) vs. median singleton 37.1 weeks GA (IQR 35.0, 38.9), P.001]. Among women presenting ≤34 weeks GA (27 twins; 108 singletons), women with singletons had a higher mean systolic blood pressure (BP) (181.1 vs. 163.5, P.001), higher mean diastolic BP (108.4 vs. 100.1, P=.002), and higher prevalence of headache (56% vs. 30%, P=.02). Among women presenting34 weeks GA (36 twins; 231 singletons), women with singletons had a higher prevalence of headache (54% vs. 28%, P=.004).Mothers and neonates of twin pregnancies complicated by severe preeclampsia do not appear to have greater morbidity and mortality compared to mothers and neonates of singleton pregnancies complicated by severe preeclampsia.

Although the incidence of significant congenital anomalies or serious trauma affecting the head and neck is relatively low, these are among the more challenging problems for the neonatologist. The ability of obstetricians to diagnose a significant number of anomalies before birth has undoubtedly improved the management of these conditions; however, the unexpected occurrence of a problem and the need to assemble the appropriate clinical team rapidly provides a great challenge. It is crucial for neonatal caretakers to be knowledgeable and skilled in diagnosis and early management, and aware of the need for appropriate consultation from a number of specialties. This article reviews, from the perspective of neonatal caregivers, the most common serious head and neck congenital anomalies and traumatic injuries that may present at or around the time of birth. The focus is on the steps necessary to manage these infants in the delivery room (especially when a prenatal diagnosis has been suggested) and during the first days of life. Many of these conditions require the participation of multiple specialists. An organized team approach involving obstetricians, neonatologists, anesthesiologists, otolaryngologists, neurosurgeons, plastic surgeons, pediatric surgeons, and oral surgeons is critical to success.

PROBLEM: Normal placentation requires modulation of proliferative cytotrophoblast to an invasive phenotype. Preeclampsia is characterized by failed cytotrophoblast invasion and arterial remodeling. Osteopontin (OPN) is an extracellular matrix protein implicated in cell adhesion, spreading, and invasion. METHOD OF STUDY: To investigate gestational age-related OPN expression, placental immunostaining was performed. To investigate the role of OPN in uteroplacental vascular pathology, placental immunostaining from pregnancies with preeclampsia (n = 12), fetal growth retardation (FGR) (n = 8), or both (n = 4) was compared with gestational age-matched controls (n = 24). RESULTS: In non-preeclamptic pregnancies, OPN immunolocalized to basal plate and intervillous cytotrophoblasts from 24-30 weeks (n = 13). In preeclampsia, OPN immunoreactivity was detected from 24-40 weeks. Cytotrophoblasts from FGR placentas were OPN-positive until 30 weeks, unless preeclampsia accompanied the FGR. In this case, cytotrophoblasts were OPN-positive from 24-40 weeks. CONCLUSIONS: The data suggest a role for OPN in cytotrophoblast invasion of the maternal vasculature/extracellular matrix during non-preeclamptic placentation, and OPN may serve as a marker for placental bed remodeling.

Appropriate temporal and spatial expression of osteopontin (OPN) in the female genital tract may be critical for successful embryo implantation and maintenance of gestation. Traditionally, experimental assessments of reproductive success have been limited to ex vivo dissection at a single time point to determine embryo number and size and are inadequate for ongoing study of the effect(s) of genetic manipulation on any individual gestation. To investigate the role of OPN in the maintenance of gestation, we developed a noninvasive, in vivo method of pregnancy surveillance suitable for murine application using magnetic resonance microscopy (MRM). Gravid wild-type mice (n =7) and mice with targeted disruption of one or both OPN alleles (OPN(-/-), n = 9; OPN(+/-), n = 3) underwent MRM on postcoital days 10.5, 15.5, and 19.5. Prenatal MRM images were used to determine embryo numbers and sizes. There were no significant differences in embryo numbers determined independently by two blinded observers (mean difference between observers = 0.04 embryos; p = 0.87). There was a significant effect of genotype on embryo size, with OPN(-/-) embryos significantly smaller at all gestational ages. However, targeted disruption of one or more OPN alleles had no effect on embryo number at any gestational age. Thus, MRM may be a powerful noninvasive method for in vivo prenatal developmental study of genetically engineered mice.

Osteopontin (OPN) is an extracellular matrix protein that has been implicated in vascular smooth muscle cell (VSMC) adhesion. We have previously described the generation of OPN-deficient VSMC that displayed altered adhesion to collagen. We have examined further the causes and consequences of this altered adhesion. OPN-deficiency was associated with a significant reduction in surface expression of alpha1 and beta1 integrins (mean fluorescence intensity alpha1: OPN-deficient 0.135+/-0.04 vs. control 0.313+/-0.05, p < 0.0001; beta1: OPN-deficient 0.398+/-0.09 vs. control 0.570+/-0.05, p < 0.004). Treatment of normal VSMC with antibody to alpha1 recapitulated the adhesion defect. OPN-deficient cells without collagen exposure had an apoptotic fraction of 1.9%, which increased to 95.7% after 24 hours exposure to collagen. Exogenous OPN added to cultures within 15 minutes of plating restored normal cell adhesion, but did not prevent cells from undergoing apoptosis. Normal VSMC had no detectable apoptosis after 24 hours incubation in suspension, whereas OPN-deficient cells had an apoptotic fraction of 37.5% when incubated in suspension under the same conditions. The data suggest that OPN-deficient VSMC have two distinct abnormalities: an alpha1beta1-mediated inability to adhere normally to collagen and an increased propensity for apoptosis.

gene NR3C1 and the association with birth weight and gestational age at delivery Jennifer Wong, Yula Ma, Luca Lambertini, Andrea Weintraub, Joanne Stone Mount Sinai School of Medicine, Maternal Fetal Medicine, New York, NY, Mount Sinai School of Medicine, Department of Preventive Medicine, New York, NY, Mount Sinai School of Medicine, Pediatrics, New York, NY OBJECTIVE: To determine the association of glucocorticoid receptor gene NR3C1 single nucleotide polymorphisms (SNPs) with birth weight and prematurity. STUDY DESIGN: This was a single center, pilot study of 80 umbilical cord blood samples collected prospectively from singleton pregnancies. DNA was isolated from each blood sample. SNPs were genotyped by Taqman assay (rs6193, rs6194, rs6195, rs6196, rs6198, rs258751) and sequencing (rs6189, rs6190). Linear regression models were calculated for birth weight (BW) and gestational age at delivery (GAd). RESULTS: The rs6195 SNP was not polymorphic in our sample, and was therefore excluded from further statistical analysis. The average BW was 3330g [1930-4660g]. The average GAd was 39.5 weeks [3241.6] with only 3 deliveries occurring prior to 37 weeks. The BW linear regression model showed a significant correlation with preterm labor, vaginal delivery, maternal Asian ethnicity, and the rs6196 variant (p 0.01; r2 0.270). The rs6196 GG genotype was associated with a 761g reduction in BW (95% CI 125-1398; p 0.02). The GAd linear regression model of gestational age at delivery also showed a significant correlation with preterm labor, betamethasone administration, neonatal intensive care unit admission, as well as the rs6196 GG genotype (p 0.01; r2 0.476). In this regression, the GG genotype was associated with an earlier GAd (95% CI 0.92-0.99; p 0.01). None of the other SNPs analyzed showed any significant correlation with either outcome. CONCLUSION: The GG genotype of the rs6196 SNP of the glucocorticoid receptor gene NR3C1 is associated with both lower birth weight and earlier gestational age at delivery. These data are consistent with existing scientific literature that correlates this and other SNP phenotypes to lower weight, BMI, waist/hip ratio, and decreased insulin resistance. This glucocorticoid-resistant phenotype may ultimately be protective postnatally among hypercortisolemic premature infants. Given the results from this interim analysis, our investigation will continue with a focus on umbilical cord blood collections from premature infants.

Human placentation requires modulation of proliferative cytotrophoblasts to an invasive phenotype to create the intervillous space. Preeclampsia is characterized by failed trophoblast invasion and remodeling of the maternal spiral arteries. OPN is a secreted extracellular matrix protein found in many tissues including human trophoblast, and has been implicated in cell adhesion, invasion, spreading, and migration. To investigate gestational age-specific expression of OPN, immunohistochemical staining of post-partum placental tissue from 13 healthy women was performed using a monoclonal antibody against OPN (MPIIIB10-1). OPN protein was localized to the cytoplasm of invasive extravillous trophoblast from 24-28 wks (N=7). After 28 wks (N=6), OPN was undetectable in the extravillous trophoblast, and was not identified in non-invasive intravillous cytotrophoblast and syncytiotrophoblast at any gestational age (N=13). To investigate the role of OPN in uteroplacental vascular pathology, immunohistochemical staining of post-partum placentas from pregnancies complicated by preeclampsia (N=6) or intrauterine growth retardation (N=2) was performed using MPIIIB10-1 and compared to staining of placentas from gestational age-matched controls without pregnancy-induced maternal vascular disease (N=13). In the preecclampsia group, there was prominent proliferation of cytotrophoblast in the basal plate with intense OPN staining, in association with morphologic evidence of compromised uteroplacental perfusion. This staining pattern was identified in all preeclamptic placentas at 24-40 wks. In contrast, the normal and IUGR placentas did not display prominent cytotrophoblast proliferation or evidence of decreased uteroplacental perfusion: OPN staining was limited to the invasive extravillous cytotrophoblast and detected only until 28 wks. The data suggests a role for OPN in trophoblast invasion of the maternal vasculature and extracellular matrix during normal placentation, where OPN may serve as a marker for uteroplacental vascular remodeling in the human fetus. In the preeclamptic pregnancy, extravillous cytotrophoblast continues to express OPN even at advanced gestational ages, which supports the speculation that intervillous fibrin/fibrinoid may be actively involved in the remodeling of the intervillous space. OPN may be critical in this process, the successful maintenance of which may necessary for fetal compensation.

FAILURE OF VASCULAR SMOOTH MUSCLE CELL (VSMC) ATTACHMENT TO COLLAGEN MATRICES RESULTS IN PROLONGED GROWTH ARREST • 150

To the Editor. The recently released Centers for Disease Control and Prevention (CDC) “Recommendations for the Prevention of Perinatal Group B Streptococcal Disease,” the American College of Obstetricians and Gynecologists and American Academy of Pediatrics recommendations, and the Canadian national consensus statement on the same subject are laudable efforts to prevent a serious and potentially devastating infection of the newborn.1-4 All properly note that the main thrust of prevention is treatment of the mother before delivery. The recommendations vary in which individuals to treat, but all recommendations call for the treatment of a large number of pregnant women in an effort to reduce the risk of early-onset newborn group B streptococcal (GBS) disease. All the recommended prevention schemes will miss some infants. One paper has suggested that 15% to 40% of early-onset GBS disease will still occur.5 Additional prevention schemes may be able to reduce the number of these …

The object of this study was to examine the effects of exogenous and endogenous prostaglandin E2 (PGE2) on the sexual behavior of female South African clawed frogs, Xenopus laevis. Ticking and leg extension, which communicate sexual unreceptivity to males, were studied in intact, ovariectomized, and ovariectomized-oviductectomized females. Injection of nanomolar amounts of PGE2 into the dorsal lymph sac significantly increased receptivity in intact, ovariectomized, and ovariectomized-oviductectomized females. The onset of the PGE2 behavioral effect occurs within 30 sec to 3 min of injection for intact and ovariectomized females; for ovariectomized-oviductectomized females, the latency period for the effect ranges from 10–20 min. PGE2 induced receptivity in doses as low as 0.03 μg/frog. Injection of the prostaglandin synthesis inhibitors, indomethacin and flurbiprofen (FBP), blocked chorionic gonadotropin- (HCG-) induced behavioral receptivity, suggesting that endogenous prostaglandin synthesis may have a role in regulating female sexual behavior. Flurbiprofen blockade of HCG-induced receptivity was reversed by PGE2 administration, suggesting that FBP's effects are PG Synthesis-Specific.