Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial.

BACKGROUND: Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. METHODS: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. DISCUSSION: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. TRIAL REGISTRATION: ( Clinicaltrials.gov ): NCT05604846.

Effects of vitamin D levels during pregnancy on prematurity: a systematic review protocol.

INTRODUCTION: Prematurity is an urgent public health problem worldwide. Recent studies associate maternal hypovitaminosis D during pregnancy with an increased risk of prematurity. However, the evidence on this association remains inconclusive, and there is lack of consensus in the literature. The exact mechanism by which low vitamin D levels may increase the risk of preterm birth is not yet fully understood. Nevertheless, it is known that vitamin D may play a role in maintaining a healthy pregnancy by regulating inflammation and immunomodulation by acting on the maternal and fetal immune systems. Inflammation and immune dysregulation are both associated with preterm birth, and low vitamin D levels may exacerbate these processes. The results of this review may have important implications for clinical practice and public health policy, particularly regarding vitamin D supplementation during pregnancy. METHODS AND ANALYSIS: A systematic review of the literature will be conducted. The search will be performed in electronic databases: CINAHL; MEDLINE; Cochrane Central Register of Controlled Trials; Cochrane Library; Academic Search Complete; Information Science and Technology Abstracts; MedicLatina; SCOPUS; PubMed; and Google Scholar, with the chronological range of January 2018 to November 2022. The search strategy will include the following Medical Subject Headings or similar terms: 'Vitamin D'; '25-hydroxyvitamin D'; 'Hypovitaminosis D'; 'Pregnancy'; 'Pregnant women'; 'Expectant mother'; 'Prematurity'; 'Premature birth'; 'Premature delivery'; 'Preterm birth'; and 'Preterm labour'. This review will include quantitative primary studies, both experimental (clinical trials) and observational (cohort, cross-sectional, and case-control). The quality of each selected study and the results obtained will be assessed by two reviewers separately, using the Cochrane risk of bias tool for evaluating randomised clinical trials or the Newcastle Ottawa Scale for non-randomised studies, following the respective checklist. In case of disagreement, a third reviewer will be consulted. ETHICS AND DISSEMINATION: This study does not involve human subjects and therefore does not require ethics approval. The results will be disseminated through publication in a peer-reviewed scientific journal and through conference presentations. All changes made to the protocol will be registered in PROSPERO, with information on the nature and justification for the changes made. PROSPERO REGISTRATION NUMBER: CRD42022303901.

Music therapy and weight gain in preterm infants: Secondary analysis of the randomized controlled LongSTEP trial.

OBJECTIVES: This study assessed the association between MT and weight gain among preterm infants hospitalized in Neonatal Intensive Care Units. METHODS: Data collected during the international, randomized, Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and their Caregivers (LongSTEP) study were compared between the MT group and the standard care (SC) group. Weights were recorded at birth, enrollment, and discharge. Weight percentiles, Z-scores, weight gain velocity, and extrauterine growth restriction (EUGR) were calculated. RESULTS: Among 201 preterm infants included, no significant differences in weight parameters (weight, weight percentiles, weight Z-scores; all p ≥ 0.23) were found between the MT group (n = 104) and the SC (n = 97) group at birth, enrollment, or discharge. No statistical differences in EUGR represented by change in Z-scores from birth to discharge were recorded between MT and SC (0.8 vs. 0.7). Among perinatal parameters, younger gestational age (p = 0.005) and male sex (p = 0.012) were associated with increased risk of EUGR at discharge. Antenatal steroid treatment, systemic infection, bronchopulmonary dysplasia, neurological morbidities, retinopathy of prematurity, necrotizing enterocolitis, parental factors (amount of skin-to-skin care, bonding, anxiety, and depression questionnaire scores), and type of enteral nutrition did not significantly influence weight gain parameters (all p > 0.05). CONCLUSIONS: In the LongSTEP study, MT for preterm infants and families was not associated with better weight parameters compared to the SC group. The degree of prematurity remains the main risk factor for unfavorable weight parameters.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Features of liver injury in 138 Chinese patients with NICCD.

OBJECTIVES: To find biochemical and molecular markers can assist in identifying serious liver damage of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) patients. METHODS: 138 patients under 13 days to 1.1 year old diagnosed of NICCD in our center from 2004 to 2020. Base on the abnormal liver laboratory tests, we divided 138 patients into three groups: acute liver failure (ALF), liver dysfunction, and non-liver dysfunction groups, then compared their clinical, biochemical and, molecular data. RESULTS: 96 % of 138 patients had high levels of citrulline and high ratio of threonine to serine, which is the distinctive feature of plasma amino acid profile for NICCD. A total of 18.1 % of 138 patients had evidence of ALF who presented the most severity hepatic damage, 51.5 % had liver dysfunction, and the remaining 30.4 % presented mild clinical symptoms (non-liver dysfunction). In ALF group, the levels of citrulline, tyrosine, TBIL, ALP, and γ-GT was significantly elevated, and the level of ALB and Fisher ratio was pronounced low. Homozygous mutations of 1,638_1660dup, IVS6+5G.A, or IVS16ins3kb in SLC25A13 gene were only found in ALF and liver dysfunction groups. Supportive treatment including medium-chain triglyceride supplemented diet and fresh frozen plasma could be life-saving and might reverse ALF. CONCLUSIONS: High level of citrulline, tyrosine, TBIL, ALP, γ-GT, and ammonia, low level of albumin, and low Fisher ratio were predictors to suggest severe liver damage in NICCD patients who may go on to develop fatal metabolic disorder. Early identification and proper therapy is particularly important for these patients.

Assessment of food supplements for the prevention of necrotizing enterocolitis in preterm neonates: A systematic review and network meta-analysis.

BACKGROUND: The network meta-analysis (NMA) investigated the efficacy of six food supplements, namely glutamine, arginine, lactoferrin, prebiotics, synbiotics, and probiotics, in preventing necrotizing enterocolitis in premature infants. METHODS: MEDLINE, Embase, and Cochrane Library were searched. Randomized controlled trials comparing different food supplements for premature infants were included. RESULTS: Probiotics (OR, 0.47; 95% CrI, 0.33-0.63), arginine (OR, 0.38; 95% CrI, 0.14-0.98), glutamine (OR, 0.30; 95% CrI, 0.079-0.90), and synbiotics (OR, 0.13; 95% CrI, 0.037-0.37). were associated with a decreased incidence of NEC. Only probiotics (OR, 0.81; 95% CrI, 0.69-0.95) and lactoferrin (OR, 0.74; 95% CrI, 0.54-0.92) achieved lower risk of sepsis. Probiotics (OR, 0.58; 95% CrI, 0.40-0.79), prebiotics (OR, 0.23; 95% CrI, 0.043-0.86), and synbiotics (OR, 0.15; 95% CrI, 0.035-0.50) were associated with lower odds of mortality. Probiotics (MD, -2.3; 95% CrI: -3.7- -0.63) appeared to have earlier age of attainment of full feeding. CONCLUSIONS: Based on this NMA, probiotics and synbiotics had the potential to be the top two preferable food supplements.

Anti-Inflammatory and Anti-Allergic Properties of Colostrum from Mothers of Full-Term and Preterm Babies: The Importance of Maternal Lactation in the First Days.

Our narrative review focuses on colostrum components, particularly those that influence the neonatal immune system of newborns. Colostrum is secreted in small volumes by the alveolar cells of the breast during the first two to five days after birth. Colostrum is poor in fat and carbohydrates, with larger protein and bioactive compounds than mature milk. It plays a crucial role in driving neonates' immunity, transferring those immunological factors which help the correct development of the neonatal immune system and support establishing a healthy gut microbiome. The newborn has an innate and adaptive immune system deficiency, with a consequent increase in infection susceptibility. In particular, neonates born prematurely have reduced immunological competencies due to an earlier break in the maternal trans-placenta transfer of bioactive components, such as maternal IgG antibodies. Moreover, during pregnancy, starting from the second trimester, maternal immune cells are conveyed to the fetus and persist in small quantities post-natal, whereby this transfer is known as microchimerism (MMc). Thus, preterm newborns are deficient in this maternal heritage, and have their own immune system under-developed, but colostrum can compensate for the lack. Early breastfeeding, which should be strongly encouraged in mothers of preterm and full-term babies, provides those immunomodulant compounds that can act as a support, allowing the newborn to face immune needs, including fronting infections and establishing tolerance. Moreover, making mothers aware that administering colostrum helps their infants in building a healthy immune system is beneficial to sustain them in the difficult post-partum period.

Hunting for the elusive target antigen in gestational alloimmune liver disease (GALD).

The prevailing concept is that gestational alloimmune liver disease (GALD) is caused by maternal antibodies targeting a currently unknown antigen on the liver of the fetus. This leads to deposition of complement on the fetal hepatocytes and death of the fetal hepatocytes and extensive liver injury. In many cases, the newborn dies. In subsequent pregnancies early treatment of the woman with intravenous immunoglobulin can be instituted, and the prognosis for the fetus will be excellent. Without treatment the prognosis can be severe. Crucial improvements of diagnosis require identification of the target antigen. For this identification, this work was based on two hypotheses: 1. The GALD antigen is exclusively expressed in the fetal liver during normal fetal life in all pregnancies; 2. The GALD antigen is an alloantigen expressed in the fetal liver with the woman being homozygous for the minor allele and the father being, most frequently, homozygous for the major allele. We used three different experimental approaches to identify the liver target antigen of maternal antibodies from women who had given birth to a baby with the clinical GALD diagnosis: 1. Immunoprecipitation of antigens from either a human liver cell line or human fetal livers by immunoprecipitation with maternal antibodies followed by mass spectrometry analysis of captured antigens; 2. Construction of a cDNA expression library from human fetal liver mRNA and screening about 1.3 million recombinants in Escherichia coli using antibodies from mothers of babies diagnosed with GALD; 3. Exome/genome sequencing of DNA from 26 presumably unrelated women who had previously given birth to a child with GALD with husband controls and supplementary HLA typing. In conclusion, using the three experimental approaches we did not identify the GALD target antigen and the exome/genome sequencing results did not support the hypothesis that the GALD antigen is an alloantigen, but the results do not yield basis for excluding that the antigen is exclusively expressed during fetal life., which is the hypothesis we favor.

Phototherapy: a new risk factor for necrotizing enterocolitis in very low birth weight preterm infants? a retrospective case-control study.

OBJECTIVE: To investigate the association between phototherapy (PT) and the development of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. STUDY DESIGN: A retrospective case-control study was conducted on VLBW infants with or without NEC (stage IIA or greater) born at ≤35 weeks' gestation in a tertiary hospital over 7 years. Sample size calculation, trend test, as well as univariate and multiple logistic regression analyses were employed. RESULTS: A total of 824 VLBW infants were reviewed, with 74 cases and 122 controls finally enrolled. The odds of NEC increased with the duration and number of PT sessions. Exposure to >120 h and >4 instances of PT were significantly associated with NEC in multivariate analysis. CONCLUSION: This is the first study suggesting a potential association between PT and development of NEC in VLBW infants. This association needs further exploration.

Antenatal steroid as an independent risk factor for vitamin K2 deficiency in newborns: A Chinese single-center, retrospective study.

OBJECTIVES: To identified vitamin K2 deficiency rate and risk factors among newborns in China and assess the importance of high-risk maternal intakes of vitamin K2. METHODS: This retrospective study was performed at the Neonatology Department, the Affiliated Hospital of Guangdong Medical University, China. Routinely collected mother-neonate hospitalization data from July 2020 to January 2021 were analyzed. In total, data from 200 neonates who had completed vitamin K2 tests were utilized to assess the prevalence of vitamin K2 deficiency and identify the potential risk factors. According to the vitamin K2 level, the neonates were divided into 2 groups: cases (vitamin K2 deficiency) and controls (no vitamin K2 deficiency). The potential risk factors for vitamin K2 deficiency were evaluated by univariate and multivariate logistic regression. RESULTS: The vitamin K2 level in 24 of the 200 neonates was undetectable (<0.05 ng/mL). The prevalence of low serum vitamin K2 (<0.1 ng/ml) was 33%. Study subjects with antenatal corticosteroids use had an approximately 5-fold greater risk of developing vitamin K2 deficiency. In the univariate analyses, small-for-gestational-age (SGA), caesarean section, maternal gestational diabetes and premature rupture of the membranes were risk factors for vitamin K2 deficiency. In the multivariate logistic regression analysis, high antenatal corticosteroids use, cesarean section, and SGA were independently associated with vitamin K2 deficiency. CONCLUSION: The present study demonstrated that antenatal corticosteroids use is independently associated with vitamin K2 deficiency. This finding highlights the importance of routine vitamin K2 supplementation in late-stage pregnant women and neonates in China.

Fewer glucose checks and decreased supplementation using dextrose gel for asymptomatic neonatal hypoglycemia.

OBJECTIVE: Evaluate the impact of a neonatal hypoglycemia (NH) clinical pathway implementing buccal dextrose gel in late preterm and term infants. STUDY DESIGN: Quality improvement study at a children's hospital associated birth center. Number of blood glucose checks, use of supplemental milk, and need for IV glucose were followed for 26-months after implementation of dextrose gel and compared to previous 16-month period. RESULTS: After QI implementation, 2703 infants were screened for hypoglycemia. Of these, 874 (32%) received at least one dose of dextrose gel. Special cause shifts with reductions in mean number of blood glucose checks per infant (pre 6.6 vs. post 5.6), use of supplemental milk (pre 42% vs. post 30%), and need for IV glucose (pre 4.8% vs. post 3.5%) were found. CONCLUSION: Incorporating dextrose gel into a clinical pathway for NH was associated with a sustained reduction in number of interventions, use of supplemental milk and need for IV glucose.

Bilious Emesis and Failure to Pass Meconium in the Nursery: A Case Study.

We present a case of an infant born to a mother with COVID-19, who at 24 hours of life was treated with a glycerin suppository for failure to pass meconium and went on to develop bilious emesis and abdominal distention as feeding continued over the next several hours. After a barium enema identified the distal obstruction, the pediatric surgical team used rectal irrigation to remove a large meconium plug, which mimicked the appearance of the descending colon on plain film, in a case of small left colon syndrome. Although intestinal obstruction in the newborn is rare, it is imperative that it is promptly diagnosed and treated appropriately to avoid negative outcomes; which, even in perhaps the mildest form of functional distal obstruction, meconium plug syndrome, can lead to an impressive clinical illness with risk of intestinal perforation and subsequent meconium peritonitis if the obstruction is not relieved.

Joint Effects of Prenatal Folic Acid Supplement with Prenatal Multivitamin and Iron Supplement on Obesity in Preschoolers Born SGA: Sex Specific Difference.

Prenatal maternal nutrient supplementation has been reported to be associated with offspring obesity, but the reports are inconsistent and have mainly ignored the differences between the total children population and children born small for gestational age (SGA). This study aimed to examine the joint effects of folic acid, iron, and multivitamin supplementation during pregnancy on the risk of obesity in preschoolers born SGA. A total of 8918 children aged 3-6.5 years born SGA were recruited from Longhua District in Shenzhen of China in 2021. Their mothers completed a structured questionnaire about the child's and parents' socio-demographic characteristics, maternal prepregnant obesity, and mothers' prenatal supplementation of folic acid, iron, and multivitamin. In addition, the children's current weight and height were measured by trained nurses. Logistic regression models were used to analyze the associations between prenatal supplementations and the current presence of childhood obesity. After controlling for potential confounders, the results of the logistic regression analysis showed that prenatal supplement of folic acid (OR = 0.72, 95% CI = 0.55~0.93) was associated with a lower likelihood of being an obese preschooler born SGA. In contrast, the ingestion of multivitamin or iron supplements during pregnancy did not seem to be related to the likelihood of childhood obesity in preschoolers born SGA. Moreover, cross-over analysis of prenatal folic acid and multivitamin obtained significant negative associations of prenatal folic acid supplement only (OR = 0.73, 95% CI = 0.55~0.97) and combination supplement of folic acid and multivitamin (OR = 0.67, 95% CI = 0.50~0.90) with obesity of preschoolers born SGA; while the cross-over analysis of prenatal folic acid and iron observed significant negative associations between obesity of preschoolers born SGA and a combination supplement of folic acid and iron (OR = 0.70, 95% CI = 0.52~0.96). Furthermore, the aforementioned significant associations were only found in girls and not in boys when the analyses were stratified by sex. Our findings suggest that the prenatal folic acid supplementation may decrease the risk of obesity in preschool girls born SGA, and that this effect may be modified by prenatal multivitamin or iron supplementation.

Routine contrast enema prior to stoma reversal seems only required following treatment for necrotizing enterocolitis: An evaluation of the diagnostic accuracy of the contrast enema.

INTRODUCTION: Contrast enemas are often made prior to stoma reversal in order to detect distal intestinal strictures distal of the stoma. If untreated these strictures can cause obstruction which might necessitate redo-surgery. However, the value of contrast enemas is unclear. Therefore, we aim to evaluate the contrast enema's diagnostic accuracy in detecting strictures in children with a stoma. METHODS: Young children (≤3 years) treated with a stoma between 1998 and 2018 were retrospectively included. The STARD criteria were followed. Patients treated for anorectal malformations and those that died before stoma reversal were excluded. Surgical identification of strictures during reversal or redo-surgery within three months was used as gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) reflected diagnostic accuracy. RESULTS: In 224 included children, strictures were found during reversal in 10% of which 95% in patients treated for necrotizing enterocolitis. Contrast enema was performed in 68% of all patients and detected 92% of the strictures. In the overall cohort, the sensitivity was 100%, specificity 98%, PPV 88% and NPV 100% whilst the AUC was 0.98. In patients treated for NEC, the sensitivity was 100%, specificity 97%, PPV 88% and NPV 100% whilst the AUC was 0.98. CONCLUSION: Strictures prior to stoma reversal seem to be mainly identified in patients treated for NEC and not in other diseases necessitating a stoma. Moreover, the contrast enema shows excellent diagnostic accuracy in detecting these strictures. For this reason we advise to only perform contrast enemas in patients treated for NEC. LEVEL OF EVIDENCE: II.

Potential Role of Bilirubin in Preventing Retinopathy of Prematurity.

BACKGROUND: One of the most common problems in preterm neonates is retinopathy of prematurity (ROP). It has been shown antioxidants may be effective in preventing the development and progression of ROP. Considering the antioxidant properties of bilirubin, we decided to investigate the bilirubin level in neonates with ROP and compare it with healthy neonates. METHODS: This case-control study was performed on VLBW neonates admitted to the NICU of Ghaem Hospital in Mashhad between 2014 and 2020 for a Jaundice evaluation. Complete neonate's characteristics, maternal history and laboratory results were collected in a questionnaire. Then the neonates were examined for ROP by a fellowship of the retina of an ophthalmologist at 32 weeks or four weeks after birth. The highest bilirubin levels during their hospitalization were also recorded. RESULTS: Of 427 neonates examined, 121 (37.7%) had a normal eye examination, and 266 (62.3%) had ROP. The mean weight, gestational age and bilirubin were 1455.8 ± 431.4 grams, 31.6 ± 2.3 weeks and 8.8 ± 2.4 mg/dl, respectively. There was a significant difference between controls and neonates with ROP with regard to birth weight, duration of intermittent positive pressure ventilation (IPPV), duration of oxygen therapy, first and fifth minute Apgar scores, the maximum level of bilirubin and gestational age (P < 0.05). It was observed that the maximum level of bilirubin was lower in neonates with higher stages of ROP. CONCLUSION: According to the results of this study, higher levels of bilirubin in neonates may be a protective factor against ROP. Moreover, increased levels of bilirubin are associated with reduced severity of ROP. Therefore, prophylaxis phototherapy in premature infants may need to be reconsidered.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Atuação da psicologia em unidade neonatal no contexto da pandemia da covid-19 / The work of psychology in a neonatal unit in the covid-19 pandemic / Actuación de la psicología en una unidad neonatal en el contexto de la pandemia de la covid-19

A pandemia de covid-19 provocou intensas mudanças no contexto do cuidado neonatal, exigindo dos profissionais de saúde a reformulação de práticas e o desenvolvimento de novas estratégias para a manutenção da atenção integral e humanizada ao recém-nascido. O objetivo deste artigo é relatar a atuação da Psicologia nas Unidades Neonatais de um hospital público de Fortaleza (CE), Brasil, durante o período de distanciamento físico da pandemia de covid-19. Trata-se de estudo descritivo, do tipo relato de experiência, que ocorreu no período de março a agosto de 2020. No contexto pandêmico, o serviço de Psicologia desenvolveu novas condutas assistenciais para atender às demandas emergentes do momento, como: atendimento remoto; registro e envio on-line de imagens do recém-nascido a seus familiares; visitas virtuais; e reprodução de mensagens de áudio da família para o neonato. Apesar dos desafios encontrados, as ações contribuíram para a manutenção do cuidado centrado no recém-nascido e sua família, o que demonstra a potencialidade do fazer psicológico.(AU)

The COVID-19 pandemic brought intense changes to neonatal care and required health professionals to reformulate practices and develop new strategies to ensure comprehensive and humanized care for newborn. This study aims to report the experience of the Psychology Service in the Neonatal Units of a public hospital in Fortaleza, in the state of Ceará, Brazil, during the social distancing period of the COVID-19 pandemic. This descriptive experience report study was conducted from March to August 2020. During the pandemic, the Psychology Service developed new care practices to meet the emerging demands of that moment, such as remote care, recordings and online submission of newborns' pictures and video images for their family, virtual tours, and reproduction of family audio messages for the newborns. Despite the challenges, the actions contributed to the maintenance of a care that is centered on the newborns and their families, which shows the potential of psychological practices.(AU)

La pandemia de la COVID-19 ha traído cambios intensos en el contexto de la atención neonatal, que requieren de los profesionales de la salud una reformulación de sus prácticas y el desarrollo de nuevas estrategias para asegurar una atención integral y humanizada al recién nacido. El objetivo de este artículo es reportar la experiencia del Servicio de Psicología en las Unidades Neonatales de un hospital público de Fortaleza, en Ceará, Brasil, durante el periodo de distanciamiento físico en la pandemia de la COVID-19. Se trata de un estudio descriptivo, un reporte de experiencia, que se llevó a cabo de marzo a agosto de 2020. En el contexto pandémico, el servicio de Psicología desarrolló nuevas conductas asistenciales para atender a las demandas emergentes del momento, tales como: atención remota; grabación y envío em línea de imágenes del recién nacido; visitas virtuales; y reproducción de mensajes de audio de la familia para el recién nacido. A pesar de los desafíos encontrados, las acciones contribuyeron al mantenimiento de la atención centrada en el recién nacido y su familia, lo que demuestra el potencial de la práctica psicológica.(AU)

Congenital syphilis in a preterm newborn with gastrointestinal disorders and postnatal growth restriction.

BACKGROUND: Congenital syphilis (CS) depends on the placental transmission of Treponema pallidum (TP) spirochetes from an infected mother to fetus during pregnancy. It shows a wide clinical variability with cutaneous and visceral manifestations, including stillbirths, neonatal death, and asymptomatic cases. Preterm infants with CS may have more severe features of disease than the term ones, due to the combined pathogenic effect of both CS and prematurity. CASE PRESENTATION: We report on a female preterm (32+6 weeks of gestation) newborn showing most of the typical CS manifestations, in addition to gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth restriction. The mother resulted positive at the syphilis screening test of the first trimester of pregnancy, but she did not undergo any treatment. At birth, our newborn was VDRL positive (antibody titer four times higher compared to the mother), and she was treated with intravenous benzathine benzylpenicillin G for 10 days (50,000 IU/Kg three times per day). Poor tolerance to enteral nutrition (abdominal distension, increased biliary type gastric secretions) was observed. A barium enema X-Ray identified a colon stenosis within the descending tract. However, the poor general conditions due to a concurrent fungal sepsis did not allow to perform any surgical procedure, and a conservative approach with total parenteral nutrition was started. The following evolution was marked by difficulties in enteral feeding including refusal of food and vomiting, to which also contributed the neurological abnormalities related to a perinatal asphyxia, and the affective deprivation for the physical absence of the mother during hospitalization. At 5 months of age, after the introduction of an amino acid-based formula (Neocate LCP Nutricia ®), an improvement of enteral feeding was observed, with no further and significantly decreased episodes of abdominal distension and vomiting respectively, and regular stool emission. A psychological support offered to the family allowed a more stable bond between the mother and her baby, thus providing a significant additional benefit to food tolerance and growth. She was discharged at 5 months of age, and included in a multidisciplinary follow-up. She at present shows global growth delay, and normal development apart from mildly increased tone of lower limbs. CONCLUSIONS: Our report highlights less common clinical CS manifestations like gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth delay. Moreover, it underlines how prematurity may worsen the clinical evolution of such congenital infection, due to the additional pathogenic effect of possible associated diseases and/or conditions like sepsis, hypoxic/ischemic injury, or use of drugs. CS may be observed also in high-income countries, with high rates of antenatal screening and availability of prenatal treatment. A multidisciplinary network must be guaranteed to the affected subjects, to ensure adequate care and improve the quality of life for patients and their families.

Diagnostic efficacy of high-frequency ultrasound and X-ray contrast enema in colonic strictures after necrotizing enterocolitis: a retrospective study.

OBJECTIVE: To compare the efficacy of high-frequency ultrasound and X-ray contrast enema in the diagnosis of colonic strictures after necrotizing enterocolitis. METHODS: This study included pediatric patients who developed progressive abdominal distension or constipation after conservative treatment for necrotizing enterocolitis at our hospital between June 2012 and April 2020. All patients had high-frequency ultrasounds and X-ray contrast enema, and we used surgery, pathology, and telephone return visits as the reference standard. Patients with colonic strictures were confirmed by surgery and pathology. A patient was considered without colonic stricture if no stricture was reported or did not have related symptoms during telephone return visits. The areas under the Receiver operating characteristic (ROC) curves were used as evaluation indexes to compare the differential efficacy of high-frequency ultrasound and X-ray contrast enema. RESULTS: A total of 81 patients have been included in this study. Among them, 49 patients were diagnosed with colonic strictures after necrotizing enterocolitis. The AUCs for high-frequency ultrasound and X-ray contrast enema were 0.990 vs 0.938, respectively (p > 0.05). CONCLUSION: The diagnostic efficacy of high-frequency ultrasound was similar to that of X-ray contrast enema, furthermore this study also demonstrates the benefits of using high-frequency ultrasound to identify colonic strictures after necrotizing enterocolitis.