NEHMO study – Real World Study to investigate the Growth and Feeding Tolerance of Infants Consuming a Formula Enriched with HMO
José Manuel Moreno Villares
A real world study with an infant formula enriched with two HMO was done in Spain in 2018. The paper was presented at the last ESPGHAN meeting in June by Dr. Enriqueta Román Riechmann, who was the main researcher of the study. Here there are some of the results of that NEHMO study.
The idea why to perform a study on the formula that is already in the market was trying to follow the regulations of the legislation. The last regulations in infant formula said that when there are new ingredients in an infant formula first of all you have to review all the previous data and then you have to set new studies to answer the question regarding the benefits of the new ingredients. (Official Journal of the European Union, 2.2.2016)
The aim of performing this real world evidence study, when there is already done a RCT (Puccio et al., JPGN 2017) was two things:
The overall purpose was to assess and document growth and feeding tolerance of healthy term infants consuming infant formula supplemented with 2’FL and LNnT for 8 weeks in a real-world setting.
The second one was to see the behaviour of that formula in a group that was not yet present in the randomized controlled studies. The mixed-fed infant group that is, they are breastfed and receive some supplement infant formula several times a day.
Once the parents had decided the type of feeding they wanted for the kids, they were offered to enter in the study and some of them received the study formula (FF), some were exclusively breastfed (BF) and some were part of the mixed-fed group.
The outcomes were growth according to the WHO standards, the feeding tolerance and measured by means of the validated questionnaire infant gastrointestinal symptoms (IGSQ). As additional outcomes. parents were asked about satisfaction within the used of the study formula. As a safety measurement, total number of ad- verse events were also recorded. (Fig.1)
The study was done in six locations all over the country during the last four months of the last year. Once the informed consent was signed and the babies entered in the study they were first visited in the outpatient clinic, have a phone call after four weeks and were seen again in the outpatient clinic at the end of the study (8 weeks). At all the visits they have anthropometry and the questionnaire on the tolerance as well as they acceptance by the families evaluated. The study was approved by the Institutional Review Board in all centers and registered in ClinicalTrials.gov (NCT04055363). (Fig.2)
According to enrollment, 207 patients were included (114 receiving formula and 63 exclusively breastfed). From those receiving any amount of formula, 82 were exclusively bottle-fed.
Finally, in the per protocol análisis, 159 infants were considered as evaluable. Drop-outs were regularly distributed in both three groups, and mainly because of non-compliance.
The first of our goals was to see growth. The results were as normal as in the randomised control trial by Puccio et al. The infants were growing normally within 0 and -1 standard deviation from the WHO standard z-scores for weight and for height and also for the head circumference, without differences between the three groups (Fig. 3).
Gastrointestinal tolerance was investigated by means of the infant gastro intestinal symptoms scale.
Infants of all the three groups in the study investigation – face to face and by phone – have no really gastrointestinal distress. They show low IGSQ composite scores at any time point. The comparable GI tolerance in formula, mixed and breast-fed infants was indicated by similar IGSQ composite scores at all time points. So the study formula was as good and well tole rated as breast feeding in all three periods.
The mean IGSQ scores of each domain were nearly the same for all of the infant groups in all three period domains, except for the stooling characteristics.For stooling, firmness was higher in formula fed group at the beginning of the study and similar to breast-fed group by the end of the 8 week period. (Fig. 4)
The incidence of AE in the study was low and comparable for all three groups, despite the high incidence rate of respiratory infections at the time of the study (fall and winter time).In three patients receiving formula adverse events were considered in relation with the formula, although not confirmed. In the satisfaction questionnaire for parents at the end of the per-protocol study most of them were satisfied with the HMO-supplemented formula (90 %) and were willing to use the formula in the follow-up after finishing this study (> 90 %).
In this first real-world-evidence study on HMO providing unique data on mixed-fed infants, infants exclusively or mixed-fed with formula supplemented with the two HMO 2’FL and LNnT had:
Age-appropriate growth in line with WHO standards and no significant difference observed between groups.
Good digestive tolerance as indicated by low IGSQ scores and compared to BF reference.
Low incidence of adverse events (AEs) / illnesses and comparable to BF reference.
High formula acceptance and parents were satisfied with the