Accidental uterine extensions in cesarean deliveries - outcome of subsequent pregnancy.

OBJECTIVES: To explore the obstetric, maternal and neonatal outcome in the subsequent pregnancy after a pregnancy with an accidental uterine extension (AUE) during cesarean delivery (CD), as well as the relationship between the different types of AUE (inferior, lateral and superior). METHODS: A retrospective cohort study of all CD with AUE in a tertiary medical center between 01/2011-01/2022. Women with a prior CD with AUE were compared to a 1:3 ratio matched control group of women with a prior CD without AUE. All AUE were defined in their direction, size and mode of suturing. CD with deliberate uterine extensions were excluded. We evaluated obstetric, maternal and neonatal outcomes in the subsequent pregnancy after a pregnancy with AUE during CD. RESULTS: Comparing women with a prior CD with AUE (n=177) to the matched control group of women with a prior CD without AUE (n=528), we found no significant differences in proportions of uterine rupture or any other major complication or adverse outcome between the groups. There were no significant differences in the outcomes of the subsequent pregnancy in relation to the characteristics of the AUE (direction, size and mode of suturing). CONCLUSIONS: Subsequent pregnancies after AUE are not associated with higher maternal or neonatal adverse outcomes including higher proportions of uterine rupture compared to pregnancies without previous AUE. Different characteristics of the AUE do not impact the outcome.

Sexual health in adolescents with inflammatory bowel disease - The paediatric gastroenterologists' point of view.

AIM: Although sexual health (SH) impairment and sexually transmitted infections (STI) are occasionally encountered in patients with inflammatory bowel disease (IBD), paediatric gastroenterologists (PedGI) do not often discuss these issues. Literature about SH in the paediatric IBD population is limited. We aimed to assess PedGI knowledge and common practice related to sexual advice and STI workups in patients with IBD. METHODS: A questionnaire comprising 25 questions addressing sexual activity in youth, SH, recommendations, and workup for STI in adolescents with IBD was sent to all registered PedGI in Israel. RESULTS: Fifty-two physicians completed the questionnaire (27 males,52%). Only 50% correctly predicted the mean age that Israeli youth start practicing sex. Seventy-five per cent responded that providers should discuss sexual activity with their patients, but only 19% do so, most often in response to a patient's query. Ninety six percent answered that they do not have enough knowledge about SH in IBD. Finally, only 2% obtain rectal swabs for STI in patients with refractory proctitis. CONCLUSION: Sexual issues and recommendations are not routinely discussed by the majority of PedGI in paediatric IBD clinics. Providers should obtain more knowledge in the field and initiate discussion of these issues with adolescent patients with IBD.

Pregnancy Outcomes after Uterine Preservation Surgery for Placenta Accreta Spectrum: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to investigate maternal and neonatal outcomes in subsequent pregnancies of women with a history of placenta accreta spectrum (PAS) compared with women without history of PAS. STUDY DESIGN: A retrospective cohort study conducted at a single tertiary center between March 2011 and January 2022. We compared women with a history of PAS who had uterine preservation surgery and a subsequent pregnancy, to a control group matched in a 1:5 ratio. The primary outcome was the occurrence of a composite adverse outcome (CAO) including any of the following: uterine dehiscence, uterine rupture, blood transfusion, hysterectomy, neonatal intensive care unit admission, and neonatal mechanical ventilation. Multivariable logistic regression was performed to evaluate associations with the CAO. RESULTS: During the study period, 287 (1.1%) women were diagnosed with PAS and delivered after 25 weeks of gestation. Of these, 32 (11.1%) women had a subsequent pregnancy that reached viability. These 32 women were matched to 139 controls. There were no significant differences in the baseline characteristics between the study and control groups. Compared with controls, the proportion of CAO was significantly higher in women with previous PAS pregnancy (40.6 vs. 19.4%, p = 0.019). In a multivariable logistic regression analysis, previous PAS (adjusted odds ratio [aOR] = 3.31, 95% confidence interval [CI] = 1.09-10.02, p = 0.034) and earlier gestational age at delivery (aOR = 3.53, 95% CI = 2.27-5.49, p < 0.001) were independently associated with CAOs. CONCLUSION: A history of PAS in a previous pregnancy is associated with increased risk of CAOs in subsequent pregnancies. KEY POINTS: · The uterine-preserving approach for PAS delivery is gaining more attention and popularity in recent years.. · Women with a previous pregnancy with PAS had higher rates of CAOs in subsequent pregnancies.. · Previous PAS pregnancy is an independent factor associated with adverse outcomes..

Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis.

OBJECTIVES: To characterize the clinical course of acute pancreatitis (AP) in pediatric inflammatory bowel disease (IBD) patients compared to children with AP without IBD and to identify risk factors associated with AP among IBD patients. METHODS: This retrospective, single-center study compared clinical characteristics of children (<19 years) with AP with and without concomitant IBD who were hospitalized 2005-2019. We also conducted a risk factor analysis of AP development in pediatric IBD. RESULTS: Sixty-eight (54% males) patients with 120 episodes of AP were admitted at a median age of 15.3 years. Thirteen patients (14 episodes) had a co-diagnosis of IBD, representing 4% of our IBD patient population. The AP-IBD patients presented with lower amylase levels compared to the non-IBD patients (160 [interquartile range, IQR: 83-231] vs. 418 [IQR: 176-874] U/L, p > 0.01), all had a mild pancreatitis, and none required invasive intervention. The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. The only risk factor for AP development among IBD patients was IBD-associated arthritis (23% vs. 3% for IBD-non-AP, p = 0.04), while extracolonic Crohn's disease and induction therapy with nutrition were negative risk factors (15% vs. 51%, p = 0.05, and 8% vs. 44%, p = 0.04, respectively). Other parameters, including disease type and medications, were nonsignificant. CONCLUSION: The clinical course of AP in pediatric IBD patients is mild. Only IBD-associated arthritis emerged as a risk factor for the development of AP, while, unexpectedly, IBD medication did not.

STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND OBJECTIVES: Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. METHODS: This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. RESULTS: Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 µg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. CONCLUSION: Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

Fertility preservation parameters in patients with haematologic malignancy: a systematic review and meta-analysis.

Patients with haematologic malignancies represent one of the most common groups referred for fertility preservation before gonadotoxic oncological treatment. The aim of this systematic review and meta-analysis was to evaluate the effect of haematologic cancer on ovarian reserve and response to ovarian stimulation compared with healthy controls. A total of eight observative studies were included in the final quantitative analysis. Despite a younger age (mean difference -4.17, 95% CI -6.20 to -2.14; P < 0.0001), patients with haematologic malignancy had lower serum anti-Müllerian hormone levels compared with the control group (MD -1.04, 95% CI -1.80 to -0.29; P = 0.007). The marginally higher total recombinant FSH dose (MD 632.32, 95% CI -187.60 to 1452.24; P = 0.13) and significantly lower peak oestradiol serum level (MD -994.05, 95% CI -1962.09 to -26.02; P = 0.04) were demonstrated in the study group compared with the healthy controls. A similar number of retrieved oocytes were achieved in both groups (MD 0.20, 95% CI -0.80 to 1.20; P = 0.69). In conclusion, haematologic malignancies may detrimentally affect ovarian function manifesting in decreased AMH serum levels despite a younger age compared with healthy controls. This effect can be overcome by the application of relevant IVF protocols and stimulation doses to achieve an adequate oocyte yield.

24-Hour Compared With 12-Hour Mifepristone-Misoprostol Interval for Second-Trimester Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare 24-hour and 12-hour mifepristone-to-misoprostol intervals for second-trimester medication abortion. METHODS: We conducted a prospective randomized controlled trial. Participants were allocated to receive mifepristone either 24 hours or 12 hours before misoprostol administration. The primary outcome was the time from the first misoprostol administration to abortion (induction time). Secondary outcomes included the time from mifepristone to abortion (total abortion time); fetal expulsion percentages at 12, 24, and 48 hours after the first misoprostol dose; side effects proportion; and pain and satisfaction scores. A sample size of 40 per group (N=80) was planned to compare the 24- and 12-hour regimens. RESULTS: Eighty patients were enrolled between July 2020 and June 2023, with 40 patients per group. Baseline characteristics were comparable between groups. Median induction time was 9.5 hours (95% CI, 10.3-17.8 hours) and 12.5 hours (95% CI, 13.5-20.2 hours) in the 24- and 12-hour interval arms, respectively ( P =.028). Median total abortion time was 33.0 hours (95% CI, 34.2-41.9 hours) and 24.5 hours (95% CI, 25.7-32.4 hours) in the 24- and 12-hour interval groups, respectively ( P <.001). At 12 hours from misoprostol administration, 25 patients (62.5%) in the 24-hour arm and 18 patients (45.0%) in the 12-hour arm completed abortion ( P =.178). At 24 hours from misoprostol administration, 36 patients (90.0%) in the 24-hour arm and 30 patients (75.0%) in the 12-hour arm had complete abortion ( P =.139). The need for additional medication or surgical treatment for uterine evacuation, pain scores, side effects, and satisfaction levels were not different between groups. CONCLUSION: A 24-hour mifepristone-to-misoprostol regimen for medication abortion in the second trimester provides a median 3-hour shorter induction time compared with the 12-hour interval. However, the median total abortion time was 8.5-hours longer in the 24-hour interval regimen. These findings can aid in shared decision making before medication abortion in the second trimester. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04160221.

Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden.

OBJECTIVE: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS. METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group. RESULTS: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations. CONCLUSIONS: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.

Factors associated with age of presentation of pediatric feeding disorder.

AIM: Understanding the association between pediatric feeding disorder (PFD) and age of presentation is limited. We aimed to investigate factors associated with PFD among different age groups. METHODS: Retrospective analysis of medical records of infants and toddlers diagnosed with PFD, according to the World Health Organization-based definition. We compared children aged 1-12 months to those aged 13-72 months. RESULTS: Included were 253 children with PFD (median [interquartile range] age 16.4 [9.5-33] months at diagnosis, 56% boys). Significantly more children in the younger age group were girls (52.6% vs. 34.4%, respectively, p = .03) and preterm (25% vs. 14%, p = .03). They had more hospitalizations (34% vs. 23%, p = .03) and needed more prescription medications (36% vs. 17%, p < .01). Additionally, disturbances in oral intake were primarily linked to feeding skills dysfunction in the younger group and nutritional dysfunction in the older group (39.6% vs. 23.7% and 55% vs. 38%, respectively, p = .02). CONCLUSIONS: Infants under 1 year old with PFD represent a distinct patient group with unique characteristics and outcomes. The age of presentation plays a significant role in children with PFD, necessitating tailored treatment strategies.

Obstetric and Early Neonatal Outcomes Following Second and Third COVID-19 Vaccination in Pregnancy.

BACKGROUND: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective. OBJECTIVES: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses. METHODS: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose. RESULTS: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (212 vs. 315 weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048-0.926, P = 0.039). CONCLUSIONS: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

Endoscopy in pediatric polyposis syndromes: why, when and how.

Single or multiple polyps are frequently encountered during colonoscopy among children and adolescents and may be indicative of hereditary polyposis syndrome (HPS). The management of children with single or multiple polyps is guided by the number of polyps, their distribution and the histological findings. Children with HPS carry a high risk of complications, including intestinal and extra-intestinal malignancies. The goals of surveillance in pediatric HPS are to treat symptoms, monitor the burden of polyps and prevent short- and long-term complications. Therefore, the management of children with HPS is based on therapeutic endoscopy. The strategy of therapeutic endoscopy is a careful assessment and characterization of the polyps and performing polypectomies using advanced endoscopic techniques. A multidisciplinary approach, comprising clinical, interventional endoscopy, cancer surveillance and support of familial and emotional aspects is essential in the management of children with HPS.

Neonatal outcomes in pregnancies complicated by placenta accreta- a matched cohort study.

PURPOSE: Pregnancies complicated by placenta accreta spectrum (PAS) are associated with severe maternal morbidities. The aim of this study is to describe the neonatal outcomes in pregnancies complicated with PAS compared with pregnancies not complicated by PAS. METHODS: A retrospective cohort study conducted at a single tertiary center between 03/2011 and 01/2022, comparing women with PAS who underwent cesarean delivery (CD) to a matched control group of women without PAS who underwent CD. We evaluated the following adverse neonatal outcomes: umbilical artery pH < 7.0, umbilical artery base excess ≤ - 12, APGAR score < 7 at 5 min, neonatal intensive care unit (NICU) admission, mechanical ventilation, hypoxic ischemic encephalopathy, seizures and neonatal death. We also evaluated a composite adverse neonatal outcome, defined as the occurrence of at least one of the adverse neonatal outcomes described above. Multivariable regression analysis was used to determine which adverse neonatal outcome were independently associated with the presence of PAS. RESULTS: 265 women with PAS were included in the study group and were matched to 1382 controls. In the PAS group compared with controls, the rate of composite adverse neonatal outcomes was significantly higher (33.6% vs. 18.7%, respectively, p < 0.001). In a multivariable logistic regression analysis, Apgar score < 7 at 5 min, NICU admission and composite adverse neonatal outcome were independently associated with PAS. CONCLUSION: Neonates in PAS pregnancies had higher rates of adverse outcomes. Apgar score < 7 at 5 min, NICU admission and composite adverse neonatal outcome were independently associated with PAS.

Dual Biologic or Small Molecule Therapy in Refractory Pediatric Inflammatory Bowel Disease (DOUBLE-PIBD): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND: Current data on dual biologic therapy in children are limited. This multicenter study aimed to evaluate the effectiveness and safety of dual therapy in pediatric patients with inflammatory bowel disease (IBD). METHODS: A retrospective study from 14 centers affiliated with the Pediatric IBD Interest and Porto Groups of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Included were children with IBD who underwent combinations of biologic agents or biologic and small molecule therapy for at least 3 months. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded. RESULTS: Sixty-two children (35 Crohn's disease, 27 ulcerative colitis; median age 15.5 [interquartile range, 13.1-16.8] years) were included. They had all failed previous biologic therapies, and 47 (76%) failed at least 2 biologic agents. The dual therapy included an anti-tumor necrosis factor agent and vedolizumab in 30 children (48%), anti-tumor necrosis factor and ustekinumab in 21 (34%) children, vedolizumab and ustekinumab in 8 (13%) children, and tofacitinib with a biologic in 3 (5%) children. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Normalization of C-reactive protein and decrease in fecal calprotectin to <250 µg/g were achieved in 75% and 64%, respectively, at 12 months of follow-up. Twenty-nine (47%) children sustained adverse events, 8 of which were regarded as serious and led to discontinuation of therapy in 6. CONCLUSIONS: Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events.

This multicenter study describes 62 children with refractory inflammatory bowel disease who received dual biologic therapy. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Several serious adverse events were reported.

Clinical implications of a cesarean scar pregnancy sonographic evaluation and reporting system.

OBJECTIVES: Recently, a new standardized sonographic evaluation system for cesarean scar pregnancies (CSP) was published. We aimed to evaluate the clinical outcomes of CSP cases according to the new sonographic evaluation and reporting system. STUDY DESIGN: A retrospective study conducted at a single tertiary center. All CSPs between 1/2011 and 4/2022 were included. Cases were evaluated by expert sonographers and classified into three categories: 1) CSP in which the largest part of the gestational sac (GS) protrudes towards the uterine cavity; 2) CSP in which the largest part of the GS is embedded in the myometrium but does not cross the serosal contour; and 3) CSP in which the GS is partially located beyond the outer contour of the cervix or uterus.Baseline characteristics, management and outcomes were compared between the three categories. RESULTS: Overall, 55 patients were diagnosed with CSP during the study period; 10 (18.1 %) type 1, 31 (56.3 %) type 2, and 14 (25.4 %) type 3. Baseline characteristics were similar among groups. Compared with type 2 and 3, patients diagnosed with CSP type 1 received less methotrexate treatment [83.9 % and 78.6 % vs. 40.0 %, respectively, p = 0.020]. The rates of need for invasive procedures, urgent procedures, major bleeding, length of hospitalization, and subsequent pregnancies were similar between groups. CONCLUSIONS: No clinically significant differences were found between groups divided by the new standardized sonographic evaluation and reporting system for CSP in pregnancy characteristics, management, and subsequent pregnancy outcomes. Further investigation is required to enable informed management of CSP based on the new sonographic reporting system.

Association of early-life exposure to acid-suppressive therapy and fractures during childhood: a retrospective cohort study.

OBJECTIVES: Increased acid-suppressive therapy (AST) usage during infancy is seen worldwide, while the data on the risk for paediatric fractures associated with these drugs are scarce. We aimed to evaluate the risk for fractures associated with early-life usage of AST. METHODS: This population-based retrospective propensity-matched cohort study included children born between 2005 and 2016 who used AST during the first year of life, and a 3:1 matched unexposed group. Study subjects were followed from the end of the first year of life until the earliest of the following: an outcome event (either fracture or non-fracture injury, separately), age of 10 or August 2022. The cumulative incidence of fractures and the HR of AST for fracture and non-fracture injury as negative control were calculated. RESULTS: A total of 13 894 eligible AST users and 41 418 propensity score-matched non-users were included in the analysis. The cumulative incidence of fracture among children with AST (23.7%) was significantly (p<0.001) higher than non-users (21.7%) corresponding to an HR of 1.11 (95% CI 1.06 to 1.16). The HR for one to two AST purchases versus none was 1.09 (95% CI 1.04 to 1.14) and the HR for 3+ AST purchases versus none was 1.25 (95% CI 1.13 to 1.39). AST was also associated with injuries by an HR of 1.09 (95% CI 1.04 to 1.13). CONCLUSIONS: AST was associated with a small but statistically significant increased incidence of fractures. We cannot exclude reporting bias or residual confounders. The clinical inference is currently unclear.

Dual-Targeted Therapy in Pediatric Inflammatory Bowel Disease: A Comprehensive Review.

Inflammatory bowel disease (IBD) is a chronic systemic immune-mediated disorder. The disease is triggered and perpetuated by a complex interplay between genetic predisposition, dysregulated immune responses, and environmental factors. Pediatric IBD is considered to be more aggressive compared with adult-onset IBD, and commonly requires more intensive pharmacological and surgical treatments. Although the use of targeted therapy, such as biologic therapy and small molecule therapy, is on the rise, there are children with IBD who are refractory to all current therapeutic options. For them, a combination of biologic agents or a biologic agent with small molecules as dual-targeted therapy (DTT) may be a possible therapeutic option. The main indications for DTT are high inflammatory burden and refractoriness to standard therapy, extra-intestinal manifestations of IBD, adverse effects of therapy, and co-existing immune-mediated inflammatory disorders. Several combination therapies were described for pediatric refractory IBD. The main ones were anti-tumor necrosis factor (TNF) agents and vedolizumab (VDZ), anti-TNF and ustekinumab (UST), VDZ and UST, and biologic agents with tofacitinib. DTT exhibits high efficacy, with high rates of clinical response and remission as well as biomarker remission. The data on endoscopic and radiologic remission are scarce. Most of the adverse effects reported under DTT were mild; however, the serious ones that had been observed mandate a profoundly cautious approach when considering it. Triple immunosuppressive therapy and combinations of biologics with emergent therapies such as selective Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators, and anti-interleukin-23 agents, are potential future regimens for children with IBD who are refractory to current therapeutic options. This review provides an update of publications on these issues.

Pediatric feeding disorders among children with parental history of feeding disorders: a distinct group of patients with unique characteristics.

To investigate factors associated with pediatric feeding disorders (PFD) among children of parents that reported to have had feeding disorders during their own childhood compared to children with PFD with no history of parental PFD. We retrospectively reviewed the medical records of children diagnosed with PFD according to the recent WHO-based definition. The demographic and clinical characteristics of children with PFD with a parental history of PFD were compared to those of children with a PFD with no history of parental PFD. Included were 231 children with PFD (median [interquartile range] age 10 months [5.5-29] at diagnosis, 58% boys) of whom 133 children had parents without PFD and 98 children had parents with PFD. Unexpectedly, children of parents without PFD had a higher rate of low birth weight (28% vs. 19%, respectively, p = 0.007), more delivery complications (10% vs. 2%, p = 0.006), more hospitalizations (33% vs. 17%, p = 0.004), more prescription medications (27% vs. 18%, p = 0.05), and a higher percent of gastrostomy tube use (6% vs. 0, p = 0.02). Moreover, more parents with PFD had academic background compared with parents without PFD (72% vs. 59%, p = 0.05). There were no significant group differences in sex, history of breastfeeding, parental marital status, or type of the child's feeding disorder.  Conclusion: PFD among children with a parental history of PFD comprise a distinct group of patients with unique characteristics and outcomes. Since parental feeding history may explain their child's PFD in highly differing ways, such information may help in devising a specific family-based and multidisciplinary treatment plan for those children. What is Known: • Pediatric feeding disorder (PFD) is relatively common and its prevalence is increasing. • Information on an association between parental PFD and their child's feeding disorder is limited. What is New: • PFD among children with a parental history of PFD comprise a distinct group of patients with various characteristics and outcomes. • The parents' feeding history during childhood may provide important clues to their child's PFD.

Reconsidering the effectiveness of low-dose aspirin in prevention of pre-eclampsia among otherwise low risk twin gestations: A historical cohort study.

OBJECTIVE: To investigate the effectiveness of low-dose aspirin (LDA) in the prevention of pre-eclampsia (PE) among otherwise low-risk twin gestations. METHODS: A historical cohort study consisting of all pregnant individuals with dichorionic diamniotic (DCDA) twin pregnancy who delivered between 2014 and 2020. Patients treated with LDA were matched by a 1:4 ratio to individuals who were not treated with LDA by age, body mass index and parity. RESULTS: During the study period, 2271 individuals carrying DCDA pregnancies delivered at our center. Of these, 404 were excluded for one or more additional major risk factors. The remaining cohort consisted of 1867 individuals of whom 142 (7.6%) were treated with LDA and were compared with a 1:4 matched group of 568 individuals who were not treated. The rate of preterm PE did not differ significantly between the two groups (18 [12.7%] in the LDA group vs. 55 [9.7%] in the no-LDA group; P = 0.294, adjusted odds ratio 1.36, 95% confidence interval 0.77-2.40). There were no other significant between-group differences. CONCLUSIONS: Low-dose aspirin treatment in pregnant individuals with DCDA twin gestations without additional major risk factors was not associated with a reduction in the rate of preterm PE.