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.

Prematurity and biliary atresia: a 30-year observational study.

AIM OF STUDY: The diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes? METHODS: Review of a single-centre prospectively maintained database. Prematurity was defined as delivery < 37/40 gestation. PBA was compared with date-matched term biliary atresia controls on a 2:1 basis. Primary outcomes were clearance of jaundice (< 20 µmol/L) and native liver survival. A retrospective assessment of liver fibrosis was made on biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and term cohorts. Data are quoted as median (range) unless indicated. A P value of ≤ 0.05 was considered statistically significant. RESULTS: 21 (female n = 14, 67%) premature infants with BA were treated in the period Jan. 1988-Dec. 2016 and compared with 41 contemporaneous term BA controls. Median gestation was 33 (29-36) weeks and birth weight 1930 (948-4230)g. Twin pregnancy (n = 10) was the leading cause for prematurity and significantly higher than the controls (48 vs. 0%; P < 0.0001). Maternal co-morbidity was high (n = 10, 48%) including pre-eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%) patients (all diagnostic) at a median of 57 (4-266) days. Delayed diagnosis (> 50 days) was seen in n = 13 but not associated with parenteral nutrition use (46 vs. 33%, P = 0.59) or phototherapy (50 vs. 83%, P = 0.19). Both BASM (33 vs. 7.5%; P = 0.01) and duodenal atresia (19 vs. 0%; P = 0.01) were seen more frequently in the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower in the premature group than the control group (2.71 vs. 3.53, P = 0.043) indicating less fibrosis but this equalized by time of subsequent KPE (P = 0.17). Primary surgery was Kasai portoenterostomy (n = 20) at an older median age than controls (65 vs. 56 days; P = 0.06). Liver transplantation was the primary procedure in one late-presenting child. There was an increased but non-significant clearance of jaundice in the PBA group [n = 12/20 (60%) vs 20/41 (48%); P = 0.23] post-KPE. Native liver survival and true survival were not different (P = 0.58 and 0.23). CONCLUSIONS: PBA infants have similar outcomes to term infants, despite delayed diagnosis and higher frequency of the syndromic form. The high incidence of discordant twins supports the theory that epigenetic modifications could contribute to the pathogenesis of BA. LEVEL OF EVIDENCE: IIIc Retrospective Matched Cohort Study.

Human milk and breastfeeding in surgical infants.

Human milk and breastfeeding represent the nutritional normative standards for term and preterm newborns. With the term "surgical infants" we refer to all newborns who undergo surgery during the first days of life and who are assisted in the neonatal intensive care unit during the postoperative period and then in the neonatal surgery unit. There are many obstacles to breastfeeding these newborns. The "barriers" include the unstable clinical conditions before and after surgery, the period of separation between the mother and child, and often the lack of attention to breastfeeding. Few studies have assessed if newborns with surgical diseases are breastfeed and if human milk is beneficial for their outcome. We believe that the best option is to offer them their own mother's milk through the promotion and support of breastfeeding. A specific program focused on the needs of these vulnerable children should be created. Furthermore the surgical and pediatric staff of the neonatal surgery unit should be informed and trained to increase such a program's feasibility.

Human milk fortifier: an occult cause of bowel obstruction in extremely premature neonates.

BACKGROUND: Human milk fortifier (HMF) is used in neonatal units throughout North America to facilitate growth of preterm infants. Little data is available on the gastrointestinal side effects and potential adverse events. The purpose of this paper was to present a series of infants presenting with bowel obstruction associated with HMF. METHODS: Cases of HMF obstruction were collected between January 2010 and December 2012. Charts were reviewed and relevant data was collected. RESULTS: During the study period, 7 premature infants presented with bowel obstruction secondary to intestinal concretions of HMF. All babies were premature with gestational ages from 25 to 27 weeks. Birth weight was less than 1000 grams in all patients. Patients presented with feeding intolerance, bilious aspirates, abdominal distension, and obstipation. Four of the patients presented with acute deterioration and required urgent surgical intervention. CONCLUSIONS: HMF is an important source of nutritional support in infants, which is felt to be safe. We present a series of infants where its use has resulted in significant complications. HMF should be used with caution in infants, especially those with a history of necrotizing enterocolitis. Further research should examine the calcium, protein, and fatty acid concentration tolerable in the gastrointestinal tract of infants.

Versajet hydrosurgery system in the debridement of skin necrosis after Ca gluconate extravasation: report of 9 infantile cases.

OBJECTIVE: The aim of the study was to evaluate the results of debridement with Versajet hydrosurgery system in patients with skin necrosis after ca gluconate extravasation. METHODS: We evaluated nine infants (mean age: 26 days; range: 1 day to 3 months) with calcium gluconate extravasation injury. Site of injury was the foot in 3 cases, the hand and wrist in 5 and the scalp in one. In all patients the skin necrosis was debrided with Versajet hydrosurgery system under general anesthesia without damaging the dermis layer. RESULTS: Following debridement all wounds healed spontaneously by re-epithelization and the mean time of full epithelization was fourteen days. No patient required a second debridement. At a minimum follow-up of 1 year minimal scar formation was noted and there was no hypertrophic scar. CONCLUSION: Versajet hydrosurgery system appears to be effective in the debridement of skin necrosis due to ca gluconate extravasation in pediatric population.

Total colonic aganglionosis--a diagnostic intricacy.

Total colonic aganglionosis (TCA) is an unusual variety of aganglionosis. Although appearing to be an extension of Hirschprung's disease (HD), it may differ from it in many ways and thus is difficult to diagnose on the basis of features applied for HD. The aim of this case report is to discuss the difficulties encountered in recognition of TCA and identification of features which can help in early diagnosis.

Intestinal failure-associated liver disease in surgical infants requiring long-term parenteral nutrition.

PURPOSE: Our aim was to determine incidence, severity, and outcome, as well as predisposing factors and underlying diagnoses, of intestinal failure-associated liver disease (IFALD) in surgical infants requiring long-term parenteral nutrition (PN). METHODS: We retrospectively studied surgical infants receiving PN for at least 28 days for congenital or acquired intestinal anomalies over a 5-year period (January 2006 to December 2010). Intestinal failure-associated liver disease was defined as type 1 (early)--persistent elevation of alkaline phosphatase for 6 weeks or longer; type 2 (established)--additional elevated total bilirubin (≥ 50 µmol/L); and type 3 (late)--additional clinical signs of end-stage liver disease. RESULTS: Eighty-seven infants required PN for at least 28 days. Intestinal failure-associated liver disease occurred in 29 infants (33%). Intestinal failure-associated liver disease was managed medically in all but 2 patients who underwent intestinal elongation. None were referred for intestinal or liver transplant. Intestinal failure-associated liver disease has been reversed in 17 (59%) of cases to date. Sixty-one children receiving long-term PN (70%) have achieved enteral autonomy, whereas 12 (14%) require home PN. Severity of IFALD was significantly associated with duration of PN and female sex. CONCLUSION: Intestinal failure-associated liver disease remains a fairly common but rarely life-threatening complication of intestinal failure in surgical infants. Intestinal failure-associated liver disease can be reversed in more than half of these children, and enteral autonomy was achieved in more than two thirds, even with minimal use of intestinal elongation. This is the first study to demonstrate an association between the severity of IFALD in surgical infants and female sex.

Use of an omega-3 fatty acid-based emulsion in the treatment of parenteral nutrition-induced cholestasis in patients with microvillous inclusion disease.

Microvillous inclusion disease is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. In this report, we discuss the use of a fish oil-based lipid emulsion in the treatment of 3 patients with microvillous inclusion disease who developed parenteral nutrition-associated liver disease.

Enteral fish oil for treatment of parenteral nutrition-associated liver disease in six infants with short-bowel syndrome.

STUDY OBJECTIVE: To evaluate the use of enteral fish oil for the treatment of parenteral nutrition-associated liver disease (PNALD). DESIGN: Retrospective case series. SETTING: Pediatric academic hospital and outpatient clinic. PATIENTS: Six parenteral nutrition-dependent infants with short-bowel syndrome and PNALD. MEASUREMENTS AND MAIN RESULTS: The six infants received supplementation with enteral fish oil, and treatment was evaluated over a 12-week period. The PNALD, as reflected by elevated total bilirubin levels, completely reversed in four of the six infants within a mean ± SD of 5 ± 2.6 weeks (range 2-8 wks) after initiation of the enteral fish oil supplementation. In addition, improvement in enteral feedings occurred after starting enteral fish oil therapy. CONCLUSION: Enteral fish oil may be an effective adjunctive treatment option for infants with PNALD, particularly for those infants with PNALD who are tolerating some amount of enteral nutrition as the result of an adequate amount of small bowel.

[Development of pediatric surgery in the next 20 years]. / Entwicklung der Kinderchirurgie in den nächsten 20 Jahren.

Pediatric surgery focuses not on an anatomic region or organ system, but on the development of a growing human being according to age. Recently, a tendency to reduce and to downgrade pediatric surgery could be observed which is due to economic reasons and an alarming lack of trained surgeons. Just as 60 years ago, general surgeons continue to operate on infants and children. However, this is a step backwards and an anachronism. Children are not small adults and pediatric surgery can be distinguished from adult surgery in many aspects, such as the spectrum of surgical diseases, the congenital malformations and frequently the indications and techniques of surgery. Pediatric surgeons, however, by themselves should specialize in centers which are focused on rare and complex diseases. Pediatric surgery should not be separated in the hospital, but integrated in a network with general surgery, traumatology, pediatrics, neonatology and specialists of the other surgical disciplines. Strict patient age limitations are not compatible with the individuality of adolescents and should be avoided. A well-equipped clinic for pediatric surgery is expensive, but a mandatory investment in the future!

Acute neonatal arterial occlusion: is thrombolysis safe and effective?

PURPOSE: We report our experience of the management of arterial occlusion in the newborn. METHODS: A case note review was carried out after ethical approval. Doppler ultrasonography confirmed the occlusion. Thrombolysis was the primary intervention. Surgery was used selectively. A good outcome was one without tissue loss or functional impairment or minimal tissue loss without functional impairment. Data are presented as medians with ranges. RESULTS: Ten patients (9 male; median gestational age, 35.5 weeks [range, 28-39 weeks]) presented on day 1 (range, 1-8 days). Initial management included systemic tissue plasminogen activator (8 patients) and surgery (2 infants in whom thrombolysis was contraindicated). Improvement was noted in 7 of 8 infants treated medically and in both who underwent surgery. Three infants had significant tissue loss. Outcome at 29 months (range, 1.3-95.4 months) was good in the remaining 7. CONCLUSIONS: A multidisciplinary approach, thrombolysis and selective surgery achieved tissue preservation and function in the majority while minimizing complications. Early referral to centers with multidisciplinary teams is recommended.

Transfusion-free arterial switch operation in a 1.7-kg premature neonate using a new miniature cardiopulmonary bypass system.

In cardiac surgery, the potentially detrimental effects of transfusions on patient outcome are increasingly appreciated. Therefore, at our institution there are continuing efforts to modify our surgical, perfusion, and blood management strategies with the aim of transfusion-free cardiac surgery even in neonates and small children. Stringent improvement of these strategies, particularly the downsizing of the cardiopulmonary bypass system, have now enabled a transfusion-free arterial switch operation in a 1700-gram prematurely born neonate.

[Pseudo-"isolated" intestinal perforation in a very low birth weight infant: exceptional presentation of Hirschsprung's disease]. / Perforation intestinale du grand prématuré en apparence "isolée": mode de révélation exceptionnel de la maladie de Hirschsprung.

Intestinal perforations in preterm newborn are characterized with high morbidity and mortality rates. They often are associated with necrotizing enterocolitis and seldom correspond to idiopathic spontaneous intestinal perforation. Perforations upstream of an intestinal organic obstruction (atresia), or of a functionnal obstruction (meconium-ileus, Hirschsprung disease) have been considered to be rare in preterm newborns. We report a case of caecal perforation with a pneumoperitoneum which occurred at 5 days of life, in a 28-week gestational age infant, that was treated by cecostomy. There were no signs of necrotizing enterocolitis. At 43 days of life, the preoperative contrast enema study revealed a left colon transition zone, suggesting a Hirschsprung disease, which was confirmed by rectal biopsies. Transanal pull-through was performed. There were no postoperative complication. This case demonstrates that an isolated intestinal perforation in very preterm newborn can reveal a Hirschsprung disease, especially if it occurs in the caecum.

Major full thickness skin burn injuries in premature neonate twins.

Burns in neonates have been reported following the use of pulse oximeters, various electrodes, chemical disinfecting agents and phototherapy blankets. Burn injuries in premature neonates are very rare and there have been no reports on major full skin thickness injuries. This case reports on preterm neonate male twins delivered at a Community Hospital. After the delivery they were placed on water warmers for 15-20 min and then transported into incubators. Burn injuries were noticed 1h after the delivery. Infant One, weight 1500 g, had an injury of 20% TBSA on his dorsum, waist and buttocks. The other infant, weight 1835 g, had an injury of 14% TBSA on the same areas. The infants were transported to the University Hospital. At the seventh day after the injury they recovered from respiratory distress and surgical procedures started. The eschar was excised deep to fascia and wounds were grafted with 0.1mm thickness skin grafts harvested from the thigh and cut into islets. Autografts were protected by overlay with fresh allograft harvested from the twins' father. Surgery procedures were performed in two steps, each second day, not exceeding 10% of total body area during excision. Donor sites healed at the eighth day after the surgery. Burn wounds healed gradually by way of spontaneous replacement of allograft and wound closure by spontaneous epithelization from the autograft islets. Eighteen days after the surgery all the grafted wounds were found epithelized. We conclude that in premature neonates relatively low temperatures may cause deep burn injuries. We recommend the delivery of preterm childbirths at well equipped facilities with staff qualified in nursing of premature neonates.

Clinical features and treatment outcome of intussusception in premature neonates.

BACKGROUND/PURPOSE: Less than 1.3% of all cases of intussusception occur in term neonates. Intussusception in premature neonates (IPN) is exceedingly rare. Its rarity and difficulty to differentiate IPN from common neonatal diseases like necrotizing enterocolitis (NEC) often delays its diagnosis. The authors set out to characterize diagnosis, treatment, and outcome of this rare condition. METHODS: The authors analyzed 2 new cases of IPN and 33 previously reported cases from the literature. RESULTS: The 35 patients with IPN had an average gestational age, postconceptual age at diagnosis, and birth weight of 28.4 +/- 0.6 weeks (all data, mean +/- SEM), 31.1 +/- 0.5 weeks, and 1,165 +/- 21 g, respectively. Gastrointestinal symptoms first presented at age 8 +/- 1 days. A preoperative diagnosis of NEC was assumed in 24 patients, delaying diagnosis by 10 +/- 2 days. Intussusception was diagnosed radiographically in 2 patients (1 contrast enema and 1 ultrasound scan) and during surgery or autopsy in the remainder. Resection was reported in 28 patients for bowel that was irreducible, necrotic, or perforated. The overall mortality rate was 20%, mainly owing to sepsis. CONCLUSIONS: Intussusception in the premature neonate often is misdiagnosed as NEC, delaying operative intervention. Contrast enema has limited diagnostic capability. Early diagnosis may be achieved with use of ultrasound scan. Intussusception can be treated successfully with resection and primary anastomosis, achieving good results.

Perinatal intussusception in premature infants.

Intussusception is common in infants aged 5 to 18 months, but there have been only 12 reports of its occurrence among premature infants. Nine of these previously reported cases with adequate data and one new case are reviewed. Many of the infants were believed to have necrotizing enterocolitis, leading to an average 12-day interval between the onset of signs and the operation. Bilious emesis or nasogastric contents, bloody stool, and intestinal dilation without pneumatosis intestinalis were common. A contrast enema showed the intussusception in only 1 of 7 cases. Most cases were diagnosed in the operating room and underwent successful primary anastomosis, with no recurrences. A pathological lead point was identified in 2 of the 10 cases. The overall mortality rate was 23%; the one death since 1970 was secondary to attempted hydrostatic reduction. These cases may represent what, in the absence of premature delivery, would have been the intrauterine development of intussusception likely leading to small bowel atresia.

Surgical procedures in colonic strictures after necrotizing enterocolitis.

Between 1982 and 1992, 22 patients were treated with colonic strictures in the course of necrotizing enterocolitis (NEC). Fourteen newborns in whom a primary enterostomy and, when necessary, resection of necrotic bowel was performed developed strictures in the diverted colon. The strictures were detected by colon contrast enema study performed on average 3 months after the first intervention. Eight additional children suffered from an ileus due to primary strictures after conservatively treated NEC, which was surgically managed by enterostomy. Closure of the enterostomy and resection of the stenotic part of the colon was performed thereafter in all 22 children as a single stage procedure. There was no insufficiency of the anastomosis nor any late stricture at follow-up 2.7 years after NEC in our patients. It is concluded therefore that reanastomosis of the enterostomy and resection of an intestinal stricture can be performed as a single stage procedure without any risk after an interval of 3 months between onset of acute NEC and reevaluation. During this interval, a close monitoring and an appropriate management of adequate supplement of electrolytes and bicarbonates is necessary. Most of our babies could be nursed at home and showed a good weight gain during this period, despite the enterostomy.

Surgical treatment of intractable cholestasis associated with total parenteral nutrition in premature infants.

We report surgical reversal of intractable total parenteral nutrition (TPN)-associated cholestasis refractory to conservative treatment in 9 premature infants. Indications for TPN were poorly tolerated enteral feedings in all patients. Five patients had undergone gastrointestinal operations; in addition, 7 of the 9 patients had had bacterial sepsis. The median duration of TPN was 28 days (range, 20 to 50 days). The median duration of preoperative full enteral nutrition after weaning from TPN was 34 days (range, 16 to 95 days). All patients had progressive conjugated hyperbilirubinemia, no excretion of Tc-labeled HIDA to the biliary tree and duodenum, and markedly elevated liver enzyme values. Intraoperative cholangiography showed normal biliary anatomy in all cases; in addition, 2 patients had gallbladder stones. Bile was hyperviscous in all patients and contained biliary sludge in 4. The biliary tree was irrigated and the liver biopsied in all patients. The gallbladder was removed from 2 patients who had stones in the gallbladder. Liver histology was consistent with TPN-associated cholestasis in all cases, and in addition, 4 cases showed significant destruction of intrahepatic bile ducts. One patient died 2 weeks postoperatively from intracerebral hemorrhage. Jaundice completely resolved in other patients within 2 weeks. HIDA-biligraphy performed 1 to 2 months postoperatively showed normal excretion of the radioactive marker to the biliary tree and duodenum in all cases. The functional abnormality in bile excretion and bile duct motility in TPN-associated cholestasis may be reversed by irrigation of the biliary tree. Surgical intervention should be considered when cholestasis is progressive and refractory to medical management.