Association between Clinical Characteristics and Microbiota in Bronchiectasis Patients Based on Metagenomic Next-Generation Sequencing Technology.

This study aimed to investigate the disparities between metagenomic next-generation sequencing (mNGS) and conventional culture results in patients with bronchiectasis. Additionally, we sought to investigate the correlation between the clinical characteristics of patients and their microbiome profiles. The overarching goal was to enhance the effective management and treatment of bronchiectasis patients, providing a theoretical foundation for healthcare professionals. A retrospective survey was conducted on 67 bronchiectasis patients admitted to The First Hospital of Jiaxing from October 2019 to March 2023. Clinical baseline information, inflammatory indicators, and pathogen detection reports, including mNGS, conventional blood culture, bronchoalveolar lavage fluid (BALF) culture, and sputum culture results, were collected. By comparing the results of mNGS and conventional culture, the differences in pathogen detection rate and pathogen types were explored, and the diagnostic performance of mNGS compared to conventional culture was evaluated. Based on the various pathogens detected by mNGS, the association between clinical characteristics of bronchiectasis patients and mNGS microbiota results was analyzed. The number and types of pathogens detected by mNGS were significantly larger than those detected by conventional culture. The diagnostic efficacy of mNGS was significantly superior to conventional culture for all types of pathogens, particularly in viral detection (p < 0.01). Regarding pathogen detection rate, the bacteria with the highest detection rate were Pseudomonas aeruginosa (17/58) and Haemophilus influenzae (11/58); the fungus with the highest detection rate was Aspergillus fumigatus (10/21), and the virus with the highest detection rate was human herpes virus 4 (4/11). Differences were observed between the positive and negative groups for P. aeruginosa in terms of common scoring systems for bronchiectasis and whether the main symptom of bronchiectasis manifested as thick sputum (p < 0.05). Significant distinctions were also noted between the positive and negative groups for A. fumigatus regarding Reiff score, neutrophil percentage, bronchiectasis etiology, and alterations in treatment plans following mNGS results reporting (p < 0.05). Notably, 70% of patients with positive A. fumigatus infection opted to change their treatment plans. The correlation study between clinical characteristics of bronchiectasis patients and mNGS microbiological results revealed that bacteria, such as P. aeruginosa, and fungi, such as A. fumigatus, were associated with specific clinical features of patients. This underscored the significance of mNGS in guiding personalized treatment approaches. mNGS could identify multiple pathogens in different types of bronchiectasis samples and was a rapid and effective diagnostic tool for pathogen identification. Its use was recommended for diagnosing the causes of infections in bronchiectasis patients.

Response to Omalizumab as an Add-On Therapy in the Treatment of Allergic Asthma in Adult Chinese Patients-A Retrospective Study.

(a) Background: Omalizumab is an anti-IgE humanized monoclonal antibody marketed in China for the conventional treatment of poorly controlled moderate-to-severe allergic asthma. Numerous clinical trials have demonstrated the effectiveness of omalizumab, but the data from studies in actual clinical treatment are still relatively limited. (b) Methods: Thirty-two patients with moderate-to-severe allergic asthma treated with omalizumab on the basis of ICS-LABA (inhaled corticosteroids/long-acting beta2-agonist) were selected. Clinical characteristics before and after treatment were collected to analyze the relationship between changes in serum total IgE levels and peripheral blood EOS (eosinophil) levels, FEV1 (forced expiratory volume in 1 second), PEF (peak expiratory flow), OCS (oral glucocorticoid) dosage, ATC (asthma control test) score, and the number of acute exacerbations and the treatment response, in order to observe the efficacy of omalizumab in addition to primary therapy, and to investigate whether baseline clinical characteristics such as serum total IgE and EOS levels could predict a treatment response. (c) Results: Using the ACT score as an evaluation, 68.75% of patients benefited from omalizumab treatment at the end of 16 weeks. The response group has a reduction in OCS dosage (p-values of 0.026 and 0.039), a significant reduction in ACT scores (both p < 0.001), and a reduction in the number of acute exacerbations (p = 0.034 and 0.025, respectively) after omalizumab treatment. The binary logistics analysis of factors affecting the effectiveness of omalizumab in the treatment of allergic asthma were total serum IgE and the presence of comorbidities (p-values of 0.039 and 0.046, respectively). (d) Conclusions: Combining omalizumab with ICS-LABA for 16 weeks significantly improves asthma symptoms in Chinese adults and can be used as an add-on treatment. In addition, high serum IgE levels and the presence of comorbidities were predictors of its therapeutic efficacy.

Clinical application of metagenomic next-generation sequencing technology in the diagnosis and treatment of pulmonary infection pathogens: A prospective single-center study of 138 patients.

INTRODUCTION: Rapid and accurate pathogen identification is essential for the treatment of pneumonia. Metagenomic next-generation sequencing (mNGS) is a newly developed technology to obtain microbial nucleic acid sequence information quickly, efficiently, and without bias. METHODS: We performed shotgun metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for pathogen identification in pneumonia in a prospective study with 138 patients from a single center. We compared the results of mNGS with standard methods including culture, staining, and targeted PCR and evaluated the clinical applicability of mNGS. RESULTS: Most of the patients (128/138, 92.75%) were cured or improved. One patient (1/138, 0.72%) died because of acute gastrointestinal bleeding, and 9 patients (9/138, 6.52%) showed no improvement. mNGS identified more bacteria (53 versus 27), fewer fungi (8 versus 31), and more viruses (16 versus 1) than standard methods. In total, treatment in 34 out of 138 cases (24.64%) was adjusted and optimized because of mNGS results. Positive mNGS results contributed to a definitive diagnosis in 23 cases (16.67%), which helped guide treatment decision by either adjusting the antibiotics without de-escalation or continuing the empirical treatment. mNGS also confirmed no active infection in 11 cases (7.97%) allowed for antibiotic de-escalation. CONCLUSION: This prospective clinical study evaluated the clinical utility of mNGS for the diagnosis of pneumonia and showed that mNGS of BALF provides valuable information for effective treatment.

Therapeutic Effects of SRT2104 on Lung Injury in Rats with Emphysema via Reduction of Type II Alveolar Epithelial Cell Senescence.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent and severe diseases worldwide with high societal and health care costs. The pathogenesis of COPD is very complicated, and no curative treatment is available. Cellular senescence promotes the development of COPD. Type II alveolar epithelial cells (AECII) play a momentous role in lung tissue repair and maintenance of alveolar homeostasis. Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to chronic inflammation and oxidative stress, regulates many pathophysiological changes including stress resistance, apoptosis, inflammation, and cellular senescence. This study aimed to investigate whether the pharmacological SIRT1 activator SRT2104 protects against AECII senescence in rats with emphysema. Our findings confirmed that SRT2104 administration reduced the pathological characteristics of emphysema and improved lung function parameters, including pulmonary resistance, pulmonary dynamic compliance, and peak expiratory flow. Moreover, SRT2104 treatment upregulated the expression of surfactant proteins A and C, SIRT1, and forkhead box O 3a (FoxO3a), decreased senescence-associated-ß-galactosidase (SA-ß-gal) activity, increased SIRT1 deacetylase activity, and downregulated the levels of p53 and p21. Therefore, SRT2104 administration protected against AECII senescence in rats with emphysema via SIRT1/FoxO3a and SIRT1/p53 signaling pathways and may provide a novel potential therapeutic strategy for COPD.

Perfluoroalkyl acids and time to pregnancy revisited: An update from the Danish National Birth Cohort.

BACKGROUND: We previously demonstrated an association between plasma perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and longer time to pregnancy (TTP) in a sample from the Danish National Birth Cohort (DNBC, 1996-2002). In this study we investigated this association in a new sample from the same cohort. METHODS: Sample 1 consisted of 440 women, and Sample 2 consisted of 1161 women from whom we previously published the associations between PFOS or PFOA and TTP. We performed sample-specific and pooled analyses using discrete-time survival analyses to estimate fecundability ratios according to PFOS and PFOA quartiles, adjusted for potential confounders chosen guided by a directed acyclic graph. We also estimated odds ratios for infertility (TTP > 12 months or infertility treatment) according to PFOS and PFOA by multivariable logistic regression. RESULTS: In Sample 1 PFOS was not associated with lower fecundability ratios or infertility, and there was a tendency towards longer TTP with increasing PFOA only in parous women. In Sample 2 previously reported associations were again seen. In the pooled analyses including both parous and nulliparous women fecundability ratios were 13-22 % lower for the three higher quartiles of PFOS or PFOA compared to the reference quartile. CONCLUSIONS: The pooled analyses were driven by the larger old sample, but we did not corroborate our previous finding of an association between high PFOS and longer TTP in the new sample. The tendency towards an association for PFOA and TTP in parous women may be due to reverse causation. Results from the new sample are more in line with the recent literature.

Hormone therapy and young-onset breast cancer.

Estrogen plus progestin hormone therapy (HT) is associated with an increased risk of postmenopausal breast cancer, but few studies have examined the impact of HT use on the risk of breast cancer in younger women. We assessed the association between estrogen plus progestin HT or unopposed estrogen HT and young-onset breast cancer using data from the Two Sister Study (2008-2010), a sister-matched study of 1,419 cases diagnosed with breast cancer before the age of 50 years and 1,665 controls. We assessed exposures up to a family-specific index age to ensure comparable opportunities for exposures and used propensity scores to control for birth cohort effects on HT use. Ever HT use was uncommon (7% and 11% in cases and controls, respectively). Use of estrogen plus progestin was not associated with an increased risk of young-onset breast cancer (odds ratio = 0.80, 95% confidence interval: 0.41, 1.59). Unopposed estrogen use was inversely associated with the risk of young-onset breast cancer (odds ratio = 0.58, 95% confidence interval: 0.34, 0.99). Duration of use, age at first use, and recency of use did not modify these associations.

Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case-control study in the Danish National Birth Cohort.

BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited. OBJECTIVES: We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children. METHODS: Among 83,389 mother-child pairs enrolled in the Danish National Birth Cohort during 1996-2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child's sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights. RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother's PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise. CONCLUSIONS: In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children.

Prenatal exposure to perfluoroalkyl substances and the risk of congenital cerebral palsy in children.

Perfluoroalkyl substances (PFASs) are persistent pollutants and endocrine disruptors that may affect fetal brain development. We investigated whether prenatal exposure to PFASs increases the risk of congenital cerebral palsy (CP). The source population for this study includes 83,389 liveborn singletons and mothers enrolled in the Danish National Birth Cohort during 1996-2002. We identified 156 CP cases by linking the cohort to the Danish National Cerebral Palsy Register, and we randomly selected 550 controls using a case-cohort design. We measured 16 PFASs in maternal plasma collected in early or midpregnancy, and 6 PFASs were quantifiable in more than 90% of the samples. We found a higher risk of CP in boys with higher maternal PFAS levels; per 1-unit (natural-log ng/mL) increase, the risk ratios were 1.7 (95% confidence interval: 1.0, 2.8) for perfluorooctane sulfonate and 2.1 (95% confidence interval: 1.2, 3.6) for perfluorooctanoic acid. We also observed a dose-response pattern of CP risk in boys per quartile of maternal level of perfluorooctane sulfonate and perfluorooctanoic acid (P for trend < 0.01). PFASs were associated with both unilateral and bilateral spastic CP subphenotypes. No association between PFASs and CP was found in girls. Prenatal exposures to PFASs may increase the risk of CP in boys, but the finding is novel and replication is needed.

Risk-adjusted hospital outcomes for children's surgery.

UNLABELLED: BACKGROUND The American College of Surgeons National Surgical Quality Improvement Program-Pediatric was initiated in 2008 to drive quality improvement in children's surgery. Low mortality and morbidity in previous analyses limited differentiation of hospital performance. METHODS: Participating institutions included children's units within general hospitals and free-standing children's hospitals. Cases selected by Current Procedural Terminology codes encompassed procedures within pediatric general, otolaryngologic, orthopedic, urologic, plastic, neurologic, thoracic, and gynecologic surgery. Trained personnel abstracted demographic, surgical profile, preoperative, intraoperative, and postoperative variables. Incorporating procedure-specific risk, hierarchical models for 30-day mortality and morbidities were developed with significant predictors identified by stepwise logistic regression. Reliability was estimated to assess the balance of information versus error within models. RESULTS: In 2011, 46 281 patients from 43 hospitals were accrued; 1467 codes were aggregated into 226 groupings. Overall mortality was 0.3%, composite morbidity 5.8%, and surgical site infection (SSI) 1.8%. Hierarchical models revealed outlier hospitals with above or below expected performance for composite morbidity in the entire cohort, pediatric abdominal subgroup, and spine subgroup; SSI in the entire cohort and pediatric abdominal subgroup; and urinary tract infection in the entire cohort. Based on reliability estimates, mortality discriminates performance poorly due to very low event rate; however, reliable model construction for composite morbidity and SSI that differentiate institutions is feasible. CONCLUSIONS: The National Surgical Quality Improvement Program-Pediatric expansion has yielded risk-adjusted models to differentiate hospital performance in composite and specific morbidities. However, mortality has low utility as a children's surgery performance indicator. Programmatic improvements have resulted in actionable data.

Prenatal exposures to perfluorinated chemicals and anthropometry at 7 years of age.

Fetal exposure to the perfluoroalkyl acids, perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), has been associated with lower birth weight and lower weight and body mass index (weight (kg)/height (m)(2)) in early infancy. It is, however, unclear if exposure to prenatal PFOS and PFOA has a lasting influence on growth. We estimated the associations between the maternal plasma level of PFOS or PFOA and the children's body mass index, waist circumference, and risk of overweight at 7 years of age. A total of 1,400 women were randomly selected from the Danish National Birth Cohort among those who provided blood samples early in pregnancy and gave birth to liveborn singletons in 1996-2002. Weight and height information at 7 years was available for 811 children. Multiple linear and logistic regression models were used for analyses. Maternal PFOS and PFOA concentrations were overall inversely but nonsignificantly associated with the children's body mass index, waist circumference, and risk of overweight at 7 years of age. In conclusion, plasma levels of PFOS and PFOA in pregnant women did not seem to have any appreciable influence on their children's anthropometry at this point in childhood.

Menopausal symptoms and the risk of young-onset breast cancer.

BACKGROUND: Women with menopausal symptoms have been reported to have reduced risk of breast cancer, possibly reflecting differences in endogenous hormone levels. We examined the associations between menopausal symptoms and breast cancer in women under age 50. METHODS: We carried out a sister-controlled case-control study, the Two Sister Study, comparing 1422 women with breast cancer diagnosed before age 50 and their 1669 sisters who were free of breast cancer and had enrolled in the prospective Sister Study cohort. History and age at first occurrence of menopause-associated symptoms (e.g. hot flashes, poor sleep or night sweats) were ascertained using computer-assisted telephone interviews. To equalise opportunity for exposure, we assessed exposures in relation to a sibship-based index age (the minimum of the age at diagnosis of the case sister and the age at interview of her control sister(s)), and estimated odds ratios using conditional logistic regression with adjustment for menopausal status and birth order. FINDINGS: Having had menopause-associated symptoms (n=706) prior to the index age was associated with reduced risk of young-onset breast cancer (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.40-0.61). Similar results were seen for hot flashes and for "other" menopausal symptoms. The association between menopausal symptoms and breast cancer risk was somewhat stronger for oestrogen receptor positive tumours than for oestrogen receptor negative tumours (heterogeneity p=0.07). Menopausal status, age at menopause, BMI and hormone replacement therapy did not modify the associations, but the inverse association between menopausal symptoms and breast cancer attenuated with increasing index age (p<0.01). INTERPRETATION: Menopause-associated symptoms were associated with markedly reduced risk of young-onset breast cancer. Further studies are needed to confirm the association and elucidate possible pathways.

Fertility drugs and young-onset breast cancer: results from the Two Sister Study.

BACKGROUND: Fertility drugs stimulate hyperovulation, which may have implications for breast cancer. We examined the association between use of fertility drugs (clomiphene citrate [CC] and follicle-stimulating hormone [FSH]) and subsequent risk of young-onset (<50 years at diagnosis) breast cancer. METHODS: We conducted the Two Sister Study, a sister-matched case-control study, by enrolling 1422 women between September 2008 and December 2010, who were younger than age 50 years at diagnosis with breast cancer and were enrolled within 4 years of diagnosis, and 1669 breast cancer-free control sisters from the Sister Study. Participants reported their use of fertility drugs (CC and FSH) and ever-users reported whether a pregnancy had resulted that lasted 10 or more (10+) weeks. Conditional logistic regression was used to estimate confounder-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for fertility drug use with or without conception of a 10+ week pregnancy. RESULTS: A total of 288 participants reported having used ovulation-stimulating drugs (193 CC only, 29 FSH only, and 66 both). Overall, women who had used fertility drugs showed a non-statistically significantly decreased risk of breast cancer, compared with nonusers (OR = 0.82, 95% CI = 0.63 to 1.08). Women who had used fertility drugs but had not conceived a 10+ week pregnancy under treatment showed a statistically significantly decreased risk of breast cancer compared with nonusers (OR = 0.62, 95% CI = 0.43 to 0.89). Women who had used fertility drugs and conceived a 10+ week pregnancy under treatment showed a statistically significantly increased risk of breast cancer compared with unsuccessfully treated women (OR = 1.82, 95% CI = 1.10 to 3.00), although their risk was not increased compared with women who had not used fertility drugs (OR = 1.13, 95% CI = 0.78 to 1.64). CONCLUSIONS: In the absence of a 10+ week pregnancy under treatment, exposure to ovulation-stimulating fertility drugs was associated with reduced risk of young-onset breast cancer. This apparent association was absent in women who conceived a 10+ week pregnancy under treatment, for whom risk was higher than that of unsuccessfully treated women, but similar to that of untreated women.

Prenatal exposure to perfluorinated chemicals and behavioral or coordination problems at age 7 years.

OBJECTIVE: Potential neurotoxic effects of perfluorinated compounds (PFCs) have been reported in highly exposed animals, but whether these chemicals are neurotoxic in humans is not known. We therefore investigated whether prenatal exposure to perfluorooctanoic acid (PFOA) or perfluorooctane sulfate (PFOS), two of the most prevalent PFCs, are associated with behavioral or coordination problems in early childhood. METHODS: We used data from the Danish National Birth Cohort, which enrolled mothers in early pregnancy, and we measured maternal blood levels of PFOA and PFOS using specimens drawn around 8 weeks of gestation. When the children reached 7 years of age, mothers completed the Strengths and Difficulties Questionnaire (SDQ, n=787) and the Developmental Coordination Disorder Questionnaire (DCDQ, n=526) to assess behavioral health and motor coordination of their children. SDQ scores above the 90th percentile were a priori defined to identify behavioral problems and DCDQ scores below the 10th percentile were defined as a potential DCD. RESULTS: The median concentrations of PFOS and PFOA in maternal blood were 34.4 ng/mL [interquartile range (IQR), 26.6-44.5] and 5.4 ng/mL (IQR, 4.0-7.1), respectively, similar to distributions reported for populations without occupational exposure. We found no association between higher SDQ scores and maternal levels of PFOS or PFOA, nor did we see any statistically significant association with motor coordination disorders. CONCLUSION: The findings suggest that background levels of PFOA and PFOS are not associated with behavioral and motor coordination problems in childhood. However, effects on other developmental end points, including cognitive, attentional, and clinical mental disorders not measured in this study, cannot be ruled out.

Prenatal exposures to perfluorinated chemicals and anthropometric measures in infancy.

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent chemicals that may affect growth early in life. The authors estimated the associations between maternal plasma levels of PFOS and PFOA and infants' weight, length, and body mass index development during the first year of life. Fourteen hundred women were randomly selected from the Danish National Birth Cohort among those who provided blood samples early in pregnancy and gave birth to liveborn singletons between 1996 and 2002. Weight and length information at 5 and 12 months of age was available for 1,010 children. Multiple linear regression models were used for analyses, and maternal PFOS and PFOA concentrations (ng/mL) were inversely related to children's weight in the first year of life: adjusted regression coefficients: 0.8 g (95% confidence interval(CI): 4.2, 2.6) at 5 months and 5.8 g (95% CI:10.4, 1.2) at 12 months for perfluorooctanesulfonate(PFOS); 9.4 g (95% CI: 28.6, 9.9) at 5 months and 19.0 g (95% CI: 44.9, 6.8) at 12 months for perfluorooctanoate(PFOA) [corrected]. A similar pattern was observed for body mass index measurements, and no associations with length were found. After sex stratification, the inverse associations with weight and body mass index were more pronounced in boys, and no clear association was seen for girls.

Prenatal exposure to PFOA and PFOS and risk of hospitalization for infectious diseases in early childhood.

OBJECTIVES: To examine whether prenatal exposure to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) is associated with the occurrence of hospitalization for infectious diseases during early childhood. METHODS: We randomly selected 1400 pregnant women and their offspring from the Danish National Birth Cohort (1996-2002) and measured PFOS and PFOA levels in maternal blood during early pregnancy. Hospitalizations for infection of the offspring were identified by the linkage to the National Hospital Discharge Register through 2008. RESULTS: Hospitalizations due to infections were not associated with prenatal exposure to PFOA and PFOS. On the contrary, the relative risks of hospitalizations ranged from 0.71 to 0.84 for the three higher quartiles of maternal PFOA levels compared with the lowest, but no dose-response pattern was found. No clear pattern was observed when results were stratified by child's age at infection, with the exception of an inverse association between maternal PFC levels and risk of hospitalization during the child's first year of life. CONCLUSIONS: These findings suggest that prenatal exposure to PFOA or PFOS is not associated with increased risk of infectious diseases leading to hospitalization in early childhood.

Maternal concentrations of perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) and duration of breastfeeding.

OBJECTIVE: Perfluorooctanoate (PFOA) has been associated with impaired lactation in mice. We examined whether maternal perfluorooctanesulfonate (PFOS) and PFOA concentrations correlated with duration of breastfeeding among women. METHODS: We randomly selected 1400 pregnant women from the Danish national birth cohort (1996-2002) and measured PFOS and PFOA concentrations in early pregnancy by using high performance liquid chromatography/tandem mass spectrometry. Self-reported data on the duration of any and exclusive breastfeeding were collected twice during telephone interviews around 6 and 18 months after the birth of the child. RESULTS: The duration of breastfeeding decreased with increasing concentrations of pregnancy PFOS and PFOA among multiparous women, for whom the adjusted odds ratios (OR) for weaning before 6 months of age were 1.20 (95% CI 1.06-1.37) per 10 ng/ml increase in PFOS concentrations and 1.23 (95% CI 1.13-1.33) per 1 ng/ml increase in PFOA concentrations. No consistent association was found for primiparous women. CONCLUSIONS: These findings suggest that PFOA and PFOS may reduce the ability to lactate, but could equally reflect reverse causation since no association was seen in primiparous women.

Maternal levels of perfluorinated chemicals and subfecundity.

BACKGROUND: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are ubiquitous man-made compounds that are possible hormonal disruptors. We examined whether exposure to these compounds may decrease fecundity in humans. METHODS: Plasma levels of PFOS and PFOA were measured at weeks 4-14 of pregnancy among 1240 women from the Danish National Birth Cohort recruited from 1996 to 2002. For this pregnancy, women reported time to pregnancy (TTP) in five categories (<1, 1-2, 3-5, 6-12 and >12 months). Infertility was defined as having a TTP of >12 months or received infertility treatment to establish this pregnancy. RESULTS: Longer TTP was associated with higher maternal levels of PFOA and PFOS (P < 0.001). Compared with women in the lowest exposure quartile, the adjusted odds of infertility increased by 70-134 and 60-154% among women in the higher three quartiles of PFOS and PFOA, respectively. Fecundity odds ratios (FORs) were also estimated using Cox discrete-time models. The adjusted FORs were virtually identical for women in the three highest exposure groups of PFOS (FOR = 0.70, 0.67 and 0.74, respectively) compared with the lowest quartile. A linear-like trend was observed for PFOA (FOR = 0.72, 0.73 and 0.60 for three highest quartiles versus lowest quartile). When all quartiles were included in a likelihood ratio test, the trends were significant for PFOS and PFOA (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: These findings suggest that PFOA and PFOS exposure at plasma levels seen in the general population may reduce fecundity; such exposure levels are common in developed countries.

Prenatal exposure to perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and maternally reported developmental milestones in infancy.

BACKGROUND: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are fluorinated organic compounds present in the general population at low concentrations. Animal studies have shown that they may affect neuromuscular development at high concentrations. OBJECTIVES: We investigated the association between plasma levels of PFOS and PFOA in pregnant women and motor and mental developmental milestones of their children. METHODS: We randomly selected 1,400 pairs of pregnant women and their children from the Danish National Birth Cohort. PFOS and PFOA were measured in maternal blood samples taken in early pregnancy. Apgar score was abstracted from the National Hospital Discharge Register in Denmark. Developmental milestones were reported by mothers using highly structured questionnaires when the children were around 6 months and 18 months of age. RESULTS: Mothers who had higher levels of PFOA and PFOS gave birth to children who had similar Apgar scores and reached virtually all of the development milestones at the same time as children born to mothers with lower exposure levels. Children who were born to mothers with higher PFOS levels were slightly more likely to start sitting without support at a later age. CONCLUSION: We found no convincing associations between developmental milestones in early childhood and levels of PFOA or PFOS as measured in maternal plasma early in pregnancy.