Accuracy of noninvasive total haemoglobin measurement for detecting anaemia in infants: a cross-sectional study in a well-child care clinic, Khon Kaen, Thailand

Abstract

Objective

Infants are at a high risk of developing anaemia, which can arise from various causes, including inappropriate feeding practices. However, few infants attend anaemia screening programmes due to poor cooperation and being time-consuming. This study evaluated the accuracy of noninvasive total haemoglobin (Hb) spot-check monitoring as part of anaemia screening in healthy infants, compared with the conventional laboratory method.

Design

A cross-sectional study was conducted using a consecutive sampling technique.

Setting

The study was carried out at the Well-Child Clinic, Khon Kaen University, Thailand.

Participants

Healthy, full-term infants aged 6–12 months who were scheduled for vaccination. Spectrophotometric haemoglobin (SpHb) was measured using Masimo Rad-67 with Rainbow DCI-mini Sensor. These values were compared with conventional laboratory analysis (HbLab) performed on the same day.

Primary and secondary outcome

Differences between Hb values using the two methods were analysed using the Bland–Altman method. Sensitivity, specificity and positive and negative predictive values (PPV and NPV) for detecting anaemia were determined. Anaemia was defined as HbLab of <11.0 g/dL.

Results

A total of 104 infants, with a median age of 9.6 (IQR 9.3, 10.9) months, were included. The prevalence of anaemia, defined by HbLab, was 38.46%. The mean SpHb was 12.20±1.10 g/dL, while the mean HbLab was 11.19±1.21 g/dL. A moderate positive correlation was observed (r=0.575, p<0.001). Bland–Altman analysis of SpHb vs HbLab showed an estimated bias of 1.007 g/dL with a 95% limit of agreement ranging from −1.091 to 3.104 g/dL. The mean bias was 1.635 g/dL (−0.617 to 3.887) in the anaemic group and 0.614 g/dL (−0.964 to 2.192) in the nonanaemic group. Using the SpHb cut-off point of <13.0 g/dL, the sensitivity and specificity of SpHb to detect anaemia were 95.0% and 35.9%, with PPV and NPV of 48.1% and 92.0%, respectively.

Conclusion

A noninvasive tool for measuring Hb, with moderate sensitivity and NPV, may provide utility for initial screening to reduce unnecessary venipuncture in infants. However, its limited specificity and PPV necessitate confirmatory testing through conventional laboratory methods for accurate diagnosis. Depending on the context and available resources, it has potential to complement existing diagnostic processes, particularly in settings where rapid and noninvasive screening is prioritised.

Trial registration number

Thai Clinical Trials Registry (TCTR20210816002).

Correspondence to Dr Suchaorn Saengnipanthkul; [email protected]

STRENGTHS AND LIMITATIONS OF THIS STUDY

• This study used noninvasive haemoglobin measurements compared with standard laboratory methods in an area with a moderate prevalence of anaemia.

• Noninvasive measurements were performed by three researchers to ensure reliability and controlled variability.

• This was a single-centre study, which limits the generalisability of the findings.

• Approximately 10% of participants did not have their spectrophotometric haemoglobin levels measured, which might affect the results and require further investigation before broader use.

• Cost-effectiveness was not addressed, which is an important factor for implementing larger-scale screening programmes.

Introduction

Anaemia is a significant global public health concern. According to the 2019 report from the WHO, the prevalence of anaemia among Thai children aged 6–59 months was 24.9%.¹ Research conducted in Thailand revealed that approximately 12.0%–41.7% of infants suffer from anaemia.^{2 3} Anaemia can be caused by nutritional deficiency, particularly that of iron, vitamin B12 or folate. Chronic medical conditions, such as infections and inflammatory disorders, can impair erythropoiesis and exacerbate anaemia. In addition, blood loss, haemolysis and genetic disorders, such as red blood cell membrane defects and thalassemia, are causes of anaemia.⁴ Iron deficiency is the most common cause of anaemia in preschool-age children. Iron deficiency in infants can affect brain development and can lead to long-term complications, such as cognitive impairment, developmental delay and behavioural problems.^{5 6} Early identification and treatment are essential for preventing complications and improving overall health and well-being.

Iron deficiency anaemia can have serious long-term effects on a child’s health if left untreated and undiagnosed. Therefore, early detection is necessary to prevent negative outcomes. However, screening for anaemia is often neglected due to the invasive nature of blood tests, such as haemoglobin (Hb), haematocrit and ferritin level measurements. The Centres for Disease Control and Prevention recommend screening for anaemia between the ages of 9 and 12 months, especially for high-risk infants, such as preterm or low-birth-weight infants, those consuming non-iron-fortified formula for more than 2 months and those introduced to cow’s milk before the age of 12 months.⁷ Similarly, the Canadian Paediatric Society recommends screening for anaemia between the ages of 9 and 12 months, focusing on high-risk infants, such as those born prematurely, low-birth-weight infants and those exclusively breastfed beyond 6 months without iron supplementation.⁸ The American Academy of Paediatrics highlights the importance of universal screening between the ages of 9 and 12 months, as iron deficiency is common during this age due to rapid growth and inadequate dietary iron.⁹ In 2014, the Royal College of Paediatricians of Thailand also recommended screening for anaemia for all Thai infants aged 6–12 months.¹⁰ Total Hb measurement using conventional laboratory methods, such as complete blood count (CBC), is the recommended screening method for anaemia. Although this method is accurate, it is invasive and requires a blood sample. Chienwittayakun et al found suboptimal adherence to anaemia screening among 9-month-old full-term infants in Bangkok, Thailand. They reported that parental education and socioeconomic status influenced compliance. Their findings underscore the necessity for enhanced public health efforts to improve screening rates and early detection of anaemia in infants.¹¹

The Department of Health, Ministry of Public Health, recommends providing a weekly dose of 12.5 mg of elemental iron to children aged 6–24 months as a preventive measure.¹² While oral iron supplementation is rational, the increasing prevalence of anaemia suggests complementary approaches such as nutritional education and screening are needed for improving anaemia prevention efforts.

According to the WHO, infants are diagnosed with anaemia when the Hb level is less than 11.0 g/dL.⁴ However, anaemia in infants remains underdiagnosed because laboratory tests for Hb require venous blood sampling, which is difficult to obtain due to the requirement of specialised personnel, significant stress to patients and family members, lack of CBC instruments in primary care hospitals and long turnaround time.¹¹ Most infants do not undergo blood tests unless anaemic symptoms or related clinical events are present. Thus, the development of a quick, accurate and noninvasive method for measuring total Hb could have several advantages in clinical practice, particularly in low- and middle-income countries.

Spectrophotometric haemoglobin (SpHb) measurement is a noninvasive method for measuring Hb levels using transcutaneous multiwavelength spectrophotometry-based technology. Masimo Rad-67 (Masimo Corporation, Irvine, CA, USA) is a commercially available, noninvasive spot-check device that can measure total Hb using the Rainbow DCI-mini Sensor. This device uses an easily applicable sensor attached to the finger or toe. The present study aimed to evaluate the accuracy of SpHb spot-check monitoring using Masimo Rad-67 compared with the gold standard measurement of Hb using the conventional laboratory method for anaemia screening in healthy infants.

Materials and methods

Study design and participants

This cross-sectional study included healthy infants aged 6–12 months who attended the Well-Child Clinic, Srinagarind Hospital, Khon Kaen University, Thailand, between January and December 2022. Infants with bleeding disorders and cyanotic or acyanotic congenital heart diseases were excluded from the study, ensuring a sample of healthy infants. Infants with cyanotic congenital heart diseases were excluded from the study due to the potential impact on spectrophotometric measurements because elevated Hb levels or abnormal oxygen saturation may exceed the device’s accurate measurement range. Participants were selected from patients attending the well-child clinic using a consecutive sampling method. All parents and guardians of eligible infants were informed about the study, and the ensuing discussion determined their willingness to participate.

Data collection

Data, including age, gender, natal history, underlying medical condition, family history of thalassemia or haemoglobinopathy, history of anaemia during the perinatal period, current medication/supplementation, dietary history, body weight, height and basic physical examination data, were collected.

Measurements

A calm and comfortable private space was provided to infants to minimise discomfort and ensure their well-being. Parents or caregivers were allowed to stay with the infant during measurement, and distraction techniques such as toys and music were used to reduce distress. The SpHb value was measured using a Masimo Rad-67 pulse CO-Oximeter equipped with a Rainbow DCI-mini Sensor (Masimo Corporation, Irvine, CA, USA; version 1.0.7.9, manufacturing year 2021). This device distinguishes between oxygenated and deoxygenated blood by assessing the capillary bed at the tip of the finger or great toe when applied for 30–60 s. The clip-like sensor is a compact, lightweight device with a durable plastic casing and is equipped with a soft, padded sensor for comfortable attachment to the patient’s finger. It detects sufficient blood perfusion after the sensor is attached and stabilisation of signal. The one-time SpHb value and the perfusion index (PI) were displayed.¹³ A digit gauge was used to select the appropriate digit. Initially, the DCI-mini Sensor was placed on the right great toe of infants weighing <10 kg. If the sensor detected low signal stability or could not record within 3 min, the left great toe and subsequently the thumb or third digits of the right hand were used. The procedure was discontinued if SpHb could not be obtained over a maximum of four separate attempts or a maximum of 10 min, whichever occurred first. The PI is the ratio of pulsatile blood flow to static blood flow in the peripheral tissue. In this study, the PI was carefully monitored during noninvasive Hb measurements because it reflects the blood flow at the measurement site and can significantly impact measurement accuracy. If the PI was below 0.5, which may indicate poor peripheral perfusion, we intervened to warm the infant’s extremities, and the measurement was repeated to ensure more reliable results. For data analysis, a PI value of <1.0 was considered low and associated with incorrect measurement results, whereas a PI value of ≥1.0 was considered high.¹⁴ This approach helped ensure that the findings were not influenced by the effect of peripheral perfusion on Hb measurement accuracy. The standard total Hb (HbLab) value was measured as a part of CBC within 1 hour after blood sampling and within 3 hours after noninvasive measurement using a Sysmex XN1500 series automated haematology analyser (Sysmex Corporation, Kobe, Japan; software version 22; manufacture year 2017). Sysmex XN1500 offers an analysis range of 0.0 to 30.0 g/dL for Hb with high precision and accuracy and is characterised by coefficients of variation (95% reliability) of ≤1.0% and accuracy within ±0.2 g/dL. These performance metrics ensure reliable and consistent quantitative assessment of Hb levels.¹⁵ The Sysmex XN-series haematology analyser is widely used for laboratory CBC. The analyser has been reported to have strong precision and consistency, as confirmed by effective internal and external quality control measures.^16–18 According to the WHO criteria, a patient with an HbLab level of <11.0 g/dL is considered to have anaemia.⁴

Sample size estimation

The sample size was calculated based on Kazanasmas et al’s study, which reported that the mean bias (95% limits of agreement (LOA)) between continuous SpHb monitoring and the conventional laboratory method in newborns was 0.05 g/dL (−1.85 to 1.96).¹⁹ A distribution-based method was used to calculate the minimal clinically important difference (MCID), paired with the maximum allowed difference of 2.5 g/dL, to assess agreement between SpHb and HbLab. Considering an alpha of 0.05 and a power of 0.80, a sample size of at least 86 participants was required to detect the agreement.

Statistical analysis

Data were collected and analysed using STATA version 15.0 (College Station, TX, USA). Data normality was tested using the Shapiro–Wilk test. Demographic data were analysed using descriptive statistics. Continuous variables were presented as mean±SD or median and IQR according to data distribution. Categorical variables were presented as frequency and percentage. The correlation between SpHb and HbLab was determined using Pearson’s correlation coefficient. Bland–Altman analysis was performed to assess the mean bias and 95% LOA of SpHb with HbLab to determine the agreement between different methods. LOA is defined as mean bias±1.96 SD.

Sensitivity/specificity and positive predictive value (PPV)/negative predictive value (NPV) were determined to assess the accuracy of SpHb. The area under the receiver operating characteristic curve was used to evaluate the overall performance of SpHb in detecting anaemia. The optimal SpHb cut-off value was initially selected based on the maximal value of Youden’s index (specificity+sensitivity − 1)²⁰ Two-by-two tables were then used to maximise the sensitivity and specificity of Masimo Rad-67 device. A P value <0.05 was considered statistically significant.

Furthermore, a comparison was performed between (1) patients with low PI (PI <1.0) and those with high PI (PI ≥1.0), (2) patients with anaemia (HbLab <11.0 g/dL) and those without anaemia (HbLab ≥11.0 g/dL), and (3) between patients with parental heterozygous thalassemia and those without evidence of parental thalassemia to better understand the effect of PI, anaemia and haemoglobinopathy on the accuracy of SpHb.

Ethical considerations

This study was registered with the Thai Clinical Trials Registry (TCTR20210816002) and approved by the Human Research Ethics Committee of Khon Kaen University (HE641289). Written informed consent was obtained from all infants’ parents or their legal guardians.

Patient and public involvement

Neither patients nor public were involved in the design, conduct or dissemination of the findings. However, patient guardians’ perspectives, concerns and feedback were discussed at the end of the procedure.

Results

A total of 115 infants were enrolled. Among them, 11 were excluded due to difficulty in obtaining SpHb measurements. Thus, 104 infants were included in the final analysis. Table 1 shows the demographic data of the infants. Of the 104 infants, 57 (54.81%) were males with a mean age of 10.59±3.52 months, and 13 (12.5%) were low-birth-weight infants. Additionally, two infants (1.9%) had a history of neonatal anaemia, 30 (28.8%) and 24 (23.1%) had a maternal and paternal history of heterozygous thalassemia, respectively, 11 (10.6%) were diagnosed with iron deficiency anaemia and 12 (11.5%) received iron supplements according to Thai government policy. The breastfeeding rate was 81.7%, with an average duration of 7.85±2.41 months. Exclusive breastfeeding for at least 6 months was observed in 72 (69.2%) infants. Forty-three (41.3%) infants were currently breastfed or receiving breastmilk. Dietary records showed that 25.0% of the infants received adequate iron intake (≥9 mg/day) according to the Thai dietary recommended intake 2020 for infants aged 6–11 months.²¹ The prevalence of anaemia, as defined by conventional laboratory Hb of <11.0 g/dL, was 38.5%. A significant number of infants with anaemia received breastfeeding compared with those without anaemia (60.0% vs 29.7%, p=0.002). Furthermore, infants with anaemia had lower median iron intake (2.86 (IQR 4.52) vs 6.38 (IQR 6.60) mg/day, p=0.002) than those without anaemia (table 2).

Table 1

Baseline characteristics of infants undergoing noninvasive haemoglobin measurement (n=104)

Variables	Number
Characteristic
Gender, male	57	(54.8%)
Age (months), mean (SD)	10.59	(3.52)
Prenatal factor
Maternal anaemia	22	(21.2%)
Maternal thalassemia trait	30	(28.8%)
Paternal thalassemia trait	24	(23.1%)
Postnatal factor
Birth weight, mean (SD)	3.02	(0.46)
Birth length, mean (SD)	48.88	(3.14)
Low birth weight (<2500 g)	13	(12.5%)
Neonatal anaemia	2	(1.9%)
Presence of anaemia	6	(5.8%)
Previously diagnosed with thalassemia	3	(2.9%)
Previously diagnosed with iron deficiency anaemia	11	(10.6%)
Feeding history
Mode of feeding
Breastmilk	31	(29.8%)
Breastmilk with formula	12	(11.5%)
Formula	61	(58.7%)
Duration of breastfeeding (n=85)
<6 months	13	(15.3%)
≥6 months	72	(84.7%)
Median (IQR)	7.85	(2.41)
Iron intake
Iron intake (mg/day), median (IQR)	4.85	(6.82)
Adequate iron intake (≥9 mg/day)	26	(25.0%)
Iron supplementation	12	(11.5%)
Anthropometry
Weight-for-age z score, mean (SD)	−0.41	(1.07)
Length-for-age z score, mean (SD)	−0.35	(1.13)
Weight-for-length z score, mean (SD)	−0.19	(1.09)
Measurements
SpHb, mean (SD)	12.20	(1.10)
Perfusion index, mean (SD)	4.10	(1.88)
HbLab, mean (SD)	11.19	(1.21)
Anaemia (HbLab <11.0 g/dL)	40	(38.5%)

HbLab, haemoglobin from conventional laboratory analysis; SpHb, Spectrophotometric determination of haemoglobin from noninvasive measurement.

Table 2

Characteristics of infants with and without anaemia defined by conventional haemoglobin of <11.0 g/dL

Variables	Participants with anaemia (n=40)		Participants without anaemia (n=64)		P value
	N	(%)	N	(%)
Characteristic
Gender, male	24	(60.0%)	33	(51.6%)	0.400*
Age (months), mean (SD)	10.29	(4.06)	10.77	(3.16)	0.523†
Prenatal factor
Maternal anaemia	10	(25.0%)	12	(18.8%)	0.448*
Maternal thalassemia trait	15	(37.5%)	15	(23.4%)	0.124*
Paternal thalassemia trait	11	(27.5%)	13	(20.3%)	0.397*
Postnatal factor
Birth weight (kg), mean (SD)	3.03	(0.43)	3.01	(0.48)	0.792†
Birth length, mean (SD)	49.00	(3.90)	48.81	(2.59)	0.789†
Low birth weight (<2500 g)	4	(10.0%)	9	(14.1%)	0.542*
Presence of anaemia	6	(15.0%)	0	(0.0%)	0.003‡
Previously diagnosed with thalassemia	3	(7.5%)	0	(0.0%)	0.054‡
Feeding history
Breastmilk	24	(60.0%)	19	(29.7%)	0.002*
Breast feeding duration, mean (SD)	8.14	(2.00)	7.64	(2.67)	0.358*
Formular fed	10	(25.0%)	46	(71.9%)	0.024*
Iron intake
Total iron intake (mg/day), median (IQR)	2.86	(4.52)	6.38	(6.60)	0.002§
Fortified iron, median (IQR)	1.35	(3.86)	4.13	(6.01)	0.015§
Adequate iron intake (≥9 mg/day)	5	(12.5%)	21	(32.8%)	0.020*
Anthropometry
Weight-for-age z score
Mean (SD)	−0.62	(1.04)	−0.28	(1.08)	0.174§
Length-for-age z score
Mean (SD)	−0.56	(1.09)	−0.21	(1.14)	0.149§
Weight-for-length z score
Mean (SD)	−0.33	(1.09)	−0.11	(1.08)	0.440§
Measurements
SpHb, mean (SD)	11.65	(1.22)	12.54	(0.86)	<0.001†
Perfusion index, mean (SD)	3.76	(1.52)	4.31	(2.07)	0.119†

*P value from X² test.

†P value from independent t-test.

‡P value from Fisher exact test.

§P value from Wilcoxon rank sum test.

In all infants, the mean SpHb value was 12.20±1.10 g/dL (range, 7.7–14.3 g/dL), whereas the mean HbLab value was 11.19±1.21 g/dL (range, 7.5–14.2 g/dL). The mean PI was 4.1±1.88, and low PI was observed in four patients. Pearson’s correlation analysis revealed a moderate positive correlation between SpHb and HbLab (correlation coefficient r=0.575; 95% CI, 0.430 to 0.691; p<0.001; online supplemental figure 1). Bland–Altman analysis revealed that the mean bias between SpHb and HbLab values was 1.007 g/dL, and the 95% LOA were −1.091 to 3.104 g/dL (p<0.01; table 3 and figure 1).

Figure 1. Bland-Altman analysis of the bias (+1.007 g/dL) and 95% limits of agreement (-1.091 to 3.104 g/dL) between Radical-67 (SpHb) and conventional laboratory analysis (HbLab).

Table 3

Agreement of haemoglobin measurements

	Haemoglobin (g/dL) mean (95%CI)	Pearson correlation		Bland-Altman analysis
		Correlation (95%CI)	P value	Mean difference (g/dL)	Limits of agreement (g/dL)
All participants, n=104
SpHb	12.20 (11.98 to 12.41)	0.575 (0.430 to 0.691)	<0.001	1.007	−1.091 to 3.104
HbLab	11.19 (10.95 to 11.43)
Anaemia (HbLab<11.0 g/dL), n=40
SpHb	11.65 (11.26 to 12.04)	0.435 (0.143 to 0.657)	0.005	1.635	−0.617 to 3.887
HbLab	10.01 (9.74 to 10.29)
Non-anaemia (tHb≥11.0 g/dL), n=64
SpHb	12.54 (12.33 to 12.76)	0.490 (0.277 to 0.657)	<0.001	0.614	−0.964 to 2.192
HbLab	11.93 (11.75 to 12.11)

HbLab, haemoglobin from conventional laboratory analysis; SpHb, Spectrophotometric determination of haemoglobin from noninvasive measurement.

Further analysis of the effect of the PI on SpHb measurement accuracy was performed by dividing participants into low PI (n=4) and high PI groups (n=100). The mean bias between SpHb and HbLab was higher in the low PI group than in the high PI group (1.33 vs 0.99 g/dL, p<0.001) (online supplemental table 1). Anaemia showed a significant change in the agreement between the two methods. The mean bias between SpHb and HbLab was higher in the anaemic group than in the nonanaemic group (1.64 vs 0.61 g/dL, p<0.001) (table 3). Furthermore, the absolute width of the LOA was greater in the anaemic group than in the nonaanemic group (~4.50 vs . 3.15 g/dL). The Masimo device tended to overestimate Hb levels, particularly in individuals with anaemia. For further investigations, we categorised the participants according to their anaemia status and assessed the degree of overestimation in each group. The findings showed a consistent trend of increasing mean difference according to the severity of anaemia (online supplemental table 2).

The overall receiver operating characteristic curve was 0.732 (95% CI, 0.632 to 0.832) (figure 2). The optimal value of SpHb with the highest sensitivity and specificity for anaemia prediction was calculated using Youden’s index. The best SpHb cut-off value was <11.5 g/dL, which showed a sensitivity of 42.5% (95% CI, 33.0 to 52.0), specificity of 89.1% (95% CI, 83.1 to 95.1), PPV of 70.8% (95% CI, 62.1 to 79.6) and NPV of 71.3% (95% CI, 62.6 to 80.0). The rate of correctly classified patients was 71.1%. Furthermore, the performance of SpHb in detecting anaemia was explored using different points (online supplemental table 3). As a screening test, a SpHb cut-off value of <13.0 g/dL provided the most appropriate sensitivity compared with HbLab with a sensitivity of 95.0% (95% CI, 90.8 to 99.2), specificity of 35.9% (95% CI, 26.7 to 45.2), PPV of 48.1 (95% CI, 38.5 to 57.7) and NPV of 92.0 (95% CI, 86.8 to 96.4).

Figure 2. Receiver operating characteristic (ROC) curve analysis of SpHb as a diagnostic tool area under the ROC curve of 0.732 (95% CI: 0.632 to 0.832).

Discussion

This study assessed the accuracy of a noninvasive Hb measurement, Masimo Rad-67, compared with the gold standard measurement of Hb by the conventional laboratory method in infants aged 6–12 months. The prevalence of anaemia in the participants was 38.5%. A similar study in Korean infants and toddlers also revealed high prevalence, especially among those aged between 9 and 12 months. Major factors contributing to severe anaemia included prolonged breastfeeding without iron fortification and low birth weight.²² Another study revealed that 11.8% of 6-month-old infants were found to be anaemic, which was associated with exclusive breastfeeding and inappropriate complementary feeding.²³ Both studies emphasised the importance of early detection through regular screening and addressing early intervention.

This study showed that SpHb was moderately correlated with HbLab (r=0.575), with a mean bias of 1.007 g/dL (95% LOA, −1.091 to 3.104). Bland–Altman analysis revealed that SpHb measurements were significantly higher than HbLab measurements, and the agreement interval was relatively wide, with an absolute width of 4.19 g/dL. However, the noninvasive device showed good concordance and a narrow absolute LOA width with HbLab in the nonanaemic group compared with the anaemic group. These findings indicate the detection of falsely high Hb levels by SpHb, particularly in infants with anaemia. Thus, SpHb measurement cannot be used interchangeably with the conventional laboratory measurement for the diagnosis of anaemia, especially in infants.

The PI values indicate the quality of the recorded SpHb values. The mean bias between SpHb and HbLab in the low PI group was greater than in the high PI group. However, we could not demonstrate the correlation due to the small number of infants in this group and thus could not compare the correlation coefficients between the PI groups.

The results showed that a SpHb value of <13.0 g/dL had a strong sensitivity (95%) and moderate NPV (92.0%) as a screening test for anaemia in healthy infants compared with the conventional laboratory measurement. Using this cut-off, we would have missed only two patients with anaemia. Furthermore, almost 50% of the nonanaemic group would not have needed venipuncture.

Most studies have been conducted to compare the accuracy of noninvasive devices with the conventional laboratory method using either continuous SpHb measurement (Radical-7) or spot-check (Pronto-7) in different populations (newborns, preschool-age children and adults) with a wide range of clinical settings (emergency and nonemergency operating rooms, emergency departments, critical care units, outpatient clinics and postpartum women) and with vastly different results.^24–28 A systematic review and meta-analysis showed a mean bias of 0.23 g/dL (95% CI, −0.16 to 0.62) between noninvasive and invasive methods, with high levels of inconsistency among studies.²⁹ Our study showed a low correlation and a wider mean difference between SpHb and HbLab. These findings contradict those of Zortéa et al, who reported that noninvasive Hb monitoring methods, including SpHb, can provide reliable results in various clinical settings. However, it is important to note the key differences between their meta-analysis and our study. Zortéa et al primarily focused on adult populations, in which motion artefacts, peripheral perfusion and cardiovascular dynamics are typically more stable than those in young infants. Furthermore, their review included trials that used continuous Hb monitoring, which led to more accurate readings than single-point readings in our study. Finally, they reported that noninvasive Hb monitoring is less reliable in low-perfusion states and lower Hb levels, which are prevalent in patients with anaemia, as observed in our study. These findings are consistent with those of our study, which showed that SpHb measurements were less reliable in anaemic infants, resulting in a lower correlation coefficient and wider LOA than in nonanaemic infants.

In 2023, Panda et al conducted a systematic review and meta-analysis of 10 studies involving 1047 neonates and 1477 paired Hb observations. The results showed a high correlation coefficient (r=0.94) between SpHb levels and laboratory measurements, indicating substantial agreement. In addition, the mean difference between the two measurements was minimal (–0.013 g/dL), indicating that noninvasive devices may serve as reliable screening tools in neonates and potentially reduce the need for frequent phlebotomy.³⁰ These findings differ from those of our study. The higher correlation in their analysis may be attributed to differences in the patient population, as neonates generally exhibit a more stable peripheral perfusion than older infants. Additionally, continuous or advanced monitoring devices were used in controlled settings in most of the studies in their review, which contributed to strong agreement. In contrast, our study included older infants in which motion, low perfusion and anaemia might have contributed to a wider mean difference and lower correlation. This highlights the need for further optimisation of SpHb devices, particularly in paediatric populations with more physiological variability. Amano et al investigated the accuracy of Radical-7 in detecting anaemia in 43 preschool children. The mean bias was −0.6 g/dL (95% LOA, −2.76 to 1.56), with 0.99% anaemia prevalence.³¹ Hsu et al reported that the Pronto-7 device provided reliable Hb values compared with the conventional laboratory method in healthy children aged 9–36 months. Their study showed a mean bias of 0.066 g/dL (95% LOA, −2.12 to 1.99). In addition, their study showed that a SpHb level of <11.5 g/dL had a sensitivity, specificity, PPV and NPV of 82%, 65%, 33% and 95%, respectively.³² These findings were consistent with those reported by Parker et al, who assessed SpHb in 112 children aged 6–59 months in Rwanda.³³ Their study reported a mean bias of −0.2 g/dL (95% LOA, −2.4 to 2.0). Based on HbLab, the prevalence of anaemia was 34.0%. Using a cut-off value of 11.5 g/dL, SpHb demonstrated a sensitivity of 66% and specificity of 70%, accurately identifying 69% of patients. Notably, when focusing on children aged 18–59 months, the sensitivity and specificity increased to 72% and 84%, respectively, indicating 80% correct classification. Further studies are needed to investigate the influence of infant’s age on accuracy. Compared with our study, these studies included older children and used continuous monitoring methods, which may have contributed to the lower mean bias observed in these studies.^31–33 In addition, continuous monitoring could help smooth out fluctuations and provide more stable estimates of Hb levels over time. In contrast, our study focused on single-point measurements, which may introduce variability due to transient physiological changes or device limitations.

Few studies have been conducted on children using Masimo Rad-67. Arai et al studied 102 paediatric patients aged 1–5 years (mean age, 3.7 years) and found that the prevalence of anaemia was only 4%, which was lower than that in our study. The authors discovered a positive correlation (r=0.548) with a mean bias of 0.188 g/dL (95% LOA, −1.613 to 1.988).³⁴ Conversely, a study was conducted on 120 Indian children (aged 6–59 months; mean age of 33.7±15.7 months) presented with acute illness, using the same device by Ramaswamy et al.³⁵ The prevalence of anaemia was found to be 75% with a mean bias of 2.49 g/dL (95% LOA, −0.3 to 5.2 g/dL), which was much more comprehensive than the bias found in our study. The sensitivity and specificity were 24.4% and 96.7%, respectively, while the PPV and NPV were 19.2% and 80.8%, respectively. Compared with similar studies using Masimo-Rad67, Arai et al³⁴ demonstrated a lower mean bias and a narrower range of the 95% LOA. Ramaswamy et al reported a higher mean bias with a broader range of 95% LOA. Both studies were conducted on participants older than those in our study (approximately 33–44 months vs 10.6 months) and in regions with a low prevalence of anaemia in Japan. We hypothesised that younger age and the presence of anaemia could impact the accuracy of SpHb measurements. Furthermore, continuous noninvasive spectrophotometry monitoring appears more precise than the spot-check method due to signal stability. The higher mean bias and wider agreement intervals highlight the variability and limitations of our study. Future research should address these issues by increasing the sample size, conducting sensitivity analysis to consider potential confounding variables and using average values from multiple measurements when using the spot-check method.

SpHb is a quick, noninvasive method for measuring adult Hb levels. However, it was initially not designed for paediatrics due to limitations such as insufficient data to support its use in children and challenges with detecting anaemia.³⁶ These limitations include motion artefacts, haemoglobinopathies, high Hb content in neonates and patients with cyanosis and interference from pigments on the skin, such as carotene, melanocytes, dark skin tone and bilirubin.^{27 37} Despite being less invasive, safe and easy to apply in paediatric patients, this device has some accuracy issues.

Our study showed that approximately 28% of the participants exhibited a potential heterozygous thalassemia status based on their parents’ Hb typing. However, only three participants were diagnosed with thalassemia disease. A previous study involving 110 children with thalassemia reported a strong correlation between SpHb values measured using Masimo Radical-7 and HbLab values.³⁸ Their study showed that this device could screen for anaemia in haemodynamically stable patients with haemoglobinopathies and make transfusion decisions when combined with clinical assessment. Further analysis was performed by subgrouping the participants based on their parents’ Hb typing. The analysis revealed that haemoglobinopathy had no significant effect on SpHb. The mean bias was 1.145 g/dL (95% LOA, −0.891 to 3.182 g/dL) in the parental heterozygous thalassemia group and 0.913 g/dL (95% LOA, −1.222 to 3.047 g/dL) in the normal group (online supplemental table 4). Based on our experience, SpHb values could not be obtained from 11 out of 115 (9.6%) participants. This may be due to the fact that infants at this age exhibit fear towards unfamiliar persons and environment, making it difficult for them to cooperate and leading to crying during measurement.^{39 40} Attaching the sensor clip to infants’ fingers proved more challenging than using the infant adhesive sensor, which provides a secure fit that closely conforms to young children’s fingers.

When evaluating the accuracy of a device for anaemia screening, it is essential to consider concerns related to its failure rate, especially in resource-constrained settings where anaemia is prevalent. Reliable diagnostic tools are crucial for timely intervention, as the inability to measure accurately could result in underdiagnosis and delayed treatment that could worsen health disparities. Strategies such as refining the device, providing operator training and implementing backup methods should be considered to address this. Future research should focus on the improvement of the device’s accuracy and reliability, particularly in real-world contexts with limited resources. Proactive acknowledging and tackling these challenges can provide more robust and accessible solutions for anaemia screening in resource-constrained settings. Additionally, noninvasive measurement methods for children receive positive parental feedback due to reduced discomfort, minimised pain, faster procedures and increased convenience compared with invasive methods.

Conventional laboratory analysis is costly and not routinely available in primary care settings. Moreover, this method is time-consuming, and venipuncture causes significant pain and stress in infants, which may lead to low adherence to anaemia screening programmes. In contrast, the noninvasive method has the advantages of easy application by minimally trained health professionals, less invasiveness and a short turnaround time as the SpHb value is displayed on a screen within a few minutes. Our analysis identified a SpHb cut-off of <13.0 g/dL as the optimal threshold for detecting anaemia risk based on its ability to provide the highest sensitivity, which is critical for screening purposes. The difference between the SpHb cut-off of <13.0 g/dL and the laboratory Hb cut-off of <11.0 g/dL reflects the inherent differences between noninvasive and laboratory-based measurements. Noninvasive Hb measurements tend to overestimate Hb levels compared with laboratory measurements due to device accuracy and factors such as motion artefacts. While this approach maximised the utility of SpHb for screening, we acknowledge that using the laboratory Hb cut-off of <11.0 g/dL might have yielded different results. These findings highlight the importance of standardising SpHb thresholds to ensure better alignment with laboratory criteria and to optimise clinical decision-making. For clinical implication, these characteristics make the device highly suitable for screening purposes, especially in high-risk groups or the early stages of a condition, where early detection is crucial. This test can help in identifying individuals who require further diagnostic evaluation while reducing unnecessary anxiety and invasive interventions. However, confirmatory tests with a CBC should be conducted due to the low specificity and PPV. The noninvasive technique offers integration into clinical practice by implementing a two-step diagnostic process in resource-constrained settings to optimise patient care and resource use efficiently. However, in a setting where infants can undergo invasive laboratory testing, the noninvasive test can be incorporated in specific scenarios that include follow-up protocols for anaemic patients. Hence, the SpHb measurement can still be a screening test, especially where conventional laboratory analysis is unavailable. This study has shown that a SpHb cut-off of <13.0 g/dL can be used as a screening tool for infants aged 6–12 months living in areas with moderate public health issues, as defined by the WHO criteria, which indicates anaemia prevalence ranging from 20%–39%.⁴ However, in areas with a high prevalence of anaemia, infants with a high risk of anaemia, such as those with low birth weight, prematurity, prolonged exclusive breastfeeding or inappropriate complementary feeding, might not be a good candidate for this noninvasive test. Therefore, conventional CBC remains the first option for screening in high-risk groups. The conventional method has the advantage of providing important information, including red blood cell indices and morphology.

The cost of the Masimo Rad-67 noninvasive Hb device, compared with traditional CBC testing, warrants consideration for its use in clinical and community settings. Initially, the SpHb device, including the reusable sensor, costs approximately 120 THB per test. However, after the device is purchased, subsequent tests using the reusable sensor cost approximately 60–80 THB each. In contrast, traditional CBC costs 120 THB per test, with additional expenses for laboratory personnel and blood collection, ranging between 50 and 120 THB per test. Although the noninvasive device may be slightly more expensive, its advantages, such as improved patient comfort, rapid results and the elimination of the need for laboratory infrastructure, make it a practical option for large-scale screening in resource-limited settings, such as schools and community health programmes. Furthermore, by reducing the reliance on skilled personnel and invasive procedures, the device could enhance screening coverage and improve compliance, particularly in underserved populations.

The Department of Health recommends providing weekly iron supplements to children aged 6–59 months, which is crucial for preventing anaemia. Despite these recommendations, the persistent prevalence of anaemia indicates that barriers to iron supplement administration remain. This study did not investigate the reasons for parental noncompliance with iron supplementation. It is necessary to understand why only 25%–60% of children receive iron supplements despite the recommendation of weekly iron supplementation by national guidelines. This may be due to factors such as parental awareness, accessibility of supplements, concerns about side effects and perceived importance of iron supplementation. Therefore, further studies investigating barriers to iron supplementation are needed to better inform targeted interventions and improve compliance, thereby reducing anaemia rates.

Noninvasive screening is clinically significant for several reasons. It enables early identification of high-risk children even before symptoms become clinically significant, which prompts timely interventions. Additionally, noninvasive screening can increase parental awareness of iron supplementation and motivate parents to adhere more closely to the recommendations. Furthermore, it enables targeted interventions in populations or regions with particularly low adherence, thereby contributing to the development of more effective anaemia prevention strategies.

Strengths and limitations

To the best of our knowledge, this is the first study to assess the use of spot-check Masimo Rad-67 for screening anaemia at a well-child care clinic among infants with a moderate prevalence of anaemia. Previous studies have been conducted on older age groups, not in healthy infants or in areas with a low prevalence of anaemia.

This study had some limitations. First, this was a single-centre study, and only three researchers performed measurements to minimise interindividual variability. Each case took approximately 4–5 min, starting with calming the infant, placing the sensor and monitoring for pulse detection while showing an SpHb value on the screen. Second, a single measurement was collected from each case, not using the average value from 2 to 3 measurements that could provide internal validity data. Third, this study focused on the evaluation of the analytical accuracy of noninvasive Hb measurement, including the analysis of mean bias and the determination of the optimal cut-off value for using the device as an anaemia screening tool. However, the cost-effectiveness or clinical utility of noninvasive methods was not explored, which are considered important factors for their broader application in clinical practice. Therefore, further studies are needed to assess the cost-effectiveness of these methods. Furthermore, evaluating how these methods can be integrated into public health strategies to promote adherence to anaemia prevention guidelines can provide valuable insights into their role in enhancing health outcomes in children.

At the time we designed our study, no prior research had evaluated spot-check Hb measurements using the Masimo Rad-67 in paediatric populations. In this study, the sample size was calculated based on a previous study that used continuous Hb monitoring in neonates.¹⁹ A distribution-based method was employed to determine clinically meaningful thresholds, as emphasised by Franceschini et al.⁴¹ This approach allows for a more flexible calculation of MCID, adjusting for the specific characteristics of the population and measurement method. This is particularly important in paediatric settings where physiological differences may affect measurement accuracy. Furthermore, a maximum allowed difference of 2.5 g/dL was used to ensure statistical power, acknowledging that this threshold may appear broader than clinically ideal, particularly in cases where Hb levels directly guide management decisions, such as the transfusion threshold. More stringent MCID thresholds, such as 1 g/dL, may be more appropriate in clinical practice to avoid overtreatment or undertreatment, especially in critically ill paediatric patients. Notably, the maximum allowed difference is relatively broad. However, it is more acceptable for screening purposes than for treatment decisions. To further refine the results, sensitivity and specificity analyses were performed to determine the optimal cut-off point for enhancing the diagnostic utility of SpHb monitoring. Further studies generating specific data for spot-check methods in paediatric populations are needed to refine MCID values and improve clinical relevance. This will help narrow the LOA and enhance the clinical utility of devices such as Masimo Rad-67 in paediatric care.

In this study, approximately 10% of the participants in the study did not have their SpHb levels measured, which could impact the accuracy and reliability of the results. This reduced the effective sample size and may have introduced bias if failures were more common in certain groups, leading to overestimation of the device’s accuracy. Most failures in this study were due to sensor attachment issues that caused unstable readings, particularly in infants weighing less than 6 kg. Excluding these failed measurements may limit the generalisability of the findings. In resource-limited settings, this could result in undiagnosed anaemia, undermine confidence in the device’s reliability and restrict screening efforts. Therefore, further studies are needed to address and reduce the high failure rate before broad implementation.

Conclusion

Masimo Rad-67 is a noninvasive Hb measurement device that demonstrates a moderate correlation with the standard Hb measurement of Hb in healthy infants. It has moderate sensitivity and negative predictive value, may serve as a useful tool for initial screening to minimise unnecessary venipuncture and alleviate stress for infants and caregivers, particularly in settings where conventional laboratory analysis is unavailable. However, the device’s low specificity and PPV underscore the need for additional confirmatory testing to ensure accurate diagnosis and appropriate management. Its limited sensitivity in detecting severe anaemia suggests it is better suited for identifying individuals with higher Hb levels (>13.0 g/dL of Hblab) rather than accurately diagnosing severe anaemia. Given these limitations, the Masimo Rad-67 should be used as an adjunct to, rather than a replacement for, traditional laboratory testing to ensure accurate diagnosis and effective clinical management.

We would like to give our deep gratitude to the parents and children. This manuscript was edited for English language by Enago.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request. Data used in the analysis will be made available to researchers upon request, in compliance with ethical guidelines and with the ethics committee’s approval.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).

Ethics approval

This study involves human participants and was approved by The Human Research Ethics Committee of Khon Kaen University (HE641289). Participants gave informed consent to participate in the study before taking part.

Footnote

Contributors Conceptualisation: SuS, PrS and LT. Data curation: SuS. Formal analysis: SuS and PrS. Funding acquisition: SuS and RU. Investigation: CT, SuS, SaS, PhS, LT and RU. Methodology: CT and SuS. Project administration: SaS. Visualisation: SuS, PhS and PrS. Writing-original draft: CT and SuS. Writing-review and editing: SaS, PhS, PrS, LT and RU. SuS is responsible for the overall content as guarantor.

Funding This study was funded by the Faculty of Medicine (Grant No:IN64321) and supported by Research and Graduate Studies, Khon Kaen University, Thailand (Grant No:NA).

Competing interests None declared.

Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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