Stress degree demonstrated in mothers with phenylketonuria or hyperphenylalaninemia infant when requested for total or partial breastfeeding replacement

Introduction

Phenylketonuria (PKU) is an inborn error of phenylalanine (phe) metabolism due to the deficiency of the hepatic enzyme phe hydroxylase activity. The disease is inherited with an autosomal recessive trade. PKU is characterized by high phe blood levels resulting in executive function impairment, convulsions and microcephaly caused by toxic effect of phe accumulation in the brain [1]. Early detection of PKU infants and proper treatment with phe-restricted diets has really minimized the more severe brain damage and psychiatric problems associated with PKU. The only therapeutic treatment includes restriction of natural protein intake supplemented with amino acid phe free medical food [2, 3]. Hyperphenylalaninemia (HPHE) is a mild type of phe metabolic disorder. The disease present lower phe blood levels than those measured in PKU due to the partial deficiency of the above mention enzyme [2]. According to the guidelines, phe blood levels should be maintained between 240 and 360 μmol/L throughout life in both types of the disorder [4]. PKU treatment is commonly characterize by total breastfeeding replacement whereas partial breastfeeding replacement is needed for HPHE infants. In both cases phe free formula is needed.

The Greek National Newborn Screening Program (GNNSP) follow the rules of τ the World Health Organization (WHO) [5]. The GNNSP is a public health tool for the detection and pickup newborns with inherited chronic metabolic disorders [6]. In Greece this program includes the measurement of biomarkers related to four diseases, which play a very important role in the early diagnoses and prevention of mental retardation, hemolysis etc. Diagnoses of PKU and HPHE infants are included in GNNSP. Both groups of infants are early discovered and put on diet during the first days of their life.

Stress is referred to psychological and physical pressure which are involved in many systems such as metabolism, muscles, memory and implication of adrenergetic mono amines [7]. Repeated stress factors usually are characteristics of modern life, can be harmful in physical and psychological damage. In general, stress management is recognized an effective treatment modality to include pharmacologic and or psychological support. Stress is considered as a physical, mental or emotional factors that cause bodily or mental tension. Stresses can be external from the environment, psychological or social situations or internal illness or from a medical procedure [7].

Breastfeeding is highly recommended for the bounding between mother and infant, consequently mother has a significant role for close relationship between herself and the newborn [8, 9]. It is well known that this relationship may improve the personality of the infant, as mother and neonate came closer [10]. Weaning is the process of replacing breast milk with formula. Maternal psychological support could be needed when breastfeeding is involuntary replaced by formula to provide help for her separation feeling of mother from her own infant [11].

In this study we aimed to determine maternal stress scores when they were obliged completely or partially replace breastfeeding with special medical formulas as the only treatment of PKU or HPHE infants. We underline that both types of these disorders are related to the same origin but with different outcome and duration of treatment.

Case presentation

The study was in accordance to Helsinki declaration (1980) and (1983) as revised in 2013, and approved by the local Ethics Committee. And took place from 01/02/05 to 31/12/16. The mean age of both groups of mothers was (28.1) years old. A total number of 50 newborns (25 PKU and 25 HPHE) were discovered by GNNSP (mean age 6 days old). The infants underwent a laboratory examination including quantitation of amino acids in plasma, dihydropterine reductase activity (DHPR) in dried blood spots (Guthrie cart). Newborns were divided in two groups according to the phe levels in their plasma: phe levels >15 mg/dL were characterize PKU (group a) and biopterine loading test (BH4) was performed. Were as the rest of then (group b) were HYPHE (phe<15 mg/dL). The diagnoses of both groups was confirmed with molecular analysis. Mothers with PKU newborns were informed about the disease and they were requested to stop breastfeeding by replacing it with phe free special formula and restricted natural protein with a common milk. Unhappily, the mothers were unable to calculate the exact quantity of breast milk witch was necessary for the special treatment of their newborns. Mothers of group b partially replaced breastfeeding by phe free medical food.

Especial questioner of stress evaluation was utilized: for the determination of Stress levels we used the checklist by Bourne [11] which can diagnose the different levels of physical and psychological symptoms of stress. These scale consistent 52 characteristics, out of them 27 physical and the rest 25 psychological. The scores 0–7 characterize low degree of stress, 8–14 was evaluated as having moderate degree, 15–21 indicated high degree, were as 22+ characterize severe stress. All participants were requested to check each item that describes a symptom they had experienced to any significant degree during the last month while they had been on breastfeeding replacement. Descriptive statistics were utilize for data analysis (% percentage). Additionally we used the Independent Samples Kruskal–Wallis test in order to find out the amelioration of stressed mothers after five sessions of psychological support (once per week) as well as to determine any statistical value between the groups of mothers on breastfeeding only vs. breastfeeding plus formula. p-Values >0.05 were considered statistically significant.

Results

As shown in Table 1, 3/25 (12.0%) mothers with PKU infants and 6/25 (24.0%) with HYPE newborns were free from stress symptoms and sings (p<0.0001). Additionally, low symptoms were demonstrated 4/25 (16.0%), in mothers with PKU newborns and 7/25 (28.0%), with HPHE infants (p<0.0001). No significant differences of moderate stress sings were found in both studied groups. Oppositely, very high statistically significant values were found in mothers with high and severe symptoms of stress of both groups (p<0.0001).

After psychological support, all symptoms and sings disappeared in group A 13/25 (54.0%) and 19/25 (76.0%) in group B (p<0.00001). Low stress symptoms appeared in 6/25 (24.0%) with PKU newborns and 5/25 (20.0%) with HPHE infants (p<0.01). Moderate stress symptoms were demonstrated 6/25 (24.0%) in group A and 1/25 (4.0%) in group B (p<0.0001). Non-significant p-values of high or severe stress symptoms were found in both groups.

Discussion

According to WHO, breastfeeding is commonly recommended for the first six months of newborn’s life [13]. More recently, a large cluster randomized trial of breastfeeding promotion using an experimental design demonstrated a large effect of breastfeeding on cognition, adding credence to the evidence for beneficial effects originated in past observational studies [14]. Other study, using meta-analysis showed that after appropriate adjustments, breastfeeding was associated with an advantage of around 3 points on tests of cognition in children born at term and around 5 points in those born preterm [15]. The implication is that, over and above social factors, one or more constituents of breast milk benefit neurodevelopment, particularly so in those born preterm, at a more sensitive stage of brain development. Weaning is the process of replacing breast milk with formula as mention above [12]. Here we may underline the sensitive bound between mothers and breastfeeding infants which support the relationship among them.

In a previous study [16], the majority of women with breast diseases who experienced increased psychological stress gave up breastfeeding sooner. In contrast in another group without any problems, mothers stopped breastfeeding themselves since they thought that they had not enough milk to feed their infants. Breast diseases during lactation are associated with higher levels of psychological stress. In our resent report, it was demonstrated that mothers with galasctosemic or phenylketonuric infants who were obliged to replace breastfeeding with special formulas in order to prevent psychomotor retardation or even fatal outcome in case of classical galactosemia. In both groups of mothers, breastfeeding replacement produced stress. Psychological support focused on the beneficial effect of formulas for the prevention of mental retardations and other complications coast by the mentioned disorders ameliorated their stress symptoms and sings [17]. Additionally, in the same study we found that mothers whose infant was on breastfeeding plus formula experienced a lesser degree of stress as compared to those who were on breastfeeding only.

In the present study, both mothers with PKU or HPHE infants experienced stress symptoms and sings. Here, we may underline that PKU mothers suffered from high or severe symptoms and sings as compared to HPHE mothers. This could be due to the partial breastfeeding replacement observed in HPHE mothers since the bοund between them and their infants was not completely destroyed. Consequently, stress originated from breastfeeding replacement in this group of mothers could not cause the same stress scores results as found in mothers with PKU infants. With regards to psychological support, both groups of mothers were ameliorated especially these with lesser degree of stress, Most HPHE mothers, turned to normal. This is easily explained since HPHE mothers continued on breastfeeding even if the partial replacement does not allow the total distraction of the bound between mothers and newborns.

During psychological support, we aimed to explain in details that through breastfeeding replacement with a phe free medical formula could achieve near to normal phe levels and avoid mental retardation of their infants. Furthermore, most mothers were already be informed that in difficult cases of PKU should be under strict phe control. Most information were taken from web medical pages in which the therapeutic process of PKU should be very careful not only by dietetic treatment but also by frequent phe levels measurement [18]. On the other hand HPHE mothers were partially satisfied because breastfeeding was not interrupted and they were convinced that their infants could have a normal mental development outcome. Additionally, they well informed that their infant would not be socially discriminated and or the quality of each life should not be much different as compared to those of healthy children. This is due to the kind of the dietetic control of HPHE children since most of them could stop being on diet before entering primary school [19]. In contrast, PKU children should always be under strict dietetic control lifelong in order to avoid not only distraction of quality of life but also social discrimination since both could lead the patients to depression [19, 20].

Conclusions

Mothers with PKU infants who were obliged to complete breastfeeding replacement experienced high and/or severe stress degrees as compared to mothers with HPHE newborns and partial breastfeeding replacement. This could be due to the information they had already received about the mental problems caused by the disease and the beneficial effects of the dietetic treatment. Additionally, psychological support ameliorated any remained stress problems by further explanation of the beneficial effects of the breastfeeding replacement by dietetic treatment.