B. Anthony Armson

A Randomized Trial of Planned Cesarean or Vaginal Delivery for Twin Pregnancy

BACKGROUND Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy. METHODS We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison. RESULTS A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the planned-vaginal-delivery group (mean number of days from randomization to delivery, 12.4 vs. 13.3; P=0.04). There was no significant difference in the composite primary outcome between the planned-cesarean-delivery group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to 1.74; P=0.49). CONCLUSIONS In twin pregnancy between 32 weeks 0 days and 38 weeks 6 days of gestation, with the first twin in the cephalic presentation, planned cesarean delivery did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00187369; Current Controlled Trials number, ISRCTN74420086.).

Perinatal outcomes in women with asthma during pregnancy

Objective To determine whether adverse perinatal outcome is associated with asthma or asthma medication use during pregnancy. Methods A retrospective cohort study was conducted of women who resided in Halifax County, Nova Scotia, and delivered between 1991 and 1993. Asthmatic women were classified into three groups, according to medication usage: no medications, beta agonists only, and steroids with or without other asthma medications. Outcomes compared among asthmatic and nonasthmatic women included maternal complications (pregnancy-induced hypertension, cesarean delivery, gestational diabetes, preterm birth, and antepartum and postpartum hemorrhage) and neonatal outcomes (low birth weight, congenital malformations, hyperbilirubinemia, and respiratory distress syndrome). Results The cohort included 817 asthmatic women and 13,709 nonasthmatic women. Overall, the prevalence of pregnancies complicated by asthma increased from 4.8% in 1991 to 6.9% in 1993. Asthmatic women were at increased risk for antepartum and postpartum hemorrhage, independent of medication usage. Asthmatic women taking steroids were at increased risk for pregnancy-induced hypertension (odds ratio [OR] 1.7; 95% confidence interval [CI] 1.0, 2.9). The only significant difference in neonatal outcome between asthma medication groups and nonasthmatic women was of an increased risk of hyperbilirubinemia in infants of women taking steroids (OR 1.9; 95% CI 1.1, 3.4). Conclusion Risk of antepartum and postpartum hemorrhage is increased in asthmatic women, independent of medication usage. The increased incidence of neonatal hyperbilirubinemia and the borderline increased risk of pregnancy-induced hypertension may be complications of steroid use or may be related to poorly controlled asthma.

The role of prenatal, obstetric and neonatal factors in the development of autism.

We conducted a linked database cohort study of infants born between 1990 and 2002 in Nova Scotia, Canada. Diagnoses of autism were identified from administrative databases with relevant diagnostic information to 2005. A factor representing genetic susceptibility was defined as having an affected sibling or a mother with a history of a psychiatric or neurologic condition. Among 129,733 children, there were 924 children with an autism diagnosis. The results suggest that among those with low genetic susceptibility, some maternal and obstetric factors may have an independent role in autism etiology whereas among genetically susceptible children, these factors appear to play a lesser role. The role of pre-pregnancy obesity and excessive weight gain during pregnancy on autism risk require further investigation.

Neonatal outcomes with placenta previa

OBJECTIVE To identify neonatal complications associated with placenta previa. METHODS This was a population-based, retrospective cohort study involving all singleton deliveries in Nova Scotia from 1988 to 1995. The study group consisted of all completed singleton pregnancies complicated by placenta previa; all other singleton pregnancies were considered controls. Patient information was collected from the Nova Scotia Atlee perinatal database. Neonatal complications were evaluated while controlling for potential confounders. The data were analyzed using chi2, Fisher exact test, and multiple logistic regression. RESULTS Among 92,983 pregnancies delivered during the study period, 305 cases of placenta previa were identified (0.33%). After controlling for potential confounders, neonatal complications significantly associated with placenta previa included major congenital anomalies (odds ratio [OR] 2.48), respiratory distress syndrome (OR 4.94), and anemia (OR 2.65). The perinatal mortality rate associated with placenta previa was 2.30% (compared with 0.78% in controls) and was explained by gestational age at delivery, occurrence of congenital anomalies, and maternal age. Although there was a higher rate of preterm births in the placenta previa group (46.56% versus 7.27%), there was no difference in birth weights between groups after controlling for gestational age at delivery. CONCLUSION Neonatal complications of placenta previa included preterm birth, congenital anomalies, respiratory distress syndrome, and anemia. There was no increased occurrence of fetal growth restriction.

Exposure assessment in epidemiologic studies of adverse pregnancy outcomes and disinfection byproducts

A major challenge in studies that examine the association between disinfection byproducts in drinking water and pregnancy outcomes is the accurate representation of a subjects exposure. We used household water samples and questionnaire information on water-use behavior to examine several aspects of exposure assessment: (i) the distribution and correlation of specific disinfection byproducts, (ii) spatial distribution system and temporal variation in byproduct levels, and (iii) the contribution of individual water-use behavior. The level of specific trihalomethanes (THMs) and haloacetic acids (HAAs) was determined for 360 household water samples in Eastern Ontario and Nova Scotia. Subjects were interviewed regarding tap water ingestion and showering and bathing practices. In both provinces, total THMs correlated highly with chloroform (correlation coefficient (r) >0.95) and less so with total HAAs (r=0.74 in Nova Scotia and r=0.52 in Ontario). The correlation between total THMs and bromodichloromethane was high in Nova Scotia (r=0.63), but low in Ontario (r=0.26). The correlation was between THM level in individual household samples, and the mean THM level during the same time period from several distribution system samples was 0.63, while a higher correlation in THM level was observed for samples taken at the same location 1 year apart (r=0.87). A correlation of 0.73 was found between household THM level and a total exposure measure incorporating ingestion, showering, and bathing behaviors. These results point to the importance of: measurement of different classes of byproducts; household rather than distribution system sampling; and, incorporation of subject behaviors in exposure assessment in epidemiologic studies of disinfection byproducts and adverse pregnancy outcomes.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth

OBJECTIVE: To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose–response relationship between number of courses of antenatal corticosteroids and neonatal size. METHODS: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. RESULTS: Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: −0.428 weeks, CI −0.10264 to −0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (−33.50 g, CI −66.27120 to −0.72880; P=.045), length (−0.339 cm, CI −0.6212 to −0.05676]; P=.019), and head circumference (−0.296 cm, −0.45672 to −0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. CONCLUSION: Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose–response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. LEVEL OF EVIDENCE: II

Evaluation of maternal fluid dynamics during tocolytic therapy with ritodrine hydrochloride and magnesium sulfate

OBJECTIVE The purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics. STUDY DESIGN Fourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data. RESULTS Ritodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine. CONCLUSIONS Sodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy.

Preterm Prelabour Rupture of Membranes: Effect of Latency on Neonatal and Maternal Outcomes

OBJECTIVES To compare risks of infection and prematurity-related outcomes according to latency periods among women with preterm prelabour rupture of membranes (PPROM). METHODS Women with PPROM occurring between 24+0 and 36+6 weeks of gestation were identified from a provincial population-based perinatal database in Nova Scotia. The primary outcomes included composite variables for serious maternal and neonatal infectious morbidity and neonatal prematurity-related morbidity. Logistic regression was used to quantify the relationship between latency period (< 24 hours, 24 hours to < 48 hours, 48 hours to < 7 days, and ≥ 7 days) and maternal and neonatal outcomes. Separate analyses were conducted for gestational age groups 24+0 to 33+6 weeks and 34+0 to 36+6 weeks. RESULTS There were 4329 women included in the cohort. The composite variables representing serious maternal or neonatal infectious morbidity were not significantly associated with latency for either gestational age group. For PPROM occurring at gestational ages of 24+0 to 33+6 weeks, the odds of neonatal prematurity-related morbidity were significantly decreased at the latency periods of 48 hours or more compared with < 24 hours latency. For PPROM at 34+0 to 36+6 weeks of gestation, the odds of prematurity-related morbidity at 48 hours to < 7 days latency was decreased compared with latencies < 24 hours (OR 0.4; 95% CI 0.2 to 0.8). CONCLUSION Postponing delivery following PPROM may contribute to less prematurity-related morbidity, even close to term, without putting mother or neonate at substantial risk for serious infectious morbidity. Generalization of these findings to other obstetric populations should be informed by the underlying risk of infection.

Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy.

BACKGROUND Vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D), has been shown in some studies to be inversely associated with gestational diabetes risk. Recently, it has been suggested that maternal smoking status may modify this relationship. We explored the association between 25(OH)D concentration and gestational diabetes and determined if there was an interaction between smoking and 25(OH)D. METHODS A nested case-control study was conducted in Halifax, Nova Scotia and Quebec City, Quebec. Women were recruited before 20 weeks gestation and 25(OH)D was measured. Cases were women who developed gestational diabetes and controls were frequency matched to cases on study site, gestational age at blood draw, and season and year of blood draw. Logistic regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI). Models were tested for multiplicative and additive interaction, which was estimated by relative excess risk due to interaction (RERI). RESULTS The study included 395 gestational diabetes cases and 1925 controls. Women who smoked during pregnancy and had 25(OH)D concentrations <30 nmol/L had an aOR = 3.73 [95% CI 1.95, 7.14] compared to non-smokers with 25(OH)D concentrations ≥50 nmol/L. Additive interaction was detected between smoking status and 25(OH)D [RERI = 2.44, 95% CI 0.03, 4.85]. CONCLUSION Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes.

Impact of Participation in the Halifax County Preterm Birth Prevention Project

OBJECTIVES (1). To determine if participation in the Halifax County Preterm Birth Prevention Project (HCPBPP) reduced the risk of preterm birth; (2). to evaluate the degree to which specific components of the HCPBPP contributed to preterm-birth risk reduction. METHODS A nested case-control study was conducted among women residing in Halifax County who gave birth at the IWK Grace Health Centre during the final year of the HCPBPP. Cases, defined as women who delivered preterm (<37 weeks), and controls, defined as women who delivered at full term, were recruited to complete interviewer-administered questionnaires. Three controls per case were sequentially selected. The exposures of interest were overall participation and compliance with specific components of the program. Univariate and multivariate statistical methods were employed to evaluate the effect of exposure to the preterm-birth prevention program. RESULTS Seventy cases and 210 controls were enrolled in the study. Although 82% of subjects participated in some aspect of the HCPBPP, only 8% of high-risk and 6% of low-risk women complied fully with program recommendations. Exposure to project educational strategies or pelvic examinations provided no protective benefit for preterm birth in low-risk or high-risk women. However, compliance with prenatal care providers recommendations to restrict activity or monitor for uterine contractions by self-palpation was associated with a marked reduction in the risk of preterm birth among low-risk women (odds ratio, 0.20; 95% confidence interval, 0.08 0.50). CONCLUSION Although full participation in the HCPBPP protocol was limited, the findings of this case-control study suggest that activity restriction and uterine activity monitoring by self-palpation may reduce the likelihood of preterm birth in women with no identifiable risk factors for prematurity.