Accepted Manuscript Effect of Umbilical Cord Milking on Morbidity and Survival in Extremely Low Gestational Age Neonates Shrena Patel , MD Erin A.S. Clark , MD Christina E. Rodriguez , MD Torri D. Metz , MD Minda Abbaszadeh , APRN Bradley A. Yoder , MD PII:
S0002-9378(14)00505-5
DOI:
10.1016/j.ajog.2014.05.037
Reference:
YMOB 9847
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 13 February 2014 Revised Date:
8 April 2014
Accepted Date: 24 May 2014
Please cite this article as: Patel S, Clark EAS, Rodriguez CE, Metz TD, Abbaszadeh M, Yoder BA, Effect of Umbilical Cord Milking on Morbidity and Survival in Extremely Low Gestational Age Neonates, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.05.037. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Effect of Umbilical Cord Milking on Morbidity and Survival in Extremely Low Gestational Age Neonates
RI PT
Shrena PATEL MD1, Erin A.S. CLARK MD2, Christina E. RODRIGUEZ MD2, Torri D. METZ MD2, Minda ABBASZADEH APRN1, Bradley A. YODER MD1 1
Division of Neonatology, University of Utah, Salt Lake City, UT
2
SC
Division of Maternal-Fetal Medicine, University of Utah, Salt Lake City, UT
Dr. Metz is now with the Departments of Obstetrics and Gynecology, Denver
M AN U
Health Medical Center, Denver, CO and the University of Colorado, Aurora, CO.
The authors report no conflict of interest.
The authors have no financial support to report for this manuscript.
TE D
Preliminary findings were presented through Abstract #52, at the American Academy of Pediatrics National Conference and Exhibition, presented by the American Academy of Pediatrics, Orlando, Florida, October 26-October 29,
EP
2013.
AC C
The authors have no disclaimer(s) to report.
Please address reprints requests to: Shrena Patel, MD
Division of Neonatology 295 Chipeta Way Salt Lake City, UT 84108 [email protected] 1
ACCEPTED MANUSCRIPT
Corresponding/Responsible author: Shrena Patel, MD
RI PT
Division of Neonatology 295 Chipeta Way Salt Lake City, UT 84108
SC
W: 801-581-7052
F: 801-585-7395 [email protected]
M AN U
C: 801-971-0391
AC C
EP
TE D
Word count: Abstract – 259, Manuscript – 3257
2
ACCEPTED MANUSCRIPT
Condensation:
In extremely low gestational age neonates, milking of the umbilical cord
stability, without adversely affecting immediate resuscitation.
RI PT
increases survival, decreases major morbidity, and improves hemodynamic
AC C
EP
TE D
M AN U
SC
Short version of title: Cord milking in extremely low gestational age neonates
3
ACCEPTED MANUSCRIPT
Abstract Objective: Delayed umbilical cord clamping benefits extremely low gestational age neonates
RI PT
(ELGANs), but has not gained wide acceptance. We hypothesized milking the
umbilical cord (MUC) would avoid resuscitation delay but improve hemodynamic stability and reduce rates for composite outcome of severe intraventricular
SC
hemorrhage (IVH), necrotizing enterocolitis (NEC), and/or death prior to
M AN U
discharge.
Study Design:
We implemented a joint Neonatal/Maternal-Fetal quality improvement process for MUC starting September 2011. The MUC protocol specified that infants born 65%; among MUC QI infants 10 (6.3%) had hematocrits > 60% with one > 65% (66.9%). None of the infants with hematocrits > 60% manifested signs of
RI PT
polycythemia-hyperviscosity syndrome 16. Bilirubin levels were no different at 24 hours age (mean values: MUC 4.7 mg/dl versus Control 4.4 mg/dl, P = 0.60),
though peak bilirubin in the first week of life was slightly but significantly higher in
SC
the MUC era compared to the historical controls ( 9.1 + 2.2 mg/dL versus 7.9 + 2.4 mg/dL, respectively; P < 0.001). Nearly all received phototherapy in the first
underwent exchange transfusion.
M AN U
week, 94% in the MUC group and 95% in the historical controls. No infants
Lower rates were found in the MUC QI period for early dopamine use and
TE D
supplemental volume administration in the first 24 hours of life, though only less dopamine use reached significance (Table 3). The lowered rates of dopamine and volume support were primarily attributable to infants born at < 27 weeks.
EP
Despite less inotrope and volume use, mean blood pressures were consistently
AC C
higher over the initial 24 hours of life in the MUC QI period (Figure 1).
Mortality and major morbidities are shown in Table 3. Infants born during the MUC era had significantly decreased risk of the composite outcome of severe IVH, NEC, and death prior to hospital discharge. The individual outcomes of severe IVH, NEC and death prior to hospital discharge were also significantly
12
ACCEPTED MANUSCRIPT
different between groups. The greatest effect appeared to be in infants < 27 weeks’ gestation (Table 3).
RI PT
Regression modeling demonstrated that the most important risk factor for the
composite outcome was gestational age at birth (Table 4). Other independent risk factors included a diagnosis of clinical chorioamnionitis and placental
SC
abruption. Regression analysis also demonstrated a significant association
between the composite outcome and birth during the MUC era compared to the
M AN U
historical control group.
5. Discussion:
In a prospective cohort of high-risk preterm infants 24 hours, n (%)
30 (19%)
45 (29%)
0.041
Maternal age (yrs), mean (SD)
RI PT
P
Maternal race, n (%)
97 (61%) 4 (3%)
M AN U
Multiple gestation, n (%) Any antenatal steroids
0.939
0.037
75%)
AC C
EP
Cesarean delivery, n (%)
TE D
# doses steroids, median (25-
a
MUC – milking of umbilical cord, bIUGR – intrauterine growth restriction, c ROM – rupture of membranes
25
ACCEPTED MANUSCRIPT
Table 2: Baseline neonatal characteristics and resuscitation prior to and after initiation of umbilical cord milking QI program. MUCa Era
Controls
(n=158)
(n=160) 27.1 (23.0, 29.9)
27.4 (23.1, 29.9)
0.010
Birth weight (g) b
880 (375, 2050)
960 (410, 1910)
0.009
Male, n (%)
8 (54%)
91 (57%)
0.490
Apgar score, 1 minute b
5 (2, 7)
4 (2, 6)
0.570
Apgar score, 5 minutes b
7 (6, 8)
7 (6, 8)
0.720
36.3 (35.8, 36.7)
36.5 (36.0, 36.8)
0.277
Blow by oxygen or CPAP Positive pressure breaths
Chest compressions
EP
Intubation
AC C
Age at intubation, minutes b
Age at surfactant, minutes b
M AN U
20 (13%)
34 (22%)
23 (14%)
13 (8%)
109 (68%)
104 (64%)
TE D
Maximum resuscitation, n (%)
SC
Gestation (weeks) b
Temperature on admission, oCb
a
P
RI PT
Historical
0.127
8 (5%)
10 (6%)
5 (4, 10)
6 (3, 11)
0.764
29 (20, 60)
38 (23, 60)
0.012
MUC – milking of umbilical cord, b Median (25th, 75th percentiles)
26
ACCEPTED MANUSCRIPT
Table 3: Comparison of neonatal outcomes prior to (“Controls”) and after (“MUCa”) initiation of umbilical cord milking QI programb MUCa
Controls
MUCa
S0002-9378(14)00505-5
DOI:
10.1016/j.ajog.2014.05.037
Reference:
YMOB 9847
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 13 February 2014 Revised Date:
8 April 2014
Accepted Date: 24 May 2014
Please cite this article as: Patel S, Clark EAS, Rodriguez CE, Metz TD, Abbaszadeh M, Yoder BA, Effect of Umbilical Cord Milking on Morbidity and Survival in Extremely Low Gestational Age Neonates, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.05.037. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Effect of Umbilical Cord Milking on Morbidity and Survival in Extremely Low Gestational Age Neonates
RI PT
Shrena PATEL MD1, Erin A.S. CLARK MD2, Christina E. RODRIGUEZ MD2, Torri D. METZ MD2, Minda ABBASZADEH APRN1, Bradley A. YODER MD1 1
Division of Neonatology, University of Utah, Salt Lake City, UT
2
SC
Division of Maternal-Fetal Medicine, University of Utah, Salt Lake City, UT
Dr. Metz is now with the Departments of Obstetrics and Gynecology, Denver
M AN U
Health Medical Center, Denver, CO and the University of Colorado, Aurora, CO.
The authors report no conflict of interest.
The authors have no financial support to report for this manuscript.
TE D
Preliminary findings were presented through Abstract #52, at the American Academy of Pediatrics National Conference and Exhibition, presented by the American Academy of Pediatrics, Orlando, Florida, October 26-October 29,
EP
2013.
AC C
The authors have no disclaimer(s) to report.
Please address reprints requests to: Shrena Patel, MD
Division of Neonatology 295 Chipeta Way Salt Lake City, UT 84108 [email protected] 1
ACCEPTED MANUSCRIPT
Corresponding/Responsible author: Shrena Patel, MD
RI PT
Division of Neonatology 295 Chipeta Way Salt Lake City, UT 84108
SC
W: 801-581-7052
F: 801-585-7395 [email protected]
M AN U
C: 801-971-0391
AC C
EP
TE D
Word count: Abstract – 259, Manuscript – 3257
2
ACCEPTED MANUSCRIPT
Condensation:
In extremely low gestational age neonates, milking of the umbilical cord
stability, without adversely affecting immediate resuscitation.
RI PT
increases survival, decreases major morbidity, and improves hemodynamic
AC C
EP
TE D
M AN U
SC
Short version of title: Cord milking in extremely low gestational age neonates
3
ACCEPTED MANUSCRIPT
Abstract Objective: Delayed umbilical cord clamping benefits extremely low gestational age neonates
RI PT
(ELGANs), but has not gained wide acceptance. We hypothesized milking the
umbilical cord (MUC) would avoid resuscitation delay but improve hemodynamic stability and reduce rates for composite outcome of severe intraventricular
SC
hemorrhage (IVH), necrotizing enterocolitis (NEC), and/or death prior to
M AN U
discharge.
Study Design:
We implemented a joint Neonatal/Maternal-Fetal quality improvement process for MUC starting September 2011. The MUC protocol specified that infants born 65%; among MUC QI infants 10 (6.3%) had hematocrits > 60% with one > 65% (66.9%). None of the infants with hematocrits > 60% manifested signs of
RI PT
polycythemia-hyperviscosity syndrome 16. Bilirubin levels were no different at 24 hours age (mean values: MUC 4.7 mg/dl versus Control 4.4 mg/dl, P = 0.60),
though peak bilirubin in the first week of life was slightly but significantly higher in
SC
the MUC era compared to the historical controls ( 9.1 + 2.2 mg/dL versus 7.9 + 2.4 mg/dL, respectively; P < 0.001). Nearly all received phototherapy in the first
underwent exchange transfusion.
M AN U
week, 94% in the MUC group and 95% in the historical controls. No infants
Lower rates were found in the MUC QI period for early dopamine use and
TE D
supplemental volume administration in the first 24 hours of life, though only less dopamine use reached significance (Table 3). The lowered rates of dopamine and volume support were primarily attributable to infants born at < 27 weeks.
EP
Despite less inotrope and volume use, mean blood pressures were consistently
AC C
higher over the initial 24 hours of life in the MUC QI period (Figure 1).
Mortality and major morbidities are shown in Table 3. Infants born during the MUC era had significantly decreased risk of the composite outcome of severe IVH, NEC, and death prior to hospital discharge. The individual outcomes of severe IVH, NEC and death prior to hospital discharge were also significantly
12
ACCEPTED MANUSCRIPT
different between groups. The greatest effect appeared to be in infants < 27 weeks’ gestation (Table 3).
RI PT
Regression modeling demonstrated that the most important risk factor for the
composite outcome was gestational age at birth (Table 4). Other independent risk factors included a diagnosis of clinical chorioamnionitis and placental
SC
abruption. Regression analysis also demonstrated a significant association
between the composite outcome and birth during the MUC era compared to the
M AN U
historical control group.
5. Discussion:
In a prospective cohort of high-risk preterm infants 24 hours, n (%)
30 (19%)
45 (29%)
0.041
Maternal age (yrs), mean (SD)
RI PT
P
Maternal race, n (%)
97 (61%) 4 (3%)
M AN U
Multiple gestation, n (%) Any antenatal steroids
0.939
0.037
75%)
AC C
EP
Cesarean delivery, n (%)
TE D
# doses steroids, median (25-
a
MUC – milking of umbilical cord, bIUGR – intrauterine growth restriction, c ROM – rupture of membranes
25
ACCEPTED MANUSCRIPT
Table 2: Baseline neonatal characteristics and resuscitation prior to and after initiation of umbilical cord milking QI program. MUCa Era
Controls
(n=158)
(n=160) 27.1 (23.0, 29.9)
27.4 (23.1, 29.9)
0.010
Birth weight (g) b
880 (375, 2050)
960 (410, 1910)
0.009
Male, n (%)
8 (54%)
91 (57%)
0.490
Apgar score, 1 minute b
5 (2, 7)
4 (2, 6)
0.570
Apgar score, 5 minutes b
7 (6, 8)
7 (6, 8)
0.720
36.3 (35.8, 36.7)
36.5 (36.0, 36.8)
0.277
Blow by oxygen or CPAP Positive pressure breaths
Chest compressions
EP
Intubation
AC C
Age at intubation, minutes b
Age at surfactant, minutes b
M AN U
20 (13%)
34 (22%)
23 (14%)
13 (8%)
109 (68%)
104 (64%)
TE D
Maximum resuscitation, n (%)
SC
Gestation (weeks) b
Temperature on admission, oCb
a
P
RI PT
Historical
0.127
8 (5%)
10 (6%)
5 (4, 10)
6 (3, 11)
0.764
29 (20, 60)
38 (23, 60)
0.012
MUC – milking of umbilical cord, b Median (25th, 75th percentiles)
26
ACCEPTED MANUSCRIPT
Table 3: Comparison of neonatal outcomes prior to (“Controls”) and after (“MUCa”) initiation of umbilical cord milking QI programb MUCa
Controls
MUCa
