Editorial on the Research Topic Dermatologic manifestations of primary immune deficiency disorders in children The introduction of genetic-based diagnosis incorporated with advanced molecular workup has revolutionized the field of primary immune deficiency disorders (PIDD). Number of PIDD is constantly increasing and the 2022 International Union of Immunological Societies (IUIS) update classifies 485 genetic disorders as PIDD (1). Corresponding with advances in PIDD diagnoses, the clinical spectrum of each PIDD is also expanding. The skin is a major site affected by PIDD. Chronic mucocutaneous candidiasis can be seen in a variety of PIDD including Signal Transducer and Activator of Transcription (STAT)1 gain-of-function (GOF) and dominant negative STAT3 variants, both characterized by impaired T helper (Th)17 immunity (2). Recurrent staphylococcal skin infections and abscesses are a well-known feature of hyper IgE syndrome (HIES) and chronic granulomatous disease (CGD) (3). In addition, PIDD can lead to unexpected skin infections, as seen in STAT1 GOF, which was reported to induce rosacea and chronic demodicosis of the skin (4). However, non-infectious dermatological presentation can also be seen in PIDD categorized as primary immune regulatory disorders (PIRD). For example, the classic severe combined immune deficiency (SCID)-related Omenn's syndrome has a severe eczema, which is induced by clones of autoreactive T cells. Autoimmune manifestations of the skin can also be found in other PIRD, such as Wiskott-Aldrich syndrome (WAS), LPS responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte-associated protein (CTLA)-4 haploinsufficiency (5). In addition, Atopic dermatitis (AD), due to skewed immunity towards Th2 response, can be seen in dominant negative STAT3 variants. AD characterizes other PIDD with skewed Th2 immunity, such as DOCK8 deficiency and CARD11-associated atopy with dominant interference of NF-kB signaling (CADINS) syndrome. Indeed, many of the children with PIDD are first being evaluated by dermatologists, rather than clinical immunologists. Thus, special attention should be given to skin involvement in PIDD. This issue of Frontiers in Pediatrics focuses on dermatologic manifestations of PIDD in children. Different articles presented in this research topic offer a broad view of the subject. Sarika et al. describes an enigmatic 8-year-old child presenting with acrofacial skin necrosis. Suspecting PIDD involving interferon immunity, immune and genetic workups were initiated, although no definite diagnosis was achieved. Shen et al. reviews the expanding clinical spectrum of inborn errors of NF-κB, with a special focus on skin manifestations and details regarding underlying mechanisms. The authors describe the different phenotypes, including ectodermal dysplasia, impaired quantities of keratinocytes and skin infiltration of inflammatory cells, via enhanced tumor necrosis factor (TNF) response. They offer differential diagnosis and suggest a genotype-phenotype correlation as diagnostic clues of inborn errors of NF-κB. Ollech et al. describe eight children with PIDD and unique dermatological presentations. This interesting cohort includes patients with common variable immunodeficiency, (CVID), SCID, DOCK8 deficiency, ataxia telangiectasia, CARD11 deficiency, MALT1 deficiency and CGD. Among unusual infectious dermatological manifestations in these children, they detail ulcerative-hemorrhagic varicella-zoster virus, atypical fungal and bacterial infections, Norwegian scabies, giant perianal verrucae and diffuse molluscum contagiosum. Huang et al. report an interesting association between interleukin (IL)-6 polymorphism and AD. This study comprises of investigation of 132 patients with AD and 100 healthy controls and found that A/G genotype of IL-6 increases the risk for development of AD, thus perhaps aiding in unveiling new methods of genetic workup for children with AD. Finally, Giancotta et al. offers an extensive review on tailored treatment for PIDD associated with atopy. This review nicely demonstrates the notion of personalized medicine, which has a significant place in the treatment of children with PIDD presenting with skin manifestations. In conclusion, dermatological manifestations of PIDD in children are common and may constitute the initial presenting feature. Collaboration between general pediatricians, dermatologists and clinical immunologists is needed to initiate prompt immunogenetic evaluation and offer better medical care for these children. OS: writing of manuscript, SC: design and revisions. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. 1. Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, et al. The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. J Clin Immunol. (2022) 42(7):1508–20. doi: 10.1007/s10875-022-01352-z PubMed Abstract | CrossRef Full Text | Google Scholar 2. Shamriz O, Tal Y, Talmon A, Nahum A. Chronic mucocutaneous candidiasis in early life: insights into immune mechanisms and novel targeted therapies. Front Immunol. (2020) 11:593289. doi: 10.3389/fimmu.2020.593289 PubMed Abstract | CrossRef Full Text | Google Scholar 3. Yu JE, Azar AE, Chong HJ, Jongco AM 3rd, Prince BT. Considerations in the diagnosis of chronic granulomatous...

Editorial on the Research Topic Insights in pediatric urology: 2021 The purpose of this research Topic is to highlight the best research topic insights of Pediatric Urology in 2021. In this collection of articles published on this subject, we have a wide selection of studies that will contribute to the further progress of the field. In this issue, authors shared their experience with various urological anomalies and their management accompanied by a literature review. We thank the authors and reviewers for sharing their experiences and making these manuscripts better. Bar-Yaakov et al. showed that decisional regret was reported by 27.5% of parents of children who underwent revision of neonatal circumcision for excess foreskin. Parents were concerned about the appearance of a penis which may resemble an uncircumcised penis and most parents do not regret the surgery (1). This study is well conducted and gives additional information to discuss with parents before indicating this surgery. However, since a non-therapeutic approach is employed most of the time, caregivers must be provided with sufficient information about the pros and cons of the surgery so that they can make the best decision and avoiding any regret in the future (2). Authors from Spain (Ordóñez et al.), described the long-term outcome of the patients with ureteropelvic junction obstruction (UPJO) treated by endoscopic retrograde balloon dilatation (ERBD). This is the largest reported case series treated endoscopically in children with primary unilateral UPJO (92 cases being younger than 18 months). An additional procedure was needed in 21% of patients and an open pyeloplasty was needed in 6.25% (n = 7) cases of technical failure. Long-term success rate was 76.8% after one dilatation, and 86.6% in those who required up to 2 dilatations. Robotic and laparoscopic pyeloplasty are now frequently done in small children and, this data is very important and useful to discuss with parents before indicating surgery (3). Benefits of minimal invasive surgery and success rate should be balanced with chances of second surgery and additional anesthesia. Xiaofei and Benzhang report a case of testicular torsion (TT) in a patient with unilateral supernumerary testis (SNT). Since timing at presentation, the twisted gonad in the hemi-scrotum with SNT could not be saved but the remaining uninvolved testicle was preserved. The authors should be congratulated for the surgical criteria and the effort to preserve normal tissue. Intravaginal TT occurred in a clockwise direction in a left testicle, contrary what happens in most cases (inward rotation), probably because testicles are in different planes and there were no scrotal attachments (4). Orchidopexy in the contralateral hemi-scrotum was a wise decision. The ideal technique for the correction of hypospadias would be one that allows for a good aesthetic and functional result, with a slit urethral meatus, correction of the penile curvature, obtaining an appropriately sized phallus and a low rate of complications. Unfortunately, so far, no technique has reached all these goals (5). Xie et al. compared two surgical techniques for proximal hypospadias, the staged TIP urethroplasty (group 1), and the Byars’ two-stage urethroplasty (group 2). The authors found a significantly lower complication rate in patients in group 1. As it was not a randomized clinical trial, the results of this study should be evaluated with caution, as less severe cases may have been selected to undergo TIP. Furthermore, follow-up is not long enough to detect complications that may occur later such as urethral strictures (5). Authors from Italy, Paraboschi et al. reported an update on the current management of pediatric urolithiasis. This important review article describes novel technologies and devices to minimize surgical complications and improve patient outcomes. Small instruments and new technological developments have led to many innovations in the surgical management of pediatric urolithiasis (Peng et al.). The devices and technologies described in this review article are changing the way surgeons plan and treat urinary stones in children. Pediatric urologists need to be up to date with these technological advances that can decrease the morbidity of patients with urinary stones. Cryptorchidism is a common medical condition routinely treated by pediatric urologists. In the case of a non-palpable testis, in around half of the cases no intraabdominal testis will be found. In the presence of a vanishing testis- also known as testicular regression syndrome (TRS), there is a debate whether surgical excision of the remnant is necessary (6). Depending on the presence of ectopic seminiferous tubules or germ cells in the remnant there is potential for malignancy. Gao et al. from China made a research handling more than 300 patients with TRS in which they found very few germ cells in testicular remnants concluding that an inguinal or scrotal exploration may not be necessary. They share good evidence in this paper which is worth reading for any surgeon dealing with this condition. Having this information handy would help in more grounded decision making for this condition. Bergel et al. from Germany, analyze in their study the safety and outcome of performing pediatric transplant exclusively in a pediatric environment. In their Institution, pediatric renal transplants were performed over a long period in the general urology and high-volume transplant setting. In 2013, the decision was made to change this setting and pediatric transplantations were since then solely carried out in the pediatric hospital setting. Their data and others showed a trend to transplant children at a younger age (7). In this manuscript they described the importance of ensuring a Pediatric medical environment that can address their challenges in perioperative care according to their individual needs. This...

Objectives: To identify craniofacial and upper airway morphological characteristics associated with the presence and severity of obstructive sleep apnea (OSA) in children.Methods: This study consisted of 82 OSA children and 77 controls (age 5–10 years). All subjects underwent cephalograms and were divided into a 5–7 age group and an 8–10 age group. Cephalometric variables were compared between OSA children and controls, and hierarchical regression analysis was performed to examine the relationship between cephalometric variables and OSA severity [expressed by the obstructive apnea–hypopnea index (OAHI)] in different age groups.Results: Increased A/N ratio, narrowed posterior airway space, decreased SNA and SNB angles, and shortened ramus height were observed among OSA children in different age groups. In the 5–7 age group, the A/N ratio and a lower gonial angle explained 40.0% and 14.7% of the variance in the OAHI, respectively. In the 8–10 age group, the BMI z-score and A/N ratio explained 25.2% and 6.6% of the variance in the OAHI, followed by a lower gonial angle and the hyoid-retrognathion distance (19.1% in total).Conclusions: Adenoid hypertrophy was a major factor associated with OSA in preschool children, whereas obesity replaced adenoid hypertrophy as the main contributor to OSA in late childhood. Several craniofacial skeletal variables such as the SNB angle, ramus height, lower gonial angle, and hyoid position are also associated with the presence and/or severity of OSA, which could be used to help recognize children at a higher risk for OSA.

Aplasia cutis congenita (ACC) is a heterogeneous disorder with a rarely reported incidence of 0.5–1 in 10,000 births. ACC can be associated with physical defects or syndromes that may help in the diagnosis, prognosis, and further evaluation of the patient. Trisomy 13 is one of the most common fetal life-limiting diagnoses associated with ACC of membranous-type scalp. The patient was born at 35 weeks of gestation via a cesarean section due to fetal distress. Upon admission to our hospital, her pertinent physical examination revealed a newborn girl with dysmorphic facial features, including widely separated eyes, downward slanting of the palpebral fissure, microphthalmia, retrognathia, and low-set ears. She had an area of loss of scalp skin and skull bone with seen brain tissue and an exposed sagittal sinus that was 6 by 5 cm in size. She had a clenched fist, overlapping fingers, and rocker bottom feet. Precordium auscultation revealed medium-pitched high-grade continuous murmur heard best at the pulmonary position with a harsh machinelike quality that often radiated to the left clavicle. Laboratory investigations include basic labs, and the TORCH screen was negative. On the 9th day of life, a chromosomal analysis showed a female karyotype with three copies of chromosome number 13 (trisomy 13) in all 20 metaphase cell counts. The patient was managed with a moist gauze dressing, topical antibiotic ointment, and povidone-iodine. However, a multidisciplinary team agreed on a do-not-resuscitate (DNR) order with no further surgical intervention as the survival rate of trisomy 13 is poor. In this article, we report a case of aplasia cutis congenita of the scalp with dura and bone defect and an exposed sagittal sinus in a newborn diagnosed with trisomy 13. It emphasizes the importance of ACC-associated syndrome, which has high mortality prior to surgical intervention.

Background: Alport syndrome (AS) and Wilson's disease (WD) are genetic diseases that could lead to kidney damage. Herein, we report the clinical features and gene variants in a patient with WD and X-linked AS.Case presentation: The proband was a 12-year-old boy diagnosed with AS coexisting with WD at the age of 11 years. The patient underwent a medical check-up when he was 4 years and 8 months. Laboratory tests revealed elevated liver enzymes, decreased serum ceruloplasmin, increased 24-h urinary copper excretion, and one variant in the ATP7B gene. Then, the patient was diagnosed with WD. After 2 months of treatment with D-penicillamine and zinc salt, his liver function had recovered to normal levels, but he presented with microscopic hematuria. The hematuria did not resolve after switching to dimercaptosuccinic acid from D-penicillamine. In addition, he presented with proteinuria 3 years later. A renal biopsy was performed more than 6 years after the patient was diagnosed with WD, and electron microscopy showed that the basement membrane thickness was uneven, layered, and focal torn. Copper staining was negative. A genetic analysis identified a hemizygous variant (c.1718G > A, p. Gly573Asp) in COL4A5 and a homozygous variant (c.2975C > T, p. Pro992leu) in ATP7B. The patient’s urine protein–creatinine ratio was less than 1.0 mg/mg after a 1 year of follow-up, after enalapril was administered for treating AS.Conclusion: This case highlights a lack of improvement in renal function after conventional treatment provides a possible indication for performing renal biopsy or genetic testing to determine the etiology in order to facilitate subsequent clinical management. Clinicians should prevent the occurrence of diagnostic inaccuracies caused by diagnostic anchoring because an accurate diagnosis is essential for achieving precise treatment and improved prognosis.

With every school shooting, debate on firearms garners national attention. Pediatricians will have to play an important role in the practice of promoting and integrating positive changes in the environment for children. Pediatricians played an important role in the early years of motor vehicular crashes to draw national attention to the epidemic and impact on children. We provide the perspective of the financial burden due to firearm injuries, contrasting it with vehicular crashes, an additional insight for pediatricians to promote firearm safety. Since 2013, fatal firearm injuries in children and adolescents have been increasing in United States (1). Lee et al. described a concerning trend for deaths in children, adolescents, and youth ages 1–24 years in the United States (2). In 2017, deaths due to firearm related injuries became the most common cause of death in this age group, surpassing deaths due to motor vehicle crashes. Lee and colleagues analyzed CDC's data from 2000 to 2020 and saw the number of firearm related deaths among children, adolescents and young adults increased from 7.3 per 100,000 persons to 10.28 per 100,000 persons. There is political will and a public cry to address firearm injuries as a public health problem, and research on trends, disparities, risk factors will help guide preventive efforts. In the United States, since 2016, the economic impact of firearm related deaths, both in terms of medical costs and the statistical value of life lost to death, is consistently greater than 1 billion dollars each year. Millions of dollars are spent caring for youth in emergency departments (3), and billions of dollars are spent on inpatient care (4, 5). CDC has ensured publicly available data through the Web-based Injury Statistics Query and Reporting System (WISQARS) (6). It is an interactive data visualization and can provide insights in trends in deaths due to various causes of injuries. WISQARS is proving to be an essential tool in identifying nature and extent of injury, fatal and non-fatal burden of such injuries, and prioritization of prevention strategies (7). To understand the economic impact of firearm injuries from 2015 to 2020, we compared the percentage change to 2015 data for fatalities and total cost (medical and value of statistical life) for both firearm injuries and motor vehicle crashes. After obtaining the data from WISQARS, data for each type of injury for each year was tabulated and the percentage increase to the previous year was calculated. The fatality data is obtained from National Vital Statistics System (NVSS) using the death certificates. For the estimate of cost of injury data is obtained from Pacific Institute of Research and Evaluation. We found that the percentage change in cost for firearm injuries or motor vehicle crashes corresponded to the mortality in that particular year, higher the mortality that year, higher the cost. Beginning in 2017, we found a striking trend with an increase in fatalities and total cost for firearm injuries and decrease in fatalities and total cost for motor vehicle crashes (Figure 1). It has been shown that since 2017, deaths due to firearm injuries became the leading cause of deaths for children, adolescents, and young adults. In 2020, deaths and total costs for firearm related injuries were 39.2% and 41% respectively, higher than in 2015. In 2019, we observed the largest drop in motor vehicle deaths (12.35%) and total costs (12%). These cost are only for fatal injuries either due to firearms or motor vehicular crashes. Figure 1. Percentage change in deaths and costs for firearm and motor vehicle fatalities in 1–24 years of age (compared to 2015). During the COVID-19 pandemic there was a surge in firearm sales and in gun deaths. We have also seen an increase in the use of firearms to commit suicide. Rural children are at increasing risk for using firearms to commit suicide. Urban children are more prone to unintentional or homicidal victims of firearm injuries. Lee and colleagues (2) present us with a comprehensive public health approach to injury reduction that has been extremely successful in preventing injury-related deaths. This should serve as a model for the public health approach to reduce firearm-related injuries and deaths. The measures implemented to prevent motor vehicle related deaths in the last 20 or more years and their efficacy in achieving that goal sit in stark contrast to the comparatively limited interventions to prevent youth firearm death and injury. Similar to the approach to motor vehicular collisions, the approach to firearm injuries can be divided into three phases to decrease the morbidity and mortality: (1) Pre-event phase (access to mental health services, child access prevention laws, licensing and permit-to-purchase requirements, extreme risk protective orders), (2) Event phase (school safety policies, “gun free zones,” magazine capacity limits, bump stock prohibitions), and (3) post event phase (medical and rehabilitation services, trauma center accreditation, EMS systems). Onus should not fall on a particular group of individuals, but each group will have to play their role if we are to decrease the mortality burden due to firearm injuries. We are seeing an increase in research funding for firearm injuries which will lead to identifying and prioritizing prevention strategies. Policy makers will have evidenced based scientific data to make informed decision for allocation of resources. One of the limitations of the study is the age group (1–24 years) arguing the higher incidence of firearm injuries in young adults and not necessarily in children. Most pediatricians are involved in the care of children and young adults up to 18 or 21 years of age. We used this age group as CDC does provide data in 5-year or 10-year age groups and data was similar to previously published study (2). While, as pediatricians, we believe that...

Instruction: The purpose of this study was to evaluate the three-year success rate of the treatment for early childhood caries (ECC) under general anesthesia in different periods (2011 and 2018).Methods: Children (<6 years old) who had severe caries and were treated under general anesthesia in 2011 and 2018 were selected and followed up by telephone appointment and clinical examination. Success rate of each treatment was determined and possible factors associated with treatment failure were evaluated.Results: There were 153 patients (with an average age of 48.55 ± 13.37 months) and a total of 2,018 teeth included in the 2011 group. In the 2018 group, there were 273 patients with an average age of 49.01 ± 12.42 months and a total of 3,796 teeth. The success rate in the 2011 group was significantly lower than that in the 2018 group. Teeth with mineral trioxide aggregate (MTA)-capped pulp survived significantly longer than those with calcium hydroxide-capped pulp. The utilization rate of preformed crown restoration was higher than that of resin restoration, and the survival time of dental restorations with preformed crown was prolonged. For posterior teeth, the success rate of indirect pulp capping and pulpotomy was also significantly higher than those without preformed crowns.Discussion: General anesthesia is a safe and effective behavioral management method for uncooperative children's dental treatment. The use of biocompatible pulp capping materials and preformed crowns improved the success rate of treatment and prolonged the survival time of affected teeth.

Editorial on the Research Topic Pediatric preventable diseases Preventable diseases are a leading cause of disability and death worldwide and prevention remains the most efficacious medical intervention, even though its effect may not be immediately apparent. The advancement of research and technology plays a crucial role in reducing child mortality from preventable diseases, leading also to improved neurophysiological development for children and adolescents. The World Health Organization advocates for national strategies to strengthen ongoing control of infectious diseases and reduce associated transmission, mortality, and morbidity. To develop appropriate immunization recommendations and implement public health policies, timely epidemiologic evaluations are crucial in understanding the circulation of infectious diseases and identifying high-risk populations in the pediatric age group. For instance, orphans and vulnerable children in African areas are a high-risk group for infectious diseases, including human immunodeficiency virus infection, as shown by socioeconomic analyses. Education of families also plays a major role: education of mothers on diarrhea management has been linked to reduced death rates (Shah et al.; Gessesse and Tarekegn). Immunization is an effective approach to prevent the substantial impact of preventable infectious diseases. Through vaccination, smallpox has been eradicated, and the prevalence of preventable infectious diseases, such as measles, diphtheria, and whooping cough, has been significantly reduced worldwide. The implementation of immunization programs has also led to a decrease in hospitalization costs and socio-economic burden. Currently, new vaccines and immunization strategies are being developed and adapted to the epidemiological burden of preventable infectious diseases. For example, different immunization options have being developed to prevent respiratory syncytial virus (RSV) infections in children. Of note, evidence indicates that RSV is responsible for almost 13 million cases of lower respiratory tract infections, 2.2 million hospitalizations, and 66,300 deaths globally each year Bont et al. Effective health messages, immunization strategies, and risk factor awareness require robust communication strategies. It is crucial to communicate the benefits of immunization strategies to parents using simple and appropriate language. Using communication methods such as social media can enhance the dissemination of health information, facilitate interactions, boost family confidence and compliance, and positively influence parental vaccination acceptance. These strategies can help reassure parents about the safety and efficacy of immunization strategies and counteract infodemics Di Mauro et al. To enhance the quality of life of children and prevent disabilities in later life, high-quality research should focus on major modifiable risk factors for non-infectious preventable pediatric diseases such as tobacco use, unhealthy diets, and physical inactivity. Early detection of high-risk behaviors is essential to achieving this goal. For instance, identifying predictors of childhood obesity can prevent long-term consequences such as metabolic syndrome and diabetes Byeon. Similarly, reducing pollution can decrease respiratory infections in children, preventing long-term sequelae such as asthma. Evidence indicates that short and long-term exposure to air pollutants, including PM2.5, may lead to respiratory diseases in children, regardless of country development status. Fine particulate's small size enables easy penetration of human barriers, causing tissue damage and lung inflammation Liu et al. Screening guidelines should also be widely implemented to prevent diseases, such as amblyopia, a common neurodevelopment disorder among children Yan et al. Secondary prevention is also essential to reduce the burden and prevent long-term consequences. For instance, the rising number of myopia cases in adolescents emphasizes the need for developing strategies to slow the progression of visual impairment and its consequences. Multifocal lenses have been proven an effective approach to controlling myopia progression, thereby avoiding complications such as macular degeneration, retinal detachment, glaucoma, and premature cataracts Chen et al. Creating a safe environment through preventive measures is crucial in avoiding pediatric diseases and disabilities caused by unintentional injuries. The ingestion of foreign bodies is a common clinical problem, particularly in the youngest age group, aged 6 months to 3 years. These children may be unaware of the risks associated with pediatric foreign body ingestion, particularly in cases of accidental ingestion of magnets or chemicals Ding et al. EB and AET contributed equally to the plan and the writing of the editorial. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Keywords: prevention, preventale diseases, children, health, immunization, education Citation: Bozzola E and Tozzi AE (2023) Editorial: Pediatric preventable diseases. Front. Pediatr. 11:1187008. doi: 10.3389/fped.2023.1187008 Received: 15 March 2023; Accepted: 16 March 2023; Published: 31 March 2023. Edited and Reviewed by: Tim S Nawrot, University of Hasselt, Belgium © 2023 Bozzola and Tozzi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted,...

Background: Premature rupture of membranes (PROM) is a common cause of extremely premature infants (EPIs) and also leads to adverse preterm complications. However, the effect of PROM on EPIs remains contradictory. This study used propensity score matching (PSM) to adjust the baseline characteristics to explore the impact of PROM on clinical outcomes of extremely premature infants (EPIs).Methods: Medical data of 470 EPIs at gestational age < 28weeks who received prenatal examination in our hospital between January 1, 2015 and December 31, 2020 were analyzed retrospectively. According to the presence or absence of PROM, they were divided into a PROM group and a non-PROM group. Ten covariates including birth weight, male sex, artificial conception, cesarean delivery, 5-min Apgar score ≤ 7, oligohydramnios, gestational hypertension, preeclampsia, antenatal steroid use, and complete steroid treatment were matched 1:1 by PSM. The major complication occurrence and mortality during hospitalization were compared between the two groups by t-test, nonparametric test or x2 test.Results: Among the 470 infants enrolled, 157 (33.4%) were in the PROM group and 313 in the no-PROM group. After matching the ten confounding factors,276 cases were successfully enrolled. The incidence of early pulmonary hypertension (EPH) and severe retinopathy of prematurity (ROP) in the PROM group were higher than those in the no-PROM group [44.2% (61/138) vs. 29.0% (40/138); 34.8% (48/138) vs. 21.7% (30/138), x² = 6.886 and 5.790, both P < 0.05]. However, there was no significant difference in the in-hospital mortality and the incidence of other major complications between the two groups (all P > 0.05).Conclusions: PROM increased the incidence of EPH and severe ROP in EPI, but had no significant impact on in-hospital mortality, length of hospital stay, and the incidence of other complications.

Infants at high biological risk of or with a neurodevelopmental disorder run a high risk of delayed school readiness. This is especially true for infants in low- and middle-income countries (LMICs). This perspective paper first summarizes evidence on intervention elements that are effective in promoting family well-being and child development in infants at high biological risk in high income countries. Crucial elements are family centeredness, goal orientation, a home setting, focus on activity and participation, and challenging the infant to explore the world and the own body by means of self-produced movements. The studies revealed that coaching as applied in COPCA (COPing and CAring for infants with special needs) is a pivotal element determining the success of intervention.The paper continues by describing COPCA and its coaching. Next, we report on two pilot studies addressing COPCA's implementation in Brazil. Finally, we discuss why COPCA is a promising early intervention program for infants at high biological risk of neurodisability in LMICs: COPCA is adapted to the families' strengths and needs, it empowers families and promotes child development therewith facilitating school readiness. Moreover, it may be delivered by tele-coaching therewith eliminating families' burden to travel to distant intervention clinics.