Leanne Dahlgren

Socioeconomic status and perinatal outcomes in a setting with universal access to essential health care services

Background: The health care system in Canada provides essential health services to all women irrespective of socioeconomic status. Our objective was to determine whether perinatal and infant outcomes varied by family income and other socioeconomic factors in this setting. Methods: We included all 92 914 women who delivered in Nova Scotia between 1988 and 1995 following a singleton pregnancy. Family income was obtained for 76 440 of these women through a confidential link to income tax records and was divided into 5 groups. Outcomes studied included pregnancy complications, preterm birth, small-for-gestational-age live birth, perinatal death, serious neonatal morbidity, postneonatal death and infant death. Logistic regression models were used to adjust for potential confounders. Results: Compared with women in the highest family income group, those in the lowest income group had significantly higher rates of gestational diabetes (crude rate ratio [RR] 1.44, 95% confidence interval [CI] 1.21–1.73), preterm birth (crude RR 1.20, 95% CI 1.06–1.35), small-for-gestational-age live birth (crude RR 1.81, 95% CI 1.66–1.97) and postneonatal death (crude RR 5.54, 95% CI 2.21–13.9). The opposite was true for rates of perinatal death (crude RR 0.74, 95% CI 0.56–0.96), and there was no significant difference between the 2 groups in the composite of perinatal death or serious neonatal morbidity (crude RR 1.01, 95% CI 0.82–1.24). Adjustment for behavioural and lifestyle factors accentuated or attenuated socioeconomic differences. Interpretation: Lower family income is associated with increased rates of gestational diabetes, small-for-gestational-age live birth and postneonatal death despite health care services being widely available at no out-of-pocket expense.

Neonatal and Delivery Outcomes in Women with Multiple Sclerosis

To determine (1) whether the risk of adverse neonatal and delivery outcomes differs between mothers with and without multiple sclerosis (MS) and (2) whether risk is differentially associated with clinical factors of MS.

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.

Perinatal outcomes in women with multiple sclerosis exposed to disease-modifying drugs

Background: The incidence of disease-modifying drug (DMD) exposure during pregnancy in multiple sclerosis (MS) is unknown and limited data exists regarding the potential harm of DMD exposure during pregnancy. Objective: To investigate the incidence and effect of in utero DMD exposure on perinatal outcomes. Methods: We conducted a retrospective analysis by linking two provincial, population-based databases, the British Columbia (BC) MS database with the BC Perinatal Database Registry. Delivery (duration of the second stage of labor, assisted vaginal delivery and Cesarean section) and neonatal (birth weight, gestational age, 5-minute Apgar score and congenital anomalies) outcomes were compared between women exposed and unexposed to a DMD within 1 month prior to conception and/or during pregnancy. Findings were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In all, 311 women with relapsing–remitting MS delivered 418 singleton babies between April 1998 and March 2009. 21/101 (21%) of births to MS women treated with DMD prior to pregnancy were exposed to a DMD. In all cases, exposure was documented as unintentional and DMD treatment was stopped within 2 months of gestation. The overall incidence of exposure was 21/418 (5%). DMD exposure was associated with a trend towards a greater risk of assisted vaginal delivery compared to the DMD naïve groups (OR = 3.0; 95% CI: 1.0–9.2). All other comparisons of perinatal outcomes were unremarkable. Conclusion: The incidence of DMD exposure was relatively low and no cases were intentional. Further studies are needed to ascertain the safety of DMD exposure during pregnancy in MS.

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.

Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance.

When contemplating a pregnancy, women treated for multiple sclerosis (MS) with a disease-modifying drug must decide to discontinue their medication before conception or risk exposing their unborn child to potential drug toxicity. Few studies exist as reference for patients and physicians, and of those available, the majority are less than ideal due to real-world constraints, ethical issues and methodological shortcomings. The authors provide a brief summary of existing animal and human data with current recommendations regarding the safety of IFN-β, glatiramer acetate, natalizumab, mitoxantrone, fingolimod and teriflunomide during pregnancy and lactation in women with MS. We also assess the quality, strengths and limitations of the existing studies including challenges with study design. The investigation of outcomes such as spontaneous abortion and congenital anomalies are highlighted with potential methodological improvements for future studies on drug safety in pregnancy suggested. The authors explore the pharmacokinetics and pharmacodynamics of the MS disease-modifying drugs for their possible mechanistic role in fetal harm and discuss the potential role of clinical trials. Future pharmacovigilance studies should continue to pursue multicenter collaboration with an emphasis on appropriate study design.

Birth hospitalization in mothers with multiple sclerosis and their newborns

Objective: To compare the duration of birth hospitalization in mothers with multiple sclerosis (MS) and their newborns relative to the general population and to investigate the impact of MS-related clinical factors on the length of birth hospitalization stays. Methods: Data from the British Columbia Perinatal Database Registry and the British Columbia MS database were linked in this retrospective cohort study. The duration of birth hospitalization in mothers with MS and their newborns (n = 432) were compared with a frequency-matched sample of the general population (n = 2,975) from 1998 to 2009. Clinical factors investigated included disease duration and disability, as measured by the Expanded Disability Status Scale. A multivariable model (generalized estimating equations) was used to analyze the association between MS and duration of birth hospitalization, adjusting for factors such as maternal age, diabetes, hypertension, and consecutive births to the same mother. Additional analyses included propensity score matching to further balance cohort characteristics. Results: Compared with the general population, the duration of birth hospitalization was not statistically or clinically different for mothers with MS or their newborns (median differences = +1.5 and +2.1 hours, respectively; adjusted p > 0.4). Lengths of birth hospitalization were not significantly associated with disease duration (adjusted p > 0.7) or level of disability (adjusted p > 0.5). Findings remained virtually unchanged after propensity score matching. Conclusions: Birth hospitalization has been understudied in women with MS. Contrary to existing studies, we found that MS was not associated with a longer birth hospitalization. This study provides assurance to expectant mothers with MS, their families, and health care providers.

Prenatally Diagnosed Microcephaly: A Review of Etiologies

Objective: To determine the incidence and etiology of prenatally diagnosed microcephaly. Methods: Retrospective review of 10 years at a tertiary obstetrical hospital. The study population consisted of 21 infants with confirmed prenatal and postnatal microcephaly. Results: There were 8 different definite/probable etiologies identified (viral, monochorionic twinning, genetic syndrome, neural tube defect, abnormal karyotype, hypoxic insult, constitutional). Conclusions: Retrospective study indicates the commonest etiologies for prenatal microcephaly are in utero infection, monochorionic twin insult, rare genetic syndrome and chromosomal anomalies.

A Review of Safety-Related Pregnancy Data Surrounding the Oral Disease-Modifying Drugs for Multiple Sclerosis

The recent approval of several oral disease-modifying drugs (DMDs) for multiple sclerosis (MS) brings promise of improved clinical effectiveness as well as greater drug compliance compared to the existing non-oral DMDs, and substantially increases patient choice and therapeutic options in the effective management of MS. However, for men and women with MS of childbearing age, concerns about the effect of oral DMDs on pregnancy and the fetus may arise. Some limited data from animal reproductive studies of oral DMDs suggest a potential increased risk of early pregnancy loss, impaired growth and birth defects. Although active surveillance mechanisms exist, there is limited data to inform clinical practice. Using existing information from published clinical trials and drug monographs, as well as recent conference proceedings, this review summarizes the mechanism of action (in relation to embryogenesis and pregnancy) and existing animal or human pregnancy-related data for approved (fingolimod, teriflunomide and dimethyl fumarate) and investigational (laquinimod and firategrast) oral DMDs for MS.

Caesarean Section on Maternal Request: Risks and Benefits in Healthy Nulliparous Women and Their Infants

OBJECTIVE To determine the risks and benefits of an elective Caesarean section (CS) at term in healthy nulliparous women. METHODS We conducted a population-based cohort study of deliveries between 1994 and 2002. Using bivariate and multivariable techniques, we compared maternal and neonatal outcomes in healthy nulliparous women who had undergone elective pre-labour CS (using breech presentation as a surrogate) with those in women who had undergone spontaneous labour with anticipated vaginal delivery (SL) at full term. RESULTS There were 1046 deliveries in the pre-labour CS group and 38 021 in the SL group. Life-threatening maternal morbidity was similar in each group. Life-threatening neonatal morbidity was decreased in the CS group (RR 0.34; 99% CI 0.12 to 0.97). Subgroup analysis of the SL group by mode of delivery demonstrated the increased neonatal risk was associated with operative vaginal delivery and intrapartum CS but not spontaneous vaginal delivery. CONCLUSION An elective pre-labour Caesarean section in a nulliparous woman at full term decreased the risk of life-threatening neonatal morbidity compared with spontaneous labour with anticipated vaginal delivery. However, the 63% of women with spontaneous labour who achieved a spontaneous vaginal delivery would not have benefited from delivery by Caesarean section. Further research is needed to better identify women with an increased likelihood of an operative vaginal or intrapartum Caesarean section, as this may assist maternity caregivers in decision-making about childbirth. Further research is also needed to determine if these findings can be confirmed in a prospective study.