Miscarriage, preterm delivery, and stillbirth: Large variations in rates within a cohort of Australian women

Objectives We aimed to use simple clinical questions to group women and provide their specific rates of miscarriage, preterm delivery, and stillbirth for reference. Further, our purpose was to describe who has experienced particularly low or high rates of each event. Methods Data were collected as part of the Australian Longitudinal Study on Women's Health, a national prospective cohort. Reproductive histories were obtained from 5806 women aged 31–36 years in 2009, who had self-reported an outcome for one or more pregnancy. Age at first birth, number of live births, smoking status, fertility problems, use of in vitro fertilisation (IVF), education and physical activity were the variables that best separated women into groups for calculating the rates of miscarriage, preterm delivery, and stillbirth. Results Women reported 10,247 live births, 2544 miscarriages, 1113 preterm deliveries, and 113 stillbirths. Miscarriage was correlated with stillbirth (r = 0.09, P<0.001). The calculable rate of miscarriage ranged from 11.3 to 86.5 miscarriages per 100 live births. Women who had high rates of miscarriage typically had fewer live births, were more likely to smoke and were more likely to have tried unsuccessfully to conceive for ≥12 months. The highest proportion of live preterm delivery (32.2%) occurred in women who had one live birth, had tried unsuccessfully to conceive for ≥12 months, had used IVF, and had 12 years education or equivalent. Women aged 14–19.99 years at their first birth and reported low physical activity had 38.9 stillbirths per 1000 live births, compared to the lowest rate at 5.5 per 1000 live births. Conclusion Different groups of women experience vastly different rates of each adverse pregnancy event. We have used simple questions and established reference data that will stratify women into low- and high-rate groups, which may be useful in counselling those who have experienced miscarriage, preterm delivery, or stillbirth, plus women with fertility intent.

The Chidiac case : another miscarriage of justice?

On 25 March 1997 the Witness program on Channel 7 screened a story about the conviction of Neil Chidiac in February 1989 for conspiracy to import a trafficable quantity of heroin in NSW. The program questioned the justice of Chidiac's conviction and filmed his recent release from prison on parole after serving over eight years in prison, still protesting his innocence. Witness featured an interview with the chief Crown witness against Chidiac, Alfred Oti, in which Oti completely repudiated the testimony he gave at the trial and admitted to lying at the behest of the police in order to secure advantages for himself...

Genetic studies on recurrent miscarriage

Recurrent miscarriage (RM) is defined as three consecutive pregnancy failures and is estimated to affect ~1% of couples trying to conceive. The cause of RM remains unknown in approximately 50% of cases. In this study, it was hypothesized that some of the underlying factors yet to be discovered are genetic. The aim was to search for mutations in genes AMN, EPCR, TM, and p53 known to cause miscarriage in mouse models and thereby find new genetic causes for unexplained miscarriages in humans. In addition, the mitochondrial genome was studied because mitochondria are involved in processes important in early development. Furthermore, sex chromosome characteristics suggested to underlie miscarriage were also studied. A total of 40 couples and 8 women with unexplained RM were collected for this study and screened for mutations in the candidate genes. Six interesting exonic or potential splice site disrupting variations were detected. However, their phenotypic effects cannot be determined without further investigations. Additionally, an association between the C11992A polymorphism of the p53 gene and RM was detected. The results indicate that women carrying the C/A or A/A genotype have a two-fold higher risk for RM than women with a C/C genotype. This strengthens the results of previous studies reporting that p53 sequence variations may cause miscarriage. The role of variation C11992A in embryonic development is, however, difficult to predict without further studies When screening the mitochondrial genome a heteroplasmic mtDNA variation was found in an unexpected high number of women, as heteroplasmic variations are reported to be rare. One novel variation and 18 previously reported polymorphisms were detected in the mitochondrial genome. Although the detected variations are likely to be neutral polymorphisms, a role in the aetiology of miscarriage cannot be excluded as some mtDNA variations may be pathogenic only when a threshold is reached. Recent publications have reported skewed X chromosome inactivation and Y chromosome microdeletions to be associated with RM. Therefore, these sex chromosome abnormalities in the context of RM were investigated. No associations between skewed X chromosome inactivation or Y chromosome microdeletions and RM in the Finnish patients were detected. Data on ancestral birthplaces of the patients were collected to study any possible geographic clustering, which would indicate a common predisposing factor. The results showed clustering of the birthplaces in eastern Finland in a subset of patients. This suggests a possibility of an enriched susceptibility gene which may contribute to RM.

Cesarean section and rate of subsequent stillbirth, miscarriage and ectopic pregnancy: a Danish register-based cohort study

Background: With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. Methods and Findings: We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. Conclusions: This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery.

The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

STUDY QUESTION Is there an association between high levels of sperm DNA damage and miscarriage?SUMMARY ANSWERMiscarriage rates are positively correlated with sperm DNA damage levels.WHAT IS KNOWN ALREADYMost ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.STUDY DESIGN, SIZE, DURATIONA systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P <0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P <0.00001).LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.STUDY FUNDING/COMPETING INTEREST(S)None.

Factor V Leiden and Prothrombin G20210A in Portuguese Women with Recurrent Miscarriage: Is it Worthwhile to Investigate?

OBJECTIVE: To compare the prevalence of factor V Leiden (FVL) and prothrombin (PT) G20210A mutations in Portuguese women with unexplained recurrent miscarriage (RM) and a control group of parous women. MATERIALS AND METHODS: FVL and PT G20210A analysis were carried out in 100 women with three or more consecutive miscarriages and 100 controls with no history of pregnancy losses. Secondary analysis was made regarding gestational age at miscarriage (embryonic and fetal losses). RESULTS: Overall, the prevalence of FVL and PT G20210A was similar in women with RM (5 and 3%) compared with controls (5 and 1%) OR 1.36 (CI 95% 0.45-4.08). In RM embryonic subgroup, PT G20210A was observed in 1.3% of women and FVL prevalence (2.6%) was inclusively lesser than that of controls. Both polymorphisms were more prevalent in women with fetal losses than in controls, although statistical significance was not reached due to the small size of the >10 weeks' subgroup. CONCLUSION: These data indicate that neither FVL nor PT G20210A is associated with RM prior to 10 weeks of gestation. Therefore, its screening is not indicated as an initial approach in Portuguese women with embryonic RM and negative personal thromboembolic history.

Influence of Anchoring on Miscarriage Risk Perception Associated with Amniocentesis

INFLUENCE OF ANCHORING ON MISCARRIAGE RISK PERCEPTION ASSOCIATED WITH AMNIOCENTESIS Publication No. ___________ Regina Nuccio, BS Supervisory Professor: Claire N. Singletary, MS, CGC Amniocentesis is the most common invasive procedure performed during pregnancy (Eddleman, et al., 2006). One important factor that women consider when making a decision about amniocentesis is the risk of miscarriage associated with the procedure. People use heuristics such as anchoring, the action of using a prior belief regarding the magnitude of risk as a frame of reference for new information to be synthesized, to better understand risks that they encounter in their lives. This study aimed to determine a woman’s perception of miscarriage risk associated with amniocentesis before and after a genetic counseling session and to determine what factors are most likely to anchor a woman’s perception of miscarriage risk associated with amniocentesis. Most women perceived the risk as low or average pre-counseling and were likely to indicate the numeric risk of amniocentesis as <1% risk. A higher percentage of patients correctly identified the numeric risk as <1% post-counseling when compared to pre-counseling. However, the majority of patients’ feeling about the risk perception did not change after the genetic counseling session (60%), regardless of how they perceived the risk before discussing amniocentesis with a genetic counselor. Those whose risk perception did change after discussing amniocentesis with a genetic counselor showed a decreased risk perception (p<0.0001). Of the multitude of factors studied, only two showed significance: having a friend or relative with a personal or family history of a genetic disorder was associated with a lower risk perception (p=0.001) and having a child already was associated with a lower risk perception (p=0.038). The lack of significant factors may reflect the uniqueness of each patient’s heuristic framework and reinforces the importance of genetic counseling to elucidate individual concerns.

EFFECT OF ANCHORING ON PERCEIVED AMNIOCENTESIS RELATED MISCARRIAGE RISK WITHIN A LATINA POPULATION

Most recognized pregnancies are completed without difficulty, yet there is always a 3-5% background risk to have a child with a birth defect. Amniocentesis, the most common type of prenatal diagnostic test, is used to detect chromosomal abnormalities, such as Down syndrome. Amniocentesis is associated with a risk of complications that can lead to a miscarriage, which is typically quoted to be between 1 in 300 and 1 in 500. Amniocentesis uptake rates are typically lowest within the Latina community, and although the factors related to this have been studied before, no specific conclusions have been reached. The general population has a difficult time interpreting risks, as individuals vary in numeracy skills as well as personal factors that can influence risk perception. A recent study by Nuccio (2010) investigated the effect of anchoring, where a patient’s prior knowledge about a subject affects her risk perception, and how it relates to the uptake of amniocentesis within a diverse population in Houston, TX. The effect of anchoring on perceived amniocentesis-related miscarriage risk within the Latina population has not been previously examined. A two-part questionnaire was completed by 96 Latinas receiving prenatal genetic counseling due to an increased risk to have a baby with a chromosome abnormality at various clinics in Houston, TX. The genetic counselor involved in the session completed a separate survey. This population was largely unfamiliar with surveys, risk figures, and prenatal testing. Only one individual was able to quantify the risk associated with amniocentesis prior to the genetic counseling. While the majority of women felt that the risk association with amniocentesis is very low to average, only 7 individuals pursued diagnostic testing through amniocentesis. Most women did not feel like the information gained from an amniocentesis would change the management of their pregnancy and/or they did not believe that their baby had a problem. Women, regardless of ethnicity, deserve individualized genetic counseling sessions that cater to their needs and desires regarding their prenatal care.