De-Kun Li

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.

Urine bisphenol-A (BPA) level in relation to semen quality

OBJECTIVE To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality. DESIGN Cohort study. SETTING Four regions in China where high exposure to BPA in the workplace existed. PATIENT(S) 218 men with and without BPA exposure in the workplace. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Semen parameters. RESULT(S) After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant. CONCLUSION(S) These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality.

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.

Bisphenol A levels in blood and urine in a Chinese population and the personal factors affecting the levels

The objective of the study was to describe the background bisphenol A (BPA) levels in urine and serum of a Chinese population without occupational exposure and to examine the personal characteristics influencing these levels. Workers from 10 factories and their family members were recruited and their peripheral blood and spot urine samples were collected. The conjugated and free BPA of the samples was assayed with high-performance liquid chromatography. The exposure levels were checked with 2-independent-samples test, and the potential personal factors influencing exposure levels were analyzed using nonlinear correlation. Of the total of 952 subjects participating in the study, urine and blood samples were taken from 97% and 93% of them, respectively. The detectable rates were 50% for urine samples and 17% for serum samples, given the detection limit of 0.31 microg/L for urine and 0.39 microg/L for serum. The arithmetic mean (AM) and geometric mean (GM) of non-creatinine-adjusted urinary BPA level were 10.45 and 0.87 microg/L, which became 24.93 and 0.38 microg/g Cr after the creatinine level was adjusted; serum BPA levels were 2.84 microg/L (AM) and 0.18 microg/L (GM). Males and those with smoking habit had higher biological burden of BPA. The results indicated that half of the study subjects had detectable BPA in their urine samples. BPA levels were influenced by gender and smoking status. The sources of non-occupational BPA exposures should be explored.

Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study

Objective To examine a reported association between use of angiotensin converting enzyme (ACE) inhibitors during the first trimester and risk of malformations in offspring. Design A population based, retrospective cohort study linking automated clinical and pharmacy databases including comprehensive electronic medical records. Participants Pregnant women and their live born offspring (465 754 mother-infant pairs) in the Kaiser Permanente Northern California region from 1995 to 2008. Main outcome measure Congenital malformation in live births. Results The prevalence of ACE inhibitor use in the first trimester only was 0.9/1000, and the use of other antihypertensive medications was 2.4/1000. After adjustment for maternal age, ethnicity, parity, and obesity, use of ACE inhibitors during the first trimester only seemed to be associated with increased risk of congenital heart defects in offspring compared with normal controls (those with neither hypertension nor use of any antihypertensives during pregnancy) (15/381 (3.9%) v 6232/400 021 (1.6%) cases, odds ratio 1.54 (95% confidence interval 0.90 to 2.62)). A similar association was observed for use of other antihypertensives (28/1090 (2.6%) cases of congenital heart defects, odds ratio 1.52 (1.04 to 2.21)). However, compared with hypertension controls (those with a diagnosis of hypertension but without use of antihypertensives) (708/29 735 (2.4%) cases of congenital heart defects), neither use of ACE inhibitors or of other antihypertensives in the first trimester was associated with increased congenital heart defects risk (odds ratios 1.14 (0.65 to 1.98) and1.12 (0.76 to 1.64) respectively). Conclusions Maternal use of ACE inhibitors in the first trimester has a risk profile similar to the use of other antihypertensives regarding malformations in live born offspring. The apparent increased risk of malformations associated with use of ACE inhibitors (and other antihypertensives) in the first trimester is likely due to the underlying hypertension rather than the medications.

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.

Relationship Between Urine Bisphenol-A Level and Declining Male Sexual Function

The adverse effect of bisphenol-A (BPA) on the male reproductive system observed in animal studies has not been well examined in human populations. BPA is potentially a serious public health problem because of its widely detected presence in the human body. This study was conducted among 427 male workers in regions where high levels of BPA exposure existed. All participants provided urine samples, which were tested for BPA concentration using high-performance liquid chromatography. Male sexual dysfunction was ascertained using standard male sexual function inventories. Male sexual dysfunction was measured in 4 domains using 7 indices. After controlling for potential confounders using linear regression, increasing urine BPA level was associated with worsening male sexual function on a continuous scale. All 7 indices demonstrated this negative linear correlation. Increasing urine BPA level was associated with decreased sexual desire (P < .001), more difficulty having an erection (P < .001), lower ejaculation strength (P < .001), and lower level of overall satisfaction with sex life (P < .01). A similar negative correlation was also observed among participants exposed to BPA from only environmental sources (no occupational exposure to BPA), although the estimates in this group were less stable because of a smaller sample size. Our results reveal a correlation between a biological measure of urine BPA level and declining male sexual function. This finding may enhance the understanding of the BPA effect in human populations, and may have important public health implications given the widespread human exposure to BPA.

A systematic review to calculate background miscarriage rates using life table analysis.

The objectives of the current study were to calculate: (1) the expected rates of miscarriage by gestational week; (2) the cumulative risk of miscarriage; and (3) the remaining risk of miscarriage for gestational weeks five through 20, through a systematic review of the literature. We searched MEDLINE for articles published in English through the end of 2009. References of articles were also searched. Four studies were identified to have the three necessary pieces of information for the proposed calculations: (1) gestational age at study entry, (2) pregnancy outcome; and (3) the gestational age at which the pregnancy outcome occurred. Data were extracted from each study and Life Table Analysis Methods were conducted. Weekly miscarriage rates varied in the early gestational weeks with the highest rate documented at >20 miscarriages per 1000 women-weeks at each week of gestation prior to week 13. By week 14, the rate for all studies became relatively comparable and fell below 10 miscarriages per 1000 woman-weeks at risk and fell even lower through week 20. The cumulative risk of miscarriage for weeks 5 through 20 of gestation ranged from 11 miscarriages per 100 women to 22 miscarriages per 100 women (11-22%). Based on data from comparable study populations, a range of background miscarriage rates by week of gestation for weeks 5 through 20, the cumulative risk of miscarriage, and the remaining risk of miscarriage are presented. Wider variation of miscarriage rates and risks occurred early in gestation (<14 weeks).

In utero exposure to bisphenol-A and its effect on birth weight of offspring☆

To examine the effect of in utero BPA exposure on the birth weight of offspring, a total of 587 children from families in which parent(s) did or did not have occupational exposure to BPA were examined. Their birth weights were obtained by an in-person interview of the mother. Parental BPA exposure level during the index pregnancy was determined through personal air sampling measurements and exposure history. After controlling for potential confounders, parental exposure to BPA in the workplace during pregnancy was associated with decreased birth weight. The association was stronger for maternal exposure which is statistically significant (P=0.02). A dose-response relationship was observed with increased BPA exposure levels in pregnancy associated with greater magnitude of decrease of birth weight in offspring (P=0.003). Our findings provide the new epidemiologic evidence suggesting that in utero exposure to BPA during pregnancy may be associated with decreased birth weight in offspring.

Occupational Exposure Levels of Bisphenol A among Chinese Workers

Occupational Exposure Levels of Bisphenol A among Chinese Workers: Yonghua He, et al. School of Public Health/WHO Collaborating Center for Occupational Health, Fudan University, PR China