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.

Socioeconomic status in adulthood of children with and without a history of seizures: A retrospective cohort study.

OBJECTIVE: Compare adulthood socioeconomic status for children with and without a history of seizures. METHODS: Retrospective cohort study using Aberdeen Children of the Nineteen Fifties (ACONF) data comprising children born 1950-1956 attending primary school 1962-1964, with follow-up data collected in 2001. Adulthood socioeconomic status was based on registrar general measure of occupational social class and categorised as high or low. We adjusted for potentially confounding variables including childhood socioeconomic status, behavioural issues (Rutter A/B scores), biological sex, school test scores, educational attainment, parental engagement with education, peer-status in school, and alcohol use in adulthood. A multivariate binary logistic regression was performed to estimate the adjusted association between children with a history of seizures of any type (for example febrile seizures, or provoked seizures of any other etiology or seizures in the context of epilepsy) or severity and adult socioeconomic status. Multiple imputation using the Monte-Carlo-Markov-Chain method accounted for missing data. RESULTS: Pooled estimates (N = 2,208) comparing children with a history of seizures (n = 81) and children without a history of seizures (n = 2,127) found no differences between these cohorts in terms of adulthood socioeconomic status in both unadjusted (Odds Ratio (OR) 1.45 [95 % CI 0.71-2.96], p = 0.31) and adjusted (1.02 [0.46, 2.24], p = 0.96) analyses. Compared to males, females were at increased odds of having a lower socioeconomic status in adulthood (1.56 [1.13-2.17], p = 0.01).Compared to those with low educational attainment, those with moderate (0.32 [0.21, 0.48], p < 0.001) and high (0.12 [0.07, 0.20], p < 0.001) educational attainment were at reduced odds of having a lower socioeconomic status in adulthood. CONCLUSION: Cognitive problems in childhood (using educational attainment and scores on primary school tests proxy markers for cognition) rather than a history of seizures per se, were associated with lower SES in a population of adults born 1950-56 in Aberdeen. This relationship may be different depending on the time in history and nation/region of study. Given the changes in health, education and social support in the management of children with seizures over time, it would be of interest to investigate outcomes in a contemporary cohort. Such studies should ideally have validated diagnoses of seizures, details on seizure characteristics such as seizure type and severity, and a large sample size using national data.

Early pregnancy outcomes of IVF cycles using donor versus partner sperm: analysis of 1 376 454 cycles recorded by the Human Fertilisation and Embryology Authority (1991-2016).

STUDY QUESTION: Are the early pregnancy outcomes of IVF pregnancies conceived with donor sperm different to those conceived with partner sperm? SUMMARY ANSWER: Pregnancies conceived with donor sperm have a lower odds of early pregnancy loss and ectopic pregnancy compared to pregnancies conceived with partner sperm. WHAT IS KNOWN ALREADY: The number of cycles using donor sperm has risen significantly in recent years. Adverse early pregnancy outcomes have a negative impact on women and their partners. The evidence available to date regarding early pregnancy outcomes for pregnancies conceived with IVF donor sperm is limited by low numbers and lower-quality studies. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of 1 376 454 cycles conceived with either donor or partner sperm between 1991 and 2016 as recorded in the Human Fertilisation and Embryology Authority (HFEA) Register. PARTICIPANTS/MATERIALS, SETTING, METHODS: The HFEA has recorded data on all fertility treatments carried out in the UK from 1991 onwards, and it publishes this data in an anonymized form. This study assessed the outcomes of all pregnancies conceived with donor sperm and compared them to those conceived with partner sperm among IVF cycles recorded in the HFEA anonymized dataset from 1991 to 2016. Cycles that included intrauterine insemination, donor oocytes, preimplantation genetic testing, oocyte thaw cycles and alternative fertility treatments were excluded. The outcomes of interest were biochemical pregnancy, miscarriage, ectopic pregnancy, stillbirth and live birth. Logistic regression was used to adjust for confounding factors including age of the female partner, cause of infertility, history of previous pregnancy, fresh or frozen cycle, IVF or ICSI, number of embryos transferred, and year of treatment. Results are reported as adjusted odds ratios (aOR) and 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: This study found reductions in the odds of biochemical pregnancy (aOR 0.82, 95% CI 0.78-0.86), miscarriage (aOR 0.93, 95% CI 0.89-0.97), and ectopic pregnancy (aOR 0.77, 95% CI 0.66-0.90) among pregnancies as a result of the use of donor sperm as opposed to partner sperm. LIMITATIONS, REASONS FOR CAUTION: This study is retrospective and limited by the constraints of routinely collected data. No data were available for maternal characteristics such as BMI, smoking and partner age, which could all be potential confounders. Clustering of multiple pregnancies within women could not be accounted for as the data are reported only at the cycle level with no maternal identifiers. WIDER IMPLICATIONS OF THE FINDINGS: This study has demonstrated that there are no increased risks of adverse pregnancy outcome with donor sperm pregnancies. The reduction in miscarriage in pregnancies using donor sperm suggests that sperm could have a role in miscarriage, as the selection process for being accepted as donor is stringent. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study. C.A. has received funding from Ferring to attend a UK meeting for trainees in reproductive Medicine. A.M. has received funding from Ferring, Cook, Merck Serono, Geodon Ritcher, and Pharmasure for speaking at, or attending, meetings relating to reproductive medicine. She has also participated in a Ferring advisory board. S.B. has received grants from Tenovus and the UK Medical Research Council. She has also been supported with a Medical Research Scotland PhD studentship. TRIAL REGISTRATION NUMBER: N/A.

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.

General and age-specific fertility rates in non-affective psychosis: population-based analysis of Scottish women.

PURPOSE: Women diagnosed with non-affective psychosis have a lower general fertility rate (GFR) and age-specific fertility rate (ASFR) than women in the general population. Contemporary data on GFR in this group remain limited, despite substantive changes in prescribing and management. We calculated contemporary estimates of the GFR and ASFR for women diagnosed with non-affective psychosis compared with the general population of women without this diagnosis. METHODS: A population-based design combined routinely collected historical maternity and psychiatric data from two representative areas of Scotland. Women were included from the NHS Grampian or Greater Glasgow and Clyde areas and were aged 15-44 between 2005 and 2013 inclusive. The 'exposed' group had a diagnosis of non-affective psychosis (ICD-10 F20-F29) and was compared to the general population of 'unexposed' women in the same geographical areas. RESULTS: Annual GFR between 2005 and 2013 for women with non-affective psychosis varied from 9.6 to 21.3 live births/1000 women per year in the exposed cohort and 52.7 to 57.8 live births/1000 women per year in the unexposed cohort, a rate ratio (RR) of 0.28 [p < 0.001; 95% CI (0.24, 0.32)]. ASFR for all 5-year age groups was lower in the exposed cohort than amongst unexposed women. CONCLUSION: We highlight continued low fertility rates in women with a diagnosis of non-affective psychosis, despite widespread availability of prolactin-sparing atypical antipsychotics. Accurate estimation of fertility rates remains crucial in developing needs-matched perinatal care for these women. Methodological improvements using routine datasets to investigate perinatal mental health are also urgently needed.

Does interpregnancy BMI change affect the risk of complications in the second pregnancy? Analysis of pooled data from Aberdeen, Finland and Malta.

OBJECTIVE: Weight management interventions during pregnancy have had limited success in reducing the risk of pregnancy complications. Focus has now shifted to pre-pregnancy counselling to optimise body weight before subsequent conception. We aimed to assess the effect of interpregnancy body mass index (BMI) change on the risk of perinatal complications in the second pregnancy. METHODS: A cohort study was performed using pooled maternity data from Aberdeen, Finland and Malta. Women with a BMI change of ±2 kg/m2 between their first and second pregnancies were compared with those who were BMI stable (remained within ±2 kg/m2). Outcomes assessed included pre-eclampsia (PE), intrauterine growth restriction (IUGR), preterm birth, birth weight, and stillbirth in the second pregnancy. We also assessed the effect of unit change in BMI for PE and IUGR. Logistic regression was used to calculate odds ratios with 95% confidence intervals. RESULTS: An increase of ≥2 kg/m2 between the first two pregnancies increased the risk of PE (1.66 (1.49-1.86)) and high birthweight (>4000 g) (1.06 (1.03-1.10)). A reduction of ≥2 kg/m2 increased the chance of IUGR (1.15 (1.01-1.31)) and preterm birth (1.14 (1.01-1.30)), while reducing the risk of instrumental delivery (0.75 (0.68-0.85)) and high birthweight (0.93 (0.87-0.98)). Reducing BMI did not significantly decrease PE risk in women with obesity or those with previous PE. A history of PE or IUGR in the first pregnancy was the strongest predictor of recurrence independent of interpregnancy BMI change (5.75 (5.30-6.24) and (7.44 (6.71-8.25), respectively). CONCLUSION: Changes in interpregnancy BMI have a modest impact on the risk of high birthweight, PE and IUGR in contrasting directions. However, a prior history of PE and IUGR is the dominant predictor of recurrence at second pregnancy.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

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.

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.

Spontaneous very preterm birth in relation to social class, and smoking: a temporal-spatial analysis of routinely collected data in Aberdeen, Scotland (1985-2010).

OBJECTIVE: To examine trends of spontaneous very preterm birth (vPTB) and its relationship with maternal socioeconomic status and smoking. METHODS: This was a population-based cohort study in Aberdeen Maternity Hospital, UK. The cohort was restricted to spontaneous singleton deliveries occurring in Aberdeen from 1985 to 2010. The primary outcome was very preterm birth which was defined as <32 weeks gestation and the comparison group was deliveries ≥37 weeks of gestation. The main exposures were parental Social Class based on Occupation, Carstairs' deprivation index and smoking during pregnancy. Logistic regression was used to estimate the association between vPTB and the exposures. RESULTS: There was an increased likelihood of vPTB in those with unskilled-occupations compared to professional-occupations [aOR:2.77 (95%CI:1.54-4.99)], in those who lived in the most deprived areas compared to those in the most affluent [aOR: 2.16 (95% CI: 1.27-3.67)] and in women who smoked compared to those who did not [aOR: 1.74 (95% CI: 1.36-2.21)]. The association with Carstairs index was no longer statistically significant when restricted to smokers but remained significant when restricted to non-smokers. CONCLUSION: The strongest risk factor for vPTB was maternal smoking while socioeconomic deprivation showed a strong association in non-smokers. Smoking cessation interventions may reduce vPTB. Modifiable risk factors should be explored in deprived areas.

Consequences of being overweight or obese during pregnancy on diabetes in the offspring: a record linkage study in Aberdeen, Scotland.

AIMS/HYPOTHESIS: Maternal obesity in pregnancy is associated with cardiovascular disease and mortality rate in the offspring. We aimed to determine whether maternal obesity is also associated with increased incidence of type 2 and type 1 diabetes in the offspring, independently of maternal diabetes as a candidate mechanistic pathway. METHODS: Birth records of 118,201 children from 1950 to 2011 in the Aberdeen Maternity and Neonatal Databank were linked to Scottish Care Information-Diabetes, the national register for diagnosed diabetes in Scotland, to identify incident and prevalent type 1 and type 2 diabetes up to 1 January 2012. Maternal BMI was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on offspring outcomes was tested using time-to-event analysis with Cox proportional hazards regression to compare outcomes in offspring of mothers in underweight, overweight or obese categories of BMI, compared with offspring of women with normal BMI. RESULTS: Offspring of obese (BMI ≥30 kg/m2) and overweight (BMI 25-29.9 kg/m2) mothers had an increased hazard of type 2 diabetes compared with mothers with normal BMI, after adjustment for gestation when weight was measured, maternal history of diabetes before pregnancy, maternal history of hypertension, age at delivery, parity, socioeconomic status, and sex of the offspring: HR 3.48 (95% CI 2.33, 5.06) and HR 1.39 (1.06, 1.83), respectively. CONCLUSIONS/INTERPRETATION: Maternal obesity is associated with increased incidence of type 2 diabetes in the offspring. Evidence-based strategies that reduce obesity among women of reproductive age and that might reduce the incidence of diabetes in their offspring are urgently required.

Planned mode of delivery after previous cesarean section and short-term maternal and perinatal outcomes: A population-based record linkage cohort study in Scotland.

BACKGROUND: Policy consensus in high-income countries supports offering pregnant women with previous cesarean section a choice between planning an elective repeat cesarean section (ERCS) or attempting a vaginal birth, known as a planned vaginal birth after previous cesarean (VBAC), provided they do not have contraindications to planned VBAC. However, robust comprehensive information on the associated outcomes to counsel eligible women about this choice is lacking. This study investigated the short-term maternal and perinatal outcomes associated with planned mode of delivery after previous cesarean section among women delivering a term singleton and considered eligible to have a planned VBAC. METHODS AND FINDINGS: A population-based cohort of 74,043 term singleton births in Scotland between 2002 and 2015 to women with one or more previous cesarean sections was conducted using linked Scottish national datasets. Logistic or modified Poisson regression, as appropriate, was used to estimate the effect of planned mode of delivery on maternal and perinatal outcomes adjusted for sociodemographic, maternal medical, and obstetric-related characteristics. A total of 45,579 women gave birth by ERCS, and 28,464 had a planned VBAC, 28.4% of whom went on to have an in-labor nonelective repeat cesarean section. Compared to women delivering by ERCS, those who had a planned VBAC were significantly more likely to have uterine rupture (0.24%, n = 69 versus 0.04%, n = 17, adjusted odds ratio [aOR] 7.3, 95% confidence interval [CI] 3.9-13.9, p < 0.001), a blood transfusion (1.14%, n = 324 versus 0.50%, n = 226, aOR 2.3, 95% CI 1.9-2.8, p < 0.001), puerperal sepsis (0.27%, n = 76 versus 0.17%, n = 78, aOR 1.8, 95% CI 1.3-2.7, p = 0.002), and surgical injury (0.17% versus 0.09%, n = 40, aOR 3.0, 95% CI 1.8-4.8, p < 0.001) and experience adverse perinatal outcomes including perinatal death, admission to a neonatal unit, resuscitation requiring drugs and/or intubation, and an Apgar score < 7 at 5 minutes (7.99%, n = 2,049 versus 6.37%, n = 2,570, aOR 1.6, 95% CI 1.5-1.7, p < 0.001). However, women who had a planned VBAC were more likely than those delivering by ERCS to breastfeed at birth or hospital discharge (63.6%, n = 14,906 versus 54.5%, n = 21,403, adjusted risk ratio [aRR] 1.2, 95% CI 1.1-1.2, p < 0.001) and were more likely to breastfeed at 6-8 weeks postpartum (43.6%, n = 10,496 versus 34.5%, n = 13,556, aRR 1.2, 95% CI 1.2-1.3, p < 0.001). The effect of planned mode of delivery on the mother's risk of having a postnatal stay greater than 5 days, an overnight readmission to hospital within 42 days of birth, and other puerperal infection varied according to whether she had any prior vaginal deliveries and, in the case of length of postnatal stay, also varied according to the number of prior cesarean sections. The study is mainly limited by the potential for residual confounding and misclassification bias. CONCLUSIONS: Among women considered eligible to have a planned VBAC, planned VBAC compared to ERCS is associated with an increased risk of the mother having serious birth-related maternal and perinatal complications. Conversely, planned VBAC is associated with an increased likelihood of breastfeeding, whereas the effect on other maternal outcomes differs according to whether a woman has any prior vaginal deliveries and the number of prior cesarean sections she has had. However, the absolute risk of adverse outcomes is small for either delivery approach. This information can be used to counsel and manage the increasing number of women with previous cesarean section, but more research is needed on longer-term outcomes.

Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies.

BACKGROUND: Despite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age. METHODS AND FINDINGS: We searched the major electronic databases Medline, Embase, and Google Scholar (January 1990-October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome. CONCLUSIONS: Our findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015013785.

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.

Cesarean section in China, Taiwan, and Hong Kong-A safe choice for women and clinicians?

Mairead Black and Sohinee Bhattacharya discuss research findings on preferences for cesarean delivery in Asian settings and share their Perspective on facilitating woman-centered birth choices in China following the end of the one-child policy.

Intergenerational Transmission of Birth Weight Across 3 Generations.

While previous studies have shown intergenerational transmission of birth weight from mother to child, whether the continuity persists across 3 generations has rarely been assessed. We used the Aberdeen Maternity and Neonatal Databank (United Kingdom) to examine the intergenerational correlations of birth weight, birth weight adjusted for gestational age and sex, and small- and large-for-gestational-age births across 3 generations among 1,457 grandmother-mother-child triads. All participants were born between 1950 and 2015. The intergenerational transmission was examined with linear regression analyses. We found that grandmaternal birth weight was associated with grandchild birth weight, independently of prenatal and sociodemographic covariates and maternal birth weight (B = 0.12 standard deviation units, 95% confidence interval: 0.07, 0.18). Similar intergenerational continuity was found for birth weight adjusted for sex and gestational age as well as for small-for-gestational-age births. In conclusion, birth weight and fetal growth showed intergenerational continuity across 3 generations. This supports the hypothesis that the developmental origins of birth weight and hence later health and disease are already present in earlier generations.

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.

Repeat induction of labour for post-term pregnancy.

BACKGROUND: A previous post-term pregnancy is thought to influence the gestation of a subsequent pregnancy. Adverse maternal and perinatal outcomes are associated with post-term pregnancy and routine induction of labour by 42+0 weeks is advised to reduce these complications. OBJECTIVE: To determine the recurrence rate of a post-term pregnancy and the need for repeat induction of labour. METHODS: This observational cohort study featured women with a first and second singleton pregnancy, based on data recorded in the Aberdeen Maternity and Neonatal Databank (1986-2012). Term and post-term pregnancies were defined as ≥37+0 - 40+6 and ≥41+0 weeks, respectively. The exposure was a post-term pregnancy and the control a term pregnancy. Logistic regression was used to assess post-term recurrence and repeat induction of labour. RESULTS: The study population consisted of 25,669 women with 33% of the women delivering post-term in their first pregnancy. In these women, the rate of a subsequent post-term pregnancy was 35.7% compared to 18.6% for women with an initial term pregnancy (adjusted odds ratio (aOR) 2.27, 95% confidence interval (CI) 2.11-2.44). Compared to women who had spontaneous term deliveries in both pregnancies, women who were induced post-term in the second pregnancy had increased odds of having been induced post-term in their first pregnancy. The adjusted odds ratio was found to be 6.08 (95% CI 5.30-6.98). CONCLUSIONS: Women with a first post-term pregnancy are less likely to labour spontaneously and more likely to have a second post-term pregnancy with a higher risk of repeat induction of labour, than women who have previously delivered at term. These findings could be useful in the counselling of women with a previous post-term pregnancy. Given that these women are less likely to labour spontaneously, the offer of an elective induction could also be considered to potentially improve maternal and perinatal outcomes.

Cumulative live birth rates following miscarriage in an initial complete cycle of IVF: a retrospective cohort study of 112 549 women.

STUDY QUESTION: In women undergoing IVF/ICSI who miscarry in their first complete cycle, what is the chance of a live birth in subsequent complete cycles, and how does this compare with those whose first complete cycle ends with live birth or without a pregnancy? SUMMARY ANSWER: After two further complete cycles of IVF/ICSI, women who had miscarried or had a live birth in their first complete cycle had a higher chance of live birth (40.9 and 49.0%, respectively) than those who had no pregnancies (30.1%). WHAT IS KNOWN ALREADY: Cumulative live birth rates (CLBRs) after one or more complete cycles of IVF have been reported previously, as have some of the risk factors associated with miscarriage, both in general populations and in those undergoing IVF. Chances of cumulative live birth after a number of complete IVF cycles involving replacement of fresh followed by frozen embryos after an initial miscarriage in a population undergoing IVF treatment have not been reported previously. STUDY DESIGN, SIZE, DURATION: National population-based cohort study of 112 549 women who started their first IVF treatment between 1999 and 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from the UK Human Fertilisation and Embryology Authority (HFEA) register on IVF/ICSI treatments, using autologous gametes were analysed. CLBRs were estimated in women who (i) had miscarriage (and no live birth), (ii) at least one live birth or (iii) no pregnancy in their first complete cycle of IVF/ICSI (including fresh and frozen embryo transfers following a single oocyte retrieval episode). A multivariable analysis was performed to assess the effect of first complete cycle outcome on subsequent CLBRs after adjusting for confounding factors such as female age, duration of infertility and cause of infertility. MAIN RESULTS AND THE ROLE OF CHANCE: In their first complete cycle, 9321 (8.3%) women had at least one miscarriage (and no live birth); 33 152 (29.5%) had at least one live birth and 70 076 (62.3%) had no pregnancies. After two further complete cycles, conservative CLBRs (which assume that women who discontinued treatment subsequently never had a live birth) were 40.9, 49.0 and 30.1%, while optimal CLBRs (which assume that women who discontinue have the same chance of live birth as those treated) were 49.5, 57.9 and 38.4% in the miscarriage, live birth and no pregnancy groups respectively. Odds of cumulative live birth for women who miscarried in their first complete cycle were 42% higher than those who had no pregnancy [odds ratio (95% CI) = 1.42 (1.34, 1.50)], and twice as high for live birth versus no pregnancy [2.04 (1.89, 2.20)]. Negative predictors for live birth in all women included tubal infertility [0.88 (0.82, 0.94)] and increasing age [18-40 years = 0.94 (0.94, 0.95); >40 years = 0.63 (0.59, 0.66) per year]. LIMITATIONS AND REASON FOR CAUTION: CLBRs could not be estimated for treatments occurring after September 2008 due to potentially incomplete data following regulatory changes regarding consent for data use in research. Additionally, covariates not included in the HFEA database (including BMI, smoking, previous history of miscarriage and gestational age at miscarriage) could not be adjusted for in our analysis. WIDER IMPLICATIONS OF THE FINDINGS: Miscarriage following IVF can be devastating for couples who are uncertain about their ultimate prognosis. Our findings will provide reassurance to these couples as they consider their options for continuing treatment. STUDY FUNDING/COMPETING INTEREST(S): N.J.C. received an Aberdeen Summer Research Scholarship funded by the Institute of Applied Health Sciences (University of Aberdeen), through the Aberdeen Clinical Academic Training Scheme. This work was supported by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06). The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office or the University of Aberdeen. The funders did not have any role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. None of the authors has any conflicts of interest to declare.

Differences in Body Mass Index between Siblings Who Are Discordant for Exposure to Antenatal Maternal Smoking.

BACKGROUND: Maternal smoking during pregnancy is associated with increased childhood body mass index (BMI), but the relationship may be due to confounding by maternal factors. This study tested the hypothesis that siblings born to mothers who begin to smoke between pregnancies will have higher BMI than older unexposed siblings. METHODS: Maternal details from the Aberdeen Maternity and Neonatal Databank were linked to the Study of Trends in Obesity in North East Scotland which holds offspring BMI at 5 years of age. Change in maternal smoking status between pregnancies was linked to offspring BMI and also to the difference in BMI between siblings. RESULTS: Maternal smoking status in successive pregnancies was linked to child BMI at age 5 years in 6581 mother-child pairs of whom 718 included sibling pars. Children whose mothers had quit, started smoking or smoked in consecutive pregnancies had higher BMI compared with those not exposed to maternal smoking. Siblings born after onset of maternal smoking had higher mean BMI z score (0.19, 95% confidence interval (CI) 0.01, 0.36) compared with unexposed older siblings. Mean BMI z score was also higher by mean of 0.10 (95% CI 0.01, 0.20) in younger sibling compared with older siblings born to mothers who smoked in both pregnancies. BMI z score was not significantly different between siblings whose mothers quit between pregnancies. CONCLUSIONS: In utero exposure to maternal smoking during pregnancy may increase the likelihood of increased BMI in childhood.