Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials. STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders. RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications. DISCUSSION: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUND: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined. METHODS: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis. RESULTS: SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 1.2 mg. The high antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP recipient analysis for antibody thresholds correlated to reduced hospitalizations found a significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (0/85; 0% versus 15/276; 5.6%) p=0.03 or ROC based cutoff: (0/94; 0% versus 15/267; 5.4%) p=0.01. CONCLUSION: In unvaccinated, seronegative CCP recipients, early transfusion of plasma units corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460. FUNDING: Defense Health Agency and others.

Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

A Pilot Study Of Aspirin Resistance In Obstructive Sleep Apnea Patients.

Purpose: Obstructive sleep apnea (OSA) leads to endothelial dysfunction and platelet hyperactivity, which are linked to increased risk of cardiovascular disease and implicated in the development of aspirin resistance. We hypothesized that aspirin resistance is prevalent among OSA patients and aimed to explore effects of continuous positive airway pressure (CPAP) therapy on aspirin responsiveness. Methods: In Phase 1, prevalence of aspirin resistance was determined cross-sectionally in a group of OSA patients (n=59) on daily low-dose aspirin (81 mg) taken before entering the study, for primary or secondary prevention. In Phase 2, aspirin responsiveness before and after initiation of CPAP therapy was compared and stratified by endothelial function in a cohort of aspirin-naïve patients with newly diagnosed OSA (n=18). Results: In Phase 1, prevalence of aspirin resistance was 17%; most patients (56%) were on CPAP therapy. In Phase 2, initiation of CPAP therapy was associated with significant improvement in endothelial function (p=0.03). The mean pre-CPAP aspirin resistance units (ARU) was 569 (SD=75). In subjects with endothelial dysfunction (44%), the mean decrease after initiation of CPAP therapy was 43 ARU (SD=81, p=0.18). In contrast, subjects with normal endothelial function experienced the mean decrease of 8 ARU (SD=116, p=0.83). Conclusion: Aspirin resistance may be prevalent among OSA patients. After initiation of CPAP therapy, we observed a trend towards improvement in aspirin responsiveness among patients with endothelial dysfunction. The role of endothelial dysfunction and aspirin resistance should be explored in further studies that focus on the effect of CPAP on cardiovascular outcomes.

Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma.

BACKGROUND: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODS: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. RESULTS: A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. CONCLUSION: Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic. Trial Registration: ClinicalTrials.gov number, NCT04373460.

Association between loop diuretic dose administered in first 24 hours of heart failure admissions and length of hospital stay.

Background: Heart failure remains one of the highest disease burdens in the USA and worldwide. Heart failure guidelines recommend starting with a higher or equal to home dose of loop diuretics in acute decompensated heart failure admissions. To date, no study has been published assessing the effect of first 24 h loop diuretic dose on length of hospital stay. Objective: We hypothesize that the higher the first 24 h loop diuretic dose to home dose ratio, the shorter the length of hospital stay will be. Design/Methods: Retrospective chart review was conducted in a community teaching hospital and included patients discharged between February, 2015 and April, 2016, with a primary diagnosis of acute decompensated heart failure. The primary outcome was the length of hospital stay. The study population was divided into three groups based on the hospital to home dose ratio. Results: Among the 609 patients included in the data analysis, there was no statistically significant difference in length of hospital stay among the study groups. Inpatient mortality and incidence of acute kidney injury were highest in the group that received a first-24-hours hospital dose that was less than their home dose. Percentage of weight loss and 30-day readmission were not statistically significantly different among the groups. Conclusion: There was no association between the dose ratio and length of hospital stay in each group. Additional randomized controlled trials need to be conducted to provide more evidence and guidance for dosing loop diuretics in acute decompensated heart failure admissions.

Disparities in gestational age-specific fetal mortality rates in the United States, 2009-2013.

PURPOSE: Although studies have examined overall temporal changes in gestational age-specific fetal mortality rates, there is little information on the current status of racial/ethnic differences. We hypothesize that differences exist between racial/ethnic groups across gestational age and that these differences are not equally distributed. METHODS: Using the 2009-2013 data from US fetal death and live birth files for non-Hispanic white (NHW); non-Hispanic black (NHB); Hispanic; and American Indian/Alaska Native (AIAN) women, we conducted analyses to examine fetal mortality rates and estimate adjusted prevalence rate ratios and 95% confidence intervals (CIs). RESULTS: There were lower risks of fetal mortality among NHB women (aPRR = 0.76; 95% CI = 0.71-0.81) and Hispanic women (aPRR = 0.89; 95% CI = 0.83-0.96) compared with NHWs at 22-23 weeks' gestation. For NHB women, the risk was higher starting at 32-33 weeks (aPRR = 1.11; 95% CI = 1.04-1.18) and continued to increase as gestational age increased. Hispanic and AIAN women had lower risks of fetal mortality compared with NHW women until 38-39 weeks. CONCLUSIONS: Further examination is needed to identify causes of fetal death within the later pregnancy period and how those causes and their antecedents might differ by race and ethnicity.

A Four-Year Trend in Serum 25-Hydroxyvitamin D Levels in Western Connecticut.

OBJECTIVE: This study describes the trends in blood vitamin D levels in a regional population from 2009-2012 through a cross-sectional study design. METHODS: Over a four-year period (2009-2012), serum levels of 25-hydroxyvitamin D [25(OH)D] have been measured using an automated enzyme immunoassay with a steadily increasing number of tests performed each year. A total of 54700 tests were performed during this period, with a 90% increase in annual tests ordered. RESULTS: Mean and median serum levels of 25(OH) D showed statistically significant increases during this period. Those with 25(OH)D levels below 10 ng/mL represented 1.45% of the subjects in 2009 and 0.3% in 2012. The decrease in the proportion of subjects with 25(OH)D levels below 20 ng/mL and below 30 ng/mL was greatest out of all the proportioned subjects. Mean and median 25(OH)D levels increased with age in males and females. CONCLUSION: These results likely reflect increased health awareness in Western Connecticut compared with national surveys showing a temporal decrease in 25(OH)D levels.

Tick-borne disease preventive practices and perceptions in an endemic area.

Lyme disease is the most commonly reported vector-borne illness in the United States. Since the institution of Nationally Notifiable surveillance efforts for Lyme disease in the United States in 1991, there has been a consistent increase in the number of reported cases. Thus, the need for targeted prevention strategies is underscored. The purpose of this study was to investigate knowledge about tick-borne diseases as well as beliefs and practices related to a variety of personal tick-borne disease prevention methods among individuals in southwestern Connecticut, a Lyme disease-endemic area. Between June and September 2014, an anonymous questionnaire was administered to 275 participants through a point-of-contact convenience sample obtained at community events in southwestern Connecticut. The questionnaire assessed individuals' general knowledge about tick-borne diseases, performance of four selected tick-borne disease prevention methods, and perceived effectiveness and burdensomeness of those four behaviors. Some 80% of participants were female; median age was 55 years (IQR 45-64 years); 30% reported having been treated for a tick-borne illness and 50% reported a family member having been treated for a tick-borne illness. Overall, participants' knowledge of tick-borne diseases was poor; the average knowledge score was only 57% (SD 22.6%). The reported frequency of performing preventive behaviors was variable. The most commonly reported behavior was performing a tick check (68%); use of tick repellent was the least commonly reported behavior (38%). Those who were more knowledgeable about Lyme disease were more likely to perform tick checks but knowledge score was not significantly associated with any of the other three behaviors studied. Respondents largely believed preventive behaviors to be effective at reducing the risk of tick-borne diseases. Belief that a prevention behavior is effective was highly correlated with performing that behavior but perceived burdensomeness does not appear to influence behavior performance. The reasons for differential uptake of preventive behaviors remains unknown; further study of barriers to performance of personal preventive behaviors is needed to better target public health interventions.

Effects of krill oil on endothelial function and other cardiovascular risk factors in participants with type 2 diabetes, a randomized controlled trial.

OBJECTIVE: The purpose of this trial was to evaluate the effect of krill oil supplementation, a source of ω-3 fatty acids, on cardiovascular disease risk factors and blood glucose control among participants with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized, double-blind controlled cross-over trial was employed. Outcomes assessed were: endothelial function, blood lipids, glucose, glycated hemoglobin, serum antioxidant level, C peptide, and calculated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores. Participants were randomized to either krill oil or olive oil supplementation for 4 weeks, underwent a 2-week washout period, and then crossed to the other supplementation for 4 weeks. All participants were then offered an additional 17 weeks of krill supplementation. Testing occurred at 3 time points: baseline, after first supplementation, and after second supplementation. Testing also occurred after an optional 17 weeks of krill oil supplementation. Difference scores were calculated for each participant in both sequences (ie, differences in outcome measures in the first and second period of the sequence). The mean and SD of the scores in the 2 sequence groups were used to test for differences between treatment effects at a significance level of p<0.05. RESULTS: A total of 47 participants were included in the initial cross-over study. Participants who received krill oil for 4 weeks had an improvement in their endothelial function and a reduction in blood C peptide levels and HOMA scores as compared with the olive oil. A total of 34 participants completed the additional 17-week supplementation period. When compared with their respective baseline measures, these participants had a statistically significant improvement in endothelial function and blood high-density lipoprotein (HDL). CONCLUSIONS: Krill oil may lead to moderate improvement of cardiovascular risks, specifically endothelial dysfunction and HDL in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: Registered with ClinicalTrials.gov: NCT02091193.

Effect of obstructive sleep apnea on frequency of stroke in patients with atrial fibrillation.

Obstructive sleep apnea (OSA) is an independent risk factor for ischemic stroke that is not included in the usual cardioembolic risk assessments for patients with atrial fibrillation (AF). The aim of this study was to investigate the impact of OSA on stroke rate in patients with AF. Patients with AF and new diagnoses of OSA were identified from retrospective chart review. Those with histories of stroke at the time of the sleep study were excluded. The primary outcome was the incidence of stroke, determined by a physician investigator blinded to the results of polysomnography. Subgroup analysis was performed among different CHADS2 and CHA2DS2-VASc scores. Of 5,138 patients screened for OSA, 402 (7.7%) had AF and 332 (6.4%) met the inclusion criteria. Among the study population, the occurrence of first-time stroke was 22.9%. Ischemic stroke was more common in patients with OSA compared with patients without (25.4% vs 8.2% respectively, p = 0.006). After controlling for age, male gender, and coronary artery disease, the association between OSA and stroke remained statistically significant, with an adjusted odds ratio of 3.65 (95% confidence interval 1.252 to 10.623). A positive dose effect of the apnea-hypopnea index on the rate of stroke was observed (p = 0.0045). Subgroup analysis showed significantly higher rates of stroke in patients with CHADS2 scores of 0 and CHA2DS2-VASc scores of 0 and 1 and co-morbid OSA. In conclusion, OSA in patients with AF is an independent predictor of stroke. This association may have important clinical implications in ischemic stroke risk stratification.

Survey of developmental milestones in internal medicine among residents and faculty.

OBJECTIVES: The published Accreditation Council for Graduate Medical Education (ACGME) milestones represent a novel method of evaluation of trainees in graduate medical education. We surveyed agroup of teaching faculty and residents, regarding the new ACGME milestones project. We obtained their input on the expected timeline for the developmental milestones and compared their responses to the ACGME recommendations. METHODS: A 42-item survey questionnaire, derived from the original 142 item publication, was completed by 26 internal medicine teaching faculty and 34 internal medicine residents. RESULTS: We found statistically significant differences in the responses given by residents and faculty compared to those in the standard recommendations. The differences were more pronounced with the residents than with the faculty. CONCLUSIONS: The results of our survey showed significantly different responses as compared to the standard recommended timelines. Since this is a novel evaluation process, substantial faculty development and resident education regarding the process can help improve its implementation. Future studies should focus on how learners might better understand and refine the milestone evaluation process.

Racial/ethnic differences in infant mortality attributable to birth defects by gestational age.

OBJECTIVE: Birth defects are a leading cause of infant mortality in the United States. Previous reports have highlighted black-white differences in overall infant mortality and infant mortality attributable to birth defects (IMBD). We evaluated the impact of gestational age on US racial/ethnic differences in IMBD. METHODS: We estimated the rate of IMBD as the underlying cause of death using the period-linked birth/infant death data for US residents for January 2003 to December 2006. We excluded infants with missing gestational age, implausible values based on Alexander's index of birth weight for gestational age norms, or gestational ages <20 weeks or >44 weeks; we categorized gestational age into 3 groups: 20 to 33, 34 to 36, and 37 to 44 weeks. Using Poisson regression, we compared neonatal and postneonatal IMBD for infants of non-Hispanic black and Hispanic mothers with that for infants of non-Hispanic white mothers stratified by gestational age. RESULTS: IMBD occurred in 12.2 per 10 000 live births. Among infants delivered at 37 to 44 weeks, blacks (and Hispanics, to a lesser degree) had significantly higher neonatal and postneonatal IMBD than whites; however, among infants delivered at 20 to 33 or 34 to 36 weeks, neonatal (but not postneonatal) IMBD was significantly lower among blacks compared with whites. CONCLUSIONS: Racial/ethnic differences in IMBD were not explained in these data by differences in gestational age. Further investigation should include an assessment of possible racial/ethnic differences in severity and/or access to timely diagnosis and management of birth defects.

The use of transthoracic echocardiography and adherence to appropriate use criteria at a regional hospital.

BACKGROUND: The sharp increase in health care costs over the past decade has prompted health care providers to reevaluate how diagnostic imaging is utilized. In response to the need for more rational use of imaging services, the American College of Cardiology Foundation and the American Society of Echocardiography have developed appropriate use criteria (AUC) for transthoracic echocardiography to guide its utilization. Although community and regional hospitals, such as Danbury Hospital, account for 85% of registered hospitals in the United States, very little is known about adherence to the AUC at these institutions. METHODS: The electronic medical records of 1,205 patients who underwent inpatient transthoracic echocardiography from January 1 to June 30, 2008, were retrospectively examined to determine the reasons for ordering the studies. The 2007 and 2011 AUC were used to classify indications as appropriate, inappropriate, or uncertain. RESULTS: Using the 2007 AUC, 86% of echocardiographic examinations were classified as appropriate. One percent had indications that were inappropriate, and there were no uncertain indications. Thirteen percent of studies were ordered for reasons not defined by the 2007 AUC. The most common appropriate indications were symptoms due to suspected cardiac etiology, initial evaluation after acute myocardial infarction, and acute chest pain with suspected myocardial ischemia. When evaluated using the 2011 AUC, appropriate and inappropriate indications increased to 97% and 2%, respectively. Ninety-three percent of undefined studies, using the 2007 AUC, could be classified using the 2011 guidelines. CONCLUSIONS: Consistent with studies conducted at university hospitals, Danbury Hospital, a regional hospital, showed good adherence to the AUC. This suggests that the AUC are valuable across a large continuum of inpatient settings and can serve as an excellent guide for utilization and appropriateness.

Estimation of the contribution of non-assisted reproductive technology ovulation stimulation fertility treatments to US singleton and multiple births.

Infertility treatments that include ovulation stimulation, both assisted reproductive technologies (ARTs) and non-ART ovulation stimulation, are associated with increased risks of multiple birth and concomitant sequelae and adverse outcomes, even among singletons. While a US surveillance system for ART-induced births is ongoing, no population-based tracking system exists for births resulting from non-ART treatments. The authors developed a multistage model to estimate the uncertain proportion of US infants born in 2005 who were conceived by using non-ART ovulation treatments. Using published surveillance data, they estimated proportions of US multiple births conceived naturally and by ART and assumed that the remainder were conceived with non-ART treatments. They used Bayesian meta-analyses to summarize published clinical studies on the multiple-gestation risk associated with non-ART ovulation treatments, applied a fetal survival factor, and used this multiple-birth risk estimate and their own estimate of the proportion of US multiple births attributable to non-ART ovulation stimulation to estimate the total (and, through subtraction, singleton) proportion of infants conceived with such treatments. On the basis of the model, the authors estimate that 4.6% of US infants born in 2005 (95% uncertainty range: 2.8%-7.1%) resulted from non-ART ovulation treatments. Notably, this figure is 4 times greater than the ART contribution.

The association between major birth defects and preterm birth.

OBJECTIVE: To evaluate the association between preterm birth and major birth defects by maternal and infant characteristics and specific types of birth defects. STUDY DESIGN: We pooled data for 1995-2000 from 13 states with population-based birth defects surveillance systems, representing about 30% of all U.S. births. Analyses were limited to singleton, live births from 24-44 weeks gestational age. RESULTS: Overall, birth defects were more than twice as common among preterm births (24-36 weeks) compared with term births (37-41 weeks gestation) (prevalence ratio [PR] = 2.65, 95% confidence interval [CI] 2.62-2.68), and approximately 8% of preterm births had a birth defect. Birth defects were over five times more likely among very preterm births (24-31 weeks gestation) compared with term births (PR = 5.25, 95% CI 5.15-5.35), with about 16% of very preterm births having a birth defect. Defects most strongly associated with very preterm birth included central nervous system defects (PR = 16.23, 95% CI 15.49-17.00) and cardiovascular defects (PR = 9.29, 95% CI 9.03-9.56). CONCLUSIONS: Birth defects contribute to the occurrence of preterm birth. Research to identify shared causal pathways and risk factors could suggest appropriate interventions to reduce both preterm birth and birth defects.

Increased risk of adverse neurological development for late preterm infants.

OBJECTIVE: To assess the risks of moderate prematurity for cerebral palsy (CP), developmental delay/mental retardation (DD/MR), and seizure disorders in early childhood. STUDY DESIGN: Retrospective cohort study using hospitalization and outpatient databases from the Northern California Kaiser Permanente Medical Care Program. Data covered 141 321 children > or =30 weeks born between Jan 1, 2000, and June 30, 2004, with follow-up through June 30, 2005. Presence of CP, DD/MR, and seizures was based on International Classification of Diseases, Ninth Revision codes identified in the encounter data. Separate Cox proportional hazard models were used for each of the outcomes, with crude and adjusted hazard ratios calculated for each gestational age group. RESULTS: Decreasing gestational age was associated with increased incidence of CP and DD/MR, even for those born at 34 to 36 weeks gestation. Children born late preterm were >3 times as likely (hazard ratio, 3.39; 95% CI, 2.54-4.52) as children born at term to be diagnosed with CP. A modest association with DD/MR was found for children born at 34 to 36 weeks (hazard ratio, 1.25; 95% CI, 1.01-1.54), but not for children in whom seizures were diagnosed. CONCLUSIONS: Prematurity is associated with long-term neurodevelopmental consequences, with risks increasing as gestation decreases, even in infants born at 34 to 36 weeks.

The relationship between cesarean delivery and gestational age among US singleton births.

The increasing trend of delivering at earlier gestational ages has raised concerns of the impact on maternal and infant health. The delicate balance of the risks and benefits associated with continuing a pregnancy versus delivering early remains challenging. Among singleton live births in the United States, the proportion of preterm births increased from 9.7% to 10.7% between 1996 and 2004. The increase in singleton preterm births occurred primarily among those delivered by cesarean section, with the largest percentage increase in late preterm births. For all maternal racial/ethnic groups, singleton cesarean section rates increased for each gestational age group. Singleton cesarean section rates for non-Hispanic black women increased at a faster pace among all preterm gestational age groups compared with non-Hispanic white and Hispanic women. Further research is needed to understand the underlying reasons for the increase in cesarean section deliveries resulting in preterm birth.

Differences in mortality between late-preterm and term singleton infants in the United States, 1995-2002.

OBJECTIVE: To assess differences in mortality between late-preterm (34-36 weeks) and term (37-41 weeks) infants. STUDY DESIGN: We used US period-linked birth/infant death files for 1995 to 2002 to compare overall and cause-specific early-neonatal, late-neonatal, postneonatal, and infant mortality rates between singleton late-preterm infants and term infants. RESULTS: Significant declines in mortality rates were observed for late-preterm and term infants at all age-at-death categories, except the late-neonatal period. Despite the decline in rates since 1995, infant mortality rates in 2002 were 3 times higher in late-preterm infants than term infants (7.9 versus 2.4 deaths per 1000 live births); early, late, and postneonatal rates were 6, 3, and 2 times higher, respectively. During infancy, late-preterm infants were approximately 4 times more likely than term infants to die of congenital malformations (leading cause), newborn bacterial sepsis, and complications of placenta, cord, and membranes. Early-neonatal cause-specific mortality rates were most disparate, especially deaths caused by atelectasis, maternal complications of pregnancy, and congenital malformations. CONCLUSIONS: Late-preterm infants have higher mortality rates than term infants throughout infancy. Our findings may be used to guide obstetrical and pediatric decision-making.