Fetal and maternal outcomes after maternal biologic use during conception and pregnancy: A systematic review and meta-analysis.

BACKGROUND: Biologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy. OBJECTIVE: To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy. SEARCH STRATEGY: PubMed and EMBASE databases were searched through January 1998-July 2021. SELECTION CRITERIA: Peer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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; I2  = 77) versus disease-matched 0.04 (95% CI 0.03-0.05. I2  = 86; p = 0.238); preterm delivery treated 0.04 (95% CI 0.10-0.14; I2  = 88) versus disease-matched 0.10 (95% CI 0.09-0.12; I2  = 87; p = 0.250); severe neonatal infection: treated 0.05 (95% CI 0.03-0.07; I2  = 88) versus disease-matched 0.05 (95% CI 0.02-0.07; I2  = 94; p = 0.970); low birthweight: treated 0.10 (95% CI 0.07-0.12; I2  = 93) versus disease-matched 0.08 (95% CI 0.07-0.09; I2  = 0; p = 0.241); pooled miscarriage: treated 0.13 (95% CI 0.10-0.15; I2  = 77) versus disease-matched 0.08 (95% CI 0.04-0.11; I2  = 5; p = 0.078); pre-eclampsia; treated 0.01 (95% CI 0.01-0.02; I2  = 0) versus disease-matched 0.01 (95% CI 0.00-0.01; I2  = 0; p = 0.193). No statistical differences in proportions were observed. GRADE certainty of findings was low to very low. CONCLUSION: We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.

Medium-Term Cardiac Outcomes in Young People with Multi-system Inflammatory Syndrome: The Era of COVID-19.

Multi-system inflammatory syndrome in children (MIS-C) causes widespread inflammation including a pancarditis in the weeks following a COVID infection. As we prepare for further coronavirus surges, understanding the medium-term cardiac impacts of this condition is important for allocating healthcare resources. A retrospective single-center study of 67 consecutive patients with MIS-C was performed evaluating echocardiographic and electrocardiographic (ECG) findings to determine the point of worst cardiac dysfunction during the admission, then at intervals of 6-8 weeks and 6-8 months. Worst cardiac function occurred 6.8 ± 2.4 days after the onset of fever with mean 3D left ventricle (LV) ejection fraction (EF) 50.5 ± 9.8%. A pancarditis was typically present: 46.3% had cardiac impairment; 31.3% had pericardial effusion; 26.8% demonstrated moderate (or worse) valvar regurgitation; and 26.8% had coronary dilatation. Cardiac function normalized in all patients by 6-8 weeks (mean 3D LV EF 61.3 ± 4.4%, p < 0.001 compared to presentation). Coronary dilatation resolved in all but one patient who initially developed large aneurysms at presentation, which persisted 6 months later. ECG changes predominantly featured T-wave changes resolving at follow-up. Adverse events included need for ECMO (n = 2), death as an ECMO-related complication (n = 1), LV thrombus formation (n = 1), and subendocardial infarction (n = 1). MIS-C causes a pancarditis. In the majority, discharge from long-term follow-up can be considered as full cardiac recovery is expected by 8 weeks. The exception includes patients with medium sized aneurysms or greater as these may persist and require on-going surveillance.

Electrocardiographic Changes in Children with Multisystem Inflammation Associated with COVID-19: Associated with Coronavirus Disease 2019.

OBJECTIVE: To analyze findings and trends on serial electrocardiograms (ECGs) in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease taken during the course of illness and at follow-up. STUDY DESIGN: We included all children presenting with MIS-C at a single center with 3 or more ECGs taken during the course of their illness. We measured ECG intervals (PR, QRSd, and QTc) and amplitudes (R-, S-, and T-waves) on each ECG and documented any arrhythmias and ST-segment changes. RESULTS: A majority of children (n = 42, 67%) showed ECG changes. The most common findings were low QRS amplitudes and transient T-wave inversion. ST changes were uncommon and included ST-segment elevation consistent with pericarditis in 1 child and acute coronary ischemia in 1 child. Arrhythmias were seen in 13 children (21%) but were benign with the exception of 1 child who was compromised by an atrial tachycardia requiring support with extracorporeal membrane oxygenation. No children were found to have high-grade atrioventricular block. CONCLUSIONS: MIS-C is associated with electrocardiographic changes over the course of the illness, with low amplitude ECGs on presentation, followed by transient T-wave inversion, particularly in the precordial leads. There was a low prevalence of ST-segment changes and tachyarrhythmias.

Maternal hypertensive disorders of pregnancy and depression or anxiety in adolescence: Findings from the Millennium Cohort Study.

BACKGROUND: The short-term effects of hypertensive disorders of pregnancy (HDP) on the health of the fetus are well known; however, their impacts on the risk of mental health in the exposed offspring are not fully understood. Our aim was to examine the association between HDP and depression/anxiety at age 17 years. METHODS: We used data from The Millennium Cohort Study, a nationally representative longitudinal study of children born in the United Kingdom. Data on HDP and potential confounders were collected when children were 9-months. Data on depression and anxiety were collected as one variable when children were aged 17 years using self-reported doctor diagnosis, and reclassified as depression/anxiety (overall), depression/anxiety with treatment, and depression/anxiety without treatment. Crude and adjusted logistic regression models were performed to examine the association between HDP and depression/anxiety, adjusting for several maternal and socio-economic factors. RESULTS: There were 9517 singleton mother-child pairs included in the analyses. Adjusted logistic regression suggested an association between HDP and depression/anxiety (adjusted odds ratio, (aOR):1.30 [95 % CI, 1.02-1.66]) at age 17 years. A similar association was observed for HDP and depression/anxiety with treatment (aOR:1.33 [95 % CI, 1.01-1.73]) and HDP and depression/anxiety without treatment (aOR: 1.30 [95 % CI, 0.80-2.12]), although the latter did not reach statistical significance. LIMITATIONS: Data on severity and classifications of HDP were not available. CONCLUSION: Exposure to HDP may be associated with an increased likelihood of depression or anxiety at age 17 years. Future research should consider severity and different classifications of HDP.

Association between intrapartum fetal pulse oximetry and adverse perinatal and long-term outcomes: a systematic review and meta-analysis protocol.

Background: Current methods of intrapartum fetal monitoring based on heart rate, increase the rates of operative delivery but do not prevent or accurately detect fetal hypoxic brain injury. There is a need for more accurate methods of intrapartum fetal surveillance that will decrease the incidence of adverse perinatal and long-term neurodevelopmental outcomes while maintaining the lowest possible rate of obstetric intervention. Fetal pulse oximetry (FPO) is a technology that may contribute to improved intrapartum fetal wellbeing evaluation by providing a non-invasive measurement of fetal oxygenation status. Objective: This systematic review and meta-analysis aims to synthesise the evidence examining the association between intrapartum fetal oxygen saturation levels and adverse perinatal and long-term outcomes in the offspring. Methods: We will include randomised control trials (RCTs), cohort, cross-sectional and case-control studies which examine the use of FPO during labour as a means of measuring intrapartum fetal oxygen saturation and assess its effectiveness at detecting adverse perinatal and long-term outcomes compared to existing intrapartum surveillance methods. A detailed systematic search of PubMed, EMBASE, CINAHL, The Cochrane Library, Web of Science, ClinicalTrials.Gov and WHO ICTRP will be conducted following a detailed search strategy until February 2024. Three authors will independently review titles, abstracts and full text of articles. Two reviewers will independently extract data using a pre-defined data extraction form and assess the quality of included studies using the Risk of Bias tool for RCTs and Newcastle-Ottawa Scale for observational studies. The grading of recommendations, assessment, development, and evaluation (GRADE) approach will be used to evaluate the certainty of the evidence. We will use random-effects meta-analysis for each exposure-outcome association to calculate pooled estimates using the generic variance method. This systematic review will follow the Preferred Reporting Items for Systematic reviews and Meta-analyses and MOOSE guidelines. PROSPERO registration: CRD42023457368 (04/09/2023).

Predicting perineal trauma during childbirth using data from a general obstetric population.

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.

Predicting risk of postpartum haemorrhage during the intrapartum period in a general obstetric population.

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.

Patient-reported outcome measures evaluating postpartum maternal health and well-being: a systematic review and evaluation of measurement properties.

OBJECTIVE: 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. DATA SOURCES: 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. STUDY ELIGIBILITY CRITERIA: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Periconceptual and prenatal alcohol consumption and neurodevelopment at age two and five years.

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.

Governance of maternity services: Effects on the management of perinatal deaths and bereavement services.

BACKGROUND: External inquiries are carried out following adverse maternal/perinatal events, to examine the care provided and make recommendations to improve it. Clinical governance ensures that organisations promote high-quality care and are accountable for the care they provide, thus contributing to its improvement. OBJECTIVE: This study examined how Irish perinatal bereavement services and the management of perinatal deaths (including events leading up to the deaths) were affected by developments in maternity services governance as described in ten Irish enquiry reports published over 14 years (2005-18). METHODS: Two clinicians collected data from the ten enquiry reports by using a specifically designed review tool. Thematic analysis was carried out, following the steps of familiarising, coding, identifying, grouping and revising themes. FINDINGS: Seven main themes were identified: workforce, leadership, management of risk, work environment, hospital oversight, national documents, data collection. Eight reports noted shortcomings in staffing levels, with a workforce that was under-resourced, and at times carried excessive workloads. The absence of 24/7 midwifery-shift leaders in maternity units resulted in problems with care at times not being escalated appropriately. The absence of a widely-owned, understood strategic plan for the management of the maternity services was mentioned in the reports from 2013. Conclusions and implications for practice The National Bereavement Care Standards were published in 2016 to address deficiencies identified in the enquiry reports and to standardise perinatal bereavement care across Irish maternity units. Though the first Irish Maternity Strategy (2016-26) was published in 2016, its implementation is incomplete. Inconsistencies remain in the definition and collection of national perinatal data, as well as concerns regarding the lack of local audit activities on pregnancy outcomes. Greater focus on hospital oversight, implementation of national documents and reliable data collection is required. To be effective and initiate positive changes in clinical services, documents such as incident reviews, national strategies and national reports including inquiries, need to include realistic recommendations with clear timelines and responsibilities for implementation.

Patient reported outcome measures in childbirth and postpartum maternal quality of life: a protocol for systematic review of measurement properties.

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.

Impact of bereavement care and pregnancy loss services on families: Findings and recommendations from Irish inquiry reports.

BACKGROUND: Pregnancy loss and the death of their baby can be overwhelming for families, especially when the loss is unexpected. The standard of bereavement care families receive around the time of pregnancy or early infant loss can have a significant impact on their psychological recovery. At times external inquiries are carried out to identify issues in the maternity care provided and make recommendations to improve its' standard. OBJECTIVE: This study aims to describe the impact of bereavement care provided to families around the time of pregnancy and/or early infant loss as stated in ten published inquiry reports related to Irish maternity services. METHODS: Using thematic analysis, issues with care encountered by bereaved parents as outlined in the reports were identified. These focussed around five main themes (communication, healthcare staff skills, maternity unit environment, post-mortem/coronial process, local incident reviews). FINDINGS: Bereavement care, as described by families in the ten reports, was not consistently individualised or respectful, resulting in additional feelings of anger and upset. Problems with clear communication of complex issues, in a manner that is understandable to bereaved families, were identified in several reports. Recommendations from the inquiry reports included that experienced and skilled staff should always be available to provide immediate support to bereaved families as appropriate, and assist families in understanding and processing information around the time of their loss. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Consistent, individualised bereavement care facilitates a seamless transition for bereaved families from diagnosis through the hospital stay to discharge and follow-up, allowing them to focus on their baby, their bereavement and their family's wellbeing. The process of consent for a perinatal post-mortem and associated concerns have evolved over the timeframe of the ten inquiries. We reflect further on this and the impacts of the other issues highlighted, as well as discussing possible improvements to address them as described in the scientific literature.