Identification of Extremely Premature Infants at Low Risk For Early-Onset Sepsis
Identification of Extremely Premature Infants at Low Risk For Early-Onset Sepsis
Identification of Extremely Premature Infants at Low Risk For Early-Onset Sepsis
BACKGROUND: Premature infants are at high risk of early-onset sepsis (EOS) relative to term abstract
infants, and most are administered empirical antibiotics after birth. We aimed to determine
if factors evident at birth could be used to identify premature infants at lower risk of EOS.
METHODS: Study infants were born at 22 to 28 weeks’ gestation in Neonatal Research Network
centers from 2006 to 2014. EOS was defined by isolation of pathogenic species from blood
or cerebrospinal fluid culture at ≤72 hours age. Infants were hypothesized as “low risk” for
EOS when delivered via cesarean delivery, with membrane rupture at delivery, and absence
of clinical chorioamnionitis. Frequency of prolonged antibiotics (≥5 days) was compared
between low-risk infants and all others. Risks of mortality, EOS, and other morbidities
were assessed by using regression models adjusted for center, race, antenatal steroid use,
multiple birth, sex, gestation, and birth weight.
RESULTS: Of 15 433 infants, 5759 (37%) met low-risk criteria. EOS incidence among infants
surviving >12 hours was 29 out of 5640 (0.5%) in the low-risk group versus 209 out of 8422
(2.5%) in the comparison group (adjusted relative risk = 0.24 [95% confidence interval,
0.16–0.36]). Low-risk infants also had significantly lower combined risk of EOS or death
≤12 hours. Prolonged antibiotics were administered to 34% of low-risk infants versus 47%
of comparison infants without EOS.
CONCLUSIONS: Delivery characteristics of extremely preterm infants can be used to identify
those with significantly lower incidence of EOS. Recognition of differential risk may help
guide decisions to limit early antibiotic use among approximately one-third of these infants.
NIH
aDivision of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; bDepartment of What’s Known on This Subject: Characteristics
Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; cBiostatistics known at birth including gestational age identify
and Epidemiology Division, RTI International, Research Triangle Park, North Carolina; dDivision of Neonatology,
infants at highest risk of early-onset sepsis (EOS). It
Duke University Medical Center, Duke University, Durham, North Carolina; eMcGovern Medical School, University
of Texas Health Science Center at Houston, Houston, Texas; fSection of Neonatology, Nationwide Children’s is unknown if delivery characteristics can be used
Hospital, The Ohio State University, Columbus, Ohio; gDepartment of Pediatrics, University of Iowa, Iowa City, to identify premature infants at lowest risk of EOS to
Iowa; hBiostatistics and Epidemiology Division, RTI International, Rockville, Maryland; iWarren Alpert Medical guide empirical antibiotic therapy.
School, Brown University and Women & Infants Hospital of Rhode Island, Providence, Rhode Island; jDepartment
of Pediatrics, School of Medicine, Stanford University, Stanford, California; kLucile Packard Children’s Hospital, What This Study Adds: Specific criteria can
Palo Alto, California; and lDepartment of Pediatrics, University of Texas Southwestern Medical Center at Dallas, identify premature infants with a 76% lower
Parkland Health & Hospital System, and Children’s Medical Center Dallas, Dallas, Texas adjusted risk for EOS. A substantial proportion
Dr Puopolo conceptualized and designed the study and reviewed and revised the manuscript; of these infants received prolonged antibiotics
Dr Mukhopadhyay designed the study and drafted the initial manuscript; Ms Hansen conducted despite their lower a priori risk. Recognition of
the statistical analyses and critically reviewed the manuscript; Drs Stoll, Cotten, and Sanchez this differential risk may reduce early antibiotic
contributed to the study concept and reviewed and revised the manuscript; Ms Hensman and exposures.
Drs Bell, Das, Van Meurs, and Wyckoff reviewed and revised the manuscript; and all authors
approved the final manuscript as submitted.
To cite: Puopolo KM, Mukhopadhyay S, Hansen NI, et al.
Identification of Extremely Premature Infants at Low Risk
for Early-Onset Sepsis. Pediatrics. 2017;140(5):e20170925
chorioamnionitis, 51; maternal age, 1 infant; gravida, 4; maternal race and/or ethnicity, 58; prenatal care, 7; maternal
infants surviving >12 hours, accounting
insulin dependent diabetes, 6; maternal hypertension, 7; antepartum hemorrhage, 4; maternal antibiotics, 54; antenatal
for the age at which assessment took steroids, 29; SGA, 4; infant sex, 4; Apgar score, 116; first temperature within 60 min, 125; temperature if within 60 min,
place. Combined death or morbidity 10; surfactant, 1 infant; nitric oxide, 17 infants; timing of enteral feeds, 3 infants; respiratory support at 24 h, 30 infants;
respiratory support day 1–3, 12 infants.
outcomes were also examined to
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TABLE 1 Continued A P value < .05 was considered
b P value by the χ2 test (categorical variables) or the Wilcoxon test (continuous variables).
c Maternal white or African American race with missing ethnicity information (4.6% of African Americans, 0.8% of whites)
significant; no adjustment was made
were classified as non-Hispanic. Other races included Asian American and/or Pacific Islander, American Indian and/or for multiple comparisons. Analyses
Alaskan native, >1 race, other not specified, with non-Hispanic ethnicity.
d Maternal magnesium sulfate use was collected beginning April 1, 2011.
were performed by using SAS version
e Infant hypotension treatment and highest base deficit were collected beginning April 1, 2011. In this group, hypotension 9.4 (SAS Institute, Cary, NC).
treatment was missing for 2 infants and highest base deficit was missing for 263 infants.
f Respiratory support was defined as any one of mechanical ventilation (high frequency or conventional), nasal
synchronized intermittent mandatory ventilation, or continuous positive airway pressure received at 24 h or during any
Results
of the first 3 d of life.
Study Population
Between January 1, 2006, and
TABLE 2 Mortality and EOS December 31, 2014, 16 185 infants
N (Column %) Low Risk of EOS Comparison Adjusted RR for with GA 22 to 28 weeks and BW 401 to
Group Outcome (95% CI): Low 1500 g were born at NRN centers. Of
Risk of EOS Versus the
Comparison Groupa
these, 640 (4%) infants with a major
congenital anomaly, 111 (0.7%) infants
All infants 5759 9674 —
Died before discharge 938 (16.3) 2629 (27.2) 0.88 (0.82–0.94)
with insufficient information (maternal
Died ≤12 h 119 (2.1) 1252 (12.9) 0.42 (0.35–0.52) clinical chorioamnionitis, 54; ROM,
EOS or death ≤12 hb 148 (2.6) 1461 (15.1) 0.36 (0.30–0.43) 43; EOS or antibiotic information, 10;
By GA, wk delivery type, 4), and 1 infant with
22 7/16 (43.8) 497/601 (82.7) 0.61 (0.35–1.05) congenital syphilis were excluded.
23 31/181 (17.1) 480/1207 (39.8) 0.50 (0.36–0.68)
24 44/662 (6.6) 200/1445 (13.8) 0.46 (0.34–0.63)
Thus, 15 433 infants were studied, of
25 21/916 (2.3) 107/1488 (7.2) 0.28 (0.18–0.45) whom 5759 (37.3%) were classified
26 19/1089 (1.7) 73/1504 (4.9) 0.29 (0.18–0.48) into the low-risk group and 9674
27 16/1353 (1.2) 50/1661 (3.0) 0.31 (0.17–0.53) (62.7%) into the comparison group.
28 10/1542 (0.6) 54/1768 (3.1) 0.17 (0.08–0.33)
EOS (incl. CONS) or death ≤12 h 165 (2.9) 1484 (15.3) 0.39 (0.33–0.46) Maternal and Infant Characteristics
Infants who survived >12 h 5640 8422 —
EOSc 29 (0.5) 209 (2.5) 0.24 (0.16–0.36) By definition, all infants in the low-risk
EOS (incl. CONS) 46 (0.8) 232 (2.8) 0.33 (0.24–0.46) group were delivered by CD, without
RR, relative risk; —, not applicable. ROM before delivery, and none had
a RRs of each outcome for infants in the low risk of EOS group versus the comparison group were adjusted for center,
maternal race and/or ethnicity, antenatal steroids, multiple birth, GA, BW, and sex.
maternal clinical chorioamnionitis
b The RRs for EOS or death within 12 h of delivery varied by GA (group GA interaction, P = .015). (Table 1). Maternal histologic
c The RRs for EOS did not vary significantly by GA (group GA interaction, P = .94). In the model assessing the interaction,
chorioamnionitis was reported for a
GA 22 and 23 wk were combined.
smaller proportion of infants in the
low-risk group versus the comparison
TABLE 3 Distribution of EOS Cases Among 5640 Infants in the Low Risk of EOS Group and 8422 group (21% vs 66%). Mothers in
Infants in the Comparison Group Who Survived >12 Hours Based on Maternal Clinical and the low-risk group were more likely
Histopathology Diagnosis of Chorioamnionitis to suffer complications such as
Clinical Chorioamnionitis No Clinical Chorioamnionitis hypertension, more likely to receive
HCa No HC No HC No HC No Pathology antenatal corticosteroids, and less
Pathology likely to receive antenatal antibiotics.
Low risk, N 0 0 0 1018 3771 851 Median gestation was higher in the
EOS cases, N (%) 0 0 0 16 (1.6) 10 (0.3) 3 low-risk group, as was the proportion
Comparison, N 1632 289 252 3081 2166 1002 of female infants, multiple births, and
EOS cases, N (%) 83 (5.1) 4 (1.4) 15 70 (2.3) 20 (0.9) 17
SGA infants. In all measures except 1
HC, histological chorioamnionitis.
a In the low-risk group, placental pathology was not performed for 820 infants; pathology was performed but results were
(nitric oxide therapy), a significantly
missing for 13 infants; and information about whether pathology was done was missing for 18 infants. In the comparison greater proportion of infants in the
group, placental pathology was not performed for 1192 infants; pathology was performed but results were missing for 34 low-risk group had markers of illness
infants; and information about whether pathology was done was missing for 28 infants.
and clinical intervention (Table 1).
account for the competing risk of death to prolonged antibiotics to have
Mortality and Early-Onset Infection
before evaluation. For analyses of low- occurred. For these analyses, combined
risk infants with and without early death or morbidity outcomes included The proportion of infants who died
prolonged antibiotics, morbidities all deaths after 7 days and before in the first 12 hours after birth was
were examined among infants who discharge to examine risk of death in smaller in the low-risk group than in
survived >7 days to allow for exposure addition to morbidity before discharge. the comparison group (Table 2). Risk
maternal race and/or ethnicity, antenatal steroids, multiple birth, GA (categorical), BW (continuous), and sex, except as
noted below. Because of the small number of infants with the outcome, center was not included in the model assessing Other Morbidities Before Discharge
risk of NEC in the first 7 d of life. Only 1 infant born at GA 22 wk had NEC or SIP in the first 7 d of life; GAs 22 and 23 wk were
combined for the purpose of assessing these outcomes. All infants born at GA 22 wk had RDS; therefore, GA 22 and 23 wk Among infants who survived >12
were combined for the purpose of assessing the outcome RDS. hours, the adjusted risks of respiratory
c PIE was collected beginning April 1, 2011.
distress syndrome, pulmonary
hemorrhage, and patent ductus
of the composite outcome of death [0.16–0.36]). The risk of EOS in the arteriosus were higher in the low-risk
within 12 hours or EOS was also low-risk group was consistently group compared with the comparison
reduced for infants in the low-risk lower than in the comparison group group (Table 4). The composite risks
group (2.6% vs 15.1%; aRR [95% for infants born at each GA, as well of death within 12 hours and each of
CI]: 0.36 [0.30–0.43]). Among infants as when CONS cases were included. pneumothorax, pulmonary interstitial
surviving >12 hours, 29 out of 5640 Escherichia coli was the most frequent emphysema, NEC, and SIP, were lower
(0.5%) in the low-risk group and 209 pathogen isolated in both the low- in the low-risk group, as was the risk
out of 8422 (2.5%) in the comparison risk group (9 out of 29 cases) and the of LOS or death within 3 days, and the
group had EOS (aRR [95% CI]: 0.24 comparison group (103 out of 209 risk of intraventricular hemorrhage
TABLE 5 Antibiotic Use in Low-Risk and Comparison Infants Surviving >12 Hours
N (Column %) or as Shown Low Risk of EOS, N = 5640 Comparison Group, N = 8422 Pa
Antibiotics for ≥5 d starting within 72 h 1940 (34.4) 4106 (48.8) <.001
Antibiotics in the absence of EOS 1911/5611 (34.1) 3897/8213 (47.4) <.001
Antibiotics in the absence of positive EOS culture (cases and contaminants)b 1890/5590 (33.8) 3862/8177 (47.2) <.001
Antibiotics in the absence of a positive blood or CSF culture result, NEC, or SIP 1771/5334 (33.2) 3649/7752 (47.1) <.001
≤7 dc
No. infants given prolonged early antibiotics per EOS case 66 19 <.001
a P value by the χ2 test.
b Of the 5640 infants in the low-risk group who survived >12 h, 50 infants with a positive blood or CSF culture result within 72 h of age were excluded (29 counted as EOS cases and 21 with
an organism considered a contaminant: 17 CONS, 3 Bacillus sp., 1 Micrococcus sp.). Of the 8422 infants in the other group, 245 were excluded (209 counted as EOS cases and 36 with an
organism considered a contaminant: 23 CONS, 3 Bacillus sp., 5 Micrococcus sp., 4 Corynebacterium sp., 1 Lactobacillus sp.).
c In the low-risk group, 256 infants with NEC, SIP, or LOS within the first 7 d of life were excluded in addition to the 50 infants previously noted (44 infants with NEC, 79 with SIP, 113 with LOS,
and 20 with ≥2 of NEC, SIP, or LOS). In the comparison group, 425 infants with NEC, SIP, or LOS within 7 d were excluded in addition to the 245 previously noted (49 infants with NEC, 110 with
SIP, 232 with LOS, and 34 with 2 or more of NEC, SIP, or LOS).
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varied by center (Fig 1). In comparison
with the incidence of EOS cases, the
proportion of infants treated with
prolonged antibiotics was many times
higher at all centers in both groups.
The lower incidence of EOS in the low- labor, unexplained fetal distress, Our findings suggest that clinicians
risk cohort confirmed our hypothesis or criteria leading to a diagnosis of did not recognize the differential
that the absence of factors that clinical chorioamnionitis. Therefore, incidence of EOS among low-risk
might reflect (eg, preterm labor) or we used CD with ROM at delivery and infants or failed to account for it
promote (eg, membrane rupture) the absence of clinical chorioamnionitis in their antibiotic management
pathogenesis of ascending infection as indirect estimators. It is likely decisions. Although prolonged
would be associated with a reduced that we included some mothers who empirical antibiotic use was lower
occurrence of infection. However, 29 labored before being taken for a among low-risk infants than among
cases of EOS were identified in the CD delivery before ROM, providing the comparison infants, the ratio
low-risk group. These cases may be opportunity for ascending infection. of prolonged antibiotics to number
due to imprecision in our definition of Prospective collection of delivery of EOS cases was 3 times higher in
these risk factors. The NRN database criteria in real-time practice could the low-risk group. Fewer low-risk
does not record presence of preterm improve capture of EOS risk factors infants died at ≤12 hours, but those
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TABLE 7 Mortality for Low-Risk Infants Who Survived >12 Hours and Morbidities in Survivors >7 Days, infants who received prolonged early
Excluding Infants With a Positive Blood or CSF Culture Result and/or With NEC or SIP ≤7 Days antibiotics despite negative blood
N (Column %)a Prolonged Early No Prolonged Adjusted RR for culture results and/or NEC or SIP in
Antibiotics (N = Early Antibiotics Outcome (95% CI): the first week of life. After adjusting
1771) (N = 3563) Prolonged Early for baseline characteristics associated
Antibiotics Versus
with increased risk of morbidity
No Antibioticsb
and mortality, we still found higher
Died >12 h and before discharge 315 (17.8) 429 (12.0) 1.16 (1.01–1.32)
subsequent mortality and increased
Died >7 d 236 (13.3) 258 (7.2) 1.52 (1.28–1.80)
Infants who survived >7 d 1692 3392 — incidence of BPD and other pulmonary
RDS 1683 (99.5) 3339 (98.4) 1.01 (1.00–1.01) outcomes among the low-risk infants
Pneumothorax 117 (6.9) 123 (3.6) 1.83 (1.38–2.43) who received prolonged early
Pulmonary hemorrhage 148 (8.7) 127 (3.7) 1.96 (1.52–2.52) antibiotics. The decision to extend
PIEc 83/664 (12.5) 76/1547 (4.9) 1.80 (1.31–2.45)
early empirical therapy may reflect a
PDA 951 (56.2) 1477 (43.6) 1.15 (1.08–1.22)
NEC >7 d 173 (10.2) 315 (9.3) 0.97 (0.80–1.17) severity of initial illness that strongly
NEC >7 d or death before discharge 346 (20.4) 469 (13.8) 1.22 (1.07–1.40) influences subsequent morbidity
SIP >7 d 55 (3.3) 40 (1.2) 1.86 (1.23–2.82) and mortality in a manner for which
SIP >7 d or death before discharge 263 (15.5) 286 (8.4) 1.46 (1.24–1.71) we could not adequately account in
LOS >7 d 436 (25.8) 746 (22.0) 1.00 (0.89–1.11)
our risk-adjusted analyses. However,
LOS >7 d or death before discharge 583 (34.5) 878 (25.9) 1.12 (1.03–1.23)
Infants evaluated with cranial imaging 1692 3365 — there is evidence for the critical role
Severe ICH or PVL 316/1687 (18.7) 321/3357 (9.6) 1.65 (1.40–1.94) of the early life microbiome in the
Infants who survived to 36 wk PMA 1500 3194 — development of neonatal immune
BPD 919/1491 (61.6) 1220/3167 (38.5) 1.28 (1.20–1.36) responses and for the significant
Of the 5640 infants in the low risk of EOS group who survived >12 h, the following 306 infants were excluded: 50 with a disruption of that microbiome
positive blood or CSF culture result within 72 h of age (29 counted as EOS cases and 21 with an organism considered a
contaminant: 17 CONS, 3 Bacillus sp., 1 Micrococcus sp.), 44 with NEC ≤7 d, 79 with SIP ≤7 d, 113 with LOS on days 4–7, and
induced by antibiotic exposure.29–33
20 with ≥2 of NEC, SIP, or LOS ≤7 d. ICH, intracranial hemorrhage; PDA, patent ductus arteriosus; PIE, pulmonary interstitial Although with this study we cannot
emphysema; RDS, respiratory distress syndrome; RR, relative risk; —, not applicable. determine why it may be, our findings
a Information was missing for survivors >7 d as follows: PDA, 2 infants; SIP, 2 infants; LOS, 2 infants; ICH and/or PVL, 13
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K. Stevenson, MD; Marian M. Adams, University of Pennsylvania, Hospital Jennifer J. Jensen, RN, BSN; Karen
MD; M. Bethany Ball, BS, CCRC; of the University of Pennsylvania, Zanetti, RN.
Magdy Ismail, MD, MPH; Andrew W. Pennsylvania Hospital, and
Wake Forest University, Baptist
Palmquist, RN; Melinda S. Proud, RCP. Children’s Hospital of Philadelphia
Medical Center, Forsyth Medical
Tufts Medical Center, Floating (U10 HD68244): Barbara Schmidt,
Center, and Brenner Children’s
Hospital for Children (U10 HD53119, MD, MSc; Haresh Kirpalani, MB, MSc;
Hospital (U10 HD40498, M01
M01 RR54): Ivan D. Frantz III, MD; Sara B. DeMauro, MD, MSCE; Aasma
RR7122): T. Michael O’Shea, MD,
John M. Fiascone, MD; Brenda L. S. Chaudhary, BS, RRT; Soraya Abbasi,
MPH; Nancy Peters, RN.
MacKinnon, RNC; Anne Furey, MPH; MD; Toni Mancini, RN, BSN, CCRC;
Dara M. Cucinotta, RN. Wayne State University, Hutzel
Ellen Nylen, RN, BSN.
Women’s Hospital, and Children’s
University of Alabama at Birmingham University of Rochester Medical Hospital of Michigan (U10
Health System and Children’s Center, Golisano Children’s Hospital, HD21385): Seetha Shankaran, MD;
Hospital of Alabama (U10 HD34216, and the University of Buffalo Athina Pappas, MD; John Barks,
M01 RR32): Waldemar A. Carlo, MD; Women’s and Children’s Hospital MD; Rebecca Bara, RN, BSN; Girija
Namasivayam Ambalavanan, MD; of Buffalo (U10 HD68263, U10 Natarajan, MD; Mary Christensen,
Monica V. Collins, RN, BSN, MaEd; HD40521, M01 RR44, UL1 TR42): RT; Stephanie A. Wiggins, MS; Diane
Shirley S. Cosby, RN, BSN. Carl T. D’Angio, MD; Dale L. Phelps, White, RT.
University of California Los Angeles, MD; Ronnie Guillet, MD, PhD; Satyan
Yale University, Yale-New Haven
Mattel Children’s Hospital, Santa Lakshminrusimha, MD; Linda J.
Children’s Hospital, and Bridgeport
Monica Hospital, Los Robles Hospital Reubens, RN, CCRC; Cassandra A.
Hospital (U10 HD27871, ULTR142,
and Medical Center, and Olive View Horihan, MS; Mary Rowan, RN;
M01 RR125): Richard A. Ehrenkranz,
Medical Center (U10 HD68270): Uday Holly I.M. Wadkins, MA; Rosemary
MD; Harris Jacobs, MD; Patricia
Devaskar, MD; Meena Garg, MD; Teresa Jensen; Melissa Bowman, MSN;
Cervone, RN; Monica Konstantino,
Chanlaw, MPH; Rachel Geller, RN, BSN. Julianne Hunn, BS; Stephanie
RN, BSN; JoAnn Poulsen, RN; Janet
Guilford, BS; Deanna Maffett, RN;
University of California San Diego Taft, RN, BSN.
Diane Prinzing; Anne Marie
Medical Center and Sharp Mary Birch Reynolds, MD, MPH; Ashley Williams,
Hospital for Women and Newborns MSEd; Karen Wynn, RN; Erica
(U10 HD40461): Neil N. Finer, Burnell, RN; Michael G. Sacilowski,
MD; David Kaegi, MD; Maynard R. MAT, CCRC.
Rasmussen, MD; Kathy Arnell, RNC;
Clarence Demetrio, RN; Wade Rich, University of Texas Southwestern Abbreviations
BSHS, RRT. Medical Center at Dallas, Parkland aRR: adjusted relative risk
Health & Hospital System, and BPD: bronchopulmonary
University of Iowa and Mercy Medical Children’s Medical Center Dallas dysplasia
Center (U10 HD53109, M01 RR59): (U10 HD40689, M01 RR633): Luc BW: birth weight
Tarah T. Colaizy, MD, MPH; Dan L. P. Brion, MD; Walid A. Salhab, MD; CD: cesarean delivery
Ellsbury, MD; John A. Widness, MD; Charles R. Rosenfeld, MD; Diana CONS: coagulase-negative
Karen J. Johnson, RN, BSN; Donia B. M. Vasil, MSN, BSN, RNC-NIC; Lijun staphylococci
Campbell, RNC-NC; Jacky R. Walker, Chen, PhD, RN; Alicia Guzman; CSF: cerebrospinal fluid
RN; Tracy L. Tud, RN. Gaynelle Hensley, RN; Lizette E. Lee, EOS: early-onset sepsis
University of Miami, Holtz Children’s RN; Melissa H. Leps, RN; Nancy A. GA: gestational age
Hospital (U10 HD21397, M01 Miller, RN; Janet S. Morgan, RN; Lara LOS: late-onset sepsis
RR16587): Shahnaz Duara, MD; Pavageau, MD. NEC: necrotizing enterocolitis
Charles R. Bauer, MD; Ruth Everett- NRN: Neonatal Research
University of Utah Medical Center,
Thomas, RN, MSN. Network
Intermountain Medical Center, LDS
PMA: postmenstrual age
University of New Mexico Health Hospital, and Primary Children’s
PVL: periventricular
Sciences Center (U10 HD53089, M01 Medical Center (U10 HD53124,
leukomalacia
RR997): Kristi L. Watterberg, MD; M01 RR64, UL1 RR25764):
ROM: rupture of membranes
Robin K. Ohls, MD; Conra Backstrom Roger G. Faix, MD; Bradley A. Yoder,
SGA: small for gestational age
Lacy, RN; Carol H. Hartenberger, MD; Karen A. Osborne, RN, BSN,
SIP: spontaneous intestinal
MPH, RN; Sandra Sundquist CCRC; Cynthia Spencer, RNC, BSN;
perforation
Beauman, MSN, RNC-NIC, Mary Kimberlee Weaver-Lewis, RN, MS; Karie
VLBW: very low birth weight
Ruffaner Hanson, RN, BSN. Bird, RN, BSN; Jill Burnett, RNC, BSN;
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has been published continuously since . Pediatrics is owned, published, and trademarked by the
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