The effect of omega-3 supplementation on pregnancy outcomes by smoking status.

BACKGROUND: Smoking during pregnancy is associated with adverse maternal and neonatal outcomes such as preterm delivery, intrauterine growth restriction, stillbirth, and low birth weight. Because smoking causes oxidative stress, some have suggested using antioxidants to counteract the effects of oxidative stress. Smokers have lower serum levels of omega-3 fatty acids, an important antioxidant, and thus, investigating whether omega-3 supplementation in smokers reduces adverse maternal and neonatal outcomes represents an important area of research. OBJECTIVE: To investigate whether the antioxidant effect of omega-3 fatty acid supplementation on the incidence of adverse pregnancy outcomes differs between smokers and nonsmokers. STUDY DESIGN: Secondary analysis of a multicenter randomized controlled trial of omega-3 supplementation for preterm delivery prevention in women with a singleton pregnancy and a history of a previous singleton spontaneous preterm delivery. Subjects were randomized to begin omega-3 or placebo before 22 weeks, which was continued until delivery. All women received 17 alpha-hydroxyprogesterone caproate intramuscularly weekly beginning between 16 and 20 weeks of gestation and continued until 36 weeks of gestation or delivery, whichever occurred first. The primary outcome was spontaneous preterm delivery. Secondary outcomes were indicated preterm delivery, any preterm delivery (spontaneous and indicated), pregnancy-associated hypertension (gestational hypertension and preeclampsia), a neonatal composite (retinopathy of prematurity, intraventricular hemorrhage grade III or IV, patent ductus arteriosus, necrotizing enterocolitis, sepsis, respiratory morbidity, or perinatal death), low birth weight (<2500 g), small for gestational age (less than the 10th percentile), and neonatal intensive care unit or intermediate nursery admission. The study population was stratified into smokers and nonsmokers, and the incidence of each outcome was compared by omega-3 supplementation versus placebo in each subgroup. Zelen tests were performed to test for homogeneity of effect in smokers and nonsmokers. RESULTS: Of 851 subjects included in the analysis, 136 (16%) smoked. Baseline characteristics between omega-3 and placebo groups did not differ in smokers or nonsmokers. Omega-3 supplementation was associated with a lower risk of spontaneous preterm delivery in smokers (relative risk, 0.56, 95% confidence interval, 0.36-0.87) but not in nonsmokers (relative risk 1.04, 95% confidence interval 0.84-1.29); P value for interaction = 0.013. Low birth weight was also less frequent in smokers receiving omega-3 supplementation (relative risk 0.57, 95% confidence interval 0.36-0.90) compared with nonsmokers (relative risk 0.93, 95% confidence interval 0.71-1.24); P value for interaction = 0.047. The effect on other secondary outcomes did not differ significantly between smokers and nonsmokers. CONCLUSION: Omega-3 supplementation in smokers may have a protective effect against recurrent spontaneous preterm delivery and low birth weight.

A qualitative assessment of the perceived risks of electronic cigarette and hookah use in pregnancy.

BACKGROUND: Studies reveal that electronic cigarette (e-cigarette) and hookah use are increasing among adolescents and young adults. However, the long-term health effects are unknown, especially with regards to pregnancy. Because of the increased use in women of reproductive age, and the unknown long-term health risks, our primary objectives were to determine the perceived risks of e-cigarette and hookah use in pregnancy, and learn common colloquial terms associated with e-cigarettes. Furthermore, we sought to determine if there is a stigma associated with e-cigarette use in pregnancy. METHODS: Eleven focus groups including 87 participants were conducted immediately following regularly scheduled CenteringPregnancy® prenatal care with women at three different clinics in the greater Houston area. A minimum of two facilitators led the groups, using ten lead-in prompts, with Spanish translation as necessary. Facilitators took notes which were compared immediately following each group discussion and each group was audio recorded and transcribed. Three facilitators utilized NVivo 9.0 software to organize the transcribed data into nodes to identify major themes. To increase rigor, transcripts were further analyzed by two obstetricians who were instructed to find the major themes. RESULTS: Analyses revealed contradicting themes concerning e-cigarette use. In general, e-cigarettes were perceived as safer alternatives to regular tobacco cigarettes, especially if used as smoking cessation devices. A major theme is that use in pregnancy is harmful to the fetus. However, it was perceived that use for smoking cessation in pregnancy may have fewer side effects. We found that a common term for e-cigarettes is "Blu." In our discussion of hookah use, participants perceived use as popular among teenagers and that use in pregnancy is dangerous for the fetus. CONCLUSIONS: Although a strong theme emerged against hookah use, we found contradicting themes in our discussions on e-cigarette use in pregnancy. It is possible that e-cigarette use will not carry the same stigma as regular cigarette smoking in pregnancy. In addition, the impression of e-cigarettes as a healthier alternative to smoking may influence use in pregnancy. Clinicians need to be prepared for questions of e-cigarette safety and efficacy as smoking cessation devices from their pregnant patients who smoke, and women who smoke and are planning to become pregnant.

In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model.

BACKGROUND: Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposure METHODS: Sprague-Dawley rat dams received either saline or 2 mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were killed on day 1 of life, and brain and lung tissues were harvested (N = 3/ group). RESULTS: We found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43-fold; p = 0.03) while acetylation is increased (1.79-fold; p = 0.031). Histone deacetylase activity is significantly decreased with nicotine exposure in brain and lung (0.11-fold; p < 0.001; 0.12-fold; p < 0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25-fold; p = 0.038). CONCLUSION: We conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of histone deacetylase activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction.

Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy?

OBJECTIVE: Late timing of intervention and maternal obesity are potential explanations for the modest effect of aspirin for preeclampsia prevention. We explored whether low-dose aspirin (LDA) is more effective in women at increased risk when initiated before 16 weeks' gestation or given to non-obese women. METHODS: Secondary analysis of a trial to evaluate LDA (60 mg/d) for preeclampsia prevention in high-risk women. Participants were randomized to LDA or placebo between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a) timing of randomization (< 16 or ≥ 16 weeks gestation) and (b) body mass index (BMI) class (non-obese and obese). The Breslow-Day test for homogeneity was used to assess for variations in effect of LDA across gestational age and BMI groups. RESULTS: Of 2503 women, 461 (18.4%) initiated LDA < 16 weeks. LDA effect was not better when initiated < 16 weeks (RR: 0.93, 95% CI: 0.67-1.31) versus ≥ 16 weeks (RR: 0.90, 95% CI: 0.75-1.08), (p value for interaction = 0.87). Similarly, LDA effect was not better in non-obese (RR: 0.91, 95% CI: 0.7-1.13) versus obese women (RR: 0.89, 95% CI: 0.7-1.13), (p value for interaction = 0.85). CONCLUSION: LDA for preeclampsia prevention was not more effective when initiated < 16 weeks or used in non-obese women at risk for preeclampsia. No particular subgroup of women was more or less likely to benefit from LDA therapy.

Higher-dose oxytocin to prevent obstetric hemorrhage at vaginal delivery-does duration of infusion matter?

OBJECTIVE: Postpartum higher-dose oxytocin (80 U) compared with lower dose (10 U) given in 500 mL over 1 hour does not decrease postpartum hemorrhage (PPH) requiring treatment, but reduces the risk of hematocrit decline ≥ 6% among women delivering vaginally. Our objective was to evaluate whether the duration of administration of oxytocin influences outcomes. STUDY DESIGN: We compared a cohort receiving a postpartum oxytocin infusion of 80 U/500 mL over 1 hour to a concurrent cohort of women receiving 80 U/500 mL over 8 hours. The primary outcome was any treatment of PPH (uterotonics, blood transfusion, tamponade, and surgery). Secondary outcomes included pre- to postdelivery median hematocrit change and hematocrit decline ≥ 6%. RESULTS: There were 653 and 676 women identified in the 1- and 8-hour cohorts, respectively. There was no difference in PPH requiring any treatment between the 1- and 8-hour cohorts (6 vs. 6%, p = 0.70). There were no differences in individual treatment components including blood transfusion (p = 0.75). Median hematocrit decline (p = 0.02) was lower in the 8-hour cohort, but there was no difference in frequency of hematocrit decline ≥ 6% (p = 0.15). Results were unchanged by multivariable adjustments. CONCLUSIONS: Postpartum higher-dose oxytocin administered over 1 hour compared with 8 hours was not associated with an increased treatment of PPH or frequency of hematocrit decline ≥ 6%.

Maternal tobacco use is associated with increased markers of oxidative stress in the placenta.

OBJECTIVE: We sought to extend our prior observations and histopathologically characterize key metabolic enzymes (CYP1A1) with markers of oxidative damage in the placental sections from smokers. STUDY DESIGN: Placental specimens were collected from term singleton deliveries from smokers (n = 10) and nonsmokers (n = 10) and subjected to a detailed histopathological examination. To quantify the extent of oxidative damage, masked score-graded (0-6) histopathology against 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxydeoxyguanisine (8-OHdG) was performed. Minimal significance (P < .05) was determined with a Fisher's exact and a 2-tailed Student t test as appropriate. RESULTS: We observed a significant increase in the presence of syncytial knots in placentas from smokers (70% vs 10%, P = .02). These gross observations were accompanied by a significant aberrant placental aromatic hydrocarbon metabolism (increased CYP1A1, 4.4 vs 2.1, P = .002) in addition to evidence of oxidative damage (4-HNE 3.4 vs 1.1, P = .00005; 8-OHdG 4.9 vs 3.1, P = .0038). CONCLUSION: We observed a strong association between maternal tobacco use and aberrant placental metabolism, syncytial knot formation, and multiple markers of oxidative damage.