Childcare stress level detection method

Abstract

To provide a method of detecting the childcare stress level of a mother of an infant(s) using a biomarker.SOLUTION: A method of detecting the childcare stress level of a mother of an infant(s) is provided, the method comprising (A) measuring the level of oxytocin in a biological sample collected from the mother of the infant(s), and (B) comparing the level of oxytocin with a reference value to detect the childcare stress level of the mother.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for detecting child-rearing stress level using a biomarker. [Background technology]

[0002] In recent years, due to factors such as the trend toward nuclear families and weakening relationships with neighbors, caregivers are in an environment where child-rearing stress can easily accumulate. Because excessive child-rearing stress poses a high risk of leading to abuse or neglect, it is necessary to identify objective indicators (markers) of child-rearing stress levels and develop care based on these indicators. However, markers of child-rearing stress levels have yet to be identified.

[0003] Cortisol and oxytocin have been found to date as biomarkers of stress (Non-Patent Document 1, Patent Document 1). However, there is no correlation between the childcare stress level and the occupational stress level of working women with infants (Non-Patent Document 2), suggesting that different stressors lead to different biomarkers. It is also known that oxytocin behaves differently depending on the stressor and the subject, and it has been reported that oxytocin decreases with the physical and mental stress of the occupation of nurses (Patent Document 1), but increases with social stress and stress related to studies in students (Non-Patent Document 3, Non-Patent Document 4). Therefore, it is necessary to clarify the behavior of biomarkers for each stressor and subject.

[0004] Under the Child Welfare Act, a child under the age of one is considered an infant, and a child over the age of one is considered a toddler, and it has been reported that the childcare stressors differ between mothers of infants and mothers of toddlers, with mothers of infants (4 months old) reporting "lack of emotional support" and "lack of childcare help," while mothers of toddlers (1 year and 6 months old) reporting "creating a place for themselves" (Non-Patent Document 5). In this way, the factors of childcare stress differ between mothers with infants and mothers with toddlers. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent Publication No. 2022-20136 [Non-patent literature]

[0006] [Non-Patent Document 1] Nomura et al., Biofeedback Research, 36, 1, 23-32, 2009 [Non-Patent Document 2] Hiraoka et al., Pediatric Health Research, 63, 6, 647-652, 2004 [Non-Patent Document 3] Jong et al., Psychoneuroendocrinology, 62, 381-388, 2015 [Non-Patent Document 4] Kuchenbecker et al., Stress, 24, 4, 370-383, 2021 [Non-Patent Document 5] Teshima, Haraguchi, Bulletin of the Faculty of Nursing, Fukuoka Prefectural University 1, 15-27, 2003 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention relates to a method for detecting the degree of parenting stress in mothers of infants using biomarkers. [Means for solving the problem]

[0008] The inventors analyzed the relationship between parenting stress and the amounts of oxytocin and cortisol in mothers' saliva and found that there was a significant negative correlation between the amount of oxytocin in the saliva of mothers with infants under one year old and the parenting stress scale score, indicating that it is possible to detect the level of parenting stress in mothers of infants using oxytocin as an indicator.

[0009] That is, the present invention relates to the following 1) to 3). 1) A method for detecting a level of parenting stress in a mother of an infant, comprising the following steps (A) and (B): (A) measuring the amount of oxytocin in a biological sample collected from the mother of the infant; (B) A process of comparing the amount of oxytocin with a reference value and detecting the mother's level of parenting stress. 2) A kit for detecting the degree of parenting stress in the mother of an infant, used in the method of 1), which contains tools and reagents necessary for collecting and storing biological samples, as well as a reagent for measuring the amount of oxytocin. 3) A system for detecting the level of parenting stress in an infant's mother, comprising an input means for inputting information on the amount of oxytocin in a biological sample taken from the infant's mother, a detection means for comparing the information on the amount of oxytocin input by the input means with a reference value and detecting the mother's level of parenting stress, and a detection result output means for outputting the results detected by the detection means. Effect of the Invention

[0010] According to the method of the present invention, it is possible to detect the level of parenting stress in mothers with infants without placing a burden on the subject, enabling early detection of stressful parent-child relationships and early intervention to reduce stress. [Brief description of the drawings]

[0011] [Figure 1] Association analysis between the total score of the mother's parenting stress index (parental aspect) and oxytocin and cortisol. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] In the present invention, the child-rearing stress of a mother of an infant means a state in which a mother of an infant is stressed in relation to child-rearing. Note that an infant refers to a child between 0 days after birth and less than 1 year of age. The state of parenting stress can be scored based on interviews and questionnaires. For example, the PSI Parenting Stress Index (General Incorporated Association Employment Problems Research Association) is considered to be one of the most effective tools for measuring parenting stress (Nara et al., Child Health Research, 610, 610-616, 1999). The PSI Parenting Stress Index calculates a total score for stress related to the "parents themselves" (parental aspects) and scores for each of the seven subscales (P1: restrictions caused by the parent role, P2: social isolation, P3: relationship with husband, P4: parental competence, P5: depression / guilt, P6: depression after discharge from hospital, P7: difficulty feeling attached to child, P8: health status), as well as a total score for stress related to the "child's characteristics" (child aspects) and scores for each of the seven subscales (C1: few responses that please the parents, C2: child's bad mood, C3: child does not meet expectations, C4: child is easily distracted / hyperactive, C5: parent is stalking / difficult to get used to people, C6: child has problems, C7: child is sensitive to stimuli / difficult to get used to things). Generally, the level of parenting stress is evaluated based on the PSI percentile table (Noriuchi et al., Sci. Rep., 9, 1658, 2019). The 20th percentile value of the total score for the parent dimension is 90, the 50th percentile value is 105, and the 80th percentile value is 121. The 20th percentile value of the total score for the child dimension is 74, the 50th percentile value is 86, and the 80th percentile value is 98. In the present invention, "high parenting stress state" refers to a state in which the parenting stress scale score (total score of parental aspects) is 121 points or more and 150 points or less, "high parenting stress state" refers to a state in which the parenting stress scale score (total score of parental aspects) is 105 points or more and less than 121 points, "low parenting stress state" refers to a state in which the parenting stress scale score (total score of parental aspects) is 90 points or more and less than 105 points, and "very low parenting stress state" refers to a state in which the score is 40 points or more and less than 90 points.

[0013] In the present invention, "detection" of parenting stress level means clarifying the presence or absence of a parenting stress state, or clarifying the degree of a parenting stress state, and can be expressed in other words as examination, measurement, judgment, evaluation support, etc. The terms "detection," "examination," "measurement," "judgment," or "evaluation" of parenting stress level in this specification do not include a diagnosis of a stress-related disease by a doctor.

[0014] As shown in the examples below, the child-rearing stress state of mothers of 3-11 month old children (infants) was significantly negatively correlated with the amount of oxytocin in the saliva of the mothers, while the child-rearing stress state of mothers of 12-24 month old children (toddlers) was not correlated with the amount of oxytocin. In addition, in the child-rearing stress state of mothers of infants, it was found that the stress caused by restrictions due to parental roles, social isolation, relationships with husbands, and the health condition of parents correlated well with the amount of oxytocin. These results indicate that, based on the amount of oxytocin in biological samples taken from the infant's mother, it is possible to detect the mother's level of parenting stress, in particular the level of stress caused by factors selected from the restrictions imposed by her role as a parent (stress due to being controlled and dominated by the child's demands and needs, and having one's own freedom restricted), social isolation (stress due to a lack of useful social support to fulfill the role of a parent), relationship with her husband (lack of emotional (empathy, encouragement, etc.) and behavioral (housework, etc.) support from her husband, stress due to single-parent parenting, etc.), and the health of the parents. Specifically, the method of the present invention for detecting a child-rearing stress level of a mother of an infant is carried out by the following steps (A) and (B). (A) measuring the amount of oxytocin in a biological sample collected from the mother of the infant; (B) A process of comparing the amount of oxytocin with a reference value and detecting the mother's level of parenting stress.

[0015] Specific examples of the biological sample collected from the mother in step (A) include blood (including plasma, serum, and blood cells (red blood cells and white blood cells)), urine, saliva, and lymphatic fluid, and preferably saliva. Examples of the fluid include blood (including plasma, serum, and blood cells), and urine, and more preferably saliva.

[0016] The method of collecting the biological sample is not particularly limited, but saliva can be collected by the spitting method, the cotton swab method, etc. For example, after rinsing the oral cavity with water, the whole saliva is spit into a specified container. After collection, the saliva is preferably immediately frozen and stored on dry ice, etc.

[0017] Oxytocin, which is measured in step (B), is a peptide hormone consisting of nine amino acid residues. Oxytocin is known to be synthesized in magnocellular neurons present in the paraventricular nucleus and supraoptic nucleus of the hypothalamus in the cerebral cortex, and released into the bloodstream from the posterior pituitary gland. The amount of oxytocin can be measured by liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), liquid chromatography tandem mass spectrometry (LC-MS / MS), gas chromatography mass spectrometry (GC-MS), or immunological methods such as enzyme-linked immunosorbent assay (ELISA), etc. The measurement conditions for these are known, and oxytocin can be easily quantified according to conventional methods. The ELISA method can be carried out, for example, using an Oxytocin ELISA kit (Enzo).

[0018] In step (B), the degree of parenting stress can be detected by comparing the amount of oxytocin with a reference value. The standard value can be determined, for example, based on statistical values ​​(e.g., average values) of oxytocin levels measured in a group of mothers with infants, one with low parenting stress (low stress group) and one with high parenting stress (high stress group).In this case, the parenting stress state can be evaluated using the parenting stress scale score (total score of parental aspects) using the aforementioned PSI parenting stress index. Comparison with a reference value can detect that the subject's level of parenting stress is high, for example, if the amount of oxytocin in a biological sample from the mother of the subject infant is lower than the amount of oxytocin from the low stress group, or is the same as or lower than the amount of oxytocin from the high stress group.

[0019] In another embodiment, for example, the parenting stress level and the amount of oxytocin are measured in a large population (a group of mothers with infants), and at least one reference value (cutoff value) is determined by statistical processing, and the parenting stress level can be evaluated by a value lower than the reference value. For example, if the amount of oxytocin in a subject is statistically significantly lower than the reference value, the subject can be detected as being in a parenting stress state, and if not, the subject can be detected as not being in a parenting stress state. Also, for example, if the amount of oxytocin in a subject is preferably 90% or less, more preferably 75% or less, and even more preferably 50% or less of the reference value, the subject can be detected as being in a parenting stress state, and if not, the subject can be detected as not being in a parenting stress state.

[0020] Furthermore, for example, appropriate evaluation criteria can be created that relate indicators for determining the degree of child-rearing stress to the amount of oxytocin, and the subject's child-rearing stress level can be detected from the subject's amount of oxytocin based on the criteria.

[0021] The kit for detecting the child-rearing stress level of an infant's mother is a kit for detecting the child-rearing stress level of a subject according to the method for detecting the child-rearing stress level of an infant's mother according to the present invention. The kit of the present invention contains tools and reagents necessary for collecting and preserving a biological sample, such as saliva, and a reagent for measuring the amount of oxytocin. For example, tools and reagents necessary for collecting and storing saliva include an instrument for collecting saliva, a reagent for storing the collected saliva, a container for storing the saliva, and the like. Reagents for measuring the amount of oxytocin include, for example, reagents for extracting and purifying oxytocin from collected biological samples, reagents for immunological measurements including antibodies that recognize oxytocin, as well as labeling reagents, buffer solutions, color-developing substrates, secondary antibodies, blocking agents, control reagents used as positive and negative controls, equipment necessary for testing, and indicators or guidance for detecting oxytocin.

[0022] The above-mentioned method of detecting a child-rearing stress level of a mother of an infant of the present invention can be executed by, for example, a system (a system for detecting a child-rearing stress level of a mother of an infant) including the following means. An input means for inputting information on the amount of oxytocin in a biological sample taken from the infant's mother, a detection means for comparing the information on the amount of oxytocin inputted by the input means with a reference value and detecting the mother's level of parenting stress, and a detection result output means for outputting the results detected by the detection means.

[0023] Such a system is physically executed by a computer system (e.g., a workstation, a personal computer, a smartphone) equipped with a central processing unit (CPU), a storage device, an input device, a display device, etc. The system may be constructed on a terminal of the mother of the infant who is the subject, or may be constructed on a terminal of an information analysis facility so that the output results are displayed on the subject's terminal via a network (e.g., a telecommunications network such as the Internet). For example, information on the amount of oxytocin in a biological sample from the mother of the infant subject, obtained by an information analysis institution, is input into the institution's computer system, and the mother's stress level is detected using a parenting stress level detection means, and the result is then output and displayed on the subject's terminal. In response to the detected stress level, the robot provides information necessary for stress reduction, such as skin care actions that evoke positive emotions, such as increasing the mother's oxytocin level (Patent 7103887), using rich cosmetics (Patent Application 2018-172697), touching a tactile object (sheet, fabric or processed fabric, hair, etc.) with the palm of the hand (Patent 6694096, Patent Application 2020-87376), skin contact (Cong et al., Early Hum. Dev., 91, 401-406, 2015), receiving a massage (Li et al., Psychoneuroendocrinology, 101, 193-203, 2019), smelling essential oils (Tarumi et al., J. Altern. Complement Med. 26, 226-230, 2020), listening to slow-tempo music (Ooishi et al., PLoS One, 12, e0189075, 2017), or making eye contact with a pet (Nagasawa et al., Science, 348, 333-6, 2015). EXAMPLES

[0024] The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples. Example 1 1. Method 1-1. Study participants The subjects of the analysis were 97 mothers of children aged 3-24 months living in the Tokyo metropolitan area.

[0025] 1-2. Childcare Stress Index Mothers' childcare stress was evaluated using the PSI Childcare Stress Index (General Incorporated Association, Employment Problems Research Association). This scale is one of the most effective tools for measuring parental childcare stress (Non-Patent Document 5). The total score of stress related to the "parents themselves" (parental aspects) and the scores of each of the seven subscales (P1: restrictions caused by the parent role, P2: social isolation, P3: relationship with husband, P4: competence as a parent, P5: depression / guilt, P6: depression after discharge from hospital, P7: difficulty feeling attached to the child, P8: health condition), as well as the total score of stress related to the "child's characteristics" (child's aspects) and the scores of each of the seven subscales (C1: few reactions that please the parent, C2: child's bad mood, C3: child does not meet expectations, C4: child is easily distracted / hyperactive, C5: follows parent / difficult to get used to people, C6: child has problems, C7: sensitive to stimuli / difficult to get used to things) were calculated.

[0026] 1-3. Saliva collection Saliva collection was conducted between 3 and 8 p.m. After rinsing the mouth with water, saliva was collected from the mothers by spitting out whole saliva into a centrifuge tube for 10 minutes. One hour prior to saliva collection, breastfeeding, eating and drinking other than water (hot water), and brushing teeth were prohibited. The collected saliva was frozen and stored at -20°C.

[0027] 1-4. Measurement of oxytocin and cortisol in saliva The supernatant (0.5-3.0 ml) of the whole saliva was collected after centrifugation. For the measurement of oxytocin, the supernatant was mixed with an equal volume of 0.1% (v / v) trifluoroacetic acid (TFA) and centrifuged again (3,000 rpm, 30 min). The supernatant was subjected to extraction on a Sep-pak C18 column (200 mg, 3 cc, Waters). First, 1.0 ml of 100% acetonitrile (ACN) was passed through the C18 column, followed by 10 ml of 0.1% TFA solution (v / v), then the saliva sample (1.0-6.0 ml) mixed with 0.1% TFA solution (v / v) was passed through, washed with 10 ml of 0.1% TFA solution (v / v), and then eluted with 3.0 ml of (95% ACN / 5% (0.1% TFA solution)) (v / v). The ACN in the eluted solution was evaporated with nitrogen gas, and the remaining solution was freeze-dried, and the freeze-dried product was dissolved in 250 μl of Assay Buffer in the Oxytocin ELISA kit (Enzo) and quantified using the kit. The protein concentration (mg / ml) in saliva before extraction was quantified based on a calibration curve made with bovine serum albumin using Bio-Rad Protein Assay (BIO-RAD), and the amount of oxytocin per unit protein was calculated. Cortisol was quantified using the supernatant after centrifugation of whole saliva using the Cortisol EIA Kit, Expanded Range, High Sensitivity, Salivary (Salimetrics).

[0028] 2.Results 2-1. Analysis of the relationship between the total score of the mother's parenting stress index (parental aspect) and oxytocin and cortisol (Figure 1) Analysis of the relationship between the total score of the Parenting Stress Index (parental aspects) and the amount of oxytocin in saliva revealed a significant negative correlation in mothers of infants (3-11 months old) (r=-0.45, p<0.05), but no significant correlation was found in mothers of toddlers (12-24 months old) (r=0.14, p=0.47). Additionally, no significant correlation was found between the total score of the parenting stress index (child aspect) and the amount of oxytocin in saliva, regardless of whether the mother was an infant or toddler (mothers of infants (3-11 months old): r = -0.1, p = 0.71; mothers of toddlers (12-24 months old): r = 0.13, p = 0.30).

[0029] Furthermore, when the correlation between the total score of the parenting stress index (parental aspect) and salivary cortisol concentration was analyzed, no significant correlation was found, regardless of whether the mother was an infant or a toddler (mothers of infants (3-11 months old): r=0.14, p=0.47, mothers of toddlers (12-24 months old): r=0.08, p=0.46). This demonstrated that oxytocin is a biomarker of parenting stress in the mothers of infants themselves.

[0030] 2-2. Analysis of the relationship between each score of the subscale of the maternal parenting stress index (parental aspect) and oxytocin and cortisol We analyzed the correlation between each score of the subscale of the Parenting Stress Index (parental aspect) and the amount of oxytocin and cortisol in the mother's saliva. The results are shown in Table 1. In mothers of infants (3-11 months old), there was a significant negative correlation between the scores of P1 (regulation caused by parental role), P2 (social isolation), P3 (relationship with husband), and P8 (parental health status) and the salivary oxytocin level. However, no significant correlation was found for cortisol in any of the subscale scores. Furthermore, in mothers of toddlers (12-24 months old), there was no significant correlation between the scores of any of the subscales and the salivary oxytocin level or cortisol concentration.

[0031] These findings indicate that oxytocin is a biomarker of parenting stress in infant mothers, including parent-related stress in terms of P1 (regulation caused by parental role), P2 (social isolation), P3 (relationship with husband), and P8 (parental health).

[0032] [Table 1]

Claims

1. A method for detecting a child-rearing stress level of a mother of an infant, comprising the following steps (A) and (B): (A) measuring the amount of oxytocin in a biological sample collected from the mother of the infant; (B) A step of comparing the amount of oxytocin with a reference value and detecting the mother's level of child-rearing stress.

2. 2. The method according to claim 1, wherein the parenting stress is stress resulting from factors selected from the group consisting of restrictions imposed by parental roles, social isolation, relationships with husbands, and the health status of parents.

3. 3. The method according to claim 1 or 2, wherein the biological sample is saliva.

4. A kit for detecting the degree of parenting stress in the mother of an infant, which is used in the method of claim 1, comprising tools and reagents necessary for collecting and storing biological samples, and a reagent for measuring the amount of oxytocin.

5. A system for detecting the level of parenting stress in an infant's mother, comprising: an input means for inputting information on the amount of oxytocin in a biological sample collected from the infant's mother; a detection means for comparing the information on the amount of oxytocin input by the input means with a reference value and detecting the mother's level of parenting stress; and a detection result output means for outputting the results detected by the detection means.

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