[Mental problems, psychosocial problems and substance use during pregnancy: a structured multidisciplinary approach reduces the child's risk]. / Psychische en psychosociale problemen of middelengebruik bij zwangeren.

AIM: To demonstrate the results of routine screening and treatment for psychiatric problems, psychosocial problems and substance use (PPS) among pregnant women in the Netherlands. This approach is advocated by the national program 'The first 1000 days', which focuses on a healthy start for (unborn) children in vulnerable situations. DESIGN: Secondary data analysis of a routine care dataset obtained from midwifery practices and hospitals throughout the Netherlands. All practices and hospitals applied systematic screening with Mind2Care. METHOD: Each Mind2Care screening results in either a negative result (no risk), an alert and/or a treatment advice based on local care pathways. Anonymous data on detected risk factors and subsequent alerts/advices from 22.141 pregnant women were analyzed. RESULTS: Of all women, 24% had at least one PPS risk factor. Accumulation of risks was present in 10% of women. Thirty-one percent of all pregnant women received at least one specific advice (15% alerts, 24% treatment advices, including overlap). CONCLUSION: One in four pregnant women has psychiatric problems, psychosocial problems and/or substance use for which guideline care is available. Implementation of Mind2Care is demanding to the obstetrical system, and requires multidisciplinary care processes of medical and social caregivers. Despite the lack of a scientific evidence on the added value of systematic detection and treatment of PPS-risks in all pregnancies, this programmatic approach is increasingly acknowledged on the national attention level as the way forward to a healthy start for every child, even if born under vulnerable conditions.

Parental Stress and Scalp Hair Cortisol in Excessively Crying Infants: A Case Control Study.

BACKGROUND: Caring for an excessively crying infant (ECI) can be stressful for mothers and fathers and is associated with mental and bonding problems. Hair cortisol offers a unique measure for the biological reaction of the body to stress over time. METHODS: In this case-control study, scalp hair cortisol concentrations (HCC) were measured using liquid chromatography-tandem mass spectrometry (LC-MS) in 35 mothers and 23 fathers and their ECIs. The control group consisted of 64 mothers and 63 fathers of non-ECIs of similar age. Parental stress, depression, anxiety and bonding were assessed using validated questionnaires. RESULTS: Mean HCC were significantly lower in mothers and fathers of ECIs (2.3 pg/mg, 95% CI 1.8-2.9 and 1.6 pg/mg, 95% CI 1.3-2.0) than that in control mothers and fathers (3.2 pg/mg, 95% CI 3.0-3.7 and 2.9 pg/mg, 95% CI 2.5-3.5). In the total group of parents and within the parents of ECIs, HCC were not associated with negative feelings. In the control group, HCC showed a positive association with stress and depression (r = 0.207, p = 0.020 and r = 0.221, p = 0.013). In infants, no differences were found in mean HCC between the ECI group and the control group. No associations were found between maternal and infant HCC, paternal and infant HCC and maternal and paternal HCC. CONCLUSION: Parents of ECIs showed significantly lower HCC than control parents, reflecting a diminished response of the hypothalamic-pituitary-adrenal (HPA) axis. More research is needed to examine whether this decrease in response is pre-existing or caused by excessive infant crying.

Distress in fathers of babies with infant colic.

AIM: The aim of this case-control study was to compare parental stress, depression, anxiety and bonding problems between fathers and mothers of babies with infant colic and parents of control infants. METHODS: Parents of 34 infants with infant colic and 67 control dyads were included. Parental feelings were assessed using validated questionnaires. RESULTS: Fathers as well as mothers of infants with infant colic showed significantly higher mean scores compared with controls on stress (20.9 ± 5.8 and 25.5 ± 7.2 vs 16.4 ± 6.1 and 14.7 ± 7.0), depression (5.6 ± 4.0 and 9.1 ± 4.8 vs 2.9 ± 2.9 and 4.0 ± 3.1), anxiety (41.9 ± 9.2 and 46.0 ± 10.2 vs 32.4 ± 8.4 and 32.2 ± 9.3) and bonding problems (16.1 ± 8.1 and 13.7 ± 5.9 vs 8.7 ± 6.3 and 5.0 ± 4.4). In fathers, after adjustments for infant and parental confounders and maternal negative feelings, depression and anxiety were significantly increased in the infant colic group (difference of 2.7 (p = 0.017) and 8.6 (p = 0.002)). CONCLUSION: In fathers of infants with infant colic, the experienced distress is strongly associated with maternal distress, except for depression and anxiety. Paediatricians should be aware of these paternal feelings as parental reassurance and support is one of the cornerstones in the treatment of infants with colic.

An exploratory study of perinatal hair cortisol concentrations in mother-infant dyads with severe psychiatric disorders versus healthy controls.

BACKGROUND: Maternal psychopathology during pregnancy is associated with negative outcomes in offspring. Increased placental transfer of maternal cortisol may contribute to mediate this association. Hair cortisol concentrations (HCCs) appear to be a good biomarker of long-term prenatal stress exposure. Little is known about the associations between severe maternal psychopathology and perinatal infant HCCs. AIMS: We assessed HCCs in the perinatal period in mother-infant dyads with and without severe psychiatric disorders. METHOD: We examined group differences in HCCs of mother-infant dyads (n = 18) subjected to severe maternal psychiatric disorders versus healthy control dyads (n = 27). We assessed the correlation of HCCs between mother and infant within both groups, and the association between current maternal symptoms and HCCs in patient dyads. RESULTS: Median (interquartile range) and distribution of HCC differed in patients compared with control mothers (U = 468.5, P = 0.03). HCCs in infants of patients did not differ from control infants (U = 250.0, P = 0.67). Subsequently, we found that HCCs within healthy control dyads were correlated (n = 27, r 0.55 (0.14), P = 0.003), but were not within patient dyads (n = 18, r 0.082 (0.13), P = 0.746). HCCs in infants of patients showed a positive correlation with maternal symptoms (n = 16, r = 0.63 (0.06), P = 0.008). CONCLUSIONS: These preliminary findings suggest that infant HCC reflect perinatal stress exposure. In infants, these early differences could influence lifetime hypothalamic-pituitary-adrenal axis functioning, which might be associated with increased susceptibility to later disease.

Prevalence and course of mood and anxiety disorders, and correlates of symptom severity in adolescents with type 1 diabetes: Results from diabetes LEAP.

OBJECTIVES: We aim to determine the prevalence and the course of anxiety and mood disorders in Dutch adolescents (12-18 years old) with type 1 diabetes, and to examine correlates of symptom severity, including parental emotional distress. METHODS: Participants were 171 adolescents and 149 parents. The Diagnostic Interview Schedule for Children-IV was used to assess current, past year and lifetime anxiety and mood disorders in adolescents. Symptom severity and diabetes distress were measured with validated questionnaires. Correlates of these symptoms were examined using hierarchical regression analyses and included demographics (adolescent sex and age), clinical factors (diabetes duration, treatment modality, most recent glycated hemoglobin A1c ; all extracted from medical charts), adolescent diabetes distress, and parent emotional distress. RESULTS: Twenty-four (14%) adolescents met the criteria for ≥1 disorder(s) in the previous 12 months. Anxiety disorders were more prevalent than mood disorders (13% vs. 4%). Lifetime prevalence of anxiety and mood disorders was 29% (n = 49). The presence of any of these disorders earlier in life (from 5 years old up to 12 months prior to assessment) was associated with disorders in the past 12 months (OR = 4.88, p = 0.001). Higher adolescent diabetes distress was related to higher symptoms of anxiety (b = 0.07, p = 0.001) and depression (b = 0.13, p = 0.001), while demographics, clinical characteristics, and parental emotional distress were not related. CONCLUSIONS: Anxiety and mood disorders are common among adolescents and related to earlier disorders. Higher diabetes distress was related to higher symptom severity. Clinicians are advised to address past psychological problems and remain vigilant of these problems.

Raising the Cut-Off Level of Anti-Tissue Transglutaminase Antibodies to Detect Celiac Disease Reduces the Number of Small Bowel Biopsies in Children with Type 1 Diabetes: A Retrospective Study.

OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.

LC-MS/MS-based reference intervals for hair cortisol in healthy children.

BACKGROUND: Human scalp hair is a valuable matrix for determining long-term cortisol concentrations, with wide-spread applicability in clinical care as well as research. However, pediatric reference intervals are lacking. The aim of this cross-sectional study is to establish age-adjusted reference intervals for hair cortisol in children and to gain insight into hair growth velocity in children up to 2 years old. METHODS: A total of 625 healthy children were enrolled through recruitment in pregnancy, infant-welfare clinics, and school visits. Scalp hair cortisol levels were measured using liquid chromatography-tandem mass spectrometry. Age-adjusted reference intervals were established in children from birth to 18 years old. Hair growth velocity was determined in children 0-2 years of age by measuring hair length at 4- to 10-week intervals. RESULTS: Hair cortisol levels were high (162.4 pg/mg, 2.5th-97.5th percentile: 28.8-961) after birth with a sharp fall in the first 3 months of life. This is followed by lower values until age 6 and then by graduated and subtle higher values to adult concentrations are reached at the age of 18 years (3.0 pg/mg, 2.5th-97.5th percentile: 0.53-17.8). Average hair growth velocity measured in mm/month was significantly lower in infants 0-6 months of age compared to children 12-24 months (3.5 versus 9.4, P < 0.001). CONCLUSIONS: This is the first study to provide age-adjusted reference intervals for hair cortisol in children from 0-18 years. Higher hair cortisol concentrations in infants might be explained by the significantly lower hair growth rate in the first year of life. The establishment of pediatric hair cortisol reference ranges broadens the potential applications of this biomarker in pediatric clinical care.

Study protocol of Diabetes LEAP: a longitudinal study examining emotional problems in adolescents with type 1 diabetes and their parents/caregivers.

BACKGROUND: Type 1 diabetes (T1D) is a chronic metabolic condition requiring intensive daily self-care to avoid both high and low blood glucose levels. Self-care and glycemic outcomes are particularly problematic in adolescence, a period known for its increased risk of emotional problems. However, the true scope of mood and anxiety disorders in adolescents with T1D is unknown. Earlier studies are limited by a small sample size, lack of diagnostic interview data, a focus on depression only, non-adolescent specific estimates, lack of information about parental emotional problems and/or a cross-sectional design. Diabetes LEAP is a two-year prospective observational cohort study examining (a) the prevalence and course of depression and anxiety in adolescents with T1D and their parents/caregivers, (b) the risk factors predicting the presence of these emotional problems, (c) their longitudinal relation with diabetes outcomes, and (d) the psychosocial care currently in place. METHODS: Adolescents (12-18 years) from 8 Dutch pediatric diabetes clinics are interviewed using the DISC-IV to establish the presence of mood and anxiety disorders in the previous 4 weeks, the previous 12 months, and lifetime. They also complete questionnaires, including CDI-2, GAD-7, and PAID-T. Parents/caregivers complete PHQ-9, GAD-7, and PAID-PR. Follow-up assessments take place after 1 and 2 years. DISCUSSION: This longitudinal study with diagnostic interviews in a large cohort of adolescents with T1D in the Netherlands will provide much needed information regarding the prevalence and course of depression and anxiety in this group, thereby opening avenues for proper recognition, prevention and timely treatment.

Gastrointestinal Symptoms in Infants of Mothers With a Psychiatric History and the Role of Depression and Bonding.

OBJECTIVES: Gastroesophageal reflux (GER), excessive crying, and constipation are common gastrointestinal symptoms in infancy of multifactorial origin in which psychosocial stress factors play an important role. The aims of this observational study were to investigate the presence of gastrointestinal symptoms in infants of mothers with or without a history of a psychiatric disorder, their association with maternal depressive symptoms, and the possible mediating role of bonding. METHODS: One hundred one mothers with a history of a psychiatric disorder and 60 control mothers were included. Infant gastrointestinal symptoms, maternal depressive symptoms, and mother-infant bonding were assessed using validated questionnaires and diagnostic criteria at 1.5 months postpartum. RESULTS: The mean total score on the Infant Gastroesophageal Reflux Questionnaire Revised reported in infants of mothers with psychiatric disorder (13.4 standard deviation 5.4) was significantly higher than that in infants of control mothers (10.8 standard deviation 5.4; P = .003). No significant differences were found in the presence of excessive crying (modified Wessel criteria and subjective experience) and constipation (ROME IV criteria) between both groups. Infant GER was associated with maternal depressive symptoms (P = 0.027) and bonding problems (P = <0.001). Constipation was related to maternal depressive symptoms (P = 0.045), and excessive crying (Wessel and subjective criteria) was associated with bonding problems (P = 0.022 and P = 0.002, respectively). The effect of maternal depressive symptomatology on infant GER symptoms and excessive crying was mediated by bonding problems. CONCLUSION: Maternal psychiatric history is associated with infant gastrointestinal symptoms, in which mother-infant bonding is a mediating factor.

BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells.

The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice. However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense mutation, affected by multisystem anomalies and profound immune deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes.

Reporting outcome measures in trials of infant colic.

OBJECTIVES: Infant colic (IC), with an estimated prevalence of 5% to 25%, has a high impact on health care costs. Furthermore, reported negative sequelae are disturbed parent-infant interaction, increased susceptibility to abdominal pain, and even child abuse. Its etiology remains unknown, leading to a wide variety in interventions. We hypothesize that definitions and outcome measures in studies on IC will be heterogeneous as well. Our objective is to systematically assess how definitions and outcome measures are reported in randomized controlled trials (RCTs) of IC. METHODS: CENTRAL, Embase, and MEDLINE/PubMed were searched from inception to December 2012. English-language systematic reviews (SRs) and RCTs concerning IC in children ages 0 to 9 months were included. Bibliographies of included SRs were searched for additional articles. Quality was assessed using the Delphi list. RESULTS: A total of 1702 studies were found; 55 articles were included (16 SRs, 39 RCTs). In 39 trials, we found 20 different definitions for IC, 11 different definitions for improvement, 28 different interventions, and 19 different outcomes. Fifty-one percent of the trials were of good methodological quality. All of the trials used parental diaries; only 31% stated that their instrument was validated. CONCLUSIONS: Too many different definitions and outcome measures for IC are used in RCTs. Only a minority of the trials reported parental perception as primary outcome. Uniform definitions, outcomes, and validated instruments are needed to make a comparison between intervention studies possible.