Advances in Diagnosis and Management of Hemodynamic Instability in Neonatal Shock

Shock in newborn infants has unique etiopathologic origins that require careful assessment to direct specific interventions. Early diagnosis is key to successful management. Unlike adults and pediatric patients, shock in newborn infants is often recognized in the uncompensated phase by the presence of hypotension, which may be too late. The routine methods of evaluation used in the adult and pediatric population are often invasive and less feasible. We aim to discuss the pathophysiology in shock in newborn infants, including the transitional changes at birth and unique features that contribute to the challenges in early identification. Special emphasis has been placed on bedside focused echocardiography/focused cardiac ultrasound, which can be used as an additional tool for early, neonatologist driven, ongoing evaluation and management. An approach to goal oriented management of shock has been described and how bed side functional echocardiography can help in making a logical choice of intervention (fluid therapy, inotropic therapy or vasopressor therapy) in infants with shock

Perinatal Outcomes of Subjects Enrolled in a Multicenter Trial with a Waiver of Antenatal Consent.

OBJECTIVE:  This study aimed to determine whether outcomes differed between infants enrolled in the PREMOD2 trial and those otherwise eligible but not enrolled, and whether the use of waiver effected these differences. STUDY DESIGN:  The multicenter PREMOD2 (PREmature infants receiving Milking Or Delayed cord clamping) trial was approved for waiver of antenatal consent by six of the nine sites institutional review boards, while three sites exclusively used antenatal consent. Every randomized subject delivered at a site with a waiver of consent was approached for postnatal consent to allow for data collection. Four of those six sites\u27 IRBs required the study team to attempt antenatal consent when possible. Three sites exclusively used antenatal consent. RESULTS:  Enrolled subjects had higher Apgar scores, less use of positive pressure ventilation, a lower rate of bronchopulmonary dysplasia, and a less frequent occurrence of the combined outcome of severe intraventricular hemorrhage or death. A significantly greater number of infants were enrolled at sites with an option of waiver of consent (66 vs. 26%, risk ratio = 2.54, CONCLUSION:  PREMOD2 trial demonstrated analytical validity limitations because of the variable mix of antenatal consent and waiver of consent. A waiver of antenatal consent for minimal risk interventional trials conducted during the intrapartum period will be more successful in enrolling a representative sample of low and high-risk infants if investigators are able to enroll all eligible subjects. CLINICAL TRIAL REGISTRATION:  ClinicalTrials.gov identifier: NCT03019367. KEY POINTS: · Waiver of consent is when informed consent cannot be obtained prior to delivery.. · Cord milking is a procedure in which blood is pushed (stripped) two to four times towards the newborn.. · Delayed clamping means the umbilical cord is not clamped immediately after birth.

Perinatal outcomes of subjects enrolled in a multicenter trial with a waiver of antenatal consent

Objective This study aimed to determine whether outcomes differed between infants enrolled in the PREMOD2 trial and those otherwise eligible but not enrolled, and whether the use of waiver effected these differences. Study Design: The multicenter PREMOD2 (PREmature infants receiving Milking Or Delayed cord clamping) trial was approved for waiver of antenatal consent by six of the nine sites institutional review boards, while three sites exclusively used antenatal consent. Every randomized subject delivered at a site with a waiver of consent was approached for postnatal consent to allow for data collection. Four of those six sites' IRBs required the study team to attempt antenatal consent when possible. Three sites exclusively used antenatal consent. Results: Enrolled subjects had higher Apgar scores, less use of positive pressure ventilation, a lower rate of bronchopulmonary dysplasia, and a less frequent occurrence of the combined outcome of severe intraventricular hemorrhage or death. A significantly greater number of infants were enrolled at sites with an option of waiver of consent (66 vs. 26%, risk ratio = 2.54, p < 0.001). At sites with an option of either approaching families before delivery or after delivery with a waiver of antenatal consent, those approached prior to delivery refused consent 40% (range 15-74% across six sites) of the time. Conclusion: PREMOD2 trial demonstrated analytical validity limitations because of the variable mix of antenatal consent and waiver of consent. A waiver of antenatal consent for minimal risk interventional trials conducted during the intrapartum period will be more successful in enrolling a representative sample of low and high-risk infants if investigators are able to enroll all eligible subjects

Umbilical cord milking in non-vigorous infants: A cluster-randomized crossover trial

BACKGROUND: Delayed cord clamping (DCC) and umbilical cord milking (UCM) provide placental transfusion to vigorous newborns. Delayed cord clamping in non-vigorous newborns may not be provided due to perceived need for immediate resuscitation. UCM is an alternative since it can be performed more quickly than DCC and may confer similar benefits. OBJECTIVE: We hypothesized that UCM would reduce admission to the neonatal intensive care unit (NICU) compared with early cord clamping (ECC) in non-vigorous newborns born between 35-42 weeks\u27 gestation. STUDY DESIGN: A pragmatic cluster-randomized crossover trial of infants born at 35-42 weeks\u27 gestation from 10 medical centers in 3 countries between January 2019 and May 2021. Centers were randomized to UCM or ECC for approximately one 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 non-vigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to UCM or ECC according to their birth hospital randomization assignment. Baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the NICU for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy (HIE). Data were analyzed by intention to treat. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 UCM, 875 ECC) and 1730 had primary outcome data for analysis (97% of eligible; 872 UCM, 858 ECC) via either informed consent (606 UCM, 601 ECC) or waiver of informed consent (266 UCM, 257 ECC). The difference in the frequency of NICU admission using predefined criteria between the UCM (23%) and ECC (28%) groups did not reach statistical significance (modeled OR 0.69, 95% CI 0.41-1.14). UCM was associated with predefined secondary outcomes including a higher hemoglobin (modeled mean difference between UCM and ECC groups 0.68 g/dL, 95% CI 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude OR 0.72, 95%CI 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled OR 0.57, 95% CI 0.33-0.99) and therapeutic hypothermia (3% vs 4%, crude OR 0.57, 95% CI 0.33-0.99). Moderate-severe HIE was significantly less common with UCM (1% vs 3%, crude OR 0.48, 95% CI 0.24-0.96). No significant difference was observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude OR 0.81, 95% CI 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSIONS: Among non-vigorous infants born at 35-42 weeks\u27 gestation, UCM did not reduce NICU admission for predefined criteria. However, infants in the UCM arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate to severe HIE and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that UCM in non-vigorous infants is feasible, safe and superior to ECC

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\u27 gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks\u27 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\u27 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