492

NEONATOLOGY

individual basis. One method is to increase the pressure by 2–4 cm H2O and
then obtain blood gas levels in 20 minutes. Another method is to use bag-and-
mask ventilation, observing the manometer to determine the amount of pressure
needed to move the chest. (See Chapter 46.)
5. Pneumothorax. See Chapter 70.
6. Hypoglycemia. See Chapter 62.
7. Polycythemia. See Chapters 71 and 122.
8. Anemia secondary to acute blood loss. See Chapter 82.
9. NEC. See Chapter 113.
10. Left-sided obstructive heart lesions. Initial stabilization with respiratory support
(endotracheal intubation and mechanical ventilation if poor respiratory effort
and hypoxemia), volume resuscitation, inotropic support with dopamine for low
cardiac output, and correction of metabolic acidosis. Immediate cardiac consulta-
tion. PGE1 is considered before diagnosis is confirmed if ductal-dependent sys-
temic blood flow is suspected. The infant should be stabilized and transferred to
a pediatric cardiac center. Surgery is usually indicated in all these patients. For a
full discussion of cardiac abnormalities, see Chapter 89.
11. Cutis marmorata. If this condition is secondary to cold stress, treat the patient as
described in Section V.B.2. If the condition persists, consider formal genetic testing
for various syndromes noted. Thyroid studies will be necessary if hypothyroidism
is suspected. If CNS dysfunction is suspected, this should be evaluated further.
12. Periventricular hemorrhage/intraventricular hemorrhage (PVH/IVH). Initial
supportive care (maintain blood pressure, stabilize blood gases, transfuse if neces-
sary, treat for seizures, etc.). After stabilization, close follow-up is required. Serial
lumbar punctures may be necessary. (See also Chapter 104.)
13. Subgaleal hemorrhage. Early recognition, appropriate resuscitation, supportive
care as in volume replacement, blood transfusion, and coagulation factors if neces-
sary. Pressure wrapping of the head is controversial.
14. Inborn errors of metabolism. See Chapter 101.
15. Seizures. See Chapter 129.
16. Hematologic problems. Blood transfusions and diagnosing and treating the spe-
cific bleeding disorder are necessary.
17. Adrenal insufficiency. Blood volume replacement and steroid therapy are usu-
ally necessary.
18. Renovascular hypertension. Usually treated with aggressive medical management.
19. Intestinal problems. See Chapters 113 and 131.
20. Enteroviral infections. Supportive management. See Chapter 92.
21. Systemic air embolism. Supportive cardiac and respiratory care. One hundred
percent oxygen therapy, hyperbaric oxygen.
22. Chronic pain. See Chapter 14.

73 Postdelivery Antibiotics
I. Problem. Two infants are born within the last hour. One infant’s mother had prema-
ture rupture of membranes (PROM) but no antibiotics. The other infant’s mother was
pretreated with antibiotics for a positive group B Streptococcus (GBS) culture taken at
36 weeks. Should a sepsis workup be done, and should antibiotics be started in either
of these newborns?
Early-onset sepsis (EOS) occurs within the first 3 days of life and is vertically
transmitted (ascending organisms from the birth canal) and can occur from ruptured
73: PostDelivery Antibiotics 493

­ embranes, inhaling or swallowing infected amniotic fluid, or an amniotic fluid leak

m
before or during labor. Sepsis in the first 3 days of life is a leading cause of morbid-
ity and mortality among preterm infants. The incidence of sepsis is 1–10 in 1000 live
births and 1 in 250 live premature births, with GBS being the most common pathogen
followed by Escherichia coli. Black preterm infants have the highest incidence and case
fatality. Since the institution of Centers for Disease Control and Prevention (CDC)
guidelines, the incidence of early-onset GBS has decreased by 80%. Late-onset sepsis is
discussed in Chapter 130, and infections of premature infants with prolonged hospital
stays may require a different workup and antibiotic choice. This on-call problem fo-
cuses on postdelivery antibiotics for early-onset or suspected sepsis. The American
Academy of Pediatrics (AAP) has a practical evidence-based approach to managing
infants with suspected and culture-proven early-onset sepsis.
II. Immediate questions
A. Are there any major risk factors for early-onset sepsis? Major risk factors are
preterm birth, low birthweight (risk factor most associated with early-onset sepsis),
rupture of membranes (ROM) >18 hours, maternal colonization with GBS (if inade-
quate intrapartum therapy), or maternal chorioamnionitis (defined as maternal fever
≥38.0°C [≥100.4°F] and a minimum of 2 of the following: maternal white blood cell
[WBC] count >15,000 mm3, maternal tachycardia [>100 beats/min], fetal tachycardia
[>160 beats/min], uterine tenderness, foul odor of the amniotic fluid).
B. Are there any other maternal risk factors for sepsis in the infant? Other risk factors
include African race, maternal malnutrition, recently acquired sexually transmitted
disease/sexually transmitted infection (STD/STI), maternal age <20 years, low socio-
economic status, and asymptomatic maternal bacteriuria. Maternal history of a previ-
ous infant with GBS infection also increases the risk of sepsis.
C. Are there other intrapartum risk factors for sepsis in the infant? These include
maternal infection, any untreated or incompletely treated infection of the mother,
and maternal fever without identifiable cause. The use of fetal scalp electrodes in the
intrapartum period increases the risk of infection in the infant. Meconium-stained
amniotic fluid and traumatic delivery are also risk factors.
D. Are there any other neonatal risk factors involved? Other risk factors include male
sex, low Apgar scores, severe depression at birth with intubation and resuscitation,
perinatal asphyxia, twin birth, and presence of the metabolic disorder galactosemia
(increased risk of gram-negative sepsis).
E. How long before delivery did the membranes rupture? ROM that occurs >18 hours
before birth is associated with an increased incidence of infection in the neonate.
F. Was the infant monitored during labor? Fetal tachycardia (>160 beats/min), espe-
cially sustained, and decelerations (usually late) can be associated with neonatal
infection. Prolonged duration of intrauterine monitoring is a risk factor for early-
onset group B streptococcal disease.
G. Did the mother have a cerclage for cervical incompetence? Cerclage increases the
risk of infection in the infant. Preterm PROM occurs in 38% of women with cerclage
in place. Retention of cerclage for more than 24 hours after PROM was found to
prolong pregnancy for more than 48 hours, but also to increase maternal chorioam-
nionitis and neonatal mortality from sepsis.
H. Are signs of sepsis present in the infant? Signs of sepsis are nonspecific and can
include apnea and bradycardia, temperature instability (hypothermia or hyperther-
mia), feeding intolerance, tachypnea, jaundice, cyanosis, poor peripheral perfu-
sion, hypoglycemia, lethargy, poor sucking reflex, increased gastric aspirates, and
irritability. Other signs include tachycardia, shock, vomiting, seizures, abnormal
rash, abdominal distention, and hepatomegaly. Neonatal sepsis is associated with
systolic and diastolic myocardial dysfunction. Bacteremia can also occur without
clinical signs.
I. Did the mother have epidural analgesia? Studies have shown an increase in mater-
nal intrapartum fever (15–20%) with the use of epidural analgesia. Because of this
494 NEONATOLOGY

fever, an increase in sepsis evaluations and antibiotic treatment was found. However,
the study did not find that epidurals caused infections or even increased the risk of
infections.
J. Was the mother tested for GBS, and did she receive antibiotics if she tested posi-
tive? There are now specific guidelines to follow after delivery if the mother was
treated for GBS.
K. Did the mother have chorioamnionitis? See definition above. Chorioamnionitis is
a major risk factor for sepsis, and its incidence varies inversely with gestational age.
Histological chorioamnionitis increases the chance of having markers of infection
(increased C-reactive proteins and neutrophilia, bacterial colonization [by gastric
lavage and ear swab] and congenital sepsis). Fourteen to twenty-eight percent of
mothers who deliver preterm infants at 22 to 28 weeks have signs of chorioam-
nionitis. Risk factors for chorioamnionitis include spontaneous labor, low parity,
multiple digital vaginal examinations, meconium-stained amniotic fluid, presence
of genital tract microorganisms, long length of labor and membrane rupture, and
internal fetal or uterine monitoring.
III. Differential diagnosis
A. Culture-proven sepsis. Cultures confirm sepsis diagnosis.
B. Suspected sepsis. An infant has nonspecific signs of sepsis or there is a high likeli-
hood that the infant has sepsis based on clinical signs. Sepsis needs to be “ruled out”
in the infant. From 18 to 33% of infants with negative blood cultures have sepsis
confirmed at autopsy.
C. Increased risk for sepsis. The infant has risk factors (preterm birth, maternal
colonization with GBS, rupture of membranes at >18 hours before birth, mother
has signs of an intra-amniotic infection) that can increase the risk of early-onset
sepsis.
D. Infant at low risk for sepsis. Newborns without the risk factors noted previously
are at low risk of sepsis.
IV. Database
A. Complete maternal, perinatal, and birth history. This should be obtained and
reviewed in an attempt to identify risk factors, as noted previously. Maternal his-
tory is just as important as the birth history. It is especially important to discuss the
diagnosis of chorioamnionitis with the obstetrics (OB) department since it has major
implications for the management of the newborn.
B. Physical examination. Observe for signs of sepsis (see above). Clinical observa-
tion is important. One study found that affect, peripheral perfusion, and respiratory
status were key predictors in sepsis compared with feeding patterns, level of activity,
and level of alertness. The maternal clinical examination should be reviewed with
the obstetrics and gynecology (OB/GYN) service. Early-onset sepsis can occur in
infants who appear healthy at birth.
C. Laboratory studies
1. Complete blood count (CBC) with differential. A single WBC count is not help-
ful when compared to serial tests. Timing of the CBC is important; an early CBC
is not recommended. CBC at 4–6 to 12 hours is optimal, after the inflammatory
response has occurred. The incidence of sepsis is increased only when the WBC
count and absolute neutrophil count is low. Some recommend interval likelihood
ratios to be used to interpret CBC instead of using normal ranges.
a. Normal total WBC. The total leukocyte count is a very unreliable indicator
of neonatal infection. Normal WBC counts may be seen in as many as 50% of
culture-proven sepsis cases. A normal WBC count does not rule out sepsis, but
a normal WBC is a better negative predictor of sepsis.
b. Abnormally low or high WBC count is worrisome. Values <6000 cells/mm3
or >30,000 cells/mm3 in the first 24 hours of life are abnormal. A band neutro-
phil count >20% is abnormal. Only half of infants with WBC <5000 cells/mm3
or WBC >20,000 cells/mm3 have positive blood cultures (BCs). Septic infants
73: PostDelivery Antibiotics 495

Table 73–1.  NEONATAL NEUTROPHIL INDICES REFERENCE RANGES FOR LATE PRETERM AND
TERM INFANTS (per mm3) AT LOW ALTITUDE

Variable Birth 12 Hours 24 Hours 48 Hours 72 Hours >120 Hours

Absolute total 1800–5400 7800–14,400 7200–12,600 4200–9000 1800–7000 1800–5400
neutrophil
counta
Total immature ≤1120 ≤1440 ≤1280 <800 <500 <500
neutrophil
countb
I:T ratioc <0.16 <0.16 <0.13 <0.13 <0.13 <0.12
a
Total count includes mature and immature forms.
b
Includes all neutrophils except segmented ones.
c
Ratio of total immature neutrophil count divided by absolute total neutrophil count (I:T), ratio of immature
to total neutrophils.
Based on data from Manroe BL, Weinberg AG, Rosenfeld CR, Browne R. The neonatal blood count in health
and disease: I. Reference values for neutrophilic cells. J Pediatr. 1979;95:89.

with a WBC count <5000 cells/mm3 are more likely to have bacterial menin-
gitis.
c. Neutropenia can be a good marker for sepsis because it occurs only in sep-
sis, asphyxia, inborn errors of metabolism (IEMs), hemolytic disease, and
pregnancy-induced maternal hypertension. The neutropenia ranges depend
on gestational age (WBC count increases with gestational age), type of deliv-
ery (vaginal births have higher WBC counts than cesarean section without
labor), type of sample (arterial samples give lower WBC counts than venous
samples), and altitude (WBC counts are higher at higher altitudes). Results
from Manroe (Table 73–1) are for late preterm and term infants at low altitudes
<500 ft. Results from Schmutz et al are for preterm to term infants at higher
altitudes, ~4800 ft.
i. Total neutrophil count is more sensitive than the total leukocyte count
but too often is normal in cases of infection. It peaks in 12 hours, and it has
a poor sensitivity and poor predictive accuracy for early-onset sepsis. See
Tables 73–1 and 73–2 for Manroe data. For high altitude (Schmutz data),
the lower and upper limits of normal for neutrophils at birth are
(a) <28 weeks’ gestation. 500–8000/mm3.
(b) 28–36 weeks’ gestation. 1000–10,500/mm3.
(c) >36 weeks’ gestation. 3500–18,000/mm3.

Table 73–2.  REFERENCE RANGES FOR NEUTROPHIL COUNTS IN VERY LOW BIRTHWEIGHT
INFANTS (<1500 G)

Age Absolute Total Neutrophil Count (mm3) (min to max)

Birth 500–6000
18 hours   2200–14,000
60 hours 1100–8800
120 hours 1100–5600
Based on data from Mouzinho A, Rosenfeld CR, Sánchez PJ, Risser R. Revised reference ranges for circulat-
ing neutrophils in very-low-birth-weight neonates. Pediatrics. 1994;94:76.
496 NEONATOLOGY

Peak values are seen 6–8 hours after birth. The lower and upper limits of
normal at that time are
(a) <28 weeks’ gestation. 1500–41,000/mm3.
(b) 28–36 weeks’ gestation. 3500–25,000/mm3.
(c) >36 weeks’ gestation. 7500–28,500/mm3.
ii. Total immature neutrophil count has poor sensitivity but better positive
predictive value. See Table 73–1.
iii. Ratio of immature to total neutrophils (I:T) has the highest sensitivity
for early-onset neonatal sepsis. The greatest value relies in its negative
predictive value; the likelihood of infection is minimal if the I:T ratio is
normal. In the majority of healthy preterm infants at <32 weeks (96%), the
I:T ratio is <0.22. The total neutrophil count can be calculated, and normal
reference ranges can be found in Tables 73–1 and 73–2.
2. Peripheral blood cultures are the gold standard for diagnosis of sepsis. Small
specimen volumes decrease the sensitivity (minimum of 1 mL per single bottle,
aerobic culture only recommended). Antibiotic removal device bottles should be
used if the mother has received any antibiotics. Acceptable ways to obtain blood
culture in a neonate: peripheral vein, arterial puncture, newly placed intravenous
catheter, umbilical artery catheter (UAC) immediately after placement. Umbilical
venous catheter (UVC) at delivery is also acceptable if the cord is adequately
prepared.
3. Urine culture is no longer recommended in infants <72 hours of age in
an early-onset sepsis workup. More appropriately done for late-onset sepsis
workup.
4. Gastric aspirates. Gram stain is of limited value and not recommended. WBCs in
the gastric aspirate represent maternal response and do not correlate with sepsis
in the neonate.
5. Body surface cultures (axilla, external ear canal, umbilical stump, groin) are not
recommended.
6. Lumbar puncture (LP) for cerebrospinal fluid (CSF) examination is controversial. 
The AAP recommends that a LP be done with positive blood culture, if the infant
deteriorates or does not respond on antibiotic therapy, and in infants whose lab
data or clinical course suggests bacterial sepsis. Approximately 13% of infants
with early-onset sepsis will also have meningitis. Infants with bacteremia have
a risk of meningitis of 23%. Blood cultures can be negative in 38% of infants
with meningitis. Infants with respiratory distress syndrome (RDS) and high-risk,
healthy-appearing infants are at low risk of meningitis.
7. Tracheal aspirate. May be of benefit for Gram stain and culture if performed
immediately after endotracheal tube placement. Some advocate this only if
pneumonia is suspected or volume of secretions increases, or in overwhelming
newborn EOS. Tracheal aspirates done after several days of intubation are of
no value.
8. Baseline serum glucose.
9. Arterial blood gas. To rule out metabolic acidosis.
10. Platelet count and coagulation studies to rule out thrombocytopenia and
disseminated intravascular coagulation (DIC). A decreased platelet count is
usually a late sign of sepsis. A low platelet count is a nonspecific and insensitive
test for sepsis.
11. Erythrocyte sedimentation rates (ESRs). Increased with infection but have a
very limited value in diagnosing or monitoring infection. A low value does not
exclude the diagnosis of sepsis.
12. Acute phase reactants (C-reactive protein [CRP] and procalcitonin [PCT]). 
Used to identify infants with sepsis. CRP is a quantitative test. An increasing CRP
is worrisome and is elevated in 50–90% of infants with sepsis. CRP increases
at 6–8 hours and peaks at 24 hours. If CRPs remain normal, sepsis is unlikely.
73: PostDelivery Antibiotics 497

The main interest in CRP is its negative predictive value if repeated over 1–3 days.
No recommendations exist on using an elevated CRP to help determine duration
of antibiotic therapy. Serum procalcitonin levels are elevated in sepsis and may
be helpful as a marker for sepsis. It can also be elevated in RDS, asphyxia, intra-
cranial hemorrhage, pneumothorax, and resuscitation. It has better sensitivity but
is less specific than CRP. Serial PCT levels may be helpful in deciding duration of
antibiotic therapy. The following is a list of predicted CRP and PCT levels with
lower and upper limits in parentheses in term and preterm infants.
a. CRP (term) in mg/dL.  Birth: 0.1 (0.01–0.65); 21 hours: 1.5 (0.2–10.0);
56–70 hours: 1.9 (0.3–13); 96 hours: 1.4 (0.2–9).
b. CRP (preterm) in mg/dL. Birth: 0.1 (0.01–0.64); 27–36 hours: 1.7 (0.3–11);
90 hours: 0.7 (0.1–4.7).
c. Procalcitonin (term) in mcg/L.  Birth: 0.08 (0.01–0.55); 24 hours: 2.9
(0.4–18.7); 80 hours: 0.3 (0.04–1.8).
d. Procalcitonin (preterm) in mcg/L. Birth: 0.07 (0.01–0.56); 21–22 hours: 6.5
(0.9–48.4); 5 days: 0.10 (0.01–0.8).
13. Laboratory tests that could be helpful in screening for sepsis but are not rou-
tinely used. Lack of availability, lack of confirmatory studies, and wide variations
in results.
a. Cytokines. Interleukins (IL-1, IL-6, IL-8), soluble IL-2 receptor, and soluble
tumor necrosis factor alpha (TNF-α) receptor have been identified; IL-6 has
been studied the most. Interleukins 6 and 8 are early sensitive markers of
infection. IL-6 is higher in infants with polycythemia.
b. Neutrophil surface antigens. CD11b is a marker for early-onset sepsis.
c. Urinary neutrophil gelatinase–associated lipocalin (NGAL). A promising
biomarker for sepsis in neonates, it is elevated in sepsis, ischemia, hypoxia,
and drug toxicity.
d. Multiple markers. Using serial and multiple investigational markers showed
the best reliability for predicting sepsis.
e. Septic scoring systems. Usually include a battery of multiple laboratory tests
(and sometimes clinical indicators of sepsis) where each test is given a number
based on the result and the total score assesses the risk of sepsis. Institutions
have devised their own septic scoring systems. Studies of scoring systems (using
a combination of the laboratory tests mentioned previously) have shown that
they all have limited value in screening for sepsis unless the score is high, with
a negative panel being a better predictor than a positive panel. They may be
helpful in deciding which healthy high-risk infants do not need antibiotics or
whether antibiotics can be stopped.
D. Imaging and other studies
1. Chest x-ray. With signs of respiratory infection, obtain a chest radiograph to rule
out pneumonia.
2. Echocardiography and Doppler imaging. To assess myocardial function. Infants
with sepsis have systolic and diastolic myocardial dysfunction.
3. Head ultrasound or magnetic resonance imaging (MRI). May be helpful in
meningitis.
V. Plan
A. General measures. For the majority of cases, a decision about whether an infant
requires a sepsis workup and antibiotics is usually straightforward. These infants
either are clinically sick or have a positive history of an increased risk for sepsis with
clinical signs, thereby making the antibiotic decision easy. However, if an infant does
not have a clear-cut history and clinical presentation, the decision is more difficult.
One single test is often not helpful and it is necessary to “repeat, repeat, and repeat”
the test. Once the decision is made to treat the infant, treatment usually involves at
least 36–48 hours of antibiotics after obtaining cultures. The following guidelines can
be used to help make the decision to treat:
498 NEONATOLOGY

1. CDC recommendations should be followed if possible. The CDC now recom-

mends universal prenatal screening for vaginal and rectal GBS of all pregnant
women at 35–37 weeks’ gestation. The following are CDC recommendations for
the management of all newborns. If antibiotics are given, use broad spectrum
for the most common causes of sepsis (IV ampicillin for GBS and coverage for
other organisms [E. coli and other gram-negative organisms]). When deciding
antibiotics, check local antibiotic resistance patterns. If there are any signs of sepsis
during the observation period, the infant should receive a full diagnostic evalua-
tion. GBS prophylaxis is indicated if there are one or more of the following:
a. Positive GBS vaginal rectal screening in late gestation (optimal at 35–37 weeks’
gestation).
b. GBS status unknown at onset of labor (culture not done, culture incomplete,
or unknown results) with one or more intrapartum risk factors, including deliv-
ery <37 weeks’ gestation, ROM ≥18 hours or intrapartum T ≥100.4°F (38.0°C),
intrapartum nucleic acid amplification test (NAAT) positive for GBS.
c. GBS bacteriuria during any trimester during the current pregnancy (intrapar-
tum antibiotic prophylaxis [IAP] not indicated if culture and sensitivity [C/S]
done before onset of labor with intact membranes).
d. History of a previous infant with invasive GBS disease.
2. CDC treatment plan for secondary prevention of early-onset GBS among all
newborns (term and preterm). See also Figure 130–1.
a. Any signs of sepsis. Full diagnostic workup (CBC with differential and platelets,
blood culture, chest x-ray [CXR] with abnormal respiratory signs, LP if stable
enough to tolerate, and sepsis is strongly suspected). Give empiric antibiotics.
b. Well infant, mother with suspected chorioamnionitis. Consultation with OB
department is important to discuss level of clinical assessment of chorioam-
nionitis. Perform a limited evaluation: Do a blood culture at birth, CBC with
differential, platelet count at birth and/or at 6–12 hours of life. Start empiric
antibiotics.
c. Well infant, mother without chorioamnionitis, and GBS prophylaxis not
indicated for the mother. Routine clinical care. If signs of sepsis develop, do
a full diagnostic evaluation and initiate antibiotics.
d. Well infant, GBS prophylaxis indicated for mother and she received ade-
quate intrapartum GBS prophylaxis (≥4 hours of IV penicillin, ampicillin, or
cefazolin before delivery). Observe for 48 hours or more; no testing necessary.
If signs of sepsis develop, do a full diagnostic evaluation and start antibiotics.
Infant may go home after 24 hours if ≥37 weeks’ gestation and discharge criteria
have been met. Well-appearing infants at gestational age (GA) of 35–36 weeks
do not routinely require diagnostic evaluations.
e. Well infant, mother had indication for GBS prophylaxis but did not receive
adequate prophylaxis.
i. Infant ≥37 weeks and ROM <18 hours. Observe infant for 48 hours or
more; no testing. Some recommend CBC and differential at 6–12 hours. If
signs of sepsis develop, do a full diagnostic evaluation and start antibiotics.
ii. Infant <37 weeks or ROM ≥18 hours. Limited evaluation (blood culture
at birth, CBC with differential at birth and/or at 6–12 hours of life) with
observation for 48 hours or more. Some experts recommend a CBC and
differential at 6–12 hours. If signs of sepsis develop, do a full diagnostic
evaluation and start antibiotics.
3. The AAP guidelines recognize the clinical challenges in this area. The concern
of overtreatment is validated by recent data showing that prolonged antibiotic
treatment >5 days in preterm infants had a higher incidence of NEC, late-onset
sepsis, and mortality. They have come up with management plans for neonates
with suspected or proven early-onset bacterial sepsis. When reviewing these
specific guidelines, remember these key points. If the mother was diagnosed
73: PostDelivery Antibiotics 499

with chorioamnionitis, it is important to talk to the obstetricians and confirm

the diagnosis since it has major treatment implications for the infant. Inadequate
IAP means the mother received another antibiotic (not penicillin, ampicillin, or
cefazolin) or received the correct antibiotic but the duration was <4 hours.
a. Any critically ill infant. Requires a complete sepsis evaluation and antibiotics
(even if there are no risk factors).
b. Any mature infant without risk factors for infection with mild find-
ings (tachypnea with or without O2 requirement). Observe for ~6 hours
after birth. With improvement (tachypnea is resolving, O2 requirement is
decreasing), antibiotics are probably not indicated but continued observa-
tion is. With worsening clinical state, obtain cultures and start antibiotics
empirically.
c. Healthy-appearing, asymptomatic infant <37 weeks with one risk factor
for sepsis. For example, intrapartum antimicrobial prophylaxis indicated but
inadequate or PROM ≥18 hours or chorioamnionitis.
i. Do blood culture at birth, WBC and differential and optional CRP at age
6–12 hours.
ii. Start broad-spectrum antibiotics. Now what?
(a) Blood culture positive. Continue antibiotics. Lumbar puncture is indi-
cated in any infant with a positive blood culture or if sepsis is highly
suspected (based on clinical signs, response to treatment, or lab results).
(b) Blood culture negative, infant well, lab values abnormal. Continue
antibiotics in the infant for a total of 72 hours if mother received antibi-
otics during labor and delivery. If at 72 hours the physical examination
is normal, the antibiotics can be discontinued.
(c) Blood cultures negative, infant well, lab values normal. Discontinue
antibiotics after 48 hours.
d. Healthy-appearing, asymptomatic infant ≥37 weeks with risk factor of
chorioamnionitis.
i. Blood culture at birth, WBC and differential and optional CRP at age
6–12 hours.
ii. Start broad-spectrum antibiotics. Now what?
(a) Blood culture positive. Continue antibiotics. Lumbar puncture is indi-
cated in any infant with a positive blood culture or if sepsis is highly
suspected (based on clinical signs, response to treatment, or lab results).
(b) Blood culture negative, infant well, lab values abnormal. Continue
antibiotics for a total of 48–72 hours in the infant if mother received
antibiotics during labor and delivery. Discontinue antibiotics at
48–72 hours if the physical examination remains normal.
(c) Blood culture negative, infant well, lab values normal. Discontinue
antibiotics and discharge by 48 hours.
e. Healthy-appearing, asymptomatic infant ≥37 weeks with risk factors for
sepsis but not chorioamnionitis. PROM ≥18 hours or intrapartum antimi-
crobial prophylaxis indicated but inadequate.
i. Observation without doing any lab tests. Acceptable if observation is
every 2–4 hours for a minimum of 24 hours.
ii. Or do lab tests.  Do WBC and differential and optional CRP at age
6–12 hours.
iii. No antibiotics necessary, observation. Now what?
(a) Lab values abnormal. Do blood culture. If the blood culture is negative
and the infant is well then discharge by 48 hours.
(a) Lab values normal. Infant well, discharge by 48 hours. Discharge at
24 hours is acceptable only if other discharge criteria are met, access to
medical care is readily available, and there is an able person who can
fully comply with instructions for home observation.
500 NEONATOLOGY

B. Antibiotic therapy
1. If the decision is to treat:
a. Obtain cultures of the blood and spinal fluid if indicated. Lumbar puncture is
indicated if there is a positive blood culture or sepsis is highly suspected based
on clinical signs or lab values, or if infants do not respond to treatment. Any
other cultures that seem appropriate should be sent to the laboratory (eg, if
there is eye discharge, send a Gram stain and culture). Tracheal aspirate Gram
stain and culture if pneumonia is suspected and there is an increase in tracheal
secretions. (Note: Tracheal aspirates need to be obtained right after endotra-
cheal tube placement to be of value in early-onset sepsis.)
b. Ampicillin and gentamicin are the antibiotics most commonly used for
empirical initial therapy in a newborn with sepsis. Once a pathogen is iden-
tified, use narrow therapy if possible unless synergism is necessary. If GBS
is documented, penicillin G or ampicillin is given, but an aminoglycoside is
often added for synergism. Recent reviews have documented that in infants
(≥32 weeks’ gestation), once-a-day gentamicin is superior to multiple doses
a day because it achieves higher peak levels and avoids toxic trough levels.
Third-generation cephalosporins are an alternative to gentamicin, but recent
studies have shown resistance and increased candidiasis with use. Cefotaxime
should only be used in infants with gram-negative meningitis. Cefotaxime and
an aminoglycoside should be used in infants with gram-negative meningitis
until susceptibility testing is back.
c. If the cultures are positive, treat accordingly. Bacteremia without source: treat
for 10 days. Uncomplicated GBS meningitis: treat for 14 days. Gram-­negative
meningitis: treat for 21 days or 14 days after obtaining a negative culture.
2. Discontinuing antibiotics is another controversial topic.
a. See AAP management guidelines above  for neonates with suspected or
proven early-onset bacterial sepsis.
b. Other recommendations
i. If the cultures are negative, the patient is doing well, and the risk of
sepsis low. Antibiotics may be stopped after 48 hours (for asymptomatic
term infants, negative cultures after 36 hours may be sufficient). A normal
I:T ratio and serial negative CRP might help determine whether antibiot-
ics can be stopped because of their high negative predictive value. Use of
procalcitonin concentrations may also be helpful in deciding when to stop
antibiotics.
ii. If the cultures are negative but the infant had signs of sepsis (clinical
sepsis). Some clinicians treat the infant for 7–10 days.
C. Beyond antibiotic therapy
1. Immunoglobulin (Ig) therapy (controversial). Endogenous immunoglobulin
synthesis begins at 24 weeks of life. Placental transfer of immunoglobulins does
not occur until later and postnatal IgG levels decrease after birth. Studies show a
reduction in mortality in proven infection but less reduction in suspected infec-
tion. In a recent review, intravenous immune globulin administration resulted in
a 3% reduction in sepsis but was not found to not have any significant effect on
mortality. The data do not support the routine use in sepsis. Some institutions give
a single dose in infants with overwhelming sepsis.
2. Fresh frozen plasma.  Its use is only indicated in disseminated intravascular
coagulation, and no benefit has been shown in septic infants.
3. Granulocyte or neutrophil transfusions. Although benefits of granulocyte trans-
fusions have been documented, there are potential serious side effects. Cochrane
review states that there is not enough evidence to either support or refute the use
in sepsis.
4. Cytokines.  Granulocyte macrophage colony-stimulating factor (GM-CSF)
and granulocyte colony-stimulating factor (G-CSF) stimulate bone marrow
74: Pulmonary Hemorrhage 501

­ eutrophils. Cochrane review states that there is not enough evidence to support
n
the use of GM-CSF or G-CSF as treatment to reduce mortality or as prophylaxis.
5. Double volume exchange transfusion. Exchange transfusion with fresh whole
blood is beneficial in severe or gram-negative neonatal sepsis, and it may be used
as a last resort. Because of significant risks and that evidence from few prospective
studies is not strong on the subject, many institutions have not advocated its use.
6. Pentoxifylline. Current evidence shows that pentoxifylline as an adjunct to anti-
biotics reduces mortality in neonatal sepsis and duration of hospitalization. The
studies have been small, and the results need to be interpreted with caution. More
research is needed.
7. Selenium/melatonin supplementation. More studies are needed before recom-
mendations can be made.
8. Lactoferrin. Cochrane review states that there is no recommendation to use or
refute the use in treatment of neonatal sepsis.

Selected References
Polin RA; Committee on Fetus and Newborn.  Management of neonates with suspected
or proven early-onset bacterial sepsis. Pediatrics 2012;129(5):1006–1015. Erratum to
Pediatrics.
Prevention of Perinatal Group B Streptococcal Disease. MMWR. Revised guidelines from
CDC, 2010. November 19, 2010/59(RR10);1–32. http://www.cdc.gov/mmwr/preview/
mmwrhtml/rr5910a1.htm. Accessed September, 2012.
Sise ME, Parravicini E, Barasch J. Urinary neutrophil gelatinase–associated lipocalin (NGAL)
identifies neonates with high probability of sepsis. Pediatrics 2012; 130(4):1053–1054.

74 Pulmonary Hemorrhage
I. Problem. Grossly bloody secretions are seen in the endotracheal tube (ETT). The inci-
dence of pulmonary hemorrhage varies from 0.8 to 12 per 1000 live births. It can be as
high as 50 per 1000 live births if high risk. The mortality rate can be as high as 50%.
Survivors of pulmonary hemorrhage require longer ventilator support, and many will
develop bronchopulmonary dysplasia/chronic lung disease. Others survivors may have
an increase in cerebral palsy, cognitive delay, seizures, and periventricular leukomalacia.
Most cases of pulmonary hemorrhage are secondary to hemorrhagic pulmonary
edema and not a true bleed.
II. Immediate questions
A. Are any other signs abnormal? Typically, an infant with pulmonary hemorrhage
is a ventilated low birthweight infant, often from a multiple birth, and 2–4 days old
(usually in the first week of life). Late gestation infants with pulmonary hemorrhage
usually have low 1- and 5-minute Apgar scores. The infant has a sudden deteriora-
tion: hypoxic, severe retractions, and may experience associated pallor, shock, apnea,
bradycardia, and cyanosis.
B. Is the infant hypoxic? Has a blood transfusion recently been given? Hypoxia or
hypervolemia (usually caused by over transfusion) may cause an acute rise in the
pulmonary capillary pressure and lead to pulmonary hemorrhage.
C. Is there bleeding from other sites? If so, coagulopathy may be present, and coagula-
tion studies should be obtained. Volume replacement with colloid or blood products
may be needed.