Understanding the course of attention deficit hyperactivity disorder in children born after a threatened preterm labor: a 6-year cohort study.

BACKGROUND: Recent research suggests that children born after suspected preterm labor may observe a potential cluster with different attention deficit hyperactivity disorder features, depending on the time of birth. However, the evolution of symptoms and their predictors remain unknown in this population. OBJECTIVE: This study aimed to examine the trajectories of attention deficit hyperactivity disorder symptoms of children born after suspected preterm labor, between ages 2 and 6 years, considering prematurity condition and comparing with controls. In addition, this study aimed to find potential modifiable predictors of evolution to enhance prognosis. STUDY DESIGN: In this prospective cohort study, 119 mother-child pairs who experienced suspected preterm labor and 60 controls were included. Patients were divided according to prematurity condition in full term (n=27), late preterm (n=55), and very preterm (n=37). Attention deficit hyperactivity disorder symptoms were assessed at ages 2 and 6 years. The association between potential modifying factors (group, time of assessment, sex, birthweight percentile, maternal history of trauma, maternal anxiety at diagnosis, and maternal anxiety during the children's assessments) and disorder trajectories was assessed by adjusting the Bayesian mixed linear models. All analyses were performed in R (version 4.3.0; R Foundation for Statistical Computing, Vienna, Austria). RESULTS: An interaction emerged between time and group, with late-preterm neonates born after suspected preterm labor being the only group to improve from ages 2 to 6 years (-2.26 points in Conners scale per percentile decrease and 0.98 probability of effect). Another interaction between time and maternal anxiety at postnatal time assessments intensified over time (0.07 and 0.84). Predictors of symptom severity included lower weight percentile at birth (-0.2 and 0.96), male sex (-2.99 and <0.99), higher maternal anxiety at diagnosis (+0.08 and 0.99), and maternal history of trauma (+0.23 and 0.98). CONCLUSION: Unlike very-preterm and full-term children, those born late preterm showed an improvement over time, probably because late-preterm children do not carry the sequelae derived from severe prematurity but benefit from close monitoring. As maternal psychopathology emerged as a determinant modifier of course and severity, it is crucial to develop targeted psychological interventions for pregnant individuals and reevaluate monitoring programs for their offspring, regardless of prematurity.

Fact-based nutrition for infants and lactating mothers-The NUTRISHIELD study.

Background: Human milk (HM) is the ideal source of nutrients for infants. Its composition is highly variable according to the infant's needs. When not enough own mother's milk (OMM) is available, the administration of pasteurized donor human milk (DHM) is considered a suitable alternative for preterm infants. This study protocol describes the NUTRISHIELD clinical study. The main objective of this study is to compare the % weight gain/month in preterm and term infants exclusively receiving either OMM or DHM. Other secondary aims comprise the evaluation of the influence of diet, lifestyle habits, psychological stress, and pasteurization on the milk composition, and how it modulates infant's growth, health, and development. Methods and design: NUTRISHIELD is a prospective mother-infant birth cohort in the Spanish-Mediterranean area including three groups: preterm infants <32 weeks of gestation (i) exclusively receiving (i.e., >80% of total intake) OMM, and (ii) exclusively receiving DHM, and (iii) term infants exclusively receiving OMM, as well as their mothers. Biological samples and nutritional, clinical, and anthropometric characteristics are collected at six time points covering the period from birth and until six months of infant's age. The genotype, metabolome, and microbiota as well as the HM composition are characterized. Portable sensor prototypes for the analysis of HM and urine are benchmarked. Additionally, maternal psychosocial status is measured at the beginning of the study and at month six. Mother-infant postpartum bonding and parental stress are also examined. At six months, infant neurodevelopment scales are applied. Mother's concerns and attitudes to breastfeeding are registered through a specific questionnaire. Discussion: NUTRISHIELD provides an in-depth longitudinal study of the mother-infant-microbiota triad combining multiple biological matrices, newly developed analytical methods, and ad-hoc designed sensor prototypes with a wide range of clinical outcome measures. Data obtained from this study will be used to train a machine-learning algorithm for providing dietary advice to lactating mothers and will be implemented in a user-friendly platform based on a combination of user-provided information and biomarker analysis. A better understanding of the factors affecting milk's composition, together with the health implications for infants plays an important role in developing improved strategies of nutraceutical management in infant care. Clinical trial registration: https://register.clinicaltrials.gov, identifier: NCT05646940.

Joint Microbiota Activity and Dietary Assessment through Urinary Biomarkers by LC-MS/MS.

Accurate dietary assessment in nutritional research is a huge challenge, but essential. Due to the subjective nature of self-reporting methods, the development of analytical methods for food intake and microbiota biomarkers determination is needed. This work presents an ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method for the quantification and semi quantification of 20 and 201 food intake biomarkers (BFIs), respectively, as well as 7 microbiota biomarkers applied to 208 urine samples from lactating mothers (M) (N = 59). Dietary intake was assessed through a 24 h dietary recall (R24h). BFI analysis identified three distinct clusters among samples: samples from clusters 1 and 3 presented higher concentrations of most biomarkers than those from cluster 2, with dairy products and milk biomarkers being more concentrated in cluster 1, and seeds, garlic and onion in cluster 3. Significant correlations were observed between three BFIs (fruits, meat, and fish) and R24h data (r > 0.2, p-values < 0.01, Spearman correlation). Microbiota activity biomarkers were simultaneously evaluated and the subgroup patterns detected were compared to clusters from dietary assessment. These results evidence the feasibility, usefulness, and complementary nature of the determination of BFIs, R24h, and microbiota activity biomarkers in observational nutrition cohort studies.

Rescue doses of antenatal corticosteroids, children's neurodevelopment, and salivary cortisol after a threatened preterm labor: a 30-month follow-up study.

BACKGROUND: Antenatal corticosteroids reduce neonatal complications when administered to women at risk for preterm birth. Moreover, antenatal corticosteroid rescue doses are recommended for women who remain at risk after the initial course. However, there is controversy about the most appropriate frequency and the exact timing of administering additional antenatal corticosteroid doses because there are potential long-term negative effects on infants' neurodevelopment and physiological stress functioning. OBJECTIVE: This study aimed to (1) to assess the long-term neurodevelopmental effects of receiving antenatal corticosteroid rescue doses in comparison with receiving only the initial course; (2) to measure the cortisol levels of infants of mothers who received antenatal corticosteroid rescue doses; (3) to examine a potential dose-response effect of the number of antenatal corticosteroid rescue doses on children's neurodevelopment and salivary cortisol. STUDY DESIGN: This study followed 110 mother-infant pairs who underwent a spontaneous episode of threatened preterm labor until the children were 30 months old, regardless of their gestational age at birth. Among the participants, 61 received only the initial course of corticosteroids (no rescue dose group), and 49 participants required at least one rescue dose of corticosteroids (rescue doses group). The follow-up was carried out at 3 different times, namely at threatened preterm labor diagnosis (T1), when the children were 6 months of age (T2), and when the children were 30 months of corrected age for prematurity (T3). Neurodevelopment was assessed using the Ages & Stages Questionnaires, Third Edition. Saliva samples were collected for cortisol level determination. RESULTS: First, the rescue doses group showed lower problem-solving skills at 30 months of age than the no rescue doses group. Second, the rescue doses group demonstrated higher salivary cortisol levels at 30 months of age. Third, a dose-response effect was found that indicated that the more rescue doses the rescue doses group received, the lower the problem-solving skills and the higher the salivary cortisol levels at 30 months of age. CONCLUSION: Our findings reinforce the hypothesis that additional antenatal corticosteroid doses provided after the initial course may have long-term effects on the neurodevelopment and glucocorticoid metabolism of the offspring. In this regard, the results raise concerns about the negative effects of repeated doses of antenatal corticosteroids in addition to a full course. Further studies are necessary to confirm this hypothesis to help physicians reassess the standard antenatal corticosteroid treatment regimens.

Temperamental and psychomotor predictors of ADHD symptoms in children born after a threatened preterm labour: a 6-year follow-up study.

Children born after threatened preterm labour (TPL), regardless of whether it ends in preterm birth, may represent an undescribed "ADHD cluster". The aim of this cohort study is to identify early temperament and psychomotor manifestations and risk factors of TPL children who present ADHD symptoms. One hundred and seventeen mother-child pairs were followed from TPL diagnosis until the child's 6 years of life. TPL children were divided according to the prematurity status into three groups: full-term TPL (n = 26), late-preterm TPL (n = 53), and very-preterm TPL (n = 38). A non-TPL group (n = 50) served as control. Temperament and psychomotor development at age 6 months and ADHD symptoms at age 6 years were assessed. Perinatal and psychosocial factors were also recorded. All TPL groups showed higher severity of ADHD symptoms compared with non-TPL children (difference in means + 4.19 for the full-term group, + 3.64 for the late-preterm group, and + 4.99 for the very-preterm group, all ps < 0.021). Concretely, very-preterm and late-preterm TPL children showed higher restless/impulsive behaviours, whereas full-term TPL children showed higher emotional lability behaviours. Higher surgency/extraversion and delayed fine motor skills at age 6 months predicted ADHD symptoms at 6 years in TPL children. Male sex, maternal state anxiety symptoms at TPL diagnosis, low parental education, and past maternal experience of traumatic events predicted higher ADHD symptoms in TPL children. Therefore, TPL children may have a higher risk for developing ADHD symptoms, presenting a phenotype that depends on the prematurity status. Moreover, the specific combination of early manifestations and risk factors suggests that TPL children may conform an undescribed group at-risk of ADHD symptoms.

Isolation and Lipidomic Screening of Human Milk Extracellular Vesicles.

Extracellular vesicles (EVs) are secreted by cells and can be found in biological fluids (e.g., blood, saliva, urine, cerebrospinal fluid, and milk). EV isolation needs to be optimized carefully depending on the type of biofluid and tissue. Human milk (HM) is known to be a rich source of EVs, and they are thought to be partially responsible for the benefits associated with breastfeeding. Here, a workflow for the isolation and lipidomic analysis of HM-EVs is described. The procedure encompasses initial steps such as sample collection and storage, a detailed description for HM-EV isolation by multistage ultracentrifugation, metabolite extraction, and analysis by liquid chromatography coupled to mass spectrometry, as well as data analysis and curation.

Are infants born after an episode of suspected preterm labor at risk of attention deficit hyperactivity disorder? A 30-month follow-up study.

BACKGROUND: An episode of suspected preterm labor may be by itself a pathologic event that may alter the normal course of pregnancy and the offspring's neurodevelopment. Certainly, the association between preterm birth and neurodevelopmental disorders can only be partially explained by the immaturity of the nervous system, as evidenced by the increased risk of attention deficit hyperactivity disorder in late-preterm infants without any neurologic alteration. OBJECTIVE: This study aimed to examine whether infants born after suspected preterm labor may be at an increased risk of developing attention deficit hyperactivity disorder. Moreover, potential obstetrical, perinatal, and psychosocial risk factors associated with attention deficit hyperactivity disorder in this population are examined. STUDY DESIGN: A prospective cohort study of 120 mother-infant pairs was conducted from the moment the mothers received a diagnosis of suspected preterm labor until the infants' 30 months of life. Infants were divided according to the prematurity status: full-term infants born after a suspected preterm labor (n=28; born at ≥37 weeks of gestation), late-preterm infants (n=56; born between 32 and <37 weeks of gestation), very-preterm infants (n=36; born before <32 weeks of gestation). At-term infants born without obstetric complications served as a control group (n=46). Infants' attention deficit hyperactivity disorder symptoms were assessed at the age of 30 months. Furthermore, obstetrical, perinatal, and psychosocial risk factors were recorded. RESULTS: All groups of infants born after a suspected preterm labor showed more attention deficit hyperactivity disorder symptoms at the age of 30 months than the control group. Concretely, very-preterm infants showed higher restless or impulsive behaviors, whereas full-term infants born after a suspected preterm labor and late-preterm infants showed higher emotional lability behaviors. Among potential risk factors, male sex and maternal experience of posttraumatic stress symptoms predicted the severity of attention deficit hyperactivity disorder symptoms in infants born after a suspected preterm labor. CONCLUSION: Infants born after a suspected preterm labor had a higher risk of developing attention deficit hyperactivity disorder symptoms, including those born at term. Infants born after a suspected preterm labor showed a distinctive phenotype and shared specific risk factors suggesting that they conform an undescribed population at risk of attention deficit hyperactivity disorder.

GC-MS analysis of short chain fatty acids and branched chain amino acids in urine and faeces samples from newborns and lactating mothers.

BACKGROUND: Short chain fatty acids (SCFAs) and branched chain amino acids (BCAAs) are frequently determined in faeces, and widely used as biomarkers of gut-microbiota activity. However, collection of faeces samples from neonates is not straightforward, and to date levels of these metabolites in newborn's faeces and urine samples have not been described. METHODS: A targeted gas chromatography - mass spectrometry (GC-MS) method for the determination of SCFAs and BCAAs in both faeces and urine samples has been validated. The analysis of 210 urine and 137 faeces samples collected from preterm (PI), term infants (TI) and their mothers was used to report faecal and urinary SCFA and BCAA levels in adult and neonatal populations. RESULTS: A significant correlation among five SCFAs and BCAAs in faeces and urine samples was observed. Reference ranges of SCFAs and BCAAs in mothers, PI and TI were reported showing infant's lower concentrations in faeces and higher concentrations in urine. CONCLUSION: This method presents a non-invasive approach for the simultaneous assessment of SCFAs and BCAAs in faecal and urine samples and the results will serve as a knowledge base for future experiments that will focus on the study of the impact of nutrition on the microbiome of lactating mothers and their infants.

Emotional regulation and psychomotor development after threatening preterm labor: a prospective study.

A threatened preterm labor (TPL) represents an adverse prenatal event that may affect fetal neurodevelopment, even in absence of prematurity. Indeed, late-preterm infants, without neurological complications, also exhibit neurodevelopment impairment with psychomotor delay as well as emotional regulation disturbances, considered early manifestations of neuropsychiatric disorders. The aim of this study is to examine the impact of TPL on infant's psychomotor development and temperament. This prospective cohort study recruited mothers who suffered from a TPL and a control group of mothers without TPL and full-term gestation (n = 61). TPL infants were classified into three groups depending on delivery time: Full-Term (n = 37), Late-Preterm (n = 66), and Very-Preterm (n = 38). Neurodevelopmental assessment was performed at 6 months using the Ages & Stages Questionnaires for psychomotor development and the Infant Behaviour Questionnaire-Revised for temperament. After controlling for potential cofounders (multiple pregnancy and in vitro fertilization), Full-Term TPL infants, relative to the control group, exhibited development delay in Communication (p = 0.044) and Personal-social domains (p = 0.005) as well as temperament disturbances with higher Negative Affect (p = 0.013), lower Positive Affect (p = 0.010), and worse Emotional Regulation (p < 0.001) compared to Control. No differences were found between Full-Term and Late-Preterm TPL infants. TPL may represent a risk factor for neurodevelopmental disturbances in the offspring, affecting both psychomotor and emotional infant competences, even when infants were born at term.

Cumulative life stressors and stress response to threatened preterm labour as birth date predictors.

PURPOSE: Preterm birth represents one of the main causes of neonatal morbimortality and a risk factor for neurodevelopmental disorders. Appropriate predictive methods for preterm birth outcome, which consequently would facilitate prevention programs, are needed. We aim to predict birth date in women with a threatened preterm labour (TPL) based on stress response to TPL diagnosis, cumulative life stressors, and relevant obstetric variables. METHODS: A prospective cohort of 157 pregnant women with TPL diagnosis between 24 and 31 weeks gestation formed the study sample. To estimate the stress response to TPL, maternal salivary cortisol, α-amylase levels, along with anxiety and depression symptoms were measured. To determine cumulative life stressors, previous traumas, social support, and family functioning were registered. Then, linear regression models were used to examine the effect of potential predictors of birth date. RESULTS: Lower family adaptation, higher Body Mass Index (BMI), higher cortisol levels and TPL diagnosis week were the main predictors of birth date. Gestational week at TPL diagnosis showed a non-linear interaction with cortisol levels: TPL women with middle- and high-cortisol levels before 29 weeks of gestation went into imminent labour. CONCLUSION: A combination of stress response to TPL diagnosis (salivary cortisol) and cumulative life stressors (family adaptation) together with obstetric factors (TPL gestational week and BMI) was the best birth date predictor. Therefore, a psychosocial therapeutic intervention program aimed to increase family adaptation and decrease cortisol levels at TPL diagnosis as well as losing weight, may prevent preterm birth in symptomatic women.

Impact of maternal age on infants' emotional regulation and psychomotor development.

BACKGROUND: Maternal age has progressively increased in industrialized countries. Most studies focus on the consequences of delayed motherhood for women's physical and mental health, but little is known about potential effects on infants' neurodevelopment. This prospective study examines the association between maternal age and offspring neurodevelopment in terms of both psychomotor development (Ages & Stages Questionnaires-3) and emotional competences (Early Childhood Behavior Questionnaire). METHODS: We evaluated a cohort of healthy pregnant women aged 20-41 years and their offspring, assessed at 38 weeks gestation (n = 131) and 24 months after birth (n = 101). Potential age-related variables were considered (paternal age, education level, parity, social support, maternal cortisol levels, and maternal anxiety and depressive symptoms). Bayesian ordinal regression models were performed for each neurodevelopmental outcome. RESULTS: Maternal age was negatively associated with poor child development in terms of personal-social skills [odds ratio (OR) -0.13, 95% confidence interval (CI) 0.77-0.99] and with difficult temperament in terms of worse emotional regulation (OR -0.13, 95% CI 0.78-0.96) and lower positive affect (OR 0.16, 95% CI 0.75-0.95). As for age-related variables, whereas maternal anxiety symptoms and cortisol levels were also correlated with poor child development and difficult temperament, maternal social support and parental educational level were associated with better psychomotor and emotional competences. CONCLUSION: Increasing maternal age may be associated with child temperament difficulties and psychomotor delay in terms of social interaction skills. Early detection of neurodevelopment difficulties in these babies would allow preventive psychosocial interventions to avoid future neuropsychiatric disorders.

Catatonía en psicosis puerperal. A propósito de un caso / Catatonia in puerperal psychosis: Presentation of a case

El objetivo del caso es hacer una revisión de la psicopatología, el diagnóstico diferencial, el manejo y la evolución, de la presentación catatoniforme de la psicosis puerperal. Para ello, ofrecemos la descripción clínica de una paciente que comienza con un episodio psicótico con síntomas catatónicos en la primera semana tras el parto. Como resultados de la revisión, encontramos que la psicosis puerperal es una entidad infrecuente, con una incidencia aproximada de 1-2 casos por cada 1000 partos, apreciándose los síntomas catatónicos en un porcentaje inferior al 5% de casos. Existe todavía gran incertidumbre sobre su tratamiento y evolución. Se concluye que, si bien se precisan más estudios, es importante el diagnóstico diferencial precoz así como la instauración temprana de tratamiento, con posterior seguimiento estrecho

The aim of this case report is to perform a review of the psychopathology, the differential diagnosis, the management, and outcome, of the presentation of the catatonic form of puerperal psychosis. To do this, the clinical description is presented of a patient whose first psychotic episode with catatonic symptoms occurred in the first week post-partum. As a result of the review, it has been found that puerperal psychosis is an uncommon condition, with an incidence of 1-2 cases per 1000 deliveries, with the catatonic symptoms being observed in less than 5% of cases. There is still great uncertainty about its treatment and outcome. It is concluded that, although more studies are required, an early differential diagnosis is important, as well as the early starting of treatment, with a subsequent close follow-up