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Supplementary File Article: Mode of Delivery and Asthma in Childhood and Adolescence: Findings from the Millennium Cohort Study. Methods: Study Population and Ethical Approval. Methods: Exposure: Mode of Delivery. Methods: Description of Potential Confounders. Data Analysis S1: Description of Sensitivity Analyses Results S1: Sensitivity Analyses. Table S1: Association between Mode of Delivery and Wheezing in the last 12 months at ages 7 and 11 years among Millennium Cohort Study Participants. Table S2: Association between Mode of Delivery and Asthma at ages 7, 11 and 14 years among Millennium Cohort Study Participants (excluding preterm births). Table S3: Association between any Caesarean section and Persistent and Adolescent asthma among Millennium Cohort Participants. Table S4: Association between Mode of Delivery and Asthma at ages 7, 11 and 14 years among Millennium Cohort Study Participants (only including participants at age 14). Table S5: Association between Mode of Delivery and Asthma at ages 7, 11 and 14 years among Millennium Cohort Study Participants. Table S6: Comparison of Maternal and Child Characteristics at Baseline and at age 14 years among Millennium Cohort Study Participants. Table S7: Association between Mode of Delivery and Loss to Follow-up at age 14 years and Asthma at age 7 years and Loss to Follow-up at age 14 years among Millennium Cohort Study Participants. Figure S1: Directed acyclic graph identifying potential confounders of a mode of delivery-asthma relationship.

The initial peak incidence of Hodgkin lymphoma (HL) occurs during reproductive years.Synthesise published literature on the relationship between HL and maternal and perinatal outcomes.Systematic search of PubMed/Medline, Cochrane Library, Scopus, Embase and Science Direct from inception to June 2022, supplemented by hand-searching reference lists.Two reviewers independently reviewed titles, abstracts and full-text articles. Published studies containing original data were eligible.Two reviewers independently extracted data and appraised study quality. Outcomes for pregnant women with a previous/current diagnosis of HL were compared separately with women never diagnosed with HL. Where data permitted, meta-analyses of odds ratios and proportions were performed. Certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.Of the 5527 studies identified, 33 met the inclusion criteria. In the groups with HL before pregnancy and HL during pregnancy, adjusted odds ratios were not statistically significant for congenital malformation (aOR 1.7, 95% CI 0.9-3.1, and aOR 1.84, 95% CI 0.81-4.15, respectively), preterm birth (PTB) (aOR 0.99, 95% CI 0.65-1.51, and aOR 6.74, 95% CI 0.52-88.03, respectively) and miscarriage (aOR 0.78, 95% CI 0.55-1.10, and aOR 0.38, 95% CI 0.05-2.72, respectively). The aORs for all other outcomes were not statistically significant, except for blood transfusion (aOR 1.38, 95% CI 1.05-1.82) and venous thromboembolism (VTE) (aOR 7.93, 95% CI 2.97-21.22) in the group for HL during pregnancy. The proportion of anaemia was also increased in this group (69%, 95% CI 57%-80% vs 4%, 95% CI 4%-5%, respectively). The GRADE certainty of findings ranged from low to very low.Rates of most adverse pregnancy outcomes among women with a previous/current HL diagnosis are not increased significantly compared with the general pregnant population. Women with HL diagnosed during pregnancy may have a higher PTB rate and increased likelihood of VTE, anaemia and blood transfusion; however, small study numbers and the low to very low GRADE certainty of findings preclude firm conclusions.

Objective: To develop and validate (both internally and externally) a prediction model examining a combination of risk factors in order to predict postpartum haemorrhage (PPH) in a general obstetric Irish population of singleton pregnancies. Study design: We used data from the National Maternal and Newborn Clinical Management System (MN-CMS), including all singleton deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019. We defined PPH as an estimated blood loss of = 1000 ml following the birth of the baby. Multivariable logistic regression with backward stepwise selection was used to develop the prediction model. Candidate predictors included maternal age, maternal body mass index, parity, previous caesarean section, assisted fertility, gestational age, fetal macrosomia, mode of delivery and history of PPH. Discrimination was assessed using the area under the receiver operating characteristic curve (ROC) C-statistic. We used bootstrapping for internal validation to assess overfitting, and conducted a temporal external validation using data from all singleton deliveries at CUMH during 2020. Results: Out of 6,077 women, 5,807 with complete data were included in the analyses, and there were 270 (4.65%) cases of PPH. Four variables were considered the best combined predictors of PPH, including parity (specifically nulliparous), macrosomia, mode of delivery (specifically operative vaginal delivery, emergency caesarean section and prelabour caesarean section), and history of PPH. These predictors were used to develop a nomogram to provide individualised risk assessment for PPH. The original apparent C-statistic was 0.751 (95% CI: 0.721, 0.779) suggesting good discriminative performance. There was minimal optimism adjustment to the C-statistic after bootstrapping, indicating good internal performance (optimism adjusted C-statistic: 0.748). Results of external validation were comparable with the development model suggesting good reproducibility. Conclusions: Four routinely collected variables (parity, fetal macrosomia, mode of delivery and history of PPH) were identified when predicting PPH in a general obstetric Irish population of singleton pregnancies. Use of our nomogram could potentially assist with individualised risk assessment of PPH and inform clinical decision-making allowing those at highest risk of PPH be actively managed.

Background and Hypothesis Intestinal microbiota is intrinsically linked to human health. Evidence suggests that the composition and function of the microbiome differs in those with schizophrenia compared with controls. It is not clear how these alterations functionally impact people with schizophrenia. We performed a systematic review and meta-analysis to combine and evaluate data on compositional and functional alterations in microbiota in patients with psychosis or schizophrenia. Study design Original studies involving humans and animals were included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE, and Cochrane were systematically searched and quantitative analysis performed. Study results Sixteen original studies met inclusion criteria (1376 participants: 748 cases and 628 controls). Ten were included in the meta-analysis. Although observed species and Chao 1 show a decrease in diversity in people with schizophrenia compared with controls (SMD = −0.14 and −0.66 respectively), that did not reach statistical significance. We did not find evidence for variations in richness or evenness of microbiota between patients and controls overall. Differences in beta diversity and consistent patterns in microbial taxa were noted across studies. We found increases in Bifidobacterium, Lactobacillus, and Megasphaera in schizophrenia groups. Variations in brain structure, metabolic pathways, and symptom severity may be associated with compositional alterations in the microbiome. The heterogeneous design of studies complicates a similar evaluation of functional readouts. Conclusions The microbiome may play a role in the etiology and symptomatology of schizophrenia. Understanding how the implications of alterations in microbial genes for symptomatic expression and clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis.

BACKGROUND: Evidence on the association between chronic hypertension and the risk of cardiovascular disease (CVD) in mothers with adverse pregnancy outcomes (APOs) is limited. We investigated the association between chronic hypertension and risk of CVD, considering the role of APOs. METHODS: We used linked electronic health records in the CALIBER platform to define a UK cohort of women with recorded births between 1997 and 2016. We conducted multivariable Cox regression to estimate the association between chronic hypertension, with and without APOs, and 12 subsequent CVD events. RESULTS: The study cohort comprised 1 784 247 births (1.2 million women); of these 12 698 (0.71%) records had chronic hypertension, and 16 499 women had incident CVD during follow-up, of which 66% occurred in women under 40 years. Chronic hypertension (versus no chronic hypertension) was associated with a 2-fold higher risk of first subsequent CVD (adjusted hazard ratios, 2.22 [95% CI, 2.03–2.42]). Compared to normotensive women without APOs, the associations were the strongest in women with chronic hypertension and APOs across the 12 CVD outcomes, varying from 9.65 (5.96–15.6) for heart failure to 2.66 (2.17–3.26) for stable angina. In women with chronic hypertension without APOs, adjusted hazard ratios varied from 5.25 (3.47–7.94) for subarachnoid hemorrhage to 1.26 (0.59–2.67) for peripheral arterial disease. In women with APOs, but without chronic hypertension, adjusted hazard ratios varied from 3.27 (2.48–4.31) for intracerebral hemorrhage to 1.33 (1.26–1.41) for stable angina. CONCLUSIONS: We found strong associations between chronic hypertension and the risk of premature CVD, with greater risk in women who additionally had APOs. Intervention programs focused on these groups might lower their risk of subsequent CVD.

Purpose To examine the association between mode of delivery (in particular caesarean section) and behavioural outcomes in offspring at six time-points between age 3 and 17 years. Methods Similar to previous work examining the association between mode of delivery and behavioural outcomes in offspring at age 7, we used maternal-reported data from the Millennium Cohort Study. Data on mode of delivery were collected when children were 9 months and categorised as spontaneous vaginal delivery, assisted vaginal delivery, induced vaginal delivery, emergency caesarean section, planned caesarean section and caesarean section after induction of labor. Data on behavioural outcomes were collected at ages 3, 5, 7, 11, 14 and 17 years using the Strengths and Difficulties Questionnaire (SDQ). Crude and adjusted logistic regression examined mode of delivery–behavioural difficulties relationship, using validated SDQ cut-off points (total SDQ ≥ 17, emotional ≥ 5, conduct ≥ 4, hyperactivity ≥ 7, peer problems ≥ 4 and prosocial behaviour ≤ 4). Multilevel models with linear splines examined the association between mode of delivery and repeated measures of SDQ. Results There were 18,213 singleton mother–child pairs included at baseline, 13,600 at age 3; 13,831 at age 5; 12,687 at age 7; 11,055 at age 11; 10,745 at age 14 and 8839 at age 17. Adjusted logistic regression suggested few associations between mode of delivery and behavioural outcomes at ages 3, 5, 11, 14 and 17 years using validated SDQ cut-off points. After correction for multiple testing, only the protective association between planned caesarean section-Conduct difficulties at age 5 years (OR 0.63, 95% CI 0.46, 0.85) and positive association between caesarean section after induction-Emotional difficulties at age 11 years (OR 1.57, 95% CI 1.19, 2.07) remained statistically significant. Multilevel modelling suggested mean SDQ scores were similar in each mode of delivery group at each time point. Conclusions Results of this study indicate that mode of delivery is unlikely to have a major impact on behavioural outcomes.

Background: Perineal trauma is a common complication of childbirth and can have serious impacts on long-term health. Few studies have examined the combined effect of multiple risk factors. We developed and internally validated a risk prediction model to predict third and fourth degree perineal tears using data from a general obstetric population. Methods: Risk prediction model using data from all singleton vaginal deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019 and 2020. Third/fourth degree tears were diagnosed by an obstetrician or midwife at time of birth and defined as tears that extended into the anal sphincter complex or involved both the anal sphincter complex and anorectal mucosa. We used univariable and multivariable logistic regression with backward stepwise selection to develop the models. Candidate predictors included infant sex, maternal age, maternal body mass index, parity, mode of delivery, birthweight, post-term delivery, induction of labour and public/private antenatal care. We used the receiver operating characteristic (ROC) curve C-statistic to assess discrimination, and bootstrapping techniques were used to assess internal validation. Results: Of 8,403 singleton vaginal deliveries, 8,367 (99.54%) had complete data on predictors for model development. A total of 128 women (1.53%) had a third/fourth degree tear. Three variables remained in the final model: nulliparity, mode of delivery (specifically forceps delivery or ventouse delivery) and increasing birthweight (per 100 gram increase) (C-statistic: 0.75, 95% CI: 0.71, 0.79). We developed a nomogram to calculate individualised risk of third/fourth degree tears using these predictors. Bootstrapping indicated good internal performance. Conclusions: Use of our nomogram can provide an individualised risk assessment of third/fourth degree tears and potentially aid counselling of women on their potential risk.

Background The aim of this study was to examine the association between hypertensive disorders of pregnancy (HDP) and behavioural outcomes in offspring at five time-points. Methods We used maternal-reported data from the Millennium Cohort Study. Data on HDP were collected when children were 9-months. Data on behavioural outcomes were collected at age 3, 5, 7, 11 and 14years using the Strengths and Difficulties Questionnaire (SDQ). Multivariate logistic regression analysis examined a HDP-behavioural difficulties relationship, using validated SDQ cut-off points. Multilevel models with linear splines examined the association between HDP and repeated measures of SDQ. Results 18,274 singleton children were included in the study at baseline, Multivariate logistic regression suggested HDP was not significantly associated with SDQ domain cut-off points at ages 3, 7 and 11years. At age 5years, HDP was associated with a 40% increased odds of behavioural difficulties based on total SDQ(≥17) (OR:1.40, 95% CI:1.03,1.91). HDP was associated with a 43% increased odds of Peer Problem difficulties at age 5 (OR:1.43, 95% CI:1.10,1.86), and a 28% increased odds of Peer Problem difficulties(≥4) at age 14 (OR:1.28, 95% CI:1.02,1.61). In the linear spline model, mean SDQ score was higher at each time-point in those exposed to HDP, although did not always reach statistical significance. Limitations Data on different classifications of HDP were unavailable; therefore, we could not examine the effect of gestational hypertension and preeclampsia separately. Conclusions While we did not find strong evidence of associations between HDP and behavioural outcomes overall, some associations between HDP and behavioural difficulties did persist at age 5 and 14years.

Objective: Maternal stress is associated with adverse child outcomes. Conception to 2-years postpartum (the first 1000 days) is a developmentally sensitive period for stress exposure. The role of maternal stress in the first 1000 days on child obesity risk is unclear. This review systematically examines the relationship between maternal stress across the first 1000 days and child obesity risk. Methods: The Cochrane Library, MEDLINE, PsycINFO, EMBASE, CINAHL, and Maternity and Infant Care were searched from inception to June 2018. Eligible studies included women who experienced maternal stress in the first 1000 days; an included a measure of maternal stress and of child anthropometrics. Results: Sixteen studies met inclusion criteria, the majority of these examined prenatal stress exposure. Inconsistent effects were observed for psychological and physiological stress responses, on child weight outcomes. Environmental stress exposures, including natural disaster and bereavement, were more consistently associated with increased obesity risk. Conclusion: This review does not provide support for the effects of psychological or physiological maternal stress on child weight outcomes; there is some evidence of associations between environmental stress exposures and greater childhood adiposity. Variation in conceptualisation and measurement of stress, timing of stress exposure, and limited examination of stress-related behaviours were noted.

Objective: Examine the association between alcohol consumption before and during pregnancy and neurodevelopmental outcomes in the offspring at two and five years. Study design: Retrospective analysis of a prospective longitudinal cohort; SCOPE-BASELINE. Data on pre-conception and prenatal alcohol consumption were obtained at 15 weeks’ gestation and categorised as abstinent, occasional-low (1-7units/week) and moderate-heavy (≥8units/week). Binge drinking was defined as ≥6 units/session. Outcome measures (Child Behaviour Checklist and Kaufman Brief Intelligence Test) were obtained at two and five years. Linear regression examined an alcohol consumption and Child Behaviour Checklist and Kaufman Brief Intelligence Test relationship, adjusting for several potential confounders. Results: Data on alcohol consumption was available for 1,507 women. Adjusted linear regression suggested few associations: pre-pregnancy occasional-low alcohol consumption was associated with lower log externalizing Child Behaviour Checklist scores (-0.264, 95% CI: −0.009, −0.520), while pre-pregnancy moderate-high levels of alcohol consumption was associated with lower Kaufman Brief Intelligence Test verbal standard scores (-0.034, 95% CI: −0.001, −0.068) and composite IQ scores (-0.028, 95% CI: −0.056, −0.0004) at five-years. In the first trimester, moderate-high levels of alcohol consumption was associated with lower internalizing Child Behaviour Checklist scores at two-years (-0.252, 95% CI: −0.074, −0.430). No significant associations were observed between number of binge episodes pre-pregnancy or binge drinking in the first trimester and Child Behaviour Checklist or Kaufman Brief Intelligence Test. Conclusions: We did not find strong evidence of associations between pre-pregnancy and early pregnancy maternal alcohol consumption and adverse neurodevelopmental outcomes at age two and five years overall. Further research examining alcohol consumption (including binge drinking) beyond 15 weeks’ gestation and subsequent neurodevelopmental outcomes is needed to examine the potential effect of alcohol consumption in later pregnancy.

Background: Chronic hypertension (CH) adversely impacts pregnancy. It remains unclear whether antihypertensive treatment alters these risks. We examined the role of antihypertensive treatment in the association between CH and adverse pregnancy outcomes. Methods: Electronic health records from the UK Caliber and Clinical Practice Research Datalink were used to define a cohort of women delivering between 1997 and 2016. Primary outcomes were preeclampsia, preterm birth (PTB), and fetal growth restriction (FGR). We used multivariable logistic regression to compare outcomes in women with CH to women without CH and propensity score matching to compare antihypertensive agents. Results: The study cohort consisted of 1 304 679 women and 1 894 184 births. 14 595 (0.77%) had CH, and 6786 (0.36%) were prescribed antihypertensive medications in pregnancy. Overall, women with CH (versus no CH), had higher odds of preeclampsia (adjusted odds ratio [aOR], 5.74 [95% CI, 5.44–6.07]); PTB (aOR, 2.53 [2.39–2.67]); and FGR (aOR, 2.51 [2.31–2.72]). Women with CH prescribed treatment (versus untreated women) had higher odds of preeclampsia (aOR, 1.17 [1.05–1.30]), PTB (1.25 [1.12–1.39]), and FGR (1.80 [1.51–2.14]). Women prescribed methyldopa (versus β-blockers) had higher odds of preeclampsia (aOR, 1.43 [1.19–1.73]); PTB (1.59 [1.30–1.93]), but lower odds of FGR (aOR, 0.66 [0.48–0.90]). Odds of adverse outcomes were similar in relation to calcium channel blockers (versus β-blockers) except for PTB (aOR, 1.94 [1.15–3.27]). Among women prescribed treatment, lower average blood pressure ( Conclusions: Treatment with antihypertensive agents and control of hypertension ameliorates some effects but higher risks of adverse outcomes persist. β-Blockers versus methyldopa may be associated with better pregnancy outcomes except for FGR. Powered trials are needed to inform optimal treatment of CH during pregnancy.

Background Gynecologic cancers are associated with high rates of venous thromboembolism (VTE), which is exacerbated by pelvic surgery and chemotherapy. Objectives The aim of this study was to develop and validate a risk score for VTE in patients with gynecologic cancer and to test the predictive ability of the score following addition of procoagulant biomarker data. Patients and methods Clinical and laboratory variables were used to develop a risk score for the prediction of VTE in patients with gynecological cancer (n = 616), which was validated in a separate cohort of patients (n = 406). Endogenous thrombin potential and D‐dimer levels were determined in a subset (n = 290) of patients and used to produce an extended score in the validation cohort. Results Multivariable regression analysis identified BMI >30, hemoglobin

Background Preterm delivery is an independent risk factor for maternal cardiovascular disease. Little is known about the association between preterm delivery and maternal renal function. This study aimed to examine whether women who experience preterm delivery are at increased risk of subsequent chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Methods Using data from the Swedish Medical Birth Register, singleton live births from 1973 to 2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Gestational age at delivery was the main exposure and treated as a time-dependent variable. Primary outcomes were maternal CKD or ESKD. Cox proportional hazard regression models were used for analysis. Results The dataset included 1,943,716 women who had 3,760,429 singleton live births. The median follow-up was 20.6 (interquartile range 9.9–30.0) years. Overall, 162,918 women (8.4%) delivered at least 1 preterm infant ( Conclusions Women with history of preterm delivery are at increased risk of CKD and ESKD. The risk is higher among women who had very preterm or extremely preterm deliveries, or whose preterm delivery was medically indicated. Women who experience spontaneous preterm delivery are at increased risk of long-term renal disease independent of preeclampsia or SGA. Preterm delivery may act as a risk marker for adverse maternal renal outcomes.

Background This study examines compliance with local travel restrictions and assesses early uptake of mask wearing, during the initial phase of the coronavirus disease of 2019 (COVID-19) pandemic in Ireland, to inform the ongoing outbreak response. Methods A series of four nationally representative telephone surveys were developed. Information was collected at a household level and from primary respondents. Multivariable logistic regression estimated the association between sociodemographic characteristics and compliance with the local travel restriction and with mask use in primary respondents. Results Household compliance with local travel restrictions was similar by region, household size and social position. 73.4% of all household members complied, with high levels maintained over time. Higher proportions reported travelling for non-permitted reasons with time. Older age, female gender and attending higher education were independently associated with compliance to local travel restrictions. Among primary respondents, no factors were independently associated with mask use. Conclusion High compliance with local travel restrictions during the early stages of the pandemic demonstrates the engagement of the population with public health guidance. Although high compliance with local travel restrictions was generally maintained over time, non-permitted activities increased. Early adoption of mask use before required by national policy or legislation provides further evidence of the responsiveness of the population.

Background: Patient centred healthcare is the corner stone to many healthcare strategies. Patient specific health needs should be at the fore of healthcare improvements and quality measurements. Patient reported outcome measures (PROM) that support real world clinical effectiveness assessments are increasingly being used to highlight domains where there is the greatest scope for change. Objectives: This systematic review aims to identify and evaluate existing patient reported assessment measures/tool(s) that can be used in developing a PROM for postpartum women. We will assess and evaluate their measurement properties in a transparent and structured way in accordance with the COSMIN guidelines. Methods: Methodological guidelines for systematic reviews of PROMs have been developed by the COSMIN initiative and will be followed for this systematic review. A systematic literature review will be performed using PubMed, CINAHL and EMBASE from inception to the present day. Two reviewers independently will judge eligibility, conduct data extraction and assess the methodological quality of each study as per COSMIN guidelines. Inclusion criteria: studies should concern PROM with an aim to evaluate measurement properties in the development or the evaluation of a PROM of interest. Included PROM will focus upon postpartum women assessing morbidity and quality of care. All peer reviewed studies with an assessment tool designed for patient completion will be considered. Exclusion criteria; abstract, letters and non-peer reviewed publications. Studies will be graded on measurement properties and quality of evidence as laid out by COSMIN. All studies and characteristics eligible for inclusion will be summarised and a recommendation to the most suitable measurement tool(s) will be given. Discussion: We will provide a comprehensive description of all available patient reported assessment tools available for childbirth and postpartum quality of life and recommend based on COSMIN guidelines the most suitable instrument(s) available for use.

Background: Existing studies have established an association between pregnancy, birth complications, and mental health in the first few weeks postpartum. However, there is no clear understanding of whether pregnancy and birth complications increase the risk of adverse maternal mental outcomes in the longer term. Research on maternal adverse mental health outcomes following pregnancy and birth complications beyond 12 months postpartum is scarce, and findings are inconsistent. Objective: This systematic review and meta-analysis will examine the available evidence on the association between pregnancy and birth complications and long-term adverse maternal mental health outcomes. Methods and analysis: We will include cohort, cross-sectional, and case-control studies in which a diagnosis of pregnancy and/or birth complication (preeclampsia, pregnancy loss, caesarean section, preterm birth, perineal laceration, neonatal intensive care unit admission, major obstetric haemorrhage, and birth injury/trauma) was reported and maternal mental disorders (depression, anxiety disorders, bipolar disorders, psychosis, and schizophrenia) after 12 months postpartum were the outcomes. A systematic search of PubMed, Embase, CINAHL, PsycINFO, and Web of Science will be conducted following a detailed search strategy until August 2022. Three authors will independently review titles and abstracts of all eligible studies, extract data using pre-defined standardised data extraction and assess the quality of each study using the Newcastle-Ottawa Scale. We will use random-effects meta-analysis for each exposure and outcome variable to calculate overall pooled estimates using the generic inverse variance method. This systematic review will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Ethical consideration: The proposed systematic review and meta-analysis is based on published data; ethics approval is not required. The results will be presented at scientific meetings and publish in a peer-reviewed journal. PROSPERO registration: CRD42022359017

Biologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy.To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy.PubMed and EMBASE databases were searched through January 1998-July 2021.Peer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data.Two authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the 'treated' group as the reference category. All studies were evaluated using an appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence.Thirty-five studies, describing 11 172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations as follows: treated 0.04 (95% CI 0.03-0.04; IWe demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.

Objective: Limited evidence exists on the role that the cause of chronic kidney disease plays in determining pregnancy outcomes. The aim of this systematic review and meta-analysis was to examine the association between chronic kidney disease and adverse pregnancy outcomes by the cause and severity of chronic kidney disease where reported. The protocol was registered under the International Prospective Register of Systematic Reviews (CRD42020211925). Data Sources: PubMed, Embase, and Web of Science were searched until May 24, 2021, supplemented with reference list checking. Study Eligibility Criteria: Studies that compared the pregnancy outcomes in women with or without chronic kidney disease were included. Two reviewers independently screened titles, abstracts, and full-text articles according to a priori defined inclusion criteria. Methods: Data extraction and quality appraisal were performed independently by 3 reviewers. The grading of recommendations, assessment, development, and evaluation approach was used to assess the overall certainty of the evidence. Random-effects meta-analyses were used to calculate the pooled estimates using the generic inverse variance method. The primary outcomes included preeclampsia, cesarean delivery, preterm birth (

Background The global Covid-19 pandemic response depends heavily on non-pharmaceutical interventions to protect population health. This aim of this study was to provide insights into levels and determinants of adherence to travel restrictions and wearing of face coverings during the early phase of the pandemic response in Ireland. Methods A series of four cross-sectional surveys were administered through random digit dialling of mobile and landline numbers during May-June 2020. Questions were asked about compliance with local travel restrictions and where relevant, the reasons for travel. A question on mask use was added to the final wave of data collection. Results Overall, across the four waves, 73.4% reported adhering to the travel restrictions and these levels were maintained over time (wave 1: 72.1%, wave 2: 73.7%, wave 3: 67.3%, wave 4: 79.7%) and were broadly similar across different socioeconomic groups. Higher proportions reported travelling for non-exempt reasons over time particularly in the final wave of data collection including exercise (from 3% in wave 1, 5% in wave 2 up to 8% in waves 3 and 4) and recreational or social activities (2% in waves 1 and 2, 4% in wave 3, up to 15% by wave 4). Overall, over two-thirds of respondents reported use of masks in the final wave, (72% of women, 65% of men) with shops or supermarkets the most common place of use. Among primary respondents, older age (Age 70+ vs. 18k-44, OR 3.2 [2.4-4.3]), attending higher education (attending vs. completed third level OR 2.2 [ 1.6-3.0]) and female gender (OR 1.2 [1.1-1.4]) were independently associated with compliance with travel restrictions. Conclusions The findings demonstrate high levels of adherence to travel restrictions during the early stages of the emerging COVID-19 pandemic, albeit with a modest trend towards reduced compliance over time. There was a high uptake of mask use in advance of relevant national guidance.

Objective Chronic kidney disease (CKD) has been linked with adverse pregnancy outcomes, but few studies have examined the influence of cause and severity. The aim of this meta-analysis was to synthesize the evidence on CKD and adverse pregnancy outcome, by cause and severity of CKD where reported. Data sources We searched PubMed, Embase, and Web of Science from inception to May 2021. Study selection and Data Extraction: Studies reporting associations between CKD and adverse pregnancy outcomes were included according to pre-defined eligibility criteria (PROSPERO protocol registration: CRD42020211925). Two reviewers independently screened titles, abstracts, and full-text articles and performed data extraction. The certainty of the evidence was assessed using the GRADE approach. Main Outcomes and Measures: We used random-effects meta-analyses to calculate pooled estimates. Primary outcomes included pre-eclampsia, Caesarean section (CS), preterm birth (PTB Results In total, 31 studies were included. The certainty of the evidence was deemed to be ‘very low' for all outcomes using the GRADE approach as expected given the observational study design. Pre-pregnancy CKD was associated with pre-eclampsia [pooled adjusted odds ratio (aOR)=2.58 (1.33-5.01)], CS [aOR=1.65 (1.21-2.25)], PTB [aOR=1.73 (1.31-2.27)] and SGA [aOR= 1.93 (1.06-3.52)]. Subgroup analyses suggested that different causes of CKD had differing risks for adverse pregnancy outcomes, and later stages of CKD, compared to earlier stages, were associated with higher odds of pre-eclampsia [crude OR = 2.77 (1.73-4.44)], PTB [4.21 (2.99-5.92)], and SGA [2.43 (1.33-4.46)]. Conclusions CKD was associated with a higher risk of adverse pregnancy outcomes, and the degree of risk varied by cause and severity. These findings highlight the need for further studies of a more robust quality evaluating the effects of cause and severity of kidney disease on adverse pregnancy outcomes. Key messages Pre-pregnancy CKD was associated with higher risk of adverse pregnancy outcomes. The risk of adverse pregnancy outcomes varied by CKD cause and severity.

Item does not contain fulltext OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

This study aimed to systematically review and evaluate postpartum health and well-being using patient-reported outcome measures across all domains of postpartum health using the COnsensus-based Standards for the selection of health Measurement INstruments guidelines.Based on a preprepared published protocol, a systematic search of PubMed, Embase, and CINAHL was undertaken to identify patient-reported outcome tools. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number CRD42021283472), and this work followed the COnsensus-based Standards for the selection of health Measurement INstruments guidelines for systematic reviews.Studies eligible for inclusion included those that assessed a patient-reported outcome measure examining postpartum women's health and well-being with no limitation on the domain. The included studies aimed to evaluate one or more measurement properties of the patient-reported outcome measure.Data extraction and the methodological assessment of the quality of the patient-reported outcome measure were assessed by 2 reviewers independently based on content validity, structural validity, internal consistency, cross-cultural validity or measurement invariance, reliability, measurement error, hypotheses testing for construct validity, and responsiveness, as defined by the COnsensus-based Standards for the selection of health Measurement INstruments. The standard used for content validity were the domains of importance to women in postpartum health and well-being proposed by the International Consortium for Health Outcomes Measurement. The outcome domains for patient-reported health status include mental health, health-related quality of life, incontinence, pain with intercourse, breastfeeding, and motherhood role transition. The quality of the methods was rated an overall rating of results, awarded a level of evidence, and assessed using the Grading of Recommendations, Assessment, Development, and Evaluations assessment tool, and a level of recommendation was awarded for each tool.There were 10,324 studies identified in the initial search, of which 29 tools were identified from 41 eligible studies included in the review. Moreover, 21 tools were awarded an "A" grading of recommendation for use as a patient-reported outcome measure in postpartum women following the COnsensus-based Standards for the selection of health Measurement Instruments standards. Of the "A"-rated tools, 17 (80%) examined the domain of mental health, 5 examined health-related quality of life, 4 examined breastfeeding, and 6 represented role transition. No "A"-recommended tool examined postpartum incontinence or pain with intercourse. Of note, 3 tools did not cover domains as recommended by the International Consortium for Health Outcomes Measurement, and 5 tools were awarded a "B" rating, requiring more research before their recommendation for use. Here, most tools were awarded very low-moderate Recommendations, Assessment, Development, and Evaluations level of evidence. Moreover, the highest quality tool identified that covered multiple domains of postpartum health and well-being was the women's Postpartum Quality-of-Life Questionnaire.This systematic review identified the best performing patient-reported outcome measures to assess postpartum health and well-being. No individual tool covers all 6 domains of postpartum health and well-being. Here, the highest quality tool found that covered multiple domains of postpartum health and well-being was the Postpartum Quality-of-Life Questionnaire. The Postpartum Quality-of-Life Questionnaire captures 4 of 6 domains of importance to women, with domains of incontinence and sexual health unevaluated. The domain of urinary incontinence was represented by the International Consultation on Incontinence Questionnaire Short Form, which requires further psychometric analysis before its recommended use. Postpartum sexual health, not represented by any tool, necessitates the development of a patient-reported outcome measure. A postpartum patient-reported outcome measure would be best provided by a combination of tools; however, further research is required before its implementation.

Background\ud \ud Many women experience fear of childbirth (FOC). While fears about childbirth may be normal during pregnancy, some women experience high to severe FOC. At the extreme end of the fear spectrum is tocophobia, which is considered a specific condition that may cause distress, affect well‐being during pregnancy and impede the transition to parenthood. Various interventions have been trialled, which support women to reduce and manage high to severe FOC, including tocophobia.\ud Objectives\ud \ud To investigate the effectiveness of non‐pharmacological interventions for reducing fear of childbirth (FOC) compared with standard maternity care in pregnant women with high to severe FOC, including tocophobia.\ud Search methods\ud \ud In July 2020, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. We contacted researchers of trials which were registered and appeared to be ongoing.\ud Selection criteria\ud \ud We included randomised clinical trials which recruited pregnant women with high or severe FOC (as defined by the individual trial), for treatment intended to reduce FOC. Two review authors independently screened and selected titles and abstracts for inclusion. We excluded quasi‐randomised and cross‐over trials.\ud Data collection and analysis\ud \ud We used standard methodological approaches as recommended by Cochrane. Two review authors independently extracted data and assessed the studies for risk of bias. A third review author checked the data analysis for accuracy. We used GRADE to assess the certainty of the evidence. The primary outcome was a reduction in FOC. Secondary outcomes were caesarean section, depression, birth preference for caesarean section or spontaneous vaginal delivery, and epidural use.\ud Main results\ud \ud We included seven trials with a total of 1357 participants. The interventions included psychoeducation, cognitive behavioural therapy, group discussion, peer education and art therapy.\ud \ud We judged four studies as high or unclear risk of bias in terms of allocation concealment; we judged three studies as high risk in terms of incomplete outcome data; and in all studies, there was a high risk of bias due to lack of blinding. We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision and inconsistency. None of the studies reported data about women's anxiety.\ud \ud Participating in non‐pharmacological interventions may reduce levels of fear of childbirth, as measured by the Wijma Delivery Expectancy Questionnaire (W‐DEQ), but the reduction may not be clinically meaningful (mean difference (MD) ‐7.08, 95% confidence interval (CI) ‐12.19 to ‐1.97; 7 studies, 828 women; low‐certainty evidence). The W‐DEQ tool is scored from 0 to 165 (higher score = greater fear).\ud \ud Non‐pharmacological interventions probably reduce the number of women having a caesarean section (RR 0.70, 95% CI 0.55 to 0.89; 5 studies, 557 women; moderate‐certainty evidence).\ud \ud There may be little to no difference between non‐pharmacological interventions and usual care in depression scores measured with the Edinburgh Postnatal Depression Scale (EPDS) (MD 0.09, 95% CI ‐1.23 to 1.40; 2 studies, 399 women; low‐certainty evidence). The EPDS tool is scored from 0 to 30 (higher score = greater depression).\ud \ud Non‐pharmacological interventions probably lead to fewer women preferring a caesarean section (RR 0.37, 95% CI 0.15 to 0.89; 3 studies, 276 women; moderate‐certainty evidence). \ud \ud Non‐pharmacological interventions may increase epidural use compared with usual care, but the 95% CI includes the possibility of a slight reduction in epidural use (RR 1.21, 95% CI 0.98 to 1.48; 2 studies, 380 women; low‐certainty evidence).\ud Authors' conclusions\ud \ud The effect of non‐pharmacological interventions for women with high to severe fear of childbirth in terms of reducing fear is uncertain. Fear of childbirth, as measured by W‐DEQ, may be reduced but it is not certain if this represents a meaningful clinical reduction of fear. There may be little or no difference in depression, but there may be a reduction in caesarean section delivery. Future trials should recruit adequate numbers of women and measure birth satisfaction and anxiety.

In recent years, high-quality evidence has been accumulating that pregnancy complications are linked to a range of chronic diseases in later life. Pregnancy is regarded as a metabolic "stress test" which may unmask women's underlying risk of future cardiovascular disease (CVD) or chronic kidney disease (CKD). However, the potential for this information to be used in long-term cardio-renal risk reduction has not been fully realised. Women who have a history of hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, intra-uterine growth restriction, or pregnancy loss are at higher risk of CVD, cerebrovascular disease, and premature mortality relative to those whose pregnancies were uncomplicated.

Importance: Prenatal stress exposure has been linked to increased risk of autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) in the offspring, although the evidence is inconsistent. Objective: This systematic review and meta-analysis was performed to systematically critically review the existing literature on the association between prenatal stress and the risk of ASD and ADHD. Data sources: Based on a registered protocol, we searched electronic databases PubMed, PsycINFO, Web of Science, Scopus and EMBASE for articles in accordance with a detailed search strategy. Study selection: Two investigators independently searched titles, abstracts and full-text articles. Cohort and case-control studies assessing prenatal exposure to stress and the risk of ASD or ADHD as an outcome measure were included. Study extraction and synthesis: Data extraction and quality assessment were performed independently by two investigators. We performed this study following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Main Outcomes and Measures: Random-effects meta-analyses were performed to calculate adjusted and unadjusted pooled estimates for prenatal stress and risk of ASD and ADHD, using the generic inverse variance method. Results: Of 1456 studies emerged from the databases, 27 studies in total met the inclusion criteria of the systematic review (15 for ASD, 12 for ADHD). Prenatal stress was significantly associated with an increased risk of both ASD (pooled OR=1.64, [95% CI=1.15 – 2.34]; I2=90%) and ADHD (pooled OR=1.72, [95% CI= 1.27-2.34]; I2=85%). A significant association between prenatal and ASD was observed in the meta-analysis of the cohort but not case-control studies. Significant associations for between prenatal stress and ASD and ADHD were observed in low to moderate quality studies but in high quality studies. Conclusions and relevance: This study suggests that prenatal stress may be associated with an increased risk of ASD and ADHD in the offspring. However, several limitations in the included literature should be noted including significant heterogeneity, potential recall bias and lack of adjustment for key potential confounders. Future research exploring this association should address the limitations in the current literature in order to test whether this association is potentially causal or attributable to methodological limitations.

Objective: To compare pregnancy outcomes for women with and without severe fear of childbirth (FOC) reported in the second trimester of pregnancy. Methods: In a prospective cohort study, 389 singleton pregnancies were followed up using medical records of participants in a study investigating FOC in Cork, Republic of Ireland. FOC was measured using the Wijma Delivery Experience Questionnaire Part A (W-DEQ A). Severe FOC was defined as W-DEQ A ≥ 85, moderate FOC, W-DEQ-A 66-84 and low FOC, W-DEQ A 0-65. Outcome measures were birthweight, birthweight centile, gestational age, and Apgar scores at 1 min and Apgar at 5 min. Linear regression was used to assess the association between FOC and each outcome measure with adjustment for maternal age, smoking, parity and marital status. Results: There was no statistically significant difference in mean birthweight (mean difference = −0.03; [95% CI: -444.69, 315.82]), mean birthweight centile (mean difference = 0.03; [95%CI: -15.97, 23.53]), or mean gestational age (mean difference = −0.06; [95%CI: -11.69, 4.82]) in women with severe FOC (n = 18) compared with women with low FOC (n = 371). In the adjusted models, there was only a slight correlation between severe FOC and Apgar scores at 1 min (mean difference = −0.09 [95%CI: -1.28, 0.32]) and Apgar scores at 5 min (mean difference = −0.18 [95%CI: -1.16, 1.08]). Conclusion: While a slight association was noted between severe FOC and Apgar scores, overall findings are reassuring and could inform educational interventions which may alleviate FOC. Awareness of FOC for health care professionals is vital to consider women's mental well-being.

Introduction There is growing evidence of the considerable impact of fear of childbirth on women's health and well‐being, but prevalence reports of high and severe fear of childbirth and reported risk factors have been inconsistent in various studies. Therefore, this study aimed to determine the prevalence of high and severe fear of childbirth, and to identify risk factors of childbirth fear. Material and methods A cross‐sectional study was conducted among a convenience sample of 882 pregnant women attending antenatal care in Cork, Ireland. Fear of childbirth was assessed using the Wijma Delivery Expectancy Questionnaire version A (W‐DEQ A) using a cut‐off ≥66 to define high fear and ≥85 to define severe fear. Associated risk factors were investigated using univariate and multivariate multinomial logistic regression analyses. Four W‐DEQ A subscales were calculated using a cut‐off ≥2.5 to determine the nature of childbirth fear. Results Overall prevalence of severe fear of childbirth was 5.3% and high fear of childbirth was 36.7%. The prevalence of severe fear of childbirth was 7.4% in nulliparous women and 4.3% in multiparous women; however, the difference was not statistically significant (P < 0.07). The prevalence of high fear of childbirth was 43% in nulliparous women and 33.6% in multiparous women, and this difference was statistically significant (P < 0.005). High fear of childbirth was associated with single marital status when compared with married or co‐habiting women (P < 0.008). In a multivariate analysis, high fear of childbirth was significantly associated with low perceived informational support (adjusted relative risk ratio 2.62, 95% confidence interval [CI] 1.34‐5.13) and possible depression (assessed by the Edinburgh Postnatal Depression Scale) (adjusted relative risk ratio 12.87, 95% CI 6.07‐27.25). In the W‐DEQ A subscales, 35.6% of women scored ≥2.5 in Negative Emotions, 29.4% scored ≥2.5 in Lack of Positive Emotions, 9.9% scored ≥2.5 in Social Isolation and 7.8% scored ≥2.5 in Moment of Birth. Conclusions Fear of childbirth is relatively common, with varying severity, and was more common in first‐time mothers. Using W‐DEQ A subscales provided additional information about the nature of the fear, in addition to severity of fear of childbirth.