Preventive Health Care Among Children of Women With Schizophrenia: A Population-Based Cohort Study.

Objective: To compare well-baby visit and vaccination schedule adherence up to age 24 months in children of mothers with versus without schizophrenia.Methods: Using administrative health data on births in Ontario, Canada (2012-2016), children of mothers with schizophrenia (ICD-9: 295; ICD-10: F20/F25; DSM-IV schizophrenia or schizoaffective disorder) (n = 1,275) were compared to children without maternal schizophrenia (n = 520,831) on (1) well-baby visit attendance, including an enhanced well-baby visit at age 18 months, and (2) vaccine schedule adherence for diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type B (DTaP-IPV-Hib), and measles, mumps, rubella (MMR). Cox proportional hazard regression models were adjusted for each of maternal sociodemographics, maternal health, and child health characteristics in blocks and all together in a fully adjusted model.Results: About 50.3% of children with maternal schizophrenia had an enhanced 18-month well-baby visit versus 58.6% of those without, corresponding to 29.0 versus 33.9 visits/100 person-years (PY), a hazard ratio (HR) of 0.82 (95% CI, 0.76-0.89). The association was dampened after adjustment for maternal sociodemographics, maternal health, and child health factors in blocks and overall, with a fully adjusted HR of 0.91 (95% CI, 0.84-0.98). Full vaccine schedule adherence occurred in 40.0% of children with maternal schizophrenia versus 46.0% of those without (22.6 vs 25.9/100 PY), yielding a HR of 0.86 (95% CI, 0.78-0.94). The association was dampened when adjusted for maternal sociodemographics and child health characteristics and became nonsignificant when adjusted for maternal health characteristics. The fully adjusted HR was 0.95 (95% CI, 0.87-1.04).Conclusions: Increased efforts to ensure that children with maternal schizophrenia receive key early preventive health care services are warranted.

Maternal Schizophrenia, Skin-to-Skin Contact, and Infant Feeding Initiation.

BACKGROUND: The World Health Organization recommends mothers and infants be in direct skin-to-skin contact immediately after birth and initiate breastfeeding as soon as possible. Little is known in women with schizophrenia. METHODS: We conducted a population-based cohort study using administrative health data from Ontario, Canada (2012-2014), comparing women with (n = 471) and without schizophrenia (n = 218 435), and their infants, on the primary outcomes of any skin-to-skin contact and opportunity to initiate breastfeeding within the first 2 h after birth. For dyads with available data, secondary outcomes of intention to breastfeed, breastfeeding support, any breastmilk, and exclusive breastmilk at discharge were assessed. Modified Poisson regression was used to generate relative risks (aRR) and 95% confidence intervals (CI), adjusted for maternal age, parity, neighbourhood income, region of residence, smoking in pregnancy, and maternal medical and non-psychotic psychiatric comorbidity for all outcomes. RESULTS: Maternal schizophrenia was associated with lower likelihood of skin-to-skin contact (65.2% vs 78.1%; aRR 0.88, 95% CI: 0.82-0.94), and breastfeeding initiation post-delivery (38.9% vs 52.6% aRR 0.80, CI: 0.71-0.90) compared to dyads unexposed to maternal schizophrenia. Secondary outcomes followed a similar pattern. The magnitude of the effect was slightly less when restricting the cohort to full-term, vaginal deliveries, not admitted to NICU, and infant not discharged to social services. CONCLUSIONS: Reduced maternal-infant skin-to-skin contact and breastfeeding initiation immediately after birth may significantly impact maternal-child bonding and the establishment breastfeeding in this population. Mothers with schizophrenia may require individualized support to promote these WHO recommended hospital practices in the early post-natal period.

Accidental injury, self-injury, and assault among children of women with schizophrenia: a population-based cohort study.

OBJECTIVE: We aimed to compare the risk for injury overall and by intent (accidental injury, self-injury, and assault) among children born to women with versus without schizophrenia. METHODS: Using health administrative data from Ontario, Canada, children born from 2003 to 2017 to mothers with (n = 3769) and without (n = 1,830,054) schizophrenia diagnosed prior to their birth were compared on their risk for child injury, captured via emergency department, hospitalization, and vital statistics databases up to age 15 years. Cox proportional hazard models generated hazard ratios for time to first injury event (overall and by intent), adjusted for potential confounders (aHR). We stratified by child sex and age at follow-up: 0-1 (infancy), 2-5 (pre-school), 6-9 (primary school), and 10-15 (early adolescence) planning to collapse age categories as needed to obtain stable and reportable estimates. RESULTS: Maternal schizophrenia was associated with elevated risk for child injury overall (105.4 vs. 89.4/1000 person-years (py), aHR 1.08, 95% CI 1.03-1.14), accidental injury (104.7 vs. 88.1/1000py, 1.08, 1.03-1.14), for self-injury (0.4 vs. 0.2/1000py, 2.14 1.18-3.85), and assault (1.0 vs. 0.3/1000py, 2.29, 1.45-3.62). By child sex, point estimates were of similar magnitude and direction, though not all remained statistically significant. For accidental injury and self-injury, the risk associated with maternal schizophrenia was most elevated in 10-15-year-olds. For assault, the risk associated with maternal schizophrenia was most elevated among children in the 0-1 and 2-5-year-old age groups. CONCLUSION: The elevated risk of child injury associated with maternal schizophrenia, especially for self-injury and assault, suggests that targeted monitoring and preventive interventions are warranted.

Cohort profile: the eLIXIR Partnership-a maternity-child data linkage for life course research in South London, UK.

PURPOSE: Linked maternity, neonatal and maternal mental health records were created to support research into the early life origins of physical and mental health, in mothers and children. The Early Life Cross Linkage in Research (eLIXIR) Partnership was developed in 2018, generating a repository of real-time, pseudonymised, structured data derived from the electronic health record systems of two acute and one Mental Health Care National Health Service (NHS) Provider in South London. We present early descriptive data for the linkage database and the robust data security and governance structures, and describe the intended expansion of the database from its original development. Additionally, we report details of the accompanying eLIXIR Research Tissue Bank of maternal and neonatal blood samples. PARTICIPANTS: Descriptive data were generated from the eLIXIR database from 1 October 2018 to 30 June 2019. Over 17 000 electronic patient records were included. FINDINGS TO DATE: 10 207 women accessed antenatal care from the 2 NHS maternity services, with 8405 deliveries (8772 infants). This diverse, inner-city maternity service population was born in over 170 countries with an ethnic profile of 46.1% white, 19.1% black, 7.0% Asian, 4.1% mixed and 4.1% other. Of the 10 207 women, 11.6% had a clinical record in mental health services with 3.0% being treated during their pregnancy. This first data extract included 947 infants treated in the neonatal intensive care unit, of whom 19.1% were postnatal transfers from external healthcare providers. FUTURE PLANS: Electronic health records provide potentially transformative information for life course research, integrating physical and mental health disorders and outcomes in routine clinical care. The eLIXIR database will grow by ~14 000 new maternity cases annually, in addition to providing child follow-up data. Additional datasets will supplement the current linkage from other local and national resources, including primary care and hospital inpatient data for mothers and their children.

Schizophrenia around the time of pregnancy: leveraging population-based health data and electronic health record data to fill knowledge gaps.

BACKGROUND: Research in schizophrenia and pregnancy has traditionally been conducted in small samples. More recently, secondary analysis of routine healthcare data has facilitated access to data on large numbers of women with schizophrenia. AIMS: To discuss four scientific advances using data from Canada, Denmark and the UK from population-level health registers and clinical data sources. METHOD: Narrative review of research from these three countries to illustrate key advances in the area of schizophrenia and pregnancy. RESULTS: Health administrative and clinical data from electronic medical records have been used to identify population-level and clinical cohorts of women with schizophrenia, and follow them longitudinally along with their children. These data have demonstrated that fertility rates in women with schizophrenia have increased over time and have enabled documentation of the course of illness in relation with pregnancy, showing the early postpartum as the time of highest risk. As a result of large sample sizes, we have been able to understand the prevalence of and risk factors for rare outcomes that would be difficult to study in clinical research. Advanced pharmaco-epidemiological methods have been used to address confounding in studies of antipsychotic medications in pregnancy, to provide data about the benefits and risks of treatment for women and their care providers. CONCLUSIONS: Use of these data has advanced the field of research in schizophrenia and pregnancy. Future developments in use of electronic health records include access to richer data sources and use of modern technical advances such as machine learning and supporting team science.

Relapse in the first three months postpartum in women with history of serious mental illness.

BACKGROUND: Relapse of serious mental illness (psychotic and bipolar disorders; SMI) in the postpartum period is potentially devastating for mother and baby. There is limited evidence on whether medication in the perinatal period is protective against postpartum relapse for women with SMI particularly non-affective psychoses. We aimed to investigate risk factors for postpartum relapse, particularly the potential prophylactic effects of medication. METHODS: Using an anonymised resource of comprehensive electronic secondary mental health care records linked with maternity data, women with history of SMI who gave birth from 2007 to 2011 were identified. Relapse was defined as admission to acute care in the first 3 months postpartum. Women who were exposed to regular medication were compared with women who were unexposed. Data were analysed by pregnancy using random effects models to account for repeated measures in women who had more than one pregnancy in the study period. RESULTS: There were 452 full term pregnancies, of which 128 (28.3%) were associated with relapse in the first 3 months postpartum, with recent relapse an independent predictor (aOR; 95% CI:1.30-2.27). There was no evidence of a prophylactic effect of medication (crude OR = 0.65; 0.34-1.25) (aOR = 0.99; 0.54-1.83), in women with non-affective or affective psychoses (interaction test p = 0.453). CONCLUSIONS: Recent relapse increases the risk of relapse in the postpartum period so women with severe illnesses with a recent history of relapse should be warned pre-conception about the high risk of relapse. The lack of evidence of a protective impact of medication prophylaxis may reflect confounding by indication.

Predictors of severe relapse in pregnant women with psychotic or bipolar disorders.

Pregnancy in women with severe mental illness is associated with adverse outcomes for mother and infant. There are limited data on prevalence and predictors of relapse in pregnancy. A historical cohort study using anonymised comprehensive electronic health records from secondary mental health care linked with national maternity data was carried out. Women with a history of serious mental illness who were pregnant (2007-2011), and in remission at the start of pregnancy, were studied; severe relapse was defined as admission to acute care or self-harm. Predictors of relapse were analysed using random effects logistic regression to account for repeated measures in women with more than one pregnancy in the study period. In 454 pregnancies (389 women) there were 58 (24%) relapses in women with non-affective psychoses and 25 (12%) in women with affective psychotic or bipolar disorders. Independent predictors of relapse included non-affective psychosis (adjusted OR = 2.03; 95% CI = 1.16-3.54), number of recent admissions (1.37; 1.03-1.84), recent self-harm (2.24; 1.15-4.34), substance use (2.15; 1.13-4.08), smoking (2.52; 1.26-5.02) and non-white ethnicity (black ethnicity: 2.37; 1.23-4.57, mixed/other ethnicity: 2.94; 1.32-6.56). Women on no regular medication throughout first trimester were also at greater risk of relapse in pregnancy (1.99; 1.05-3.75). There was no interaction between severity of illness and medication status as relapse predictors. Therefore, women with non-affective psychosis and higher number of recent acute admissions are at significant risk of severe relapse in pregnancy. Continuation of medication in women with severe mental illness who become pregnant may be protective.

Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies.

BACKGROUND: Concerns about teratogenicity and maternal and offspring complications restrict the use of lithium during pregnancy for the treatment of mood disorders. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity, and congenital malformations. METHODS: In this meta-analysis, primary data from pregnant women and their children from six international cohorts based in the community (Denmark, Sweden, and Ontario, Canada) and in clinics (the Netherlands, UK, and USA) were analysed. Pregnancies were eligible for analysis if the pregnancy resulted in a liveborn singleton between 1997 and 2015, if health-related information was available for both mother and infant, and if the mother had a mood disorder (bipolar disorder or major depressive disorder) or if she had been given lithium during pregnancy (at least two dispensations of lithium during pregnancy that were dispensed any time from 1 month before conception until the delivery, or a single lithium dispensation during pregnancy when there was at least one other lithium dispensation within 6 months before or after this date). Pregnancies during which the mother had been prescribed known teratogenic drugs were excluded. Pregnancies were grouped into a lithium-exposed group and a mood disorder reference group. The main outcome measures were pregnancy complications, delivery outcomes, neonatal readmission to hospital within 28 days of birth, and congenital malformations (major malformations and major cardiac malformations). Analyses were done at each site by use of a shared protocol. Adjusted odds ratios (aORs) and 95% CIs were calculated by use of logistic regression models, and site-specific prevalence rates and ORs were pooled by use of random-effects meta-analytical models. FINDINGS: 22   124 eligible pregnancies were identified across the six cohorts, of which 727 pregnancies were eligible for inclusion in the lithium-exposed group (557 [77%] from register-based cohorts and 170 [23%] from clinical cohorts). Lithium exposure was not associated with any of the predefined pregnancy complications or delivery outcomes. An increased risk for neonatal readmission within 28 days of birth was seen in the lithium-exposed group compared with the reference group (pooled prevalence 27·5% [95% CI 15·8-39·1] vs 14·3% [10·4-18·2]; pooled aOR 1·62, 95% CI 1·12-2·33). Lithium exposure during the first trimester was associated with an increased risk of major malformations (pooled prevalence 7·4% [95% CI 4·0-10·7] vs 4·3% [3·7-4·8]; pooled aOR 1·71, 95% CI 1·07-2·72) but for major cardiac malformations the difference was not significant (2·1% [0·5-3·7] vs 1·6% [1·0-2·1]; pooled aOR 1·54, 95% CI 0·64-3·70). INTERPRETATION: Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy-in particular those associated with use of lithium during the first trimester-against its effectiveness at reducing relapse. FUNDING: None.

The prevalence and correlates of self-harm in pregnant women with psychotic disorder and bipolar disorder.

Women with severe mental illness are at increased risk of suicide in the perinatal period, and these suicides are often preceded by self-harm, but little is known about self-harm and its correlates in this population. This study aimed to investigate the prevalence of suicidal ideation and self-harm, and its correlates, in women with psychotic disorders and bipolar disorder during pregnancy. Historical cohort study using de-identified secondary mental healthcare records linked with national maternity data. Women pregnant from 2007 to 2011, with ICD-10 diagnoses of schizophrenia and related disorders, bipolar disorder or other affective psychoses were identified. Data were extracted from structured fields, natural language processing applications and free text. Logistic regression was used to examine the correlates of self-harm in pregnancy. Of 420 women, 103 (24.5 %) had a record of suicidal ideation during the first index pregnancy, with self-harm recorded in 33 (7.9 %). Self-harm was independently associated with younger age (adjusted odds ratio (aOR) 0.91, 95 % CI 0.85-0.98), self-harm in the previous 2 years (aOR 2.55; 1.05-6.50) and smoking (aOR 3.64; 1.30-10.19). A higher prevalence of self-harm was observed in women with non-affective psychosis, those who discontinued or switched medication and in women on no medication at the start of pregnancy, but these findings were not statistically significant in multivariable analyses. Suicidal thoughts and self-harm occur in a significant proportion of pregnant women with severe mental illness, particularly younger women and those with a history of self-harm; these women need particularly close monitoring for suicidality.

The characteristics and health needs of pregnant women with schizophrenia compared with bipolar disorder and affective psychoses.

BACKGROUND: Most women with psychotic disorders and bipolar disorders have children but their pregnancies are at risk of adverse psychiatric and fetal outcome. The extent of modifiable risk factors - both clinical and socio-demographic - is unclear as most studies have used administrative data or recruited from specialist tertiary referral clinics. We therefore aimed to investigate the socio-demographic and clinical characteristics of an epidemiologically representative cohort of pregnant women with affective and non-affective severe mental illness. METHODS: Women with severe mental illness were identified from a large electronic mental health case register in south London, and a data linkage with national maternity Hospital Episode Statistics identified pregnancies in 2007-2011. Data were extracted using structured fields, text searching and natural language processing applications. RESULTS: Of 456 pregnant women identified, 236 (51.7%) had schizophrenia and related disorders, 220 (48.3%) had affective psychosis or bipolar disorder. Women with schizophrenia and related disorders were younger, less likely to have a partner in pregnancy, more likely to be black, to smoke or misuse substances and had significantly more time in the two years before pregnancy in acute care (inpatient or intensive home treatment) compared with women with affective disorders. Both groups had high levels of domestic abuse in pregnancy (recorded in 18.9%), were from relatively deprived backgrounds and had impaired functioning measured by the Health of the Nation Outcome Scale. Women in the affective group were more likely to stop medication in the first trimester (39% versus 25%) whereas women with non-affective psychoses were more likely to switch medication. CONCLUSIONS: A significant proportion of women, particularly those with non-affective psychoses, have modifiable risk factors requiring tailored care to optimize pregnancy outcomes. Mental health professionals need to be mindful of the possibility of pregnancy in women of childbearing age and prescribe and address modifiable risk factors accordingly.

The association of dementia with upper arm and waist circumference in seven low- and middle-income countries: the 10/66 cross-sectional surveys.

BACKGROUND: Weight loss in dementia contributes to morbidity and mortality but the distribution of anthropometric change and its consistency between populations are less clear. Our aim was to investigate and compare the associations of dementia with waist and upper arm circumference in elders from seven low- and middle-income nations. METHODS: Cross-sectional surveys were conducted of 15,022 residents aged 65 years and older in Cuba, Mexico, Venezuela, Peru, Dominican Republic, China, and India. Dementia was assessed using a cross-culturally validated algorithm, and anthropometric measurements were taken. Associations with dementia and dementia severity (clinical dementia rating scale) were investigated in linear regression models, with fixed-effects meta-analyses used to investigate between-country heterogeneity. RESULTS: Dementia and increased dementia severity were both associated with smaller arm and waist circumferences with little evidence of confounding by sociodemographic and health status. Associations between dementia/clinical dementia rating and arm circumference were homogeneous between countries (Higgins I(2) 0% and 7%, respectively), whereas those with waist circumference were more heterogeneous (Higgins I(2) 67% and 62%, respectively). CONCLUSIONS: Although cross-sectional, our findings are consistent with prospective observations of weight loss in dementia and suggest loss of both muscle and fat-the former being consistent across different settings and the latter being more context dependent.