Sarka Lisonkova

Influence of definition based versus pragmatic birth registration on international comparisons of perinatal and infant mortality: population based retrospective study

Objectives To examine variations in the registration of extremely low birthweight and early gestation births and to assess their effect on perinatal and infant mortality rankings of industrialised countries. Design Retrospective population based study. Setting Australia, Canada, European countries, and the United States for 2004; Australia, Canada, and New Zealand for 2007. Population National data on live births and on fetal, neonatal, and infant deaths. Main outcome measures Reported proportions of live births with birth weight/gestational age of less than 500 g, less than 1000 g, less than 24 weeks, and less than 28 weeks; crude rates of fetal, neonatal, and infant mortality; mortality rates calculated after exclusion of births under 500 g, under 1000 g, less than 24 weeks, and less than 28 weeks. Results The proportion of live births under 500 g varied widely from less than 1 per 10 000 live births in Belgium and Ireland to 10.8 per 10 000 live births in Canada and 16.9 in the United States. Neonatal deaths under 500 g, as a proportion of all neonatal deaths, also ranged from less than 1% in countries such as Luxembourg and Malta to 29.6% in Canada and 31.1% in the United States. Rankings of countries based on crude fetal, neonatal, and infant mortality rates differed substantially from rankings based on rates calculated after exclusion of births with a birth weight of less than 1000 g or a gestational age of less than 28 weeks. Conclusions International differences in reported rates of extremely low birthweight and very early gestation births probably reflect variations in registration of births and compromise the validity of international rankings of perinatal and infant mortality.

Maternal morbidity associated with early-onset and late-onset preeclampsia.

OBJECTIVE: To examine temporal trends in early-onset compared with late-onset preeclampsia and associated severe maternal morbidity. METHODS: The study included all singleton deliveries in Washington State between 2000 and 2008 (N=670,120). Preeclampsia onset was determined using hospital records linked to birth certificates. Severe maternal morbidity was defined as any potentially life-threatening condition. Logistic regression was used to obtain adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS: The preeclampsia rate was 3.0 per 100 singleton births, and increased slightly from 2.9 to 3.1 between 2000 and 2008. Rates of early-onset and late-onset disease were 0.3% and 2.7%, respectively. The temporal increase was significant only for early-onset disease (4.5%/year; 95% CI 2.3–5.8%) after adjustment for changes in maternal characteristics. Maternal death rates were higher among women with early-onset (42.1/100,000 deliveries) and late-onset preeclampsia (11.2/100,000) compared with women without preeclampsia (4.2/100,000). The rate of severe maternal morbidity (excluding obstetric trauma) was 12.2 per 100 deliveries in the early-onset group (aOR 3.7, 95% CI 3.2–4.3), 5.5 per 100 deliveries in the late-onset group (aOR 1.7, 95% CI 1.6–1.9), and approximately 3 per 100 in women without preeclampsia. Early-onset preeclampsia conferred a substantially higher risk of cardiovascular, respiratory, central nervous system, renal, hepatic, and other morbidity. However, rates of obstetric trauma were significantly lower among women with preeclampsia. CONCLUSION: Women with early-onset and late-onset preeclampsia have significantly higher rates of specific maternal morbidity compared with women without early-onset and late-onset disease. LEVEL OF EVIDENCE: II

Association Between Maternal Chronic Conditions and Congenital Heart Defects A Population-Based Cohort Study

Background— This study quantifies the association between maternal medical conditions/illnesses and congenital heart defects (CHDs) among infants. Methods and Results— We carried out a population-based study of all mother-infant pairs (n=2 278 838) in Canada (excluding Quebec) from 2002 to 2010 using data from the Canadian Institute for Health Information. CHDs among infants were classified phenotypically through a hierarchical grouping of International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada codes. Maternal conditions such as multifetal pregnancy, diabetes mellitus, hypertension, and congenital heart disease were defined by use of diagnosis codes. The association between maternal conditions and CHDs and its subtypes was modeled using logistic regression with adjustment for maternal age, parity, residence, and other factors. There were 26 488 infants diagnosed with CHDs at birth or at rehospitalization in infancy; the overall CHD prevalence was 116.2 per 10 000 live births, of which the severe CHD rate was 22.3 per 10 000. Risk factors for CHD included maternal age ≥40 years (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.39–1.58), multifetal pregnancy (aOR, 4.53; 95% CI, 4.28–4.80), diabetes mellitus (type 1: aOR, 4.65; 95% CI, 4.13–5.24; type 2: aOR, 4.12; 95% CI, 3.69–4.60), hypertension (aOR, 1.81; 95% CI, 1.61–2.03), thyroid disorders (aOR, 1.45; 95% CI, 1.26–1.67), congenital heart disease (aOR, 9.92; 95% CI, 8.36–11.8), systemic connective tissue disorders (aOR, 3.01; 95% CI, 2.23–4.06), and epilepsy and mood disorders (aOR, 1.41; 95% CI, 1.16–1.72). Specific CHD subtypes were associated with different maternal risk factors. Conclusions— Several chronic maternal medical conditions, including diabetes mellitus, hypertension, connective tissue disorders, and congenital heart disease, confer an increased risk of CHD in the offspring.

International comparisons of preterm birth: higher rates of late preterm birth are associated with lower rates of stillbirth and neonatal death.

Please cite this paper as: Lisonkova S, Sabr Y, Butler B, Joseph K. International comparisons of preterm birth: higher rates of late preterm birth are associated with lower rates of stillbirth and neonatal death. BJOG 2012;119:1630–1639.

The Effect of Maternal Age on Adverse Birth Outcomes: Does Parity Matter?

OBJECTIVES To examine the effect of parity on the association between older maternal age and adverse birth outcomes, specifically stillbirth, neonatal death, preterm birth, small for gestational age, and neonatal intensive care unit admission. METHODS We conducted a retrospective cohort study of singleton births in British Columbia between 1999 and 2004. In the cohort, 69 023 women were aged 20 to 29, 25 058 were aged 35 to 39, and 4816 were aged 40 and over. Perinatal risk factors, obstetric history, and birth outcomes were abstracted from the British Columbia Perinatal Database Registry. Logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals for adverse outcomes in the two older age groups compared with the young control subjects. RESULTS Compared with younger control subjects, women aged 35 to 39 years had an aOR of stillbirth of 1.5 (95% CI 1.2 to 1.9) and women aged >or= 40 years also had an aOR of 1.5 (95% CI 1.0 to 2.4). The aOR for NICU admission was 1.2 (95% CI 1.0 to 1.3) in women aged 35 to 39 years and 1.4 (95% CI 1.1 to 17) in women aged >or= 40 years compared with younger control subjects. The risk of preterm birth and SGA differed by parity. The aOR for preterm birth compared with younger primiparas was 1.5 (95% CI 1.4 to 1.7) for women aged 35 to 39 years and 1.6 (95% CI 1.3 to 2.0) for women aged >or= 40 years. In multiparas the aOR for preterm birth was 1.1 (95% CI 1.1 to 1.2) in women aged 35 to 39 and 1.3 (95% CI 1.1 to 1.5) in women >or= 40 years. The aOR for SGA in primiparas was 1.2 (95% CI 1.1 to 1.4) for women aged 35 to 39 and 1.4 (95% CI 1.1 to 1.7) for women aged >or= 40 years. The risk of neonatal death was not significantly different between groups. CONCLUSION Older women were at elevated risk of stillbirth, preterm birth, and NICU admission regardless of parity. Parity modified the effect of maternal age on preterm birth and SGA. Older primiparas were at elevated risk for SGA, but no association between age and SGA was found in multiparas. Older primiparas were at higher risk of preterm birth than older multiparas compared with younger women.

Temporal trends in neonatal outcomes following iatrogenic preterm delivery.

BackgroundPreterm birth rates have increased substantially in the recent years mostly due to obstetric intervention. We studied the effects of increasing iatrogenic preterm birth on temporal trends in perinatal mortality and serious neonatal morbidity in the United States.MethodsWe used data on singleton and twin births in the United States, 1995-2005 (n = 36,399,333), to examine trends in stillbirths, neonatal deaths, and serious neonatal morbidity (5-minute Apgar ≤3, assisted ventilation ≥30 min and neonatal seizures). Preterm birth subtypes were identified using an algorithm that categorized live births <37 weeks into iatrogenic preterm births, births following premature rupture of membranes and spontaneous preterm births. Temporal changes were quantified using odds ratios (OR) and 95% confidence intervals (CI).ResultsAmong singletons, preterm birth increased from 7.3 to 8.8 per 100 live births from 1995 to 2005, while iatrogenic preterm birth increased from 2.2 to 3.7 per 100 live births. Stillbirth rates declined from 3.4 to 3.0 per 1,000 total births from 1995-96 to 2004-05, and neonatal mortality rates declined from 2.4 to 2.1 per 1,000 live births. Temporal declines in neonatal mortality/morbidity were most pronounced at 34-36 weeks gestation and larger among iatrogenic preterm births (OR = 0.75, CI 0.73-0.77) than among spontaneous preterm births (OR = 0.82, CI 0.80-0.84); P < 0.001. Similar patterns were observed among twins, with some notable differences.ConclusionIncreases in iatrogenic preterm birth have been accompanied by declines in perinatal mortality. The temporal decline in neonatal mortality/serious neonatal morbidity has been larger among iatrogenic preterm births as compared with spontaneous preterm births.

Birth Outcomes Among Older Mothers in Rural Versus Urban Areas: A Residence-Based Approach

PURPOSE We examined the association between rural residence and birth outcomes in older mothers, the effect of parity on this association, and the trend in adverse birth outcomes in relation to the distance to the nearest hospital with cesarean-section capacity. METHODS A population-based retrospective cohort study, including all singleton births to 35+ year-old women in British Columbia (Canada), 1999-2003. We compared birth outcomes in rural versus urban areas, and between 3 distance categories to a hospital (<50, 50-150, >150 km). Outcomes included labor induction, cesarean section, stillbirth, perinatal death, preterm birth (<37 weeks), small-for-gestational-age, large-for-gestational-age, and neonatal intensive care unit admission. We used multivariate regression to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CIs). FINDINGS Among the 29,698 subjects, 11.5% lived in rural areas; 5% lived within 50-150 km; and 1.1% lived >150 km from a hospital. Rural women were at lower risk of primary and repeat cesarean section (OR = 0.9, CI: 0.9-1.0; OR = 0.7, CI: 0.6-0.9) and small-for-gestational-age (OR = 0.8, CI: 0.7-0.9) births; they were at increased risk for perinatal death (OR = 1.5, CI: 1.1-2.1) and large-for-gestational-age (OR = 1.1, CI: 1.1-1.2) births. The association was stronger among multiparous versus primiparous women. No differences in emergency cesarean section, preterm birth, or neonatal intensive care admission were found, regardless of parity. Perinatal mortality increased with distance from hospital; OR = 1.5 (CI: 1.1-2.1) per distance category. CONCLUSIONS Older women in rural versus urban areas had a lower rate of cesarean section and increased risk of perinatal death. The risk of perinatal death increased with the distance to hospital. Further studies need to evaluate the contribution of underlying perinatal risks, access to care, and decision making regarding referral and transport.

Optimal timing of delivery in pregnancies with pre‐existing hypertension

Please cite this paper as: Hutcheon J, Lisonkova S, Magee L, von Dadelszen P, Woo H, Liu S, Joseph K. Optimal timing of delivery in pregnancies with pre‐existing hypertension. BJOG 2011;118:49–54.

Confounding by Indication and Related Concepts

The term confounding by indication is increasingly used in the literature, although the concept has lost much of its original meaning. The literature includes instances where confounding by indication is equated with confounding in general or reverse causality, and other instances where it is used to refer to confounding by contraindication. In this paper, we review concepts related to confounding by indication in studies of intended effects, confounding by indication and contraindication in studies of unintended effects, and confounding by extraneous aspects of the indication. We also discuss non-experimental methods to address confounding by indication, including design strategies (e.g., restriction to a domain free of the indication) and statistical techniques (e.g., propensity score matching). We argue for greater conceptual and semantic clarity with regard to the different forms of confounding by indication and conclude that non-experimental methods do not adequately address this bias in studies of intended effects when the indication defies quantification.

Caregiver-reported health outcomes of preschool children born at 28 to 32 weeks' gestation.

Objective: We conducted a population-based survey of caregivers of all preschoolers at 42 months of age who had been admitted at birth in 1996–1997 to a tertiary neonatal intensive care unit in British Columbia (BC), Canada. Methods: In this paper, we examine health status (measured by Health Status Classification System [HSCS-PS]), health-related quality of life (HRQL) (measured by Infant and Toddler Quality of Life Questionnaire), and behavioral outcomes (measured by Child Behavior Checklist) of the preschoolers in the sample who were born at 28–32 weeks gestational age (GA) in comparison to those born at <28 weeks GA. In addition, we compare these outcomes to health status, HRQL, and behavioral outcomes of a cohort of healthy full-term infants identified from the primary care practices at two of the hospital sites in BC in 1996–1997. Results: From the total identified sample of 555 children, the survey was completed for 50 children born at <28 weeks GA, 201 children born at 28–32 weeks GA, and 393 healthy full-term subjects. The developmental outcomes of the preschoolers born at 28–32 weeks GA was very similar to those born at <28 weeks GA. We also found increased parental report of problems related to health status and HRQL among the 28–32 weeks GA group. When compared with the term cohort, the 28–32 weeks GA group had poorer outcomes in all HRQL domains. Conclusion: This study discusses the importance of continued neurodevelopmental follow-up care of infants born at 28–32 weeks GA in addition to those infants born <28 weeks GA.