The role of a community health worker-delivered preconception and pregnancy intervention in achieving a more positive pregnancy experience: the Bukhali trial in Soweto, South Africa.

BACKGROUND: A patient-centered, human-rights based approach to maternal care moves past merely reducing maternal mortality and morbidity, towards achieving a positive pregnancy experience. When evaluating an intervention, particularly in the context of the complex challenges facing maternal care in South Africa, it is therefore important to understand how intervention components are experienced by women. We aimed to qualitatively explore (i) factors influencing the pregnancy and postpartum experience amongst young women in Soweto, South Africa, and (ii) the influence of Bukhali, a preconception, pregnancy, and early childhood intervention delivered by community health workers (CHWs), on these experiences. METHODS: Semi-structured, in-depth interviews were conducted with 15 purposively sampled participants. Participants were 18-28-year-old women who (i) were enrolled in the intervention arm of the Bukhali randomized controlled trial; (ii) were pregnant and delivered a child while being enrolled in the trial; and (iii) had at least one previous pregnancy prior to participation in the trial. Thematic analysis, informed by the positive pregnancy experiences framework and drawing on a codebook analysis approach, was used. RESULTS: The themes influencing participants' pregnancy experiences (aim 1) were participants' feelings about being pregnant, the responsibilities of motherhood, physical and mental health challenges, unstable social support and traumatic experiences, and the pressures of socioeconomic circumstances. In terms of how support, information, and care practices influenced these factors (aim 2), four themes were generated: acceptance and mother/child bonding, growing and adapting in their role as mothers, receiving tools for their health, and having ways to cope in difficult circumstances. These processes were found to be complementary and closely linked to participant context and needs. CONCLUSION: Our findings suggest that, among women aged 18-28, a CHW-delivered intervention combining support, information, and care practices has the potential to positively influence women's pregnancy experience in South Africa. In particular, emotional support and relevant information were key to better meeting participant needs. These findings can help define critical elements of CHW roles in maternal care and highlight the importance of patient-centred solutions to challenges within antenatal care. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201903750173871, 27/03/2019.

Caregiving experiences and practices: qualitative formative research towards development of integrated early childhood development interventions targeting Kenyans and refugees in Nairobi's informal settlements.

BACKGROUND: Evidence is needed to understand factors that influence child development and caregiving experiences, especially in marginalized contexts, to inform the development and implementation of early childhood development (ECD) interventions. This study explores caregiving practices for young children in an urban informal settlement with Kenyans and embedded refugees, and identifies factors shaping these caregiving experiences, to inform the design and development of potentially appropriate ECD interventions. METHODS: A qualitative formative study, which included 14 focus group discussions (n = 125 participants), and 13 key informant interviews was conducted between August and October 2018. Purposive sampling approaches were used to select a diverse range of respondents including caregivers of children below three years of age and stakeholders of Kenyan nationality and refugees. Data were analysed using a thematic approach and the Nurturing Care Framework was used as an interpretative lens. RESULTS: There was a fusion of traditional, religious and modern practices in the care for young children, influenced by the caregivers' culture, and financial disposition. There were mixed views/practices on nutrition for young children. For example, while there was recognition of the value for breastfeeding, working mothers, especially in the informal economy, found it a difficult practice. Stimulation through play was common, especially for older children, but gaps were identified in aspects such as reading, and storytelling in the home environment. Some barriers identified included the limited availability of a caregiver, insecurity, and confined space in the informal settlement, all of which made it difficult for children to engage in play activities. Physical and psychological forms of discipline were commonly mentioned, although few caregivers practiced and recognized the need for using non-violent approaches. Some overarching challenges for caregivers were unemployment or unstable sources of income, and, particularly for refugee caregivers, their legal status. CONCLUSION: These findings point to the interplay of various factors affecting optimal caregiving for young children in an urban informal settlement with Kenyans and refugees. Integrated ECD interventions are needed for such a mixed population, especially those that strive to anchor along caregivers' social support system, co-designed together with community stakeholders, that ideally focus on parent skills training promoting nurturing care and economic empowerment.

A qualitative exploration of the reasons and influencing factors for pregnancy termination among young women in Soweto, South Africa: a Socio-ecological perspective.

BACKGROUND: Pregnancy termination is an essential component of reproductive healthcare. In Southern Africa, an estimated 23% of all pregnancies end in termination of pregnancy, against a backdrop of high rates of unintended pregnancies and unsafe pregnancy terminations, which contributes to maternal morbidity and mortality. Understanding the reasons for pregnancy termination may remain incomplete if seen in isolation of interpersonal (including family, peer, and partner), community, institutional, and public policy factors. This study therefore aimed to use a socio-ecological framework to qualitatively explore, in Soweto, South Africa, i) reasons for pregnancy termination amongst women aged 18-28 years, and ii) factors characterising the decision to terminate. METHODS: In-depth interviews were conducted between February to March 2022 with ten participants of varying parity, who underwent a termination of pregnancy since being enrolled in the Bukhali trial, set in Soweto, South Africa. A semi-structured, in-depth interview guide, based on the socioecological domains, was used. The data was analysed using reflexive thematic analysis, and a deductive approach. RESULTS: An application of the socio-ecological framework indicated that the direct reasons to terminate a pregnancy fell into the individual and interpersonal domains of the socioecological framework. Key reasons included financial dependence and insecurity, feeling unready to have a child (again), and a lack of support from family and partners for the participant and their pregnancy. In addition to these reasons, Factors that characterised the participants' decision experience were identified across all socio-ecological domains and included the availability of social support and (lack of) accessibility to termination services. The COVID-19 pandemic and resultant lockdown policies also indirectly impacted participants' decisions through detrimental changes in interpersonal support and financial situation. CONCLUSIONS: Amongst the South African women included in this study, the decision to terminate a pregnancy was made within a complex structural and social context. Insight into the reasons why women choose to terminate helps to better align legal termination services with women's needs across multiple sectors, for example by reducing judgement within healthcare settings and improving access to social and mental health support.

In South Africa, where the number of unintended pregnancies is high, we need an improved understanding of the main reasons why women terminate their pregnancies and what factors characterise this decision. Aside from individual factors, this should also be seen within the context of their environment, including relationships, community, and institutions. We therefore aimed to explore women's reasons for choosing to terminate their pregnancy through semi-structured in-depth interviews with participants. We included ten participants from Soweto, South Africa, who had undergone a pregnancy termination. The main reasons for terminating a pregnancy had to do with personal factors and reasons related to their social relationships and support. These included financial insecurity, not feeling ready to have a child (again), and lack of support from family or partners. We also found factors that characterised how the participant experienced the decision, such as barriers to getting a safe (legal) pregnancy termination. We found that amongst South African women, the decision to terminate is made in the context of their complex (social) environment. Insight into the reasons why women choose to terminate helps to better align legal termination services with women's needs, for example by reducing judgement within healthcare settings and improving access to social and mental health support.

Maternal major depression during early pregnancy is associated with impaired child executive functioning at 4.5 years of age.

BACKGROUND: Maternal depression is a serious condition that affects up to 1 in 7 pregnancies. Despite evidence linking maternal depression to pregnancy complications and adverse fetal outcomes, there remain large gaps in its identification and treatment. More work is needed to define the specific timing and severity of depression that most urgently requires intervention, where feasible, to protect maternal health and the developing fetus. OBJECTIVE: This study aimed to examine whether the timing and severity of maternal depression and/or anxiety during pregnancy affect child executive functioning at age 4.5 years. Executive functioning in the preschool years is a strong predictor of both school readiness and long-term quality of life. STUDY DESIGN: This longitudinal observational pregnancy cohort study included a sample of 323 mother-child dyads taking part in the Ontario Birth Study, an open pregnancy cohort in Toronto, Ontario, Canada. Maternal symptoms of depression and anxiety were assessed at 12 to 16 and 28 to 32 weeks of gestation and at the time of child testing at age 4.5 years using the 4-item Patient Health Questionnaire. Child executive functioning was measured during a home visit using standardized computerized administration of the Flanker test (a measure of attention) and the Dimensional Change Card Sort (a measure of cognitive flexibility). Stepwise linear regressions, controlling for possible confounding variables, were used to assess the predictive value of continuous measures of maternal depression and/or anxiety symptoms at each assessment time on the Flanker test and Dimensional Change Card Sort. Posthoc general linear models were used to assess whether maternal depression severity categories (no symptom, mild symptoms, or probable major depressive disorder) were helpful in identifying children at risk. RESULTS: Across all children, after controlling for potential confounds, greater maternal depressive symptoms at weeks 12 to 16 weeks of gestation predicted worse performance on both the Flanker test (ΔR2=0.058; P<.001) and the Dimensional Change Card Sort (ΔR2=0.017; P=.018). Posthoc general linear modeling further demonstrated that the children of mothers meeting the screening criteria for major depression in early pregnancy scored 11.3% lower on the Flanker test and 9.8% lower on the Dimensional Change Card Sort than the children of mothers without maternal depressive symptoms in early pregnancy. Mild depressive symptoms had no significant effect on executive function scores. There was no significant effect of anxiety symptoms or maternal antidepressant use in early pregnancy or pandemic conditions or maternal symptoms in later pregnancy or at the time of child testing on either the Flanker or Dimensional Change Card Sort results. CONCLUSION: This study demonstrated that fetal exposure to maternal major depression, but not milder forms of depression, at 12 to 16 weeks of gestation is associated with impaired executive functioning in the preschool years. Child executive functioning is crucial for school readiness and predicts long-term quality of life. This emphasizes an urgent need to improve the recognition and treatment of maternal major depression, particularly in early pregnancy, to limit its negative effects on the patient and on child cognitive development.

Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials.

OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

Maternal acetaminophen use and cognitive development at 4 years: the Ontario Birth Study.

BACKGROUND: Studies have suggested a link between prenatal maternal acetaminophen use and adverse developmental outcomes in children. However, there exists a knowledge gap regarding overall cognitive development and use of acetaminophen, especially concerning the timing of use in pregnancy. This study aimed to characterize the relationship between maternal acetaminophen use and cognitive development at 4 years. METHODS: This analysis included data collected throughout pregnancy and delivery from women in the Ontario Birth Study prospective cohort from 2013 to 2019 and from the NIH Toolbox Early Childhood Cognition battery administered to 4-year-old children between 2018 and 2021 (n = 436). The exposure was maternal acetaminophen use and the primary outcome was a cognition composite score. The relationship between exposure and outcome was determined using Poisson regression with a robust error variance. RESULTS: We did not observe any association between maternal acetaminophen intake any time before or during pregnancy and low cognition composite score of offspring. The IRR of suboptimal overall cognition was 1.38 (0.78-2.45), 1.22 (0.67-2.22), 0.80 (0.44-1.47), and 1.56 (0.74-3.29) for maternal use of acetaminophen before, in early, late, or overall pregnancy, respectively. CONCLUSION: Current data do not provide evidence to support a relationship of maternal acetaminophen use during pregnancy with adverse cognitive effects at 4 years. IMPACT: Acetaminophen use during pregnancy may influence the risk of child neurocognitive disorders, but there is conflicting evidence of its relationship to sub-clinical measures of cognitive development such as executive function. The study design allowed us to examine the role of timing of acetaminophen use in its relationship with cognitive development, based on a validated and standardized tablet-administered instrument for children, instead of a teacher or parent report. We did not observe a clear relationship between maternal acetaminophen use at different timepoints during pregnancy and child cognitive development.

Decidual Inflammation Drives Chemokine-Mediated Immune Infiltration Contributing to Term Labor.

Infiltration of maternal peripheral leukocytes into the uterine tissues is a critical event occurring before, during, and after term labor (TL). In this article, we investigate the contribution of uterine smooth muscle (myometrium) and pregnant endometrium (decidua) to the inflammatory process during human TL. We hypothesize that labor-related physiological inflammation is orchestrated by uterine-secreted cytokines, which dually activate the uterine vascular endothelium and maternal leukocytes to promote their adhesion and infiltration into the uterus. Using Luminex and ELISA assays, we examine a full range of cytokines (45 proteins) in media conditioned by primary decidual and myometrial cells from TL and term not in labor (TNL) women. The effect of conditioned media on the activation of human uterine microvascular endothelial cells was measured by qPCR and on peripheral leukocytes by flow cytometry. Transendothelial migration of calcein-labeled primary leukocytes toward media was assessed by fluorometry. Stromal decidual cells secrete significantly higher levels of multiple cytokines compared with myometrial cells (p < 0.05) and significantly more cytokines during TL than TNL. These cytokines activate uterine microvascular endothelial cells through the upregulation of cell adhesion molecule VCAM-1 and peripheral leukocytes by upregulation of CD11b. Furthermore, multiple cytokines secreted from the TL decidua and myometrium significantly increase migration of granulocytes, monocytes, and lymphocytes compared with TNL (p < 0.05), which was blocked by a broad-spectrum chemokine inhibitor (FX125L). These data reveal the critical role for decidual- and myometrial-secreted cytokines in the activation of inflammatory pathways leading to labor. We suggest that these pathways represent targets for therapeutic intervention during preterm labor.

Navigating relationship dynamics, pregnancy and fatherhood in the Bukhali trial: a qualitative study with men in Soweto, South Africa.

BACKGROUND: South Africa has a complex range of historical, social, political, and economic factors that have shaped fatherhood. In the context of the Bukhali randomised controlled trial with young women in Soweto, South Africa, a qualitative study was conducted with the male partners of young women who had become pregnant during the trial. This exploratory study aimed to explore individual perceptions around relationship dynamics, their partner's pregnancy, and fatherhood of partners of young women in Soweto, South Africa. METHODS: Individual, in-depth interviews were conducted with male partners (fathers, n = 19, 25-46 years old) of Bukhali participants. A thematic approach was taken to the descriptive and exploratory process of analysis, and three final themes and subthemes were identified: (1) relationship dynamics (nature of relationship, relationship challenges); (2) pregnancy (feelings about the pregnancy, effect of the pregnancy on their relationship, providing support during pregnancy; and 3) fatherhood (view of fatherhood, roles of fathers, influences on views and motivation, challenges of fatherhood). RESULTS: While most male participants were in a committed ("serious") relationship with their female partner, less than half of them were cohabiting. Most reported that their partner's pregnancy was not planned, and shared mixed feelings about the pregnancy (e.g., happy, excited, shocked, nervous), although their views about fatherhood were overwhelmingly positive. Many were concerned about how they would economically provide for their child and partner, particularly those who were unemployed. Participants identified both general and specific ways in which they provided support for their partner, e.g., being present, co-attending antenatal check-ups, providing material resources. For many, the most challenging aspect of fatherhood was having to provide financially. They seemed to understand the level of responsibility expected of them as a father, and that their involvement and presence related to love for and connection with their child. Participants' responses indicated that there were some changes in the norms around fatherhood, suggesting that there is a possibility for a shift in the fatherhood narrative in their context. CONCLUSIONS: These findings suggest that the complex array of factors influencing fatherhood in South Africa continue to play out in this generation, although promising changes are evident.

Exclusive breastfeeding can attenuate body-mass-index increase among genetically susceptible children: A longitudinal study from the ALSPAC cohort.

Recent discoveries from large-scale genome-wide association studies (GWASs) explain a larger proportion of the genetic variability to BMI and obesity. The genetic risk associated with BMI and obesity can be assessed by an obesity-specific genetic risk score (GRS) constructed from genome-wide significant genetic variants. The aim of our study is to examine whether the duration and exclusivity of breastfeeding can attenuate BMI increase during childhood and adolescence due to genetic risks. A total sample of 5,266 children (2,690 boys and 2,576 girls) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was used for the analysis. We evaluated the role of breastfeeding (exclusivity and duration) in modulating BMI increase attributed to the GRS from birth to 18 years of age. The GRS was composed of 69 variants associated with adult BMI and 25 non-overlapping SNPs associated with pediatric BMI. In the high genetic susceptible group (upper GRS quartile), exclusive breastfeeding (EBF) to 5 months reduces BMI by 1.14 kg/m2 (95% CI, 0.37 to 1.91, p = 0.0037) in 18-year-old boys, which compensates a 3.9-decile GRS increase. In 18-year-old girls, EBF to 5 months decreases BMI by 1.53 kg/m2 (95% CI, 0.76 to 2.29, p<0.0001), which compensates a 7.0-decile GRS increase. EBF acts early in life by delaying the age at adiposity peak and at adiposity rebound. EBF to 3 months or non-exclusive breastfeeding was associated with a significantly diminished impact on reducing BMI growth during childhood. EBF influences early life growth and development and thus may play a critical role in preventing overweight and obesity among children at high-risk due to genetic factors.

The selective progesterone receptor modulator-promegestone-delays term parturition and prevents systemic inflammation-mediated preterm birth in mice.

BACKGROUND: Progesterone, acting via its nuclear receptors called progesterone receptors, promotes myometrial relaxation during pregnancy, and suspension of this activity triggers labor. We previously found that 20α-hydroxysteroid dehydrogenase causes a local withdrawal of progesterone in the term and preterm myometrium by converting the progesterone into an inactive form before it accesses the progesterone receptors. OBJECTIVE: We hypothesized that a selective progesterone receptor modulator called promegestone, which is not metabolized by 20α-hydroxysteroid dehydrogenase, would sustain progesterone receptor signaling and prevent/delay term labor and preterm labor in mice. STUDY DESIGN: In the term labor mouse model, promegestone (0.2 mg/dam) or a vehicle were administered subcutaneously in timed-pregnant CD-1 mice at gestational days 15, 16, and 17 (term gestational days, 19.5). In the inflammation preterm labor model, pregnant mice received promegestone or a vehicle on gestational days 15, 16, and 17, which was 24 hours before, immediately before, and 24 hours after systemic bacterial endotoxin (50 µg intraperitoneal; lipopolysaccharide group) or vehicle (saline) administration. The maternal and fetal tissues were collected on gestational day 16 6 hours after lipopolysaccharide±promegestone injection and at term gestational day 18.75. The protein levels of 10 cytokines were measured by multiplex immunoassay in maternal plasma and amniotic fluid. Myometrial, decidual, and placental messenger RNA levels of multiple cytokines and procontractile proteins were evaluated by real-time polymerase chain reaction and confirmed by immunoblotting. RESULTS: Promegestone prevented term labor and maintained mice pregnancy postterm >24 hours. The litter size and fetal weights were not different from the controls. Promegestone prevented systemic bacterial-endotoxin-induced preterm labor in 100% of the mice, blocked uterine contractions, significantly inhibited all systemic inflammation-induced myometrial cytokines, and partially inhibited decidual and placental inflammation. Promegestone did not prevent bacterial-endotoxin-induced fetal toxicity. CONCLUSION: Promegestone a selective progesterone receptor modulator that binds progesterone receptors with high affinity and is not metabolized by 20α-hydroxysteroid dehydrogenase could completely suppress term parturition and systemic bacterial-endotoxin-induced preterm birth in mice. We suggest that such selective progesterone receptor modulators may represent a potential therapeutic approach to the prevention of preterm labor in women at high risk of preterm birth.

Human leukocyte antigen HLA-C, HLA-G, HLA-F, and HLA-E placental profiles are altered in early severe preeclampsia and preterm birth with chorioamnionitis.

BACKGROUND: The extravillous trophoblast expresses each of the nonclassical major histocompatibility complex class I antigens-human leukocyte antigens E, F, and G-and a single classical class I antigen, human leukocyte antigen C. We recently demonstrated dynamic expression patterns of human leukocyte antigens C, G, and F during early extravillous trophoblast invasion and placentation. OBJECTIVE: This study aimed to investigate the hypothesis that the immune inflammatory mediated complications of pregnancy such as early preeclampsia and preterm labor may show altered expression profiles of nonclassical human leukocyte antigens. STUDY DESIGN: Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were performed on placental villous tissues and basal plate sections from term nonlaboring deliveries, preterm deliveries, and severe early-onset preeclampsia, both with and without small-for-gestational-age neonates. RESULTS: Human leukocyte antigen G is strongly and exclusively expressed by the extravillous trophoblast within the placental basal plate, and its levels increase in pregnancies complicated by severe early-onset preeclampsia with small-for-gestational-age neonates relative to those of healthy term controls. Human leukocyte antigen C shows a similar profile in the extravillous trophoblast of preeclamptic pregnancies, but significantly decreases in the villous placenta. Human leukocyte antigen F protein levels are decreased in both extravillous trophoblast and villous placenta of severe early-onset preeclamptic pregnancies, both with and without small-for-gestational-age neonates, compared with those found in term and preterm birth deliveries. Human leukocyte antigen E decreases in blood vessels in placentas from preeclamptic pregnancies relative to its levels in term and preterm birth deliveries. Placental levels of human leukocyte antigens F and C are increased in cases of preterm birth with chorioamnionitis relative to those of cases of idiopathic preterm birth. CONCLUSION: Dysregulation of placental human leukocyte antigen expression at the maternal-fetal interface may contribute to compromised maternal tolerance in preterm birth with chorioamnionitis and excessive maternal systemic inflammation associated with severe early-onset preeclampsia.

Maternal prenatal psychological distress and vitamin intake with children's neurocognitive development.

BACKGROUND: Maternal prenatal psychological distress (PPD) is increasingly linked to sub-optimal child neurodevelopment. Daily intake of prenatal vitamin during pre-conception and early pregnancy may ameliorate the effects of PPD on cognition in the offspring. METHODS: PPD was assessed in early (12-16 weeks) and late (28-32 weeks) gestation in the Ontario Birth Study. Prenatal vitamin supplement intake information was collected in early gestation. Child cognition at 4 years was assessed using the NIH Toolbox. Poisson regression was used to investigate associations between PPD and/or prenatal vitamin intake and child cognition. RESULTS: Four hundred and eighteen mother-child dyads were assessed. Moderate-severe PPD experienced during early gestation was associated with reduced cognition (adjusted incidence rate ratio (IRRadj) = 3.71, 95% confidence interval (CI): 1.57-8.77, P = 0.003). Daily intake of prenatal vitamins was not associated with cognition (IRRadj = 1.34, 95% CI: 0.73-2.46, P = 0.34). Upon stratification, the experience of mild-severe PPD with daily intake of prenatal vitamins was associated with higher incident rates of suboptimal cognition compared to children of women with daily prenatal vitamin intake without any episode of PPD (IRRadj = 2.88, 95% CI: 1.1-7.4). CONCLUSIONS: Moderate-severe PPD in early pregnancy is associated with poor cognition in children and daily intake of prenatal vitamin did not ameliorate this association. IMPACT: Our findings expand on existing literature by highlighting that exposure to prenatal psychological distress (PPD), in moderate-to-severe form, in the early stages of pregnancy, can have detrimental effects on the offspring's cognitive development at 4 years. Overall, prenatal vitamin intake did not ameliorate the effects of PPD. Early screening and treatment of prenatal maternal mental illness is crucial.

Cross-sectional associations between mental health indicators and social vulnerability, with physical activity, sedentary behaviour and sleep in urban African young women.

BACKGROUND: Relationships between mental health and multiple health behaviours have not been explored in young South African women experiencing social constraints. The aim of this study was to identify associations between mental health indicators and risk factors with physical activity, sedentary behaviour, and sleep, amongst young women living in Soweto, a predominantly low-income, urban South African setting. METHODS: For this cross-sectional study, baseline measurements for participants (n = 1719, 18.0-25.9 years old) recruited for the Healthy Life Trajectories Initiative were used including: physical activity, sedentary behaviour (sitting, screen and television time), sleep (duration and quality), depression and anxiety indicators, emotional health, adverse childhood experiences, alcohol-use risk; social vulnerability, self-efficacy, and social support. RESULTS: Multiple regression analyses showed that depression (ß = 0.161, p < 0.001), anxiety (ß = 0.126, p = 0.001), adverse childhood experiences (ß = 0.076, p = 0.014), and alcohol-use risk (ß = 0.089, p = 0.002) were associated with poor quality sleep. Alcohol-use risk was associated with more screen time (ß = 0.105, p < 0.001) and television time (ß = 0.075, p < 0.016). Social vulnerability was associated with lower sitting time (ß = - 0.187, p < 0001) and screen time (ß = - 0.014, p < 0.001). Higher self-efficacy was associated with more moderate- to vigorous-intensity physical activity (ß = 0.07, p = 0.036), better-quality sleep (ß = - 0.069, p = 0.020) and less television time (ß = - 0.079, p = 0.012). Having no family support was associated with more sitting time (ß = 0.075, p = 0.022). Binomial logistic regression analyses supported these findings regarding sleep quality, with anxiety and depression risk doubling the risk of poor-quality sleep (OR = 2.425, p < 0.001, OR = 2.036, p = 0.003 respectively). CONCLUSIONS: These findings contribute to our understanding of how mental health indicators and risk factors can be barriers to health behaviours of young women in Soweto, and that self-efficacy and social support can be protective for certain of these behaviours for these women. Our results highlight the uniqueness of this setting regarding associations between mental health and behaviours associated with non-communicable diseases risk.

A community engagement approach for an integrated early childhood development intervention: a case study of an urban informal settlement with Kenyans and embedded refugees.

BACKGROUND: Community engagement is crucial for the design and implementation of community-based early childhood development (ECD) programmes. This paper aims to share key components and learnings of a community engagement process for an integrated ECD intervention. The lessons shared are drawn from a case study of urban informal settlement with embedded refugees in Nairobi, Kenya. METHODS: We conducted three stakeholder meetings with representatives from the Ministry of Health at County and Sub-County, actors in the ECD sector, and United Nations agency in refugee management, a transect walk across five villages (Ngando, Muslim, Congo, Riruta and Kivumbini); and, six debrief meetings by staff from the implementing organization. The specific steps and key activities undertaken, the challenges faced and benefits accrued from the community engagement process are highlighted drawing from the implementation team's perspective. RESULTS: Context relevant, well-planned community engagement approaches can be integrated into the five broad components of stakeholder engagement, formative research, identification of local resources, integration into local lives, and shared control/leadership with the local community. These can yield meaningful stakeholder buy-in, community support and trust, which are crucial for enabling ECD programme sustainability. CONCLUSION: Our experiences underscore that intervention research on ECD programmes in urban informal settlements requires a well-planned and custom-tailored community engagement model that is sensitive to the needs of each sub-group within the community to avoid unintentionally leaving anyone out.

Prevalence, Incidence, and Persistence of Postpartum Anxiety, Depression, and Comorbidity: A Cohort Study Among Women in Havana Cuba.

OBJECTIVE: To estimate the prevalence, incidence, and persistence of postpartum anxiety, depression, and comorbid symptoms over the first 6 months postpartum in a cohort of Havana women and to evaluate the sensitivity, specificity, and predictive power of the Edinburgh Postnatal Depression Scale (EPDS) and the State-Trait Anxiety Inventory (STAI) at 4 weeks postpartum on depressive and anxiety symptoms at 12 and 24 weeks. METHOD: A cohort study with 273 women in Havana, Cuba. Participants were assessed at 4, 12, and 24 weeks postpartum for anxiety, depression, and comorbid symptoms. RESULTS: Prevalence rates were highest at 4 weeks postpartum: 20.0% women reported elevated levels of anxiety and 16.4% reported depressive symptoms. The prevalence of comorbid anxiety and depression was 5.8%. While rates of anxiety steadily decreased to 13.8% at 24 weeks, rates of depression persisted to 24 weeks postpartum with 14.5% still experiencing elevated symptoms. Comorbid anxiety and depression decreased across time. There were limited sensitivity and poor predictive values for both the STAI and the EPDS. CONCLUSION: This study is the first to examine perinatal mental illness in Cuba. While anxiety and depression rates found among Cuban women are lower than those reported in other low-income countries, the rates paralleled high-income countries.

Pro-inflammatory signals induce 20α-HSD expression in myometrial cells: A key mechanism for local progesterone withdrawal.

Metabolism of progesterone (P4) by the enzyme 20α hydroxysteroid dehydrogenase (20α-HSD) in myometrial cells is postulated to be a mechanism for P4 withdrawal, which occurs concomitant to uterine inflammation (physiologic or infection-induced) and associated activation of transcription factors: NF-кB and AP-1, common to term and preterm labour. We found that 20α-HSD protein is significantly increased in human myometrium during term labour, and in mouse uterus during term and preterm labour. Treatment of human myometrial cells with the pro-inflammatory mediators, lipopolysaccharide (LPS, mimicking infection) and 12-O-tetradecanoylphorbol-13-acetate (TPA, mimicking inflammation), induced 20α-HSD gene expression and increased 20α-HSD protein abundance. LPS treatment decreased P4 release into the culture medium and resulted in up-regulation of GJA1 in the hTERT-HM cells. The NF-кB /AP-1 transcription factors mediated effects of LPS and TPA on 20α-HSD gene transcription. Both pro-inflammatory stimuli induced 20α-HSD promoter activity in LPS/TPA-treated cells which was significantly attenuated by inhibition of NF-кB (JSH: 20 µM) or AP-1 signalling (T5224: 10 µM). Deletion of NF-кB consensus sites abrogated LPS-mediated promoter induction, while removal of AP-1 sites reversed the TPA-mediated induction of 20α-HSD promoter. We conclude that inflammatory stimuli (physiologic or pathologic) that activate NF-кB or AP-1 induce 20α-HSD transcription and subsequent local P4 withdrawal resulting in up-regulation of GJA1 and activation of myometrium that precedes labour.

Hypoxia alters the expression of ACE2 and TMPRSS2 SARS-CoV-2 cell entry mediators in hCMEC/D3 brain endothelial cells.

The mechanisms by which the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induces neurological complications remain to be elucidated. We aimed to identify possible effects of hypoxia on the expression of SARS-CoV-2 cell entry mediators, angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) protein, in human brain endothelial cells, in vitro. hCMEC/D3 cells were exposed to different oxygen tensions: 20% (Control group), 8% or 2% O2 (Hypoxia groups). Cells were harvested 6-, 24- and 48 h following hypoxic challenge for assessment of mRNA and protein, using qPCR and Western Blot. The response of the brain endothelial cells to hypoxia was replicated using modular incubator chambers. We observed an acute increase (6 h, p < 0.05), followed by a longer-term decrease (48 h, p < 0.05) in ACE2 mRNA and protein expression, accompanied by reduced expression of TMPRSS2 protein levels (48 h, p < 0.05) under the more severe hypoxic condition (2% O2). No changes in levels of von Willebrand Factor (vWF - an endothelial cell damage marker) or interleukin 6 (IL-6 - a pro-inflammatory cytokine) mRNA were observed. We conclude that hypoxia regulates brain endothelial cell ACE2 and TMPRSS2 expression in vitro, which may indicate human brain endothelial susceptibility to SARS-CoV-2 infection and subsequent brain sequelae.

Expression of severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across gestation and at the maternal-fetal interface in pregnancies complicated by preterm birth or preeclampsia.

BACKGROUND: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 cell entry mediators, angiotensin-converting enzyme 2 and transmembrane protease serine 2, at the human maternal-fetal interface. There is also no information as to whether the expression of these mediators is altered in pregnancies complicated by preeclampsia or preterm birth. This is important because the expression of decidual and placental angiotensin-converting enzyme 2 and transmembrane protease serine 2 across gestation may affect the susceptibility of pregnancies to vertical transmission of severe acute respiratory syndrome coronavirus 2. OBJECTIVE: This study aimed to investigate the expression pattern of specific severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across human pregnancy and in paired samples of decidua and placenta in pregnancies complicated by preterm birth or preeclampsia compared with those in term uncomplicated pregnancies. STUDY DESIGN: In this study, 2 separate cohorts of patients, totaling 87 pregnancies, were included. The first cohort was composed of placentae from first- (7-9 weeks), second- (16-18 weeks), and third-trimester preterm (26-31 weeks) and third-trimester term (38-41 weeks) pregnancies (n=5/group), whereas the second independent cohort included matched decidua and placentae from pregnancies from term uncomplicated pregnancies (37-41 weeks' gestation; n=14) and pregnancies complicated by preterm birth (26-37 weeks' gestation; n=11) or preeclampsia (25-37 weeks' gestation; n=42). Samples were subjected to quantitative polymerase chain reaction and next-generation sequencing or RNA sequencing for next-generation RNA sequencing for angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA expression quantification, respectively. RESULTS: In the first cohort, angiotensin-converting enzyme 2 and transmembrane protease serine 2, exhibited a gestational age-dependent expression profile, that is, angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA was higher (P<.05) in the first-trimester placenta than in second-trimester, preterm birth, and term placentae (P<.05) and exhibited a negative correlation with gestational age (P<.05). In the second cohort, RNA sequencing demonstrated very low or undetectable expression levels of angiotensin-converting enzyme 2 in preterm birth, preeclampsia, and term decidua and in placentae from late gestation. In contrast, transmembrane protease serine 2 was expressed in both decidual and placental samples but did not change in pregnancies complicated by either preterm birth or preeclampsia. CONCLUSION: The increased expression of these severe acute respiratory syndrome coronavirus 2 cell entry-associated genes in the placenta in the first trimester of pregnancy compared with those in later stages of pregnancy suggests the possibility of differential susceptibility to placental entry to severe acute respiratory syndrome coronavirus 2 across pregnancy. Even though there is some evidence of increased rates of preterm birth associated with severe acute respiratory syndrome coronavirus 2 infection, we found no increase in mRNA expression of angiotensin-converting enzyme 2 or transmembrane protease serine 2 at the maternal-fetal interface.

Food insecurity, diet quality and body composition: data from the Healthy Life Trajectories Initiative (HeLTI) pilot survey in urban Soweto, South Africa.

OBJECTIVE: To determine whether food security, diet diversity and diet quality are associated with anthropometric measurements and body composition among women of reproductive age. The association between food security and anaemia prevalence was also tested. DESIGN: Secondary analysis of cross-sectional data from the Healthy Life Trajectories Initiative (HeLTI) study. Food security and dietary data were collected by an interviewer-administered questionnaire. Hb levels were measured using a HemoCue, and anaemia was classified as an altitude-adjusted haemoglobin level < 12·5 g/dl. Body size and composition were assessed using anthropometry and dual-energy x-ray absorptiometry. SETTING: The urban township of Soweto, Johannesburg, South Africa. PARTICIPANTS: Non-pregnant women aged 18-25 years (n 1534). RESULTS: Almost half of the women were overweight or obese (44 %), and 9 % were underweight. Almost a third of women were anaemic (30 %). The prevalence rates of anaemia and food insecurity were similar across BMI categories. Food insecure women had the least diverse diets, and food security was negatively associated with diet quality (food security category v. diet quality score: B = -0·35, 95 % CI -0·70, -0·01, P = 0·049). Significant univariate associations were observed between food security and total lean mass. However, there were no associations between food security and body size or composition variables in multivariate models. CONCLUSIONS: Our data indicate that food security is an important determinant of diet quality in this urban-poor, highly transitioned setting. Interventions to improve maternal and child nutrition should recognise both food security and the food environment as critical elements within their developmental phases.

Overexpression of miR-210-3p Impairs Extravillous Trophoblast Functions Associated with Uterine Spiral Artery Remodeling.

Hsa-miR-210-3p has been reported to be upregulated in preeclampsia (PE); however, the functions of miR-210-3p in placental development are not fully understood, and, consequently, miR-210-3p's role in the pathogenesis of PE is still under investigation. In this study, we found that overexpression of miR-210-3p reduced trophoblast migration and invasion, extravillous trophoblast (EVT) outgrowth in first trimester explants, expression of endovascular trophoblast (enEVT) markers and the ability of trophoblast to form endothelial-like networks. In addition, miR-210-3p overexpression significantly downregulated the mRNA levels of interleukin-1B and -8, as well as CXC motif ligand 1. These cytokines have been suggested to play a role in EVT invasion and the recruitment of immune cells to the spiral artery remodeling sites. We also showed that caudal-related homeobox transcription factor 2 (CDX2) is targeted by miR-210-3p and that CDX2 downregulation mimicked the observed effects of miR-210-3p upregulation in trophoblasts. These findings suggest that miR-210-3p may play a role in regulating events associated with enEVT functions and its overexpression could impair spiral artery remodeling, thereby contributing to PE.