Amanda Skoll

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

Trends in Optimal, Suboptimal, and Questionably Appropriate Receipt of Antenatal Corticosteroid Prophylaxis

OBJECTIVE: To conduct a population-based study to assess rates of optimal, suboptimal, and questionably appropriate administration of antenatal corticosteroid (betamethasone or dexamethasone) use. METHODS: All live births in Nova Scotia, Canada, from 1988 to 2012 were included in the study. Temporal trends in optimal (proportion of live births at 24–34 weeks of gestation exposed to antenatal corticosteroids between 24 hours and 7 days before delivery), suboptimal (proportion of live births at 24–34 weeks of gestation exposed to antenatal corticosteroids less than 24 hours or more than 7 days before delivery), and questionably appropriate exposure to antenatal corticosteroids (proportion of live births 35 weeks of gestation or greater exposed to antenatal corticosteroids) were quantified using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 246,459 live births between 1988 and 2012, 2.5% received a partial or a full course of antenatal corticosteroids. The rate of antenatal corticosteroid exposure for neonates born between 28 and 32 weeks of gestation increased from 39.5% in 1988–1992 to 79.3% in 2008–2012, whereas exposure for those born at 33–34 weeks of gestation increased from 14.3 to 49.7%. Optimal antenatal corticosteroid receipt increased from 10% in 1988 to 23% in 2012 (OR 2.7, 95% CI 1.6–4.5), suboptimal administration increased from 7 to 34% (OR 6.7, 95% CI 3.9–11.6), and questionably appropriate administration increased from 0.2% in 1988 to 1.7% in 2012 (OR 7.5, 95% CI 4.9–11.3). Of the women who received antenatal corticosteroids in 2012, 52% delivered at 35 weeks of gestation or greater. CONCLUSION: Temporal increases in optimal exposure to antenatal corticosteroids have been matched by increases in suboptimal and questionably appropriate receipt of antenatal corticosteroids, highlighting the need for accurate preterm delivery prognostic models. LEVEL OF EVIDENCE: II

Impaired NLRP3 inflammasome activity during fetal development regulates IL-1β production in human monocytes.

Interleukin‐1β (IL‐1β) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed the extent of variability within the Toll‐like receptor (TLR)/NLRP3 inflammasome pathways in human neonates. We show that immature low CD14 expressing/CD16pos monocytes predominate before 33 weeks of gestation, and that these cells lack production of the pro‐IL‐1β precursor protein upon LPS stimulation. In contrast, high levels of pro‐IL‐1β are produced within high CD14 expressing monocytes, although these cells are unable to secrete mature IL‐1β. The lack of secreted IL‐1β in these monocytes parallels a reduction of NLRP3 induction following TLR stimulation resulting in a lack of caspase‐1 activity before 29 weeks of gestation, whereas expression of the apoptosis‐associated speck‐like protein containing a CARD and function of the P2×7 receptor are preserved. Our analyses also reveal a strong inhibitory effect of placental infection on LPS/ATP‐induced caspase‐1 activity in cord blood monocytes. Lastly, secretion of IL‐1β in preterm neonates is restored to adult levels during the neonatal period, indicating rapid maturation of these responses after birth. Collectively, our data highlight important developmental mechanisms regulating IL‐1β responses early in gestation, in part due to a downregulation of TLR‐mediated NLRP3 expression. Such mechanisms may serve to limit potentially damaging inflammatory responses in a developing fetus.

Hierarchical Maturation of Innate Immune Defences in Very Preterm Neonates

Background: Preterm neonates are highly vulnerable to infection. Objectives: To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses. Methods: Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TLR5 (flagellin) and TLR7/8 (R848), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term. Results: TLR responses develop asynchronously in preterm neonates, whereby responses to TLR7/8 were more mature and were followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses. Conclusions: The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group.

Timing of delivery for pregnancies with congenital diaphragmatic hernia

Please cite this paper as: Hutcheon J, Butler B, Lisonkova S, Marquette G, Mayer C, Skoll A, Joseph K. Timing of delivery for pregnancies with congenital diaphragmatic hernia. BJOG 2010;117:1658–1662.

Perinatal and maternal morbidity and mortality among term singletons following midcavity operative vaginal delivery versus caesarean delivery

To quantify severe perinatal and maternal morbidity/mortality associated with midcavity operative vaginal delivery compared with caesarean delivery.

Association Between Prepregnancy Body Mass Index and Severe Maternal Morbidity

Importance Although high body mass index (BMI) is associated with adverse birth outcomes, the association with severe maternal morbidity is unclear. Objective To examine the association between prepregnancy BMI and severe maternal morbidity. Design, Setting, and Participants Retrospective population-based cohort study including all singleton hospital births in Washington State, 2004-2013. Demographic data and morbidity diagnoses were obtained from linked birth certificates and hospitalization files. Exposures Prepregnancy BMI (weight in kilograms divided by height in meters squared) categories included underweight (<18.5), normal BMI (18.5-24.9), overweight (25.0-29.9), obesity class 1 (30.0-34.9), obesity class 2 (35.0-39.9), and obesity class 3 (≥40). Main Outcomes and Measures Composite severe maternal morbidity or mortality included life-threatening conditions and conditions leading to serious sequelae (eg, amniotic fluid embolism, hysterectomy), complications requiring intensive care unit admission, and maternal death. Logistic regression was used to obtain adjusted odds ratios (ORs) and adjusted rate differences with 95% confidence intervals, adjusted for confounders (eg, maternal age and parity). Results Overall, 743 630 women were included in the study (mean age, 28.1 [SD, 6.0] years; 41.4% nulliparous). Prepregnancy BMI was distributed as follows: underweight, 3.2%; normal weight, 47.5%; overweight, 25.8%; obesity class 1, 13.1%; obesity class 2, 6.2%; and obesity class 3, 4.2%. Rates of severe maternal morbidity or mortality were 171.5, 143.2, 160.4, 167.9, 178.3 and 202.9 per 10 000 women, respectively. Adjusted ORs were 1.2 (95% CI, 1.0-1.3) for underweight women; 1.1 (95% CI, 1.1-1.2) for overweight women; 1.1 (95% CI, 1.1-1.2) for women with class 1 obesity; 1.2 (95% CI, 1.1-1.3) for women with class 2 obesity; and 1.4 (95% CI, 1.3-1.5) for women with class 3 obesity compared with women with normal BMI. Absolute risk increases (adjusted rate differences per 10 000 women, compared with women with normal BMI) were 28.8 (95% CI, 12.2-47.2) for underweight women, 17.6 (95% CI, 10.5-25.1) for overweight women, 24.9 (95% CI, 15.7-34.6) for women with class 1 obesity, 35.8 (95% CI, 23.1-49.5) for women with class 2 obesity, and 61.1 (95% CI, 44.8-78.9) for women with class 3 obesity. Conclusions and Relevance Among pregnant women in Washington State, low and high prepregnancy BMI, compared with normal BMI, were associated with a statistically significant but small absolute increase in severe maternal morbidity or mortality.

Perinatal and maternal morbidity and mortality after attempted operative vaginal delivery at midpelvic station

BACKGROUND: Increased use of operative vaginal delivery (i.e., forceps or vacuum application), of which 20% occurs at midpelvic station, has been advocated to reduce the rate of cesarean delivery. We aimed to quantify severe perinatal and maternal morbidity and mortality associated with attempted midpelvic operative vaginal delivery. METHODS: We studied all term singleton deliveries in Canada between 2003 and 2013, by attempted midpelvic operative vaginal or cesarean delivery with labour (with and without prolonged second stage). The primary outcomes were composite severe perinatal morbidity and mortality (e.g., convulsions, assisted ventilation, severe birth trauma and perinatal death), and composite severe maternal morbidity and mortality (e.g., severe postpartum hemorrhage, shock, sepsis, cardiac complications, acute renal failure and death). RESULTS: The study population included 187 234 deliveries. Among women with dystocia and prolonged second stage of labour, midpelvic operative vaginal delivery was associated with higher rates of severe perinatal morbidity and mortality compared with cesarean delivery (forceps, adjusted odds ratio [AOR] 1.81, 95% confidence interval [CI] 1.24 to 2.64; vacuum, AOR 1.81, 95% CI 1.17 to 2.80; sequential instruments, AOR 3.19, 95% CI 1.73 to 5.88), especially with higher rates of severe birth trauma. Rates of severe maternal morbidity and mortality were not significantly different after operative vaginal delivery, although rates of obstetric trauma were higher (forceps, AOR 4.51, 95% CI 4.04 to 5.02; vacuum, AOR 2.70, 95% CI 2.35 to 3.09; sequential instruments, AOR 4.24, 95% CI 3.46 to 5.19). Among women with fetal distress, similar associations were seen for severe birth trauma and obstetric trauma, although vacuum was associated with lower rates of severe maternal morbidity and mortality (AOR 0.52, 95% CI 0.33 to 0.80). Associations tended to be stronger among women without a prolonged second stage. INTERPRETATION: Midpelvic operative vaginal delivery is associated with higher rates of severe birth trauma and obstetric trauma, whereas overall rates of severe perinatal and maternal morbidity and mortality vary by indication and operative instrument.

Ecological association between operative vaginal delivery and obstetric and birth trauma

BACKGROUND: Increased use of operative vaginal delivery (use of forceps, vacuum or other device) has been recommended to address high rates of cesarean delivery. We sought to determine the association between rates of operative vaginal delivery and obstetric trauma and severe birth trauma. METHODS: We carried out an ecological analysis of term, singleton deliveries in 4 Canadian provinces (2004–2014) using data from the Canadian Institute for Health Information. The primary exposure was mode of delivery. The primary outcomes were obstetric trauma and severe birth trauma. RESULTS: Data on 1 938 913 deliveries were analyzed. The rate of obstetric trauma was 7.2% in nulliparous women, and 2.2% and 2.7% among parous women without and with a previous cesarean delivery, respectively, and rates of severe birth trauma were 2.1, 1.7 and 0.7 per 1000, respectively. Each 1% absolute increase in rates of operative vaginal delivery was associated with a higher frequency of obstetric trauma among nulliparous women (adjusted rate ratio [ARR] 1.06, 95% confidence interval [CI] 1.05–1.06), parous women without a previous cesarean delivery (ARR 1.10, 95% CI 1.08–1.13) and parous women with a previous cesarean delivery (ARR 1.11, 95% CI 1.07–1.16). Operative vaginal delivery was associated with more frequent severe birth trauma, but only in nulliparous women (ARR 1.05, 95% CI 1.03–1.07). In nulliparous women, sequential vacuum and forceps instrumentation was associated with the largest increase in obstetric trauma (ARR 1.44, 95% CI 1.35–1.55) and birth trauma (ARR 1.53, 95% CI 1.03–2.27). INTERPRETATION: Increases in population rates of operative vaginal delivery are associated with higher population rates of obstetric trauma, and in nulliparous women with severe birth trauma.

Women’s Health Themes Across the Undergraduate Medical Curriculum at the University of British Columbia

OBJECTIVE The overall objective of the project was to determine whether the current MD undergraduate curriculum at the University of British Columbia (UBC) met the minimum competencies in womens health according to available guidelines. METHODS Ovid and MEDLINE were searched for information on womens health topics in medical undergraduate curricula. The Association of Professors of Obstetrics and Gynaecology (APOG) and the Association of Professors of Gynecology and Obstetrics (APGO) medical student objectives were used as a framework for evaluation of the UBC curriculum. The APGO womens health care competencies for medical students were also compared with these objectives. A comprehensive review ouate of the medical curriculum at UBC was then carried out to analyze whether, when, and where the APOG and APGO objectives were met. RESULTS Of the 93 womens health competencies outlined by APGO, only two were not formally addressed in the UBC curriculum. Almost two thirds (60 of the 93) of the competencies are covered in the obstetrics and gynaecology third-year clerkship, which is just one of the 14 teaching settings available for potential coverage of the womens health care competencies. CONCLUSION Topics in womens health appear to be well addressed by the UBC medical undergraduate curriculum, although this review was unable to determine whether and how extensively these topics were actually delivered.