Perinatal Epidemiology Research Articles

Perinatal deaths in twin and singleton infants in Ireland: A comparison of characteristics and causes.

Twin pregnancies are associated with significantly higher perinatal mortality (PM) rates compared to singletons, primarily due to complications like fetal growth restriction, preterm birth, and congenital anomalies. This study aimed to compare the characteristics associated with PM in twin pregnancies and compare maternal and obstetric factors and cause of death among twins and singletons in the Republic of Ireland. Data spanning 2011 to 2022 from the National Perinatal Epidemiology Centre's annual perinatal mortality clinical audit included 4494 perinatal deaths. Maternal characteristics, antenatal care factors and cause of death were analysed with relative risk calculated using national Hospital In-Patient Enquiry data. Pearson's chi-squared tests studied the difference between mortality in twins and singletons. Twins accounted for 10.4% of all perinatal deaths, despite representing only 3.6% of total births. The PM rate for twins was 17.3 per 1000 births, 3.1 times higher than for singletons. Early neonatal deaths (ENNDs) were more frequent in twins (54.2%), while stillbirths predominated among singletons (68.6%). Younger maternal age and lower BMI were associated with higher PM risks in twins. A considerable proportion of twin deaths with major congenital anomalies or birth before 28weeks gestation occurred in non-tertiary hospitals, suggesting limitations in referral pathways to centres with appropriate neonatal expertise. Twin pregnancies pose a higher risk of perinatal mortality, particularly among younger mothers and preterm births. The findings highlight the need for updated guidelines that prioritise early risk assessment, targeted interventions, and improved referral systems.

Perinatal mortality in women in minority ethnic groups in Ireland (2011-2021)

Abstract Women in minority ethnic groups (MEG) have been consistently overrepresented in the National Perinatal Epidemiology Centre (NPEC) Perinatal Mortality (PM) reports in Ireland (IE). International research, report similar findings. A secondary analysis of NPEC PM national clinical audit data (2011-21) examined factors associated with PM in women in MEG and differences between these and white women. Maternal sociodemographic and obstetric characteristics, maternal medical history, infant characteristics and PM outcomes of women in MEG were analysed and compared with women of white ethnicity with χ2 tests. There were 4314 PMs in IE from 2011-21; 2896 stillbirths (SB) and 1418 early neonatal deaths (ENND). Women in MEG who experienced PM were younger (p < 0.001) and 46% were employed (vs 75% of white women, p < 0.001). A greater proportion of women in MEG had previous pregnancies (77% vs 68%, p < 0.001), and more than twice as many had ≥3 previous completed pregnancies versus white women (26% vs. 12%, p < 0.001). Women in MEG also had more previous pregnancy medical issues (49% vs 38%, p = 0.001). Twice as many women in MEG had their first prenatal appointment after 20 weeks’ gestation or never received prenatal care (p < 0.001). Analysing by type of PM, statistically significant differences persisted for all these variables in both SB and ENND groups. Women in MEG experienced more placental conditions and obstetric factors as causes of PM, but fewer congenital anomalies compared to white women (p = 0.047). These differences only persisted in the SB group when data was analysed by type of PM. Factors highlighted in this study such as employment, parity, and prenatal care access may explain the over-representation of women in MEG in PM. These findings provide further knowledge useful to create targeted interventions (e.g. initiatives to improve maternal health literacy for women in MEG). Further studies are needed to promote change that would specifically address these systemic inequities. Key messages • Data shows systemic inequities that may contribute to the over-representation of women in minority ethic groups in perinatal mortalities. Clear and tangible changes are needed to address these issues. • Further research needs to clarify factors restricting access of women in minority ethic groups to prenatal care and promote interventions to ensure adequate prenatal care is available and accessible.

Lack of consensus on the definition of severe congenital heart defects for research: A challenge for comparing international studies.

Lack of consensus on the definition of severe congenital heart defects for research: A challenge for comparing international studies.

Research Priorities to Support Women Veterans' Reproductive Health and Health Care Within a Learning Health Care System.

Research Priorities to Support Women Veterans' Reproductive Health and Health Care Within a Learning Health Care System.

Issue Information

Paediatric and Perinatal EpidemiologyVolume 37, Issue 4 p. i-iii ISSUE INFORMATIONFree Access Issue Information First published: 08 May 2023 https://doi.org/10.1111/ppe.12903AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume37, Issue4Special Issue: Big Data in Perinatal Epidemiology Methodologic ConsiderationsMay 2023Pages i-iii RelatedInformation

8th ABM/EABM European Regional Conference May 11–13, 2023 Split, Croatia

8^th ABM/EABM European Regional Conference May 11–13, 2023 Split, Croatia

Homage to Dr. Murray Enkin and the complexity of evidence-based medicine.

Homage to Dr. Murray Enkin and the complexity of evidence-based medicine.

Cerebral palsy as a public health indicator.

Cerebral palsy as a public health indicator.

The matrix revolutions: How databases and database linkages will transform epidemiologic research.

The matrix revolutions: How databases and database linkages will transform epidemiologic research.

Summarising multiple bounds of the average causal effect in Mendelian randomisation.

Summarising multiple bounds of the average causal effect in Mendelian randomisation.

Rigour and reproducibility in perinatal and paediatric epidemiologic research using big data.

Rigour and reproducibility in perinatal and paediatric epidemiologic research using big data.

Protective role of the placental efflux transporter BCRP/ABCG2 in the relationship between prenatal cadmium exposure, placenta weight, and size at birth

Background and aimPlacental efflux transporter proteins, such as BCRP, reduce the placental and fetal toxicity of environmental contaminants but have received little attention in perinatal environmental epidemiology. Here, we evaluate the potential protective role of BCRP following prenatal exposure to cadmium, a metal that preferentially accumulates in the placenta and adversely impacts fetal growth. We hypothesized that individuals with a reduced function polymorphism in ABCG2, the gene encoding BCRP, would be most vulnerable to the adverse impacts of prenatal cadmium exposure, notably, smaller placental and fetal size. MethodsWe measured cadmium in maternal urine samples at each trimester and in term placentas from UPSIDE-ECHO study participants (NY, USA; n = 269). We fit adjusted multivariable linear regression and generalized estimating equation models to examine log-transformed urinary and placental cadmium concentrations in relation to birthweight, birth length, placental weight, and fetoplacental weight ratio (FPR) and stratified models by ABCG2 Q141K (C421A) genotype. ResultsOverall 17% of participants expressed the reduced-function ABCG2 C421A variant (AA or AC). Placental cadmium concentrations were inversely associated with placental weight (β = −19.55; 95%CI: −37.06, −2.04) and trended towards higher FPR (β = 0.25; 95%CI: −0.01, 0.52) with stronger associations in 421A variant infants. Notably, higher placental cadmium concentrations in 421A variant infants were associated with reduced placental weight (β = −49.42; 95%CI: 98.87, 0.03), and higher FPR (β = 0.85, 95%CI: 0.18, 1.52), while higher urinary cadmium concentration was associated with longer birth length (β = 0.98; 95%CI: 0.37, 1.59), lower ponderal index (β = −0.09; 95%CI: 0.15, −0.03), and higher FPR (β = 0.42; 95%CI: 0.14, 0.71). ConclusionsInfants with reduced function ABCG2 polymorphisms may be particularly vulnerable to the developmental toxicity of cadmium as well as other xenobiotics that are BCRP substrates. Additional work examining the influence of placental transporters in environmental epidemiology cohorts is warranted.

Characterisation of personalised air pollution exposure in pregnant women participating in a birth cohort study.

Air pollution is a health risk in pregnant women and children. Despite the importance of refined exposure assessment, the characterisation of personalised air pollution exposure remains a challenge in paediatric and perinatal epidemiology. We used portable personal air monitors to characterise personalised exposure to air pollutants in pregnant women. Between November 2019 and May 2022, we offered personal air monitors to pregnant women participating in a birth cohort in New York City. During pregnancy, women used air monitors, which measured particulate matter (PM), nitrogen dioxide (NO2 ), and volatile organic compounds (average use=14 days). Data were stored in real-time on a secure database via synchronisation with a smartphone application. Of 497 women who agreed to use air monitors, 273 women (55%) were successful in using air monitors for longer than a day. For these participants, we identified daily patterns of exposure to air pollutants using functional principal component analysis (3827 days of air monitoring). Compared to women with no pollution data (n=224), women who successfully used monitors were more likely to be non-Hispanic White and Asian (vs. Hispanic), nulliparous, unemployed, married/partnered, and received the device in-person (vs. mailed). We identified different daily patterns of exposure to air pollutants. The most dominant pattern for all pollutants was low exposure levels with little variations within 24 h, followed by a pattern that showed differences between day and night levels. NO2 had higher daily variations compared to PM. Small wearables are useful for the measurement of personalised air pollution exposure in birth cohorts and identify daily patterns that cannot be captured otherwise. Successful participation, however, depends on certain individual characteristics. Future studies should consider strategies in design and analysis to account for selective participation.

The challenges of time for studies on the population effects of the COVID-19 pandemic on perinatal outcomes.

The challenges of time for studies on the population effects of the COVID-19 pandemic on perinatal outcomes.

Neighbourhood-related socioeconomic perinatal health inequalities: An illustration of the mediational g-formula and considerations for the big data context.

Advances in computing power have enabled the collection, linkage and processing of big data. Big data in conjunction with robust causal inference methods can be used to answer research questions regarding the mechanisms underlying an exposure-outcome relationship. The g-formula is a flexible approach to perform causal mediation analysis that is suited for the big data context. Although this approach has many advantages, it is underused in perinatal epidemiology and didactic explanation for its implementation is still limited. The aim of this was to provide a didactic application of the mediational g-formula by means of perinatal health inequalities research. The analytical procedure of the mediational g-formula is illustrated by investigating whether the relationship between neighbourhood socioeconomic status (SES) and small for gestational age (SGA) is mediated by neighbourhood social environment. Data on singleton births that occurred in the Netherlands between 2010 and 2017 (n=1,217,626) were obtained from the Netherlands Perinatal Registry and linked to sociodemographic national registry data and neighbourhood-level data. The g-formula settings corresponded to a hypothetical improvement in neighbourhood SES from disadvantaged to non-disadvantaged. At the population level, a hypothetical improvement in neighbourhood SES resulted in a 6.3% (95% confidence interval [CI] 5.2, 7.5) relative reduction in the proportion of SGA, that is the total effect. The total effect was decomposed into the natural direct effect (5.6%, 95% CI 5.1, 6.1) and the natural indirect effect (0.7%, 95% CI 0.6, 0.9). In terms of the magnitude of mediation, it was observed the natural indirect effect accounted for 11.4% (95% CI 9.2, 13.6) of the total effect of neighbourhood SES on SGA. The mediational g-formula is a flexible approach to perform causal mediation analysis that is suited for big data contexts in perinatal health research. Its application can contribute to providing valuable insights for the development of policy and public health interventions.

Exploring the utility of synthetic data to extract more value from sensitive health data assets: A focused example in perinatal epidemiology.

Privacy, access and security concerns can hinder the availability of health data for research. The use of synthesised data in place of de-identified electronic health records (EHRs) presents an opportunity to conduct research while minimising privacy concerns. To examine whether synthesised data can replicate two prenatal epidemiological associations: between prenatal smoking and lower birthweight, and between prenatal mood disorders and lower birthweight, using data synthesised from de-identified health administrative data collections. We generated two synthetic datasets, using parametric and non-parametric data generating methods, and examined the synthetic data for evidence of privacy concerns. Next, univariable and multivariable logistic regression was utilised to estimate the associations in both synthetic datasets, with results then compared to the real data. Both synthesised datasets performed well in identifying the reduction in birthweight associated with prenatal smoking, while the non-parametric data underestimated the reduction in birthweight associated with prenatal mood disorders. Improbable relationships between some variables were identified in the parametric synthesised data, however, these can be addressed with simple rules during data synthesis. No duplicate rows (i.e., exact copies of de-identified data) were found in the parametric data, while only 0.6% of the rows in the non-parametric data were duplicated. Both synthesised datasets performed well in replicating the statistical properties of the original data while addressing privacy issues. Data synthesis methods provide an opportunity for researchers to utilise health data while managing privacy and security concerns.

Validation of claims-based algorithms to identify non-live birth outcomes.

Perinatal epidemiology studies using healthcare utilization databases are often restricted to live births, largely due to the lack of established algorithms to identify non-live births. The study objective was to develop and validate claims-based algorithms for the ascertainment of non-live births. Using the Mass General Brigham Research Patient Data Registry 2000-2014, we assembled a cohort of women enrolled in Medicaid with a non-live birth. Based on ≥1 inpatient or ≥2 outpatient diagnosis/procedure codes, we identified and randomly sampled 100 potential stillbirth, spontaneous abortion, and termination cases each. For the secondary definitions, we excluded cases with codes for other pregnancy outcomes within ±5 days of the outcome of interest and relaxed the definitions for spontaneous abortion and termination by allowing cases with one outpatient diagnosis only. Cases were adjudicated based on medical chart review. We estimated the positive predictive value (PPV) for each outcome. The PPV was 71.0% (95% CI, 61.1-79.6) for stillbirth; 79.0% (69.7-86.5) for spontaneous abortion, and 93.0% (86.1-97.1) for termination. When excluding cases with adjacent codes for other pregnancy outcomes and further relaxing the definition, the PPV increased to 80.6% (69.5-88.9) for stillbirth, 86.6% (80.5-91.3) for spontaneous abortion and 94.9% (91.1-97.4) for termination. The PPV for the composite outcome using the relaxed definition was 94.4% (92.3-96.1). Our findings suggest non-live birth outcomes can be identified in a valid manner in epidemiological studies based on healthcare utilization databases.

Remembering Marian MacDorman.

Remembering Marian MacDorman.

Impact of female obesity and assisted reproduction on uncomplicated pregnancies and healthy births: a study of 428 336 births in Flanders.

What is the impact of BMI on uncomplicated pregnancies and healthy births in women who did or did not have medically assisted reproduction (MAR, i.e. ART or hormonal stimulation without manipulation of eggs or embryos) in the Flanders region (Belgium)? Women with a higher BMI who use MAR are at the highest risk of pregnancy and birth complications. Medically assisted reproduction (MAR) is used increasingly worldwide and is associated with increased risk of adverse perinatal outcomes. Obesity is also increasing globally and obese women are more likely to seek MAR since obesity is associated with infertility. When obese women undergo MAR, the risk of adverse outcomes may be enhanced but it is not clear to what extent. We conducted a registry-based study using the data from the Study Centre for Perinatal epidemiology database for years 2009-2015, region of Flanders, Belgium. This included 428 336 women. The average age was 30.0 years (SD 4.78), 194 061 (45.31%) were nulliparous, and 6.3% (n = 26 971) conceived with MAR. We examined the association of BMI and MAR with the following composite primary outcomes: 'uncomplicated pregnancy and birth' and 'healthy baby'. We conducted Poisson regression and adjusted for maternal age, parity, gestational weight gain, smoking and previous caesarean section. In our study, 36.80% (n = 157 623) of women had an uncomplicated pregnancy and birth according to the definition used. The predicted probability of having an uncomplicated pregnancy and birth for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.33 (0.32 to 0.35), while it was 0.28 (0.24 to 0.32) for women who used hormonal stimulation and 0.26 (0.22 to 0.29) for women who used IVF/ICSI. This probability reduced with increasing BMI category for both MAR and non-MAR users. For women with a BMI of 30 kg/m2, the predicted probability of having an uncomplicated pregnancy and birth was 0.28 (0.26 to 0.30) for women who conceived spontaneously, and 0.22 (0.16 to 0.29) and 0.20 (0.14 to 0.26) for women who used hormonal stimulation only or IVF/ICSI, respectively. The predicted probability of having a healthy baby for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.92 (0.91 to 0.93), 0.89 (0.87 to 0.92) for women who used hormonal stimulation only and 0.85 (0.84 to 0.87) for women who used IVF/ICSI. The database did not include data on socio-economic status, pre-pregnancy morbidities and paternal BMI. Subsequently, we could not adjust for these factors in the analysis. Obese women who use MAR are at the highest risk of pregnancy and birth complications. This increase in interventions also has cost and resource implications which is relevant for funding policies. Weight loss interventions prior to MAR seem plausible but their (cost-) effectiveness needs urgent investigation. F.W. received an Erasmus Plus training grant to visit A.B., L.A. and R.D. and conducted this study during this visit. The authors have no competing interest to declare. N/A.

ANZARD Data Linkage – Agreement Between Births Recorded by Clinics and in NSW Perinatal Data Collection

Background: Fertility clinics submit treatment data on all ART cycles to the Australian and New Zealand Assisted Reproductive Technology Database (ANZARD) as part of their accreditation. The National Perinatal Epidemiology and Statistics Unit (NPESU), who manages ANZARD, is undertaking a study involving the linkage of ANZARD to state and commonwealth datasets to investigate health outcomes of infants born from fertility treatments. Aim: To describe the creation and performance of the linked dataset and to evaluate the agreement between births recorded by clinics and those recorded in state perinatal data collections (PDC). Method: The linked dataset was created by linking the ANZARD to NSW and ACT administrative datasets (performed by NSW Centre for Health Record Linkage (CHeReL)) and to Medicare Benefits Scheme and Pharmaceutical Benefits Schedule (performed by AIHW). The CHeReL’s Master Linkage Key (MLK) was used as a bridge between ANZARD’s statistical linkage key and state administrative datasets. Linkage rates and concordance between births recorded in ANZARD and PDCs was evaluated. Results: A 96.7% linkage rate was achieved between women recorded in ANZARD and CHeReL’s MLKs. A reconciliation of ANZARD-recorded births among NSW residents found that 94.2% (95% CI: 93.9-94.4%) of births were also recorded in NSW/ACT PDCs. A proportion of the missing births could be to women who had ART treatment in NSW but birthed in a different Australian state or country. A high concordance rate (>99%) was found in plurality status and birth outcome between ANZARD and PDCs. Conclusion: High linkage rates can be achieved with partially identifiable data and population spines, such as the CHeReL’s MLK, can be successfully used to link clinical registries and administrative datasets. This linkage resource will provide invaluable information on the safety of the ART and non-ART treatment, and the role of subfertility on the fertility treatments for Australia and beyond.