Folic acid sensitive birth defects in association with intrauterine exposure to folic acid antagonists

Since the protective effect of folic acid (FA) on birth defects is well known, it is reasonable to assume intrauterine exposure to FA antagonists increases the risk on these defects. We have therefore performed case-control analyses to investigate the risk of intrauterine exposure to FA antagonists, using data on births from the EUROCAT Northern Netherlands registry from 1997 to 2002. Of the 815 cases, 11 were exposed to a FA antagonist compared to 16 of the 1402 controls. For FA sensitive defects as a group, the study showed no effect after exposure to a FA antagonist (odds ratio (OR)=1.18, 95% CI: 0.55-2.57). We found no effect after exposure to a dihydrofolate reductase inhibitor (DHFRI) (OR 0.44, 95% CI: 0.12-1.54), but we did find a statistically significant effect after exposure to an antiepileptic drug (OR=3.45, 95% CI: 1.04-11.48). This study supports the findings of various other studies on the teratogenicity of antiepileptics. An association between DHFRIs and FA sensitive defects was not found.     

A case-control study on determinants of rickets

A case-control study on rickets was performed on 156 cases and 307 controls admitted to Birla pediatric wards, Yekatit 12 Hospital. The following factors were significantly (p < 0.05) associated with diagnosis of rickets in univariate analysis: male gender, being a twin, abnormal birth weight, malnutrition, higher birth order, higher number of siblings, having a caretaker who is not the mother, lower education of the caretaker, having a caretaker who is not housewife, and with protective effect, exposure to sunshine (in number of days per week, duration of daily exposure in minutes, and not wearing clothes during exposure). In multivariate analysis, the following factors remained independently associated with diagnosis of rickets in children: being a twin (OR = 5.86, 95% CI = 1.40-24.50), history of high birth weight (OR = 8.94, 95% CI = 2.30-34.70), moderate and severe malnutrition (OR = 5.64, 95% CI = 2.30-13.80 for severe malnutrition when compared to normal weight), having the grand mother as caretaker (OR = 19.80, 95% CI = 3.70-104.70), and with protective effect, exposure to sunshine (OR associated with an increase of one day of exposure per week = 0.65, 95% CI 0.55-0.77; OR associated with daily exposure of more than 30 minutes, when compared to less than 15 minutes = 0.24, 95% CI = 0.09-0.64; and OR associated with being nude while exposed to sunshine = 0.32, 95% CI = 0.14-0.73). There was no significant difference between cases and controls in marital status or religion of the caretakers.     

Association of maternal arsenic exposure with birth size: A systematic review and meta-analysis

ObjectivesChronic exposure to arsenic during pregnancy or early life continues to be a major global health problem worldwide, affecting hundreds of millions of people. However, its effects on birth size are uncertain. The aim of this study is to summarized the association between maternal arsenic exposure and birth size.MethodsA comprehensive literature search was conducted on the maternal arsenic exposure and birth size (birth weight, birth length, head circumference and chest circumference) through databases (PubMed, Qvid Medline, Web of Science, Cochrane and EMBASE), the last search was in March 2019. Heterogeneity was testes by using the Q statistic and stratifying for epidemiological factors. The possibility of publication bias was assessed through Begg’s test.ResultsA total of 12 studies provided sufficient data were included. Meta-analysis revealed that maternal arsenic exposure was associated with the decrease of birth weight (β = −25.0 g; 95% CI: −41.0, −9.0) and head circumference (β = −0.12 cm; 95% CI: −0.24, −0.01) in random-effect model, birth length (β = −0.12 cm; 95% CI: −0.17, −0.07) in fixed-effect model, no significant reduction was suggested in chest circumference (β = −0.74 cm; 95% CI: −1.78, 0.3). In addition, we found that the birth weight decreased stronger in women living in the Americas, or appling the exposure marker of urine.ConclusionsMaternal arsenic exposure is associated with the decrease of the birth weight, length and head circumference. Millions of people are still exposured to high-level arsenic, therefore, high quality epidemiologic studies that involve large samples are necessary to determine the precise relationships between maternal arsenic exposure with birth size. And that effective mitigation measures are also need to prevent arsenic exposure in women of reproductive age.     

孕妇年龄与围产期胎儿出生缺陷关联的回顾性队列研究

目的 探究孕妇年龄与围产期胎儿发生出生缺陷的关系.方法 采用回顾性队列研究方法,对2009-2012年广东省21个地市共58家医院出生缺陷监测网络数据的孕妇年龄和胎儿出生缺陷进行分析,计算出生缺陷率及其RR值,以确定孕妇年龄与出生缺陷的关联.结果 2009-2012年共有789,319例围产期胎儿,出生缺陷有29,114例,出生缺陷发生率为369/万.孕妇年龄为＜20岁、20～24岁、25～29岁、30～34岁和＞35岁的出生缺陷率分别为365.43/万、358.02/万、355.30/万、379.41/万和439.74/万,其中25～29岁的出生缺陷率最低(RR:0.97;95％CI:0.90-1.05),＞35岁最高(RR:1.20;95％CI:1.10-1.30).结论 孕妇年龄与胎儿发生出生缺陷的关系密切,应加强孕妇尤其是高龄孕妇的孕前、孕早期保健宣传,并开展产前筛查、产前诊断和新生儿疾病筛查工作,避免和减少出生缺陷发生,提高出生人口素质.     

Reproductive disorders among male and female greenhouse workers

The aim of this study was to evaluate reproductive disorders in male and female greenhouse workers. In 2002, data were collected from 4872 Dutch greenhouse workers and 8133 referents through postal questionnaires with detailed questions on reproductive disorders of the most recent pregnancy, lifestyle habits, and occupational exposures (e.g. pesticides) prior to conception. Different reproductive outcome measures were compared between 957 male and 101 female greenhouse workers and 1408 referents by means of logistic regression analyses. The analyses of primigravidous couples showed a slightly elevated risk of prolonged TTP (OR(women)=1.9; 95% CI: 0.8-4.4) and an increased risk of spontaneous abortion among female greenhouse workers (OR(women)=4.0; 95% CI: 1.1-14.0). A decreased risk of preterm birth was found among male greenhouse workers (OR(men)=0.1; 95% CI: 0.03-0.5). This study may offer some evidence for the hypothesis that pesticide exposure affects human reproduction leading to spontaneous abortion and possibly to prolonged time-to-pregnancy.     

冷冻胚胎移植激素替代周期治疗后单胎和双胎的新生儿结局:一项回顾性队列研究

目的：分析冻融胚胎移植（frozen embryo transfer,FET）患者激素替代周期（hormone replacement therapy,HRT）对单胎和双胎新生儿结局的影响。方法：收集广州医科大学附属第三医院生殖医学中心随访信息系统2009年1月至2019年12月FET患者接受HRT和自然周期（natural cycles,NC）内膜准备的新生儿信息,按单胎和双胎形成2个队列进行回顾性研究,分别以单因素和多因素Logistic回归分析探讨HRT和先天性畸形、早产、低出生体质量的相关性。结果：共纳入12 989例新生儿,其中单胎新生儿HRT组4 440例,NC组3 543例;双胎新生儿HRT组2 766例,NC组2 240例。经多因素Logistic回归分析结果显示,HRT不是单胎先天性畸形（OR=0.84,95% CI：0.53~1.34）、早产（OR=0.97,95% CI：0.82~1.14）和低出生体质量（OR=0.98,95% CI：0.81~1.18）的独立影响因素（P>0.05）。HRT也不是双胎先天性畸形（0R=0.27,95% CI：0.06~1.26）、早产（OR=1.37,95% CI：0.87~2.15）和低出生体质量（OR=0.94,95% CI：0.80~1.11）的独立影响因素（P>0.05）。结论：FET患者HRT不影响单胎和双胎新生儿的先天性畸形、早产和低出生体质量发生。     

Achilles tendon rupture and its association with fluoroquinolone antibiotics and other potential risk factors in a managed care population

BACKGROUND: Case reports and observational studies have implicated fluoroquinolone antibiotic exposure as a risk factor for Achilles tendon rupture (ATR), an uncommon condition for which there are few formal studies. We sought to quantify the strength of association between exposure to fluoroquinolone antibiotics and the occurrence of ATR, accounting for other risk factors. METHODS: This was a case-control study nested within a health insurer cohort. Cases of ATR were identified and confirmed using patterns of health insurance claims that were validated through sampled medical record review. Information on risk factors, including fluoroquinolone exposure, came from health insurance claims. RESULTS: There were 947 cases of ATR and 18 940 controls. A dispensing of a fluoroquinolone antibiotic in the past 6 months was more common among ATR cases than controls, although not significantly so (odds ratio (OR) = 1.2; 95% confidence interval (CI) = 0.9-1.7), and exposure to a higher cumulative fluoroquinolone dose was more strongly associated (OR = 1.5, 95%CI = 1.0-2.3). Other risk factors for ATR were trauma (OR = 17.2, 95%CI = 14.0-20.2), male sex (OR = 3.0, 95%CI = 2.6-3.5), injected corticosteroid administration (OR = 2.2, 95%CI = 1.6-2.9), obesity (OR = 2.0, 95%CI = 1.2-3.1), rheumatoid arthritis (OR = 1.9, 95%CI = 1.0-3.7), skin or soft tissue infections (OR = 1.5, 95%CI = 0.9-2.3), oral corticosteroids (OR = 1.4, 95%CI = 1.0-1.8), and non-fluoroquinolone antibiotics (OR = 1.2, 95%CI = 1.1-1.5). CONCLUSIONS: The elevation in ATR risk associated with fluoroquinolones was similar in magnitude to that associated with oral corticosteroids or non-fluoroquinolone antibiotics. Trauma and male sex were more strongly associated with ATR, as were obesity and injected corticosteroids.     

Cryptorchidism and hypospadias in the Sicilian district of Ragusa and the use of pesticides

The aim of the study was to explore the role of environmental exposures to pesticides in the birth prevalence of hypospadias and cryptorchidism, in the 12 agricultural municipalities of Ragusa Sicily. Data on the birth prevalence of the two birth defects were obtained from the local pediatric services for the period 1998-2002. Municipalities were ranked according to the degree of "pesticide impact" on the basis of three quantitative criteria of intensity of agricultural activities of the population. We found a significantly higher birth prevalence of hypospadias with increasing "pesticide impact" (trend test, P=0.003). The association with cryptorchidism was not statistically significant, but when the two birth defects were pooled together, the linear trend was significant (trend test, P=0.001).     

Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes

For the appropriate protection of human health it is necessary to accurately estimate the health effects of human exposure to toxic compounds. In the present review, epidemiological studies on the health effects of human exposure to organophosphorus (OP) and pyrethroid (PYR) insecticides have been critically assessed. This review is focused on studies where the exposure assessment was based on quantification of specific biomarkers in urine or plasma. The 49 studies reviewed used different epidemiological approaches and analytical methods as well as different exposure assessment methodologies. With regard to OP pesticides, the studies reviewed suggested negative effects of prenatal exposure to these pesticides on neurodevelopment and male reproduction. Neurologic effects on adults, DNA damage and adverse birth outcomes were also associated with exposure to OP pesticides. With regard to exposure to PYR pesticides, there are currently few studies investigating the adverse health outcomes due to these pesticides. The effects studied in relation to PYR exposure were mainly male reproductive effects (sperm quality, sperm DNA damage and reproductive hormone disorders). Studies' findings provided evidence to support the hypothesis that PYR exposure is adversely associated with effects on the male reproductive system. The validity of these epidemiological studies is strongly enhanced by exposure assessment based on biomarker quantification. However, for valid and reliable results and conclusions, attention should also be focused on the validity of the analytical methods used, study designs and the measured toxicants characteristics.     

Associations of xenobiotic-metabolizing enzyme genotypes PON1Q192R, PON1L55M and CYP1A1*2A MspI with pathological symptoms of a rural population in south Greece

Paraoxonases and cytochromes P450 constitute two major classes of xenobiotic-metabolizing enzymes involved in the detoxification of pesticide chemicals. In this study, we examined the distribution of two common genetic polymorphisms of the paraoxonase 1 gene and one common polymorphism of the CYP1A1 gene, in relation to pathological diseases occurring in a rural population. Blood and hair samples were collected from 220 participants of an agricultural cohort in the south of Greece for genotype and pesticide analysis. Demographic information and disease status of the participants was obtained by questionnaire, medical examination and medical record. Organochlorine pesticides and metabolites (DDTs, HCHs) were extracted from hair and analyzed using gas chromatography combined with mass spectrometry techniques. Our results indicate exposure of the rural population of Amaliada to organophosphate and past exposure to organochlorine pesticides. Genotypic analysis of PON1Q192R, PON1L55M and CYP1A1*2A MspI polymorphisms was performed using PCR-RFLP. The PON1 192R and 55M alleles absence was significantly associated with hypertension (OR: 2.59; 95% CI: 1.10-6.09) and hepatitis (OR: 21.43; 95% CI: 2.53-181.50), respectively, as indicated from backward logistic regression. Although the presence of PON1 192R allele significantly affected the occurrence of prostate hyperplasia (OR: 0.35; 95% CI: 0.03-0.40), no associations were obtained between the paraoxonase serum activity or the CYP1A1 genotype and the disease status.     

Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES)

Diethylstilbestrol (DES), a synthetic estrogen used in pregnancy during the 1950s and 1960s, provides a model for potential health effects of endocrine disrupting compounds in the environment. We evaluated prenatal exposure to DES, based on medical record review, in relation to gestational length, fetal growth, and age at menarche in 4429 exposed and 1427 unexposed daughters. DES exposure was associated with an increase in preterm birth (odds ratio (OR)=2.97; 95% CI=2.27, 3.87), and a higher risk of small for gestational age (SGA) (OR=1.61; 95% CI=1.31, 1.98). The association between DES exposure and early menarche was borderline, with stronger effects when early menarche was defined as ≤ 10 years (OR=1.41 95% CI=0.97, 2.03) than defined as ≤ 11 years (OR=1.16; 95% CI=0.97, 1.39). This study provides evidence that prenatal DES exposure was associated with fetal growth and gestational length, which may mediate associations between DES and health outcomes in later life.     

Neuropsychological effects of long-term exposure to organophosphate pesticides

Cholinesterase inhibitors, such as carbamates and organophosphates (OPs), are widely used as insecticides and pesticides and may be stored as biological weapons. The massive use of these products, along with a lack of personal protective equipment on the job, and accidental and intentional ingestions, has produced a great number of poisonings in farmers. A large part of the employment and income in southeastern Spain is concentrated in intensive greenhouse agriculture in which growers are exposed to a varying degree of subsymptomatic doses of a combination of pesticides, mainly OPs and carbamates. We conducted a cross-sectional survey of workers in high-exposure conditions to assess possible neurobehavioral deficits, using a wide array of tasks to test neuropsychological functioning and emotional status. Linear and logistic regression series revealed the importance of the variable "years working with pesticides" as a measure of cumulative exposure for risk of worsened perceptive function performance (odds ratio (OR)=6.93, 95% confidence interval (CI): 1.52-31.51), visuomotor praxis (OR=5.00, 95% CI: 1.22-20.40) and integrative task performance time (OR=4.12, 95% CI: 1.18-14.39) with no relation to plasma cholinesterase activity as a measure of recent exposure. This association was statistically significant after controlling for confounds (age and educational level). The findings showed association of long-term exposure and worse performance in neuropsychological functions, which is interpreted as evidence of a chronic effect of cumulative high exposure to OPs and carbamates.     

Prenatal exposure to misoprostol and congenital anomalies: systematic review and meta-analysis

The present systematic review was proposed with the objective of estimating the risk of congenital anomalies and other adverse events in children exposed to misoprostol during fetal life. The data source consisted of case–control studies that analyzed the effect of prenatal exposure to misoprostol on the pregnancy outcome, which were located in electronic databases and published up to June 2005. The outcomes of interest included congenital anomalies, fetal death, low birth weight and prematurity. The odds ratios (OR) for the individual studies were pooled by meta-analysis. Sensitivity tests and heterogeneity analysis were performed. Four studies involving 4899 cases of congenital anomalies and 5742 controls were included in accordance with the selection criteria. None of the studies analyzed other adverse effects from misoprostol on the outcome from gestation. Increased risks of congenital anomalies related to misoprostol use were found for any congenital defect (OR = 3.56; 95% CI: 0.98–12.98), Möbius sequence (OR = 25.31; 95% CI: 11.11–57.66) and terminal transverse limb defects (OR = 11.86; 95% CI: 4.86–28.90). In conclusion, prenatal exposure to misoprostol is associated with an increased risk of Möbius sequence and terminal transverse limb defects.     

Maternal vaccination and preterm birth: using data mining as a screening tool

OBJECTIVE: The main purpose of this study was to identify possible associations between medicines used in pregnancy and preterm deliveries using data mining as a screening tool. SETTINGS: Prospective cohort study. METHODS: We used data mining to identify possible correlates between preterm delivery and medicines used by 92,235 pregnant Danish women who took part in the Danish National Birth Cohort (DNBC). We then evaluated the association between one of the identified exposures (vaccination) and the risk for preterm birth by using logistic regression. The women were classified into groups according to their exposure to vaccination. The regression analyses were adjusted for the following covariates: parity, infant's gender, maternal Body-Mass Index (BMI), age, smoking, drinking, job, number of inhabitants in the place of residence, infections, diabetes, high blood pressure and preeclampsia. MAIN OUTCOME MEASURE: Preterm birth, a delivery occurring before the 259th day of gestation (i.e., less than 37 full weeks). RESULTS: Data mining had indicated that maternal vaccination (among other factors) might be related to preterm birth. The following regression analysis showed that, the women who reported being vaccinated shortly before or during gestation had a slightly higher risk of giving preterm birth (O.R. = 1.14; 95% CI 1.04-1.25) as compared to the non-vaccinated group. CONCLUSION: Whether the association between maternal vaccination and the risk for preterm birth found here is causal or not deserves further studies. Data mining, especially with additional refinements, may be a valuable and very efficient tool to screen large databases for relevant information which can be used in clinical and public health research.     

门诊老年患者潜在不适当用药对全因住院时长和住院药品费用的影响

目的:研究门诊老年人使用潜在不适当用药(PIM)对患者全因住院时长和住院费用的影响。方法:回顾性分析北京市医保数据库2016年7-9月数据。纳入的患者年龄≥65岁,应用Beers Criteria 2015版识别PIM。暴露PIM的定义为在3个月内被处方至少一个PIM。结局事件定义为患者在暴露于PIM或非PIM 14 d后(≥14 d)发生住院。通过门诊数据中患者ID匹配住院数据的患者ID,抓取发生住院的患者信息,计算这些患者的住院时长和住院药品费用。结果:研究共纳入506 214位患者,中位年龄74岁(范围65～105岁),50.10%为女性。门诊老年人服用PIM后发生住院的患者共5 200人(1.03%)。服用PIM=0,PIM=1,PIM=2、PIM≥3后住院天数分别10.00 d(7.00,14.00),11.00 d(7.00,15.00),11.00 d(8.00,14.00)和11.00 d(7.00,14.00),组间差异有统计学意义(P=0.01);服用PIM=0,PIM=1,PIM=2,PIM≥3后住院费用分别13 488.42元(8 926.00,20 914.3...     

Pesticide exposures and developmental outcomes: the epidemiological evidence

Since the advent of DDT as an insecticide in the late 1930s, billions of kilograms of pesticide active ingredient have been sold in North America and around the world. In recent years, there has been a heightened public awareness of pesticides and child health and a number of epidemiologic studies linked pre- and postnatal exposures to pesticides to a number of adverse developmental outcomes, including fetal death, intrauterine growth restriction, preterm birth, and birth defects. Given this, it was felt prudent to critically appraise the evidence for periconceptual pesticide exposures and developmental outcomes. The epidemiological evidence for specific pesticide classes, families, and active ingredients were examined and summarized and recommendations were made for how to improve future studies in order to address the current pitfalls and gaps in the studies in this area. Many of the studies suffered from poor exposure estimation, relying on job title only and/or the exposure category "any pesticide" as a measure of exposure, and there was limited or inadequate evidence to support causality for all associations examined.     

A population-based case-crossover and case-control study of alcohol and the risk of injury

OBJECTIVE: This study investigated the relationship between alcohol and the risk of acute injury, examining both short-term (drinking over a few hours) and long-term exposures (past-month hazardous drinking and current alcohol use disorders). METHOD: The study was a case-crossover and population-based case control study. Cases (N = 2,517; 1,432 men) were injured patients recruited from all three emergency departments in Boone County, Missouri. Each case's alcohol consumption in the 6 hours prior to injury was compared to his or her consumption the day before in a case-crossover analysis. Community controls (N = 1,856; 948 men) were recruited by telephone and matched to cases by age, gender, day of week and hour. Case-control analyses examined recent alcohol consumption (past 6 hours), past-month hazardous drinking and past-year alcohol use disorders. RESULTS: The odds ratios (ORs) for injury associated with short-term alcohol exposure were similar, whether cases were compared with themselves (case-crossover analyses) or with others (case-control analyses). After 1 or 2 drinks in a 6-hour interval, the ORs were 1.8 (95% confidence interval [CI]: 1.3-2.6) and 1.5 (0.96-2.2), respectively. Similar dose-response curves were seen in the two comparisons, with ORs of 6.2 and 3.7, respectively, after 3 or 4 drinks and 9.5 and 13.5 after 5 or 6 drinks. For past-month hazardous drinking, the OR was 1.7 (95% CI: 1.2-2.3). Current alcohol dependence was associated with injury (OR = 1.9; 95% CI: 1.5-2.6), but alcohol abuse was not (OR = 0.9; 95% CI: 0.8-1.1). CONCLUSIONS: Alcohol's effect on injury risk is related more strongly to acute exposure than to measures of long-term exposure. The risk is significant even at low levels of consumption.