Children with functional gastrointestinal disorders with and without co-existing nausea: A comparison of clinical and psychological characteristics.

BACKGROUND: Nausea co-existing with functional gastrointestinal disorders (FGIDs) has been suggested to negatively impact physical and psychological factors in children. This study aims to compare clinical and psychological characteristics of a large cohort of pediatric patients with an FGID with and without nausea. METHODS: Patients of two previous randomized controlled trials were included, the first assessing the effect of hypnotherapy (HT) in 260 children fulfilling Rome criteria of irritable bowel syndrome (IBS) or functional abdominal pain (FAP), the second examining the effect of HT in 100 children with nausea in children with either functional nausea (FN) or functional dyspepsia (FD). At inclusion, demographics, clinical features, including the presence of nausea, depression and anxiety, somatization, and health-related quality of life (QoL) were assessed in patients. KEY RESULTS: In total, 355 patients with IBS (n = 131), FAP (n = 127), FN (n = 62), and FD (n = 35) were included, of which 255 (72%) patients experienced nausea versus 100 (28%) without nausea. Age at onset of symptoms was higher in children experiencing nausea (12.0y vs. 9.0y, p = 0.000). Significantly higher somatization, anxiety and depression scores, and lower health-related QoL were reported for children with nausea. There were no significant differences between children with only nausea and children with nausea and abdominal pain. CONCLUSIONS AND INFERENCES: Children with nausea, either with or without abdominal pain, report higher somatization scores, increased anxiety and depression, and lower overall QoL, compared to children with pain-related FGIDs without accompanying nausea. Addressing the presence of nausea in children with FGIDs seems essential to customize their treatment and improve overall quality of life.

Skills or Pills: Randomized Trial Comparing Hypnotherapy to Medical Treatment in Children With Functional Nausea.

BACKGROUND & AIMS: The potential effectiveness of gut-directed hypnotherapy (HT) is unknown for pediatric chronic nausea. This randomized controlled trial compared HT with standard medical treatment (SMT). METHODS: One hundred children (ages, 8-18 y) with chronic nausea and fulfilling functional nausea (FN) or functional dyspepsia (FD) criteria were allocated randomly (1:1) to HT or SMT, with a 3-month intervention period. Outcomes were assessed at baseline, at the halfway point, after treatment, and at the 6- and 12-month follow-up evaluation. Children scored nausea symptoms in a 7-day diary. The primary outcome was treatment success, defined as a reduction in nausea of 50% or more, at the 12-month follow-up evaluation. Secondary outcomes included adequate relief of nausea. RESULTS: After treatment and at the 6-month follow-up evaluation, there was a trend toward higher treatment success in the HT group compared with the SMT group (45% vs 26%, P = .052; and 57% vs 40%, P = .099, respectively). At 12 months, treatment success was similar in both groups (60% in the HT group and 55% in the SMT group; P = .667). In the FN group, significantly higher success rates were found for HT, but no differences were found in patients with FD. Adequate relief was significantly higher in the HT group than in the SMT group at the 6-month follow-up evaluation (children: 81% vs 55%, P = .014; parents: 79% vs 53%; P = .016), but not at the 12-month follow-up evaluation. CONCLUSIONS: HT and SMT were effective in reducing nausea symptoms in children with FN and FD. In children with FN, HT was more effective than SMT during and after the first 6 months of treatment. Therefore, HT and SMT, applied separately or in combination, should be offered to children with FN as a treatment option (Clinical trials registration number: NTR5814).

The risk and protective factors of heightened prenatal anxiety and depression during the COVID-19 lockdown.

While pregnant women are already at-risk for developing symptoms of anxiety and depression, this is heightened during the COVID-19 pandemic. We compared anxiety and depression symptoms, as indicators of psychological distress, before and during COVID-19, and investigated the role of partner, social network and healthcare support on COVID-19-related worries and consequently on psychological distress. A national survey, conducted during the first lockdown in The Netherlands, assessed COVID-19 experiences and psychological distress (N = 1421), whereas a comparison sample (N = 1439) was screened for psychological distress in 2017-2018. During COVID-19, the percentage of mothers scoring above the questionnaires' clinical cut-offs doubled for depression (6% and 12%) and anxiety (24% and 52%). Women reported increased partner support during COVID-19, compared to pre-pandemic, but decreased social and healthcare support. Higher support resulted in lower COVID-19-related worries, which in turn contributed to less psychological distress. Results suggest that a global pandemic exerts a heavy toll on pregnant women's mental health. Psychological distress was substantially higher during the pandemic than the pre-pandemic years. We identified a protective role of partner, social, and healthcare support, with important implications for the current and future crisis management. Whether increased psychological distress is transient or persistent, and whether and how it affects the future generation remains to be determined.

Probiotics as a treatment for prenatal maternal anxiety and depression: a double-blind randomized pilot trial.

Probiotic use may be an efficacious treatment option to effectively manage symptoms of prenatal maternal anxiety and depression. Our primary aim was to test feasibility and acceptability for a probiotic randomized controlled trial (RCT) in pregnant women with pre-existing symptoms. This double-blind pilot RCT included 40 pregnant women with low-risk pregnancies and elevated depressive symptoms and/or anxiety. Once daily, participants orally consumed a probiotic (Ecologic Barrier) or a placebo, from 26 to 30 weeks gestation until delivery. A priori key progression criteria for primary outcomes were determined to decide whether or not a full RCT was feasible and acceptable. Secondary outcomes included depressive symptoms, anxiety, stress, and maternal bonding to offspring. In 19 months, 1573 women were screened; following screening, 155 women (10%) were invited for participation, of whom 135 (87%) received study information, and 40 women (30%) were included. Four out of six a priori determined criteria for success on feasibility and acceptability were met. After 8 weeks of intervention, there was no significant difference between the probiotic and placebo groups for secondary outcomes. The pilot trial was feasible and acceptable, but hampered by recruitment method and study design. Secondary endpoints did not reveal differences between the groups for improving maternal mood.

Prenatal Anxiety and Depression: Treatment Uptake, Barriers, and Facilitators in Midwifery Care.

Background: While many women experience prenatal symptoms of anxiety and/or depression (PSAD), treatment uptake rates are relatively low. Left untreated, symptoms can unfavorably affect maternal and infant health. The first aim of this study was to identify the treatment uptake rate and modalities of treatment received in a community sample of Dutch pregnant women. The second aim was to investigate reasons for not engaging in treatment and to describe facilitators for treatment uptake. The third aim was to determine facilitators and barriers for self-disclosure of feelings to midwives. Materials and Methods: Data were collected from a convenience sample of 1439 Dutch women with low-risk mid-term pregnancies in midwifery care. PSAD was assessed with online questionnaires on symptoms. Reasons, facilitators, and barriers were determined with checklists and open questions. Data were analyzed using conventional content analysis and open code quantification. Results: Only 15% of women with PSAD (scoring above cutoffs; 22% of the full sample) received treatment. Psychotherapy was the most commonly received treatment. The main reason for not engaging in treatment was regarding PSAD as a natural part of pregnancy (71%). The main facilitator to engage in treatment was referral by midwives (16%), and for self-disclosure was the midwife asking about PSAD (59%), whereas not asking formed the main barrier for self-disclosure (23%). Conclusions: Relatively few pregnant women received treatment for PSAD. Midwives play an essential role in identifying and referring women for treatment. Routine screening may be a starting point to offer support and, if needed, referral.

Human milk cortisol and immune factors over the first three postnatal months: Relations to maternal psychosocial distress.

BACKGROUND: Many biologically active factors are present in human milk including proteins, lipids, immune factors, and hormones. The milk composition varies over time and shows large inter-individual variability. This study examined variations of human milk immune factors and cortisol concentrations in the first three months post-partum, and their potential associations with maternal psychosocial distress. METHODS: Seventy-seven healthy mothers with full term pregnancies were enrolled, of which 51 mothers collected morning milk samples at 2, 6 and 12 weeks post-delivery. Maternal psychosocial distress was assessed at 6 weeks post-delivery using questionnaires for stress, anxiety, and depressive symptoms. Immune factors were determined using multiplex immunoassays and included innate immunity factors (IL1ß, IL6, IL12, IFNγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1ß), growth factors (IL5, IL7, GCSF, GMCSF, TGFß2) and immunoglobulins (IgA, total IgG, IgM). Cortisol was quantified using liquid chromatography-tandem mass spectrometry. A linear mixed effects model was fit to test whether stress, anxiety, and depressive symptoms individually predicted human milk cortisol concentrations after accounting for covariates. Repeated measurement analyses were used to compare women with high (n = 13) versus low psychosocial distress (n = 13) for immune factors and cortisol concentrations. RESULTS: Virtually all immune factors and cortisol, with the exception of the granulocyte-macrophage colony-stimulating factor (GMCSF), were detected in the human milk samples. The concentrations of the immune factors decreased during the first 3 months, while cortisol concentrations increased over time. No correlation was observed between any of the immune factors and cortisol. No consistent relationship between postnatal psychosocial distress and concentrations of immune factors was found, whereas higher psychosocial distress was predictive of higher cortisol concentrations in human milk. CONCLUSION: In the current study we found no evidence for an association between natural variations in maternal distress and immune factor concentrations in milk. It is uncertain if this lack of association would also be observed in studies with larger populations, with less uniform demographic characteristics, or with women with higher (clinical) levels of anxiety, stress and/or depressive symptoms. In contrast, maternal psychosocial distress was positively related to higher milk cortisol concentrations at week 2 post-delivery. Further investigation on maternal psychosocial distress in relation to human milk composition is warranted.

Human Milk Microbiome and Maternal Postnatal Psychosocial Distress.

Human milk contains many bioactive components, including bacteria, which are transferred to the developing infant through breastfeeding. Milk bacteria appear to, amongst others, originate from the maternal gut. A mother's postnatal psychosocial distress may alter maternal gut microbiota, which in turn may affect the bacteria present in milk. The aim of this study was to explore whether maternal postnatal psychosocial distress was related to alterations in the relative abundances of specific bacteria and to milk microbial diversity. Healthy mothers (N = 77; N = 51 with complete data) collected breast milk samples at 2, 6, and 12 weeks postpartum and filled in mood questionnaires on experienced stress, anxiety, and depressive symptoms at 6 weeks postpartum. A metataxonomic approach (16S rRNA gene sequencing (region V3 and V4) using Illumina MiSeq technology) was used to assess bacterial abundances and diversity. For the group as a whole, an increase in diversity of the milk bacterial community was observed during the first 3 months of breastfeeding (Shannon index). This general increase in diversity appears to be explained by an increase of Lactobacillus and other minor genera, together with a decrease in Staphylococcus. With respect to psychological distress and milk microbial composition, no significant differences in the relative abundance of major bacterial genera were detected between women with high (N = 13) and low (N = 13) psychosocial distress. However, progressive and distinct changes in the content of Firmicutes, Proteobacteria, and Bacteroidetes at the phylum level and Acinetobacter, Flavobacterium, and Lactobacillus at the genera level were observed in milk samples of women with low psychosocial distress. With respect to milk microbial diversity, high maternal psychosocial distress, compared to low maternal psychosocial distress, was related to significantly lower bacterial diversity in milk at 3 months post-delivery. Anxiety, stress, and depressive symptoms separately were unrelated to specific bacterial profiles. The current study suggests a potential relation between maternal psychosocial distress and milk microbiota, providing first evidence of a possible mechanism through which post-partum psychological symptoms may affect infant development and health.

Probiotics in pregnancy: protocol of a double-blind randomized controlled pilot trial for pregnant women with depression and anxiety (PIP pilot trial).

BACKGROUND: Maternal prenatal depressive or anxiety symptoms are associated with adverse maternal and infant health outcomes. With prevalence rates of maternal prenatal depression and anxiety ranging between 10 and 20%, attempts to identify effective interventions to reduce symptoms are priority. There are indications that probiotics can reduce symptoms of maternal depression or anxiety. Probiotics ingested by the mother may thus offer a promising and accessible intervention to complement existing treatments. METHODS: The Probiotics in Pregnancy (PIP) pilot trial is a double-blind, placebo-controlled, randomized pilot trial. While one group orally consumes a probiotic mixture (Ecologic® Barrier; 2,5 × 109 colony forming units/g; 2 g; daily), the other group consumes a placebo, from between 26 and 30 weeks gestation until delivery. Subjects are randomly allocated (1:1) to the intervention or placebo group. Forty healthy pregnant women with symptoms of depression or anxiety and uncomplicated pregnancies at randomization will be included. The primary aim is to determine the feasibility and acceptability of a probiotic trial to reduce symptoms of maternal depression or anxiety in pregnancy. The secondary aim is to exploratorily compare the potential effect of probiotics, compared to placebo, on depressive and/or anxiety symptoms, maternal stress (i.e. reported/hair cortisol), maternal vaginal and intestinal microbiota, and by possibly affecting maternal mood and microbiota, maternal bonding to offspring, infant microbiota and infant crying. DISCUSSION: Results of this pilot trial will help determine whether or not to proceed with a full trial after the pilot trial, and if so, whether revisions should be made to the study protocol and procedures before conducting a full randomized controlled trial. Additionally, they are expected to provide insights into whether changes in psychological, behavioral and biological parameters can be attributed to the probiotic intervention. TRIAL REGISTRATION: Netherlands Trial Register, NTR6219 . Registered on 28 February 2017.

Gut-directed hypnotherapy versus standard medical treatment for nausea in children with functional nausea or functional dyspepsia: protocol of a multicentre randomised trial.

INTRODUCTION: The treatment of chronic functional nausea or nausea due to functional dyspepsia in children is generally symptomatic. Moreover, these disorders pose a risk for worse psychosocial and health outcomes in children. Hypnotherapy (HT), by its ability to positively influence gastrointestinal and psychosocial functioning, may be an effective treatment for chronic nausea. METHODS AND ANALYSIS: To test efficacy, this multicentre, parallel, randomised controlled, open label trial evaluates whether gut-directed HT is superior to standard medical treatment (SMT) for reducing nausea. The study will be conducted at eleven academic and non-academic hospitals across the Netherlands. A total of 100 children (8-18 years), fulfilling the Rome IV criteria for chronic idiopathic nausea or functional dyspepsia with prominent nausea, will be randomly allocated (1:1) to receive HT or SMT. Children allocated to the HT group will receive six sessions of HT during 3 months, while children allocated to the SMT group will receive six sessions of SMT+supportive therapy during the same period. The primary outcome will be the difference in the proportion of children with at least 50% reduction of nausea, compared with baseline at 12 months' follow-up. Secondary outcomes include the changes in abdominal pain, dyspeptic symptoms, quality of life, anxiety, depression, school absences, parental absence of work, healthcare costs and adequate relief of symptoms, measured directly after treatment, 6 and 12 months' follow-up. If HT proves effective for reducing nausea, it may become a new treatment strategy to treat children with chronic functional nausea or functional dyspepsia with prominent nausea. ETHICS AND DISSEMINATION: Results of the study will be publicly disclosed to the public, without any restrictions, in peer-reviewed journal and international conferences. The study is approved by the Medical Research Ethics Committees United (MEC-U) in the Netherlands. TRIAL REGISTRATION NUMBER: NTR5814.

Pharmacological treatments for functional nausea and functional dyspepsia in children: a systematic review.

INTRODUCTION: Chronic idiopathic nausea (CIN) and functional dyspepsia (FD) cause considerable strain on many children's lives and their families. Areas covered: This study aims to systematically assess the evidence on efficacy and safety of pharmacological treatments for CIN or FD in children. CENTRAL, EMBASE, and Medline were searched for Randomized Controlled Trials (RCTs) investigating pharmacological treatments of CIN and FD in children (4-18 years). Cochrane risk of bias tool was used to assess methodological quality of the included articles. Expert commentary: Three RCTs (256 children with FD, 2-16 years) were included. No studies were found for CIN. All studies showed considerable risk of bias, therefore results should be interpreted with caution. Compared with baseline, successful relief of dyspeptic symptoms was found for omeprazole (53.8%), famotidine (44.4%), ranitidine (43.2%) and cimetidine (21.6%) (p = 0.024). Compared with placebo, famotidine showed benefit in global symptom improvement (OR 11.0; 95% CI 1.6-75.5; p = 0.02). Compared with baseline, mosapride versus pantoprazole reduced global symptoms (p = 0.011; p = 0.009). One study reported no occurrence of adverse events. This systematic review found no evidence to support the use of pharmacological drugs to treat CIN or FD in children. More high-quality clinical trials are needed. ABBREVIATIONS: AP-FGID: Abdominal Pain Related Functional Gastrointestinal Disorders; BART: Biofeedback-Assisted Relaxation Training; CIN: Chronic Idiopathic Nausea; COS: Core Outcomes Sets; EPS: Epigastric Pain Syndrome; ESPGHAN: European Society for Pediatric Gastroenterology Hepatology and Nutrition; FAP: Functional Abdominal Pain; FD: Functional Dyspepsia; GERD: Gastroesophageal Reflux Disease; GES: Gastric Electrical Stimulation; H2RAs: H2 Receptor Antagonists; IBS: irritable bowel syndrome; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; PDS: Postprandial Distress Syndrome; PPIs: Proton Pump Inhibitor; PROMs: Patient Reported Outcome Measures; RCTs: Randomized Controlled Trials; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants.

Infant colic: mechanisms and management.

Infant colic is a commonly reported phenomenon of excessive crying in infancy with an enigmatic and distressing character. Despite its frequent occurrence, little agreement has been reached on the definition, pathogenesis or the optimal management strategy for infant colic. This Review aims to delineate the definitional entanglement with the Rome IV criteria, which were published in 2016, as the leading, most recent diagnostic criteria. Moreover, neurogenic, gastrointestinal, microbial and psychosocial factors that might contribute to the pathophysiology of infant colic are explored. This Review underlines that a comprehensive medical history and physical examination in the absence of alarm symptoms serve as guidance for the clinician to a positive diagnosis. It also highlights that an important aspect of the management of infant colic is parental education and reassurance. Management strategies, including behavioural, dietary, pharmacological and alternative interventions, are also discussed. Owing to a lack of large, high-quality randomized controlled trials, none of these therapies are strongly recommended. Finally, the behavioural and somatic sequelae of infant colic into childhood are summarized.