Why anaemia in infants can’t be solved by iron supplementation alone: Notes from the ethnic underground

Aim: Our objective was to estimate the trends in incidence of anaemia among Israeli infants aged 9 to 18 months. Methods: This was a cross-sectional retrospective study for the years 2002, 2007 and 2012 in two districts. Data was analyzed for geographic distribution, age, infant’s haemoglobin level, ethnic origin, type of clinic where the infants received treatment, iron prescriptions dispensed to each child, and the mother’s last haemoglobin level before delivery. Results: The prevalence in District A for the aforementioned timeline was 16.2%, 9.9% and 8.1%, respectively (P<0.000). Prevalence was signifi cantly higher in the non-Jewish versus the Jewish population. In District B prevalence was 10.8%, 11.6%, and 8.7%, respectively, and signifi cantly higher in the non-Jewish (17.5%, 18.6%, and14.1%) than in the general Jewish population (9.0%, 9.8% and 7.5%). Among the ultra-Orthodox urban Jews, prevalence was 14.5% 14.9 %, and 11.3%, respectively. Conclusions: Anaemia in infants is multifactorial in origin and depends on both inherent biological as well as environmental factors. Effective early prevention mitigates factors across ethnoand economic divisions. Current knowledge on the subject: World Health Organization estimates anaemia prevalence at 47.4% and as affecting 293 million young children globally. The highest prevalence is in Africa (67.6%) and South-East Asia (65.5%). In the Eastern Mediterranean, the prevalence is 46% and around 20% in other WHO regions. In the United States, 7% to 9% of toddlers (1 to 3 years old) have iron defi ciency, and 2% to 3% have iron defi ciency anaemia ). In Iran the frequency of IDA was 4% and in Jordan 72%. In Israel the prevalence rate of anaemia in the year 2006 was 15.5%. Contribution of our study to knowledge: In districts A and B there was a signifi cant decrease in the percentages of prevalence of anaemia through the years 20012002, 2006-2007, and 2011-2012. Analysis of the total sample of district A revealed an almost 50% decrease, i.e. from 16.2% to 8.1%. In district B, the percentages in Jews dropped from 9% to 7.5%, in the non-Jews from 17.5% to 14.1%, and in the Ultra-Orthodox from 14.5% to 11.3%. Research Article Why anaemia in infants can’t be solved by iron supplementation alone: Notes from the ethnic underground Lutfi Jaber1-3* and Gary Diamond2,3 1The Bridge to Peace Community Pediatric Center, Taibe 40400, Israel 2Department of Neurology and Child Development, Schneider Children’s Medical Center of Israel, Kaplan Street 14, Petah Tikva 4920235, Israel 3Sackler Faculty of Medicine, Tel Aviv University, P.O.B 39040. Ramat Aviv, 69978, Israel Received: 20 April, 2020 Accepted: 15 May, 2020 Published: 16 May, 2020 *Corresponding author: L Jaber, MD, Professor, The Bridge to Peace Community Pediatric Center, Box 27, Taibe 40400, Israel, Tel: +972-9-799-2655; Fax: +972-9799-5276; E-mail: ORCID: http://orcid.org/0000-0003-4599-3053


Introduction
World Health Organization (WHO) estimates anaemia prevalence at 47.4% and as aff ecting 293 million young children globally. The highest prevalence is in Africa (67.6%) and South-East Asia (65.5%). In the Eastern Mediterranean, the prevalence is 46% and around 20% in other WHO regions [1]. In the United Citation: Jaber  families, those of Afro-American or Hispanic origin and other immigrant groups, obese children [7], progeny with a history of prematurity, or low birth weight [7], as well as exclusively breastfed infants [8], those on non-iron-fortifi ed formula without iron supplement, or infants introduced to cow's milk before their fi rst birthday. It was demonstrated that a high prevalence of anaemia in pre-school children (12%), causally linked to ID related to dietary factors, is common in areas of socioeconomic deprivation [9]. Iron defi ciency anaemia and ID without anaemia during infancy and childhood can have long lasting detrimental eff ects on neurodevelopment. Since 1985 the Israeli Ministry of Health has adopted recommendations for the prevention of IDA in infants. Around the age of 12 months, a routine Haemoglobin (Hb) screening is also recommended for all infants [10].
The purpose of this study was to use the comprehensive computerized database of the Clalit Health Services (CHS) to analyze contributing factors to anaemia among the population of CHS-insured 9 to 18 month old Israeli infants.
This study is a follow-up to a previous survey conducted in 2006 [6].

Methods
The study was conducted using the data from the years 2002, The study population included all CHS-insured infants aged 9 to 18 months for whom Complete Blood Counts (CBCs) were universally performed. The blood samples were analyzed for CBC using Coulter analysis and for the ferritin concentration using a radioimmunoassay [11].
Infants suff ering from chronic diseases were excluded.
Data included age, gender, ethnic origin, infant's Hb level, mother's last Hb value before delivery, and the number of iron prescriptions dispensed to each child by CHS pharmacies.

This study was approved by the Human Subjects Protection
Program of the Clalit Health Services Ethics Board. The WHO recommends a Hb level of 110 g/dL as a cut-off point for the diagnosis of anaemia in the paediatric population [1]. However IDA was defi ned as a Hb level of <105 g/dL. The Nelson Textbook of Pediatrics recommends a level of 105 g/dL as the cutoff point for the diagnosis of anaemia in infants aged 9 to 18 months [12].
In those infants with repeat Hb analysis, only the fi rst value was included. Mothers were matched with their children using the database that includes family demographic data. Only the last CBC performed before delivery was included. In our study pregnant women were considered to be anemic if their Hb values were <110 g/dL.

Statistical analysis
The data were analyzed using BMDP software. Continuous variables are expressed as means ± SDs. Pearson's chi-square test or Fisher's exact test was used, as appropriate, for analysis of between-group diff erences in discrete variables. Analysis of variance was used for continuous variables. A P value of ≤0.05 was considered signifi cant.

Results
Prevalence of anaemia among infants in District A for the aforementioned timeline was 16.2%, 9.9% and 8.1% (percentage from the total sample), respectively (P<0.000). Prevalence was signifi cantly higher in the non-Jewish (21.2%, 11.2%, and 10.1%) compared with the Jewish population (11.1%, 8.7%, and 7.0%) (Table1). In 2012 the prevalence of anaemia in District A was found to be higher in infants aged 9 to10 months old than in the 11 to 18 month age group. The lowest prevalence of anaemia (7.5%) was found among children treated at designated Paediatric Health Centers.
The In an associated study from another region (District B) less data was available, but diff erences were found in prevalence of anaemia according to ethnic and socioeconomic background (Table 2).
A correlation was found between the presence of anaemia in infants and the presence of anaemia found in their mothers.
Thus, infants born to anaemic mothers are more prone to develop IDA than infants born to mothers who have a satisfactory iron balance. In our study, the incidence of IDA in infants born to anaemic mothers was signifi cantly higher (10%) than in infants born to non-anaemic mothers (7.3%, P<0.000).
The impact of nutritionally disadvantaged mothers extends well beyond the pregnancy, and their poor nutritional legacy impacts on the future ability of the child to achieve his innate potential.
was more common in infants in the Ultra-Orthodox Jewish and non-Jewish populations ( Table 2). The reasons for this vary, and include ethnic, genetic, and environmental factors, and especially among poorer families with low access to iron supplementation.
Multiparty, frequent deliveries, and prolonged breastfeeding in Israel, are more common in the non-Jewish and the Ultra-Orthodox Jewish groups. This may partially explain the diff erences between the three populations studied [13].
Further studies are needed to identify the causes of the high rate of anaemia in the absence of ID, such as hemoglobinopathy, infections, and the lack of nutritional factors other than iron.
More signifi cant eff orts should be made among the non-Jewish population to analyze the causes of IDA in this group. Thereafter, special eff orts should be made to minimize the prevalence of anaemia.
Currently, such a program, based on recent studies, is being prepared and implemented in the CHS.
In addition, we have developed several quality indicators for the assessment and treatment of anaemia in infants. We also believe that screening for ID and IDA should be carried out early in a child's development (i.e., at 9 months of age) when prevention is essential for better developmental outcomes.

Discussion
Anaemia is common among Israeli infants mainly from a low socioeconomic status background. The decrease in prevalence over time among these infants could be attributed to several causes, such as the strict criteria that was used for establishing cut-off s, as well as to the national program for the prevention of IDA in infants. In addition, feeding infants with iron-fortifi ed cereals is commonplace, as is the adherence to recommended prophylactic iron supplementation.
We found that the lower incidence among infants treated in health centers attended by paediatricians may be related to the higher awareness of these physicians regarding the importance of preventing IDA in infants. In our study, there was a clear correlation between maternal Hb levels tested before delivery, and the frequency of IDA in their off spring.
In an associated study from a diff erent, more urbanized population, a comparison of anaemia rates among infants from non-Jewish, Ultra-Orthodox Jewish, and the general Jewish (more affl uent) backgrounds, revealed that anaemia