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.

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.

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.

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.

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.

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.

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.

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.

Thin-for-gestational age infants are at increased risk of neurodevelopmental delay at 2†years.

BACKGROUND: Infants born small-for-gestational age (SGA) are at increased risk of developmental difficulties. Identifying those most at risk is challenging. We examined the effect of neonatal body composition and customised birthweight centiles on neurocognitive and behavioural outcomes at age 2. STUDY DESIGN: Prospective cohort study of term infants from the Cork BASELINE Birth Cohort Study classified into the following exposure groups: a birth weight <10th customised centile (SGA, n=51); body fat percentage at birth <10th centile (thin-for-gestational age (TGA, n=51)) or both SGA and TGA infants (small- and thin-for-gestational age (STGA), n=13). The SGA, TGA and STGA groups were compared with a reference (unexposed) group of appropriate-for-gestational age (AGA, n=189) infants. Outcome was assessed at 24 months using the Bayley Scales of Infant Development Version III and the Child Behaviour Checklist. RESULTS: Outcomes in the SGA infants did not differ significantly from the AGA group. TGA infants had significantly lower scores across all three domains, with a 0.35, 0.38 and 0.41 SD reduction in language, cognitive and motor scale scores, respectively. STGA infants had poorer cognitive outcome with a median cognitive scale score of 90 (IQR 85-95) compared with 95 (IQR 90-100) in the AGA reference group, p=0.005. The adjusted OR of developmental delay at 2 years was 5.00 (95% CI 1.46 to 17.13, p=0.010) in the STGA group. CONCLUSION: TGA infants, in particular those born STGA, are at increased risk of developmental delay at 2 years compared with the AGA infants.

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.

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.

Incidence of surgical site infection following caesarean section: a systematic review and meta-analysis protocol.

INTRODUCTION: Caesarean section (CS) rates have increased globally during the past three decades. Surgical site infection (SSI) following CS is a common cause of morbidity with reported rates of 3-15%. SSI represents a substantial burden to the health system including increased length of hospitalisation and costs of postdischarge care. The definition of SSI varies with the postoperative follow-up period among different health systems, resulting in differences in the reporting of SSI incidence. We propose to conduct the first systematic review and meta-analysis to determine the pooled estimate for the overall incidence of SSI following CS. METHODS AND ANALYSIS: We will perform a comprehensive search to identify all potentially relevant published studies on the incidence of SSI following CS reported from 1992 in the English language. Electronic databases including PubMed, CINAHL, EMBASE and Scopus will be searched using a detailed search strategy. Following study selection, full-text paper retrieval, data extraction and synthesis, we will appraise study quality and risk of bias and assess heterogeneity. Incidence data will be combined where feasible in a meta-analysis using Stata software and fixed-effects or random-effects models as appropriate. This systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ETHICS AND DISSEMINATION: Ethical approval is not required as this review will use published data. The review will evaluate the overall incidence of SSI following CS and will provide the first quantitative estimate of the magnitude of SSI. It will serve as a benchmark for future studies, identify research gaps and remaining challenges, and emphasise the need for appropriate prevention and control measures for SSI post-CS. A manuscript reporting the results of the systematic review and meta-analysis will be submitted to a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: CRD42015024426.

Birth by Caesarean Section and the Risk of Adult Psychosis: A Population-Based Cohort Study.

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n= 1,345,210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) (χ(2)for heterogeneityP= .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment.

Neonatal outcomes following elective caesarean delivery at term: a hospital-based cohort study.

OBJECTIVE: To assess neonatal outcomes following elective caesarean delivery (CD) at term (≥37 + 0 weeks gestation). METHODS: A retrospective cohort study was conducted in a single Irish maternity hospital. Elective CDs at term between August 2008 and July 2012 were reviewed. Outcome measures were admission to the neonatal intensive care unit (NICU), length of stay, respiratory complications, hypoglycaemia, jaundice, newborn sepsis and medical interventions. RESULTS: A total of 4242 women had an elective CD at term, accounting for approximately 15% of all term deliveries. Admission rate to the NICU at 37 weeks gestation was 21.8% versus 10% at 39 weeks (p for trend <0.0001). Similar trends of decreasing risk with later gestational age were noted for the other outcomes. An increased odds of admission to the NICU at 37 weeks [adjusted odds ratio (OR) 2.48 (95% CI 1.28, 4.79)] and at 38 weeks [OR 1.34, 95% CI 1.02, 1.77] compared to the reference of 39 weeks gestation was found. CONCLUSIONS: This study supports evidence that, with regard to neonatal outcome, 39 weeks gestational age is the optimal delivery time. Heightened awareness of the increased risk of neonatal morbidity, when delivery is performed electively before 39 weeks, is warranted among healthcare workers.

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.

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.