Beyond TORCH: A narrative review of the impact of antenatal and perinatal infections on the risk of disability.

Infections and inflammation during pregnancy or early life can alter child neurodevelopment and increase the risk for structural brain abnormalities and mental health disorders. There is strong evidence that TORCH infections (i.e., Treponema pallidum, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes virus) alter fetal neurodevelopment across multiple developmental domains and contribute to motor and cognitive disabilities. However, the impact of a broader range of viral and bacterial infections on fetal development and disability is less well understood. We performed a literature review of human studies to identify gaps in the link between maternal infections, inflammation, and several neurodevelopmental domains. We found strong and moderate evidence respectively for a higher risk of motor and cognitive delays and disabilities in offspring exposed to a range of non-TORCH pathogens during fetal life. In contrast, there is little evidence for an increased risk of language and sensory disabilities. While guidelines for TORCH infection prevention during pregnancy are common, further consideration for prevention of non-TORCH infections during pregnancy for fetal neuroprotection may be warranted.

Feeding volume advancement in preterm neonates: A level 4 neonatal intensive care unit quality improvement initiative.

INTRODUCTION: Because of provider variability in feeding guideline application, a quality improvement (QI) initiative was begun to better standardize feeding initiation and advancement for preterm infants. Our specific, measurable, achievable, relevant, and timely aims included decreasing the time to reach full feeds by 35% and reducing the duration of central lines by 30% over 12 months in infants born between 25 and 30 weeks' gestation or with birth weight between 600 and 1250 g. METHODS: Registered dietitians tracked central line days, parenteral nutrition (PN), enteral nutrition, fortification, guideline adherence, anthropometrics, necrotizing enterocolitis (NEC) cases, and central line-associated bloodstream infections (CLABSIs). QI progress charts were reviewed monthly. RESULTS: Mean central line days decreased from 7.3 to 5.8. Days of PN decreased from 6.7 to 5.1. The day of life that enteral feeds were started decreased from 1.1 to 0.5. The number of days between starting enteral feeds and adding fortification decreased from 3.4 to 2.3 days. Full enteral feeds were achieved on average 2 days earlier. Birth weight was regained at around 10.2 days of life before the guideline was implemented and at a mean of 9.6 days after the guideline. There was no increase in cases of CLABSI or diagnoses of NEC. CONCLUSION: After implementation of this feeding QI initiative at a level 4 neonatal intensive care unit, central line duration and PN use were decreased and infants reached full enteral feeds earlier without changes in cases of NEC, CLABSI, or time to regain birth weight.

Effectiveness of a care bundle for primary prevention of intraventricular hemorrhage in high-risk neonates: a Bayesian analysis.

OBJECTIVE: To determine whether an intraventricular hemorrhage (IVH) prevention bundle featuring midline-elevated positioning reduced IVH among high-risk infants. STUDY DESIGN: In a retrospective study design, we compared outcomes of infants <1250 grams birth weight or <30 weeks gestation before (N = 205) and after (N = 360) implementation of an IVH prevention bundle, using Bayesian and frequentist logistic regression to determine whether the intervention decreased any grade IVH. RESULTS: In both the Bayesian and frequentist analyses, there was no difference in odds of any grade IVH before and after the implementation of the prevention bundle (OR 0.993; 95% Credible Interval 0.751-1.323 and OR 1.23; 95% Confidence Interval 0.818-1.864 respectively). Bias analyses suggested that these results were robust to bias from potential deaths attributable to IVH. CONCLUSION: In this retrospective analysis, we found no evidence for a protective effect of an IVH prevention bundle on IVH incidence among high-risk neonates at a level IV NICU.

Mixed-method study to assess the feasibility, acceptability and early effectiveness of the Hospital to Home programme for follow-up of high-risk newborns in a rural district of Central Uganda: a study protocol.

INTRODUCTION: A follow-up programme designed for high-risk newborns discharged from inpatient newborn units in low-resource settings is imperative to ensure these newborns receive the healthiest possible start to life. We aim to assess the feasibility, acceptability and early outcomes of a discharge and follow-up programme, called Hospital to Home (H2H), in a neonatal unit in central Uganda. METHODS AND ANALYSIS: We will use a mixed-methods study design comparing a historical cohort and an intervention cohort of newborns and their caregivers admitted to a neonatal unit in Uganda. The study design includes two main components. The first component includes qualitative interviews (n=60 or until reaching saturation) with caregivers, community health workers called Village Health Team (VHT) members and neonatal unit staff. The second component assesses and compares outcomes between a prospective intervention cohort (n=100, born between July 2019 and September 2019) and a historical cohort (n=100, born between July 2018 and September 2018) of infants. The historical cohort will receive standard care while the intervention cohort will receive standard care plus the H2H intervention. The H2H intervention comprises training for healthcare workers on lactation, breast feeding and neurodevelopmentally supportive care, including cue-based feeding, and training to caregivers on recognition of danger signs and care of their high-risk infants. Infants and their families receive home visits until 6 months of age, or longer if necessary, by specially trained VHTs. Quantitative data will be analysed using descriptive statistics and regression analysis. All results will be stratified by cohort group. Qualitative data will be analysed guided by Braun and Clarke's thematic analysis technique. ETHICS AND DISSEMINATION: This study protocol was approved by the relevant Ugandan ethics committees. All participants will provide written informed consent. We will disseminate through peer-reviewed publications and key stakeholders and public engagement. TRIAL REGISTRATION NUMBER: ISRCTN51636372; Pre-result.

Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State.

BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001). CONCLUSION: Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.

Factors Associated With Opioid Prescribing for Distal Upper Extremity Fractures at a Pediatric Emergency Department.

OBJECTIVE: The aims of this study were to describe the prescribing patterns of oxycodone for patients with distal upper extremity fractures and to evaluate factors that influence the quantity of oxycodone prescribed at discharge. METHODS: We retrospectively studied oxycodone prescriptions for patients with upper extremity fractures presenting to a single center tertiary pediatric emergency department (ED) from June 1, 2014, to May 31, 2016. We used logistic regression models to evaluate the association of opioid administration in the ED, fracture reduction under ketamine sedation, initial pain scores (low, medium, and high), patient demographics, and type of prescriber (residents, attendings, fellows, and advanced registered nurse practitioners) with oxycodone prescription at discharge and the number of doses prescribed (≤12 or >12 doses). RESULTS: A total of 1185 patients met the inclusion criteria. Of these, 669 (56%) were prescribed oxycodone at discharge. Children with fractures requiring reduction had 13 times higher odds [95% confidence interval (CI), 9.45-20.12] of receiving an oxycodone prescription compared with children with fractures not requiring reduction. Opioid administration in the ED was associated with 7.5 times higher odds (95% CI, 5.41-10.51) of receiving an outpatient prescription. Children were more likely to have a higher quantity of oxycodone prescribed if they had a fracture reduction in the ED [odds ratio (OR), 1.73; 95% CI, 1.20-2.50], received an opioid in the ED (OR, 2.13; 95% CI, 1.43-3.20), or received their prescription from an emergency medicine resident (OR, 2.8; 95% CI, 1.44-5.74). CONCLUSIONS: Opioid prescribing differs based on patient- and provider-related factors. Given the variability in prescribing patterns, changing suggested opioid prescriptions in the electronic medical record may lead to more consistent practice and therefore decrease unnecessary prescribing while still ensuring adequate outpatient analgesia.

The fetal origins of mental illness.

The impact of infections and inflammation during pregnancy on the developing fetal brain remains incompletely defined, with important clinical and research gaps. Although the classic infectious TORCH pathogens (ie, Toxoplasma gondii, rubella virus, cytomegalovirus [CMV], herpes simplex virus) are known to be directly teratogenic, emerging evidence suggests that these infections represent the most extreme end of a much larger spectrum of injury. We present the accumulating evidence that prenatal exposure to a wide variety of viral and bacterial infections-or simply inflammation-may subtly alter fetal brain development, leading to neuropsychiatric consequences for the child later in life. The link between influenza infections in pregnant women and an increased risk for development of schizophrenia in their children was first described more than 30 years ago. Since then, evidence suggests that a range of infections during pregnancy may also increase risk for autism spectrum disorder and depression in the child. Subsequent studies in animal models demonstrated that both pregnancy infections and inflammation can result in direct injury to neurons and neural progenitor cells or indirect injury through activation of microglia and astrocytes, which can trigger cytokine production and oxidative stress. Infectious exposures can also alter placental serotonin production, which can perturb neurotransmitter signaling in the developing brain. Clinically, detection of these subtle injuries to the fetal brain is difficult. As the neuropsychiatric impact of perinatal infections or inflammation may not be known for decades after birth, our construct for defining teratogenic infections in pregnancy (eg, TORCH) based on congenital anomalies is insufficient to capture the full adverse impact on the child. We discuss the clinical implications of this body of evidence and how we might place greater emphasis on prevention of prenatal infections. For example, increasing uptake of the seasonal influenza vaccine is a key strategy to reduce perinatal infections and the risk for fetal brain injury. An important research gap exists in understanding how antibiotic therapy during pregnancy affects the fetal inflammatory load and how to avoid inflammation-mediated injury to the fetal brain. In summary, we discuss the current evidence and mechanisms linking infections and inflammation with the increased lifelong risk of neuropsychiatric disorders in the child, and how we might improve prenatal care to protect the fetal brain.

Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.

Importance: The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero. Objective: To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy. Design, Setting, and Participants: A total of 1 791 520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018. Exposures: Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection. Main Outcomes and Measures: Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring. Results: A total of 1 791 520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32 125 813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; depression: HR, 1.24; 95% CI, 0.88-1.73) or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30; 95% CI, 1.04-1.61) and were robust to moderate unknown confounding. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero. Conclusions and Relevance: These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child's life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.

Factors Affecting Length of Postoperative Hospitalization for Pediatric Cardiac Operations in a Large North American Registry (1982-2007).

Surgical treatment of congenital heart disease represents a major cause of pediatric hospitalization and healthcare resource use. Larger centers may provide more efficient care with resulting shorter length of postoperative hospitalization (LOH). Data from 46 centers over 25 years were used to evaluate whether surgical volume was an important determinant of LOH using a competing risk regression strategy that concurrently accounted for deaths, transfers, and discharges with some time interactions. Earlier discharge was more likely for infants and older children compared to neonates [subhazard ratios at postoperative day 6 of 1.64 (99 % confidence interval (CI) 1.57, 1.72) and 2.67 (99 % CI 2.53, 2.80), respectively], but less likely for patients undergoing operations in Risk Adjustment for Congenital Heart Surgery categories 2, 3, 4, and 5/6 compared to category 1 [subhazard ratios at postoperative day 6 of 0.66 (99 % CI 0.64, 0.68), 0.34 (95 % CI 0.33, 0.35), 0.28 (99 % CI 0.27, 0.30), and 0.10 (99 % CI 0.09, 0.11), respectively]. There was no difference by sex [non-time-dependent subhazard ratio 1.019 (99 % CI 0.995, 1.040)]. For every 100-operation increase in center annual surgical volume, the non-time-dependent subhazard for discharge was 1.035 (99 % CI 1.006, 1.064) times greater, and center-specific exponentiated random effects ranged from 0.70 to 1.42 with a variance of 0.023. The conditional discharge rate increased with increasing age and later era. No sex-specific difference was found. Centers performing more operations discharged patients sooner than lower volume centers, but this difference appears to be too small to be of clinical significance. Interestingly, unmeasured institutional characteristics estimated by the center random effects were variable, suggesting that these played an important role in LOH and merit further investigation.

Hiatal hernia repair in laparoscopic adjustable gastric banding and laparoscopic Roux-en-Y gastric bypass: a national database analysis.

Hiatal hernia (HH) repairs are commonly done concomitantly with laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB) to decrease gastroesophageal reflux disease (GERD). There is limited evidence about the additional surgical risk these combined procedures engender. We used the United States Nationwide Inpatient Sample 2004-2009 to compare mortality risk, prolonged length of stay (PLOS), and perioperative adverse events using propensity score-matched analysis. We repeated the analysis after removing patients diagnosed with GERD. There were 42,272 weighted patients undergoing LRYGB alone representing 206,559 discharges nationally and an additional 1,945 and 9,060, respectively, undergoing LRYGB + HH repair. For LAGB, there were 10,558 records representing 52,901 LAGB-only discharges and 1,959 representing 9,893 LAGB + HH repair discharges. Thirty-eight percent (95 % CI: 36, 41 %) of the patients in the LRYGB-only group had GERD compared to 55 % (51, 59 %) in the LRYGB + HH repair group. Among the LAGB groups, 31 % (28, 34 %) of LAGB-only patients had GERD compared to 44 % (38, 49 %) in the LAGB + HH repair group. We find that the average treatment effect on the treated (considering the concomitant procedure as treatment and the single procedure as control) for PLOS was -0.12353 (-0.15909, -0.08797) between the LRYGB groups and -0.04353 (-0.07488, -0.01217) for the LAGB groups. We find no evidence of increased risk of perioperative adverse events among patients undergoing concomitant HH repair with LRYGB or LAGB. Patients undergoing the combined procedure appear to be at lower risk of PLOS; this may be due to surgical training norms.

Gastric bypass after liver transplantation.

Few data are available for assessing the outcomes of bariatric surgery for patients who have undergone orthotopic liver transplantation (OLT). The University of Minnesota bariatric surgery database and transplant registry were retrospectively reviewed to identify patients who had undergone OLT and then open Roux-en-Y gastric bypass (RYGB) surgery between 2001 and 2009. Comorbidity-appropriate laboratory values, body mass indices (BMIs), histopathology reports, and immunosuppressive regimens were collected. Seven patients were identified with a mean age of 55.4 ± 8.64 years and a mean follow-up of 59.14 ± 41.49 months from the time of RYGB. The mean time between OLT and RYGB was 26.57 ± 8.12 months. The liver disease etiologies were hepatitis C (n = 4), jejunoileal bypass surgery (n = 1), hemangioendothelioma (n = 1), and alcoholic cirrhosis (n = 1). There were 2 deaths for patients with hepatitis C 6 and 9 months after bariatric surgery due to multiple-organ dysfunction syndrome and metastatic esophageal squamous carcinoma, respectively. One patient with hepatitis C required a reversal of the RYGB because of malnutrition and an inability to tolerate oral intake. Four of the 7 patients had type 2 diabetes mellitus (T2DM), 4 had hypertension, and 6 patients had dyslipidemia. All patients were on immunosuppressive medications, but only 4 were on corticosteroids. Glycemic control was improved in all surviving patients with T2DM. The mean BMI was 34.27 ± 5.51 kg/m(2) before OLT and 44.34 ± 6.08 kg/m(2) before RYGB; it declined to 26.47 ± 5.53 kg/m(2) after RYGB. In conclusion, in this case series of patients undergoing RYGB after OLT, we observed therapeutic weight loss, improved glycemic control, and improved high-density lipoprotein levels in the presence of continued dyslipidemia. RYGB may have contributed to the death of 1 patient due to multiple-organ dysfunction syndrome.

Benefits and complications of the duodenal switch/biliopancreatic diversion compared to the Roux-en-Y gastric bypass.

BACKGROUND: Despite providing superb excess weight loss and increased resolution of comorbid diseases, such as type 2 diabetes mellitus, compared to other bariatric procedures, the duodenal switch/ biliopancreatic diversion (DS/BD) has not gained widespread acceptance among patients and physicians. In this study, we investigated outcomes, symptoms and complications among postsurgical DS patients compared to RYGB patients. METHODS: We used propensity scores to retrospectively match patients who underwent DS/BD between 2005 and 2010 to comparable Roux-en-Y gastric bypass (RYGB) patients. We then reviewed patient charts, and surveyed patients using the University of Minnesota Bariatric Surgery Outcomes Survey tool to track outcomes, comorbid illnesses and complications. RESULTS: One hundred ninety consecutive patients underwent primary DS/BD between 2005 and 2010 at the University of Minnesota Medical Center. There were 178 patients available for follow-up (93.7%) who were matched to 139 RYGB patients. Type 2 diabetes, hypertension, and hyperlipidemia all significantly improved in each group. Improvements were significantly higher in the DS/BD group. Percent total weight loss was not different between groups. Loose stools and bloating symptoms were more frequently reported among DS/BD patients. With the exception of increased emergency department visits among DS/BD patients (P < .01), overall complication rates were not significantly different between DS/BD and RYGB. There was no difference in mortality rates between the groups. CONCLUSION: The DS/BD is a robust procedure that engenders both superior weight loss and improvement of major comorbidities. Complication and adverse event rates are similar to those of RYGB.