A rapid review of measures to support people in isolation or quarantine during the Covid-19 pandemic and the effectiveness of such measures.

This rapid review aimed to identify measures available to support those in isolation or quarantine during the coronavirus disease 2019 (Covid-19) pandemic, and determine their effectiveness in improving adherence to these recommendations and or reducing transmission. The rapid review consisted of two elements, the first was a review of guidance published by national and international agencies relating to measures to support those in isolation (due to case status) or quarantine (due to close contact status) during the Covid-19 pandemic. Five categories of support measures were identified in the international guidance, they were: Psychological, addiction and safety supports, Essential supplies, Financial aid, Information provision and Enforcement. The second element was a rapid literature review of the effectiveness of measures used to support individuals in isolation or quarantine during any pandemic or epidemic setting, due to respiratory pathogens. A systematic search of published peer-reviewed articles and nonpeer-reviewed pre-prints was undertaken from 1 January 2000 to 26 January 2021. Two Australian publications met the inclusion criteria, both based on data from a survey undertaken during the 2009 H1N1 pandemic. The first reported that 55% of households were fully compliant with quarantine recommendations, and that there was increased compliance reported in households that understood what they were meant to do compared with those who reported that they did not (odds ratio [OR]: 2.27, 95% confidence interval [CI]: 1.35-3.80). The second reported that access to paid sick and or carer's leave did not predict compliance with quarantine recommendations (OR: 2.07, 95% CI: 0.82-5.23). Neither reported on reduction in transmission.

Laboratory-based testing for hepatitis C infection using dried blood spot samples: A systematic review and meta-analysis of diagnostic accuracy.

The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratory-based anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n = 25; I2  = 81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n = 20; I2  = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n = 5; I2  = 37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.

Pharmacological interventions to prevent Covid-19 disease: A rapid review.

The aim of this rapid review was to determine the effectiveness of pharmacological interventions (excluding vaccines) to prevent coronavirus disease 2019 (Covid-19) or reduce the severity of disease. A systematic search of published peer-reviewed articles and non-peer-reviewed pre-prints was undertaken from 1 January 2020 to 17 August 2021. Four randomised controlled trials (RCTs) and one non-RCT were included; three trials (two RCTs and one non-RCT) tested ivermectin with or without carrageenan. While all reported some potential protective effect of ivermectin, these trials had a high risk of bias and the certainty of evidence was deemed to be 'very low'. One RCT tested bamlanivimab compared to placebo and reported a significantly reduced incidence of Covid-19 in the intervention group; this trial had a low risk of bias however the certainty of evidence was deemed 'very low'. The fifth RCT tested casirivimab plus imdevimab versus placebo and reported that the combination of monoclonal antibodies significantly reduced the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, viral load, duration of symptomatic disease and the duration of a high viral load; this trial was deemed to have a low risk of bias, and the certainty of evidence was 'low'. The designations 'low' and 'very low' regarding the certainty of evidence indicate that the estimate of effect is uncertain and therefore is unsuitable for informing decision-making. At the time of writing, there is insufficient high quality evidence to support the use of pharmacological interventions to prevent Covid-19.

Chronic kidney disease and adverse pregnancy outcomes: a systematic review and meta-analysis.

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 (<37 weeks' gestation), and small for gestational age babies. RESULTS: Of 4076 citations, 31 studies were included. Prepregnancy chronic kidney disease was significantly associated with a higher odds of preeclampsia (pooled crude odds ratio, 8.13; [95% confidence interval, 4.41-15], and adjusted odds ratio, 2.58; [1.33-5.01]), cesarean delivery (adjusted odds ratio, 1.65; [1.21-2.25]), preterm birth (adjusted odds ratio, 1.73; [1.31-2.27]), and small for gestational age babies (adjusted odds ratio, 1.93; [1.06-3.52]). The association with stillbirth was not statistically significant (adjusted odds ratio, 1.67; [0.96-2.92]). Subgroup analyses indicated that different causes of chronic kidney disease might confer different risks and that the severity of chronic kidney disease is associated with a risk of adverse pregnancy outcomes, as pregnancies with later stages of chronic kidney disease had higher odds of preeclampsia, preterm birth, and small for gestational age babies than those at earlier stages. The grading of recommendations, assessment, development, and evaluation certainty of the evidence overall was "very low". CONCLUSION: This meta-analysis quantified the associations between prepregnancy chronic kidney disease and adverse pregnancy outcomes, both overall and according to the cause and severity of the disease. These findings might support the clinicians aiming to counsel women having chronic kidney disease by allowing them to tailor their advice according to cause and severity of the chronic kidney disease. We identified the gaps in the literature, and further studies examining the effect of specific kidney diseases and other clinical characteristics (eg, proteinuria, hypertension) on adverse pregnancy outcomes are warranted.

Interventions for fear of childbirth including tocophobia.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: We included seven trials with a total of 1357 participants. The interventions included psychoeducation, cognitive behavioural therapy, group discussion, peer education and art therapy. 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. 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). 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). 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). 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).  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). AUTHORS' CONCLUSIONS: 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.

The prevalence and risk factors of fear of childbirth among pregnant women: A cross-sectional study in Ireland.

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.

Different insulin types and regimens for pregnant women with pre-existing diabetes.

BACKGROUND: Insulin requirements may change during pregnancy, and the optimal treatment for pre-existing diabetes is unclear. There are several insulin regimens (e.g. via syringe, pen) and types of insulin (e.g. fast-acting insulin, human insulin). OBJECTIVES: To assess the effects of different insulin types and different insulin regimens in pregnant women with pre-existing type 1 or type 2 diabetes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 October 2016), ClinicalTrials.gov (17 October 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 17 October 2016), and the reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared different insulin types and regimens in pregnant women with pre-existing diabetes.We had planned to include cluster-RCTs, but none were identified. We excluded quasi-randomised controlled trials and cross-over trials. We included studies published in abstract form and contacted the authors for further details when applicable. Conference abstracts were superseded by full publications. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, conducted data extraction, assessed risk of bias, and checked for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: The findings in this review were based on very low-quality evidence, from single, small sample sized trial estimates, with wide confidence intervals (CI), some of which crossed the line of no effect; many of the prespecified outcomes were not reported. Therefore, they should be interpreted with caution. We included five trials that included 554 women and babies (four open-label, multi-centre, two-arm trials; one single centre, four-arm RCT). All five trials were at a high or unclear risk of bias due to lack of blinding, unclear methods of randomisation, and selective reporting of outcomes. Pooling of data from the trials was not possible, as each trial looked at a different comparison.1. One trial (N = 33 women) compared Lispro insulin with regular insulin and provided very low-quality evidence for the outcomes. There were seven episodes of pre-eclampsia in the Lispro group and nine in the regular insulin group, with no clear difference between the two groups (risk ratio (RR) 0.68, 95% CI 0.35 to 1.30). There were five caesarean sections in the Lispro group and nine in the regular insulin group, with no clear difference between the two groups (RR 0.59, 95% CI 0.25 to 1.39). There were no cases of fetal anomaly in the Lispro group and one in the regular insulin group, with no clear difference between the groups (RR 0.35, 95% CI 0.02 to 8.08). Macrosomia, perinatal deaths, episodes of birth trauma including shoulder dystocia, nerve palsy, and fracture, and the composite outcome measure of neonatal morbidity were not reported.2. One trial (N = 42 women) compared human insulin to animal insulin, and provided very low-quality evidence for the outcomes. There were no cases of macrosomia in the human insulin group and two in the animal insulin group, with no clear difference between the groups (RR 0.22, 95% CI 0.01 to 4.30). Perinatal death, pre-eclampsia, caesarean section, fetal anomaly, birth trauma including shoulder dystocia, nerve palsy and fracture and the composite outcome measure of neonatal morbidity were not reported.3. One trial (N = 93 women) compared pre-mixed insulin (70 NPH/30 REG) to self-mixed, split-dose insulin and provided very low-quality evidence to support the outcomes. Two cases of macrosomia were reported in the pre-mixed insulin group and four in the self-mixed insulin group, with no clear difference between the two groups (RR 0.49, 95% CI 0.09 to 2.54). There were seven cases of caesarean section (for cephalo-pelvic disproportion) in the pre-mixed insulin group and 12 in the self-mixed insulin group, with no clear difference between groups (RR 0.57, 95% CI 0.25 to 1.32). Perinatal death, pre-eclampsia, fetal anomaly, birth trauma including shoulder dystocia, nerve palsy, or fracture and the composite outcome measure of neonatal morbidity were not reported.4. In the same trial (N = 93 women), insulin injected with a Novolin pen was compared to insulin injected with a conventional needle (syringe), which provided very low-quality evidence to support the outcomes. There was one case of macrosomia in the pen group and five in the needle group, with no clear difference between the different insulin regimens (RR 0.21, 95% CI 0.03 to 1.76). There were five deliveries by caesarean section in the pen group compared with 14 in the needle group; women were less likely to deliver via caesarean section when insulin was injected with a pen compared to a conventional needle (RR 0.38, 95% CI 0.15 to 0.97). Perinatal death, pre-eclampsia, fetal anomaly, birth trauma including shoulder dystocia, nerve palsy, or fracture, and the composite outcome measure of neonatal morbidity were not reported.5. One trial (N = 223 women) comparing insulin Aspart with human insulin reported none of the review's primary outcomes: macrosomia, perinatal death, pre-eclampsia, caesarean section, fetal anomaly, birth trauma including shoulder dystocia. nerve palsy, or fracture, or the composite outcome measure of neonatal morbidity.6. One trial (N = 162 women) compared insulin Detemir with NPH insulin, and supported the outcomes with very low-quality evidence. There were three cases of major fetal anomalies in the insulin Detemir group and one in the NPH insulin group, with no clear difference between the groups (RR 3.15, 95% CI 0.33 to 29.67). Macrosomia, perinatal death, pre-eclampsia, caesarean section, birth trauma including shoulder dystocia, nerve palsy, or fracture and the composite outcome of neonatal morbidity were not reported. AUTHORS' CONCLUSIONS: With limited evidence and no meta-analyses, as each trial looked at a different comparison, no firm conclusions could be made about different insulin types and regimens in pregnant women with pre-existing type 1 or 2 diabetes. Further research is warranted to determine who has an increased risk of adverse pregnancy outcome. This would include larger trials, incorporating adequate randomisation and blinding, and key outcomes that include macrosomia, pregnancy loss, pre-eclampsia, caesarean section, fetal anomalies, and birth trauma.

Worldwide prevalence of tocophobia in pregnant women: systematic review and meta-analysis.

INTRODUCTION: Tocophobia is defined as a severe fear of pregnancy and childbirth. There is increasing evidence that tocophobia may have short-term and long-term adverse effects on mother and baby. We performed a systematic review and meta-analysis to determine the global prevalence of tocophobia in pregnancy. MATERIAL AND METHODS: Relevant articles were identified through searching six relevant databases: MEDLINE, CINAHL, Pubmed, PsycINFO, Maternity & Infant Care and Scopus between 1946 and April 2016. We used search terms for tocophobia prevalence in pregnant women that we agreed on with a medical librarian. There were no language restrictions. Two review authors independently assessed data for inclusion, extracted data and assessed quality using a standardized appraisal tool. Meta-analysis was performed to determine the overall pooled-prevalence of tocophobia. Several subgroup and sensitivity analyses were conducted. RESULTS: Thirty-three studies were included in the systematic review from 18 countries of which data from 29 studies were used in the meta-analysis of 853 988 pregnant women. Definition of tocophobia varied, whereas prevalence rates ranged between 3.7 and 43%. The overall pooled prevalence of tocophobia, using a random-effects model, was 14% (95% CI 0.12-0.16). Significant heterogeneity was observed (I2 = 99.25%, p = 0.00), which was not explained in subgroup analyses including tocophobia definition used, screening trimester and parity. CONCLUSION: The prevalence of tocophobia is estimated at 14% and appears to have increased in recent years (2000 onwards). Considerable heterogeneity (99.25%) was noted that may be attributed to lack of consensus on the definition of tocophobia, so our results should be interpreted with caution.

Trial of labour after caesarean section and the risk of neonatal and infant death: a nationwide cohort study.

BACKGROUND: Caesarean section (CS) rates are increasing worldwide and as a result repeat CS is common. The optimal mode of delivery in women with one previous CS is widely debated and the risks to the infant are understudied. The aim of the current study was to evaluate if women with a trial of labour after caesarean (TOLAC) had an increased odds of neonatal and infant death compared to women with an elective repeat CS (ERCS). METHODS: A population register-based cohort study was conducted in Denmark between 1982 and 2010. All women with two deliveries [in which the first was a CS, and the second was an uncomplicated, term delivery (n = 61,626)] were included in the study. Logistic regression models were used to report adjusted odds ratios (AOR) and 95% confidence intervals (CI) of the odds of death according to mode of delivery. The main outcome measures were neonatal death (early and late) and infant death. RESULTS: Women with a TOLAC had an increased odds of neonatal death (AOR 1 · 87, 95% CI 1 · 12 to 3 · 12) due to an increased risk of early neonatal death (AOR 2 · 06, 95% CI 1 · 19 to 3 · 56) and no effect on late neonatal death (AOR 0 · 97, 95% CI 0 · 22 to 4 · 32), or infant death (AOR 1 · 12, 95% CI 0 · 79 to 1 · 59) when compared to the reference group of women with an ERCS. There was evidence of a cohort effect as the increased odds of neonatal death (AOR 3 · 89, 95% CI 1 · 33 to 11 · 39) was most significant in the earlier years (1982-1991) and gradually disappeared (AOR 1 · 01, 95% CI 0 · 44 to 2 · 31) in the later years (2002-2010). CONCLUSIONS: Although an increased risk of neonatal death was found in women with a TOLAC, there was evidence of a cohort effect, which showed this increased odds disappearing over time. Advances in modern healthcare including improved monitoring and earlier detection of underlying pregnancy complications may explain the findings.

The Terrorist Attacks and the Human Live Birth Sex Ratio: a Systematic Review and Meta-Analysis.

AIM: The live birth sex ratio is defined as male/total births (M/F). Terrorist attacks have been associated with a transient decline in M/F 3-5 months later with an excess of male losses in ongoing pregnancies. The early 21st century is replete with religious/politically instigated attacks. This study estimated the pooled effect size between exposure to attacks and M/F. Registration number CRD42016041220. METHODS: PubMed and Scopus were searched for ecological studies that evaluated the relationship between terrorist attacks from 1/1/2000 to 16/6/2016 and M/F. An overall pooled odds ratio (OR) for the main outcome was generated using the generic inverse variance method. RESULTS: Five studies were included: 2011 Norway attacks; 2012 Sandy Hook Elementary School shooting; 2001 September 11 attacks; 2004 Madrid and 2005 London bombings. OR at 0.97 95% CI (0.94-1.00) (I2 = 63%) showed a small statistically significant 3% decline in the odds (p = 0.03) of having a male live birth 3-5 months later. For lone wolf attacks there was a 10% reduction, OR 0.90 95% CI (0.86-0.95) (p = 0.0001). CONCLUSION: Terrorist (especially lone wolf) attacks were significantly associated with reduced odds of having a live male birth. Pregnancy loss remains an important Public Health challenge. Systematic reviews and meta-analyses considering other calamities are warranted.

Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis.

BACKGROUND: Given the growing prevalence of birth by Caesarean section (CS) worldwide, it is important to understand any long-term effects CS delivery may have on a child's development. We assessed the impact of mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a systematic review of the literature in PubMed, Embase, CINAHL, PsycINFO and Web of Science up to 28 February 2014. No publication date, language, location or age restrictions were employed. RESULTS: Thirteen studies reported an adjusted estimate for CS-ASD, producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40). Two studies reported an adjusted estimate for CS-ADHD, producing a pooled OR of 1.07 (95% CI: 0.86, 1.33). CONCLUSIONS: Delivery by CS is associated with a modest increased odds of ASD, and possibly ADHD, when compared to vaginal delivery. Although the effect may be due to residual confounding, the current and accelerating rate of CS implies that even a small increase in the odds of disorders, such as ASD or ADHD, may have a large impact on the society as a whole. This warrants further investigation.

The impact of obstetric mode of delivery on childhood behavior.

PURPOSE: We investigated the hypothesis that mode of delivery affects childhood behavior and motor development and examined whether there are sex-specific associations, i.e., whether males and females have different risk estimates. METHODS: Families with infants born between December 2007 and May 2008 (N = 11,134) were randomly selected and recruited to the Growing Up in Ireland study. Mode of delivery was classified into spontaneous vaginal delivery; instrumental vaginal delivery; emergency Cesarean section (CS); and elective CS. The 'Ages and Stages Questionnaire' was completed at age 9-months and the 'Strengths and Difficulties Questionnaire' at 3 years. Data were weighted to represent the national sample (N = 73,662) and multivariate logistic regression was used for the statistical analyses. RESULTS: At age 9 months, elective CS was associated with a delay in personal social skills [adjusted odds ratio, aOR 1.24; (95% confidence interval, CI 1.04, 1.48)] and gross motor function [aOR 1.62, (95% CI 1.34, 1.96)], whereas emergency CS was associated with delayed gross motor function [aOR 1.30, (95% CI 1.06, 1.59)]. At age 3 years there was no significantly increased risk of an abnormal total SDQ score across all modes of delivery. CONCLUSIONS: Children born by elective CS may face a delay in cognitive and motor development at age 9 months. No increase in total SDQ score was found across all modes of delivery. Further investigation is needed to replicate these findings in other populations and explore the potential biological mechanisms.

Cesarean section and rate of subsequent stillbirth, miscarriage, and ectopic pregnancy: a Danish register-based cohort study.

BACKGROUND: With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. METHODS AND FINDINGS: We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. CONCLUSIONS: This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery. Please see later in the article for the Editors' Summary.

Does a Caesarean section increase the time to a second live birth? A register-based cohort study.

STUDY QUESTION: Does a primary Caesarean section influence the rate of, and time to, subsequent live birth compared with vaginal delivery? SUMMARY ANSWER: Caesarean section was associated with a reduction in the rate of subsequent live birth, particularly among elective and maternal-requested Caesareans indicating maternal choice plays a role. WHAT IS KNOWN ALREADY: Several studies have examined the relationship between Caesarean section and subsequent birth rate with conflicting results primarily due to poor epidemiological methods. STUDY DESIGN, SIZE, DURATION: This Danish population register-based cohort study covered the period from 1982 to 2010 (N = 832 996). PARTICIPANTS/MATERIALS, SETTING, METHODS: All women with index live births were followed until their subsequent live birth or censored (maternal death, emigration or study end) using Cox regression models. MAIN RESULTS AND THE ROLE OF CHANCE: In all 577 830 (69%) women had a subsequent live birth. Women with any type of Caesarean had a reduced rate of subsequent live birth (hazard ratio [HR] 0.86, 95% confidence intervals [CI] 0.85, 0.87) compared with spontaneous vaginal delivery. This effect was consistent when analyses were stratified by type of Caesarean: emergency (HR 0.87, 95% CI 0.86, 0.88), elective (HR 0.83, 95% CI 0.82, 0.84) and maternal-requested (HR 0.61, 95% CI 0.57, 0.66) and in the extensive sub-analyses performed. LIMITATIONS, REASONS FOR CAUTION: Lack of biological data to measure a woman's fertility is a major limitation of the current study. Unmeasured confounding and limited availability of data (maternal BMI, smoking, access to fertility services and maternal-requested Caesarean section) as well as changes in maternity care over time may also influence the findings. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date and shows that Caesarean section is most likely not causally related to a reduction in fertility. Maternal choice to delay or avoid childbirth is the most plausible explanation. Our findings are generalizable to other middle- to high-income countries; however, cross country variations in Caesarean section rates and social or cultural differences are acknowledged. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by the National Perinatal Epidemiology Centre, Cork, Ireland and conducted as part of the Health Research Board PhD Scholars programme in Health Services Research (Grant No. PHD/2007/16). L.C.K. is a Science Foundation Ireland Principal Investigator (08/IN.1/B2083) and the Director of the SFI funded Centre, INFANT (12/RC/2272). The authors have no competing interests to declare.

Caesarean delivery and subsequent pregnancy interval: a systematic review and meta-analysis.

BACKGROUND: Caesarean delivery has increased worldwide, however, the effects on fertility are largely unknown. This systematic review aims to compare subsequent sub-fertility (time to next pregnancy or birth) among women with a Caesarean delivery to women with a vaginal delivery. METHODS: Systematic review of the literature including seven databases: CINAHL; the Cochrane Library; Embase; Medline; PubMed; SCOPUS and Web of Knowledge (1945 - October 2012), using detailed search-strategies and reference list cross-checking. Cohort, case-control and cross-sectional studies were included. Two assessors reviewed titles, abstracts, and full articles using standardised data abstraction forms and assessed study quality. RESULTS: 11 articles were eligible for inclusion in the systematic review, of these five articles which adjusted for confounders were combined in a meta-analysis, totalling 750,407 women using fixed-effect models. Previous Caesarean delivery was associated with an increased risk of sub-fertility [pooled odds ratio (OR) 0.90; 95% CI 0.86, 0.93]. Subgroup analyses by parity [primiparous women: OR 0.91; 95% CI 0.87, 0.96; not limited to primiparous women: OR 0.81; 95% CI 0.73, 0.90]; by publication date (pre-2000: OR 0.80, 95% CI 0.68, 0.94; post-2000: OR 0.90, 95% CI 0.86, 0.94); by length of follow-up (<10 years: OR 0.81, 95% CI 0.73, 0.90; >10 years: OR 0.91, 95% CI 0.87, 0.96); by indication for mode of delivery (specified: 0.92, 95% CI 0.88, 0.97; not specified: OR 0.81, 95% CI 0.73, 0.90); by cohort size (<35,000: OR 0.79, 95% CI 0.67, 0.92; >35,000: OR 0.90, 95% CI 0.87, 0.95), by definition of sub-fertility used divided into (birth interval [BI]: OR 0.89, 95% CI 0.84, 0.94; inter-pregnancy interval [IPI]: OR 0.91, 95% CI 0.85, 0.97; and categorical measures: OR 0.81, 95% CI 0.73, 0.90); continuous measures: OR 0.91, 95% CI 0.87, 0.96) were performed. Results of the six studies not included in the meta-analysis (which did not adjust for confounders) are presented individually. CONCLUSIONS: The meta-analysis shows an increased waiting time to next pregnancy and risk of sub-fertility among women with a previous Caesarean delivery. However, included studies are limited by poor epidemiological methods such as variations in the definition of time to next pregnancy, lack of confounding adjustment, or details of the indication for Caesarean delivery. Further research of a more robust methodological quality to better explore any underlying causes of sub-fertility and maternal intent to delay childbearing is warranted.

Child mortality as predicted by nutritional status and recent weight velocity in children under two in rural Africa.

WHO has released prescriptive child growth standards for, among others, BMI-for-age (BMI-FA), mid-upper arm circumference-for-age, and weight velocity. The ability of these indices to predict child mortality remains understudied, although growth velocity prognostic value underlies current growth monitoring programs. The study aims were first to assess, in children under 2, the independent and combined ability of these indices and of stunting to predict all-cause mortality within 3 mo, and second, the comparative abilities of weight-for-length (WFL) and BMI-FA to predict short-term (<3 mo) mortality. We used anthropometry and survival data from 2402 children aged between 0 and 24 mo in a rural area of the Democratic Republic of Congo with high malnutrition and mortality rates and limited nutritional rehabilitation. Analyses used Cox proportional hazard models and receiver operating characteristic curves. Univariate analysis and age-adjusted analysis showed predictive ability of all indices. Multivariate analysis without age adjustment showed that only very low weight velocity [HR = 3.82 (95%CI = 1.91, 7.63); P < 0.001] was independently predictive. With age adjustment, very low weight velocity [HR = 3.61 (95%CI = 1.80, 7.25); P < 0.001] was again solely retained as an independent predictor. There was no evidence for a difference in predictive ability between WFL and BMI-FA. This paper shows the value of attained BMI-FA, a marker of wasting status, and recent weight velocity, a marker of the wasting process, in predicting child death using the WHO child growth standards. WFL and BMI-FA appear equivalent as predictors.

Patients' spirituality perspectives at the end of life: a qualitative evidence synthesis.

BACKGROUND: Understanding patient perceptions of their spiritual needs when approaching the end of life is essential to support the delivery of patient-centred care. AIM: To conduct a qualitative evidence synthesis on spirituality and spiritual care needs at the end of life in all healthcare settings from the patients' perspective. DESIGN: Studies were included where they were primary qualitative studies exploring spirituality in patients with a life expectancy of 12 months or less in any setting. Two reviewers independently screened titles, extracted data and conducted methodological quality appraisal. A thematic synthesis was conducted. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) - Confidence in the Evidence from Reviews of Qualitative research (CERQual) was used to summarise the certainty of the evidence. DATA SOURCES: Six databases (Medline, Embase, Cochrane, CINAHL, PsycINFO, Applied Social Science Index and Abstracts) were searched from inception up to January 2019. RESULTS: Fifty papers (42 unique datasets), incorporating data from 710 patients were included. Studies recruited from a mix of inpatient, outpatient, hospice and community settings across 12 different countries. Three overarching themes were generated: the concept of spirituality, spiritual needs and distress, and spiritual care resources. Relationships were an intrinsic component of spirituality. CONCLUSION: Meeting patients' spiritual needs is an integral part of end-of-life care. This work emphasises that supporting relationships should be a central focus of spiritual care for patients at the end of life. PROSPERO REGISTRATION NUMBER: CRD42019122062.

The Impact of Caesarean Section on the Risk of Childhood Overweight and Obesity: New Evidence from a Contemporary Cohort Study.

Caesarean section (CS) rates are increasing globally and exceed 50% in some countries. Childhood obesity has been linked to CS via lack of exposure to vaginal microflora although the literature is inconsistent. We investigated the association between CS birth and the risk of childhood obesity using the nationally representative Growing-Up-in-Ireland (GUI) cohort. The GUI study recruited randomly 11134 infants. The exposure was categorised into normal vaginal birth (VD) [reference], assisted VD, elective (planned) CS and emergency (unplanned) CS. The primary outcome measure was obesity defined according to the International Obesity Taskforce criteria. Statistical analysis included multinomial logistic regression with adjustment for potential confounders. Infants delivered by elective CS had an adjusted relative risk ratio (aRRR) = 1.32; [95% confidence interval (CI) 1.01-1.74] of being obese at age three years. This association was attenuated when macrosomic children were excluded (aRRR = 0.99; [95% CI 0.67-1.45]). Infants delivered by emergency CS had an increased risk of obesity aRRR = 1.56; [95% CI 1.20-2.03]; this association remained after excluding macrosomic children. We found insufficient evidence to support a causal relationship between elective CS and childhood obesity. An increased risk of obesity in children born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora.

Comorbid depression and risk of lower extremity amputation in people with diabetes: systematic review and meta-analysis.

OBJECTIVE: To compare the risk of lower extremity amputation (LEA) in people with diabetes with and without comorbid depression. RESEARCH DESIGN AND METHODS: A systematic review of the published literature was conducted. Six databases were searched including PubMed, CINAHL, EMBASE, Medline, the Cochrane Library and PsycARTICLES from inception to 22 June 2016, using a detailed search strategy and cross-checking of reference lists for potentially eligible studies published in English. No date restrictions were employed. All studies were reviewed independently for inclusion by two review authors. Data extraction was performed using a standardized data abstraction form, and study quality was assessed independently by two reviewers. A meta-analysis was performed reporting pooled hazard ratios (HRs) and 95% CIs in Review Manager software. RESULTS: In total, seven studies were eligible for inclusion in the systematic review. Data on 767 997 patients from five studies were included in the meta-analysis. Pooled estimates across the studies were obtained using a random-effects model due to significant heterogeneity (I2=87%). People with diabetes and depression had an increased hazard of LEA (HR 1.76, 95% CI 1.19 to 2.60) compared to people with diabetes and no depression. CONCLUSIONS: Based on the available evidence, comorbid depression appears to increase the risk of LEA in people with diabetes. Limited data were available, however, with significant heterogeneity between studies. Further research is needed to inform intervention and clinical practice development in the management of diabetes.