Autistic children and adolescents with frequent restricted interest and repetitive behavior showed more difficulty in social cognition during mask-wearing during the COVID-19 pandemic: a multisite survey.

BACKGROUND: The public health measures enacted in order to control the coronavirus disease (COVID-19) pandemic have caused considerable changes to daily life. For autistic children and adolescents, adapting to the "new normal," including mask-wearing, may be difficult because of their restricted interest and repetitive behavior (RRB) characteristics. We aimed to examine the relationships between RRB characteristics and the impact of mask-wearing on their social communications during the pandemic. METHODS: We recruited participants with a clinical diagnosis of autism spectrum disorder based on DSM-5 diagnostic criteria from two outpatient clinics in Tokyo, Japan, between November 2020 and April 2021 using a convenience sampling methodology. As a result, the participants consisted of 102 children and adolescents (mean (SD) age = 11.6 (5.3)). We collected data on RRB characteristics frequency before and during the pandemic using the CoRonavIruS Health Impact Survey (CRISIS) - Adapted for Autism and Related Neurodevelopmental conditions (AFAR). We then conducted factor analyses to compute the RRB severity composite scores, which are divided into lower- (e.g., sensory seeking), and higher-order (e.g., restricted interest). We also investigated mask-wearing culture using a bespoke questionnaire, and using Spearman's rank correlation analyses, we examined the relationships between before pandemic RRB characteristics, and the impact of mask-wearing on social communications during the pandemic. RESULTS: We found that children and adolescents who exhibited lower-order RRB before the pandemic had difficulties in going-out with mask-wearing (rho = -0.25, q = .031), more challenges with mask-wearing (rho = - 0.34, q = .0018), and difficulty in referring to others' emotions while wearing masks (rho = - 0.36, q = .0016). We also found an association between higher-order RRB before the pandemic and an uncomfortable sensation (rho = - 0.42, q = .0002) and difficulties in referring to other's emotions while wearing masks (rho = - 0.25, q = .031). CONCLUSIONS: We revealed that various behaviors, such as sensory seeking, repetitive motor mannerisms and movements, and rituals and routines, undertaken before the pandemic could be important predictors of difficulties with mask-wearing and social communication for autistic children and adolescents during the pandemic. Caregivers and teachers wearing masks may need to provide extra support for social communication to autistic children and adolescents showing RRB characteristics frequently.

Clinical guide for women with mental health problems during the perinatal period.

Pregnancy and childbirth have various effects on the physical as well as mental aspects of women. Therefore, appropriate considerations must be given to the mental health of pregnant women. The Guideline Review Committee of the Japanese Society of Psychiatry and Neurology launched a liaison meeting for the Japanese Society of Psychiatry and Neurology and the Japan Society of Obstetrics and Gynecology, with a view to creating a "Clinical guide for women with mental health problems during the perinatal period" by cooperation of these two fields. After repeated discussions with input from both academic societies, they jointly formulated the "Clinical guide for women with mental health problems during the perinatal period: Overview" in May 2020, and reported its "Detailed Contents" in April 2021. We hope that this guide, which is the English overview of the detailed guide, will contribute to the mental health of pregnant women, facilitating healthy pregnancies and childbirth.

Pregnant women's opinions toward prenatal pretest genetic counseling in Japan.

In-person models of genetic counseling (GC) have been the common method in Japan for pregnant women to receive GC. However, recent increases in the number of pregnant women considering undergoing prenatal testing have made it challenging to retain individualized in-person care. To explore pregnant women's opinions toward pretest GC models and the ideal time duration, a self-administered questionnaire survey was conducted for women at their first prenatal visit. A total of 114 valid respondents (93.4%) were included in the analyses. Of these, 80.7% of women preferred in-person GC, followed by classroom (9.6%), group (3.5%), and telegenetic-based GC (2.6%). Women with experience in undergoing prenatal testing significantly did not prefer in-person GC (p = 0.05). Sixty-two women (54.4%) preferred a duration of 15-29 min for pretest GC sessions, followed by 30-59 min (28.9%) and <15 min (14.9%). Women's preference of ≥30 min in length was significantly associated with anhedonia, singleton pregnancies, acquaintance with people with trisomy 21, and awareness of prenatal testing. Women who were unaware of the need for agreement with the partner for prenatal testing and who did not know the average life expectancy of a trisomy 21 patient significantly preferred <15 min in length over other durations. While the majority of women preferred in-person GC for <30 min, their preferences varied by their background characteristics, experiences, attitudes, and knowledge. These findings will help establish a prenatal GC system offering a choice of GC models in Japan; however, further large-scale studies are needed to confirm these findings.

Factors affecting the grieving process after perinatal loss.

BACKGROUND: Factors associated with the grief process in response to perinatal loss have been investigated. However, few studies focused on the intrapersonal factors, such as developmental and personality traits. Hence, this study aimed to investigate medical and psychosocial risk factors, including inter- and intrapersonal factors for the development of complicated grief following perinatal loss, while considering emotional support. METHODS: A total of 50 patients who were treated for grief due to perinatal loss at the National Center for Child Health and Development were divided into two groups according to the treatment period (< 6 months: n = 28; ≥ 6 months: n = 22). We compared medical and psychosocial variables between the two groups using the χ2 test and t test. All data were further analyzed using a logistic regression model to adjust for confounding effects. RESULTS: Patients who had traits of developmental/personality disorders (adjusted odds ratio [OR]: 7.21, 95% confidence interval (CI): 1.21-42.9, P = .030), and those treated with psychoactive drugs (adjusted OR: 5.77, 95% CI 1.09-30.5, P = .039) required a longer treatment period (≥ 6 months). CONCLUSIONS: Patients with personality/developmental traits and those with active psychiatric symptoms required a more extended treatment period in response to loss, suggesting the accumulation of negative factors in these patients; thus, more intensive and specialized care is necessary for these patients. Precise analysis of the coping style, attachment style, communication skills, and life history including relationship with the original family of the patients may have implications on the approach toward patients with complicated grief after perinatal loss. Studies with larger sample size are required to increase the reliability of the present findings, and future research should address the effects of the differential attachment and coping styles of patients with developmental/personality traits on the grief process.

Plasma estradiol levels and antidepressant effects of omega-3 fatty acids in pregnant women.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) reduce depressive symptoms through an anti-inflammatory effect, and injection of both omega-3 PUFAs and estradiol (E2) induces antidepressant-like effects in rats by regulating the expression of inflammatory cytokines. The aims of this study were to examine the association of increased E2 during pregnancy with depressive symptoms and with inflammatory cytokines in women who were and were not supplemented with omega-3 PUFAs. METHODS: Pregnant women with Edinburgh Postnatal Depression Scale scores ≥9 were recruited at 12-24 weeks of gestation. The participants were randomly assigned to receive 1800 mg omega-3 fatty acids (containing 1206 mg eicosapentaenoic acid [EPA]) or placebo for 12 weeks. E2, omega-3 PUFAs, high-sensitivity C-reactive protein, interleukin-6, and adiponectin were measured at baseline and at the 12-week follow-up. Multivariable regression analyses were conducted to examine the association of the changes of E2 and omega-3 PUFAs with the changes in depressive symptoms and with the changes of inflammatory cytokines at follow-up by intervention group. RESULTS: Of the 108 participants in the trial, 100 (92.6%) completed the follow-up assessment including blood sampling. Multivariable regression analyses revealed that the increase of EPA and E2 was significantly associated with a decrease in depressive symptoms among the participants assigned to the omega-3 group, but not among those assigned to the placebo group. Neither E2 nor any PUFAs were associated with a change in inflammatory cytokines. CONCLUSION: Supplementation with EPA and increased levels of E2 during pregnancy might function together to alleviate antenatal depression through a mechanism other than anti-inflammation.

An integrated community mental healthcare program to reduce suicidal ideation and improve maternal mental health during the postnatal period: the findings from the Nagano trial.

BACKGROUND: During the perinatal period, suicides are more likely to occur in those with depression and who are not receiving active treatment at the time of death. Suicide is a common outcome in people with suicide ideation. We developed an intervention program taking care of comprehensive perinatal maternal mental healthcare to prevent suicide ideation. We hypothesized that our intervention program could reduce postnatal suicide ideation and improve maternal mental health. METHODS: We performed a controlled trial to examine the usual postnatal care plus a maternal suicide prevention program (the intervention group) compared with usual postnatal care alone, which comprised home visits by public health nurses without mental health screening (the control group) in Nagano city, Japan. In total, 464 women were included; 230 were allocated to the control group and 234 to the intervention group. The intervention had three components: 1) all the women received postnatal mental health screening by public health nurses who completed home visits during the neonatal period, 2) the intervention was administered by a multidisciplinary clinical network, and 3) systematic follow-up sheets were used to better understand bio-psycho-social characteristics of both the mothers and their infants and develop responsive care plans. We measured the participants' mental health at 3-4 months postpartum (T1) and 7-8 months postpartum (T2) using the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Suicidal ideation was significantly lower in the intervention group compared with the control group at T1 (p = 0.014); however, this significant between-group difference did not continue to T2 (p = 0.111). We measured the intervention effects on maternal mental health using the total score of the EPDS, which was significantly improved in the intervention group compared with the control group at T1. Here, the significant difference continued to T2 (p = 0.049). CONCLUSIONS: Our results indicate that our program may reduce maternal suicidal ideation at 3-4 months postnatally and improve women's mental health during the postnatal periods of 3-4 to 7-8 months. Postnatal maternal mental healthcare, including services to reduce suicide ideation, should be included as an important component of general postnatal care. TRIAL REGISTRATION: Name of registry: A multidisciplinary intervention program for maternal mental health in perinatal periods. UMIN Clinical Trials Registry number: UMIN000033396 . Registration URL: https://upload.umin.ac.jp/cgibin/ctr/ctr_view_reg.cgi?recptno=R000038076 Registration date: July 15, 2018. Registration timing: retrospective.

The burden of disease and the cost of illness attributable to child maltreatment in Japan: long-term health consequences largely matter.

BACKGROUND: Child maltreatment leads to enormous adverse short- and long-term health outcomes. The aim of this study is to estimate the burden of disease and the cost of illness attributable to child maltreatment in Japan. METHODS: An incidence-based top-down cost of illness analysis was conducted to estimate medical costs and burden of disease attributable to child maltreatment based on a societal perspective. The assessment included short-term and long-term medical costs and burden of disease measured by Disability-Adjusted Life Years (DALYs) that generates mortality and morbidities, based on several national surveys and systematic review. We considered the main types of child maltreatment as exposure, for which the incidence was obtained from literature review. Based on population attributable fractions (PAFs), burden of disease of physical and mental health consequences attributable to child maltreatment were estimated. Then DALYs were converted into monetary value. The lifetime economic burden was finally estimated by combining with medical costs and subject to sensitivity analysis. RESULTS: The lifetime disease burden expressed in DALYs was estimated at 1,047,580 DALYs (95% CI 788,388 - 1326,80 DALYs) for the cohort victims in 2016. Based on the incidence according to literature review, the overall lifetime economic burden was 50.24 billion USD, equivalent to 1.3 million times of gross domestic product (GDP) per capita. Among the total economic burden, costs of suffering and pain based on DALYs were accounting for 81.3%. These estimates were 7-8 times of conservative estimates which used incidence data from official reported cases. CONCLUSIONS: This study found that the national lifetime cost was huge and equivalent to 1.3 million GDP per capita, and its burden of disease was approximately equal to that of colon and rectum cancers or stomach cancer. Our findings particularly in terms of revealed the considerable burden of disease in long term and potential effects of the strengthened maternal and child care as the preventive strategy.

Integrated mental health care in a multidisciplinary maternal and child health service in the community: the findings from the Suzaka trial.

BACKGROUND: Perinatal mental health problems such as mood disorders are common. We propose a new multidisciplinary health service intervention program providing continuous support to women and their children from the start of pregnancy till after childbirth. The aim of this study was to examine the effects of the program with respect to making women's mental health better in the postpartum period and improving the state of care for women and their children in the perinatal period. METHODS: We performed a controlled study to investigate the effectiveness of the program in Suzaka City, Japan. The women's mental health status was assessed using the Edinburgh Postnatal Depression Scale (EPDS) 3 months postpartum. Of 349 women, 210 were allocated to the intervention group and 139 to the control group. From April 2014 to March 2015, the number of the pregnant women who were followed-up by the multidisciplinary meeting in the intervention and control groups were 60 and 4, respectively. In the same period, the number of the pregnant women who were identified as requiring intensive care were 21 and 2, respectively. RESULTS: The total EPDS score, which was the primary outcome of the present study, differed significantly between the intervention and control groups (Mean [SD] = 2.74 (2.89) and 4.58 [2.62], respectively; p < 0.001). The number of the women receiving counseling from a public health nurse (5.3% in intervention group, 0.7% in control group, p = 0.02), attending maternal seminars (attendant ratio: 46% whereas 16%, p = 0.01), and receiving home visits by public health nurses (home visit ratio: 93.8% whereas 82.6%, p < 0.001) was significantly higher in the intervention group compared to the control group. CONCLUSIONS: The present study indicates that continuum support provided by integrated mental health care through a multidisciplinary maternal and child health service in the community can make women's mental health better in the postpartum period and help women and their children receive more health services from public health nurses. TRIAL REGISTRATION: Name of registry: Research for the effectiveness of a multi-professional health service intervention program of continuum supports for mother and child which starts for pregnancy periods to enhance maternal mental health. UMIN Clinical Trials Registry number: UMIN000032424 . Registration date: April 29th, 2018. Registration timing: retrospective.

Allergic diseases in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis.

BACKGROUND: Reports of frequent manifestation of allergic diseases in children with attention deficit hyperactivity disorder (ADHD) have been the subject of mounting clinical interest. However, evidence supporting the association between ADHD and allergies is inconsistent and has yet to be systematically reviewed. The objective of this study was to compile and assess available studies on the association between ADHD and allergic diseases in children. METHODS: A comprehensive search using MEDLINE, EMBASE, the Cochrane library, and CINAHL databases was completed in 23 November 2015. The inclusion criteria for studies were that the research assessed allergic diseases in children, 18 years of age and younger, with a diagnosis of ADHD and that a distinct comparison group was incorporated. Any comparative studies, encompassing both randomized controlled trials and observational studies, were considered for inclusion. Two review authors independently assessed the quality of the selected studies by the use of validated assessment tools, performed data extraction and conducted meta-analysis according to Cochrane Collaboration guidelines. RESULTS: Five eligible studies were included in this systematic review. Of these studies, three were case-control and two were cross sectional studies. A majority of information from the five studies was classified as having low or unclear risk of bias. The meta-analysis showed an association between children with ADHD and asthma compared with the control groups (OR: 1.80, 95% CI: 1.57 - 2.07; five studies, low quality of evidence), but did not indicate an association between food allergy and ADHD (OR: 1.13, 95% CI: 0.88 - 1.47; three studies very low quality of evidence). The odds of experiencing allergic rhinitis, atopic dermatitis, and allergic conjunctivitis were slightly higher in children with ADHD compared with control groups, though a substantial statistical heterogeneity was notable in the overall effect estimates. CONCLUSIONS: The findings from this review and meta-analysis show that children with ADHD are more likely to have asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis than their counterparts. Interventions including strategies for managing allergies in children with ADHD would be beneficial.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

BACKGROUND: Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. METHODS: The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. DISCUSSION: The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

A Comparison of Self-Rated and Female Partner-Rated Scales in the Assessment of Paternal Prenatal Depression.

Maternal depression has been widely studied but paternal depression is often overlooked. Depression in men is generally more difficult to detect as the symptoms are not apparent. Furthermore, Japanese couples tend to suppress their real emotions to avoid confrontation. We aimed to investigate the reliability and validity of the K6, K10 and PHQ-9 in assessing the mental health status of men when used by their pregnant partners, as well as the prevalence of paternal prenatal depression in a Japanese study sample. A total of 136 couples participated in this study. The prevalence of paternal prenatal depression reported by the men themselves was higher compared to that reported by their female partners (K6, 10.3 %; K10, 6.6 %; PHQ-9, 3.7 % vs. K6-FP, 2.2 %; K10-FP, 1.5 %; PHQ-9-FP, 0 %, respectively). Mental health issues in men may not be accurately rated by their female partners, suggesting the importance of self-rating and direct consultation.

Interventions for expectant and new parents who are at increased risk for perpetrating child abuse and neglect: protocol for a systematic review and meta-analysis.

INTRODUCTION: The prevention of child abuse and neglect is an urgent matter given the serious effects persisting into adulthood, and the increased risk of the offspring of abused children being abusive themselves. Intervening as early as possible may prevent abuse that can begin in infancy. Although several systematic reviews have investigated the effects of interventions on populations who are at increased risk for perpetrating child abuse and neglect, few studies have focused on women or interventions that start during perinatal periods. This study aims to describe a systematic review to examine the effects of interventions to prevent child abuse and neglect that begin during pregnancy and immediately after childbirth (less than 1 year). The study will involve performing a systematic review and meta-analysis based on the latest research articles and a broader literature search. METHODS AND ANALYSIS: The protocol was prepared using the 2015 statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature search will be performed using the MEDLINE, PsycINFO, Embase and Cochrane Central Register of Controlled Trials databases from inception onward. Randomised controlled trials of interventions that begin during pregnancy or the first year postpartum, designed to prevent child abuse and neglect in families who are at increased risk for these issues, will be included. Data collection, quality assessment and statistical syntheses will be conducted by following the methods in the protocol that are predefined. Any index of child maltreatment will be included as a primary outcome. A meta-analysis and sub-group analyses will be considered based on the characteristics of interventions. ETHICS AND DISSEMINATION: This study does not require ethical approval. The findings will be presented at conferences and will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021266462.

The characteristics of children referred to a child protection team in Japan and factors associated with decision-making: A retrospective study using a medical database.

BACKGROUND: Despite the potential efficacy of hospital-based multidisciplinary child protection team (CPTs), research analyzing Japanese CPT databases is scarce. OBJECTIVE: We aimed to describe the characteristics of children and families reported to a CPT in Japan and investigate factors associated with the substantiation of maltreatment. PARTICIPANTS AND SETTING: This retrospective, cross-sectional study took place in a national children's hospital in Japan and included 350 children who were reported to CPTs between April 2014 and March 2018. METHODS: Univariable and multivariable logistic regression analyses were conducted using the CPT database and medical records. RESULTS: Among 350 cases, 33.4 % were substantiated. Children of <6 years of age comprised 73.4 % of the cases. The majority (67.7 %) received an injury-related diagnosis and physical maltreatment was suspected in 68.3 % of cases. In the univariable analysis, older age, a primary diagnosis other than injury, reporting department, psychological maltreatment, witnessing intimate partner violence, maltreatment by relatives other than biological father or mother, developmental disability, emotional/behavioral difficulty or psychological disorder, maternal/paternal psychological difficulty, and maternal history of maltreatment were significantly associated with substantiation. When adjusted for demographic, child and familial factors, a diagnosis other than injury (AOR 2.02, 95 % CI = 1. 11-3.65) and parental psychological difficulties (AOR 2.49, 95 % CI = 1.37-4.55) were independently associated with substantiation. CONCLUSION: Most cases reported to our CPT were young children with an injury-related diagnosis. Substantiation was associated with a diagnosis other than injury and parental psychological difficulties. Further prospective and comprehensive studies are needed to establish universal guidelines for databases of hospital-based CPTs.

Transfer of brotizolam, periciazine, and sulpiride in cord blood and breast milk, and alprazolam in breast milk: a case report.

BACKGROUND: A high prevalence of mental disorders including depression, anxiety, somatoform, and dissociative disorder is reported during pregnancy, however, information on the transfer of antipsychotics across the placenta and into breast milk is limited. We evaluated brotizolam, periciazine and sulpiride in cord blood, maternal serum, and breast milk, and alprazolam in breast milk. CASE PRESENTATION: A 38-year-old woman with dissociative disorder was treated with brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and alprazolam during lactation. The drug concentration ratios for both cord blood and maternal serum were 33.3 and 61.5% for brotizolam and sulpiride, respectively, and periciazine (metabolite of propericiazine) was not detected in the cord blood. In breast milk, alprazolam (0.9 ng/mL), sulpiride (445.8 ng/mL), and periciazine (0.3 ng/mL) concentrations were noted at 7.5 h after the last dose on postpartum, whereas brotizolam was not detected. The relative infant doses via breast milk were 1.4, 2.7 and 0.02% of the maternal daily dose, respectively. The neonate had no congenital anomalies and did not experience any severe withdrawal symptoms after birth. CONCLUSION: Use of brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and use of alprazolam during lactation were acceptable in this case.

Presence of Hypnotics in the Cord Blood and Breast Milk, with No Adverse Effects in the Infant: A Case Report.

Background: Hypnotics are frequently used for insomnia in pregnant and lactating women. This case study assessed zolpidem concentrations in the cord blood and breast milk and ramelteon concentrations in the breast milk of a woman who was treated with zolpidem and ramelteon for insomnia. Materials and Methods: Zolpidem concentrations were measured in maternal serum, breast milk, and cord blood. Concentrations of ramelteon and M-II, an active ramelteon metabolite, were measured in maternal serum and breast milk. Case Report: A 46-year-old female patient diagnosed with insomnia received 5-10 mg/day zolpidem during pregnancy and lactation and 8 mg/day ramelteon during lactation. A male infant weighing 3,329 g was born at 38 weeks' gestation, with no congenital abnormalities found during pregnancy or at birth. The infant was normal at the 1-month postpartum checkup. The maternal/placental ratio of zolpidem concentrations was 0.1 at 7.4 hours after maternal dosing, similar to that reported in previous studies. The calculated relative infant dose through breast milk based on the maximum drug concentration in breast milk at 2.2 hours after maternal dosing was 2.7% for zolpidem and 0.2% for ramelteon. Ramelteon and its metabolite (M-II) concentrations in the breast milk were equivalent to those in the maternal serum, although the infant exposure of these drugs was low for an oral dose. Conclusions: In the current case, zolpidem transferred into the placenta and breast milk, and ramelteon transferred into the breast milk. Further studies should assess the safety of zolpidem and ramelteon in fetus and breastfed infants.

Transfer of Zolpidem to Cord Blood and Breast Milk: A Case Series Evaluating Zolpidem Serum Levels and Outcomes in Birth and Suckling Infants.

Background: Zolpidem is used for insomnia in pregnant and lactating women. Although zolpidem has been shown to cross the placenta and to be secreted into breast milk, it would not be expected to cause any adverse effects in newborn and breastfed infants. However, there is no relevant information on serum zolpidem levels in the newborn and breastfed infant from zolpidem-treated mother. This study aimed to present the outcomes of zolpidem exposure into infant who was delivered or breastfed by a zolpidem-treated mother. Methods: In this case series, zolpidem-treated pregnant women were recruited between September 2019 and April 2022, and maternal serum, cord blood, breast milk, and infants' serum were collected, and the zolpidem concentration in each sample was evaluated. Childbirth outcomes, including 1-month health care checkup, were also evaluated. Results: Three cases were recruited during investigation period. No spontaneous abortion or preterm live deliveries occurred. Oxygen intervention was required in one term infant, but the findings resolved on postpartum day 1. No medical intervention was required in other three infants. Zolpidem was not detected in infants' serum even after breastfeeding. There are no abnormal developmental findings in any of the infants in their 1-month health checkups. Conclusions: Zolpidem transferred into fetal circulation in utero and breast milk, however no harmful findings existed in infants during pregnancy and lactation. Exposure doses through breastfeeding is small, which may be a cause of rare detection from the infants' serum. Due to the limited number of cases, larger studies and integrated review are needed.

Trazodone Levels in Maternal Serum, Cord Blood, Breast Milk, and Neonatal Serum.

Background: Trazodone is used to treat anxiety disorder, insomnia, and sleep disorders, which occur in ∼15% of pregnant and lactating women. However, pharmacokinetic information on the transfer of trazodone and its active metabolite, 1-m-chlorophenylpiperazine (mCPP), across the placenta or into breast milk is limited. In this study, we describe the pharmacokinetic profile of trazodone and mCPP concentrations in maternal and neonatal blood and breast milk. Case Presentation: A 44-year-old female received oral trazodone 50 mg once daily during pregnancy (28-38 gestational weeks) and lactation, along with etizolam for anxiety disorder with depressive syndrome. A male infant weighing 2,918 g was born at 38 weeks of gestation. Because of persistent respiratory disturbance, oxygenation was initiated immediately after birth, and the infant was admitted in the neonatal intensive care unit for 5 days. No pulmonary dysfunction or birth defects were detected, and no medication and circulatory support were needed during admission. Trazodone and mCPP concentrations in cord blood at 7.4 hours after maternal dosing were 267.6 and 22.8 ng/mL, respectively, which were comparable with maternal serum levels. The trazodone and mCPP concentrations in breast milk collected 7.2 hours after maternal dosing were 50.2 and 3.2 ng/mL, respectively. The infant developed normally, with no drug-related adverse effects at the 1-, 3-, and 6-month postpartum checkups. Conclusion: Trazodone and its active metabolite were transferred into placenta and breast milk. However, their effects in utero could not be clarified. Further studies are warranted to assess the safety of trazodone in fetuses and breastfed infants.