Efficacy of intravenous immunoglobulin following plasma exchange in the management of ABO haemolytic disease of the newborn

Abstract

Background and Objectives

To evaluate the efficacy of intravenous immunoglobulin (IVIG) after plasma exchange (PE) in neonates with ABO haemolytic disease of the newborn (ABO‐HDN) by assessing serum biomarkers, neurodevelopment and quality of life.

Materials and Methods

A total of 162 neonates with ABO‐HDN were randomly assigned to four groups: Control (n = 39), IVIG (n = 42), PE (n = 41) and IVIG + PE (n = 40). Serum markers, Neonatal Behavioural Neurological Assessment (NBNA), Echelle Douleur Inconfort Nouveau‐Ne and Paediatric Quality of Life Inventory (PedsQL4.0) scores were evaluated.

Results

The IVIG + PE group showed the most significant improvement in prealbumin (PA), total bile acid (TBA), total bilirubin (TBIL), procalcitonin (PCT), high‐sensitivity C reactive protein (hs‐CRP) and antibody titre levels (p < 0.05). Neurodevelopment, comfort and quality of life were significantly enhanced, with reduced jaundice duration and hospitalization time. Adverse event rates were lower in all treatment groups than in the control group (p < 0.05).

Conclusion

IVIG following PE improves serum biomarkers, antibody titre levels, neurodevelopment and quality of life in ABO‐HDN, supporting its clinical application.

Highlights.

• Intravenous immunoglobulin administration after plasma exchange synergistically improves clinical outcomes in ABO haemolytic disease of the newborn (ABO‐HDN) neonates, significantly reducing jaundice duration and hospitalization time.

• Combination therapy optimizes serum biomarkers and rapidly normalizes prealbumin, total bile acid, total bilirubin, procalcitonin and high‐sensitivity C reactive protein within 7 days, indicating enhanced haemolysis control and reduced inflammation.

• Also, the newborns treated with the combination showed superior neurodevelopment and quality of life scores.

INTRODUCTION

Haemolytic disease of the newborn (HDN) is an immune haemolytic disease caused by maternal–foetal blood group incompatibility, 85% of which is ABO‐HDN, with clinical features such as jaundice, anaemia, extramedullary haematopoiesis and hydrops foetalis, which is one of the most important factors of neonatal disability and death [1, 2]. Clinical treatment of ABO‐HDN is mainly based on phototherapy, which can inhibit the level of bilirubin and other harmful factors through blue light irradiation to alleviate the condition of the child, which is rapid and has little toxic side effects. Still, it cannot remove haemolysis‐related antibodies, which can easily lead to recurrence [3, 4]. Plasma exchange (PE) is often used with phototherapy because of its high efficiency in removing haemolysis‐related factors [5, 6]. This method is capable of rapidly removing haemolysis‐related antigens, antibody‐like substances and excess bilirubin by separating plasma from other blood components through membrane filtration, which can rapidly improve the physiological status of patients in a short period [7, 8]. However, in many autoimmune diseases, the prolonged treatment process of PE is detrimental to the physiological state of the patient, leading to bottlenecks in therapeutic efficacy, and the therapeutic efficacy is maximized by the combination of intravenous immunoglobulin (IVIG) [9, 10]. IVIG contains a full range of antibody profiles derived from the plasma of several thousands of healthy donors and can effectively suppress antibodies derived from the plasma of the mother's child during the treatment of ABO‐HDN. In the clinical treatment, IVIG can effectively inhibit the destruction of foetal erythrocytes by maternal haemolysis‐associated antibodies, thereby improving the symptoms of haemolysis in infants with ABO‐HDN [11, 12]. This study was conducted to implement the combination of PE and IVIG in infants with ABO‐HDN, to break through the bottleneck of the existing therapeutic methods and provide a theoretical basis for the design of a clinical treatment plan for ABO‐HDN.

MATERIALS AND METHODS

Clinical characteristics

One hundred and eighty‐one infants with HDN who underwent treatment in our hospital from November 2020 to November 2023 were selected. After applying the inclusion and exclusion criteria, 11 were screened out and 8 were withdrawn in the middle of the study due to various circumstances; finally, 162 were included in this study. The infants were numbered according to the order of admission to the hospital and were divided into the control group (n = 39), IVIG group (n = 42), PE group (n = 41) and IVIG + PE group (n = 40) by using the random number table method. There was no significant difference in the general clinical data in the four groups (p > 0.05, see Table 1). Inclusion criteria were as follows: there was ABO blood group mismatch between the infant and their mothers; gestational age of the infant was 35–40 weeks, and the age of the infant was 1–30 days; the infant was breastfed and formula‐fed and without any congenital defects or major diseases; and the family members did not have psychiatric disorders or communication disorders. Exclusion criteria were, infant with malignant neoplastic disease; infant with psychiatric disease and low level of cooperation during surgery; neonates born to mothers with clinically significant alloantibodies other than anti‐A or anti‐B (e.g., anti‐D, anti‐Kell, anti‐E, etc.); infant who had already received relevant surgical treatments; infant who was allergic to the medication related to this study; and infant who died or suffered from severe cardiac arrhythmia after the surgery. The infant and their families were informed about the study process and signed an informed consent form. The study was approved by the Ethics Committee of the hospital (no. 2024090312). All patients included in the study have signed informed consent forms. Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.

TABLE 1.

Comparison of clinical characteristics in four groups, n (%), $\overline{x}\pm s$.

	Control (n = 39)	IVIG (n = 42)	PE (n = 41)	IVIG + PE (n = 40)	F/χ 2/H	p
Gender					1.830	0.608
Male	18 (46.15)	21 (50.00)	23 (57.10)	24 (60.00)
Female	21 (53.85)	21 (50.00)	18 (43.90)	16 (40.00)
Gestational age (weeks)	37.22 ± 1.03	37.85 ± 0.82	37.44 ± 0.95	36.98 ± 0.77	6.971	<0.001
Days of age (days)	6.32 ± 0.53	6.48 ± 0.65	6.41 ± 0.74	6.39 ± 0.68	0.408	0.748
Birth weight (kg)	3.13 ± 0.36	3.11 ± 0.27	3.15 ± 0.25	3.16 ± 0.21	0.263	0.852
Blood type					0.432	0.933
A	19 (48.72)	19 (45.24)	20 (48.78)	21 (52.50)
B	20 (51.28)	23 (54.76)	21 (51.22)	19 (47.50)
Maternal age (years)	29.67 ± 4.53	30.17 ± 4.21	29.85 ± 4.37	29.75 ± 5.02	0.096	0.962
Maternal anti‐A/B IgG titre					0.528	0.997
≤1:64	13 (33.33)	16 (38.10)	14 (34.15)	13 (32.50)
1:128	12 (30.77)	13 (30.95)	14 (34.15)	13 (32.50)
≥1:256	14 (35.90)	13 (30.95)	13 (31.71)	14 (35.00)

Abbreviations: IVIG, intravenous immunoglobulin; PE, plasma exchange; IgG, immunoglobulin G.

Methods

All infants were given formula feeding, intravenous nutrition, maintenance of normal blood glucose, water‐electrolyte and acid–base balance and other routine treatments when necessary. The infants were treated with light therapy for which they were placed in a special light box for intermittent irradiation of double‐sided light for 12 h at a time and their jaundice condition was observed after one irradiation. The time of irradiation therapy was appropriately prolonged if the degree of reduction of jaundice was less than 110 μmol/L. If there was a rebound, another session was carried out. To ensure the safety of all enrolled infants, any infant whose total serum bilirubin level met or exceeded the threshold for exchange transfusion based on the hour‐specific bilirubin nomogram, or who showed clinical signs of acute bilirubin encephalopathy, was immediately withdrawn from the study and was made to undergo double‐volume exchange transfusion. In the IVIG group, 1.0 g/kg/day of gamma globulin was administered intravenously at the beginning of the treatment and continued for 2 days. In the PE group, the infants underwent PE. The procedure was performed via the femoral vein as deep venous access, secured by an experienced paediatric intensivist with ultrasound guidance as needed. To ensure haemodynamic stability, a Fresenius Kabi Com.Tec Apheresis System with a low‐volume circuit was utilized; the circuit was primed with packed red blood cells or 5% albumin to minimize fluctuations in the infant's blood volume. Throughout the procedure, vital signs were continuously monitored, and prophylactic intravenous calcium gluconate was administered to prevent citrate‐induced hypocalcaemia from the fresh frozen plasma (FFP) replacement fluid. The plasma volume for each infant was calculated based on a blood volume of 80 mL/kg and a haematocrit of 50%. A daily exchange volume of 1–1.5 times the child's estimated plasma volume was replaced for 3 days using a mixture of FFP and a 5% albumin solution as the replacement fluid. In the IVIG + PE group, after 3 days of PE treatment, the infants were treated with intravenous gamma globulin in the same way as in the IVIG group. During the hospitalization period, the medical and nursing staff were also required to take symptomatic treatment measures according to the clinical conditions of the infants, such as corrective treatment for acidosis and anti‐infective treatment for infections. The treatment time of the four groups was 7 days, and the corresponding indexes were tested after 1, 3 and 7 days of treatment. After 1, 3 and 7 months of treatment, the infants and their families were visited again.

Ethics statement

This study was approved by The First Affiliated Hospital of Xi'an Jiaotong University (2024090312) and was performed in accordance with the Declaration of Helsinki.

Observation index

Time to improve the clinical symptoms

The time to improve the clinical symptoms of the infants in the four groups was tested, and the relevant indices included jaundice regression time, blue light treatment time and hospitalization time.

Serum indicator

Before treatment and 1, 3 and 7 days after treatment, 5 mL venous blood of the infants was collected early in the morning and placed in a procoagulant tube, and the serum was separated at a centrifugation speed of 3000 rpm, a centrifugation radius of 5 cm and a centrifugation time of 15 min to obtain the supernatant layer of the serum. Prealbumin (PA), total bile acid (TBA), total bilirubin (TBIL), procalcitonin (PCT) and high‐sensitivity C reactive protein (hs‐CRP) were measured by immunoturbidimetric assay.

Antibody titre measurement

Before treatment and at 3 and 7 days after treatment, venous blood was collected from the infants and placed in procoagulant tubes. Serum was separated by centrifugation at 3000 rpm for 15 min. The anti‐A/B immunoglobulin G (IgG) antibody titre, reflecting the load of pathogenic antibodies in the neonatal circulation, was measured in the obtained serum using a standard tube haemagglutination technique at room temperature. The titre was recorded as the reciprocal of the highest serum dilution producing visible agglutination.

Neonatal Behavioural Neurological Assessment

The neurodevelopment of the infants in the four groups was assessed using the Neonatal Behavioural Neurological Assessment (NBNA) score [13] before treatment, after 7 days of treatment and after 1 and 3 months of treatment. The score ranges from 0 to 40, with higher scores indicating better neurobehavioural competence of the infants.

Comfort

The Echelle Douleur Inconfort Nouveau‐Ne (EDIN) [14] was used to assess the comfort level of the infants in the four groups before treatment, after 7 days of treatment and after 1 and 3 months of treatment; the scores are inversely proportional to the comfort level.

Quality of life

The infant's quality of life was evaluated before treatment, after 7 days of treatment and at the return visit after 1 and 3 months of treatment using the Paediatric Quality of Life Inventory (PedsQL4.0) Generic Core Scales [15], which consists of four modules: physical function, emotional function, social function and role function score. The score ranges from 0 to 100 for each module, with higher scores indicating better quality of life.

Adverse effects

Adverse effects and their incidence during the treatment of infants were counted. Relevant indicators included fever, rash, vomiting and diarrhoea.

Data analysis

Data were analysed by SPSS 24.0. Measurements were expressed as ($\overline{x}\pm s$) and the one‐way analysis of variance test was used. Non‐normally‐distributed data were expressed as median with interquartile range (IQR), and the Kruskal–Wallis H test was used. Counts were expressed as n (%) and the χ ² test was used. p < 0.05 indicated a significant difference in the data.

RESULTS

Comparison of time to improve the clinical symptoms among four groups

Jaundice regression time, blue light treatment time and hospitalization time in the IVIG, PE and IVIG + PE groups were all significantly shorter than those in the control group (p < 0.05); there was no significant difference in time to improve the clinical symptoms between the IVIG and PE groups (p > 0.05), while jaundice regression time, blue light treatment time and hospitalization time in the IVIG + PE group were all significantly shorter than those in the IVIG and PE groups (p < 0.05, Figure 1).

FIGURE 1.

(a) Jaundice regression time of the four groups. (b) Blue light treatment time of the four groups. (c) Hospitalization time of the four groups. ^#Compared with control p < 0.05. *Compared with intravenous immunoglobulin (IVIG) + plasma exchange (PE) p < 0.05.

Comparison of serum indicator before and after intervention among four groups

After 1, 3 and 7 days of treatment, PA levels showed a significant increasing trend (p < 0.05), whereas TBA, TBIL, PCT and hs‐CRP levels showed a significant decreasing trend (p < 0.05); among them, PA levels in the IVIG, PE and IVIG + PE groups were significantly higher than those in the control group, whereas TBA, TBIL, PCT and hs‐CRP were significantly lower (p < 0.05); there was no significant difference in the serum indices in the IVIG and PE groups (p > 0.05), and PA levels in the IVIG + PE group were significantly lower than in the control group (p < 0.05); there was no significant difference in the serum indices between the IVIG and PE groups (p > 0.05), whereas PA levels in the IVIG + PE group were significantly higher than those in IVIG and PE groups. Also, TBA, TBIL, PCT and hs‐CRP were significantly lower than those in IVIG and PE groups (p < 0.05, Figure 2).

FIGURE 2.

(a) Prealbumin (PA) level of the four groups. (b) Total bile acid (TBA) level of the four groups. (c) Total bilirubin (TBIL) level of the four groups. (d) Procalcitonin (PCT) level of the four groups. (D) High‐sensitivity C reactive protein (hs‐CRP) level of the four groups. ^Compared with before treatment p < 0.05. ^%Compared with 1 day after treatment p < 0.05. ^&Compared with 3 days after treatment p < 0.05. ^#Compared with control p < 0.05. *Compared with intravenous immunoglobulin (IVIG) + plasma exchange (PE) p < 0.05.

Comparison of neonatal antibody titre levels among the four groups

Before treatment, there was no significant difference in the baseline antibody titre levels among the four groups of infants. After treatment, the distribution of antibody titres showed a highly significant difference (p < 0.001), with the IVIG + PE group showing the most pronounced antibody clearance effect (Table 2).

TABLE 2.

Comparison of anti‐A/B IgG titre before and after treatment, median (interquartile range).

Group	Before treatment	After 3 days treatment	After 7 days treatment
Control (n = 39)	1:128 (1:64–1:256)	1:128 (1:64–1:256)	1:128 (1:64–1:256)
IVIG (n = 42)	1:128 (1:64–1:256)	1:112 (1:56–1:224)	1:96 (1:48–1:192)
PE (n = 41)	1:128 (1:64–1:256)	1:64 (1:32–1:128)	1:32 (1:16–1:64)
IVIG + PE (n = 40)	1:128 (1:64–1:256)	1:32 (1:16–1:64)	1:16 (1:8–1:32)
H	0.043	85.2	112.5
p	0.998	<0.001	<0.001

Abbreviations: IVIG, intravenous immunoglobulin; PE, plasma exchange; IgG, immunoglobulin G.

Comparison of neurobehavioural competence and comfort before and after intervention among the four groups

After 7 days, 1 month and 3 months of treatment, the NBNA scores showed a significant upward trend (p < 0.05). The NBNA scores of the IVIG group, PE group and the IVIG + PE group were significantly higher than those in the control group (p < 0.05); there was no significant difference in the scores of the IVIG group and PE group (p > 0.05), and the NBNA scores of the IVIG + PE group were significantly higher than those of the IVIG group and PE group (p < 0.05, Figure 3a).

FIGURE 3.

(a) Neonatal Behavioural Neurological Assessment (NBNA) score of the four groups. (b) Echelle Douleur Inconfort Nouveau‐Ne (EDIN) score of the four groups. ^Compared with before treatment p < 0.05. ^%Compared with 7 days after treatment p < 0.05. ^&Compared with 1 month after treatment p < 0.05. ^#Compared with control p < 0.05. *Compared with intravenous immunoglobulin (IVIG) + plasma exchange (PE) p < 0.05.

After 7 days, 1 month and 3 months of treatment, EDIN scores showed a significant decreasing trend (p < 0.05); after 7 days and after 1 month of treatment, EDIN scores of the IVIG, PE and IVIG + PE groups were significantly lower than those of the control group (p < 0.05); there was no significant difference in the scores of the IVIG and PE groups (p > 0.05), and the IVIG + PE group EDIN scores were significantly lower than those of IVIG and PE groups (p < 0.05, Figure 3b).

Comparison of quality of life before and after intervention among four groups

After 7 days, 1 month and 3 months of treatment, there was a significant upward trend in PedsQL4.0 scores (p < 0.05); among them, the various PedsQL4.0 scores of the IVIG group, PE group and IVIG + PE group—namely physiological functioning, emotional functioning, social functioning and role functioning scores—were significantly higher than those of the control group (p < 0.05). There was no significant difference in the IVIG group or the PE group in the various PedsQL4.0 scores (p > 0.05), whereas the PedsQL4.0 scores of IVIG + PE group—physiological function, emotional function, social function and role function scores—were significantly higher than those of the IVIG and PE groups (p < 0.05, Figure 4).

FIGURE 4.

(a) Physical function score of the four groups. (b) Emotional function score of the four groups. (c) Social function score of the four groups. (d) Role function score of the four groups. ^Compared with before treatment p < 0.05. ^%Compared with 7 days after treatment p < 0.05. ^&Compared with 1 month after treatment p < 0.05. ^#Compared with control p < 0.05. *Compared with intravenous immunoglobulin (IVIG) + plasma exchange (PE) p < 0.05.

Comparison of the incidence of adverse reactions after treatment among four groups

After treatment, the incidence of adverse reactions in infants in the IVIG group, PE and IVIG + PE groups was significantly lower than that in the control group (p < 0.05). There was no significant difference in the incidence of adverse reactions in the IVIG, PE or IVIG + PE group (p > 0.05, Table 3).

TABLE 3.

Comparison of the incidence of adverse reactions after treatment among four groups, n (%).

Groups	Fever	Rash	Vomiting	Diarrhoea	Incidence of adverse reactions
Control (n = 39)	3 (7.69)	2 (5.13)	5 (12.82)	3 (7.69)	13 (33.33)
IVIG (n = 42)	2 (4.76)	0 (0.00)	0 (0.00)	2 (4.76)	4 (9.52) #
PE (n = 41)	0 (0.00)	0 (0.00)	3 (7.32)	2 (4.88)	5 (12.20) #
IVIG + PE (n = 40)	0 (0.00)	0 (0.00)	1 (2.50)	0 (0.00)	1 (2.50) #
χ 2					17.100
p					<0.001

Abbreviations: IVIG, intravenous immunoglobulin; PE, plasma exchange.

^# Compared with control p < 0.05.

DISCUSSION

ABO‐HDN is caused by activation of the reticuloendothelial system and complement to destroy antibody‐coated erythrocytes, and occurs in approximately 15%–25% of pregnancies. It is a common cause of neonatal hospital admissions [16, 17, 18]. Light therapy, which is commonly used in clinical practice, has shown limited improvement in the symptoms of haemolysis in infants with ABO‐HDN and often needs to be combined with other measures [19]. In the treatment of various autoimmune diseases, PE and IVIG can effectively inhibit autoimmunity, and IVIG after PE treatment can also significantly improve the efficacy [11, 12, 20]. In this section, we will discuss the effects of PE followed by IVIG on infants with ABO‐HDN in light of the results obtained in this study.

The results of the study showed that all the serum indices of each group improved after treatment, among which the rising trend of PA and the decreasing trend of TBA, TBIL, PCT and hs‐CRP in the PE group were more obvious. In the process of PE treatment, the use of a 0.2–0.6‐μm pore size filter membrane can effectively filter harmful factors and inflammatory factors in the blood, and synergize with the destructive effect of light therapy on TBIL, and so on, which can effectively promote the decline of TBA, TBIL, PCT and hs‐CRP expression levels in the blood of the patients [21]. At the same time, the plasma supplemented during the replacement process contains a large number of plasma proteins, which can effectively prevent the destruction of erythrocytes and promote the improvement of the organism's blood environment, further promoting blood circulation [22]. Therefore, the reduction of the level of TBIL and other toxic substances is more obvious and the improvement of the clinical conditions of the infants is more rapid when PE treatment is coordinated with light therapy than with light therapy alone.

Huang et al. [23] showed that IVIG can effectively inhibit the expression of harmful factors such as TBA and TBIL in the blood of infants with HDN. Meanwhile, some studies on haemolytic diseases have also found that IVIG could compete with immune antibodies to bind to erythrocytes, inhibit the phagocytosis of sensitized erythrocytes by mononuclear macrophages, as well as seal the erythrocytes, protect the erythrocytes from being destroyed and thus promote blood circulation and improve the therapeutic effect [24, 25]. Building on this foundation, the sequential application of PE prior to IVIG creates a synergistic mechanism ideally suited for severe cases. Studies have shown that the severity of ABO‐HDN is fundamentally driven by the maternal titre of anti‐A/B IgG antibodies, with higher levels predicting more vigorous haemolysis and poorer outcomes [4, 16]. The children in this study had significant antibody‐mediated diseases. IVIG exerts its therapeutic effects primarily through antigen competition and immune regulation rather than relying on sustained plasma concentration peaks. The superior efficacy of the combined IVIG + PE regimen can thus be interpreted as a successful strategy to counter this high antibody burden. PE rapidly reduces the pathogenic antibody load [5, 7], while subsequent IVIG provides sustained immunomodulation [11, 12]. This profound reduction in the pathogenic antibody load and haemolytic activity is precisely what underlies the significant neurodevelopmental benefits observed in the combination group. After treatment, the combination therapy group (IVIG + PE) exhibited the strongest antibody clearance capability, which corresponds to the best clinical outcomes observed in this group. This finding provides direct laboratory evidence for the superiority of the combined treatment regimen. In diseases such as ABO‐HDN, infants treated with IVIG can prevent the occurrence of haematological or neurodevelopmental problems by effectively improving the symptoms of foetal oedema and anaemia [16, 26]. The results of the present study showed that the NBNA scores of the infants in the IVIG group increased more significantly than those of the control group, which shows that IVIG treatment can promote the improvement of clinical outcomes and normalize the neurobehavioural development of the infants.

The improvement of clinical symptoms in the IVIG and PE groups was more rapid than that in the control group, but significantly less rapid than in the IVIG + PE group. This is because prolonged PE treatment is prone to side effects such as transfusion reactions, citrate toxicity and alkalosis, which can damage the physiological state of the child and lead to a bottleneck in the therapeutic efficacy [27]. First‐time users of IVIG are prone to inflammatory rebound, which can also affect the improvement of the effect [28]. A study on the autoimmune disease Guillain–Barré syndrome showed that both IVIG and PE were effective in inhibiting the patient's autoimmune system from attacking the nervous system, and there was no significant difference in the efficacy of the two [20]. Combined with the results of the present study, it can be seen that the respective side effects of IVIG and PE both limit their inhibitory effect on the symptoms of haemolysis, so there is no significant difference in the improvement of clinical symptoms between the two groups of children, which is similar to the results of the previous study on Guillain–Barré syndrome. Compared with that of the IVIG and PE groups, the advantage of the IVIG + PE group is that the children in this group, after the filtration of harmful factors and inflammatory factors in the blood by the filtration membrane of PE and the supplementation of plasma proteins, synergized with the erythrocyte sealing and inhibition of harmful factors by IVIG, so that the trend of increase in PA and the trend of decrease in TBA, TBIL, PCT and hs‐CRP were more obvious. In addition, IVIG can improve the blood environment and promote blood flow by protecting erythrocytes and slowing down problems such as transfusion reactions caused by PE; at the same time, due to the filtration of inflammatory factors by PE, the rebound of inflammation levels caused by IVIG cannot cause more side effects [29]. With the improvement of various types of harmful factors and the reduction of side effects, the clinical symptoms of the children improved rapidly and the neurobehavioural ability affected by harmful factors also improved; the quality of life of the children also improved. Furthermore, no episodes of symptomatic hypocalcaemia or other serious adverse events attributable to PE were observed, which may be due to the routine prophylactic calcium supplementation and close monitoring employed during the procedure. The recorded adverse events (primarily mild gastrointestinal symptoms) were manageable and did not compromise safety.

In conclusion, the combination of PE and IVIG can promote the normal development of neurobehaviour in children by adequately improving their serum indices, thus contributing to changes in their quality of life. This study has several limitations. First, it was a single‐centre study with a relatively limited sample size. Second, the monitoring of serum biochemical indicators was confined to the acute treatment phase (7 days). Future research should involve multi‐centre trials with larger cohorts, coupled with longitudinal biochemical monitoring to enable a more comprehensive assessment of the long‐term therapeutic efficacy.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

Hu Y, Nie J. Efficacy of intravenous immunoglobulin following plasma exchange in the management of ABO haemolytic disease of the newborn. Vox Sang. 2026;121:1032–1040.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.