Sinéad M. O’Neill

Advanced maternal age and adverse pregnancy outcome: evidence from a large contemporary cohort.

Background Recent decades have witnessed an increase in mean maternal age at childbirth in most high-resourced countries. Advanced maternal age has been associated with several adverse maternal and perinatal outcomes. Although there are many studies on this topic, data from large contemporary population-based cohorts that controls for demographic variables known to influence perinatal outcomes is limited. Methods We performed a population-based cohort study using data on all singleton births in 2004–2008 from the North Western Perinatal Survey based at The University of Manchester, UK. We compared pregnancy outcomes in women aged 30–34, 35–39 and ≥40 years with women aged 20–29 years using log-linear binomial regression. Models were adjusted for parity, ethnicity, social deprivation score and body mass index. Results The final study cohort consisted of 215,344 births; 122,307 mothers (54.19%) were aged 20–29 years, 62,371(27.63%) were aged 30–34 years, 33,966(15.05%) were aged 35–39 years and 7,066(3.13%) were aged ≥40 years. Women aged 40+ at delivery were at increased risk of stillbirth (RR = 1.83, [95% CI 1.37–2.43]), pre-term (RR = 1.25, [95% CI: 1.14–1.36]) and very pre-term birth (RR = 1.29, [95% CI:1.08–1.55]), Macrosomia (RR = 1.31, [95% CI: 1.12–1.54]), extremely large for gestational age (RR = 1.40, [95% CI: 1.25–1.58]) and Caesarean delivery (RR = 1.83, [95% CI: 1.77–1.90]). Conclusions Advanced maternal age is associated with a range of adverse pregnancy outcomes. These risks are independent of parity and remain after adjusting for the ameliorating effects of higher socioeconomic status. The data from this large contemporary cohort will be of interest to healthcare providers and women and will facilitate evidence based counselling of older expectant mothers.

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

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

The Impact of Caesarean Section on the Risk of Childhood Overweight and Obesity: New Evidence from a Contemporary Cohort Study

Caesarean section (CS) rates are increasing globally and exceed 50% in some countries. Childhood obesity has been linked to CS via lack of exposure to vaginal microflora although the literature is inconsistent. We investigated the association between CS birth and the risk of childhood obesity using the nationally representative Growing-Up-in-Ireland (GUI) cohort. The GUI study recruited randomly 11134 infants. The exposure was categorised into normal vaginal birth (VD) [reference], assisted VD, elective (planned) CS and emergency (unplanned) CS. The primary outcome measure was obesity defined according to the International Obesity Taskforce criteria. Statistical analysis included multinomial logistic regression with adjustment for potential confounders. Infants delivered by elective CS had an adjusted relative risk ratio (aRRR) = 1.32; [95% confidence interval (CI) 1.01–1.74] of being obese at age three years. This association was attenuated when macrosomic children were excluded (aRRR = 0.99; [95% CI 0.67–1.45]). Infants delivered by emergency CS had an increased risk of obesity aRRR = 1.56; [95% CI 1.20–2.03]; this association remained after excluding macrosomic children. We found insufficient evidence to support a causal relationship between elective CS and childhood obesity. An increased risk of obesity in children born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora.

Trial of labour after caesarean section and the risk of neonatal and infant death: a nationwide cohort study

BackgroundCaesarean section (CS) rates are increasing worldwide and as a result repeat CS is common. The optimal mode of delivery in women with one previous CS is widely debated and the risks to the infant are understudied. The aim of the current study was to evaluate if women with a trial of labour after caesarean (TOLAC) had an increased odds of neonatal and infant death compared to women with an elective repeat CS (ERCS).MethodsA population register-based cohort study was conducted in Denmark between 1982 and 2010. All women with two deliveries [in which the first was a CS, and the second was an uncomplicated, term delivery (n = 61,626)] were included in the study. Logistic regression models were used to report adjusted odds ratios (AOR) and 95% confidence intervals (CI) of the odds of death according to mode of delivery. The main outcome measures were neonatal death (early and late) and infant death.ResultsWomen with a TOLAC had an increased odds of neonatal death (AOR 1 · 87, 95% CI 1 · 12 to 3 · 12) due to an increased risk of early neonatal death (AOR 2 · 06, 95% CI 1 · 19 to 3 · 56) and no effect on late neonatal death (AOR 0 · 97, 95% CI 0 · 22 to 4 · 32), or infant death (AOR 1 · 12, 95% CI 0 · 79 to 1 · 59) when compared to the reference group of women with an ERCS. There was evidence of a cohort effect as the increased odds of neonatal death (AOR 3 · 89, 95% CI 1 · 33 to 11 · 39) was most significant in the earlier years (1982–1991) and gradually disappeared (AOR 1 · 01, 95% CI 0 · 44 to 2 · 31) in the later years (2002–2010).ConclusionsAlthough an increased risk of neonatal death was found in women with a TOLAC, there was evidence of a cohort effect, which showed this increased odds disappearing over time. Advances in modern healthcare including improved monitoring and earlier detection of underlying pregnancy complications may explain the findings.

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

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

PP26 Caesarean Delivery and Subsequent Birth Interval, Ectopic Pregnancy, Miscarriage or Stillbirth-a Danish Register-based Cohort Study

Background Despite high caesarean delivery rates worldwide, limited data are available on the effect of a prior caesarean delivery on subsequent fertility. Aim To estimate the time to next birth and the risk of miscarriage, ectopic pregnancy and stillbirth in women with a prior caesarean delivery compared to women with a prior vaginal delivery. Methods Using Danish registry data we identified a cohort of women giving birth between 1982 and 2010 (n = 833,162). The cohort was followed from the index birth until the next birth or censoring by death, emigration or study end (31/12/2010). Women with an index caesarean section were compared to women with an index vaginal birth by stratified Cox regression models using SAS version 9.2 Results Women with an index caesarean were less likely to have a subsequent delivery and had an increased time to next birth (HR 0.83 [95% CI 0.82, 0.84]). Sub-group analyses by smoking status, history of fertility services, maternal BMI, preterm birth & low birth weight did not modify results. Analyses for ectopic pregnancy and miscarriage showed no increased HR among women with a prior caesarean section; however a significantly increased HR for subsequent stillbirth was reported (1.16 [1.04, 1.28]). Conclusion Prior caesarean delivery, particularly elective and maternally requested caesareans were associated with an increased time to next birth. An increased hazard ratio of stillbirth in subsequent deliveries but not ectopic pregnancy or miscarriage among women with an index caesarean was also found.

PP25 Caesarean Section and Subsequent Pregnancy Interval - A Systematic Review

Background Caesarean section rates have increased significantly in the past three decades, with one in four babies in the United Kingdom (UK) delivered operatively. In light of this, the National Institute for Health and Clinical Excellence (NICE) updated their caesarean section guidelines to give women the right to request a caesarean section without any medical indication. With the long term consequences of caesarean section on fertility unknown, further research is warranted. Objective To compare pregnancy interval between women with a previous caesarean to women with a previous vaginal delivery. Methods Study Design: Systematic review of the published literature. CINAHL, Cochrane library, Embase, Medline, PubMed, SCOPUS and Web of Knowledge databases were searched (1945-October 2012), using a detailed search-strategy and cross-checking of references. Cohort, case-control and cross-sectional studies were eligible. Two assessors individually reviewed titles, abstracts and full articles to identify eligible studies, using a standardised data-abstraction form and assessed study quality. A meta-analysis was not suitable due to between-study heterogeneity. Results Data synthesis: Over 9,184 titles were screened, with 12 articles included. Four studies reported an increased waiting time to next pregnancy following a previous caesarean section delivery. However, variations in the definition of time to next pregnancy or birth used, as well as lack of adjustment for confounders, small sample size, inability to identify the indication for caesarean section, short follow-up time and lack of stratification by number of previous pregnancies were all obvious limitations. Eight studies reported no association between a previous caesarean section delivery and subsequent pregnancy interval. These were methodologically more superior with larger sample sizes, population-based registries, and detailed obstetrical information including indication for mode of delivery and long follow-up periods Discussion Evidence on the relationship between caesarean delivery and pregnancy interval is conflicting. Residual confounding is possible and further research of better methodological quality is required to assess whether any delay in pregnancy interval is causal or as a result of parental choice to delay childbirth.

PP.18 Caesarean Section and Time to Next Birth, Ectopic Pregnancy, Miscarriage or Stillbirth-A Danish Register-Based Study

Aim Estimate time to next birth, risk of miscarriage, ectopic pregnancy or stillbirth in women with primary Caesareans. Methods Danish population-registry cohort of births from 1982–2010 (n = 833,162). Analysis using Cox-regression models. Results Prior Caesarean group had longer birth intervals. No increased risk of ectopic pregnancy or miscarriage, but significantly increased risk of stillbirth among women with a prior Caesarean. Conclusion Prior Caesareans were associated with an increased birth interval and increased risk of stillbirth compared to vaginal deliveries. Abstract PP.18 Table Birth Interval Ectopic Miscarriage Stillbirth Delivery adj.HR (95% CI) Vaginal 1 Instrumental 1.08(1.07,1.09) 0.91(0.86,0.96) 1.03(1.01,1.05) 0.95(0.84,1.08) Elective CS 0.83(0.82,0.84) 1.02(0.95,1.09) 0.92(0.90,0.95) 1.10(0.94,1.30) Acute CS 0.89(0.88,0.90) 1.03(0.99,1.0) 0.98(0.96,1.00) 1.16(1.04,1.28) MRCS 0.64(0.60,0.69) 1.04(0.69,1.57) 0.78(0.66,.092) 0.54(0.13,2.18) Instrumental: vacuum/forceps; CS:Caesarean-section; MRCS: Maternally-Requested CS

OP45 Caesarean Section and Subsequent Fetal Death: Systematic Review and Meta-Analysis

Background Spontaneous miscarriage (the death of a fetus before 20 weeks of pregnancy), occurs in 10–15% of recognised pregnancies. Stillbirth (the death of a fetus after 24 weeks of pregnancy), occurs in approximately one in every 200 deliveries. The cause of miscarriage and stillbirth is frequently unknown. However, there is some evidence to suggest that previous Caesarean delivery may be a risk factor. Objective: to compare the risk of fetal death in subsequent pregnancy by mode of delivery. Methods This was a systematic review of relevant studies identified through CINAHL, the Cochrane library, Embase, Medline, PubMed, SCOPUS and Web of Knowledge (1945 - November 2011), using a comprehensive search strategy, and cross-checking of reference lists. Study selection: cohort and case-control studies reporting on Caesarean delivery and spontaneous miscarriage or stillbirth. Two reviewers independently assessed titles, abstracts, and full articles to identify eligible studies, using a standardised data collection form. Results Miscarriage: From 6,857 titles identified, eight articles were included, totalling 147,017 women and 12,682 events. Odds ratios (ORs) were combined using a fixed-effect model to estimate the overall association using Review Manager Software. From the meta-analysis, the pooled OR estimate of miscarriage among women who previously delivered by Caesarean versus vaginally, was 1.11 [95% CI 1.06,1.17]. The OR of miscarriage was 1.26 [95% CI 0.54,2.92] for one case-control study, 1.11 [95% CI 1.06,1.17] for seven cohort studies and 1.11 [95% CI 1.06,1.17] for primiparous women (eight studies). Stillbirth: From 6,857 studies identified, seven articles were included, totalling 1,661,335 pregnancies and 5,741 events. ORs were combined using a random effect model (due to the heterogeneity of included studies) to estimate the overall association. From the meta-analysis, the pooled OR estimate of stillbirth among women who previously delivered by Caesarean versus vaginally, was 1.32 [95% CI 1.11,1.57]. The OR of stillbirth was 1.30 [95% CI 1.03,1.64] for primiparous women (five studies), 1.40 [95% CI 1.24,1.59] for multiparous women (two studies), 1.80 [95% CI 1.27,2.55] for studies including all stillbirths (five studies) and, 1.20 [95% CI 1.02,1.42] for studies including only unexplained antepartum stillbirths (three studies). Conclusion Caesarean delivery compared to vaginal delivery is associated with an increased risk of spontaneous miscarriage by 11% and stillbirth by 32% in subsequent pregnancies. In light of the recently published National Institute for Health and Clinical Excellence (NICE) guidelines, which support a woman’s right to request a Caesarean delivery without medical reason, there is an urgent need to establish whether mode of delivery has a causal effect on risk of fetal death.