Gastroschisis and Cumulative Stressor Exposures.

BACKGROUND: Gastroschisis, a congenital defect of the abdominal wall, occurs disproportionately more in offspring of young mothers and has been increasing in prevalence over the past decades. A wide range of exposures have been reported in association with an increased gastroschisis risk, independent of mother's age; many have also been correlated with stress responses. METHODS: We explored cumulative exposures to such stressor exposures among 1,261 mothers of gastroschisis cases and 10,682 mothers of controls in the National Birth Defects Prevention Study (1997-2011). We considered 16 exposures as stressors in the first trimester: fever, genitourinary infection, anti-herpetic medication use, injury, bronchodilator use, cigarette smoking, alcohol intake, illicit drug use, prescription opioid use, oral contraceptive use, interpregnancy interval < 12 months, residential move, aspirin use, ibuprofen use, venlafaxine use, and paroxetine use. RESULTS: Mothers of cases reported more stressor exposures than controls. For 1, 2, 3, and ≥ 4 stressor exposures compared with none, the age-adjusted odds ratios (95% confidence interval) were 1.3 (1.1, 1.6), 1.7 (1.4, 2.1), 2.5 (2.0, 3.1), and 3.6 (2.9, 4.4), respectively. When we weighted cumulative stress scores according to the magnitude of stressor-specific odds ratios, similar associations were observed. Cumulative stressor exposure did not account for the strong inverse association between age and gastroschisis risk. CONCLUSIONS: These findings show that gastroschisis risk appears to increase with accumulation of widely different types of exposures, consistent with the hypothesis that stress-induced inflammation might play an etiologic role.

Two Decades of ICU Utilization and Hospital Outcomes in a Comprehensive Cancer Center.

OBJECTIVE: To investigate ICU utilization and hospital outcomes of oncological patients admitted to a comprehensive cancer center. DESIGN: Observational cohort study. SETTING: The University of Texas MD Anderson Cancer Center. PATIENTS: Consecutive adults with cancer discharged over a 20-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Cochran-Armitage test for trend was used to evaluate ICU utilization and hospital mortality rates by primary service over time. A negative binomial log linear regression model was fitted to the data to investigate length of stay over time. Among 387,306 adult hospitalized patients, the ICU utilization rate was 12.9%. The overall hospital mortality rate was 3.6%: 16.2% among patients with an ICU stay and 1.8% among non-ICU patients. Among those admitted to the ICU, the mean (SD) admission Sequential Organ Failure Assessment score was 6.1 (3.8) for all ICU patients: 7.3 (4.4) for medical ICU patients and 4.9 (2.8) for surgical ICU patients. Hematologic disorders were associated with the highest hospital mortality rate in ICU patients (42.8%); metastatic disease had the highest mortality rate in non-ICU patients (4.2%); sepsis, pneumonia, and other infections had the highest mortality rate for all inpatients (8.5%). CONCLUSIONS: This study provides a longitudinal view of ICU utilization rates, hospital and ICU length of stay, and severity-adjusted mortality rates. Although the data arise from a single institution, it encompasses a large number of hospital admissions over two decades and can serve as a point of comparison for future oncological studies at similar institutions. More studies of this nature are needed to determine whether consolidation of cancer care into specialized large-volume facilities may improve outcomes, while simultaneously sustaining appropriate resource utilization and reducing unnecessary healthcare costs.

Maternal exposure to radiographic exams and major structural birth defects.

BACKGROUND: An increasing number of radiologic exams are performed in the United States, but very few studies have examined the effects of maternal exposure to radiologic exams during the periconceptional period and birth defects. OBJECTIVES: To assess the association between maternal exposure to radiologic exams during the periconceptional period and 19 categories of birth defects using a large population-based study of birth defects. METHODS: We studied 27,809 case mothers and 10,200 control mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. Maternal exposure to radiologic exams that delivered ionizing radiation to the urinary tract, lumbar spine, abdomen, or pelvis were identified based on the mother's report of type of radiologic exams, organ or body part scanned and the month during which the exam occurred RESULTS: Overall, 0.9% of mothers reported exposure to one of these types of radiographic exams during the periconceptional period. We observed significant associations between maternal exposure during the first trimester and isolated Dandy-Walker malformation (odds ratio = 7.7; 95% confidence interval, 1.8-33) and isolated d-transposition of the great arteries (odds ratio = 3.8; 95% confidence interval, 1.4-10.3). However, the result for isolated Dandy-Walker malformation was based on only two exposed cases. CONCLUSION: These results should be interpreted cautiously because multiple statistical tests were conducted and measurements of exposure were based on maternal report. However, our results may be useful for generating hypotheses for future studies. Birth Defects Research (Part A) 106:563-572, 2016. © 2016 Wiley Periodicals, Inc.

Sociodemographic and hispanic acculturation factors and isolated anotia/microtia.

BACKGROUND: It has been observed in several studies that infants with anotia/microtia are more common among Hispanics compared with other racial/ethnic groups. We examined the association between selected Hispanic ethnicity and acculturation factors and anotia/microtia in the National Birth Defects Prevention Study. METHODS: We examined data from mothers of 351 infants with isolated anotia/microtia and 8435 unaffected infants from the National Birth Defects Prevention Study with an expected delivery date from 1997 to 2007. Sociodemographic, maternal, and acculturation factors (e.g., age, maternal education, household income, body mass index, gestational diabetes, folic acid, smoking, alcohol intake, study center, parental birthplace, and years lived in the United States, maternal language) were assessed as overall risk factors and also as risk factors among subgroups of Hispanics (United States- and foreign-born) versus non-Hispanic whites. RESULTS: Compared with non-Hispanic whites, both United States- and foreign-born Hispanic mothers demonstrated substantially higher odds of delivering infants with anotia/microtia across nearly all strata of sociodemographic and other maternal factors (adjusted odds ratios range: 2.1-11.9). The odds of anotia/microtia was particularly elevated among Hispanic mothers who emigrated from Mexico after age five (adjusted odds ratios = 4.88; 95% confidence interval = 2.93-8.11) or who conducted the interview in Spanish (adjusted odds ratios = 4.97; 95% confidence interval = 3.00-8.24). CONCLUSION: We observed that certain sociodemographic and acculturation factors are associated with higher risks of anotia/microtia among offspring of Hispanic mothers.

Sunspot activity and birth defects among Texas births (1999-2016).

BACKGROUND: Building on findings that linked higher levels of sunspot (SS) activity with a range of health and adverse birth outcomes, we sought to understand how SS activity over a 17-year time period may be correlated with the occurrence of birth defects. METHODS: Data from the Texas Birth Defects Registry, vital events from the Texas Center for Health Statistics, and mean monthly numbers of sunspots from the National Oceanic and Atmospheric Administration were utilized. Poisson regression was used to calculate crude/adjusted prevalence ratios (cPRs/aPRs) and 95% confidence intervals for three quartiles (Q) of increasing SS activity (compared to a referent of low activity) and 44 birth defects (31 non-cardiac; 13 cardiac) with estimated dates of conception from 1998 to 2016. RESULTS: We found moderately protective aPRs (range: 0.60-0.89) in a little over half of the case groups examined in our quartiles of higher SS activity (19 non-cardiac; 6 cardiac), after adjusting for maternal age, race/ethnicity, and education. Particularly protective aPRs in the highest SS quartiles (Q3-4) were noted for: anophthalmia, cataract, gastroschisis, trisomy 18, ventricular septal defects, atrial septal defects, and pulmonary valve atresia or stenosis. Conversely, modestly elevated aPRs were noted for two defect groups (agenesis, aplasia, and hypoplasia of the lung and microcephaly [Q2-3]). Following an additional adjustment of year of conception, results remained similar although many of the estimates were attenuated. CONCLUSION: The seemingly protective associations between increasing SS activity may be an artifact of increasing spontaneous abortions that occur following conception during these periods of heightened SS activity.

Associations between maternal reports of periconceptional fever from miscellaneous causes and structural birth defects.

BACKGROUND: Associations between birth defects and fevers attributed to colds, influenza, and urinary tract infections (UTIs) have been observed in previous studies. Our aim was to study associations between birth defects and fevers attributed to other causes. METHODS: We analyzed data from 34,862 participants in the National Birth Defects Prevention Study, a multistate case-control study of major structural birth defects. Using multivariable logistic regression, we assessed the association between maternal report of fever during early pregnancy due to causes other than colds, influenza, or UTI and 36 categories of birth defects. RESULTS: Maternal reports of fever due to other causes were associated with significantly elevated odds ratios ranging from 1.93 to 10.60 for 8 of 36 birth defects, primarily involving the spine, limbs, and heart (spina bifida, intestinal atresia, intercalary limb deficiency, transverse limb deficiency, congenital heart defect with heterotaxy, tetralogy of Fallot, pulmonary atresia and atrial septal defect, not otherwise specified). CONCLUSION: Our data suggests fever itself or other physiologic changes associated with many infections are associated with some birth defects. Women who are pregnant or planning to become pregnant may want to consider speaking with their healthcare provider about the best ways to avoid infections that may cause fever and for guidance on how to treat fevers during pregnancy.

Pre-Zika descriptive epidemiology of microcephaly in Texas, 2008-2012.

BACKGROUND: There are limited population-based studies on microcephaly. We characterized the epidemiology of microcephaly in Texas during a 5-year period (2008-2012), prior to the Zika epidemic in the Western hemisphere (2015). The associations of suspected risk factors were compared across four clearly defined case groups. METHODS: Data from the Texas Birth Defects Registry were used to calculate the prevalence of congenital microcephaly and crude and adjusted prevalence ratios using Poisson regression. Twelve maternal and infant factors were assessed across case groups, which included total (explained + unexplained), explained (e.g., syndromic), unexplained, and severe unexplained microcephaly (head circumference <3rd percentile). RESULTS: The birth prevalence for total and total severe microcephaly were 14.7 and 4.8 per 10,000 livebirths, respectively. For explained and unexplained cases, significantly elevated risks were noted for mothers who were older (35+), less educated (≤12 years), diabetic (pre-pregnancy or gestational), or had a preterm delivery. Unlike explained cases, however, mothers who were non-White or smoked had an increased risk for unexplained microcephaly. Furthermore, young maternal age (<20), multiparity, and higher BMI reduced the risk for unexplained microcephaly. For severe unexplained cases, the risk profile was similar to that for all unexplained cases-with the exception of null associations noted for diabetes and birth year. CONCLUSIONS: We found that risk patterns for microcephaly varied across case groupings. Risk factors included maternal race/ethnicity, age, and smoking during pregnancy. Among severe unexplained cases, notable positive associations were seen among mothers who were non-Hispanic Black or less educated, while inverse associations were noted for obesity.

Thyroid Medication Use and Birth Defects in the National Birth Defects Prevention Study.

BACKGROUND: Thyroid disorders are common among reproductive-aged women, with hypothyroidism affecting 2 to 3% of pregnancies, and hyperthyroidism affecting an additional 0.1 to 1%. We examined associations between thyroid medications and individual birth defects using data from the National Birth Defects Prevention Study (NBDPS). METHODS: The NBDPS is a multisite, population-based, case-control study that included pregnancies with estimated delivery dates from 1997 to 2011. We analyzed self-reported thyroid medication use from mothers of 31,409 birth defect cases and 11,536 unaffected controls. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for birth defects with five or more exposed cases, controlling for maternal age, race/ethnicity, and study center. Crude ORs and exact 95% CIs were estimated for defects with 3 to 4 exposed cases. RESULTS: Thyroid hormone was used by 738 (2.3%) case and 237 (2.1%) control mothers, and was associated with anencephaly (OR = 1.68; 95% CI, 1.03-2.73), holoprosencephaly (OR = 2.48; 95% CI, 1.13-5.44), hydrocephaly (1.77; 95% CI, 1.07-2.95) and small intestinal atresia (OR = 1.81; 95% CI, 1.04-3.15). Anti-thyroid medication was used by 34 (0.1%) case and 10 (<0.1%) control mothers, and was associated with aortic valve stenosis (OR = 6.91; 95% CI, 1.21-27.0). CONCLUSION: While new associations were identified, our findings are relatively consistent with previous NBDPS analyses. Our findings suggest thyroid medication use is not associated with most birth defects studied in the NBDPS, but may be associated with some specific birth defects. These results should not be interpreted to suggest that medications used to treat thyroid disease are teratogens, as the observed associations may reflect effects of the underlying thyroid disease. Birth Defects Research 109:1471-1481, 2017.© 2017 Wiley Periodicals, Inc.

Place of Death among Hospitalized Patients with Cancer at the End of Life.

BACKGROUND: The majority of hospital deaths in the United States occur after ICU admission. The characteristics associated with the place of death within the hospital are not known for patients with cancer. OBJECTIVE: The study objective was to identify patient characteristics associated with place of death among hospitalized patients with cancer who were at the end of life. METHODS: A retrospective cohort study design was implemented. Subjects were consecutive patients hospitalized between 2003 and 2007 at a large comprehensive cancer center in the United States. Multinomial logistic regression analysis was used to identify patient characteristics associated with place of death (ICU, hospital following ICU, hospital without ICU) among hospital decedents. RESULTS: Among 105,157 hospital discharges, 3860 (3.7%) died in the hospital: 42% in the ICU, 14% in the hospital following an ICU stay, and 44% in the hospital without ICU services. Individuals with the following characteristics had an increased risk of dying in the ICU: nonlocal residence, newly diagnosed hematologic or nonmetastatic solid tumor malignancies, elective admission, surgical or pediatric services. A palliative care consultation on admission was associated with dying in the hospital without ICU services. CONCLUSIONS: Understanding existing patterns of care at the end of life will help guide decisions about resource allocation and palliative care programs. Patients who seek care at dedicated cancer centers may elect more aggressive care; thus the generalizability of this study is limited. Although dying in a hospital may be unavoidable for patients who have uncontrolled symptoms that cannot be managed at home, palliative care consultations with patients and their families in advance regarding end-of-life preferences may prevent unwanted admission to the ICU.

An evaluation of differences in risk factors for individual types of surgical site infections after colon surgery.

BACKGROUND: Most studies and national programs aggregate the different types of surgical site infections (SSIs) potentially masking and misattributing risk. Determining that risk factors for superficial, deep, and organ space SSIs are unique is essential to improve SSI rates. METHODS: This cohort study utilized data of 59,365 patients who underwent colon resection at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program from 2007 to 2009. Four independent, multivariable, predictive models were developed to assess the unique associations between risk factors and each SSI group: Superficial, deep, organ space, and an aggregate of all 3 types of SSIs. RESULTS: Overall, 13% of colon cases developed SSIs: Superficial (8%), deep (1.4%), and organ space (3.8%). Each model was different. Morbidly obese patients were more likely to develop SSIs than normal weight patients across all models; however, risk factors common to all models (eg, body mass index [BMI], duration of operation, wound class, laparoscopic approach) had very different levels of risk. Unique risks for superficial SSIs include diabetes, chronic obstructive pulmonary disease, and dyspnea. Deep SSIs had the greatest magnitude of association with BMI and the greatest incidence of wound disruption (19.8%). Organ space SSIs were often owing to anastomotic leaks and were uniquely associated with disseminated cancer, preoperative dialysis, preoperative radiation treatment, and a bleeding disorder, suggesting a physically frail or compromised patient may put the anastomosis at risk. CONCLUSION: Risk factors for superficial, deep, and organ space SSI differ. More effective prevention strategies may be developed by reporting and examining each type of SSI separately.