Childbirth fear in the USA during the COVID-19 pandemic: key predictors and associated birth outcomes.

Background and objectives: Childbirth fear, which has been argued to have an adaptive basis, exists on a spectrum. Pathologically high levels of childbirth fear is a clinical condition called tokophobia. As a chronic stressor in pregnancy, tokophobia could impact birth outcomes. Many factors associated with tokophobia, including inadequate labor support, were exacerbated by the COVID-19 pandemic. Methodology: We used longitudinally collected data from a convenience sample of 1775 pregnant persons in the USA to evaluate the association between general and COVID-19 pandemic-related factors and tokophobia using the fear of birth scale. We also assessed associations between tokophobia, low birth weight and preterm birth when adjusting for cesarean section and other covariates among a subset of participants (N = 993). Results: Tokophobia was highly prevalent (62%). Mothers who self-identified as Black (odds ratio (OR) = 1.90), had lower income (OR = 1.39), had less education (OR = 1.37), had a high-risk pregnancy (OR = 1.65) or had prenatal depression (OR = 4.95) had significantly higher odds of tokophobia. Concerns about how COVID-19 could negatively affect maternal and infant health and birth experience were also associated with tokophobia (ORs from 1.51 to 1.79). Tokophobia was significantly associated with increased odds of giving birth preterm (OR = 1.93). Conclusions and implications: Tokophobia increases the odds of preterm birth and is more prevalent among individuals who are Black, have a lower income, and have less education. Tokophobia may, therefore, be an underappreciated contributor to inequities in US birth outcomes. The COVID-19 pandemic likely compounded these effects.

An internet-based survey on the circumstances of food-induced reactions following the diagnosis of IgE-mediated food allergy.

BACKGROUND: Despite careful avoidance measures, food allergic patients have a significant risk of anaphylactic episodes. Risk situations need to be identified for more efficient preventive measures. METHODS: Responders to an internet-based survey on the awareness of food anaphylaxis were invited to relate the circumstances of their most severe reaction following the diagnosis of IgE-mediated food allergy. Items of the questionnaire included the circumstances of the reaction and the treatment, as well as questions related to reactions occurring at specific categories of sites (i.e. home, schools, or restaurants). RESULTS: Fifty-one of the returned questionnaires (34.1%) corresponded to the study criteria. The median age of the subjects was 7 years (range 0.5-61), with 33/51 (64.7%) being less than 16 years of age. Reactions were reported to peanuts (24/51; 47.1%), milk (12/51; 23.5%), tree nuts (6/51; 11.8%), fish and shellfish (5/51; 9.8%), and others (3/51; 5.8%). Reactions occurred at home (13/51; 25.5%), in restaurants (9/51; 17.6%), at school or daycare or kindergarten (8/51; 15.7%), at a relative or friend's home (7/51; 13.7%), at sites of leisure activities (6/51; 11.8%), at work (3/51; 5.9%), in church or a hospital ward (2/51; 3.9% each), or in a food store (1/51; 2.0%). In severe reactions (37/51; 72.5%) epinephrine was administered in 28/37 (75.7%) of the responders. Finally, while most reactions happened after ingestion of the food (40/51; 78.4%), others were reported after skin contact exclusively (8/51; 16%), or after inhalation (3/51; 5.9%). CONCLUSION: Food induced-anaphylaxis in patients aware of their allergy happens most often at sites considered as safe (i.e. home, schools, workplace, hospitals). Better strategies to avoid accidental reactions include clear labelling of forbidden foods and increased information at all levels. These might dramatically reduce the risk of food-induced anaphylaxis in food allergy sufferers.

Lower femoral neck bone mineral density in prepubertal former preterm girls.

The purpose of this case-control study was to determine bone mineral content and areal bone mineral density at various skeletal sites in former preterm girls, aged 7-9 years, and to compare these data with age-matched term controls. Subjects included 25 white, prepubertal, former preterm girls (gestational age 30.8 +/- 0.3 weeks, birthweight 1461 +/- 56 g [mean +/- SEM]). Controls included 50 healthy, white, prepubertal girls born at term and matched for age (two controls per case). Measurements included anthropometric variables, calcium intake according to a food-frequency questionnaire, bone mineral content (BMC; grams), and areal bone mineral density (aBMD; grams per square centimeter), using dual-energy X-ray absorptiometry (DXA) at six skeletal sites. Thirteen preterm girls and 13 age-matched term controls were reassessed 1 year after the first DXA measurement. The former preterm girls were similar to controls in terms of age and height, but were lighter (24.6 +/- 0.6 vs. 27.0 +/- 0.6 kg, p = 0.02). They also reported a higher median calcium intake (1058 vs. 759 mg/day, p = 0.004). aBMD was lower in former preterms compared with controls at the level of the radial metaphysis (0.283 +/- 0.006 vs. 0.298 +/- 0.004, p = 0.04), femoral neck (0.593 +/- 0.011 vs. 0.638 +/- 0.010, p = 0.007), and total hip (0.596 +/- 0.012 vs. 0.640 +/- 0.010, p = 0.007), but was similar between the two groups at the radial diaphysis (0.437 +/- 0.004 vs. 0.436 +/- 0.004) and femoral diaphysis (1.026 +/- 0.015 vs. 1.030 +/- 0.011). Femoral neck aBMD remained lower compared with controls in the subgroup of preterm girls reassessed after 1 year (0.608 +/- 0.017 vs. 0.672 +/- 0.020, p = 0.02). In random effects models for longitudinal data, taking into account the effects of age, weight, and height on aBMD (dependent variable), femoral neck aBMD remained lower in former preterms (p < 0.001). Prepubertal former preterm girls showed growth recovery, but had lower aBMD at the hip and radial metaphysis than age-matched term controls, despite spontaneously higher calcium intake. Preterm girls had similar aBMD results compared with controls at sites with predominantly cortical bone (radial and femoral diaphysis), which are known to be more sensitive to calcium intake.

Effects of cisapride on ventricular depolarization-repolarization and arrhythmia markers in infants.

To study prospectively the effects of cisapride on ventricular repolarization, depolarization, and arrhythmia markers in neonates, we determined before and three days after starting cisapride (1 mg/kg/day): corrected QT interval (QTc) and QT dispersion (QTd) on standard ECGs, and duration of filtered QRS (fQRS) and of low amplitude (<40 microV) terminal signals (LAS40, ms) and root mean square of the last 40 ms (RMS40, microV) using high-gain signal-averaged ECG (SAECG). Twenty-four term and 11 preterm infants (gestational age 23-35 weeks) were studied at a median chronological age of 32 days. QTc and QTd were not different between term and preterm infants. Cisapride lengthened QTc (mean +/- SD; ms: 396.6 +/- 24.8 before vs. 417.0 +/- 35.2 after, p < 0.001). Three term and two preterm infants (5/35 = 14%; 95% CI: 5-30%) had a QTc >450 ms after cisapride. QTd after cisapride increased significantly in all infants with prolonged QTc. Filtered QRS, LAS40, and RMS40 before and after cisapride were within our normal values. We conclude that cisapride prolongs ventricular repolarization in neonates and infants without altering depolarization. Although no clinical arrhythmias were observed the dose of 0.8 mg/kg/day should not be exceeded.

An Internet-based survey of anaphylactic reactions to foods.

BACKGROUND: A favorable outcome of anaphylaxis depends on the rapidity of adequate initial management and epinephrine injection. However, few data on the management of anaphylactic reactions are available. The aim of this study was to investigate the management and awareness of anaphylaxis to foods by mean of an Internet-based survey. METHODS: Visitors to a website with information on food allergy were invited to join the survey. Items in the survey included the management of anaphylactic reactions, investigations done by the diagnosing physician, and information given to the responder in anticipation of a new anaphylactic reaction. RESULTS: Almost all of the 264 responders were from North America, Europe, Australia, or New Zealand (263/264). The most recent reaction was treated by epinephrine injection in 68.7% (180/262) of cases, or by antihistamines in 14.1% (37/262). Epinephrine was the first treatment for the most severe reaction in only 43.9% (101/230), while antihistamines were given first in 43.5% (100/230). One-third (62/210 = 29.5%) of the responders diagnosed by a physician received neither a diagnostic blood test nor a skin test. Responders diagnosed by an allergist were more often investigated (91/105 = 86.7%) than those diagnosed by a pediatrician or an internist (29/44 = 65.9%), a general practitioner (22/45 = 48.9%), or another physician (6/16 = 37.5%) (P < 0.001). Most responders had received instructions on how to deal with a new episode of anaphylaxis (244/263 = 92.8%). Responders instructed by an allergist were most frequently satisfied with the instructions (115/131 = 87.8%). CONCLUSION: A large number of responders did not receive epinephrine for treatment of their most severe, or most recent anaphylactic reaction, and did not undergo allergy tests. The conventional management of anaphylaxis might still be improved.

Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localising signs.

UNLABELLED: Fever without localising signs in very young children remains a diagnostic problem. Until present, a clinical scoring system combined with leucocyte count, urine analysis and determination of CRP are recognised as being helpful to identify patients at risk of serious bacterial illness. In this study we asked the question whether the determination of procalcitonin (PCT), interleukin (IL)-6, IL-8 and interleukin-1 receptor antagonist (IL- Ra) was superior to these commonly used markers for the prediction of a serious bacterial infection (SBI). Children, 7 days to 36 months of age, with a rectal temperature above 38 degrees C and without localising signs of infection were prospectively enrolled. For each infant, we performed a physical examination, a clinical score according to McCarthy, a complete white cell count, an urine analysis and a determination of CRP. We further determined PCT, IL-6, IL-8, and IL-1Ra concentrations and compared their predictive value with those of the usual management of fever without localising signs. Each infant at risk of SBI had blood culture, urine and cerebrospinal fluid cultures when indicated, and received antibiotics until culture results were available. A total of 124 children were included of whom 28 (23%) had SBI. Concentrations of PCT, CRP and IL-6 were significantly higher in the group of children with SBI but IL-8 and IL-1Ra were comparable between both groups. PCT showed a sensitivity of 93% and a specificity of 78% for detection of SBI and CRP had a sensitivity of 89% and a specificity of 75%. CONCLUSION: Compared to commonly used screening methods such as the McCarthy score, leucocyte count and other inflammatory markers such as interleukin-6, interleukin-8 and interleukin- receptor antagonist, procalcitonin and C-reactive protein offer a better sensitivity and specificity in predicting serious bacterial infection in children with fever without localising signs.

Vitamin D supplementation during infancy is associated with higher bone mineral mass in prepubertal girls.

The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and/or areal bone mineral density (aBMD) in later childhood. The design was a retrospective cohort study. One hundred and six healthy prepubertal Caucasian girls (median age, 8 yr; range, 7-9 yr) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a questionnaire sent to participating families and their pediatricians. Bone area (square centimeters) and bone mineral content (grams) were determined by dual energy x-ray absorptiometry at six skeletal sites. Vitamin D receptor (VDR) 3'-gene polymorphisms (BsmI) were also determined. The supplemented (n = 91) and unsupplemented (n = 15) groups were similar in terms of season of birth, growth in the first year of life, age, anthropometric parameters, and calcium intake at time of dual energy x-ray absorptiometry. The supplemented group had higher aBMD at the level of radial metaphysis (mean +/- SEM, 0.301+/-0.003 vs. 0.283+/-0.008; P = 0.03), femoral neck (0.638+/-0.007 vs. 0.584+/-0.021; P = 0.01), and femoral trochanter (0.508+/-0.006 vs. 0.474+/-0.016; P = 0.04). At the lumbar spine level aBMD values were similar (0.626+/-0.006 vs. 0.598+/-0.019; P = 0.1). In a multiple regression model taking into account the effects of vitamin D supplementation, height, and VDR genotype on aBMD (dependent variable), femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group (P = 0.02). Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls.

Intestinal permeability before and after ibuprofen in families of children with Crohn's disease.

BACKGROUND: Members of a subset of first-degree relatives of adults with Crohn's disease have been shown to have an increased baseline intestinal permeability and/or an exaggerated increase in intestinal permeability after the administration of acetylsalicylic acid. PURPOSE: To determine intestinal permeability in unaffected first-degree relatives of children with Crohn's disease before and after the administration of an ibuprofen challenge. METHODS: Lactulose-mannitol ratios, a measure of intestinal permeability, were determined in 14 healthy control families (41 subjects) and 14 families with a child with Crohn's disease (36 relatives, 14 probands) before and after ingestion of ibuprofen. An upper reference limit was defined using the control group as mean +/- 2 SD. RESULTS: The proportion of healthy, first-degree relatives with an exaggerated response to ibuprofen (20%, 95% CI 7% to 33%) was significantly higher than controls (P = 0.003). The exaggerated response was more common among siblings than among parents of pediatric probands. CONCLUSIONS: Members of a subset of first-degree relatives of children with Crohn's disease have an exaggerated increase in intestinal permeability after ibuprofen ingestion. These findings are compatible with there being a genetic link between abnormalities of intestinal permeability and Crohn's disease.

Catch-up growth in children treated with home enteral nutrition.

OBJECTIVE: This study was designed to determine the effect of home enteral nutrition on the outcomes of growth and the relationship between growth and entrance anthropometric criteria. METHODS: We reviewed the medical records of 78 consecutive children (median age, 20 months) who were enrolled in the home enteral feeding program at the Alberta Children's Hospital (Calgary, Alberta, Canada) between 1993 and 1995. Weights, heights, and weight-for-heights were expressed as Z scores, using the Centers for Disease Control and Prevention anthropometric growth curve software. To evaluate growth outcome, the total group was further subdivided using anthropometric criteria into appropriate, wasted, or stunted at the time of entry to the program. In a subgroup of 36 children on whom anthropometric data was available for a median length of 5.7 months, Z scores were compared at 3 points in time: before entry, at time of entry, and last follow-up. RESULTS: Patients were classified into five main groups: 11 (14%) had pulmonary disease, 26 (33%) had a gastrointestinal disorder, 21 (27%) had congenital defects, 10 (13%) had a neurologic disorder, and the remaining 10 (13%) had a variety of other illnesses, including malignancies and metabolic disorders. Patients were on the program for a median duration of 8.9 months. It was found that during the period of support within the program, enteral feeding was successful in improving weight-for-age Z scores by 0.42 standard deviations but the effect on height-for-age Z scores and weight-for-height Z scores did not reach significance for this population. The subgroup of 36 children on whom longitudinal anthropometric data was available before entering the program was found to have had a significant drop in weight Z scores between the time before program entry (median length of time, 5.7 months) and the time of program entry, which indicates that these children were falling off the growth curve before commencing enteral feeding. To evaluate growth outcome, the total group was further subdivided using anthropometric criteria into appropriate, wasted, or stunted at the time of entry to the program. In the group of appropriate growth patients, while in the program, 50% had catch-up growth for weight (positive change in Z scores) and 33% for height. In the wasted patients, 92% improved their weight percentile and 75% their height percentile. In the stunted group, 71% had catch-up growth for weight and 74% for height. CONCLUSION: We concluded that the enteral feeding program was able to promote catch-up growth or maintain growth along percentiles in the majority of children.

Plasma L-arginine concentration, oxygenation index, and systemic blood pressure in premature infants.

OBJECTIVE: To determine the relationships between plasma L-arginine concentrations and the severity of respiratory distress syndrome (RDS) or systemic blood pressure in premature infants. DESIGN: Prospective, observational study. SETTING: Neonatal intensive care, tertiary referral hospital. SUBJECTS: Fifty-three premature infants. INTERVENTIONS: We measured arginine and nutritional intake, plasma arginine concentration, total amino acid concentrations, and blood pressure on days 3, 7, 14, and 21 of life. In 33 infants who received assisted ventilation, oxygenation index could be calculated to reflect the severity of RDS. The relationships between plasma arginine and oxygenation index or blood pressure were analyzed using multiple linear regression. MEASUREMENTS AND MAIN RESULTS: On day 3, plasma arginine concentrations were decreased compared with normal published values. Arginine concentrations increased with the day of life of measurement (p < .001) and with arginine intake (p < .001). After adjusting for arginine intake and day of life, an inverse relationship was found between oxygenation index and plasma arginine concentrations: (p = .025). No similar relationship was found between oxygenation index and the concentration of total amino acids. A weak positive relationship was found between plasma arginine concentration and systemic blood pressure. CONCLUSIONS: Increments in the oxygenation index, reflective of an increased severity of RDS, are associated with a decrease in plasma arginine concentration. This finding may reflect arginine consumption by the nitric oxide synthase pathway in the lungs of premature infants with RDS, or may be explained by increased arginine catabolism. The lack of a similar relationship between total plasma amino acids and oxygenation index supports the first interpretation.

Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis.

OBJECTIVE: To determine whether L-arginine concentrations (the substrate for nitric oxide synthesis) are lower in premature infants in whom necrotizing enterocolitis (NEC) develops than in unaffected infants. METHODS: We measured arginine and nutritional intake, plasma arginine, glutamine, total amino acids, and ammonia concentrations in 53 premature infants (mean gestational age +/- SD: 27 +/- 1.7 weeks) at risk of NEC. Measurements were done on days 3, 7, 14 and 21 and just before treatment in infants with NEC. RESULTS: Necrotizing enterocolitis developed in 11 infants between postnatal days 1 and 26. On day 3, plasma arginine concentrations were decreased compared with normal published values (mean +/- SE, 41 mumol/L +/- 4). Arginine concentrations increased with day of life of measurement (p < 0.001) and arginine intake (p < 0.001). Plasma arginine concentrations were significantly lower at the time of diagnosis in infants with NEC compared with control subjects, even after adjusting for arginine intake and day of life (p = 0.032). Plasma glutamine and total amino acid concentrations were not significantly different in infants with NEC compared with control subjects. Plasma ammonia concentrations were elevated on day 3 (mean +/- SE, 72 +/- 3.3 mumol/L) and decreased with postnatal age (p < 0.001) and increasing plasma arginine concentrations (p < 0.001). CONCLUSION: Plasma arginine concentrations are decreased at the time of diagnosis in premature infants with NEC. The potential benefit of arginine supplementation in the prevention of the disease deserves evaluation.

Mitochondrial abnormalities of liver in two children with citrullinaemia.

Citrullinaemia is a rare inborn error of urea-cycle metabolism. Two affected children are reported in whom progressive metabolic instability suggested the possibility of hepatopathy or an ongoing hepatic mitochondrial injury. A percutaneous liver biopsy was performed in each patient. Electron-microscopic findings were similar in both cases. Approximately 20% of the mitochondria were abnormally enlarged with paracrystalline inclusions and electron-dense bodies of different sizes and shapes present in the matrix. The specificity of these findings is discussed in the context of previous reports of ultrastructural abnormalities in the hepatocytes of patients with inborn errors of the urea cycle. It is speculated that the mitochondrial abnormalities in citrullinaemia may be related to the accumulation of citrulline in the mitochondria which may eventually manifest as metabolic instability.