Growing-Up Milk: A Good Strategy to Prevent Iron Deficiency in Young Children

© Robert Hrovat on Unsplash

In France, the strategy for preventing iron deficiency in young children is partly based on the recommendation to use iron-fortified infant formula – including growing-up milk – when breastfeeding is discontinued. But what is the real contribution of these products in preventing iron deficiency? A research team from Inserm, AP-HP and Université de Paris within the Center of Research in Epidemiology and Statistics (Cress) studied the iron intake from diet and the occurrence of deficiency in 561 two-year-olds in France from 2016 to 2017. The researchers found that the consumption of iron-fortified infant formula very significantly reduced the risk of iron deficiency and met the recommended daily nutrition requirements for nearly half of the children. These results, published in Clinical Nutrition, support France’s prevention strategy and call for special attention to be paid to underprivileged families, whose children are most affected by iron deficiency.

Iron deficiency is considered the most common micronutrient deficiency worldwide, particularly in industrialized countries. When it occurs in newborns and young children, it is strongly suspected of being associated with adverse short- and long-term neurocognitive effects, such as decreased learning and memory abilities, and visual and auditory neurosensory impairment.

For infants over 1 year of age, the recommended average daily requirement for iron is 5 mg[1]. When the blood level of ferritin (a protein that stores iron) is below 12 µg/L, a young child is considered to be deficient.

In France, the strategy to prevent iron deficiency is partly based on the recommendation of systematic and prolonged consumption of iron-enriched infant formula – particularly so-called “growing-up” milk from 1 to 3 years of age – when breastfeeding is discontinued, in order to supplement intake from the diet, which is rarely sufficient for this age group.

In order to examine the relevance of this prevention strategy, the work of a research team from Inserm, AP-HP and Université de Paris within the Center of Research in Epidemiology and Statistics – Cress (Inserm/Université de Paris/Université Sorbonne Paris Nord/INRAE), coordinated by Anne-Sylvia Sacri and Martin Chalumeau, compared iron intake from the diet, with and without the consumption of growing-up milk, and the occurrence of deficiency in 561 two-year-olds with no health conditions affecting iron metabolism. Between 2016 and 2017, almost 120 pediatric practices throughout France took part, thanks to the Activ and Afpa networks.

For each child, a questionnaire in which the parents noted all foods consumed over three non-consecutive 24-hour periods allowed the researchers to determine the amount of iron ingested daily. Analyses showed that when the consumption of growing-up milk (used by 73% of the participants) was not taken into account, dietary iron intake did not meet the recommended requirement of 5 mg/day for 63% of the children compared to 18% when it was taken into account.

The consumption of growing-up milk therefore enabled 45% of children to meet the recommended nutritional requirements for iron.

In a second step, the ferritin level was measured from a blood sample. Of the 561 children studied, 37 (7%) were iron deficient. Blood ferritin levels were significantly higher in children consuming growing-up milk at 24 months or since the age of 10 months. It was significantly lower in those consuming cow’s milk at 24 months or who started drinking it before that age.

The onset of iron deficiency was further reduced the longer growing-up milk was consumed, even in small quantities (upwards of 200 mL/day).

This suggests that regular iron intake is a better way to prevent iron deficiency than heavy supplementation over a short period of time,” states Sacri.

She goes on to say: “These results support national strategies for the prevention of iron deficiency based on the recommendation to consume iron-fortified infant milk after 12 months of age. These milks appear to be a simple solution for supplementing young children with iron to meet the recommended daily nutritional requirements. “

The researchers also found that iron deficiency was associated with a history of prematurity. It was also more common in large families and in those with markers of social disadvantage.

“Special attention must be paid to these more vulnerable populations. They must be targeted more specifically by prevention and surveillance policies,” concludes Chalumeau.


[1] According to the recommendations of the European Food Safety Authority (EFSA)

Publication of a multicentre observational study, in the journal JAMA Neurology, to identify risk factors for the severity of COVID-19 in patients with multiple sclerosis in France

Multiple sclerosis (MS), red cells are dying (cell death). Astrocytes exposed to glycotoxic factor. ©Inserm/RIEGER F.

A study, aimed at identifying the risk factors for the severity of COVID-19 in patients with multiple sclerosis in France, was carried out by teams from the neurology department of the Pitié-Salpêtrière hospital AP -HP, from the Brain Institute (Inserm / CNRS / Sorbonne University) at the Pitié-Salpêtrière hospital AP-HP, from Sorbonne University and the neurology service of the Strasbourg CHU. This work was carried out with the participation of all the centers and neurologists involved in the management of multiple sclerosis, thanks to the national networks FCRIN4MS, the French Observatory of MS (OFSEP) and the Société Francophone of the SEP (SFSEP).

The results of this study, which were published on June 26, 2020 in the journal JAMA Neurology, led to the publication of the first registry on multiple sclerosis and COVID-19. This register made it possible to provide concrete information in real time to guide the management of patients during the epidemic.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, which mainly affects young adults, and which can be responsible for a neurological handicap. In recent years, several immunosuppressive or immunomodulatory treatments have enabled major advances in the care of patients.

From the start of the COVID-19 epidemic, neurologists and patients have had many questions regarding the risk of COVID in patients with multiple sclerosis, particularly in relation to their basic therapy. We therefore set up a multicentre observational study whose objective is to identify the risk factors for COVID-19 severity in patients with multiple sclerosis in France.

More than 350 patients were included in the registry, and the teams identified as main factor of COVID-19 severity neurological handicap (measured by the EDSS score), followed by age and obesity, these 2 factors have also been identified in the general population. Conversely, long-term MS treatments are not associated with a higher risk of severe COVID. The mortality rate was 3.5%, slightly higher than the expected rate in this population with an average age of 44 years.

This is the first registry published on multiple sclerosis and COVID-19. It provided concrete, real-time information to guide the management of patients during the epidemic.

Discovery: Stopping inclusions in two treatment groups

After the inclusions in the hydroxychloroquine arm stopped, both arms testing the lopinavir/ritonavir combination with or without interferon beta were stopped in the Solidarity and Discovery clinical trials. Given the adaptive nature of the Solidarity trial and its European Discovery “daughter” trial, a reflection is underway on the evolution of the protocol. Publications in international peer-reviewed journals are in preparation concerning both the evaluation of hydroxychloroquine and lopinavir/ritonavir.

 The Solidarity and Discovery clinical trials, whose objective is to test the efficacy and safety of medicines repurposed for the indication of SARS-CoV-2 infection requiring hospitalization, announced today the definitive cessation of inclusions in the groups of patients receiving the lopinavir/ritonavir antivirals with or without interferon beta.

This decision is based on the recommendations for termination made by the independent data monitoring panels of the two trials. These were based on the lack of efficacy on mortality of hospitalised patients for the lopinavir/ritonavir compared to standard therapy. On the other hand, in the Discovery trial, which thoroughly analyzed adverse events in treated patients, the independent committee highlighted the significantly higher frequency of serious adverse events based on clinical laboratory data related to renal function in the two groups of patients receiving the lopinavir/ritonavir combination, particularly in intensive care patients. It should be added that the UK Recovery trial also stopped the lopinavir/ritonavir treatment arm for lack of efficacy.

A communication in the form of publications in international peer-reviewed journals will detail the results. In addition, given the adaptive nature of the Solidarity trial and its European “daughter” trial Discovery, a reflection is underway on the evolution of the protocol. In addition to the ongoing evaluation of Remdesivir and interferon, this includes the possibility of testing new treatments.

The pandemic linked to the SARS-CoV-2 virus responsible for Covid-19 disease continues to progress. The Solidarity global therapeutic clinical trial organized by WHO continues to include approximately 500 patients per week, particularly in South America, in the Middle East and in Asia where the epidemic remains active. The current total number of patients included in Solidarity is more than 5,500 worldwide, of which 760 patients are part of the Discovery trial. France is the 2nd largest contributor in terms of number of patients.

Artemisia miracle plant, really?

The composition and quality of non-pharmaceutical remedies based on Artemisia vary greatly due in particular to differences in the composition of the plant materials used. © Krzysztof Ziarnek, Kenraiz / CC BY-SA

Native to Asia, the Artemisia plant has been used in traditional Chinese medicine for centuries. Nearly 400 species of the plant now grow around the world, including Artemisia annua (annual mugwort). It is from this species that artemisinin is extracted, the active ingredient contained in the main antimalarial treatments used to treat the disease today.

For several years now, a debate has been raging in the scientific community about the efficacy of various non-pharmaceutical products based on Artemisia, such as infusions or herbal products. While some believe that these plant-based treatments have a role to play in the fight against malaria, particularly in endemic and remote areas, most researchers point to the lack of solid efficacy data.

The issue has not finished being discussed, especially since in the context of the Covid-19 pandemic, Artemisia is once again in the spotlight after the Malagasy president announced that a drink based on extracts from the plant, called Covid-Organics, could be a cure for the new coronavirus SARS-CoV-2.

Other African countries have already followed suit, including the Democratic Republic of the Congo, which wants to launch a clinical trial to measure the effectiveness of Artemisia annua herbal tea in the treatment of Covid-19. Canal Détox is taking stock of the situation in order to cut short the preconceived ideas about this plant described by some as “miraculous”.

Treating malaria and avoiding resistance

The treatment of malaria recommended by WHO is now based on artemisinin-based combination therapies (ACTs). The idea is to combine an artemisinin derivative, which acts quickly and effectively to eliminate parasites, with a drug to prevent their recurrence. The aim of this therapeutic combination is therefore to achieve a cure for the patient by completely eliminating the parasite from the blood to prevent it from evolving into a serious and potentially fatal form. It should be noted that artemisinin derivatives are no longer used alone as monotherapies since 2017 to prevent the emergence of resistant strains of the Plasmodium falciparum parasite.

In some malaria-endemic areas of the world, however, access to ACTs may be limited or too costly for patients. For this reason, the use of the whole plant containing artemisinin, particularly in the form of herbal tea, has been promoted by various actors. This natural treatment would work because of the presence of artemisinin and other compounds in the plant, interacting together to reduce the number of parasites in the blood. To eliminate all infectious agents in the blood, a sufficiently high dose of herbal tea would have to be taken, at the risk of a new malaria crisis.

Problem: the composition and quality of non-pharmaceutical remedies based on Artemisia vary greatly due in particular to differences in the composition of the plant materials used, which can be influenced by various genetic and environmental factors (temperature, time and place of harvest, etc.). Similarly, the method of preparation of herbal teas and the dose of active ingredient contained in them are not standardized, and may also vary from one product to another. If these treatments can therefore improve the symptoms of certain patients, uncontrolled and often insufficient doses can lead to therapeutic failure: not all parasites are eliminated, the disease may reappear.

Furthermore, artemisinin resistance also has a greater likelihood of developing and spreading when a parasites population is exposed to too low levels of this active ingredient. Finally, the potential toxicity of herbal tea has not been accurately assessed in all populations and safety data are still patchy.

Conducting clinical trials

Some believe that the use of the whole plant would have an added value compared to ACTs because compounds other than artemisinin could have activity against the parasite, or could act in synergy with it, improving its efficacy and bioavailability, for a more powerful anti-malarial effect. The administration of the plant would thus not be similar to a monotherapy containing only one active principle against the parasite, but to a therapy containing several active principles acting in concert. This would reduce the risk of parasites developing resistance.

Several studies, mainly in vitro, have been conducted on the subject. The results are still contradictory and difficult to apply to humans, but on the whole, they suggest that the activity of other plant components against P. falciparum, such as flavonoids, is negligible compared to that of artemisinin. Finally, while some compounds do indeed appear to work in synergy with artemisinin, the risk is that they are rapidly degraded in the herbal tea.

To test the efficacy and safety of these non-pharmaceutical therapies, rigorous clinical trials are necessary. The main studies of the in vivo efficacy of Artemisia extracts have mainly been carried out using animal models of malaria. The results are of definite interest and advance research, but they cannot be applied as they stand to humans.

Clinical studies that have been conducted, while they appear to rule out the risk of adverse effects at this time, have often been conducted on a small sample of patients, with many methodological biases and/or too short a follow-up period, thus compromising the significance of the efficacy results.

Further research efforts are needed to resolve this debate. As a first step, it would be crucial to conduct better quality studies to test the hypothesis that the plant, when administered as a herbal tea and in sufficient quantity, contains several active ingredients against the parasite, acting or not acting synergistically. It is also clear that the debate cannot be resolved without new therapeutic trials based on more robust methodology and good clinical practice, including populations particularly at risk for malaria, such as pregnant women and children.

What about Covid-19?

While it is mainly another anti-malarial drug, hydroxychloroquine, that has been the talk of the town in the midst of the Covid-19 pandemic, the debate on the efficacy of Artemisia annua against Covid has also been launched following the announcement by several African governments expressing interest in the Malagasy remedy Covid-Organics and in general in this plant in the treatment of the disease.

This interest in Artemisia in the context of coronavirus epidemics is not new. Already during the SARS epidemic in China in the early 2000s, studies had highlighted the antiviral properties of the plant’s extracts. Clinical trials on the effects of traditional Chinese medicine (including the use of Artemisia) had been conducted. Positive effects had been reported on some patients, although their methodological rigour had been criticized.

The idea was recently echoed in an editorial published in the journal Nature Plants in March, suggesting that some herbal treatments could be interesting complementary therapies to drug treatments. However, this hypothesis should be rigorously tested to ensure that plants do not interact with drug treatments given to patients.

In Germany, scientists have initiated in vitro studies to test the efficacy of plant extracts against SARS-CoV-2. The team evaluated its activity against SARS-CoV-2 in a monkey lung cell model, and suggested that Artemisia herbal teas would have an antiviral effect. The hypothesis of an anti-inflammatory effect of the plant has been put forward, but no clinical data have been provided to date to support it. These results should therefore be taken with caution, especially since no figures on the extent of the antiviral effect have been shared and nothing has yet been published, either in preprint or in a peer-reviewed journal.

The plant therefore opens up interesting avenues of research, but in the absence of robust data or longer-term studies with controlled doses of Artemisia annua extracts, it does not currently constitute a treatment against Covid-19. Very rigorous clinical trials, conducted in a multidisciplinary manner with a solid methodology are therefore more than ever necessary to reach a conclusion in this thorny debate.


This text was produced with the support of Inserm researcher Eric D’Ortenzio, scientific coordinator of REACTing and Benoît Gamain, Research Director CNRS UMR-S 1134, Inserm/University of Paris.