Antenatal and neonatal exposure to SARS-CoV-2 and children's development: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review of the impact of antenatal and neonatal exposure to SARS-CoV-2 on developmental outcomes in preterm and term-born infants. METHODS: We searched Embase, Emcare, MEDLINE, PsycINFO, Web of Science and grey literature on May 27, 2022 and updated on May 8, 2023. Studies defining exposure with a positive SARS-CoV-2 protein or genetic material, used a contemporaneous non-exposed cohort, and reported developmental outcomes up to 2 years of age were included. RESULTS: Four out of 828 screened studies were included. Meta-analysis included 815 infants screened for developmental delay (n = 306 exposed; n = 509 non-exposed) between 3- and 11-months of age. Among term-born infants, we did not find an increased risk of delay in communication (odd's ratio: 0.73 (95% CI: 0.24-2.24)), gross motor (1.50 (0.62, 3.62)), fine motor (2.90 (0.58, 14.43)), problem-solving (1.19 (0.54, 2.66)) or personal-social development (1.93 (0.78, 4.75)) in exposed infants. The number of preterm-born infants in the exposed (n = 37) and comparison cohorts (n = 41) were too few to report meaningful comparisons. CONCLUSION: Evidence regarding the potential impact of antenatal or neonatal exposure to SARS-CoV-2 infection on developmental outcomes in early infancy is limited and inconsistent. Larger cohorts with outcomes beyond the first year of life are needed. IMPACT: The current evidence examining associations between SARS-CoV-2 exposure during the neonatal period and developmental outcomes in infancy is limited by there being few studies with extremely small sample sizes. Based on sparse data there was no consistent association between antenatal or neonatal exposure to SARS-CoV-2 infection and an adverse impact on developmental outcomes below 12 months of age for babies born preterm or at term. This study highlights that larger cohorts with outcomes assessed beyond the first year are needed to determine the potential longer-term impact of SARS-CoV-2 infection exposure on child development.

Postpartum haemorrhage and risk of cardiovascular disease in later life: A population-based record linkage cohort study.

OBJECTIVE: To investigate the association between postpartum haemorrhage (PPH) and subsequent cardiovascular disease. DESIGN: Population-based retrospective cohort study, using record linkage between Aberdeen Maternity and Neonatal Databank (AMND) and Scottish healthcare data sets. SETTING: Grampian region, Scotland. POPULATION: A cohort of 70 904 women who gave birth after 24 weeks of gestation in the period 1986-2016. METHODS: We used extended Cox regression models to investigate the association between having had one or more occurrences of PPH in any (first or subsequent) births (exposure) and subsequent cardiovascular disease, adjusted for sociodemographic, medical, and pregnancy and birth-related factors. MAIN OUTCOME MEASURES: Cardiovascular disease identified from the prescription of selected cardiovascular medications, hospital discharge records or death from cardiovascular disease. RESULTS: In our cohort of 70 904 women (with 124 795 birth records), 25 177 women (36%) had at least one PPH. Compared with not having a PPH, having at least one PPH was associated with an increased risk of developing cardiovascular disease, as defined above, in the first year after birth (adjusted hazard ratio, aHR 1.96; 95% confidence interval, 95% CI 1.51-2.53; p < 0.001). The association was attenuated over time, but strong evidence of increased risk remained at 2-5 years (aHR 1.19, 95% CI 1.11-1.30, P < 0.001) and at 6-15 years after giving birth (aHR 1.17, 95% CI 1.05-1.30, p = 0.005). CONCLUSIONS: Compared with women who have never had a PPH, women who have had at least one episode of PPH are twice as likely to develop cardiovascular disease in the first year after birth, and some increased risk persists for up to 15 years.

Long-term healthcare utilization and costs of babies born after assisted reproductive technologies (ART): a record linkage study with 10-years' follow-up in England.

STUDY QUESTION: Is the long-term health care utilization of children born after ART more costly to the healthcare system in England than children born to mothers with no fertility problems? SUMMARY ANSWER: Children born after ART had significantly more general practitioner (GP) consultations and higher primary care costs up to 10 years after birth, and significantly higher hospital admission costs in the first year after birth, compared to children born to mothers with no fertility problems. WHAT IS KNOWN ALREADY: There is evidence that children born after ART are at an increased risk of adverse birth outcomes and a small increased risk of rare adverse outcomes in childhood. STUDY DESIGN, SIZE, DURATION: We conducted a longitudinal study of 368 088 mother and baby pairs in England using a bespoke linked dataset. Singleton babies born 1997-2018, and their mothers, who were registered at GP practices in England contributing data to the Clinical Practice Research Datalink (CPRD), were identified through the CPRD GOLD mother-baby dataset; this data was augmented with further linkage to the mothers' Human Fertilisation and Embryology Authority (HFEA) Register data. Four groups of babies were identified through the mothers' records: a 'fertile' comparison group, an 'untreated sub-fertile' group, an 'ovulation induction' group, and an ART group. Babies were followed-up from birth to 28 February 2021, unless censored due to loss to follow-up (e.g. leaving GP practice, emigration) or death. PARTICIPANTS/MATERIALS, SETTING, METHODS: The CPRD collects anonymized coded patient electronic health records from a network of GPs in the UK. We estimated primary care costs and hospital admission costs for babies in the four fertility groups using the CPRD GOLD data and the linked Hospital Episode Statistics (HES) Admitted Patient Care (APC) data. Linear regression was used to compare the care costs in the different groups. Inverse probability weights were generated and applied to adjust for potential bias caused by attrition due to loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: Children born to mothers with no fertility problems had significantly fewer consultations and lower primary care costs compared to the other groups throughout the 10-years' follow up. Regarding hospital costs, children born after ART had significantly higher hospital admission costs in the first year after birth compared to those born to mothers with no fertility problems (difference = £307 (95% CI: 153, 477)). The same pattern was observed in children born after untreated subfertility and ovulation induction. LIMITATIONS, REASONS FOR CAUTION: HFEA linkage uses non-donor data cycles only, and the introduction of consent for data use reduced the availability of HFEA records after 2009. The fertility groups were derived by augmenting HFEA data with evidence from primary care records; however, there remains some potential misclassification of exposure groups. The cost of neonatal critical care is not captured in the HES APC data, which may cause underestimation of the cost differences between the comparison group and the infertility groups. WIDER IMPLICATIONS OF THE FINDINGS: The findings can help anticipate the financial impact on the healthcare system associated with subfertility and ART, particularly as the demand for these treatments grows. STUDY FUNDING/COMPETING INTEREST(S): C.C. and this work were funded by a UK Medical Research Council Career Development Award [MR/L019671/1] and a UK MRC Transition Support Award [MR/W029286/1]. X.H. is an Australia National Health and Medical Research Council (NHMRC) Emerging Leadership Fellow [grant number 2009253]. The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.

Amniotic band syndrome and limb body wall complex in Europe 1980-2019.

Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019 and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980-2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly seen in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor.

Neonatal outcomes of maternal SARS-CoV-2 infection in the UK: a prospective cohort study using active surveillance.

BACKGROUND: Newborns may be affected by maternal SARS-CoV-2 infection during pregnancy. We aimed to describe the epidemiology, clinical course and short-term outcomes of babies admitted to a neonatal unit (NNU) following birth to a mother with confirmed SARS-CoV-2 infection within 7 days of birth. METHODS: This is a UK prospective cohort study; all NHS NNUs, 1 March 2020 to 31 August 2020. Cases were identified via British Paediatric Surveillance Unit with linkage to national obstetric surveillance data. Reporting clinicians completed data forms. Population data were extracted from the National Neonatal Research Database. RESULTS: A total of 111 NNU admissions (1.98 per 1000 of all NNU admissions) involved 2456 days of neonatal care (median 13 [IQR 5, 34] care days per admission). A total of 74 (67%) babies were preterm. In all, 76 (68%) received respiratory support; 30 were mechanically ventilated. Four term babies received therapeutic hypothermia for hypoxic ischaemic encephalopathy. Twenty-eight mothers received intensive care, with four dying of COVID-19. Eleven (10%) babies were SARS-CoV-2 positive. A total of 105 (95%) babies were discharged home; none of the three deaths before discharge was attributed to SARS-CoV-2. CONCLUSION: Babies born to mothers with SARS-CoV-2 infection around the time of birth accounted for a low proportion of total NNU admissions over the first 6 months of the UK pandemic. Neonatal SARS-CoV-2 was uncommon. STUDY REGISTRATION: ISRCTN60033461; protocol available at http://www.npeu.ox.ac.uk/pru-mnhc/research-themes/theme-4/covid-19 . IMPACT: Neonatal unit admissions of babies born to mothers with SARS-CoV-2 infection comprised only a small proportion of total neonatal admissions in the first 6 months of the pandemic. A high proportion of babies requiring neonatal admission who were born to mothers with confirmed SARS-CoV-2 infection were preterm and had neonatal SARS-CoV-2 infection and/or other conditions associated with long-term sequelae. Adverse neonatal conditions were more common in babies whose SARS-CoV-2-positive mothers required intensive care compared to those whose SARS-CoV-2-positive mothers who did not.

The impact of a universal late third-trimester scan for fetal growth restriction on perinatal outcomes in term singleton births: A prospective cohort study.

OBJECTIVE: To investigate perinatal mortality, morbidity and obstetric intervention following the introduction of a universal late third-trimester ultrasound scan for growth restriction. DESIGN: Prospective cohort study. SETTING: Oxfordshire (OUH), UK. POPULATION: Women with a non-anomalous singleton pregnancy undergoing pregnancy care and term delivery at OUH with an estimated due date (EDD) of birth between 1 January 2014 and 30 September 2019. METHODS: Universal ultrasound for fetal growth restriction between 35+0 and 36+6 weeks was introduced in 2016. The outcomes of the next 18 631 eligible term pregnancies were compared, adjusting for covariates and time, with the previous 18 636 who had clinically indicated ultrasounds only. 'Screen-positives' for growth restriction were managed according to a pre-determined protocol which included non-intervention for some small-for-gestational-age babies. MAIN OUTCOME MEASURES: Extended perinatal mortality, a composite of mortality or encephalopathy Grade II-III, and expedited birth. Other outcomes included composite adverse outcomes used elsewhere, detection of low birthweight and birth from 37+0 to 38+6 weeks. RESULTS: Extended perinatal deaths decreased 27% and severe morbidity decreased 33% but neither change was statistically significant (adjusted odd ratio [aOR] 0.53, 95% confidence interval [C1] 00.18-1.56 and aOR 0.71, 95% CI 0.31-1.63). Expedited births changed from 35.2% to 37.7% (aOR 0.99, 95% CI 0.92-1.06). Birthweight (<10th centile) detection using fetal biometry alone was 31.4% and rose to 40.5% if all abnormal scan parameters were used. CONCLUSION: Improvements in mortality and severe morbidity subsequent to introducing a universal ultrasound for growth restriction are encouraging but remain unclear. Little change in intervention is possible. The antenatal detection of low birthweight remains poor but improves where markers of growth restriction are used.

Vulnerable newborn types: Analysis of population-based registries for 165 million births in 23 countries, 2000-2021.

OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.

Women's awareness of perinatal mental health conditions and the acceptability of being asked about mental health in two regions in India: a qualitative study.

BACKGROUND: Mental health conditions are common during pregnancy and the first year after childbirth. Early detection allows timely support and treatment to be offered, but identifying perinatal mental health conditions may be challenging due to stigma and under-recognition of symptoms. Asking about symptoms of mental health conditions during routine antenatal and postnatal appointments can help to identify women at risk. This study explores women's awareness of perinatal mental health conditions, their views on the acceptability of being asked about mental health and any preference for specific assessment tools in two regions in India. METHODS: Focus group discussions (FGDs) were conducted with pregnant, post-partum and non-perinatal women in Kangra, Himachal Pradesh (northern India) and Bengaluru, Karnataka (southern India). Settings included a hospital antenatal clinic and obstetric ward, Anganwadi Centres and Primary Health Centres. FGDs were facilitated, audio-recorded and transcribed. Narratives were coded for emerging themes and analysed using thematic analysis. RESULTS: Seven FGDs including 36 participants were conducted. Emerging themes were: manifestations of and contributors to mental health conditions; challenges in talking about mental health; and the acceptability of being asked about mental health. Difficult familial relationships, prioritising the needs of others and pressure to have a male infant were cited as key stressors. Being asked about mental health was generally reported to be acceptable, though some women felt uncomfortable with questions about suicidality. No preference for any specific assessment tool was reported. CONCLUSIONS: Women face many stressors during the perinatal period including difficult familial relationships and societal pressure to bear a male infant. Being asked about mental health was generally considered to be acceptable, but questions relating to suicidality may be challenging in a community setting, requiring sensitivity by the interviewer. Future studies should assess the acceptability of mental health assessments in 'real world' antenatal and postnatal clinics and explore ways of overcoming the associated challenges in resource-constrained settings.

Epidemiology of aplasia cutis congenita: A population-based study in Europe.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital anomaly characterized by localized or widespread absence of skin at birth, mainly affecting the scalp. Most information about ACC exists as individual case reports and medium-sized studies. OBJECTIVES: This study aimed to investigate the epidemiology of ACC, using data from a large European network of population-based registries for congenital anomalies (EUROCAT). METHODS: Twenty-eight EUROCAT population-based registries in 16 European countries were involved. Poisson regression models were exploited to estimate the overall and live birth prevalence, to test time trends in prevalence between four 5-year periods and to evaluate the impact of the change of coding for ACC from the unspecific ICD9-BPA code to the specific ICD10 code. Proportions of ACC cases associated with other anomalies were reported. RESULTS: Five hundred cases were identified in the period 1998-2017 (prevalence: 5.10 per 100,000 births). Prevalence across 5-year periods did not differ significantly and no significant differences were evident due to the change from ICD9 to ICD10 in ACC coding. Heterogeneity in prevalence was observed across registries. The scalp was the most common site for ACC (96.4%) and associated congenital anomalies were present in 33.8% of cases. Patau and Adams-Oliver syndromes were the most frequent among the associated chromosomal anomalies (88.3%) and the associated genetic syndromes (57.7%), respectively. 16% of cases were associated with limb anomalies and 15.4% with congenital heart defects. A family history of ACC was found in 2% of cases. CONCLUSION: To our knowledge, this is the only population-based study on ACC. The EUROCAT methodologies provide reliable prevalence estimates and proportions of associated anomalies.

Planned mode of birth after previous cesarean section and risk of undergoing pelvic floor surgery: A Scottish population-based record linkage cohort study.

BACKGROUND: The global rise in cesarean sections has led to increasing numbers of pregnant women with a history of previous cesarean section. Policy in many high-income settings supports offering these women a choice between planned elective repeat cesarean section (ERCS) or planned vaginal birth after previous cesarean (VBAC), in the absence of contraindications to VBAC. Despite the potential for this choice to affect women's subsequent risk of experiencing pelvic floor disorders, evidence on the associated effects to fully counsel women is lacking. This study investigated the association between planned mode of birth after previous cesarean section and the woman's subsequent risk of undergoing pelvic floor surgery. METHODS AND FINDINGS: A population-based cohort study of 47,414 singleton term births in Scotland between 1983 to 1996 to women with 1 or more previous cesarean sections was conducted using linked Scottish national routine datasets. Cox regression was used to investigate the association between planned as well as actual mode of birth and women's subsequent risk of having any pelvic floor surgery and specific types of pelvic floor surgery adjusted for sociodemographic, maternal medical, and obstetric-related factors. Over a median of 22.1 years of follow-up, 1,159 (2.44%) of the study population had pelvic floor surgery. The crude incidence rate of any pelvic floor surgery per 1,000 person-years was 1.35, 95% confidence interval (CI) 1.27 to 1.43 in the overall study population, 1.75, 95% CI 1.64 to 1.86 in the planned VBAC group and 0.66, 95% CI 0.57 to 0.75 in the ERCS group. Planned VBAC compared to ERCS was associated with a greater than 2-fold increased risk of the woman undergoing any pelvic floor surgery (adjusted hazard ratio [aHR] 2.38, 95% CI 2.03 to 2.80, p < 0.001) and a 2- to 3-fold increased risk of the woman having surgery for pelvic organ prolapse or urinary incontinence (aHR 3.17, 95% CI 2.47 to 4.09, p < 0.001 and aHR 2.26, 95% CI 1.79 to 2.84, p < 0.001, respectively). Analysis by actual mode of birth showed these increased risks were only apparent in the women who actually had a VBAC, with the women who needed an in-labor non-elective repeat cesarean section having a comparable risk of pelvic floor surgery to those who had an ERCS. The main limitation of this study is the potential for misclassification bias. CONCLUSIONS: This study suggests that among women with previous cesarean section giving birth to a singleton at term, planned VBAC compared to ERCS is associated with an increased risk of the woman subsequently undergoing pelvic floor surgery including surgery for pelvic organ prolapse and urinary incontinence. However, these risks appear to be only apparent in women who actually give birth vaginally as planned, highlighting the role of vaginal birth rather than labor in pelvic floor dysfunction requiring surgery. The findings provide useful additional information to counsel women with previous cesarean section about the risks and benefits associated with their future birth choices.

Elective freezing of embryos versus fresh embryo transfer in IVF: a multicentre randomized controlled trial in the UK (E-Freeze).

STUDY QUESTION: Does a policy of elective freezing of embryos, followed by frozen embryo transfer result in a higher healthy baby rate, after first embryo transfer, when compared with the current policy of transferring fresh embryos? SUMMARY ANSWER: This study, although limited by sample size, provides no evidence to support the adoption of a routine policy of elective freeze in preference to fresh embryo transfer in order to improve IVF effectiveness in obtaining a healthy baby. WHAT IS KNOWN ALREADY: The policy of freezing all embryos followed by frozen embryo transfer is associated with a higher live birth rate for high responders but a similar/lower live birth after first embryo transfer and cumulative live birth rate for normal responders. Frozen embryo transfer is associated with a lower risk of ovarian hyperstimulation syndrome (OHSS), preterm delivery and low birthweight babies but a higher risk of large babies and pre-eclampsia. There is also uncertainty about long-term outcomes, hence shifting to a policy of elective freezing for all remains controversial given the delay in treatment and extra costs involved in freezing all embryos. STUDY DESIGN, SIZE, DURATION: A pragmatic two-arm parallel randomized controlled trial (E-Freeze) was conducted across 18 clinics in the UK from 2016 to 2019. A total of 619 couples were randomized (309 to elective freeze/310 to fresh). The primary outcome was a healthy baby after first embryo transfer (term, singleton live birth with appropriate weight for gestation); secondary outcomes included OHSS, live birth, clinical pregnancy, pregnancy complications and cost-effectiveness. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples undergoing their first, second or third cycle of IVF/ICSI treatment, with at least three good quality embryos on Day 3 where the female partner was ≥18 and <42 years of age were eligible. Those using donor gametes, undergoing preimplantation genetic testing or planning to freeze all their embryos were excluded. IVF/ICSI treatment was carried out according to local protocols. Women were followed up for pregnancy outcome after first embryo transfer following randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 619 couples randomized, 307 and 309 couples in the elective freeze and fresh transfer arms, respectively, were included in the primary analysis. There was no evidence of a statistically significant difference in outcomes in the elective freeze group compared to the fresh embryo transfer group: healthy baby rate {20.3% (62/307) versus 24.4% (75/309); risk ratio (RR), 95% CI: 0.84, 0.62 to 1.15}; OHSS (3.6% versus 8.1%; RR, 99% CI: 0.44, 0.15 to 1.30); live birth rate (28.3% versus 34.3%; RR, 99% CI 0.83, 0.65 to 1.06); and miscarriage (14.3% versus 12.9%; RR, 99% CI: 1.09, 0.72 to 1.66). Adherence to allocation was poor in the elective freeze group. The elective freeze approach was more costly and was unlikely to be cost-effective in a UK National Health Service context. LIMITATIONS, REASONS FOR CAUTION: We have only reported on first embryo transfer after randomization; data on the cumulative live birth rate requires further follow-up. Planned target sample size was not obtained and the non-adherence to allocation rate was high among couples in the elective freeze arm owing to patient preference for fresh embryo transfer, but an analysis which took non-adherence into account showed similar results. WIDER IMPLICATIONS OF THE FINDINGS: Results from the E-Freeze trial do not lend support to the policy of electively freezing all for everyone, taking both efficacy, safety and costs considerations into account. This method should only be adopted if there is a definite clinical indication. STUDY FUNDING/COMPETING INTEREST(S): NIHR Health Technology Assessment programme (13/115/82). This research was funded by the National Institute for Health Research (NIHR) (NIHR unique award identifier) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care. J.L.B., C.C., E.J., P.H., J.J.K., L.L. and G.S. report receipt of funding from NIHR, during the conduct of the study. J.L.B., E.J., P.H., K.S. and L.L. report receipt of funding from NIHR, during the conduct of the study and outside the submitted work. A.M. reports grants from NIHR personal fees from Merck Serono, personal fees for lectures from Merck Serono, Ferring and Cooks outside the submitted work; travel/meeting support from Ferring and Pharmasure and participation in a Ferring advisory board. S.B. reports receipt of royalties and licenses from Cambridge University Press, a board membership role for NHS Grampian and other financial or non-financial interests related to his roles as Editor-in-Chief of Human Reproduction Open and Editor and Contributing Author of Reproductive Medicine for the MRCOG, Cambridge University Press. D.B. reports grants from NIHR, during the conduct of the study; grants from European Commission, grants from Diabetes UK, grants from NIHR, grants from ESHRE, grants from MRC, outside the submitted work. Y.C. reports speaker fees from Merck Serono, and advisory board role for Merck Serono and shares in Complete Fertility. P.H. reports membership of the HTA Commissioning Committee. E.J. reports membership of the NHS England and NIHR Partnership Programme, membership of five Data Monitoring Committees (Chair of two), membership of six Trial Steering Committees (Chair of four), membership of the Northern Ireland Clinical Trials Unit Advisory Group and Chair of the board of Oxford Brain Health Clinical Trials Unit. R.M. reports consulting fees from Gedeon Richter, honorarium from Merck, support fees for attendance at educational events and conferences for Merck, Ferring, Bessins and Gedeon Richter, payments for participation on a Merck Safety or Advisory Board, Chair of the British Fertility Society and payments for an advisory role to the Human Fertilisation and Embryology Authority. G.S. reports travel and accommodation fees for attendance at a health economic advisory board from Merck KGaA, Darmstadt, Germany. N.R.-F. reports shares in Nurture Fertility. Other authors' competing interests: none declared. TRIAL REGISTRATION NUMBER: ISRCTN: 61225414. TRIAL REGISTRATION DATE: 29 December 2015. DATE OF FIRST PATIENT'S ENROLMENT: 16 February 2016.

Planned mode of birth after previous caesarean section and women's use of psychotropic medication in the first year postpartum: a population-based record linkage cohort study.

BACKGROUND: Policy in many high-income settings supports giving pregnant women with previous caesarean section a choice between an elective repeat caesarean section (ERCS) or planning a vaginal birth after previous caesarean (VBAC), provided they have no contraindications to VBAC. Despite the potential for this choice to influence women's mental health, evidence about the associated effect to counsel women and identify potential targets for intervention is limited. This study investigated the association between planned mode of birth after previous caesarean and women's subsequent use of psychotropic medications. METHODS: A population-based cohort study of 31 131 women with one or more previous caesarean sections who gave birth to a term singleton in Scotland between 2010 and 2015 with no prior psychotropic medications in the year before birth was conducted using linked Scottish national datasets. Cox regression was used to investigate the association between planned mode of birth and being dispensed psychotropic medications in the first year postpartum adjusted for socio-demographic, medical, pregnancy-related factors and breastfeeding. RESULTS: Planned VBAC (n = 10 220) compared to ERCS (n = 20 911) was associated with a reduced risk of the mother being dispensed any psychotropic medication [adjusted hazard ratio (aHR) 0.85, 95% confidence interval (CI) 0.78-0.92], an antidepressant (aHR 0.83, 95% CI 0.76-0.90), and at least two consecutive antidepressants (aHR 0.83, 95% CI 0.75-0.91) in the first year postpartum. CONCLUSIONS: Women giving birth by ERCS were more likely than those having a planned VBAC to be dispensed psychotropic medication including antidepressants in the first year postpartum. Further research is needed to establish the reasons behind this new finding.

Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes.

BACKGROUND: Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. METHODS: In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. RESULTS: Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35-3.86, p = 0.002). CONCLUSIONS: Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. IMPACT: Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort.

Placenta accreta spectrum - variations in clinical practice and maternal morbidity between the UK and France: a population-based comparative study.

OBJECTIVE: To compare the management and outcomes of women with placenta accreta spectrum (PAS) in France and the UK. DESIGN: Two population-based cohorts. SETTING: All obstetrician-led hospitals in the UK and maternity hospitals in eight French regions. POPULATION: A cohort of 219 women with PAS in France and a cohort of 154 women with PAS in the UK. METHODS: The management and outcomes of women with PAS were compared between the UK and France. MAIN OUTCOME MEASURES: Median blood loss, severe postpartum haemorrhage (≥3 l), postpartum infection and damage to surrounding organs. RESULTS: The management of PAS differed between the two countries: a larger proportion of women with PAS in the UK had a caesarean hysterectomy compared with France (43% vs 26%, p < 0.001), whereas in France a larger proportion of women with PAS received a uterus-preserving approach compared with the UK (36% vs 19%, p < 0.001). The total median blood loss in the UK was 3 l (IQR 1.7-6.5 l), compared with 1 l (IQR 0.5-2.5 l) in France; more women with PAS had a severe postpartum haemorrhage (PPH) in the UK compared with women with PAS in France (58% vs 21%, p < 0.001) [Correction added on 06 May 2022, after first online publication: '24 hour' has been changed to 'total' in the preceding sentence]. There was no difference between the UK and French populations for postpartum infection or organ damage. CONCLUSIONS: The UK and France have very different approaches to managing PAS, with more women in France receiving a uterine-conserving approach and more women in the UK undergoing caesarean hysterectomy. A life-threatening haemorrhage was more common in the UK than in France, which may be the result of differential management and/or the organisation of the healthcare systems. In women with placenta accreta spectrum, severe haemorrhage was more common in the UK than in France. TWEETABLE ABSTRACT: In women with placenta accreta spectrum, severe haemorrhage was more common in the UK than in France.

Refinement of the Well-being in Pregnancy (WiP) questionnaire: cognitive interviews with women and healthcare professionals and a validation survey.

BACKGROUND: Measuring positive and negative aspects of well-being during pregnancy and childbirth is important for both healthy women and women who are living with long-term health conditions (LTCs). This study aimed to further refine the Well-being in Pregnancy (WiP) questionnaire and to incorporate LTC specific items where appropriate. METHODS: A multi-method study. Cognitive interviews with pregnant or postpartum women (n = 11) and consultations with healthcare professionals (n = 11) and public representatives (n = 4) were conducted to explore the acceptability of existing WiP items and content. Items were refined and subsequently administered on an online survey (n = 768). Item reduction steps and exploratory factor analysis were performed on survey data. Convergent validity was examined using Pearson correlation coefficients to compare relationships with other included validated assessments. RESULTS: Following amendments to three items, the addition of eight core WiP items and five LTC specific items, a total of 25 items were considered relevant and appropriate for use with pregnant women. Analysis of survey data reduced the questionnaire to 12 items measuring three core WiP scales; 1) Concerns over support after birth, 2) Positive pregnancy and, 3) Confidence about motherhood, and a five item standalone LTC specific scale. All scales demonstrated good validity and internal reliability. Scores for the three core scales moderately correlated with established well-being measures indicating that they were measuring similar, yet distinct concepts. CONCLUSIONS: Analyses confirmed good psychometric properties of the refined WiP questionnaire. The use of pregnancy specific well-being measures, such as the WiP, provide a route into asking women in more detail about how their care may be tailored to support them and also facilitates positive conversations with women about how care and experience of pregnancy and childbirth may be enhanced further.

Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort.

INTRODUCTION: There is a lack of population level data on risk factors and impact of severe COVID-19 in pregnancy. The aims of this study were to determine the characteristics, and maternal and perinatal outcomes associated with severe COVID-19 in pregnancy compared with those with mild and moderate COVID-19 and to explore the impact of timing of birth. MATERIAL AND METHODS: This was a secondary analysis of a national, prospective cohort study. All pregnant women admitted to hospital in the UK with symptomatic SARS-CoV-2 from March 1, 2020 to October 31, 2021 were included. The severity of maternal infection (need for high flow or invasive ventilation, intensive care admission or died), pregnancy and perinatal outcomes, and the impact of timing of birth were analyzed using multivariable logistic regression. RESULTS: Of 4436 pregnant women, 13.9% (n = 616) had severe infection. Women with severe infection were more likely to be aged ≥30 years (adjusted odds ratio [aOR] aged 30-39 1.48, 95% confidence interval [CI] 1.20-1.83), be overweight or obese (aOR 1.73, 95% CI 1.34-2.25 and aOR 2.52 95% CI 1.97-3.23, respectively), be of mixed ethnicity (aOR 1.93, 95% CI 1.17-3.21) or have gestational diabetes (aOR 1.43, 95% CI 1.09-1.87) compared with those with mild or moderate infection. Women with severe infection were more likely to have a pre-labor cesarean birth (aOR 8.84, 95% CI 6.61-11.83), a very or extreme preterm birth (28-31+ weeks' gestation, aOR 18.97, 95% CI 7.78-14.85; <28 weeks' gestation, aOR 12.35, 95% CI 6.34-24.05) and their babies were more likely to be stillborn (aOR 2.51, 95% CI 1.35-4.66) or admitted to a neonatal unit (aOR 11.61, 95% CI 9.28-14.52). Of 112 women with severe infection who were discharged and gave birth at a later admission, the majority gave birth ≥36 weeks (85.7%), noting that three women in this group (2.7%) had a stillbirth. CONCLUSIONS: Severe COVID-19 in pregnancy increases the risk of adverse outcomes. Information to promote uptake of vaccination should specifically target those at greatest risk of severe outcomes. Decisions about timing of birth should be informed by multidisciplinary team discussion; however, our data suggest that women with severe infection who do not require early delivery have mostly good outcomes but that those with severe infection at term may warrant rapid delivery.

Management of Gastroschisis: Results From the NETS2G Study, a Joint British, Irish, and Canadian Prospective Cohort Study of 1268 Infants.

OBJECTIVE: In infants with gastroschisis, outcomes were compared between those where operative reduction and fascial closure were attempted ≤24 hours of age (PC), and those who underwent planned closure of their defect >24 hours of age following reduction with a pre-formed silo (SR). SUMMARY OF BACKGROUND DATA: Inadequate evidence exists to determine how best to treat infants with gastroschisis. METHODS: A secondary analysis was conducted of data collected 2006-2008 using the British Association of Pediatric Surgeons Congenital Anomalies Surveillance System, and 2005-2016 using the Canadian Pediatric Surgery Network.28-day outcomes were compared between infants undergoing PC and SR. Primary outcome was number of gastrointestinal complications. Interactions were investigated between infant characteristics and treatment to determine whether intervention effect varied in sub-groups of infants. RESULTS: Data from 341 British and Irish infants (27%) and 927 Canadian infants (73%) were used. 671 infants (42%) underwent PC and 597 (37%) underwent SR. The effect of SR on outcome varied according to the presence/absence of intestinal perforation, intestinal matting and intestinal necrosis. In infants without these features, SR was associated with fewer gastrointestinal complications [aIRR 0.25 (95% CI 0.09-0.67, P = 0.006)], more operations [aIRR 1.40 (95% CI 1.22-1.60, P < 0.001)], more days PN [aIRR 1.08 (95% CI 1.03-1.13, P < 0.001)], and a higher infection risk [aOR 2.06 (95% CI 1.10-3.87, P = 0.025)]. In infants with these features, SR was associated with a greater number of operations [aIRR 1.30 (95% CI 1.17-1.45, P < 0.001)], and more days PN [aIRR 1.06 (95% CI 1.02-1.10, P = 0.003)]. CONCLUSIONS: In infants without intestinal perforation, matting, or necrosis, the benefits of SR outweigh its drawbacks. In infants with these features, the opposite is true. Treatment choice should be based upon these features.

Epidemiology of Pierre-Robin sequence in Europe: A population-based EUROCAT study.

BACKGROUND: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. OBJECTIVE: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. METHODS: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. RESULTS: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age <25 for total (PRR 1.26, 95% CI 1.05, 1.51) and isolated cases (PRR 1.33, 95% CI 1.00, 1.64). Survival of chromosomal cases (94.2%) and multiple anomaly cases (95.3%) were lower than survival of isolated cases (99.4%). CONCLUSIONS: This epidemiological study using a large series of cases of PRS provides insights into the epidemiological profile of PRS in Europe. We observed an association with higher maternal age, but further investigations are needed to test potential risk factors for PRS.

Validated screening tools to identify common mental disorders in perinatal and postpartum women in India: a systematic review and meta-analysis.

BACKGROUND: Perinatal common mental disorders are associated with significant adverse outcomes for women and their families, particularly in low- and middle-income settings. Early detection through screening with locally-validated tools can improve outcomes. METHODS: We searched MEDLINE, Embase, PsycINFO, Global Health, Cochrane Library, Web of Science and Google Scholar for articles on the validation of screening tools for common mental disorders in perinatal women in India, with no language or date restrictions. Quality was assessed using the QUADAS-2 tool. We used bivariate and hierarchical summary receiver operating characteristic models to calculate pooled summary estimates of sensitivity and specificity. Heterogeneity was assessed by visualising the distance of individual studies from the summary curve. RESULTS: Seven studies involving 1003 women were analysed. All studies assessed the validity of the Edinburgh Postnatal Depression Scale (EPDS) in identifying perinatal depression. No validation studies of any other screening tools were identified. Using a common threshold of ≥13 the EPDS had a pooled sensitivity and specificity of 88·9% (95%CI 77·4-94·9) and 93·4 (95%CI 81·5-97·8), respectively. Using optimal thresholds (range ≥ 9 to ≥13) the EPDS had a pooled sensitivity and specificity of 94·4% (95%CI 81·7-98·4) and 90·8 (95%CI 83·7-95·0), respectively. CONCLUSION: The EPDS is psychometrically valid in diverse Indian settings and its use in routine maternity care could improve detection of perinatal depression. Further research is required to validate screening tools for other perinatal common mental disorders in India.

Exploring the use of health and wellbeing measures during pregnancy and the first year following birth in women living with pre-existing long-term conditions: qualitative interviews with women and healthcare professionals.

BACKGROUND: One way in which care for pregnant and postpartum women living with long-term health conditions (LTCs) may be improved is through the adoption of standardised measures to provide evidence of health outcomes and wellbeing from the woman's perspective. AIM: The study explores the views of pregnant and postpartum women living with LTCs, and healthcare professionals to better understand the potential value of using standardised health and wellbeing measures within this patient population. METHODS: Qualitative semi-structured telephone interviews were conducted to explore the perceived value of using measures with pregnant and postpartum women living with LTCs within maternity services. Participants were asked to provide feedback on three exemplar measures: the Long Term Conditions Questionnaire, the Wellbeing in Pregnancy Questionnaire and the EuroQol EQ-5D-5L instrument. Thematic analysis was used in the analysis of the transcripts. RESULTS: Eleven women and 11 healthcare professionals took part in semi-structured interviews. Analysis identified five themes as relevant to the use of measures within maternity services: 1) Improving care, 2) Assessing outcomes, 3) Interpretation and application of data, 4) Engagement challenges and implementation and, 5) Women and healthcare professionals alignment. CONCLUSIONS: Despite varying prior experience and expressing some questions about implementation, respondents were cautiously positive about the use of standardised health and wellbeing measures. Their use offers the opportunity for both affected women and healthcare professionals caring for them to collectively identify and assess important areas of unmet needs and improve outcomes. Incorporating the perspectives of women with LTC's will help bring awareness to elements of women centred care which health services may seek to address.