Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial.

OBJECTIVE: To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy (ICP), based on their presenting characteristics, would benefit from treatment with ursodeoxycholic acid (UDCA). DESIGN: Secondary analysis of the PITCHES trial (ISRCTN91918806). SETTING: United Kingdom. POPULATION OR SAMPLE: 527 women with ICP. METHODS: Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman's response to treatment with UDCA. MAIN OUTCOME MEASURES: Bile acid concentration and itch score. RESULTS: In women with baseline bile acid concentrations less than 40 µmol/l, treatment with UDCA resulted in increased post-randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.00-1.41, P = 0.048). A test of interaction showed no significance (P = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (-6.0 mm, 95% CI -11.80 to -0.21, P = 0.042), with a test of interaction not showing significance (P = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. CONCLUSIONS: There was no subgroup of women with ICP in whom a beneficial effect of treatment with UDCA on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. TWEETABLE ABSTRACT: PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus.

The impact of pre-eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy - analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study).

OBJECTIVE: To examine the association between pre-eclampsia definition and pregnancy outcome. DESIGN: Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. SETTING: International multicentre randomised controlled trial (RCT). POPULATION: In all, 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. MAIN OUTCOME MEASURES: Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth. RESULTS: Of 979/987 women with informative data, 280 (28.6%) progressed to pre-eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre-eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62-79% versus 36-50%), lower specificities (range 53-65% versus 72-82%), and similar or higher diagnostic odds ratios and 'true-positive' to 'false-positive' ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre-eclampsia definition improved sensitivity (74-87%). CONCLUSIONS: A broad (versus restrictive) pre-eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre-eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values. TWEETABLE ABSTRACT: A broad (versus restrictive) pre-eclampsia definition better identifies the risk of adverse pregnancy outcomes.

Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis.

BACKGROUND: Early reports of COVID-19 in pregnancy described management by caesarean, strict isolation of the neonate and formula feeding. Is this practice justified? OBJECTIVE: To estimate the risk of the neonate becoming infected with SARS-CoV-2 by mode of delivery, type of infant feeding and mother-infant interaction. SEARCH STRATEGY: Two biomedical databases were searched between September 2019 and June 2020. SELECTION CRITERIA: Case reports or case series of pregnant women with confirmed COVID-19, where neonatal outcomes were reported. DATA COLLECTION AND ANALYSIS: Data were extracted on mode of delivery, infant infection status, infant feeding and mother-infant interaction. For reported infant infection, a critical analysis was performed to evaluate the likelihood of vertical transmission. MAIN RESULTS: Forty nine studies included information on mode of delivery and infant infection status for 655 women and 666 neonates. In all, 28/666 (4%) tested positive postnatally. Of babies born vaginally, 8/292 (2.7%) tested positivecompared with 20/374 (5.3%) born by Caesarean. Information on feeding and baby separation were often missing, but of reported breastfed babies 7/148 (4.7%) tested positive compared with 3/56 (5.3%) for reported formula fed ones. Of babies reported as nursed with their mother 4/107 (3.7%) tested positive, compared with 6/46 (13%) for those who were reported as isolated. CONCLUSIONS: Neonatal COVID-19 infection is uncommon, rarely symptomatic, and the rate of infection is no greater when the baby is born vaginally, breastfed or remains with the mother. TWEETABLE ABSTRACT: Risk of neonatal infection with COVID-19 by delivery route, infant feeding and mother-baby interaction.

Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials.

OBJECTIVE: To explore the effect on perinatal outcome of different fetal monitoring strategies for early-onset fetal growth restriction (FGR). METHODS: This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age. RESULTS: Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P < 0.01). The rate of survival without impairment at 2 years was lowest in pregnancies that underwent immediate delivery (70% (95% CI, 61-78%)) or delayed delivery with monitoring by CTG (69% (95% CI, 57-82%)), increased in those monitored using cCTG only in both GRIT (80% (95% CI, 68-91%)) and TRUFFLE (77% (95% CI, 70-84%)), and was highest in pregnancies monitored using cCTG and DV Doppler (84% (95% CI, 80-89%)) (P < 0.01 for trend). CONCLUSIONS: This analysis supports the hypothesis that the optimal method for fetal monitoring in pregnancies complicated by early-onset FGR is a combination of cCTG and DV Doppler assessment. TRIAL REGISTRATION: GRIT ISRCTN41358726 and TRUFFLE ISRCTN56204499. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Análisis comparativo de los resultados a los 2 años de edad en los ensayos GRIT y TRUFFLE OBJETIVO: Examinar el efecto sobre el resultado perinatal de diferentes estrategias de monitoreo del feto para la restricción del crecimiento fetal (RCF) de inicio precoz. MÉTODOS: Este estudio realizó un análisis de cohortes de datos de participantes individuales en dos ensayos multicéntricos europeos de métodos de monitoreo fetal para la RCF: el Estudio de Intervención en la Restricción del Crecimiento (GRIT, por sus siglas en inglés) y el Ensayo Europeo de Flujo Umbilical y Fetal (TRUFFLE, por sus siglas en inglés). Se incluyeron todas las mujeres de GRIT (n = 238) y de TRUFFLE (n = 503) que habían sido asignadas al azar entre 26 y 32 semanas de gestación. Las mujeres se agruparon según el método de intervención y monitoreo: parto inmediato (GRIT) o parto diferido con monitoreo mediante cardiotocografía convencional (CTG) (GRIT), solo CTG digital (cCTG, por sus siglas en inglés) (GRIT y TRUFFLE) o cCTG y Doppler del conducto de Arancio (DV) (TRUFFLE). La medida de resultado primaria fue la supervivencia sin deterioro del desarrollo neurológico a los dos años de edad. RESULTADOS: La edad gestacional al momento del parto y el peso al nacer fueron similares en ambos estudios. La tasa de mortalidad fetal fue similar entre los grupos de GRIT y TRUFFLE, pero la muerte neonatal y tardía fue más frecuente en el grupo de GRIT (18% vs 6%; P < 0,01). La tasa de supervivencia sin deterioro a los dos años fue más baja en los embarazos que se sometieron a un parto inmediato (70% (IC 95%, 61-78%)) o a un parto tardío con monitoreo mediante CTG (69% (IC 95%, 57-82%)), más alta en los monitoreados solo mediante cCTG en GRIT (80% (IC 95%, 68-91%)) y TRUFFLE (77% (IC 95%, 70-84%)), y mayor aun en los embarazos monitoreados mediante cCTG y Doppler DV (84% (IC 95%, 80-89%)) (P < 0,01 para tendencia). CONCLUSIONES: Este análisis apoya la hipótesis de que el método óptimo para el monitoreo fetal en los embarazos complicados por RCF de inicio precoz es una combinación de cCTG y evaluación Doppler DV. INSCRIPCIÓN DEL ENSAYO: GRIT ISRCTN41358726 y TRUFFLE ISRCTN56204499. © 2019 Los autores. Ultrasonido en Obstetricia y Ginecología publicado por John Wiley & Sons Ltd. en nombre de la Sociedad Internacional de Ultrasonido en Obstetricia y Ginecología.

The cost-effectiveness of universal late-pregnancy screening for macrosomia in nulliparous women: a decision analysis.

OBJECTIVE: To identify the most cost-effective policy for detection and management of fetal macrosomia in late-stage pregnancy. DESIGN: Health economic simulation model. SETTING: All English NHS antenatal services. POPULATION: Nulliparous women in the third trimester treated within the UK NHS. METHODS: A health economic simulation model was used to compare long-term maternal-fetal health and cost outcomes for two detection strategies (universal ultrasound scanning at approximately 36 weeks of gestation versus selective ultrasound scanning), combined with three management strategies (planned caesarean section versus induction of labour versus expectant management) of suspected fetal macrosomia. Probabilities, costs and health outcomes were taken from literature. MAIN OUTCOME MEASURES: Expected costs to the NHS and quality-adjusted life-years (QALYs) gained from each strategy, calculation of net benefit and hence identification of most cost-effective strategy. RESULTS: Compared with selective ultrasound, universal ultrasound increased QALYs by 0.0038 (95% CI 0.0012-0.0076), but also costs by £123.50 (95% CI 99.6-149.9). Overall, the health gains were too small to justify the cost increase given current UK thresholds cost-effective policy was selective ultrasound coupled with induction of labour where macrosomia was suspected. CONCLUSIONS: The most cost-effective policy for detection and management of fetal macrosomia is selective ultrasound scanning coupled with induction of labour for all suspected cases of macrosomia. Universal ultrasound scanning for macrosomia in late-stage pregnancy is not cost-effective. TWEETABLE ABSTRACT: Universal late-pregnancy ultrasound screening for fetal macrosomia is not warranted.

Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study.

OBJECTIVES: To assess the prevalence of congenital uterine anomalies, including arcuate uterus, and their effect on reproductive outcome in subfertile women undergoing assisted reproduction. METHODS: Consecutive women referred for subfertility between May 2009 and November 2015 who underwent assisted reproduction were included in the study. As part of the initial assessment, each woman underwent three-dimensional transvaginal sonography. Uterine morphology was classified using the modified American Fertility Society (AFS) classification of congenital uterine anomalies proposed by Salim et al. If the external contour of the uterus was uniformly convex or had an indentation of < 10 mm, but there was a cavity indentation, it was defined as arcuate or septate. Arcuate uterus was further defined as the presence of a concave fundal indentation with a central point of indentation at an obtuse angle. Subseptate uterus was defined as the presence of a septum, not extending to the cervix, with the central point of the septum at an acute angle; if the septum extended to the internal cervical os, the uterus was defined as septate. Reproductive outcomes, including live birth, clinical pregnancy and preterm birth, were compared between women with a normal uterus and those with a congenital uterine anomaly. Subgroup analysis by type of uterine morphology and logistic regression analysis adjusted for age, body mass index, levels of anti-Müllerian hormone, antral follicle count and number and day of embryo transfer were performed. RESULTS: A total of 2375 women were included in the study, of whom 1943 (81.8%) had a normal uterus and 432 (18.2%) had a congenital uterine anomaly. The most common anomalies were arcuate (n = 387 (16.3%)) and subseptate (n = 16 (0.7%)) uterus. The rate of live birth was similar between women with a uterine anomaly and those with a normal uterus (35% vs 37%; P = 0.47). The rates of clinical pregnancy, mode of delivery and sex of the newborn were also similar between the two groups. Preterm birth before 37 weeks' gestation was more common in women with uterine anomalies than in controls (22% vs 14%, respectively; P = 0.03). Subgroup analysis by type of anomaly showed no difference in the incidence of live birth and clinical pregnancy for women with an arcuate uterus, but indicated worse pregnancy outcome in women with other major anomalies (P = 0.042 and 0.048, respectively). CONCLUSIONS: Congenital uterine anomalies as a whole, when defined using the modified AFS classification, do not affect clinical pregnancy or live-birth rates in women following assisted reproduction, but do increase the incidence of preterm birth. The presence of uterine abnormalities more severe than arcuate uterus significantly worsens all pregnancy outcomes. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Inadvertent P-hacking among trials and systematic reviews of the effect of progestogens in pregnancy? A systematic review and meta-analysis.

BACKGROUND: Progestogens have been evaluated in numerous trials and meta-analyses, many of which concluded they were effective. However, two large trials PROMISE and OPPTIMUM have recently concluded that progesterone was ineffective. This raises the possibility that earlier studies and reviews had been biased by either selective publication or selective choice of outcomes, so called "P-hacking". OBJECTIVES: To compare the findings all progestogen trials and systematic reviews with those of trials with pre-registered primary outcomes which avoided selective outcome reporting. SEARCH STRATEGY: Search of PubMed, the Cochrane Library and trial registries. Registration PROSPERO CRD42016035303. SELECTION CRITERIA: Systematic reviews of randomised trials comparing progestogen with placebo in pregnancy and the individual trials included in those reviews. The subset of trials reporting a pre-registered primary outcome were compared with the totality of trials and reviews. DATA COLLECTION AND ANALYSIS: For reviews all outcomes were included. For individual trials all outcomes reported in the systematic reviews were included. For the comparison group we recorded the registered primary outcome from trials that were either registered before they started, or registered during the recruitment phase and also double blind. MAIN RESULTS: Nineteen of twenty-nine meta-analyses concluded that progestogens were effective. Twenty-two trials reported their pre-registered primary outcomes. There was no effect of progesterone on primary registered dichotomous outcome RR 1.00 (95% CI 0.94-1.07). Only one of the 22 showed a nominally statistically significant benefit. AUTHOR'S CONCLUSIONS: When evaluated in registered double-blind trials with analysis restricted to predefined primary outcomes, progestational agents in pregnancy are ineffective. TWEETABLE ABSTRACT: Progestogens to prevent pregnancy loss, an example of P-hacking.

Labour induction near term for women aged 35 or over: an economic evaluation.

OBJECTIVE: Induction of labour at 39 weeks for nulliparous women aged 35 years and over may prevent stillbirths and does not increase caesarean births, so it may be popular. But the overall costs and benefits of such a policy have not been compared. DESIGN: A cost-utility analysis alongside a randomised controlled trial (the 35/39 trial). SETTING: Obstetric departments of 38 UK National Health Service hospitals and one UK primary-care trust. POPULATION: Nulliparous women aged 35 years or over on their expected due date, with a singleton live fetus in a cephalic presentation. METHODS: Costs were estimated from the National Health Service and Personal Social Services perspective and quality-adjusted life-years (QALYs) were calculated based on patient responses to the EQ-5D at baseline and 4 weeks. MAIN OUTCOME MEASURES: Data on antenatal care, mode of delivery, analgesia in labour, method of induction, EQ-5D (baseline and 4 weeks postnatal) and participant-administered postnatal health resource use data were collected. RESULTS: The intervention was associated with a mean cost saving of £263 and a small additional gain in QALYs (though this was not statistically significant), even without considering any possible QALY gains from stillbirth prevention. CONCLUSION: A policy of induction of labour at 39 weeks for women of advanced maternal age would save money. TWEETABLE ABSTRACT: A policy of induction of labour at 39 weeks of gestation for women of advanced maternal age would save money.

Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial.

OBJECTIVE: To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension. DESIGN: Secondary analysis of CHIPS Trial cohort. SETTING: International randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation. METHODS: Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors. MAIN OUTCOME MEASURES: CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks. RESULTS: Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32-0.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), pre-eclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85). CONCLUSION: These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes. TWEETABLE ABSTRACT: There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.

Control of Hypertension In Pregnancy Study randomised controlled trial-are the results dependent on the choice of labetalol or methyldopa?

OBJECTIVE: To determine whether the difference in outcomes between 'less tight' (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) in the CHIPS Trial (ISRCTN 71416914, http://pre-empt.cfri.ca/;CHIPS) depended on the choice of labetalol or methyldopa, the two most commonly used antihypertensive agents in CHIPS. DESIGN: Secondary analysis of CHIPS Trial data. SETTING: International multicentre randomised controlled trial (94 sites, 15 countries). POPULATION OR SAMPLE: A total of 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: Logistic regression was used for comparisons of 'less tight' versus 'tight' control among women treated with labetalol (but not methydopa) versus methyldopa (but not labetalol). Analyses were adjusted for the influence of baseline factors, including use of any antihypertensive therapy at randomisation. MAIN OUTCOME MEASURES: Main CHIPS Trial outcomes: primary (perinatal loss or high-level neonatal care for > 48 hours), secondary (serious maternal complications), birthweight < 10th centile, severe maternal hypertension, pre-eclampsia, and delivery at < 34 or < 37 weeks. RESULTS: Of 987 women in CHIPS, antihypertensive therapy was taken by 566 women at randomisation (labetalol 111 ['less tight'] versus 127 ['tight'] or methyldopa 126 ['less tight'] versus 117 ['tight']) and 815 women after randomisation (labetalol 186 ['less tight'] versus 247 ['tight'] and methyldopa by 98 ['less tight'] versus 126 ['tight']). Following adjustment, odds ratios for outcomes in 'less tight' versus 'tight' control were similar between antihypertensive groups according to 'at randomisation' and 'after randomisation' therapy. CONCLUSION: Outcomes for 'less tight' versus 'tight' control were not dependent on use of methyldopa or labetalol. TWEETABLE ABSTRACT: In the CHIPS Trial, maternal and infant outcomes were not dependent on use of labetalol or methyldopa.

Antenatal magnetic resonance imaging versus ultrasound for predicting neonatal macrosomia: a systematic review and meta-analysis.

BACKGROUND: Fetal macrosomia is associated with an increased risk of adverse maternal and neonatal outcomes. OBJECTIVES: To compare the accuracy of antenatal two-dimensional (2D) ultrasound, three-dimensional (3D) ultrasound, and magnetic resonance imaging (MRI) in predicting fetal macrosomia at birth. SEARCH STRATEGY: Medline (1966-2013), Embase, the Cochrane Library and Web of Knowledge. SELECTION CRITERIA: Cohort or diagnostic accuracy studies of women with a singleton pregnancy, who had third-trimester imaging to predict macrosomia (>4000 g, >4500 g or >90th or >95th centile). DATA COLLECTION AND ANALYSIS: Two reviewers screened studies, performed data extraction and assessed methodological quality. The bivariate model was used to obtain summary sensitivities, specificities and likelihood ratios. MAIN RESULTS: Fifty-eight studies (34 367 pregnant women) were included. Most were poorly reported. Only one study assessed 3D ultrasound volumetry. For predicting birthweight >4000 g or >90th centile, the summary sensitivity for 2D ultrasound (Hadlock) estimated fetal weight (EFW) >90th centile or >4000 g (29 studies) was 0.56 (95% CI 0.49-0.61), 2D ultrasound abdominal circumference (AC) >35 cm (four studies) was 0.80 (95% confidence interval [95% CI] 0.69-0.87) and MRI EFW (three studies) was 0.93 (95% CI 0.76-0.98). The summary specificities were 0.92 (95% CI 0.90-0.94), 0.86 (95% CI 0.74-0.93) and 0.95 (95% CI 0.92-0.97), respectively. CONCLUSION: There is insufficient evidence to conclude that MRI EFW is more sensitive than 2D ultrasound AC (which is more sensitive than 2D EFW); although it was more specific. Further primary research is required before recommending MRI EFW for use in clinical practice. TWEETABLE ABSTRACT: Systematic review of antenatal imaging to predict macrosomia. MRI EFW is more sensitive than ultrasound EFW.

The dangers of the day of birth.

OBJECTIVE: To compare the risk of fetal death on the day of childbirth, with the risk of death at other ages, and with the risks of some hazardous activities, on a common scale of risk per day. DESIGN: Review of publicly available data. SETTING UK SAMPLE: Data extracted from the Office of National Statistics and other sources. METHODS: Data from the Office of National Statistics and other sources were used to calculate death rates at different ages expressed as rates per day of life. Death rates for different activities were also calculated as risks per day, or risks per activity, as appropriate. All risks were expressed in micromorts, the number of one in a million chances of dying. Figures on life expectancy (LE) were used to compare potential life years lost. MAIN OUTCOME MEASURES: Daily, or unit of activity, risk of dying for different activities compared with the risk of dying on the day of childbirth. RESULTS: The risk of dying on the day of birth (0.43 per 1000, or 430 micromorts) exceeds that of any other average day of life until the 92nd year. It is comparable with other apparently more dangerous activities, such as undergoing major surgery. For comparison, the average risk of non-natural death per day and the increased risk from smoking one cigarette or travelling 200 miles by car are all about 1 micromort. CONCLUSIONS: The lifetime risk of death in childbirth is low, but is concentrated in a short period, making being born a high-risk activity. Parents considering interventions to reduce these risks should be made aware of this.

Reproductive outcomes in women with congenital uterine anomalies: a systematic review.

OBJECTIVE: Congenital uterine anomalies are common but their effect on reproductive outcome is unclear. We conducted a systematic review to evaluate the association between different types of congenital uterine anomaly and various reproductive outcomes. METHODS: Searches were performed using MEDLINE, EMBASE, the Cochrane Library and Web of Science. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Uterine defects were grouped into arcuate uteri, canalization defects (septate and subseptate uteri) and unification defects (unicornuate, bicornuate and didelphys uteri). Pooled risk ratios (RR) with 95% confidence intervals (CI) were computed using random effects models. RESULTS: We identified nine studies comprising 3805 women. Meta-analysis showed that arcuate uteri were associated with increased rates of second-trimester miscarriage (RR, 2.39; 95% CI, 1.33-4.27, P = 0.003) and fetal malpresentation at delivery (RR, 2.53; 95% CI, 1.54-4.18; P < 0.001). Canalization defects were associated with reduced clinical pregnancy rates (RR, 0.86; 95% CI, 0.77-0.96; P = 0.009) and increased rates of first-trimester miscarriage (RR, 2.89; 95% CI; 2.02-4.14; P < 0.001), preterm birth (RR, 2.14; 95% CI, 1.48-3.11; P < 0.001) and fetal malpresentation (RR, 6.24; 95% CI, 4.05-9.62; P < 0.001). Unification defects were associated with increased rates of preterm birth (RR, 2.97; 95% CI, 2.08-4.23; P < 0.001) and fetal malpresentation (RR, 3.87; 95% CI, 2.42-6.18; P < 0.001). CONCLUSIONS: Canalization defects reduce fertility and increase rates of miscarriage and preterm delivery. None of the unification defects reduces fertility but some are associated with miscarriage and preterm delivery. Arcuate uteri are specifically associated with second-trimester miscarriage. All uterine anomalies increase the chance of fetal malpresentation at delivery.

The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review.

BACKGROUND: The prevalence of congenital uterine anomalies in high-risk women is unclear, as several different diagnostic approaches have been applied to different groups of patients. This review aims to evaluate the prevalence of such anomalies in unselected populations and in women with infertility, including those undergoing IVF treatment, women with a history of miscarriage, women with infertility and recurrent miscarriage combined, and women with a history of preterm delivery. METHODS: Searches of MEDLINE, EMBASE, Web of Science and the Cochrane register were performed. Study selection and data extraction were conducted independently by two reviewers. Studies were grouped into those that used 'optimal' and 'suboptimal' tests for uterine anomalies. Meta-analyses were performed to establish the prevalence of uterine anomalies and their subtypes within the various populations. RESULTS: We identified 94 observational studies comprising 89 861 women. The prevalence of uterine anomalies diagnosed by optimal tests was 5.5% [95% confidence interval (CI), 3.5-8.5] in the unselected population, 8.0% (95% CI, 5.3-12) in infertile women, 13.3% (95% CI, 8.9-20.0) in those with a history of miscarriage and 24.5% (95% CI, 18.3-32.8) in those with miscarriage and infertility. Arcuate uterus is most common in the unselected population (3.9%; 95% CI, 2.1-7.1), and its prevalence is not increased in high-risk groups. In contrast, septate uterus is the most common anomaly in high-risk populations. CONCLUSIONS: Women with a history of miscarriage or miscarriage and infertility have higher prevalence of congenital uterine anomalies compared with the unselected population.