Roxana Odouli

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study

Abstract Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage. Design Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview. Setting Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States. Participants 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days. Main outcome measures Pregnancy outcomes up to 20 weeks of gestation. Results 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use. Conclusion Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.

A population-based prospective cohort study of personal exposure to magnetic fields during pregnancy and the risk of miscarriage.

To study the effect of magnetic fields on the risk of miscarriage, we conducted a population-based prospective cohort study among pregnant women within a large health maintenance organization. All women with a positive pregnancy test at less than 10 weeks of gestation and residing in the San Francisco area were contacted for participation in the study. We conducted in-person interviews to obtain information on risk factors for miscarriage and other potential confounders. All participants were also asked to wear a magnetic field-measuring meter for 24 hours and to keep a diary of their activities. Pregnancy outcomes were obtained for all participants by searching the health maintenance organization’s databases, reviewing medical charts, and telephone follow-up. We used the Cox proportional hazard model for examining the magnetic field-miscarriage association. A total of 969 subjects were included in the final analyses. Although we did not observe an association between miscarriage risk and the average magnetic field level, miscarriage risk increased with an increasing level of maximum magnetic field exposure with a threshold around 16 milligauss (mG). The rate ratio (RR) associated with magnetic field exposure ≥16 mG (vs <16 mG) was 1.8 [95% confidence interval (CI) = 1.2–2.7]. The risk remained elevated for levels (in tertiles) of maximum magnetic field exposure ≥16 mG. The association was stronger for early miscarriages (<10 weeks of gestation) (RR = 2.2, 95% CI = 1.2–4.0) and among “susceptible” women with multiple prior fetal losses or subfertility (RR = 3.1, 95% CI = 1.3–7.7). After excluding women who indicated that their daily activity pattern during the measurements did not represent their typical daily activity during pregnancy, the association was strengthened; RR = 2.9 (95% CI = 1.6–5.3) for maximum magnetic field exposure ≥16 mG, RR = 5.7 (95% CI = 2.1–15.7) for early miscarriage, and RR = 4.0 (95% CI = 1.4–11.5) among the susceptible women. Our findings provide strong prospective evidence that prenatal maximum magnetic field exposure above a certain level (possibly around 16 mG) may be associated with miscarriage risk. This observed association is unlikely to be due to uncontrolled biases or unmeasured confounders.

Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study

OBJECTIVE The objective of the study was to examine whether the risk of miscarriage is associated with caffeine consumption during pregnancy after controlling for pregnancy-related symptoms. STUDY DESIGN This was a population-based prospective cohort study. RESULTS An increasing dose of daily caffeine intake during pregnancy was associated with an increased risk of miscarriage, compared with no caffeine intake, with an adjusted hazard ratio (aHR) of 1.42 (95% confidence interval 0.93 to 2.15) for caffeine intake of less than 200 mg/day, and aHR of 2.23 (1.34 to 3.69) for intake of 200 or more mg/day, respectively. Nausea or vomiting during pregnancy did not materially affect this observed association, nor did the change in intake pattern of caffeine during pregnancy. In addition, the magnitude of the association appeared to be stronger among women without a history of miscarriage (aHR 2.33, 1.48 to 3.67) than that among women with such a history (aHR 0.81, 0.34 to 1.94). CONCLUSION Our results demonstrated that high doses of caffeine intake during pregnancy increase the risk of miscarriage, independent of pregnancy-related symptoms.

Presence of depressive symptoms during early pregnancy and the risk of preterm delivery: a prospective cohort study

BACKGROUND The impact of prenatal depression on pregnancy outcomes is largely unknown. METHODS We conducted a population-based prospective cohort study among pregnant women of the Kaiser Permanente Medical Care Program to examine the impact of prenatal depression on the risk of preterm delivery. We interviewed pregnant women in their early pregnancy. Womens depressive symptoms were ascertained using the standard Center for Epidemiological Studies Depression Scale (CESD). The presence of significant prenatal depressive symptoms and severe depressive symptoms was determined by CESD scores > or =16 and > or =22, respectively. RESULTS Among the 791 participants who answered CESD questions and delivered a live birth, after controlling for potential confounders using the Cox proportional hazard regression, women with CESD scores > or =16 had almost twice the risk of preterm delivery compared with women without depressive symptoms: adjusted hazard ratio (aHR) = 1.9, 95% confidence interval (CI) 1.0-3.7. The risk of preterm delivery increased with increasing severity of depression: aHR = 1.6 (CI 0.7-3.6) for CESD 16-21 and aHR = 2.2 (CI 1.1-4.7) for CESD > or =22. The risk of preterm delivery associated with prenatal depression appears to be exacerbated by low educational level, a history of fertility problems and the presence of obesity and stressful events. The observed associations were not confounded by the use of antidepressants, although some of the associations did not reach statistical significance. CONCLUSIONS Our findings show that pregnant women with depressive symptoms are at increased risk of preterm delivery and, in addition, provide preliminary evidence that social and reproductive risk factors as well as obesity and stressful events may exacerbate the effect.

Use of a dummy (pacifier) during sleep and risk of sudden infant death syndrome (SIDS) : population based case-control study

Abstract Objectives To examine the association between use of a dummy (pacifier) during sleep and the risk of sudden infant death syndrome (SIDS) in relation to other risk factors. Design Population based case-control study. Setting Eleven counties in California. Participants Mothers or carers of 185 infants whose deaths were attributed to SIDS and 312 randomly selected controls matched for race or ethnicity and age. Main outcome measure Use of a dummy during sleep determined through interviews. Results The adjusted odds ratio for SIDS associated with using a dummy during the last sleep was 0.08 (95% confidence interval 0.03 to 0.21). Use was associated with a reduction in risk in every category of sociodemographic characteristics and risk factors examined. The reduced risk associated with use seemed to be greater with adverse sleep conditions (such as sleeping prone or on side and sleeping with a mother who smoked), although the observed interactions were not significant. In addition, use of a dummy may reduce the impact of other risk factors for SIDS, especially those related to adverse sleep environment. For example, infants who did not use a dummy and slept prone or on their sides (v on their back) had an increased risk of SIDS (2.61, 1.56 to 4.38). In infants who used dummies, there was no increased risk associated with sleeping position (0.66, 0.12 to 3.59). While cosleeping with a mother who smoked was also associated with increased risk of SIDS among infants who did not use a dummy (4.5, 1.3 to 15.1), there was no such association among those who did (1.1, 0.1 to 13.4). Conclusions Use of a dummy seems to reduce the risk of SIDS and possibly reduces the influence of known risk factors in the sleep environment.

Effectiveness of Seasonal Trivalent Influenza Vaccine for Preventing Influenza Virus Illness Among Pregnant Women: A Population-Based Case-Control Study During the 2010–2011 and 2011–2012 Influenza Seasons

BACKGROUND Although vaccination with trivalent inactivated influenza vaccine (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE) studies of TIV in pregnant women have assessed laboratory-confirmed influenza outcomes. METHODS We conducted a case-control study over 2 influenza seasons (2010-2011 and 2011-2012) among Kaiser Permanente health plan members in 2 metropolitan areas in California and Oregon. We compared the proportion vaccinated among 100 influenza cases (confirmed by reverse transcription polymerase chain reaction) with the proportions vaccinated among 192 controls with acute respiratory illness (ARI) who tested negative for influenza and 200 controls without ARI (matched by season, site, and trimester). RESULTS Among influenza cases, 42% were vaccinated during the study season compared to 58% and 63% vaccinated among influenza-negative controls and matched ARI-negative controls, respectively. The adjusted VE of the current season vaccine against influenza A and B was 44% (95% confidence interval [CI], 5%-67%) using the influenza-negative controls and 53% (95% CI, 24%-72%) using the ARI-negative controls. Receipt of the prior seasons vaccine, however, had an effect similar to receipt of the current seasons vaccine. As such, vaccination in either or both seasons had statistically similar adjusted VE using influenza-negative controls (VE point estimates range = 51%-76%) and ARI-negative controls (48%-76%). CONCLUSIONS Influenza vaccination reduced the risk of ARI associated with laboratory-confirmed influenza among pregnant women by about one-half, similar to VE observed among all adults during these seasons.

Neonatal hyperbilirubinemia and risk of autism spectrum disorders.

Objective. To investigate the association between neonatal hyperbilirubinemia and autism spectrum disorders (ASD). Methods. We conducted a large case-control study nested within the cohort of singleton term infants born between 1995 and 1998 at a northern California Kaiser Permanente hospital. Case subjects (n = 338) were children with an ASD diagnosis recorded in Kaiser Permanente outpatient databases; control subjects (n = 1817) were children without an ASD diagnosis, who were randomly sampled and frequency-matched to case subjects according to gender, birth year, and birth hospital. Results. Approximately 28% of case and control subjects received ≥1 bilirubin test in the first 30 days of life. No case-control differences were observed for maximal bilirubin levels of ≥15 mg/dL (10.1% vs 12.1%), ≥20 mg/dL (2.1% vs 2.5%), or ≥25 mg/dL (0.3% vs 0.2%). Compared with children whose maximal neonatal bilirubin levels were <15 mg/dL or not measured, children with any degree of bilirubin level elevation were not at increased risk of ASD, after adjustment for gender, birth facility, maternal age, maternal race/ethnicity, maternal education, and gestational age (for bilirubin levels of 15-19.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.5-1.2; for bilirubin levels of 20-24.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.3-1.6; for bilirubin levels of ≥25 mg/dL: odds ratio: 1.1; 95% confidence interval: 0.1-11.2). Conclusion. These data suggest that neonatal hyperbilirubinemia is not a risk factor for ASD.

Congenital anomalies associated with autism spectrum disorders.

This study examined whether major congenital structural anomalies identified in infancy occurred more frequently in children later diagnosed with autism spectrum disorders (ASD; n=417; 341 males, 76 females) than in comparison children (n=2,067; 1,681 males, 386 females). Participants were sampled from infants born at Kaiser Permanente Northern California facilities between 1995 and 1999 who remained health plan members for at least 2 years (n=88,163). Comparison children were frequency-matched to children with ASD according to sex, birth year, and birth hospital. Congenital anomalies were diagnosed in 10.8% of children with ASD and 6.2% of comparison children (crude odds ratio [ORc] 1.8, 95% confidence interval [CI] 1.3-2.6). This association remained significant after adjustment for key maternal and infant covariates (adjusted OR [ORa] 1.7, 95% CI 1.1-2.4). Almost all organ-system anomaly categories were more prevalent in children with ASD, however only gastrointestinal anomalies were significantly associated with ASD in adjusted analyses (1.9 vs 0.4%, ORa 5.1, 95% CI 1.8-14.1).

Maternal Exposure to Magnetic Fields During Pregnancy in Relation to the Risk of Asthma in Offspring

OBJECTIVE To determine whether maternal exposure to high levels of magnetic fields (MFs) during pregnancy is associated with the risk of asthma in offspring. DESIGN A prospective cohort study. SETTING Kaiser Permanente Northern California. PARTICIPANTS Pregnant Kaiser Permanente Northern California members in the San Francisco area. MAIN OUTCOME MEASURES Asthma was clinically diagnosed among 626 children who were followed up for as long as 13 years. All participants carried a meter to measure their MF levels during pregnancy. RESULTS After adjustment for potential confounders, a statistically significant linear dose-response relationship was observed between increasing maternal median daily MF exposure level in pregnancy and an increased risk of asthma in offspring: every 1-mG increase of maternal MF level during pregnancy was associated with a 15% increased rate of asthma in offspring (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04-1.27). Using the categorical MF level, the results showed a similar dose-response relationship: compared with the children whose mothers had a low MF level (median 24-hour MF level, ≤0.3 mG) during pregnancy, children whose mothers had a high MF level (>2.0 mG) had more than a 3.5-fold increased rate of asthma (aHR, 3.52; 95% CI, 1.68-7.35), while children whose mothers had a medium MF level (>0.3-2.0 mG) had a 74% increased rate of asthma (aHR, 1.74; 95% CI, 0.93-3.25). A statistically significant synergistic interaction was observed between the MF effect and a maternal history of asthma and birth order (firstborn). CONCLUSION Our findings provide new epidemiological evidence that high maternal MF levels in pregnancy may increase the risk of asthma in offspring.

Use of a Fan During Sleep and the Risk of Sudden Infant Death Syndrome

OBJECTIVE To examine the relation between room ventilation during sleep and risk of sudden infant death syndrome (SIDS). DESIGN Population-based case-control study. SETTING Eleven California counties. PARTICIPANTS Mothers of 185 infants with a confirmed SIDS diagnosis and 312 randomly selected infants matched on county of residence, maternal race/ethnicity, and age. Intervention Fan use and open window during sleep. Main Outcome Measure Risk of SIDS. RESULTS Fan use during sleep was associated with a 72% reduction in SIDS risk (adjusted odds ratio [AOR], 0.28; 95% confidence interval [CI], 0.10-0.77). The reduction in SIDS risk seemed more pronounced in adverse sleep environments. For example, fan use in warmer room temperatures was associated with a greater reduction in SIDS risk (AOR, 0.06; 95% CI, 0.01-0.52) compared with cooler room temperatures (0.77; 0.22-2.73). Similarly, the reduction associated with fan use was greater in infants placed in the prone or side sleep position (AOR, 0.14; 95% CI, 0.03-0.55) vs supine (0.84; 0.21-3.39). Fan use was associated with a greater reduction in SIDS risk in infants who shared a bed with an individual other than their parents (AOR, 0.15; 95% CI, 0.01-1.85) vs with a parent (0.40; 0.03-4.68). Finally, fan use was associated with reduced SIDS risk in infants not using pacifiers (AOR, 0.22; 95% CI, 0.07-0.69) but not in pacifier users (1.99; 0.16-24.4). Some differences in the effect of fan use on SIDS risk did not reach statistical significance. CONCLUSION Fan use may be an effective intervention for further decreasing SIDS risk in infants in adverse sleep environments.