The longitudinal effects of stress and fear on psychiatric symptoms in mothers during the COVID-19 pandemic.

The COVID-19 pandemic has been particularly difficult for mothers. Women with a history of peripartum depression (PPD) may be vulnerable to relapse. We sought to understand changes in depressive and anxious symptoms throughout the pandemic and which stressors increased symptoms in women with a history of PPD. In June 2020, all US participants with a history of PPD (n = 12,007) in the global MomGenes Fight PPD study were invited to the COVID-19 follow-up study. Respondents (n = 2163, 18%) were sent biweekly and then monthly surveys until January 31, 2022. We employed time-varying effects models to evaluate trajectories of depressive (patient health questionnaire, PHQ-9) and anxious (generalized anxiety disorder, GAD-7) symptoms and to estimate longitudinal associations between perceived stress, fears, COVID-19 case rates, and symptoms. Peaks of PHQ-9, GAD-7, PSS, and perceived COVID-19 risk scores corresponded with timing of national COVID-19 case surges. High perceived stress was the strongest predictor of PHQ-9 (beta = 7.27; P = 1.48e - 38) and GAD-7 (beta = 7.73; P = 6.19e - 70). Feeling lack of control and unlikely to survive increased PHQ-9 and GAD-7 scores by 2 points. COVID-19 case rates, pandemic restrictions, and region were not independently associated with symptoms. This study suggests that the collective trauma of the pandemic has significantly affected mothers with a history of PPD, exemplified by high levels of perceived stress and the strong association with depressive and anxious symptoms. The next pandemic phase is uncertain, but will continue to influence mental health collectively and dynamically. Interventions must be flexible and responsive and should address fear, trauma, and feelings of control, particularly for mothers with a history of PPD.

Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?

OBJECTIVE: Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. STUDY DESIGN: We conducted a nested case-control study within the Norwegian Mother, Father and Child Birth Cohort (1999-2008) of 2,596 mother-child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. RESULTS: Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). CONCLUSION: Evidence for gene-smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene-environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures. KEY POINTS: · Maternal and fetal genotype may differentially influence preeclampsia.. · Smoking-related genes did not strongly modify smoking-preeclampsia association.. · Smoking cessation reduced strength of gene by smoking interactions..

A Family Based Study of Carbon Monoxide and Nitric Oxide Signalling Genes and Preeclampsia.

BACKGROUND: Preeclampsia is thought to originate during placentation, with incomplete remodelling and perfusion of the spiral arteries leading to reduced placental vascular capacity. Nitric oxide (NO) and carbon monoxide (CO) are powerful vasodilators that play a role in the placental vascular system. Although family clustering of preeclampsia has been observed, the existing genetic literature is limited by a failure to consider both mother and child. METHODS: We conducted a nested case-control study within the Norwegian Mother and Child Birth Cohort of 1545 case-pairs and 995 control-pairs from 2540 validated dyads (2011 complete pairs, 529 missing mother or child genotype). We selected 1518 single-nucleotide polymorphisms (SNPs) with minor allele frequency >5% in NO and CO signalling pathways. We used log-linear Poisson regression models and likelihood ratio tests to assess maternal and child effects. RESULTS: One SNP met criteria for a false discovery rate Q-value <0.05. The child variant, rs12547243 in adenylate cyclase 8 (ADCY8), was associated with an increased risk (relative risk [RR] 1.42, 95% confidence interval [CI] 1.20, 1.69 for AG vs. GG, RR 2.14, 95% CI 1.47, 3.11 for AA vs. GG, Q = 0.03). The maternal variant, rs30593 in PDE1C was associated with a decreased risk for the subtype of preeclampsia accompanied by early delivery (RR 0.45, 95% CI 0.27, 0.75 for TC vs. CC; Q = 0.02). None of the associations were replicated after correction for multiple testing. CONCLUSIONS: This study uses a novel approach to disentangle maternal and child genotypic effects of NO and CO signalling genes on preeclampsia.

Efficacy of Virtual Care for Depressive Disorders: Systematic Review and Meta-analysis.

BACKGROUND: The COVID-19 pandemic has created an epidemic of distress-related mental disorders such as depression, while simultaneously necessitating a shift to virtual domains of mental health care; yet, the evidence to support the use of virtual interventions is unclear. OBJECTIVE: The purpose of this study was to evaluate the efficacy of virtual interventions for depressive disorders by addressing three key questions: (1) Does virtual intervention provide better outcomes than no treatment or other control conditions (ie, waitlist, treatment as usual [TAU], or attention control)? (2) Does in-person intervention provide better outcomes than virtual intervention? (3) Does one type of virtual intervention provide better outcomes than another? METHODS: We searched the PubMed, EMBASE, and PsycINFO databases for trials published from January 1, 2010, to October 30, 2021. We included randomized controlled trials of adults with depressive disorders that tested a virtual intervention and used a validated depression measure. Primary outcomes were defined as remission (ie, no longer meeting the clinical cutoff for depression), response (ie, a clinically significant reduction in depressive symptoms), and depression severity at posttreatment. Two researchers independently selected studies and extracted data using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias was evaluated based on Agency for Healthcare and Research Quality guidelines. We calculated odds ratios (ORs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes. RESULTS: We identified 3797 references, 24 of which were eligible. Compared with waitlist, virtual intervention had higher odds of remission (OR 10.30, 95% CI 5.70-18.60; N=619 patients) and lower posttreatment symptom severity (SMD 0.81, 95% CI 0.52-1.10; N=1071). Compared with TAU and virtual attention control conditions, virtual intervention had higher odds of remission (OR 2.27, 95% CI 1.10-3.35; N=512) and lower posttreatment symptom severity (SMD 0.25, 95% CI 0.09-0.42; N=573). In-person intervention outcomes were not significantly different from virtual intervention outcomes (eg, remission OR 0.84, CI 0.51-1.37; N=789). No eligible studies directly compared one active virtual intervention to another. CONCLUSIONS: Virtual interventions were efficacious compared with control conditions, including waitlist control, TAU, and attention control. Although the number of studies was relatively small, the strength of evidence was moderate that in-person interventions did not yield significantly better outcomes than virtual interventions for depressive disorders.

Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression.

OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).

Clustering Longitudinal Blood Pressure Trajectories to Examine Heterogeneity in Outcomes Among Preeclampsia Cases and Controls.

[Figure: see text].

Provider Counseling and Women's Family Planning Decisions in the Postpartum Period.

Introduction: Provider counseling may influence women's postpartum family planning decisions. Materials and Methods: We conducted an anonymous Internet-based cross-sectional survey of postpartum women regarding multiple topics, including prenatal/postpartum care and family planning. We used multivariable logistic regression to determine associations between quantity of provider counseling (indexed as number of family planning topics discussed with a health care provider) and women's decisions regarding contraception and pregnancy spacing. Results: From January to May 2016, 2,850 women completed the survey and met inclusion criteria. Among this group, the majority were white (93%), ≥30 years (63%), and had obtained a college degree or higher (74%). Approximately half (49%) desired an interpregnancy interval (IPI) >2 years, and the minority (21%) used a highly effective contraceptive method (defined as long-acting reversible contraception or sterilization). The majority of women (56%) had received counseling on three to six family planning topics (defined as "more counseling" in regression models). Women who received more counseling were more likely to use a highly effective contraceptive method (adjusted odds ratio [AOR] 1.33, confidence interval [95% CI] 1.09-1.62) but were not more likely to desire an IPI >2 years (AOR 0.96, 95% CI 0.81-1.14). Desired IPI modified the association between provider counseling and contraception (p = 0.06 for interaction): Among those desiring an IPI >2 years, more counseling was associated with use of a highly effective contraceptive method (AOR 1.58, 95% CI 1.23-2.03), but this was not observed among those desiring a shorter IPI (AOR 1.05, 95% CI 0.73-1.49). Conclusions: Contraceptive decisions depend on both provider counseling and patient goals.

Oxytocin during breastfeeding and maternal mood symptoms.

This study aimed to quantify the relationship between postpartum depression and anxiety, oxytocin, and breastfeeding. We conducted a longitudinal prospective study of mother-infant dyads from the third trimester of pregnancy to 12 months postpartum. A sample of 222 women were recruited to complete the Beck Depression Inventory II and Spielberger State-Trait Anxiety Inventory-state subscale, participate in observed infant feeding sessions at 2 and 6 months postpartum, and provide venous blood samples during feeding. Maternal venous oxytocin levels in EDTA-treated plasma and saliva were determined by enzyme immunoassay with extraction and a composite measure of area under the curve (AUC) was used to define oxytocin across a breastfeeding session. Linear regression was used to estimate associations between postpartum depression and anxiety as predictors and oxytocin AUC during breastfeeding as the outcome at both 2 and 6 months postpartum. Mixed models accounting for correlations between repeated oxytocin measures were used to quantify the association between current depression and/or anxiety symptoms and oxytocin profiles during breastfeeding. We found no significant differences in oxytocin AUC across a feed between depressed or anxious women and asymptomatic women at either 2 or 6 months postpartum. Repeated measures analyses demonstrated no differences in oxytocin trajectories during breastfeeding by symptom group but possible differences by antidepressant use. Our study suggests that external factors may influence the relationship between oxytocin, maternal mood symptoms, and infant feeding.

The Lactational Effects of Contraceptive Hormones: an Evaluation (LECHE) Study.

OBJECTIVE: To estimate the proportion of women for whom use of hormonal contraception was associated with reporting a decreased breast milk supply. STUDY DESIGN: The Lactational Effects of Contraceptive Hormones: an Evaluation ("LECHE") Study was an anonymous, internet-based, exploratory, cross-sectional survey of postpartum women using approximately 70 questions. Women were eligible to participate in the survey if they were 18 years or older, had a singleton infant between 3 and 9 months of age, had breastfed this infant for any amount of time and could read English. The survey included questions about breastfeeding, reproductive health, demographic characteristics and the timing of postpartum events. RESULTS: A total of 3971 participants clicked on the survey. Our final study population included 2922 participants. Overall, 1201 (41%) reported having had milk supply concerns at some point in the first 12 weeks postpartum. The median time from birth until milk supply concerns was 3 weeks (IQR 1-7). Eight hundred fifty-two women (29%) started hormonal contraception in the first 12 weeks postpartum. Fifteen percent (127/852) of women reported new or additional milk supply concerns after starting hormonal contraception. Reported milk supply concerns were higher for women who used hormonal contraception than those who did not (44% vs. 40%; p=.05) Adjusted hazard ratios (HRs) assessing the association between contraceptive use and time to milk supply concerns were not statistically significant (HR 1.18, 95% confidence interval 0.94-1.47 for any type of hormonal contraception). CONCLUSIONS: This study found a slightly increased proportion of reported milk supply concerns among women who started hormonal contraception. IMPLICATIONS: It is important for caregivers in the postpartum period to recognize the potential for multiple factors, including initiation of hormonal contraception, to affect breastfeeding. Patient-centered counseling can help elicit women's values and preferences regarding breastfeeding and pregnancy prevention.

Genetic risk scores for major psychiatric disorders and the risk of postpartum psychiatric disorders.

Postpartum psychiatric disorders are heritable, but how genetic liability varies by other significant risk factors is unknown. We aimed to (1) estimate associations of genetic risk scores (GRS) for major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ) with postpartum psychiatric disorders, (2) examine differences by prior psychiatric history, and (3) compare genetic and familial risk of postpartum psychiatric disorders. We conducted a nested case-control study based on Danish population-based registers of all women in the iPSYCH2012 cohort who had given birth before December 31, 2015 (n = 8850). Cases were women with a diagnosed psychiatric disorder or a filled psychotropic prescription within one year after delivery (n = 5829 cases, 3021 controls). Association analyses were conducted between GRS calculated from Psychiatric Genomics Consortium discovery meta-analyses for MD, BD, and SCZ and case-control status of a postpartum psychiatric disorder. Parental psychiatric history was associated with postpartum psychiatric disorders among women with previous psychiatric history (OR, 1.14; 95% CI 1.02-1.28) but not without psychiatric history (OR, 1.08; 95% CI: 0.81-1.43). GRS for MD was associated with an increased risk of postpartum psychiatric disorders in both women with (OR, 1.44; 95% CI: 1.19-1.74) and without (OR, 1.88; 95% CI: 1.26-2.81) personal psychiatric history. SCZ GRS was only minimally associated with postpartum disorders and BD GRS was not. Results suggest GRS of lifetime psychiatric illness can be applied to the postpartum period, which may provide clues about distinct environmental or genetic elements of postpartum psychiatric disorders and ultimately help identify vulnerable groups.

Increased Rate of ASCUS Diagnosis With Concomitant Request for High-Risk Human Papillomavirus Reflex Testing May Be Due to Cognitive Bias.

OBJECTIVES: To determine if concomitant high-risk human papillomavirus (HPV-HR) reflex testing may bias the cytologic interpretation of Papanicolaou (Pap) tests. METHODS: Percentage of atypical squamous cells of undetermined significance (ASCUS) and HPV-HR positivity was compared between Pap tests with HPV-HR cotesting and HPV-HR reflex testing for ASCUS, with subset analysis of cytopathologists' experience. RESULTS: ASCUS in the reflex group (41.5%) was significantly higher than the cotesting group (33.0%) (P = .02). There was no difference in HPV-HR positivity or ASCUS/squamous intraepithelial lesion (SIL) ratios between the two groups. The cytopathologists' experience inversely correlated with the proportion of ASCUS but did not explain the higher reflex group ASCUS. CONCLUSIONS: HPV-HR reflex testing may introduce bias in cytologic diagnosis, making it more likely that an ASCUS diagnosis is rendered. HPV-HR and ASCUS/SIL ratios were similar between the groups, so cytopathologist performance was not significantly affected. There was no effect of cytopathologists' experience.

Familiality of Psychiatric Disorders and Risk of Postpartum Psychiatric Episodes: A Population-Based Cohort Study.

OBJECTIVE: Postpartum psychiatric disorders are common and morbid complications of pregnancy. The authors sought to evaluate how family history of psychiatric disorders is associated with postpartum psychiatric disorders in proband mothers with and without a prior psychiatric history by assessing degree of relationship, type of disorder, and sex of family members. METHOD: The authors linked Danish birth and psychiatric treatment registers to evaluate familial risk of postpartum psychiatric episodes in a national population-based cohort. Probands were first-time mothers who were born in Denmark in 1970 or later and who gave birth after age 15 and before Dec. 31, 2012 (N=362,462). The primary exposure was a diagnosed psychiatric disorder in a relative. Cox regression models were used to estimate the hazard ratio of postpartum psychiatric disorders in proband mothers. RESULTS: The relative risk of psychiatric disorders in the postpartum period was elevated when first-degree family members had a psychiatric disorder (hazard ratio=1.45, 95% CI=1.28-1.65) and highest when proband mothers had a first-degree family member with bipolar disorder (hazard ratio=2.86, 95% CI=1.88-4.35). Associations were stronger among proband mothers with no previous psychiatric history. There were no notable differences by sex of the family member. CONCLUSIONS: Family history of psychiatric disorders, especially bipolar disorder, is an important risk factor for postpartum psychiatric disorders. To assist in identification of women at risk for postpartum psychiatric disorders, questions related to female and male first-degree relatives with bipolar disorder are of the highest importance and should be added to routine clinical screening guidelines to improve prediction of risk.

Etonogestrel-Releasing Contraceptive Implant for Postpartum Adolescents: A Randomized Controlled Trial.

STUDY OBJECTIVE: To compare immediate postpartum insertion of the contraceptive implant to placement at the 6-week postpartum visit among adolescent and young women. DESIGN: Non-blinded, randomized controlled trial. SETTING AND PARTICIPANTS: Postpartum adolescents and young women ages 14-24 years who delivered at an academic tertiary care hospital serving rural and urban populations in North Carolina. INTERVENTIONS: Placement of an etonogestrel-releasing contraceptive implant before leaving the hospital postpartum, or at the 4-6 week postpartum visit. MAIN OUTCOME MEASURES: Contraceptive implant use at 12 months postpartum. RESULTS: Ninety-six participants were randomized into the trial. Data regarding use at 12 months were available for 64 participants, 37 in the immediate group and 27 in the 6-week group. There was no difference in use at 12 months between the immediate group and the 6-week group (30 of 37, 81% vs 21 of 27, 78%; P = .75). At 3 months, the immediate group was more likely to have the implant in place (34 of 37, 92% vs 19 of 27, 70%; P = .02). CONCLUSION: Placing the contraceptive implant in the immediate postpartum period results in a higher rate of use at 3 months postpartum and appears to have similar use rates at 12 months compared with 6-week postpartum placement. Providing contraceptive implants to adolescents before hospital discharge takes advantage of access to care, increases the likelihood of effective contraception in the early postpartum period, appears to have no adverse effects on breastfeeding, and might lead to increased utilization at 1 year postpartum.