Clinical Case Study of ABO Hemolytic Disease in Full-term

Newborns Complicated with Neonatal Pneumonia and

Intracranial Hemorrhage

Yan Jin

Department of Neonatology, the People’s Hospital of Baise, Baise, Guangxi, China

Keywords: Newborn, ABO Hemolytic Disease, Neonatal Pneumonia, Intracranial Hemorrhage.

Abstract: ABO Hemolytic Disease of Newborn (ABO-HDN) is the most common cause of blood-incompatible

Hemolytic Disease in China. In this paper, the clinical characteristics of full-term ABO-HDN

complicated with pneumonia and intracranial hemorrhage were summarized, and the corresponding

clinical data were collected by using retrospective study methods, and the full-term infants meeting the

ABO-HDN diagnostic criteria were selected as research objects. The differences in minimum

hemoglobin, age at onset (h), and incidence of anemia among ABO-HDN patients with or without

complications (neonatal pneumonia, intracranial hemorrhage) were compared. To investigate the

influence of pneumonia and intracranial hemorrhage on the clinical manifestations of term ABO-HDN.

1 INTRODUCTION

Hemolytic disease of the newborn (HDN), caused by

inconsistent maternal and infant blood groups, is one

of the common causes in neonatal hyperconjugated

bilirubinemia (Jeon, Calhoun, Pothiawala, et al

2000). There are different degrees of clinical

manifestations of neonatal hemolytic disease. The

fetus may have varying degrees of anemia after

delivery. The clinical manifestations are pale,

jaundice, hypoglycemia and edema. However, when

the hemolytic immune response is severe,

hyperunconjugated bilirubinemia will occur, and

bilirubin encephalopathy may occur, resulting in

damage to the central nervous system, More serious

cases can occur early spontaneous abortion or late

stillbirth (Li 2020). This study retrospectively

analyzed the clinical data of ABO-HDN children

who met the diagnosis and treatment criteria in

full-term neonatal Pediatrics, and discussed the

clinical manifestations and influence of ABO

hemolytic disease complicated with pneumonia and

intracranial hemorrhage.

https://orcid.org/0000-0002-3465-7057

2 SUBJECTS AND METHODS

2.1 Study Subjects

2.1.1 Selection of the Study Subjects

According to the diagnostic criteria of ABO-HDN of

newborns in practical neonatology (4th Edition),

according to the ABO blood group of mother and

child (the mother is type O blood, the child is type A

or B blood, and the mother and child Rh blood group

are positive), jaundice ABO-HDN was diagnosed as

positive by serological test, antibody release test

(ART) or direct antiglobulin test (DAT); 127

full-term newborns who met the diagnostic criteria of

ABO-HDN were selected from the neonatal

department of the people's Hospital of Baise City in

2020.

2.1.2 Diagnosis Criteria for Related

Comorbidities and Complications

Diagnostic criteria for anemia: anemia was

diagnosed according to the diagnostic criteria in

Pediatrics (8th Edition) for neonatal anemia, which

was defined as hemoglobin <145g/L, and could be

classified into 4 degrees according to the

hemoglobin content: mild in patients with a range of

Jin, Y.

Clinical Case Study of ABO Hemolytic Disease in Full-term Newborns Complicated with Neonatal Pneumonia and Intracranial Hemorrhage.

DOI: 10.5220/0011370300003438

In Proceedings of the 1st International Conference on Health Big Data and Intelligent Healthcare (ICHIH 2022), pages 367-372

ISBN: 978-989-758-596-8

367

144-120g/L, moderate in those with a range of ~

90g/L, severe in those with a range of <60g/L, and

extremely severe in those with a range of <60g/L.

Neonatal pneumonia (NP) diagnostic criteria:

according to the practical neonatology fourth edition

neonatal pneumonia section, eligible for the

following ① mother has a history of vaginitis in the

third trimester, or the presence of premature rupture

of membranes for more than 24 hours before

delivery, or the newborn has a history of close

contact with respiratory tract disease after delivery;

② Clinically, they had symptoms and signs of

exocytosis and foam, nasal obstruction, rhinorrhea,

cough, shortness of breath, cyanosis, and rales in

lungs; ③ Sputum culture may reveal pathogenic

bacteria, chest radiograph or chest CT suggests

increased lung texture, blurring, disturbance or

patchy hyperdense shadow, etc; ④ Except for

neonatal wet lung, congenital lung disease, the

clinical diagnosis was neonatal pneumonia.

Diagnostic criteria of Intracranial hemorrhage

(ICH) : according to the 4th edition of Practical

Neonatology, Intracranial hemorrhage refers to

hemorrhage caused by Intracranial blood vessel

rupture, including ① periventricular -

intraventricular hemorrhage; ② Subdural

hemorrhage; ③ Subarachnoid hemorrhage; ④

Parenchymal hemorrhage; ⑤ Hemorrhage in

cerebellum, thalamus and basal ganglia. The

diagnosis can be made with characteristic imaging

changes of intracranial hemorrhage on head CT

examination.

Diagnostic criteria for bilirubin encephalopathy

(Du, Ma, et al 2014): ① have hyperbilirubinemia

with peak total bilirubin > 342 umol / L or (and) a

rise velocity > 8.5 umol/L, > 35 weeks' gestation;

② The early clinical manifestations are

characterized by poor mental responsiveness,

drowsiness, poor sucking, a weak cry, and

hypotonia, followed by irritability, fever,

convulsions, hypertonia, and opisthotonus, and in

severe cases, death; ③ On cranial MRI, the basal

ganglia globus pallidus appears hyperintense on

T1WI (acute phase) and weeks later on T2WI; ④

Prolongation of all wave latencies or even hearing

loss can be seen at brainstem auditory evoked

potentials (BAEP), and the early changes of BAEP

are mostly reversible.

2.2 Research Methods

SPSS statistics 16.0 software was used for statistical

analysis. The counting data were described by the

number of cases and percentage (n,%). The

measurement data were described by mean±standard

deviation (

SX ±

), and the differences between

groups were compared by independent sample t-test,

analysis of variance and chi square test.

3 ANALYSIS OF CLINICAL DATA

In this study, there were 68 cases of complicated

neonatal pneumonia and 59 cases of uncomplicated

neonatal pneumonia, which accounted for 53.5%,

46.5% of the total cases, respectively; There were 24

cases of combined intracranial hemorrhage and 103

cases without combined intracranial hemorrhage,

accounting for 18.9% and 81.1% of the total,

respectively. Of the children with combined

intracranial hemorrhage, 21 had subarachnoid

hemorrhage and 3 had patchy hemorrhages in the

brain parenchyma.

In this study, there were 127 cases of

ABO-HDN, 50 cases (39.4%) were complicated

with mild anemia, 22 cases (17.3%) with moderate

anemia, 1 case (0.8%) with severe anemia, and 8

cases (6.3%) with bilirubin encephalopathy.

4 GROUPING ANALYSIS OF

ABO-HDN

4.1 Comparison of the Effects of

Having and not Having Neonatal

Pneumonia on Minimum

Hemoglobin, Age at onset (h), and

Incidence of Anemia

Included studies were stratified into no neonatal

pneumonia group and combined neonatal pneumonia

group using independent samples t-test to compare

the lowest hemoglobin between the two groups

Differences in age at onset (h), chi square test was

used to compare the differences in the incidence of

anemia. As can be seen from table 1, the combined

neonatal pneumonia group had a lower nadir

hemoglobin than the group without neonatal

pneumonia, and the results were statistically

significant (P<0.05), but there was no statistical

difference in age at onset (h), incidence of anemia

(P>0.05).

ICHIH 2022 - International Conference on Health Big Data and Intelligent Healthcare

368

Table 1: Comparison of the incidence of neonatal pneumonia in minimum hemoglobin, age at disease onset (h) and anemia

incidence.

class (n)

Minimum Hb (g / L)

（

sx ±

）

Age at disease onset(h)

（

sx ±

1）

Anemia

incidence

(%)

neonatal pneumonia

(

n=68

)

134.88±22.26 21.88±12.32 63.2%

No neonatal pneumonia

(

n=59

)

142.61±19.09 27.28±19.94 50.8%

t value/χ2value -2.08 -1.86 1.98*

P value 0.04 0.07 0.16

Note: * Use the chi-square test;1 x refers to the mean, s refers to the standard deviation; 2 The denominator of the incidence

of anaemia was 127 term ABO-HDN cases enrolled.

4.2 Comparison of Effects of Presence

or Absence of Concomitant

Intracranial Hemorrhage on

Minimum Hemoglobin, Age at

Onset (h), Anemia

Patients were divided into no intracranial

hemorrhage and intracranial hemorrhage groups

using independent samples t-test to compare the

lowest hemoglobin between the two groups

Difference in age at onset (h), chi square test was

used to compare the difference in anemia incidence.

As can be seen from table 2, there was no significant

difference in the lowest hemoglobin, age at onset

(h), anemia incidence between the groups (P > 0.05).

Table 2: Comparison of the incidence of intracranial hemorrhage in minimum hemoglobin, age at onset (h) and anemia.

class (n)

Minimum Hb (g / L)

sx ±

Age at disease onset (h)

sx ±

Anemia incidence2

(%)

Have intracranial

hemorrhage (n=24)

131.83±25.48 20.95±13.84 70.8%

No intracranial

hemorrhage (n=103)

140.02±19.80 25.19±16.97 54.4%

t value/χ2value -1.72 -1.14 2.16*

P value 0.09 0.26 0.14

Note: * Use the chi-square test;1 x refers to the mean, s refers to the standard deviation; 2 The denominator of the incidence of anaemia

was 127 term ABO-HDN cases enrolled.

4.3 ABO-HDN Characteristics in

Concurrent Bilirubin

Encephalopathy

There were 8 full-term abo-hdn cases complicated

with bilirubin encephalopathy, including 2 cases

without complications and 6 cases with

complications. Among the full-term abo-hdn cases

with complications, there were 2 cases of neonatal

pneumonia, 1 case of intracranial hemorrhage and 3

cases of neonatal pneumonia + intracranial

hemorrhage.

Among the 8 cases, the highest total bilirubin

value was 207.0 umol/L, the highest value was 587.3

umol/L, the lowest hemoglobin value was 100 g/L,

and the high value was 150g/L. Anemia occurred in

7 cases, including mild anemia in 3 cases and

moderate anemia in 4 cases. Age at onset (h) as early

as 9 h, as late as 27 h, age at first presentation (h) as

early as 21 h, and as late as 168 h. There were 2

cases without comorbidities and 6 cases with

comorbidities, including 2 cases with complicated

neonatal pneumonia, 1 case with combined

intracranial hemorrhage, and 3 cases with combined

neonatal pneumonia + intracranial hemorrhage, see

tables 3.

Clinical Case Study of ABO Hemolytic Disease in Full-term Newborns Complicated with Neonatal Pneumonia and Intracranial Hemorrhage

369

Table 3: Concurrent bilirubin encephalopathy ABO-HDN.

Project

Maximum total

bilirubin

(umol/L)

lowest Hb

(g/L)

Age at

disease

onset (h)

Age at

first visit

(h)

Combined with

neonatal

pneumonia

Concomitant

intracranial

hemorrhage

case 1 291.9 150 20.27 32.27 + -

case 2 244.7 123 23.5 35.5 + +

case 3 284.0 117 9 21 + +

case 4 207.0 111 14 26 - -

case 5 348.9 132 16 40 - +

case 6 587.3 121 24 168 + +

case 7 277.1 100 27 39 + -

case 8 362.1 112 24 58 - -

Note: -indicates unmerge, + indicates merger.

5 UNIVARIATE ANALYSIS OF

MODERATE AND SEVERE

ANEMIA IN ABO-HDN

The 127 full-term ABO-HDN cases included in the

study were analyzed according to whether moderate

or severe anemia occurred.The relevant values are

shown in Table 4.

As shown in Table 5, there was no statistical

difference in the results of moderate and severe

anemia caused by neonatal pneumonia and

intracranial hemorrhage at term ABO-HDN (P >

0.05).

Table 4: Table of Related Factors.

project assignment

Combined with neonatal pneumonia not have =0

have =1

Concomitant intracranial hemorrhage not have =0

have =1

Table 5: Results of a univariate analysis affecting the moderate and severe anemia of ABO-HDN at term.

project classify

No moderate or severe

anemia occurred

(n=104)

Moderate and

severe anemia

occurred (n=23)

χ2value P value

Combined with

neonatal

neumonia

have 52 16 2.90 0.09

Concomitant

intracranial

hemorrhage

have 17 7 2.44 0.12

Note: * P <0.05 has statistical differences.

6 CONCLUSIONS

This study discusses whether full-term ABO-HDN

children are grouped with neonatal pneumonia and

intracranial hemorrhage, and compares the

differences in minimum hemoglobin, age at onset (h)

and incidence of anemia. Through analysis, it is

found that the full-term ABO-HDN group with

neonatal pneumonia treated in Baise people's

hospital is lower than the group without neonatal

pneumonia in minimum hemoglobin, The results

were statistically significant (P<0.05). There was no

significant difference in the lowest hemoglobin, age

at onset (h) and incidence of anemia in patients with

ICHIH 2022 - International Conference on Health Big Data and Intelligent Healthcare

370

intracranial hemorrhage (P> 0.05).The analysis is as

follows:

6.1 Complications Associated with

ABO-HDN Hemolysis

Among the cases enrolled in this study, 68 cases

(53.5%) were complicated with neonatal pneumonia,

and 59 cases (46.5%) were not. 24 cases (18.9%) had

intracranial hemorrhage, 103 cases (81.1%) had no

intracranial hemorrhage.

Hemolytic disease of newborn is a kind of

passive immune disease, the occurrence of which

depends on whether maternal and infant blood

groups are inconsistent (Simmons, Savage 2015,

Wei, Saller, Sutherland 2001). The pathogenesis is

that maternal blood group antibody IgG, which can

destroy fetal red blood cells, enters the child's body

and causes hemolysis(Yogev-Lifshitz, Leibovitch,

Schushan-Eisen, et al 2016).There was no statistical

significance in minimum hemoglobin, age at onset

(h) and incidence of anemia in patients with

ABO-HDN complicated with intracranial

hemorrhage (P>0.05).Intracranial hemorrhage can

cause extravascular hemolysis, jaundice, when the

amount of bleeding, also can be accompanied by

anemia. There are more kinds of the disease, such as

periventricular - intraventricular hemorrhage,

subdural hemorrhage, subarachnoid hemorrhage,

parenchymal hemorrhage, cerebellum, thalamus,

basal ganglia and other parts of the hemorrhage.

Among them, subarachnoid hemorrhage is more

common in infants, most of which are small and

clinically asymptomatic. A few of which are large

and stimulate the brain parenchyma, causing

corresponding nervous system symptoms, such as

lethargy, low response, repeated convulsions, and

central respiratory abnormalities. This study

combined intracranial hemorrhage cases, 21 cases of

subarachnoid hemorrhage, less blood loss, hemolysis

reaction was not significant, outside the blood

vessels to term ABO-HDN anemic, onset time have

a significant impact, whether other types of

intracranial hemorrhage in full-term ABO-HDN

anemic, onset time, remains to be further validation.

The lowest hemoglobin in the group with

neonatal pneumonia was lower than that in the group

without neonatal pneumonia (134.88±22.26,

142.61±19.09), and the results were statistically

significant (P<0.05). Although there was no

difference in the incidence of anemia, it was still

necessary to be vigilant that the ABO-HDN with

neonatal pneumonia was more prone to anemia.

Because when the body with infection, will produce

the INF alpha, IL - 1, TNF and other cytokines,

these cytokines can activate mononuclear

macrophage, the macrophage chemotaxis,

devouring, such as immunity strengthening, lead to

increased red blood cells in the spleen, liver damage,

extravascular hemolysis, aggravating the

pathophysiology of hemolysis, so still need to the

attention of the clinicians.

6.2 Factors Associated with

Concurrent Bilirubin

Encephalopathy

Bilirubin encephalopathy, generally seen in neonates

with severe or very severe hyperconjugated

bilirubinemia. The occurrence of the disease is

closely related to serum free bilirubin, albumin,

blood-brain barrier integrity.

Serum free bilirubin is lipid soluble and can

penetrate the blood-brain barrier, and when

conjugated with albumin is converted into

water-soluble conjugated bilirubin, it cannot cross

the blood-brain barrier and achieves the effect of

protecting nerve cells. The rate of movement of free

bilirubin from plasma to brain is limited by (1)

surface area and permeability of the capillary

endothelium, (2) transit time through the capillary

bed, (3) albumin / bilirubin conjugation and

dissociation rates, and (4) blood flow per unit

area(Wennberg 2000).

Serum free bilirubin usually exists in the form of

conjugation with albumin, when the body causes a

rapid increase in free bilirubin for a short period of

time because of some diseases, such as hemolytic

disease of the newborn, or some substances compete

with free bilirubin for the albumin binding site,

resulting in decreased binding of albumin to free

bilirubin, such as some cephalic antibiotics,

sulfonamides, indomethacin and other drugs, And

when the integrity of the BBB is compromised,

conditions such as intercurrent infections,

intracranial hemorrhage, or increased blood flow,

such as hypercapnia, promote the transport of free

bilirubin to the brain(Govaert, Lequin, Swarte, et al.

2003).

Most of the early neonatal BBB development is

not perfect, especially the newborns less than 72

hours after birth, the BBB is not yet intact, the

endothelium is fenestrated, the endothelial basement

membrane is thin, part of the endothelium has no

continuous basement membrane, glial membrane is

not complete, etc., can affect the BBB integrity. At

this time, serum free bilirubin rapidly increases and

can be at risk for concurrent bilirubin

Clinical Case Study of ABO Hemolytic Disease in Full-term Newborns Complicated with Neonatal Pneumonia and Intracranial Hemorrhage

371

encephalopathy. The age at onset of the eight cases

in this study complicated by bilirubin

encephalopathy were all within 48 hours of birth and

required attention from clinicians. For newborns less

than 72 hours after birth, close monitoring of

bilirubin should be performed, along with

observation for clinical signs of early presentation of

bilirubin encephalopathy, and aggressive

intervention to try to prevent the emergence of

bilirubin encephalopathy.

Studies have shown (Ma, Shi, et al. 2012) that

the risk of developing bilirubin encephalopathy

increases with comorbid infections, intracranial

hemorrhage, and other conditions. There were 8

cases of concurrent bilirubin encephalopathy in this

study, 2 cases without comorbidities, and 6 cases

with existing comorbidities, including 2 cases of

combined neonatal pneumonia, 1 case of combined

intracranial hemorrhage, and 3 cases of combined

neonatal pneumonia+intracranial hemorrhage, which

was in keeping with related studies. The small

number of cases with concurrent bilirubin

encephalopathy in this study precludes further

statistical testing, and further analyses with larger

samples are warranted in the future. In clinical

practice, attention should be paid to the presence of

comorbidities such as: neonatal pneumonia,

intracranial hemorrhage in abo-hdn cases, and

vigilance for concurrent bilirubin encephalopathy.

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