Risk of spontaneous preterm birth elevated after first cesarean delivery at full dilatation: a retrospective cohort study of over 30,000 women.

BACKGROUND: Having a cesarean delivery at full dilatation has been associated with increased subsequent risk of spontaneous preterm birth. The Aberdeen Maternity and Neonatal Databank provides a rare opportunity to study subsequent pregnancy outcomes after a previous cesarean delivery at full dilatation over 40 years, with an ability to include a detailed evaluation of potential confounding factors. OBJECTIVE: This study aimed to investigate if having an initial cesarean delivery at full dilatation is associated with spontaneous preterm birth or other adverse pregnancy outcomes in the subsequent pregnancy. STUDY DESIGN: A retrospective cohort study was conducted including women with a first and second pregnancy recorded within the Aberdeen Maternity and Neonatal Databank between 1976 and 2017, where previous cesarean delivery at full dilatation at term in the first birth was the exposure. The primary outcome was spontaneous preterm birth (defined as spontaneous birth <37 weeks). Multivariate logistic regression was used to investigate any association between cesarean delivery at full dilatation and the odds of spontaneous preterm birth. Cesarean delivery at full dilatation in previous pregnancy was compared with: (1) any other mode of birth, and (2) individual modes of birth, including planned cesarean delivery, cesarean delivery in first stage of labor (<10-cm dilatation), and vaginal birth (including spontaneous vaginal birth, nonrotational forceps, Kielland forceps, vacuum-assisted birth, breech vaginal birth). Other outcomes such as antepartum hemorrhage and mode of second birth were also compared. RESULTS: Of the 30,253 women included, 900 had a previous cesarean delivery at full dilatation in the first pregnancy. Women with previous cesarean delivery at full dilatation had a 3-fold increased risk of spontaneous preterm birth in a second pregnancy (unadjusted odds ratio, 2.63; 95% confidence interval, 1.82-3.81; adjusted odds ratio, 3.31; 95% confidence interval, 2.17-5.05) compared with those with all other modes of first birth, adjusted for maternal age, diabetes mellitus, body mass index, smoking, preeclampsia, antepartum hemorrhage, socioeconomic deprivation (Scottish Index of Multiple Deprivation 2016), year of birth, and interpregnancy interval (in second pregnancy). When compared with women with vaginal births only, women with cesarean delivery at full dilatation had 5-fold increased odds of spontaneous preterm birth (adjusted odds ratio, 5.37; 95% confidence interval, 3.40-8.48). Compared with first spontaneous vaginal birth, first instrumental births (nonrotational forceps, Kielland forceps, and vacuum births) were not associated with increased risk of spontaneous preterm birth in the second birth. After an initial cesarean delivery at full dilatation, 3.7% of women had a repeated cesarean delivery at full dilatation and 48% had a planned cesarean delivery in the second birth. CONCLUSION: This study is a substantial addition to the body of evidence on the risk of subsequent spontaneous preterm birth after cesarean delivery at full dilatation, and demonstrates a strong association between cesarean delivery at full dilatation in the first birth and spontaneous preterm birth in subsequent pregnancy, although the absolute risk remains small. This is a large retrospective cohort and includes a comprehensive assessment of potential confounding factors, including preeclampsia, antepartum hemorrhage, and lengths of first and second stage of labor. Future research should focus on understanding possible causality and developing primary and secondary preventative measures.

Maternal and perinatal outcomes of prolonged second stage of labour: a historical cohort study of over 51,000 women.

BACKGROUND: Prolonged second stage of labour has been associated with adverse maternal and perinatal outcomes. The maximum length of the second stage from full dilatation to birth of the baby remains controversial. Our aim was to determine whether extending second stage of labour was associated with adverse maternal and perinatal outcomes. METHODS: A retrospective cohort study was conducted using routinely collected hospital data from 51592 births in Aberdeen Maternity Hospital between 2000 and 2016. The hospital followed the local guidance of allowing second stage of labour to extend by an hour compared to national guidelines since 2008 (nulliparous and parous). The increasing duration of second stage of labour was the exposure. Baseline characteristics, maternal and perinatal outcomes were compared between women who had a second stage labour of (a) ≤ 3 h and (b) > 3 h duration for nulliparous women; and (a) ≤ 2 h or (b) > 2 h for parous women. An additional model was run that treated the duration of second stage of labour as a continuous variable (measured in hours). All the adjusted models accounted for: age, BMI, smoking status, deprivation category, induced birth, epidural, oxytocin, gestational age, baby birthweight, mode of birth and parity (only for the final model). RESULTS: Each hourly increase in the second stage of labour was associated with an increased risk of obstetric anal sphincter injury (aOR 1.21 95% CI 1.16,1.25), having an episiotomy (aOR 1.48 95% CI 1.45, 1.52) and postpartum haemorrhage (aOR 1.27 95% CI 1.25, 1.30). The rates of caesarean and forceps delivery also increased when second stage duration increased (aOR 2.60 95% CI 2.50, 2.70, and aOR 2.44 95% CI 2.38, 2.51, respectively.) Overall adverse perinatal outcomes were not found to change significantly with duration of second stage on multivariate analysis. CONCLUSIONS: As the duration of second stage of labour increased each hour, the risk of obstetric anal sphincter injuries, episiotomies and PPH increases significantly. Women were over 2 times more likely to have a forceps or caesarean birth. The association between adverse perinatal outcomes and the duration of second stage of labour was less convincing in this study.

Perinatal outcomes in singleton live births after blastocyst transfer: an analysis of 60,926 in vitro fertilization cycles from the United Kingdom.

OBJECTIVE: To compare perinatal outcomes between singleton live births after blastocyst-stage and cleavage-stage fresh embryo transfer using data from all United Kingdom licensed fertility clinics. DESIGN: A cohort study. SETTING: Not applicable. PATIENT(S): A total of 60,926 in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles resulting in a singleton live birth after blastocyst-stage and cleavage-stage fresh embryo transfer between 2012 and 2018. INTERVENTION(S): Baseline characteristics between IVF/ICSI blastocyst and cleavage-stage transfer groups were compared using the χ2 test for categorical/dichotomized variables and the Mann-Whitney test for continuous variables. Statistical significance was set at <.05. Association between perinatal outcomes and blastocyst transfer compared with cleavage-stage transfer was assessed using multinomial logistic regression, adjusting for confounders selected using directed acyclic graphs (95% confidence interval [CI], adjusted relative risk ratio [aRRR]). A subgroup analysis included cycles in women undergoing their first IVF/ICSI cycle. MAIN OUTCOMES MEASURE(S): Gestational age at birth and birth weight. RESULT(S): The blastocyst group comprised 42,677 IVF/ICSI cycles and cleavage-stage group 18,249 cycles. There was likely little to no difference in the risk of preterm (aRRR, 1.07; 95% CI, 1.00-1.15) and very preterm birth (aRRR, 1.05; 95% CI, 0.91-1.21) in singleton live births after fresh blastocyst and cleavage-stage transfer. Risks of low birth weight (aRRR, 1.02; 95% CI, 0.95-1.09), very low birth weight (aRRR 0.96; 95% CI, 0.83-1.11), high birth weight (aRRR, 0.97; 95% CI, 0.90-1.04), and very high birth weight (aRRR, 0.91; 95% CI, 0.77-1.08) were likely similar between the groups. The findings were consistent in the subgroup analysis. CONCLUSION(S): Fresh blastocyst transfer does not appear to have a negative impact on gestational age at birth and birth weight in singleton live births compared with fresh cleavage-stage transfer.

A comparison of perinatal outcomes following fresh blastocyst or cleavage stage embryo transfer in singletons and twins and between singleton siblings.

STUDY QUESTION: Are perinatal outcomes following fresh blastocyst versus fresh cleavage stage embryo transfer (ET) different in singletons, twins, and between singleton siblings? SUMMARY ANSWER: Singleton babies conceived following fresh blastocyst, versus cleavage stage, ET are less likely to be small for gestational age (SGA) or to have a congenital anomaly (a result confirmed by comparing singleton siblings), while singletons born following fresh blastocyst ET were at a higher risk of being large for gestational age (LGA) than their sibling born following fresh cleavage stage ET. WHAT IS KNOWN ALREADY: Blastocyst stage transfer is now the preferred strategy in most IVF units. Previous studies have suggested that babies conceived through blastocyst transfer are at increased risk of preterm birth and LGA. STUDY DESIGN SIZE DURATION: A national population-based retrospective cohort study was performed using linked Human Fertilisation and Embryology Authority (HFEA) data on 130 516 IVF and ICSI livebirths occurring from 103 062 women between 2000 and 2017. PARTICIPANTS/MATERIALS SETTING METHODS: We included women who had at least one singleton livebirth resulting from IVF/ICSI fresh embryo treatment, using their own eggs and partner's sperm. A linked HFEA dataset was analysed using a multilevel framework, which accommodated repeated IVF cycles resulting in livebirths in the same woman. A population-averaged robust Poisson model was used for binary outcomes and a multinomial logistic regression model was used for categorical outcomes. Unadjusted and adjusted risk ratios (aRRs) (95% CI) were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: There were 130 516 livebirths in 103 062 women, including 86 630 singletons, 43 886 twin births, and 5384 pairs of singleton siblings. In comparison with fresh cleavage stage ET, fresh blastocyst stage transfer in singletons was associated with a lower risk of low birthweight (aRR = 0.92; 95% CI 0.86, 0.99), lower risk of being SGA (0.83; 0.78, 0.89), and lower risk of congenital anomaly (0.79; 0.71, 0.89). This analysis did not show an increase in risk associated with preterm birth (1.00; 0.94, 1.06), high birthweight (0.99; 0.93, 1.06), LGA (0.99; 0.93, 1.05), and the chance of healthy singleton baby (1.00; 1.00, 1.02). Twins resulting from fresh blastocyst stage ET were at slightly higher risk of preterm birth (1.05; 1.02, 1.10) compared with twins conceived following fresh cleavage stage ET. There was insufficient evidence for an association with the other perinatal outcomes. Singleton siblings born following fresh blastocyst stage ET were at a higher risk of being LGA (1.57; 1.01, 2.46) and at lower risk of having a congenital anomaly (0.52; 0.28, 0.97) compared to their singleton siblings born following cleavage stage ET. There was some evidence of excess risk of preterm birth (1.42; 0.97, 2.23) associated with blastocyst stage transfer. However, we could not confirm an association between blastocyst stage ET and low birthweight (1.35; 0.81, 2.27), high birthweight (1.19; 0.80, 1.77), and the chance of being a healthy baby (0.97; 0.86, 1.09). LIMITATIONS REASONS FOR CAUTION: This was an observational study where we were unable to adjust for some key confounders, such as maternal smoking status and BMI, which may change from one pregnancy to another and are not recorded in the HFEA dataset. WIDER IMPLICATIONS OF THE FINDINGS: In the largest study of its kind, our analysis of singleton siblings, corrected for unmeasured, non-time varying maternal factors, confirms the previously reported association between blastocyst transfer and LGA babies, and shows a reduced risk of congenital anomaly following blastocyst transfer. Our sibling analysis did not confirm a decreased risk of low birthweight following blastocyst transfer. Overall, absolute risks are low and there is insufficient evidence to challenge the practice of extended culture of embryos. STUDY FUNDING/COMPETING INTERESTS: This project is financed by an NHS Grampian Endowment Research Grant, project number 17/052. One of the authors, S.B., was the Editor in Chief of HROpen until 31 December 2022 and would have been in that role when the paper was first submitted. As an invited speaker, S.B. has received travel expenses, accommodation and honoraria from Merck, Organon, and Ferring. A.M. has received travel expenses, accommodation, and honoraria from Merck Serono, Cook Medical, Pharmasure, Gedeon Richter, and Ferring. D.J.M. is currently a HROpen Associate Editor. TRIAL REGISTRATION NUMBER: N/A.

Comparison of perinatal outcomes after frozen or fresh embryo transfer: separate analyses of singleton, twin, and sibling live births from a linked national in vitro fertilization registry.

OBJECTIVE: To determine whether perinatal outcomes following frozen vs. fresh embryo transfer (ET) differ within singletons, within sets of twins, and between siblings. DESIGN: Population-based retrospective cohort study. SETTING: Academic Medical School PATIENT(S): 200,075 live births in 151,561 women who underwent in vitro fertilization with frozen or fresh ET between 1992 and 2017. MAIN OUTCOME MEASURE(S): Gestational age at birth, birthweight, congenital anomaly, and healthy baby (≥37 weeks of gestation, birthweight 2,500-4,000 g, no congenital malformations). RESULT(S): There were 200,075 live births in 151,561 women including 132,679 singletons, 33,698 sets of twins, and 5,723 pairs of singleton siblings. In singletons, frozen ET was associated with a lower risk of very preterm birth (adjusted relative risk [aRR], 0.83; 95% confidence interval [CI], 0.73, 0.94), preterm birth (aRR, 0.93; 95% CI, 0.88, 0.97), low birthweight (<2,500 g) (aRR, 0.72; 95% CI, 0.68, 0.77), small for gestational age (aRR, 0.66; 95% CI, 0.62, 0.70) and congenital anomaly (aRR, 0.85; 95% CI, 0.78, 0.94), but higher risk of high birthweight (>4,000 g) (aRR, 1.64; 95% CI, 1.58, 1.72) and large for gestational age (aRR, 1.62; 95% CI, 1.55, 1.70) in comparison with fresh ET. In twins, frozen ET was associated with lower risk of very preterm birth (aRR, 0.84; 95% CI, 0.73, 0.97), and low birthweight (aRR, 0.72; 95% CI, 0.68, 0.77), but with a higher chance of a healthy baby (aRR, 1.11; 95% CI, 1.06, 1.16) compared to fresh ET. Singletons conceived following frozen ET had a lower risk of low birthweight (aRR, 0.56; 95% CI, 0.44, 0.74) and being small for gestational age (aRR, 0.54; 95% CI, 0.42, 0.68) than a singleton sibling born after a fresh ET. Frozen ET also was associated with higher risk of high birthweight (aRR, 1.85; 95% CI, 1.54, 2.24) and being large for gestational age (aRR, 1.81; 95% CI, 1.50, 2.20), and also were less likely to be preterm (aRR, 0.81; 95% CI, 0.67, 0.99). CONCLUSION(S): Our key finding is that singletons born following a frozen ET are less likely to be small for gestational age than a singleton sibling born following fresh ET but are more likely to be large for gestational age.

Maternal over-the-counter analgesics use during pregnancy and adverse perinatal outcomes: cohort study of 151 141 singleton pregnancies.

OBJECTIVES: To identify any associations between in utero exposure to five over-the-counter (non-prescription) analgesics (paracetamol, ibuprofen, aspirin, diclofenac, naproxen) and adverse neonatal outcomes. DESIGN: Retrospective cohort study using the Aberdeen Maternity and Neonatal Databank. PARTICIPANTS: 151 141 singleton pregnancies between 1985 and 2015. MAIN OUTCOME MEASURES: Premature delivery (<37 weeks), stillbirth, neonatal death, birth weight, standardised birthweight score, neonatal unit admission, APGAR score at 1 and 5 min, neural tube and amniotic band defects, gastroschisis and, in males, cryptorchidism and hypospadias. RESULTS: 83.7% of women taking over-the-counter analgesics reported first trimester use when specifically asked about use at their first antenatal clinic visit. Pregnancies exposed to at least one of the five analgesics were significantly independently associated with increased risks for premature delivery <37 weeks (adjusted OR (aOR)=1.50, 95% CI 1.43 to 1.58), stillbirth (aOR=1.33, 95% CI 1.15 to 1.54), neonatal death (aOR=1.56, 95% CI 1.27 to 1.93), birth weight <2500 g (aOR=1.28, 95% CI 1.20 to 1.37), birth weight >4000 g (aOR=1.09, 95% CI 1.05 to 1.13), admission to neonatal unit (aOR=1.57, 95% CI 1.51 to 1.64), APGAR score <7 at 1 min (aOR=1.18, 95% CI 1.13 to 1.23) and 5 min (aOR=1.48, 95% CI 1.35 to 1.62), neural tube defects (aOR=1.64, 95% CI 1.08 to 2.47) and hypospadias (aOR=1.27, 95% CI 1.05 to 1.54 males only). The overall prevalence of over-the-counter analgesics use during pregnancy was 29.1%, however it rapidly increased over the 30-year study period, to include over 60% of women in the last 7 years of the study. This makes our findings highly relevant to the wider pregnant population. CONCLUSIONS: Over-the-counter (non-prescription) analgesics consumption during pregnancy was associated with a substantially higher risk for adverse perinatal health outcomes in the offspring. The use of paracetamol in combination with other non-steroidal anti-inflammatory drugs conferred the highest risk. The increased risks of adverse neonatal outcomes associated with non-prescribed, over-the-counter, analgesics use during pregnancy indicate that healthcare guidance for pregnant women regarding analgesic use need urgent updating.

Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial.

BACKGROUND: The benefit of fractional exhaled nitric oxide (FeNO) in guiding asthma treatment is uncertain. We evaluated the efficacy of adding FeNO to symptom-guided treatment in children with asthma versus only symptom-guided treatment. METHODS: RAACENO was a multicentre, parallel, randomised, controlled, phase 3 trial done in 35 secondary care centres and 17 primary care recruitment sites (only seven primary care sites managed to recruit patients) in the UK. Patients with a confirmed asthma diagnosis, aged 6-15 years, prescribed inhaled corticosteroids, and who received a course of oral corticosteroids for at least one asthma exacerbation during the 12 months before recruitment were included. Participants were randomly assigned to either FeNO plus symptom-guided treatment (intervention) or symptom-guided treatment alone (standard care) using a 24 h in-house, web-based randomisation system. Participants and the clinical and research teams were not masked to the group allocation. A web-based algorithm gave treatment recommendations based on the Asthma Control Test (ACT) or Childhood ACT (CACT) score; current asthma treatment; adherence to study treatment in the past 3 months; and use of FeNO (in the intervention group). Follow-up occurred at 3-month intervals for 12 months. The primary outcome was any asthma exacerbation treated with oral corticosteroids in the 12 months after randomisation, assessed in the intention-to-treat population. This study is registered with the International Standard Randomised Controlled Trial Registry, ISRCTN67875351. FINDINGS: Between June 22, 2017, and Aug 8, 2019, 535 children were assessed for eligibility, 20 were ineligible and six were excluded post-randomisation. 509 children were recruited and at baseline, the mean age of participants was 10·1 years (SD 2·6), and 308 (60·5%) were male. The median FeNO was 21 ppb (IQR 10-48), mean predicted FEV1 was 89·6% (SD 18·0), and median daily dose of inhaled corticosteroids was 400 µg budesonide equivalent (IQR 400-1000). Asthma was partly or fully controlled in 256 (50·3%) of 509 participants. The primary outcome, which was available for 506 (99%) of 509 participants, occurred in 123 (48·2%) of 255 participants in the intervention group and 129 (51·4%) of 251 in the standard care group, the intention-to-treat adjusted odds ratio (OR) was 0·88 (95% CI 0·61 to 1·27; p=0·49). The adjusted difference in the percentage of participants who received the intervention in whom the primary outcome occurred compared with those who received standard care was -3·1% (-11·9% to 5·6%). In 377 (21·3%) of 1771 assessments, the algorithm recommendation was not followed. Adverse events were reported by 27 (5·3%) of 509 participants (15 in the standard care group and 12 in the intervention group). The most common adverse event was itch after skin prick testing (reported by eight participants in each group). INTERPRETATION: We found that the addition of FeNO to symptom-guided asthma treatment did not lead to reduced exacerbations among children prone to asthma exacerbation. Asthma symptoms remain the only tool for guiding treatment decisions. FUNDING: National Institute for Health Research.

Predicting personalized cumulative live birth following in vitro fertilization.

OBJECTIVE: To develop in vitro fertilization (IVF) prediction models to estimate the individualized chance of cumulative live birth at two time points: pretreatment (i.e., before starting the first complete cycle of IVF) and posttreatment (i.e., before starting the second complete cycle of IVF in those couples whose first complete cycle was unsuccessful). DESIGN: Population-based cohort study. SETTING: National data from the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System. PATIENT(S): Based on 88,614 women who commenced IVF treatment using their own eggs and partner's sperm in SART member clinics. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The pretreatment model estimated the cumulative chance of a live birth over a maximum of three complete cycles of IVF, whereas the posttreatment model did so over the second and third complete cycles. One complete cycle included all fresh and frozen embryo transfers resulting from one episode of ovarian stimulation. We considered the first live birth episode, including singletons and multiple births. RESULT(S): Pretreatment predictors included woman's age (35 years vs. 25 years, adjusted odds ratio 0.69, 95% confidence interval 0.66-0.73) and body mass index (35 kg/m2 vs. 25 kg/m2, adjusted odds ratio 0.75, 95% confidence interval 0.72-0.78). The posttreatment model additionally included the number of eggs from the first complete cycle (15 vs. 9 eggs, adjusted odds ratio 1.10, 95% confidence interval 1.03-1.18). According to the pretreatment model, a nulliparous woman aged 34 years with a body mass index of 23.3 kg/m2, male partner infertility, and an antimüllerian hormone level of 3 ng/mL has a 61.7% chance of having a live birth over her first complete cycle of IVF (and a cumulative chance over three complete cycles of 88.8%). If a live birth is not achieved, according to the posttreatment model, her chance of having a live birth over the second complete cycle 1 year later (age 35 years, number of eggs 7) is 42.9%. The C-statistic for all models was between 0.71 and 0.73. CONCLUSION(S): The focus of previous IVF prediction models based on US data has been cumulative live birth excluding cycles involving frozen embryos. These novel prediction models provide clinically relevant estimates that could help clinicians and couples plan IVF treatment at different points in time.

The association between opening a short stay paediatric assessment unit and trends in short stay hospital admissions.

BACKGROUND: Many inpatient facilities in Scotland have opened short stay paediatric assessment units (SSPAU) which are clinical areas separate from the usual inpatient ward area and these are where most short stay (also called zero day) admissions are accommodated. Here we describe the effect of opening short stay paediatric assessment units (SSPAU) on the proportion of zero day admissions relative to all emergency admissions. METHODS: Details of all emergency medical paediatric admissions to Scottish hospitals between 2000 and 2013 were obtained, including the number of zero day admissions per month and health board (i.e. geographic region). The month and year that an SSPAU opened in each health board was provided by local clinicians. RESULTS: SSPAUs opened in 7 health boards, between 2004 and 2012. Health boards with an SSPAU had a slower rise in zero day admissions compared to those without SSPAU (0.6% per month [95% CI 0.04, 0.09]. Across all 7 health boards, opening an SSPAU was associated with a 13% [95% CI 10, 15] increase in the proportion of zero day admissions. When considered individually, zero day admissions rose in four health boards after their SSPAU opened, were unchanged in one and fell in two health boards. Independent of SSPAUs opening, there was an increase in the proportion of all admissions which were zero day admissions (0.1% per month), and this accelerated after SSPAUs opened. CONCLUSION: Opening an SSPAU has heterogeneous outcomes on the proportion of zero day admissions in different settings. Zero day admissions could be reduced in some health boards by understanding differences in clinical referral pathways between health boards with contrasting trends in zero day admissions after their SSPAU opens.

Does admission prevalence change after reconfiguration of inpatient services? An interrupted time series analysis of the impact of reconfiguration in five centres.

BACKGROUND: Service reconfiguration of inpatient services in a hospital includes complete and partial closure of all emergency inpatient facilities. The "natural experiment" of service reconfiguration may give insight into drivers for emergency admissions to hospital. This study addressed the question does the prevalence of emergency admission to hospital for children change after reconfiguration of inpatient services? METHODS: There were five service reconfigurations in Scottish hospitals between 2004 and 2018 where emergency admissions to one "reconfigured" hospital were halted (permanently or temporarily) and directed to a second "adjacent" hospital. The number of emergency admissions (standardised to /1000 children in the regional population) per month to the "reconfigured" and "adjacent" hospitals was obtained for five years prior to reconfiguration and up to five years afterwards. An interrupted time series analysis considered the association between reconfiguration and admissions across pairs comprised of "reconfigured" and "adjacent" hospitals, with adjustment for seasonality and an overall rising trend in admissions. RESULTS: Of the five episodes of reconfiguration, two were immediate closure, two involved closure only to overnight admissions and one with overnight closure for a period and then closure. In "reconfigured" hospitals there was an average fall of 117 admissions/month [95% CI 78, 156] in the year after reconfiguration compared to the year before, and in "adjacent" hospitals admissions rose by 82/month [32, 131]. Across paired reconfigured and adjacent hospitals, in the months post reconfiguration, the overall number of admissions to one hospital pair slowed, in another pair admissions accelerated, and admission prevalence was unchanged in three pairs. After reconfiguration in one hospital, there was a rise in admissions to a third hospital which was closer than the named "adjacent" hospital. CONCLUSIONS: There are diverse outcomes for the number of emergency admissions post reconfiguration of inpatient facilities. Factors including resources placed in the community after local reconfiguration, distance to the "adjacent" hospital and local deprivation may be important drivers for admission pathways after reconfiguration. Policy makers considering reconfiguration might consider a number of factors which may be important determinants of admissions post reconfiguration.

Family history and risk of miscarriage: A systematic review and meta-analysis of observational studies.

INTRODUCTION: Miscarriage, a spontaneous pregnancy loss at <24 weeks' gestation, is a common complication of pregnancy but the etiologies of miscarriage and recurrent miscarriage are not fully understood. Other obstetric conditions such as preeclampsia and preterm birth, which may share similar pathophysiology to miscarriage, exhibit familial patterns, suggesting inherited predisposition to these conditions. Parental genetic polymorphisms have been associated with unexplained miscarriage, suggesting there could be a genetically inherited predisposition to miscarriage. This systematic review and meta-analysis of observational studies aimed to assess the association between family history of miscarriage and the risk of miscarriage in women. MATERIAL AND METHODS: A systematic review and meta-analysis of observational studies was carried out in accordance with Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Electronic searches using databases (MEDLINE, EMBASE and CINAHL) were carried out to identify eligible studies from 1946 until 2019. Observational studies (cohort or case-control) were included. Human studies only were included. Participants were women of reproductive age. Exposure was a family history of one or more miscarriage(s). The primary outcome was miscarriage in women. Abstracts were screened and data were extracted by two independent reviewers. Study quality was assessed using Critical Appraisal Skills Program (CASP) tools. Data were pooled from individual studies using the Mantel-Haenszel method to produce pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Systematic review registration number (PROSPERO): CRD42019127950. RESULTS: Thirteen studies were identified in the systematic review; 10 were eligible for inclusion in the meta-analysis. Twelve studies reported an association between family history of miscarriage and miscarriage in women. In all, 41 287 women were included in the meta-analysis. Women who miscarried were more likely to report a family history of miscarriage (pooled unadjusted OR 1.90, 95% CI 1.37-2.63). Overall study quality and size varied, with few adjusting for confounding factors. Results should be interpreted with caution as the associations presented are based on unadjusted analyses only. CONCLUSIONS: Women who miscarry may be more likely to have a family history of miscarriage. Further research is required to confirm or refute the findings.

Testing the twin testosterone transfer hypothesis-intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland.

STUDY QUESTION: Does having a male co-twin influence the female twin's reproductive outcomes? SUMMARY ANSWER: Women with a male co-twin had the same chances of being pregnant and having children compared to same-sex twin pairs. WHAT IS KNOWN ALREADY: According to the twin testosterone transfer (TTT) hypothesis, in an opposite-sex twin pregnancy, testosterone transfer from the male to the female co-twin occurs. A large body of literature supports the negative impact of prenatal testosterone exposure on female's reproductive health in animal models; however, evidence from human studies remains controversial. STUDY DESIGN, SIZE, DURATION: This cohort study included all dizygotic female twins in the Aberdeen Maternity and Neonatal Databank (Scotland) born before 1 January 1979. The 317 eligible women were followed up for 40 years for any pregnancies and the outcome of those pregnancies recorded in the same database. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fertility outcomes (number of pregnancies, number of livebirths and age at first pregnancy) were compared between women with a male co-twin (exposed group, n = 151) and those with a female co-twin (unexposed group, n = 166). Population averaged models were used to estimate odds ratios (OR) and 95% CI for all outcomes with adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in chances of having pregnancies (adj. OR 1.33; 95% CI 0.72, 2.45) and livebirths (adj. OR 1.22; 95% CI 0.68, 2.18) between women from same-sex and opposite-sex twin pairs. Women with a male co-twin were more likely to smoke during pregnancy and, in the unadjusted model, were younger at their first pregnancy (OR 2.13; 95% CI 1.21, 3.75). After adjusting for confounding variables (year of birth and smoking status) the latter finding was no longer significant (OR 1.67; 95% CI 0.90, 3.20). LIMITATIONS, REASONS FOR CAUTION: The dataset was relatively small. For women without a pregnancy recorded in the databank, we assumed that they had not been pregnant. WIDER IMPLICATIONS OF THE FINDINGS: Despite the evidence from animal studies concerning the adverse effects of prenatal testosterone exposure on female health, our results do not support the TTT hypothesis. The finding that women with a male co-twin are more likely to smoke during pregnancy highlights the importance of considering post-socialisation and social effects in twin studies. STUDY FUNDING/COMPETING INTEREST(S): European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie project PROTECTED (grant agreement No. 722634) and FREIA project (grant agreement No. 825100). No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Changing risk factors for placental abruption: A case crossover study using routinely collected data from Finland, Malta and Aberdeen.

OBJECTIVE: To evaluate the effects of changes in risk factors between the first two pregnancies on the occurrence of placental abruption (PA) in the same woman. METHODS: Routinely collected obstetric data from Aberdeen Maternity and Neonatal Databank, the Maltese National Obstetric Information System and the Finnish Medical Birth Register were aggregated. Records of the first two singleton pregnancies from women who had PA in one pregnancy but not the other, were identified from this pooled dataset. A case-crossover study design was used; cases were pregnancies with abruption and matched controls were pregnancies without abruption in the same woman. Conditional logistic regression was used to investigate changes in risk factors for placental abruption in pregnancies with and without abruption. RESULTS: A total of 2,991 women were included in the study. Of these 1,506 (50.4%) had PA in their first pregnancy and 1,485 (49.6%) in a second pregnancy. Pregnancies complicated by preeclampsia {194 (6.5%) versus 115 (3.8%) adj OR 1.69; (95% CI 1.23-2.33)}, antepartum haemorrhage of unknown origin {556 (18.6%) versus 69 (2.3%) adjOR 27.05; 95% CI 16.61-44.03)} and placenta praevia {80 (2.7%) versus 21 (0.7%) (adjOR 3.05; 95% CI 1.74-5.36)} were associated with PA. Compared to 20 to 25 years, maternal age of 35-39 years {365 (12.2) versus 323 (10.8) (adjOR 1.32; 95% CI 1.01-1.73) and single marital status (adjOR 1.36; 95% CI 1.04-1.76) were independently associated with PA. Maternal smoking, BMI and fetal gender were not associated with PA. CONCLUSION: Advanced maternal age, pregnancies complicated with unexplained bleeding in pregnancy, placenta praevia and preeclampsia were independently associated with a higher risk of placental abruption.

Inherited susceptibility to miscarriage: a nested case-control study of 31,565 women from an intergenerational cohort.

BACKGROUND: Miscarriage can be a devastating outcome for couples, and most miscarriages are unexplained. Many adverse obstetric outcomes (such as preeclampsia, preterm birth, and growth restriction) are thought to be inherited. It is possible that these conditions could share similar pathophysiologic mechanisms (such as endothelial dysfunction) with miscarriage. Therefore, it was hypothesized that there could be a susceptibility to miscarriage transmitted from mother to daughter. OBJECTIVE: This study aimed to investigate the association between a maternal history of miscarriage and the risk of miscarriage in daughters. STUDY DESIGN: A case-control study nested within an intergenerational cohort was conducted. Mother-daughter pairs were identified from the intergenerational cohort within the Aberdeen Maternity and Neonatal Databank, United Kingdom. A mother's history of miscarriage was the exposure. The primary outcome was miscarriage in daughters. There were 31,565 mother-daughter pairs who were eligible for inclusion. A population average model that used generalized estimating equations with robust standard errors was used to estimate the odds of a mother's history of miscarriage in daughters with a miscarriage compared with daughters with only livebirths. This method accounted for clustering of daughters within mothers, and multiadjusted analyses were performed to include confounders at the daughter's pregnancy level. RESULTS: Daughters who miscarried had 11% greater odds of being born to mothers with a history of miscarriage (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). Daughters with recurrent miscarriage (≥2) were also more likely to be born to a mother with a history of miscarriage (adjusted odds ratio, 1.25; 95% confidence interval, 1.04-1.49). CONCLUSION: There may be an inherited predisposition to miscarriage transmitted from mother to daughter. Future research should investigate genetic or familial environmental factors that may predispose women to miscarriage.

Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer: a retrospective analysis of 67 147 IVF/ICSI cycles.

STUDY QUESTION: Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos? SUMMARY ANSWER: Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby. WHAT IS KNOWN ALREADY: Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann-Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5% confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95% CIs were calculated in the sub-group analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5% CI, 0.79-1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5% CI, 0.63-1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5% CI, 0.53-1.34), low birth weight (LBW) (aRR, 0.92; 99.5% CI, 0.73-1.16), high birth weight (HBW) (aRR, 0.94; 99.5% CI, 0.75-1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5% CI, 0.66-1.65). The risk of congenital anomaly was 16% higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5% CI, 0.90-1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5% CI, 0.93-1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5% CI, 1.01-1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95% CI, 1.00-1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95% CI, 1.12-1.81). LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle. WIDER IMPLICATIONS OF THE FINDINGS: Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer. STUDY FUNDING/COMPETING INTEREST(S): The research activity of Dr Nicola Marconi was funded by the scholarship 'A. Griffini-J. Miglierina', Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Weight-Based Guide Overestimates Endotracheal Tube Tip Position in Extremely Preterm Infants.

OBJECTIVE: To evaluate the association between endotracheal tube (ETT) tip position and adverse pulmonary outcomes using chest X-ray (CXR) in extremely preterm infants in whom ETT insertion length was estimated using weight + 6 guide (adding 6 cms to the infant's weight in kg). STUDY DESIGN: CXRs of 85 infants performed in the first week were reviewed for right-sided atelectasis, air leaks, and uneven lung inflation. The first CXR was later reviewed to document the ETT tip. Regression analysis was performed to find the association between ETT tip position and adverse outcome after adjusting for other confounders. RESULTS: Forty (46%) infants had ETT tip placement between the first and second thoracic vertebrae (optimal position) compared with 45 (53%) who had the ETT tip placement outside this range (suboptimal position). Infants with suboptimal ETT were ventilated for a longer period (6.1 vs. 15.9 days; p = 0.004). The odds of adverse outcomes was 11.6 (95% confidence interval: 3.03, 44.1) times higher among infants who did not have ETT at the optimal position compared with infants who had ETT at the optimal position. CONCLUSION: Weight + 6 guide is not recommended to estimate ETT insertion length in extremely preterm infants. Gestation-based guide may be more appropriate to estimate ETT insertion length in this group of infants.

Inherited predisposition to stillbirth: an intergenerational analysis of 26,788 mother-daughter pairs.

BACKGROUND: Previous evidence suggests that placental dysfunction, which includes preeclampsia, is inherited from mother to daughter, but heritability of stillbirth has never been investigated. OBJECTIVE: The purpose of this study was to investigate whether there is an inherited predisposition to stillbirth that is transmitted from mother to daughter. STUDY DESIGN: We carried out a nested case-control study within the intergenerational cohort held in the Aberdeen Maternity and Neonatal Databank. All mothers who had at least 1 daughter in Aberdeen, United Kingdom, between 1949 and 2000 were included. Mother-daughter pairs were linked with the use of the Scottish Community Health Index number. The main exposure was the mother's history of stillbirth. The primary outcome was stillbirth in any of the daughter's pregnancies. A population average model that used generalized estimating equations with robust standard errors was used to estimate odds of a mother's history of stillbirth in daughters with a stillbirth compared with daughters with only livebirths. This method accounted for clustering of daughters within mothers, and multi-adjusted analyses were performed to include confounders at the daughter's pregnancy level. RESULTS: Among the daughters, 384 had a history of ≥1 stillbirths (cases); 26,404 only ever had livebirths (control subjects). We found no statistically significant association between mothers' history of stillbirth (adjusted odds ratio, 0.63; 95% confidence interval, 0.24-1.63) or miscarriage (adjusted odds ratio, 1.01; 95% confidence interval, 0.71-1.42) and stillbirth in daughters. CONCLUSION: This is the first study to investigate an inherited predisposition to stillbirth. There was no evidence of an inherited predisposition to stillbirth transmitted from mother to daughter.

Intervention thresholds and cesarean section rates: A time-trends analysis.

INTRODUCTION: To improve understanding of rising cesarean section (CS) rates in the UK, this study assessed the relation between clinician thresholds for performing CS for delayed labor progress or suspected fetal distress and corresponding CS rates in Aberdeen, UK. MATERIAL AND METHODS: Time-trends analysis of term births from 1988 to 2012 in a population of nulliparous women (N = 53 745) in Aberdeen, UK, using Chi-square test for trend, and binary logistic regression. Data were obtained from the Aberdeen Maternity and Neonatal Databank. RESULTS: Unplanned CS rates per quintile increased from 11.0% (1391/12 686) to 21.1% (2383/11 273) between 1988 and 2012, while planned CS rates increased from 2.7% (338/12 686) to 5.2% (591/11 273). The median duration of labor before CS for delayed progress per quintile decreased from 17.2 (IQR 12.5-22.3) to 13.1 hours (9.6-16.9) before first stage CS and from 17.1 (12.6-22.3) to 15.3 (11.5-19.1) hours before second stage CS (P < .001). The proportion of CS for suspected fetal distress performed with evidence of fetal acidosis declined from 23.4% (98/418) to 17.4% (106/608) per quintile (P < .01). Neonatal unit admission (adjusted OR 1.99, 95% CI 1.85-2.14) was more likely following unplanned CS than vaginal births. Birth trauma was less likely following both unplanned (adjusted OR 0.48, 95% CI 0.39-0.60) and planned (adjusted OR 0.33, 95% CI 0.18-0.63) CS. CONCLUSION: Increased CS rates can be partly attributed to lowered clinical thresholds for intrapartum CS. Higher CS rates are associated with less birth trauma for the offspring.