Week 1: Clinical Trials and General Neonatology Neonatal Clinical Trials I Tuesday, June 9 4:30-6:00 pm EDT Moderators Ira Adams-Chapman Annemarie Stroustrup

EDT Abstract Title Presenting Author

4:30 pm Introduction & General Information

4:35 pm 3375446 Phase II Clinical Trial of Autologous Cord Blood Cells for Neonates with Hypoxic-Ischemic Encephalopathy Michael Cotten

4:45 pm 3374554

A Randomized Trial of Laparotomy versus Peritoneal Drainage in Extremely Low Birth Weight Infants with Necrotizing Enterocolitis or Isolated Intestinal Perforation: Outcomes through 18-22 Months Corrected Age Martin Blakely

4:55 pm 3342765

A randomized trial of higher versus lower hemoglobin transfusion thresholds for extremely low birth weight (ELBW) infants: The Transfusion of Prematures (TOP) Trial Haresh Kirpalani

5:05 pm 3380521

Listen to your Mother: A randomized clinical trial of maternal speech exposure on structural brain connectivity in preterm newborns Katherine Travis

5:15 pm 3376008

Magnetic Non-Invasive Auricular Acupuncture for Infant Comfort: A Multicenter Randomized Controlled Trial in Preterm Infants Requiring Eye-exam for Retinopathy of Prematurity (ROP) Georg Schmolzer

5:25 pm 3374217

Early Higher Parenteral Lipid Intake Decreases Extra-Uterine Growth Restriction in Very Preterm Infants: A Randomized Controlled Trial Wissam Alburaki

5:35 pm 3377315

Chlorhexidine Cord Care versus Dry Cord Care in Preterm Neonates less than 32 weeks gestation: An Open-label Randomized Controlled Trial Shashi Dhir

5:45 pm Wrap Up

Note: Schedule subject to change based on presenter availability.

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CONTROL ID: 3375446TITLE: Phase II Clinical Trial of Autologous Cord Blood Cells for Neonates with Hypoxic-Ischemic EncephalopathyPRESENTER: Charles Micheal Cotten

AUTHORS (LAST NAME, FIRST NAME): Cotten, Charles M.1; Fisher, Kimberley A.1; Malcolm, William1;Gustafson, Kathryn1; Das, Abhik8; El-Dib, Mohamed3; Shankaran, Seetha6; Weiss, Michael D.7; Salas, Ariel A.5; Bates,Sara V.2; Flibotte, John4; Kurtzberg, Joanne1

AUTHORS/INSTITUTIONS: C.M. Cotten, K.A. Fisher, W. Malcolm, K. Gustafson, J. Kurtzberg, Pediatrics, Duke University, Durham, North Carolina, UNITED STATES;S.V. Bates, Pediatrics, MGH, Boston, Massachusetts, UNITED STATES;M. El-Dib, Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, Massachusetts, UNITED STATES; J. Flibotte, Pediatrics/ Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, UNITED STATES; A.A. Salas, Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, UNITED STATES;S. Shankaran, Pediatrics, Wayne State University, Detroit, Michigan, UNITED STATES;M.D. Weiss, Pediatrics, University of Florida, Gainesville, Florida, UNITED STATES;A. Das, Biostatistics and Epidemiology, RTI International, Rockville, Maryland, UNITED STATES;CURRENT CATEGORY: NeonatologyCURRENT SUBCATEGORY: Neonatal Clinical TrialsKEYWORDS: HIE, Cord Blood Cells , Clinical Trial.SESSION TITLE: Neonatal Clinical Trials I |Neonatal Clinical Trials ISESSION TYPE: Webinar|PlatformABSTRACT BODY: Background: In neonatal animal models of hypoxic-ischemic brain injury administration of nucleated cells from human umbilical cord blood (UCB) have been shown to improve anatomic and neuro-functional outcomes. We previously demonstrated safety and feasiblity of collection, preparation and infusion of autologous volume and red blood cell-reduced UCB cells for infants treated with hypothermia for moderate to severe hypoxic-ischemic encephalopathy (HIE) in a phase I trial (Cotten J Peds 2014).

Objective: Conduct a prospective multisite, double-blind, placebo-controlled, randomized clinical trial of autologous UCB cell infusions in infants receiving hypothermia for moderate-severe HIE.

Design/Methods: Infants >35 weeks gestational age treated with hypothermia for moderate or severe HIE based on NICHD hypothermia trial entry criteria with UCB available for infusion in the first 48 postnatal hours were eligible. Thestudy intervention included up to 2 infusions of either placebo derived from whole UCB or 2-5 x 107 cells/kg of volume and red-blood cell reduced UCB. Demographics, clinical characteristics, and hospital outcomes were compared. The primary outcome was death or disability defined as survival with score <85 in cognitive, motor or language Bayley Scales of Infant and Toddler Development (BSIDIII) at 12 - 15 months.

Results: Due to slow enrollment, the study was closed to accrual 4 years after the first of 10 study sites initiated screening. Ninety-six infants treated with hypothermia were screened; 36 infants were enrolled. The primary reason for exculsion was lack of UCB collection (Fig 1). Demographics and clinical characterisitics at randomization of the infants in each group were similar (Table 1). One infant in each group died during initial hospitalization (Table 2). Two infants from each group were lost to follow-up. Four of 16 (25%) cell recipients and 9 of 16 (56%) placebo recipients with known outcomes died or had at least one BSIDIII score <85 (p = 0.07); relative risk ratio = 0.42 (95% CI: 0.16, 1.07)(Table 3).

Conclusion(s): This phase II multisite randomized trial indicates that infusion of autologous UCB cells is safe, but also indicates that UCB collection at deliveries requiring resuscitation is challenging. While the 1 year outcome results are promising, further studies inclusive of efforts to optimize autologous UCB collection and assess safety and longer term neurodevelopmental efficacy outcomes are warranted, as are efforts to develop a more readily available, safe, efficacious cell product.

Figure 1. Study Population

Table 1. Baseline Characteristics

Table 2. Hospital Outcomes

Table 3. One year outcomes

IMAGE CAPTION:Figure 1. Study Population

Table 1. Baseline Characteristics

Table 2. Hospital Outcomes

Table 3. One year outcomes

CONTROL ID: 3374554TITLE: A Randomized Trial of Laparotomy versus Peritoneal Drainage in Extremely Low Birth Weight Infants with Necrotizing Enterocolitis or Isolated Intestinal Perforation: Outcomes through 18-22 Months Corrected AgePRESENTER: Martin Blakely

AUTHORS (LAST NAME, FIRST NAME): Blakely, Martin1; Tyson, Jon2; Lally, Kevin P.3; Hintz, Susan R.4;Eggleston, Barry5; Stevenson, David K.6; Besner, Gail E.10; Das, Abhik7; Ohls, Robin K.8; Truog, William E.9; Nelin,Leif D.10; Poindexter, Brenda11; Pedroza, Claudia12; Stoll, Barbara J.13; Higgins, Rosemary D.14

AUTHORS/INSTITUTIONS: M. Blakely, Pediatric Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, UNITED STATES;J. Tyson, University of Texas Med School, Houston, Texas, UNITED STATES;K.P. Lally, Pediatric Surgery, McGovern Medical School at UTHealth, Houston, Texas, UNITED STATES;S.R. Hintz, Pediatrics/ Neonatology, Stanford University, Palo Alto, California, UNITED STATES;B. Eggleston, RTI International, Research Triangle Park, North Carolina, UNITED STATES;D.K. Stevenson, Pediatrics, Stanford University, Stanford, California, UNITED STATES;A. Das, Biostatistics and Epidemiology, RTI International, Rockville, Maryland, UNITED STATES;R.K. Ohls, Pediatrics, University of Utah, Salt Lake City, Utah, UNITED STATES;W.E. Truog, Pediatrics, Children's Mercy-Kansas City and the University of Missouri-Kansas City School of Medicine,Kansas City, Missouri, UNITED STATES;G.E. Besner, L.D. Nelin, Neonatology, Nationwide Children's Hospital, Columbus, Ohio, UNITED STATES;B. Poindexter, Pediatric and Newborn Medicine, Cincinnati Children's, Cincinnati, Ohio, UNITED STATES;C. Pedroza, Pediatrics, McGovern Medical School, Houston, Texas, UNITED STATES;B.J. Stoll, McGovern Medical School at UTHealth, Houston, Texas, UNITED STATES;R.D. Higgins, Global and Community Health, George Mason University, Fairfax, Virginia, UNITED STATES;CURRENT CATEGORY: NeonatologyCURRENT SUBCATEGORY: Neonatal Clinical TrialsKEYWORDS: necrotizing enterocolitis , surgery, intestinal perforation.SESSION TITLE: Neonatal Clinical Trials I |Neonatal Clinical Trials ISESSION TYPE: Webinar|PlatformABSTRACT BODY: Background: Extremely low birth weight infants with surgical NEC or isolated intestinal perforation (IP) have a highrisk of death and survivors usually have neurologic impairment (NDI). The impact of initial laparotomy versus peritonealdrainage on outcomes at 18-22 months corrected age is unknown.

Objective: We compared outcomes of initial laparotomy with peritoneal drain placement and investigated whether thepreferred initial treatment depends on the preoperative diagnosis (NEC or IP).

Design/Methods: This was a 20-center randomized trial with primary outcome of death or NDI at 18-22 monthscorrected age. Frequentist and Bayesian analyses were preplanned. Randomization was stratified according to center andhigher/lower risk strata (based on gestational age, birth weight, use of vasopressors or high frequency at enrollment, pH,FiO2, and surgeon's preoperative diagnosis of NEC or IP).

Results: We randomly assigned 310 infants to undergo either initial laparotomy or peritoneal drainage (Figure 1).Baseline characteristics were similar in each treatment group. There was a significant interaction between preoperativediagnosisand the initial treatment group impact on outcomes (p=0.03). Among 95 infants with a preoperative diagnosis ofNEC, death or NDI occurred in 29 (69%) after laparotomy and in 44 infants (85%) with drainage (adjusted relative risk[aRR], 0.81; 95% confidence interval [CI], 0.64 - 1.04; Bayesian posterior probability of benefit with laparotomy [P-TB]= 97%. In 213 infants with preoperative diagnosis of IP, the primary outcome occurred in 68 (69%) after laparotomy andin 64 (63%) with drainage (aRR 1.11, 95% CI: 0.95 - 1.31; Bayesian P-TB = 20%). In NEC infants, 17 (40%) died afterlaparotomy and 27 (51%) died after drainage (aRR 0.77, 95% CI: 0.52-1.13; Bayesian P-TB = 84%). Among 162 infantswith initial drainage, 81 (50%) had a subsequent laparotomy versus 35 of 146 (24%) with initial laparotomy, p=0.00).

Conclusion(s): The relative impact of initial surgical treatment on outcomes was signficantly impacted by thepreoperative diagnosis of NEC or IP. In infants with NEC, initial laparotomy reduced the likelihood of death or NDI at18-22 months, whereas with IP it did not. Laparotomy was beneficial with regards to mortality, as well as with specificneurodevelopmental impairments, in NEC infants. With a preoperative diagnosis of IP, outcomes generally favored initialdrainage.

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CONTROL ID: 3342765TITLE: A randomized trial of higher versus lower hemoglobin transfusion thresholds for extremely low birth weight (ELBW) infants: The Transfusion of Prematures (TOP) TrialPRESENTER: Haresh Kirpalani

AUTHORS (LAST NAME, FIRST NAME): Kirpalani, Haresh1; Bell, Edward F.2; Hintz, Susan R.3; Tan, Sylvia4; Schmidt, Barbara6; Chaudhary, Aasma18; Johnson, Karen J.2; Crawford, Margaret M.4; Newman, Jamie E.4; Vohr, BettyR.5; Carlo, Waldemar10; D'Angio, Carl T.7; Kennedy, Kathleen12; Ohls, Robin K.13; Poindexter, Brenda8; Schibler,Kurt14; Whyte, Robin9; Widness, John A.2; Zupancic, John11; Brambilla, Donald4; Higgins, Rosemary D.16; Das,Abhik15; National Institute of Child Health and Human Development, Eunice Kennedy Shriver17

AUTHORS/INSTITUTIONS: H. Kirpalani, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, UNITED STATES;E.F. Bell, K.J. Johnson, J.A. Widness, University of Iowa, Iowa City, Iowa, UNITED STATES;S.R. Hintz, Pediatrics/ Neonatology, Stanford University, Palo Alto, California, UNITED STATES;S. Tan, M.M. Crawford, J.E. Newman, D. Brambilla, RTI International, Washington, District of Columbia, UNITED

STATES;B.R. Vohr, Pediatrics, Women & Infants Hospital, Providence, Rhode Island, UNITED STATES;B. Schmidt, University of Pennsylvania, Philadelphia, Pennsylvania, UNITED STATES;C.T. D'Angio, University of Rochester, Rochester, New York, UNITED STATES;B. Poindexter, Perinatal Institute, Cincinnati Children's, Cincinnati, Ohio, UNITED STATES;R. Whyte, Pediatrics, Dalhousie University, Halifax, Nova Scotia, CANADA;W. Carlo, University of Alabama at Birmingham, Birmingham, Alabama, UNITED STATES;J. Zupancic, Neonatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, UNITED STATES;K. Kennedy, University Texas at Houston, Houston, Texas, UNITED STATES;R.K. Ohls, University of Utah Primary Children's Hospital, Salt Lake City, Utah, UNITED STATES;K. Schibler, Perinatal Institute, Cincinnati Children's, Cincinnati, Ohio, UNITED STATES;A. Das, Biostatistics and Epidemiology, RTI International, Rockville, Maryland, UNITED STATES;R.D. Higgins, George Mason University, Fairfax, Virginia, UNITED STATES;E. National Institute of Child Health and Human Development, Pregnancy & Perinatology, NICHD, Bethesda, Maryland,UNITED STATES;A. Chaudhary, Neonatology, CHOP, Bloomfield Hills, Michigan, UNITED STATES;CURRENT CATEGORY: NeonatologyCURRENT SUBCATEGORY: Neonatal Clinical TrialsKEYWORDS: Red cell transfusion, Extremely low birthweight infants, Randomized controlled trial.SESSION TITLE: Neonatal Clinical Trials I |Neonatal Clinical Trials ISESSION TYPE: Webinar|PlatformABSTRACT BODY: Background: Post-hoc analysis of a prior RCT suggests lower rates of neurodevelopmental impairment (NDI) at 18-21months among ELBW infants transfused at higher hemoglobin levels.

Objective: We hypothesized that a higher hemoglobin transfusion threshold decreases the risk of NDI at 22-26 monthscorrected for prematurity.

Design/Methods: Infants BW ≤1000 g and GA 22-29 weeks were consented and enrolled at participating NICHD-Neonatal Research Network NICUs within 48 hours of birth. Randomization into a Higher or Lower hemoglobin groupwas stratified by center and BW. Prescribed hemoglobin thresholds for transfusions differed by approximately 2 g/dl (20g/L) between the groups. Deviations from the transfusion algorithms were categorized as protocol violations or protocol-compliant (e.g. pre-surgery) by 2 observers without knowledge of the treatment allocation. Intervention continued to 36wk PMA, or discharge if earlier. Primary outcome at 22-26 months was: Death prior to 22-26 months or at least one of:Cognitive delay (BSID-III < 85); Cerebral palsy with GMFCS level ≥ II; Severe vision or hearing impairment. To detectan absolute difference of 7% from a baseline risk of 53.5% (alpha 0.05 and 80% power), and allowing for loss to follow-up (FU), required 1,824 infants.

Results: We enrolled 1,824 infants (911 Higher; 913 Lower) at 19 sites. Results are not shown by allocation, as final FUvisits are scheduled into January 2020. Figure 1 shows the study flow as of 11/21/2019. Mean (SD) of the entire cohort:GA 25.9 (1.5) wk, BW 756 (151) g, age at study entry 27.3 (12.7) hrs; 47.9% were male. Total transfusions = 9,865; byGA: 22+1 to 25 weeks (n=4,747 or 48%); 25+1to 29 weeks (n=5,118). Figure 2 shows hemoglobin values by group overtime. There was significant separation between groups (P<0.0001). Only 3.5% of all transfusions were classified asprotocol violations; the top 2 reasons were physician preference (n=76 or 23%) and respiratory status (n=60 or 18%). Todate ascertainment of the primary outcome is complete for 1,679/1,824 (92.1%). So far, 558/1,398 (39.9%) children areknown to have NDI; and 281/1,731 (16.2%) are known to have died before FU.

Conclusion(s): Compliance with the TOP trial transfusion algorithm to 36 weeks PMA was high. Mean hemoglobinsdiffered between groups by about 2 g/dl. Preliminary ascertainment rate for the primary outcome is 92.1%. Primaryoutcome will be available by treatment group for presentation at PAS. (NICHD and NHLBI)

Figure 1: TOP Trial Study Flow (as of 12/1/19)

Figure 2: Pre-Transfusion Hemoglobin Separation by Group (g/dl)

IMAGE CAPTION:Figure 1: TOP Trial Study Flow (as of 12/1/19)

Figure 2: Pre-Transfusion Hemoglobin Separation by Group (g/dl)

CONTROL ID: 3380521TITLE: Listen to your Mother: A randomized clinical trial of maternal speech exposure on structural brain connectivity in preterm newbornsPRESENTER: Katherine elizabeth Travis

AUTHORS (LAST NAME, FIRST NAME): Travis, Katherine E.1; Feldman, Heidi M.2; Dodson, Cory K.3;Marchman, Virginia A.3; Scala, Melissa4; Yeom, Kristen3

AUTHORS/INSTITUTIONS: K.E. Travis, pediatrics, Stanford, Stanford, California, UNITED STATES;H.M. Feldman, Pediatrics, Stanford, Palo Alto, California, UNITED STATES;C.K. Dodson, V.A. Marchman, K. Yeom, Psychology, Stanford University, Stanford, California, UNITED STATES; M. Scala, Pediatrics/Neonatology, Stanford University, San Francisco, California, UNITED STATES;CURRENT CATEGORY: NeonatologyCURRENT SUBCATEGORY: Neonatal Clinical TrialsKEYWORDS: Preterm birth, Clinical Trial, Brain development.SESSION TITLE: Neonatal Clinical Trials I |Neonatal Clinical Trials ISESSION TYPE: Webinar|PlatformABSTRACT BODY: Background: Behavioral research in infants has demonstrated the importance of speech input for language learning. Studies have yet to establish how speech exposure during infancy contributes to the maturation of brain structures relevant to speech.

Objective: This study used a randomized controlled trial to determine if enhanced speech exposure changes structural brain connectivity in preterm (PT) newborns.

Design/Methods: Participants (N=44) were PT newborns (24-31 weeks gestational age (GA) at birth), recruited when they were medically stable. Exclusion criteria included complications of PT birth known to affect brain structure (e.g., cystic periventricular leukomalacia, hydrocephalous). Newborns were randomly assigned to treatment (T: n=21) or standard of care (C: n=23) groups. The treatment was enhanced maternal speech exposure, accomplished by playing audio recordings of each baby’s own mother reading a children’s book via an iPod placed in their crib/incubator for 2.67 hours/day (2x10mins/hour between 10pm-6am). Infants in the C group had the iPod set-up, but were not played recordings. Families and medical staff were blinded to treatment. High-angular resolution diffusion MRI scans were collected as part of routine MRI imaging at near term equivalent age. Treatment effects on structural connectivity were assessed using mean diffusivity (MD) as the pre-registered primary outcome metric (NCT02847689) from frontal and posterior regions of the corpus callosum (CC).

Results: The T and C groups were matched on all medical, demographic, and experimental variables. Newborns in the T group had significantly lower MD in the superior frontal CC compared to the C group (F(1,22)=6.054, p=0.02) . The

group difference remained after controlling for GA (F(1,21)=6.09, p=0.02). Group status (T vs C) contributed significantunique variance above GA, doubling the amount of variance accounted in the model (Total R2=37%).

Conclusion(s): Findings demonstrate that increased exposure to maternal speech causes changes in structural brainconnectivity at near term equivalent ages. Lower MD in the T group implies greater white matter maturation. Thesefindings have important implications for understanding the neural bases of brain and of language development. Thepresent findings also suggest that providing increased speech exposure as part of clinical care may be beneficial topediatric populations that have limited exposure to maternal speech.

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CONTROL ID: 3376008TITLE: Magnetic Non-Invasive Auricular Acupuncture for Infant Comfort: A Multicenter Randomized Controlled Trial in Preterm Infants Requiring Eye-exam for Retinopathy of Prematurity (ROP)PRESENTER: Georg Schmolzer

AUTHORS (LAST NAME, FIRST NAME): Gan, Kimberly M.2; Oei, Ju Lee2; QUAH-SMITH, Im5; Ahmad Kamar,Azanna4; LORDUDASS, Alexis A.4; Liem, Kian D.3; Lindrea, Kwee B.4; Daly, Mary2; Mangat, Avneet K.1; Gaunker,Nilima2; Schmolzer, Georg1

AUTHORS/INSTITUTIONS: A.K. Mangat, G. Schmolzer, University of Alberta, Edmonton, Alberta, CANADA; K.M. Gan, J. Oei, M. Daly, N. Gaunker, Newborn Care, Royal Hospital for Women, Randwick, New South Wales, AUSTRALIA;K.D. Liem, Neonatology, Amalia Children's Hospital, Radboudumc, Nijmegen, NETHERLANDS;A. Ahmad Kamar, A.A. LORDUDASS, K.B. Lindrea, PAEDIATRICS, UNIVERSITY OF MALAYA, Kuala Lumpur, WILAYAH PERSEKUTUAN, MALAYSIA;I. QUAH-SMITH, University of New South Wales, Sydney, New South Wales, AUSTRALIA;CURRENT CATEGORY: NeonatologyCURRENT SUBCATEGORY: Neonatal Clinical TrialsKEYWORDS: Acupuncture, Retinopathy of Prematurity, Pain.SESSION TITLE: Neonatal Clinical Trials I |Neonatal Clinical Trials ISESSION TYPE: Webinar|PlatformABSTRACT BODY: Background: Auricular acupuncture may decrease pain from common procedures like heel pricks in newborns but its effects on longer and more stressful stressors such as eye examinations for retinopathy of prematurity (ROP), are uncertain. Our study’s objective was to evaluate the efficacy of magnetic auricular acupuncture (MAA) to decrease pain related to ROP examinations in preterm infants.

Design/Methods: Multicentre randomised controlled trial at three sites (Australia, Canada, and Malaysia) was conducted. Infants were eligible for the study if they were >32 weeks corrected gestation, required an ROP examination and not sedated. and received parental consent. A total of 132 infants were randomized to MAA (n = 64) or placebo (P, N=68). MAA stickers or placebo were placed on both ears by an unblinded investigator. Pain was assessed by blinded clinical staff with the Premature Infant Pain Profile or the Neonatal Pain Agitation Sedation Scale, which were then transformed into Z-scoresfor analysis.

Results: Infants were of similar gestation (standard deviation (SD): MAA: 28 (3), P:27± 2 weeks),birthweight (MAA:1014 (296), P:952 (273) g) and postnatal age (MAA:7 (3) P:7 (3) weeks) atrandomization. Z-scores for pain before (MAA: -0.6 (0.4), P: -0.7 (0.4)) and during (MAA:1.1(0.8), P:1. (0.7)) ROP examinations were similar between groups but were significantly lower 1hour post procedure in MAA infants (MAA: -0.7 (0.3, P: -0.4 (0.4)). * MAA was associated withsignificantly lower pain z-scores (Odds Ratio 4.03 (95% Confidence Interval, 1.05-15.54),p=0.04) after accounting for confounders (age, gestation, gender). Heart rates were alsosignificantly lower in the MAA group during ROP examination (MAA:172 (22), P:184 (18)bpm. * No adverse events were noted.

Conclusion(s): MAA may reduce physiological pain responses in infants during and after more prolonged

stressful procedures such as ROP examination. Assessment of long-term effects are warranted.

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CONTROL ID: 3374217TITLE: Early Higher Parenteral Lipid Intake Decreases Extra-Uterine Growth Restriction in Very Preterm Infants: A Randomized Controlled TrialPRESENTER: WISSAM ALBURAKI

AUTHORS (LAST NAME, FIRST NAME): ALBURAKI, WISSAM1; Yusuf, Kamran1; Alshaikh, Belal1

AUTHORS/INSTITUTIONS: W. ALBURAKI, K. Yusuf, B. Alshaikh, University of Calgary, Calgary, Alberta, CANADA;CURRENT CATEGORY: NeonatologyCURRENT SUBCATEGORY: Neonatal Clinical TrialsKEYWORDS: intravenous lipid emulsions, postnatal weight loss, extra-uterine growth restriction.SESSION TITLE: Neonatal Clinical Trials I |Neonatal Clinical Trials ISESSION TYPE: Webinar|PlatformABSTRACT BODY: Background: Approximately 43-65% of very low birth weight (VLBW) infants develop extra-uterine growth restriction (EUGR). EUGR is associated with a significant increase in the risk of neurodevelopmental impairment. Inadequate early postnatal nutrition results in excessive weight loss that cannot be explained by the physiologic contraction of body water alone. EUGR and postnatal growth failure are usually associated with negative early energy and nitrogen balance in the first week of life. Growth trajectories after initial weight loss have similar slopes regardless of gestational age, which indicates that the early excessive weight loss is a lead cause for EUGR.

Objective: To examine whether early higher lipid intake in the first week after birth in VLBW infants results in less weight loss compared to the traditional provision of intravenous lipid and subsequently reduces the incidence of EUGR.

Design/Methods: This was a randomized, open-label, controlled trial of appropriate-for-gestational age VLBW infants. Lipid intake in the control group started at 0.5-1 g/kg/day and increased daily by 0.5-1 g/kg/day until 3 g/kg/day was reached. The intervention group was started on 2 g/kg/day then increased to 3 g/kg/day the following day. Triglyceride levels were measured the day after the start and after each increase in lipid intake.

Results: Among the 176 infants assessed for eligibility, eighty-three were included in the trial. Infants in the intervention group were started on lipid earlier (13.8±7.8 vs. 17.5±7.8 h; p=0.03) and had higher cumulative lipid intake in the first 7 days of age (13.5±4.2 vs. 10.9±3.5 g/kg; p=0.004) that led to a protein to energy ratio closer to the recommended values. Infants in the intervention group had a lower percentage of weight loss (10.4±3.6 vs. 12.7±4.6; p=0.02). The mean triglyceride level was higher in the intervention group (1.91± 0.79 vs. 1.49±0.54 mmol/L; p=0.01), however, hypertriglyceridemia was similar between the two groups at 2 and 3 g/kg/day of lipid intake. Enteral energy and protein intake calculated weekly between time of parenteral nutrition discontinuation and 36 weeks corrected gestational age(CGA) were similar between the 2 groups. EUGR at 36 weeks CGA was significantly lower in the intervention group (38.6% vs. 67.6%; p=0.009).

Conclusion(s): In VLBW infants, the provision of an early and higher dose of parenteral lipid in the first week of life results in less weight loss and lower incidence of EUGR.

Table 1. Maternal and Neonatal characteristics

Table 2. Clinical Outcomes and laboratory findings

Fig 1: Total fluid intake in the first week of life.

Figure 2: Protein to Energy ratio.

IMAGE CAPTION:Table 1. Maternal and Neonatal characteristics

Table 2. Clinical Outcomes and laboratory findings

Fig 1: Total fluid intake in the first week of life.

Figure 2: Protein to Energy ratio.

CONTROL ID: 3377315TITLE: Chlorhexidine Cord Care versus Dry Cord Care in Preterm Neonates less than 32 weeks gestation: An Open-label Randomized Controlled TrialPRESENTER: Shashi Kant Dhir

AUTHORS (LAST NAME, FIRST NAME): Dhir, Shashi K.1; Dutta, Sourabh1; Bagga, Rashmi1; Kumar, Praveen1

AUTHORS/INSTITUTIONS: S.K. Dhir, S. Dutta, R. Bagga, P. Kumar, Division of Neonatology, Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India, Chandigarh, INDIA;CURRENT CATEGORY: NeonatologyCURRENT SUBCATEGORY: Neonatal Clinical TrialsKEYWORDS: Adverse Health Outcome, Chlorhexidine cord care, Neonatal mortality.SESSION TITLE: Neonatal Clinical Trials I |Neonatal Clinical Trials ISESSION TYPE: Webinar|PlatformABSTRACT BODY: Background: Chlorhexidine cord care has been shown to be effective in community based settings with high neonatal mortality. However, the few studies of Chlorhexidine cord care in hospital births have shown conflicting results. Amongst hospitalized preterm infants in developing countries, those between 26-32 weeks have the highest proportional mortality.

Objective: Research question: Among preterm neonates < 32 weeks(P), will once daily application of 4% Chlorhexidine on umbilical cord(I) as compared to Dry cord care(C) decrease a composite ‘adverse health outcome’(O) by 25%(E)?

Design/Methods: Design: Open-label randomized controlled trialParticipants: Inborn neonates 260/7 to 316/7 weeksIntervention: 4% Chlorhexidine once daily application on umbilical cord till 3 days after cord separation or Dry Cord CarePrimary Outcome: ‘Adverse health outcome’-Occurrence of any 1 of the following :(a)neonatal mortality (b)proven or probable sepsis (c)necrotizing enterocolitis(NEC) ≥stage 2 (d)retinopathy of prematurity(ROP) needing treatment(e)intraventricular hemorrhage(IVH)>grade 2 (f)bronchopulmonary dysplasia(BPD)Randomization: Stratified block randomization (260/7 to 286/7 and 290/7 to 316/7 weeks)with variable block size. Serially numbered opaque envelopes were used for allocation concealment.

Results: A total of 566 neonates were randomized to Chlorhexidine (283) and Dry cord care (283). Primary outcome was available in 564 of 566 enrolled. The incidence of primary composite ‘adverse health outcome’ did not differ between Chlorhexidine and Dry cord care [60.5% vs 60.4 %; RR 1.00(95% CI -0.88 to 1.14)].However, neonatal mortality was lower in Chlorhexidine group [22.1% vs. 31.1%; RR 0.71(95% CI 0.53 to 0.94)]. On a priori planned sub-group analysis,the lower mortality was specifically seen in 290/7 to 316/7 week strata [9.3% vs 15.2%; RR 0.62(95% CI 0.89 to 0.97)]. There were no differences in the incidence of BPD, NEC, ROP or IVH. There were no local adverse effects of Chlorhexidine application.

Conclusion(s): Chlorhexidine was not superior to Dry cord care in decreasing the incidence of a composite adversehealth outcome but it decreased neonatal mortality in 290/7-316/7 weeks gestation sub-group, albeit with wide 95% CIs. A larger trial with mortality as the primary outcome is required in this gestation sub-group.Trial registration: CTRI/2018/04/013259 (Clinical Trial Registry of India)

Funding: Indian Council of Medical Research thesis grant

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