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Aims/hypothesis Pre-existing diabetes is associated with an increased risk of stillbirth, but few studies have excluded the effect of congenital anomalies. This study used data from a long-standing population-based survey of women with pre-existing diabetes to investigate the risks of fetal and infant death and quantify the contribution of glycaemic control. Methods All normally formed singleton offspring of women with pre-existing diabetes (1,206 with type 1 diabetes and 342 with type 2 diabetes) in the North of England during 1996–2008 were identified from the Northern Diabetes in Pregnancy Survey. RRs of fetal death (≥20 weeks of gestation) and infant death were estimated by comparison with population data from the Northern Perinatal Morbidity and Mortality Survey. Predictors of fetal and infant death in women with pre-existing diabetes were examined by logistic regression. Results The prevalence of fetal death in women with diabetes was over four times greater than in those without (RR 4.56 [95% CI 3.42, 6.07], p  < 0.0001), and for infant death it was nearly doubled (RR 1.86 [95% CI 1.00, 3.46], p  = 0.046). There was no difference in the prevalence of fetal death ( p  = 0.51) or infant death ( p  = 0.70) between women with type 1 diabetes and women with type 2 diabetes. There was no evidence that the RR of fetal and infant death had changed over time ( p  = 0.95). Increasing periconception HbA 1c concentration above 49 mmol/mol (6.6%) (adjusted odds ratio [aOR] 1.02 [95% CI 1.00, 1.04], p  = 0.01), prepregnancy retinopathy (aOR 2.05 [95% CI 1.04, 4.05], p  = 0.04) and lack of prepregnancy folic acid consumption (aOR 2.52 [95% CI 1.12, 5.65], p  = 0.03) were all independently associated with increased odds of fetal and infant death. Conclusions/interpretation Pre-existing diabetes is associated with a substantially increased risk of fetal and infant death in normally formed offspring, the effect of which is largely moderated by glycaemic control.

The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was \"probable active,\" and for testing and treatment coverage. Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary.

To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0-74.1]; I(2) = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8-17.2]; I(2) = 95.9%; P < 0.001). Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women.

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35+ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10000 births was 22.0 (95% CI 21.7-22.4) for trisomy 21, 5.0 (95% CI 4.8-5.1) for trisomy 18 and 2.0 (95% CI 1.9-2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9-11.5) for trisomy 21, 1.04 (95% CI 0.96-1.12) for trisomy 18 and 0.48 (95% CI 0.43-0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence.

Abstract Objective To develop and test a new classification system for stillbirths to help improve understanding of the main causes and conditions associated with fetal death. Design Population based cohort study. Setting West Midlands region. Subjects 2625 stillbirths from 1997 to 2003. Main outcome measures Categories of death according to conventional classification methods and a newly developed system (ReCoDe, relevant condition at death). Results By the conventional Wigglesworth classification, 66.2% of the stillbirths (1738 of 2625) were unexplained. The median gestational age of the unexplained group was 237 days, significantly higher than the stillbirths in the other categories (210 days; P < 0.001). The proportion of stillbirths that were unexplained was high regardless of whether a postmortem examination had been carried out or not (67% and 65%; P = 0.3). By the ReCoDe classification, the most common condition was fetal growth restriction (43.0%), and only 15.2% of stillbirths remained unexplained. ReCoDe identified 57.7% of the Wigglesworth unexplained stillbirths as growth restricted. The size of the category for intrapartum asphyxia was reduced from 11.7% (Wigglesworth) to 3.4% (ReCoDe). Conclusion The new ReCoDe classification system reduces the predominance of stillbirths currently categorised as unexplained. Fetal growth restriction is a common antecedent of stillbirth, but its high prevalence is hidden by current classification systems. This finding has profound implications for maternity services, and raises the question whether some hitherto “unexplained” stillbirths may be avoidable.

Background Expertise and resources may be important determinants of outcome for extremely preterm babies. We evaluated the effect of place of birth and perinatal transfer on survival and neonatal morbidity within a prospective cohort of births between 22 and 26 weeks of gestation in England during 2006. Methods We studied the whole population of 2460 births where the fetus was alive at the admission of the mother to hospital for delivery. Outcomes to discharge were compared between level 3 (most intensive) and level 2 maternity services, with and without transfers, and by activity level of level 3 neonatal unit; ORs were adjusted for gestation at birth and birthweight for gestation (adjusted ORs (aOR)). Findings Of this national birth cohort, 56% were born in maternity services with level 3 and 34% with level 2 neonatal units; 10% were born in a setting without ongoing intensive care facilities (level 1). When compared with level 2 settings, risk of death in level 3 services was reduced (aOR 0.73 (95% CI 0.59 to 0.90)), but the proportion surviving without neonatal morbidity was similar (aOR 1.27 (0.93 to 1.74)). Analysis by intended hospital of birth confirmed reduced mortality in level 3 services. Following antenatal transfer into a level 3 setting, there were fewer intrapartum or labour ward deaths, and overall mortality was higher for those remaining in level 2 services (aOR 1.44 (1.09 to 1.90)). Among level 3 services, those with higher activity had fewer deaths overall (aOR 0.68 (0.52 to 0.89)). Interpretation Despite national policy, only 56% of births between 22 and 26 weeks of gestation occurred in maternity services with a level 3 neonatal facility. Survival was significantly enhanced following birth in level 3 services, particularly those with high activity; this was not at the cost of increased neonatal morbidity.

Background. Human cytomegalovirus (CMV) is the most common congenital infection in developed countries and is a known cause of intrauterine fetal death. We examined CMV infection in stillbirths and the relationship with histopathological findings at autopsy. Methods. We collected liver, kidney, and placenta specimens from 130 stillbirths. CMV DNA and protein were detected using polymerase chain reaction and immunohistochemistry, along with routine autopsy of stillborn infants. Results. Overall, CMV DNA was detected in 15% of singleton, > 20-week stillborn infants. CMV DNA was detected in kidney (9%), liver (11%), and placenta (5%) specimens, with 75% of infections confirmed by immunohistochemistry. Fetal thrombotic vasculopathy was the only histopathological abnormality associated with CMV infection (in 60% CMV-infected vs 28% uninfected stillbirths P = .010). Conclusions. Stillbirth has multiple etiologies. However, the detection of CMV DNA in 15% of fetal tissues or placentae suggests a strong association between CMV infection in pregnancy and stillbirth. Molecular testing during postmortem investigation has an important role to determine the contribution of CMV infection.

As compared with mortality in hospitals with high-level, high-volume neonatal intensive care units (NICUs), the mortality among very-low-birth-weight infants was higher at NICUs with lower levels of care and lower patient volumes. Although these data cannot prove cause and effect, the results suggest that increased regional consolidation of perinatal care is feasible and might reduce mortality among very-low-birth-weight infants. As compared with mortality in hospitals with high-level, high-volume neonatal intensive care units (NICUs), the mortality among very-low-birth-weight infants was higher at NICUs with lower levels of care and lower patient volumes. Paralleling the literature on adult care, 1 – 3 many studies of neonatal care have shown a lower mortality rate in hospitals with higher volumes of patients than in those with lower volumes. 4 – 7 Other studies have examined the association between the level of neonatal care and outcomes. Neonatal care is formally regionalized, with assigned levels of care and specific guidelines that define the characteristics of infants who should be delivered, and cared for, at each level of care. Each neonatal intensive care unit (NICU) that offers a lower level of care must have a formal contractual relationship with a NICU that . . .

Objective To estimate the incidence and outcomes of cervical intraepithelial neoplasia (CIN) and cervical cancer in pregnancy. Methods We conducted a population-based cohort study using the United States Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999 to 2008. The incidence of CIN and cervical cancer was measured and logistic regression analysis used to estimate the adjusted effect of CIN and cervical cancer on obstetrical outcomes. Results There were 8,826,137 births over a 10-year period of which 11,755 were among women with CIN and 294 among women with cervical cancer. Compared with controls, women with CIN were younger, had lower annual incomes, and more likely to be on Medicaid while women with cancer were more likely to be older. Women with CIN had lower rates of cesarean delivery but higher rates of transfusions and cesarean hysterectomies, while women with cancer had higher rates of cesarean deliveries, transfusions and cesarean hysterectomies. There were no significant increase of thrombosis; maternal death, instrumental delivery, IUGR, PPROM or intrauterine death was found. Conclusion CIN and cervical cancer are rare in pregnancy. Although there is a greater risk of transfusion/hysterectomy, overall major maternal and neonatal morbidity does not appear to be increased.

Antithrombin (AT) deficiency is a rare hereditary thrombophilia with a mean prevalence of 0.02 % in the general population, associated with a more than ten-fold increased risk of venous thromboembolism (VTE). Within this multicenter retrospective clinical analysis, female patients with inherited AT deficiency were evaluated concerning the type of inheritance and extent of AT deficiency, medical treatment during pregnancy and postpartally, VTE risk as well as maternal and neonatal outcome. Statistical analysis was performed with SPPS for Windows (19.0). A total of 18 pregnancies in 7 patients were evaluated, including 11 healthy newborns ≥37th gestational weeks (gw), one small for gestational age premature infant (25th gw), two late-pregnancy losses (21st and 28th gw) and four early miscarriages. Despite low molecular weight heparin (LMWH) administration, three VTE occurred during pregnancy and one postpartally. Several adverse pregnancy outcomes occurred including fetal and neonatal death, as well as severe maternal neurologic disorders occurred. Patients with substitution of AT during pregnancy in addition to LMWH showed the best maternal and neonatal outcome. Close monitoring with appropriate anticoagulant treatment including surveillance of AT levels might help to optimize maternal and fetal outcome in patients with hereditary AT deficiency.