Antidepressant discontinuation before or during pregnancy and risk of psychiatric emergency in Denmark: A population-based propensity score-matched cohort study.

BACKGROUND: Women prescribed antidepressants face the dilemma of whether or not to continue their treatment during pregnancy. Currently, limited evidence is available on the efficacy of continuing versus discontinuing antidepressant treatment during pregnancy to aid their decision. We aimed to estimate whether antidepressant discontinuation before or during pregnancy was associated with an increased risk of psychiatric emergency (ascertained by psychiatric admission or emergency room visit), a proxy measure of severe exacerbation of symptoms/mental health crisis. METHODS AND FINDINGS: We carried out a propensity score-matched cohort study of women who gave birth to live-born singletons between January 1, 1997 and June 30, 2016 in Denmark and who redeemed an antidepressant prescription in the 90 days before the pregnancy, identified by Anatomical Therapeutic Chemical (ATC) code N06A. We constructed 2 matched cohorts, matching each woman who discontinued antidepressants before pregnancy (N = 2,669) or during pregnancy (N = 5,467) to one who continued antidepressants based on propensity scores. Maternal characteristics and variables related to disease severity were used to generate the propensity scores in logistic regression models. We estimated hazard ratios (HRs) of psychiatric emergency in the perinatal period (pregnancy and 6 months postpartum) using stratified Cox regression. Psychiatric emergencies were observed in 76 women who discontinued antidepressants before pregnancy and 91 women who continued. There was no evidence of higher risk of psychiatric emergency among women who discontinued antidepressants before pregnancy (cumulative incidence: 2.9%, 95% confidence interval [CI]: 2.3% to 3.6% for discontinuation versus 3.4%, 95% CI: 2.8% to 4.2% for continuation; HR = 0.84, 95% CI: 0.61 to 1.16, p = 0.298). Overall, 202 women who discontinued antidepressants during pregnancy and 156 who continued had psychiatric emergencies (cumulative incidence: 5.0%, 95% CI: 4.2% to 5.9% versus 3.7%, 95% CI: 3.1% to 4.5%). Antidepressant discontinuation during pregnancy was associated with increased risk of psychiatric emergency (HR = 1.25, 95% CI: 1.00 to 1.55, p = 0.048). Study limitations include lack of information on indications for antidepressant treatment and reasons for discontinuing antidepressants. CONCLUSIONS: In this study, we found that discontinuing antidepressant medication during pregnancy (but not before) is associated with an apparent increased risk of psychiatric emergency compared to continuing treatment throughout pregnancy.

Antidepressant use during pregnancy and risk of adverse neonatal outcomes: A comprehensive investigation of previously identified associations.

OBJECTIVE: Prenatal antidepressant use is widespread. Observational studies have investigated the neonatal effects of prenatal antidepressant exposure with inconclusive results. We aimed to comprehensively investigate the associations between prenatal antidepressant exposure and the most commonly studied adverse neonatal outcomes: preterm birth, birthweight, poor neonatal adaptation, persistent pulmonary hypertension of the neonate (PPHN), neonatal admission and congenital malformations. METHODS: We included 45,590 singletons (born 1997-2015) whose mothers used antidepressants within one year before pregnancy. Children were categorised into two groups: continuation (antidepressant use before and during pregnancy) or discontinuation (antidepressant use before but not during pregnancy). We applied random-effects logistic and linear regressions, adjusting for covariates. RESULTS: After adjusting for confounders, prenatal antidepressant exposure was associated with a 2.3 day (95% CI -2.9; -2.0) decrease in gestational age and a 51 g (95% CI -62g; -41 g) decrease in birthweight. The continuation group was at increased risk for moderate-to-late preterm birth (32-37 weeks) (aOR = 1.43; 95%CI 1.33; 1.55), moderately low birthweight (1500-2499 g) (aOR = 1.28; 95%CI 1.17; 1.41), postnatal adaptation syndrome (aOR = 2.59; 95%CI 1.87; 3.59) and neonatal admission (aOR = 1.52; 95%CI 1.44; 1.60) compared to the discontinuation group. CONCLUSION: Prenatal antidepressant exposure was associated with small decreases in gestational age and birthweight, as well as higher risk for moderate-to-late preterm birth, moderately low birthweight, neonatal admission and postnatal adaptation syndrome. No differences in risk were found for PPHN, or congenital malformations. The causality of the observed associations cannot be established due to the potential for unmeasured residual confounding linked to the underlying disease.

SARS-CoV-2 during pregnancy and associated outcomes: Results from an ongoing prospective cohort.

BACKGROUND: The COVID-19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Questions remain about how SARS-CoV-2 impacts pregnant individuals and their children. OBJECTIVE: To expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. METHODS: The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT-PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. RESULTS: The SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS-CoV-2 RT-PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. CONCLUSION: Seropositivity for SARS-CoV-2 without RT-PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

Management of lithium dosing around delivery: An observational study.

OBJECTIVES: Recommendations on lithium dosing around delivery vary, with several guidelines suggesting that lithium should be discontinued prior to delivery. We aimed to evaluate the validity of these recommendations by investigating 1) maternal lithium blood level changes following delivery, and 2) the association between neonatal lithium blood levels at delivery and neonatal outcomes. METHODS: In this retrospective observational cohort study, we included women with at least one lithium blood level measurement during the final week of pregnancy and the first postpartum week. For aim 2, we included a subcohort of women with neonates for whom neonatal lithium blood levels (obtained from the umbilical cord or a neonatal vein puncture within 24 hours of delivery) were available. RESULTS: There were a total of 233 maternal lithium blood level measurements; 55 (23.6%) in the week before delivery and 178 (76.4%) in the week after. There was no association between time and lithium blood level/dose ratio (Pearson correlation coefficient -0.03, P = .63). Additionally, we included a total of 29 neonates for whom a lithium measurement was performed within 24 hours postpartum. Maternal and neonatal lithium blood levels were strongly correlated. We observed no associations between neonatal lithium blood levels at delivery and neonatal outcomes. CONCLUSION: Based on our findings, we do not recommend lowering the dosage or discontinuation of lithium prior to delivery. Stable dosing can prevent subtherapeutic lithium serum levels, which is especially important in the postpartum period when relapse risks are highest.

Dispensing patterns of selective serotonin reuptake inhibitors before, during and after pregnancy: a 16-year population-based cohort study from the Netherlands.

Management of mental illness in the perinatal period with antidepressants is controversial, since evidence emerged on potential harmful effects to the unborn child. However, over time, the dispensing of antidepressants in the perinatal period has increased. We examined perinatal dispensing patterns over time and the role of a recently issued guideline in this regard. We identified a 16-year cohort of 153,952 Dutch pregnancies with a delivery date between January 1999 and December 2014. Data included exposure to selective serotonin reuptake inhibitors (SSRIs) related to phases of pregnancy (preconception, pregnancy and delivery, post-delivery). The chi-square test for trends was used. With standard logistic regression, we explored the influence of patient characteristics on continuation of SSRIs during pregnancy. A persistent significant rise of dispensing rates in all phases was observed, with the largest increase during pregnancy (from 0.8% in 1999/2000 to 2.1% in 2013/2014, chi-square for trend = 141.735, p < 0.001). A substantial change of practice in terms of the SSRI used (less paroxetine) and the policy towards continuation into pregnancy (more continuation over time) was visible. Concomitant use of psycholeptics halved the probability of continuation of SSRIs (OR 0.50, 95%CI 0.43-0.55, p < 0.01). Dispensing rates of SSRIs steadily increased last 16 years, especially during pregnancy, caused by an increase in the proportion of women continuing their medication during pregnancy. In view of the demonstrated impact of uncertainty regarding effectiveness and safety of SSRIs in pregnancy, future research should involve more detailed outcome research of SSRIs as it is, and research into viable alternatives.

Guidelines on treatment of perinatal depression with antidepressants: An international review.

OBJECTIVE: Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice. METHODS: An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients. RESULTS: Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines. CONCLUSION: During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.

Vesicoureteral Reflux in Kidney Transplantation.

BACKGROUND: Vesicoureteral reflux (VUR) is frequently found after transplantation, but its impact on graft function, urine tract infection, and graft loss remains uncertain. Therefore our objective was to evaluate the effects of VUR on the outcome of renal transplantation. MATERIAL AND METHODS: We included 1008 adult renal transplant recipients of whom a 1-week posttransplant voiding cystourethrogram was available. Study end points included occurrence of bacteriuria, renal function, and graft survival. RESULTS: In total, 106 (10.5%) of 1008 graft recipients had a diagnosis of VUR on voiding cystography. The incidence of bacteriuria was comparable in the reflux and nonreflux group (17% vs 17.4%, P = .91). There was no significant difference in renal function at 3 months and 1 year in patients with and without VUR. One- and 5-year graft survival in patients with VUR was 85.8% and 82.1% compared to 87.3% and 83.0% in patients without VUR ( P = .68 and P = .80). CONCLUSION: Posttransplant VUR has no correlations with early bacteriuria, renal function, and graft survival.

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.

BACKGROUND: Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. METHODS/DESIGN: 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk. DISCUSSION: This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR4694 ; registration date: 16-jul-2014.

Management of Lithium Dosing Around Delivery: An Observational Study.

Objectives: Recommendations on lithium dosing around delivery vary, with several guidelines suggesting that lithium should be discontinued prior to delivery. We aimed to evaluate the validity of these recommendations by investigating 1) maternal lithium blood level changes following delivery, and 2) the association between neonatal lithium blood levels at delivery and neonatal outcomes. Methods: In this retrospective observational cohort study, we included women with at least one lithium blood level measurement during the final week of pregnancy and the first postpartum week. For aim 2, we included a subcohort of women with neonates for whom neonatal lithium blood levels (obtained from the umbilical cord or a neonatal vein puncture within 24 hours of delivery) were available. Results: There were a total of 233 maternal lithium blood level measurements; 55 (23.6%) in the week before delivery and 178 (76.4%) in the week after. There was no association between time and lithium blood level/dose ratio (Pearson correlation coefficient -0.03, P = .63). Additionally, we included a total of 29 neonates for whom a lithium measurement was performed within 24 hours postpartum. Maternal and neonatal lithium blood levels were strongly correlated. We observed no associations between neonatal lithium blood levels at delivery and neonatal outcomes. Conclusion: Based on our findings, we do not recommend lowering the dosage or discontinuation of lithium prior to delivery. Stable dosing can prevent subtherapeutic lithium serum levels, which is especially important in the postpartum period when relapse risks are highest.Appeared originally in Bipolar Disord 2021; 23:49-54.

Increased postpartum anxiety symptoms after perinatal SARS-CoV-2 infection in a large, prospective pregnancy cohort in New York City.

Numerous studies reported an increase of postpartum mood symptoms during the COVID-19 pandemic. Yet, the link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and perinatal mental health is less well understood. We investigated the associations between prenatal SARS-CoV-2 infection and postpartum depressive and anxiety symptoms, including examinations of infection timing and pandemic timeline. We included 595 participants from Generation C, a prospective pregnancy cohort in New York City (2020-2022). Prenatal SARS-CoV-2 infection was determined via laboratory or medical diagnosis. Depression and anxiety symptoms were measured 4-12 weeks postpartum using the Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder questionnaire (GAD), respectively. Quantile regressions were conducted with prenatal SARS-CoV-2 infection as exposure and continuously measured EPDS and GAD scores as outcomes. We reran the analyses in those with COVID-19-like symptoms in the trimester during which infection occurred. 120 (20.1%) participants had prenatal SARS-CoV-2 infection. After adjusting for socio-demographic, obstetric and other maternal health factors, prenatal SARS-CoV-2 infection was associated with higher median postpartum anxiety scores (b = 0.55, 95% CI = 0.15; 0.96). Late gestation infection (b = 1.15, 95% CI = 0.22; 2.09) and symptomatic infection (b = 1.15, 95% CI = 0.12; 2.18) were also associated with higher median postpartum anxiety scores. No associations were found with depressive symptoms. The associations were not moderated by time since the start of the pandemic. This study suggests that prenatal SARS-CoV-2 infection increases the risk of postpartum anxiety symptoms among participants reporting median anxiety symptoms. Given that this association was not affected by pandemic timing and that SARS-CoV-2 transmission continues, individuals infected with SARS-CoV-2 during pregnancy should be monitored for postpartum anxiety symptoms.

SARS-CoV-2 infection, inflammation and birth outcomes in a prospective NYC pregnancy cohort.

Associations between antenatal SARS-CoV-2 infection and pregnancy outcomes have been conflicting and the role of the immune system is currently unclear. This prospective cohort study investigated the interaction of antenatal SARS-CoV-2 infection, changes in cytokine and HS-CRP levels, birthweight and gestational age at birth. 2352 pregnant participants from New York City (2020-2022) were included. Plasma levels of interleukin (IL)-1ß, IL-6, IL-17A and high-sensitivity C-reactive protein (HS-CRP) were quantified in blood specimens obtained across pregnancy. Quantile and linear regression models were conducted to 1) assess the impact of antenatal SARS-CoV-2 infection, overall and by timing of detection of SARS-CoV-2 positivity (< 20 weeks versus ≥ 20 weeks), on birthweight and gestational age at delivery; 2) examine the relationship between SARS-CoV-2 infection and maternal immune changes during pregnancy. All models were adjusted for maternal demographic and obstetric factors and pandemic timing. Birthweight models were additionally adjusted for gestational age at delivery and fetal sex. Immune marker models were also adjusted for gestational age at specimen collection and multiplex assay batch. 371 (15.8%) participants were infected with SARS-CoV-2 during pregnancy, of which 98 (26.4%) were infected at < 20 weeks gestation. Neither SARS-CoV-2 infection in general nor in early or late pregnancy was associated with lower birthweight nor earlier gestational age at delivery. Further, we did not observe cytokine or HS-CRP changes in response to SARS-CoV-2 infection and thus found no evidence to support a potential association between immune dysregulation and the diversity in pregnancy outcomes following infection.

The incidence of depressive episodes is different before, during, and after pregnancy: A population-based study.

BACKGROUND: Depressive episodes during pregnancy are widely investigated but it is still unknown whether pregnancy is a high-risk period compared to the pre-pregnancy period. Therefore, we aimed to investigate the incidence and recurrence of depressive episodes before, during, and after pregnancy. METHODS: In the current population-based registry study, we calculated monthly incidence and recurrence of psychiatric inpatient admissions and outpatient psychiatric contact for depressive episodes. We identified a population consisting of all first childbirths in Denmark from 1999 through 2015 (N = 392,287). RESULTS: Incidence of inpatient admission during pregnancy was lower than before pregnancy. After childbirth, a significant increase in first-time and recurrent psychiatric inpatient admissions was observed, especially in the first months. In contrast, outpatient psychiatric treatment incidence and recurrence were increased both during pregnancy as well as in the postpartum period, as compared to pre-pregnancy. LIMITATIONS: Analyses were performed on depressive episodes representing the severe end of the spectrum, questioning generalizability to milder forms of depression treated outside psychiatric specialist treatment facilities. CONCLUSION: We found a different pattern of severe episodes of depression compared to moderate episodes before, during, and after pregnancy. In light of our findings and those of others, we suggest distinguishing between timing of onset in the classification of depression in the perinatal period: Depression with pregnancy onset OR with postpartum onset (instead of the current DSM classifier "with perinatal onset"), as well as severity of depression, which is important for both clinical and future research endeavors.

Intergenerational impact of childhood trauma on hair cortisol concentrations in mothers and their young infants.

Background: Alterations in stress regulation and function of the hypothalamic-pituitary-adrenal (HPA) axis during infancy may be a risk factor for the development of psychopathology later in life. Maternal childhood trauma, depression, anxiety and stressful life events are individually associated with HPA axis dysregulation. Less is known about their interdependent influence on maternal and infant stress regulation in at risk populations. In a sample of mothers with a history of depressive-, and/or anxiety disorders and their infants we explored if a history of maternal childhood trauma, current depressive and anxiety symptomatology, and recent life events were associated with maternal and infant long-term cortisol levels three months postpartum. Methods: Data were available of 89 mothers and 49 infants. All mothers fulfilled criteria for a lifetime depressive or anxiety disorder. Diagnosis was established with a diagnostic interview. Current depressive symptomatology was assessed with the Edinburgh Postnatal Depression Scale (EPDS), current anxiety with the State-Trait Anxiety Inventory (STAI), maternal childhood trauma with the Childhood Trauma Questionnaire (CTQ) and recent life events with the Everyday Problem Checklist (EPC). Maternal and infant hair cortisol concentrations (HCC) were quantified with liquid chromatography with tandem mass spectrometry (LC-MS/MS) three months after birth. Total scores of the CTQ and subscales, EPDS, STAI, and EPC were regressed on maternal and infant HCC using regression analyses. Differences in HCC regarding trauma history were tested with t-tests. Potential confounders were identified and adjusted for. Results: In regression analyses, a positive curvilinear relationship was found between CTQ total score and maternal HCC (n = 83, B = 0.076, SE 0.033, p = .021), but not for current depression (n = 88, B = -0.001, SE 0.011, p = .931), current anxiety (n = 88, B = 0.002, SE 0.004, p = .650) or recent life events (n = 89, B = 0.018, SE 0.032, p = .568). Analyses were adjusted for confounders. A negative linear relationship was found between maternal CTQ score and infant HCC (n = 49, ß = -0.264, B = -0.006, SE 0.003, p = .052), but not for current maternal depression (n = 45, ß = -0.182, B = -0.011, SE 0.008, p = .164), current maternal anxiety (n = 45, ß = -0.209, B = -0.005, SE 0.003, p = .113) or recent life events (n = 46, ß = -0.128, B = -0.022, SE 0.023, p = .325). Analyses were adjusted for relevant infant hair characteristics. Specifically, maternal emotional and physical neglect were related to HCC in both mothers and infants. Conclusions: Results suggest that maternal childhood trauma is more prominent in altering maternal and infant long-term cortisol levels than perinatal depressive and anxiety symptomatology or recent life stressors in mothers with a history of depressive and/or anxiety disorders, and their infants. As infants of mothers with psychopathology are at increased risk for later psychiatric disease, future studies should investigate the interplay of possible risk factors for transgenerational transmission, intra-uterine programming of the HPA axis, including (epi-)genetic phenomena, of the HPA axis, and the influence of parenting impairment.

Impact of prenatal COVID-19 vaccination on delivery and neonatal outcomes: Results from a New York City cohort.

Research suggest prenatal vaccination against coronavirus disease-19 (COVID-19) is safe. However, previous studies utilized retrospectively collected data or examined late pregnancy vaccinations. We investigated the associations of COVID-19 vaccination throughout pregnancy with delivery and neonatal outcomes. We included 1,794 mother-neonate dyads enrolled in the Generation C Study with known prenatal COVID-19 vaccination status and complete covariate and outcome data. We used multivariable quantile regressions to estimate the effect of prenatal COVID-19 vaccination on birthweight, delivery gestational age, and blood loss at delivery; and Poisson generalized linear models for Caesarean delivery (CD) and Neonatal Intensive Care Unit (NICU) admission. Using the above methods, we estimated effects of trimester of vaccine initiation on these outcomes. In our sample, 13.7% (n = 250) received at least one prenatal dose of any COVID-19 vaccine. Vaccination was not associated with birthweight (ß = 12.42 g [-90.5, 114.8]), gestational age (ß = 0.2 days [-1.1, 1.5]), blood loss (ß = -50.6 ml [-107.0, 5.8]), the risks of CD (RR = 0.8; [0.6, 1.1]) or NICU admission (RR = 0.9 [0.5, 1.7]). Trimester of vaccine initiation was also not associated with these outcomes. Our findings suggest that there is no associated risk between prenatal COVID-19 vaccination and adverse delivery and neonatal outcomes in a cohort sample from NYC.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Titer Levels in Pregnant Individuals After Infection, Vaccination, or Both.

We examined differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses in pregnant individuals with natural, vaccine-induced, or combined immunity. Participants had live or nonlive births between 2020 and 2022, were seropositive (SARS-CoV-2 spike protein, anti-S), and had available mRNA vaccination and infection information (n=260). We compared titer levels among three immunity profiles: 1) natural immunity (n=191), 2) vaccine-induced immunity (n=37), and 3) combined immunity (ie, natural and vaccine-induced immunity; n=32). We applied linear regression to compare anti-S titers between the groups, controlling for age, race and ethnicity, and time between vaccination or infection (whichever came last) and sample collection. Anti-S titers were 57.3% and 94.4% lower among those with vaccine-induced and natural immunity, respectively, compared with those with combined immunity ( P <.001, P =.005).

The influence of structural racism, pandemic stress, and SARS-CoV-2 infection during pregnancy with adverse birth outcomes.

BACKGROUND: Structural racism and pandemic-related stress from the COVID-19 pandemic may increase the risk of adverse birth outcomes. OBJECTIVE: Our objective was to examine associations between neighborhood measures of structural racism and pandemic stress with 3 outcomes: SARS-CoV-2 infection, preterm birth, and delivering small-for-gestational-age newborns. Our secondary objective was to investigate the joint association of SARS-CoV-2 infection during pregnancy and neighborhood measures with preterm birth and delivering small-for-gestational-age newborns. STUDY DESIGN: We analyzed data of 967 patients from a prospective cohort of pregnant persons in New York City, comprising 367 White (38%), 169 Black (17%), 293 Latina (30%), and 87 Asian persons (9%), 41 persons of other race or ethnicity (4%), and 10 of unknown race or ethnicity (1%). We evaluated structural racism (social/built structural disadvantage, racial-economic segregation) and pandemic-related stress (community COVID-19 mortality, community unemployment rate increase) in quartiles by zone improvement plan code. SARS-CoV-2 serologic enzyme-linked immunosorbent assay was performed on blood samples from pregnant persons. We obtained data on preterm birth and small-for-gestational-age newborns from an electronic medical record database. We used log-binomial regression with robust standard error for clustering by zone improvement plan code to estimate associations of each neighborhood measure separately with 3 outcomes: SARS-CoV-2 infection, preterm birth, and small-for-gestational-age newborns. Covariates included maternal age, parity, insurance status, and body mass index. Models with preterm birth and small-for-gestational-age newborns as the dependent variables additionally adjusted for SARS-CoV-2 infection. RESULTS: A total of 193 (20%) persons were SARS-CoV-2-seropositive, and the overall risks of preterm birth and small-for-gestational-age newborns were 8.4% and 9.8%, respectively. Among birthing persons in neighborhoods in the highest quartile of structural disadvantage (n=190), 94% were non-White, 50% had public insurance, 41% were obese, 32% were seropositive, 11% delivered preterm, and 12% delivered a small-for-gestational-age infant. Among birthing persons in neighborhoods in the lowest quartile of structural disadvantage (n=360), 39% were non-White, 17% had public insurance, 15% were obese, 9% were seropositive, 6% delivered preterm, and 10% delivered a small-for-gestational-age infant. In adjusted analyses, structural racism measures and community unemployment were associated with both SARS-CoV-2 infection and preterm birth, but not small-for-gestational-age infants. High vs low structural disadvantage was associated with an adjusted relative risk of 2.6 for infection (95% confidence interval, 1.7-3.9) and 1.7 for preterm birth (95% confidence interval, 1.0-2.9); high vs low racial-economic segregation was associated with adjusted relative risk of 1.9 (95% confidence interval, 1.3-2.8) for infection and 2.0 (95% confidence interval, 1.3-3.2) for preterm birth; high vs low community unemployment increase was associated with adjusted relative risk of 1.7 (95% confidence interval, 1.2-1.5) for infection and 1.6 (95% confidence interval, 1.0-2.8) for preterm birth. COVID-19 mortality rate was associated with SARS-CoV-2 infection but not preterm birth or small-for-gestational-age infants. SARS-CoV-2 infection was not independently associated with birth outcomes. We found no interaction between SARS-CoV-2 infection and neighborhood measures on preterm birth or small-for-gestational-age infants. CONCLUSION: Neighborhood measures of structural racism were associated with both SARS-CoV-2 infection and preterm birth, but these associations were independent and did not have a synergistic effect. Community unemployment rate increases were also associated with an increased risk of preterm birth independently of SARS-CoV-2 infection. Mitigating these factors might reduce the impact of the pandemic on pregnant people.

Discontinuation of antidepressants: Is there a minimum time on treatment that will reduce relapse risk?

BACKGROUND: Several national guidelines include recommendations for a minimum duration of antidepressant treatment, but these vary from 4-9 months after remission. We aimed to investigate whether there is an optimal minimum duration of antidepressant treatment to reduce relapse risk. METHODS: A Danish population-based cohort study among 89,442 adults who initiated antidepressants for depression treatment aged 18-60 years, from 2006-2015. We defined antidepressant discontinuation as ≥30 days without treatment. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) to indicate the risk of restarting antidepressants among those who discontinued antidepressants with <4, 4-6, and 7-9 months of use compared with discontinuation after 10-12 months. RESULTS: For individuals on antidepressant treatment <4, 4-6, 7-9 and 10-12 months, cumulative incidence of restarting treatment within one year was 37.4% (95% CI: 36.9-37.8%), 35.1% (95% CI: 34.6-35.7%), 35.0% (95% CI: 34.2-35.8%) and 32.8% (95% CI: 31.7-34.0%), respectively. Individuals on antidepressants <10 months versus 10-12 months had higher risk of restarting antidepressants: the HR for antidepressant treatment <4 months was 1.21 (95% CI: 1.16-1.27), 4-6 months 1.11 (95% CI: 1.06-1.17), and 7-9 months 1.09 (95% CI: 1.04-1.15). LIMITATIONS: We were not able to ascertain the reasons why individuals discontinued antidepressants, and systematic errors from unmeasured confounders cannot be ruled out. CONCLUSIONS: Based on our findings, a minimum of 10-12 months of treatment appears to be preferable if there is concern about relapse after discontinuation.

Long-term outcome of postpartum psychosis: a prospective clinical cohort study in 106 women.

OBJECTIVE: We aimed to investigate the outcome of postpartum psychosis over a four-year follow-up, and to identify potential clinical markers of mood/psychotic episodes outside of the postpartum period. METHODS: One hundred and six women with a diagnosis of first-onset mania or psychosis during the postpartum period were included in this prospective longitudinal study. Women were categorized into either (1) recurrence of non-postpartum mood/psychotic episodes or (2) mania/psychosis limited to the postpartum period. We summarize the longitudinal course of the illness per group. We used a logistic regression model to identify clinical predictors of recurrence of mood/psychotic episodes outside of the postpartum period. RESULTS: Over two thirds of the women included in this study did not have major psychiatric episodes outside of the postpartum period during follow-up. The overall recurrence rate of mood/psychotic episodes outside the postpartum period was ~ 32%. Of these women, most transitioned to a bipolar disorder diagnosis. None of the women fulfilled diagnostic criteria for schizophrenia or schizophreniform disorder. No clinical markers significantly predicted recurrence outside of the postpartum period. CONCLUSIONS: For the majority of women with first-onset postpartum psychosis, the risk of illness was limited to the period after childbirth. For the remaining women, postpartum psychosis was part of a mood/psychotic disorder with severe non-postpartum recurrence, mainly in the bipolar spectrum. No clinical predictors for risk of severe episodes outside the postpartum period emerged. Our findings add to previous evidence suggesting a fundamental link between postpartum psychosis and bipolar disorder, which may represent two distinct diagnoses within the same spectrum.

Long-term prenatal effects of antidepressant use on the risk of affective disorders in the offspring: a register-based cohort study.

To investigate the association between intrauterine antidepressant exposure and offspring affective disorders over an 18-year follow-up period using Danish national registers. We included 42,988 singletons born during 1998-2011 and followed-up until 2016, death, emigration, or date of first affective disorder diagnosis. Children were categorised into two groups according to maternal antidepressant use within 2 years before and during pregnancy: continuation (use before and during pregnancy) or discontinuation (use before but not during pregnancy). The outcome was an affective disorders diagnosis in the offspring based on secondary/tertiary care records and primary care prescription data. Hazard ratios (HR) of affective disorders were estimated using Cox regression models. To consider confounding by shared environmental or genetic factors, we investigated the effect of paternal antidepressant use on the risk for affective disorders. Affective disorders were diagnosed in 1538 children. Children whose mothers continued antidepressants during pregnancy had an increased risk of affective disorders (HR = 1.20, 95% CI = 1.08-1.34), compared with children whose mothers discontinued before pregnancy. Similarly, continued paternal antidepressant use during pregnancy was associated with higher risk for offspring affective disorders (HR = 1.29, 95% CI = 1.12-1.49), compared to discontinuation. Based on data from primary and secondary/tertiary care, maternal antidepressant use during pregnancy was associated with an increased risk of affective disorders in the offspring. As similar associations were observed in children whose fathers continued antidepressant use across the pregnancy period, the observed association may be attributable to the underlying parental psychopathology, rather than the direct intrauterine exposure to antidepressants.

Long-Term Effects of Intrauterine Exposure to Antidepressants on Physical, Neurodevelopmental, and Psychiatric Outcomes: A Systematic Review.

OBJECTIVE: Reviews on child outcomes following in utero antidepressant exposure have focused on short-term outcomes. However, several recent individual studies reported on adverse physical, neurodevelopmental, and psychiatric outcomes beyond infancy and early childhood. The objective of this systematic review was to establish the long-term effects of prenatal antidepressant exposure on physical, neurodevelopmental, and psychiatric outcomes in individuals aged 4 years and older. DATA SOURCES: Embase, MEDLINE Ovid, Web of Science, Cochrane Central, and Google Scholar were systematically searched for all relevant articles, written in English and published prior to November 8, 2018, using terms describing antidepressants, pregnancy, and developmental outcomes. STUDY SELECTION: All original research articles on long-term outcomes of prenatal antidepressant exposure were eligible for inclusion. After screening and removal of duplicates, a total of 34 studies were identified. DATA EXTRACTION: Included articles were qualitatively analyzed to determine inconsistency, indirectness, imprecision, and study bias. RESULTS: The identified studies demonstrated statistically significant associations between prenatal antidepressant exposure and a range of physical, neurodevelopmental, and psychiatric outcomes. Yet, the risk of confounding by indication was high. When controlling for confounders, 5 studies investigating physical outcomes (asthma, cancer, body mass index [BMI], epilepsy) found no association except conflicting outcomes for BMI. Eighteen studies examining neurodevelopmental outcomes (cognition, behavior, IQ, motor development, speech, language, and scholastic outcomes) found no consistent associations with antidepressant exposure after taking confounders into account. Eleven studies investigated psychiatric outcomes. After adjusting for confounders, prenatal antidepressant exposure was associated with affective disorders but not with childhood psychiatric outcomes (eg, autism spectrum disorders, attention-deficit/hyperactivity disorder). CONCLUSIONS: Reported associations between in utero exposure to antidepressants and physical, neurodevelopmental, and psychiatric outcomes, in large part, seem to be driven by the underlying maternal disorder. When limiting confounding by indication, prenatal exposure to antidepressants was significantly associated only with offspring BMI and affective disorders.