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ABSTRACT: IMPORTANCE Most children with end-stage kidney disease (ESKD) are treated with dialysis prior to transplant. It is not known whether their outcomes have changed in recent years. OBJECTIVE To determine if all-cause, cardiovascular, and infection-related mortality rates for children and adolescents beginning dialysis improved between 1990 and 2010. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of patients younger than 21 years initially treated with dialysis for ESKD, recorded in the United States Renal Data System between 1990 and 2010. Children with a prior kidney transplant were excluded. We used Cox proportional hazard models to estimate the hazard ratios (HRs) for mortality associated with a 5-year increment in year of ESKD treatment initiation. Primary analyses censored observation at kidney transplant. MAIN OUTCOMES AND MEASURES All-cause, cardiovascular, and infection-related mortality. RESULTS A total of 3450 children younger than 5 years and 19 951 children 5 years or older started dialysis from 1990-2010. Of those younger than 5 years, 705 died during dialysis treatment (98.8/1000 person-years); mortality rates were 112.2 and 83.4 per 1000 person-years in those initiating dialysis in 1990-1994 and 2005-2010, respectively. Of those 5 years and older at treatment initiation, 2270 died during dialysis treatment (38.6/1000 person-years). Their mortality rates were 44.6 and 25.9 per 1000 person-years in those initiating dialysis in 1990-1994 and 2005-2010, respectively. Each 5-year increment in calendar year of dialysis initiation was associated with an adjusted HR of 0.80 (95% CI, 0.75-0.85) among children younger than 5 years at initiation and an HR of 0.88 (95% CI, 0.85-0.92) among those 5 years and older. CONCLUSIONS AND RELEVANCE In the United States, there was a substantial decrease in mortality rates over time among children and adolescents initiating ESKD treatment with dialysis between 1990 and 2010. Further research is needed to determine the specific factors responsible for this decrease.
JAMA The Journal of the American Medical Association 05/2013; · 30.03 Impact Factor
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ABSTRACT: Although second-trimester blood corticotrophin-releasing hormone (CRH) levels are robustly associated with preterm birth, the findings with respect to cortisol have been inconsistent, as have been those relating stress hormones to measured stressors and maternal distress.
We measured plasma CRH, adrenocorticotrophic hormone (ACTH), cortisol, cortisol-binding globulin, oestradiol and progesterone at 24-26 weeks in a nested case-control study of 206 women who experienced spontaneous preterm birth and 442 term controls. We also related the hormonal levels to measures of environmental stressors, perceived stress and maternal distress (also assessed at 24-26 weeks) and to placental histopathology.
With the exception of an unexpectedly low oestradiol : progesterone ratio among cases (adjusted odds ratio = 0.5 [95% confidence interval 0.3, 0.8] for ratios above the median in controls), none of the hormonal measures was independently associated with spontaneous preterm birth; placental histopathological evidence of infection/inflammation, infarction or decidual vasculopathy; or measures of maternal stress or distress. CRH levels were positively associated with cortisol, but not with ACTH, whereas ACTH was also positively associated with cortisol.
Our findings suggest an intact pituitary-adrenal axis and confirm the positive feedback effect of cortisol on (placental) CRH. Neither of these hormonal pathways, however, was strongly linked to maternal stress/distress or to the risk of spontaneous preterm birth.
Paediatric and Perinatal Epidemiology 05/2013; 27(3):237-46. · 2.31 Impact Factor
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ABSTRACT: Age at transplant and graft failure risk are associated in young kidney transplant recipients. The risk of graft failure may also vary by current age, irrespective of age at transplant. We sought to estimate age-specific graft failure rates in young kidney transplant recipients and to estimate the relative hazards of graft failure at different ages, compared with at the age of 25 to 29 years.
We evaluated 90,689 patients recorded in the United States Renal Data System database who received a first transplant when younger than 40 years (1988-2009); 18,310 were younger than 21 years at transplant. Time-dependent Cox models with time-varying covariates were used to estimate the association between age (time-dependent) and death-censored graft failure risk, adjusted for time since transplant and other potential confounders.
There were 31,857 graft failures over a median follow-up of 5.9 years (interquartile range, 2.5-10.5 years; maximum, 21.8 years). Crude age-specific graft failure rates were highest in 19 year olds (6.6 per 100 person-years). Compared with individuals with the same time since transplant observed at 25 to 29 years of age, death-censored graft failure rates were highest in 17 to 24 year olds (hazard ratio, 1.20; [95% confidence interval 1.13, 1.27] for 17-20 year olds and 1.20 [1.13, 1.26] for 21-24 year olds; both P<0.0001) and lowest in 5 to 12 year olds (hazard ratio, 0.60; [0.53, 0.68] for 5-9 year olds and 0.56 [0.49, 0.64] for 10-12 year olds; both P<0.0001).
Among first kidney transplant recipients younger than 40 years, older adolescents and young adults (17-24 years) have the highest risk of graft failure, irrespective of age at transplant.
Transplantation 12/2011; 92(11):1237-43. · 4.00 Impact Factor
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ABSTRACT: Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers.
From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit.
In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054).
Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1.
BMC Pregnancy and Childbirth 11/2011; 11:91. · 2.83 Impact Factor
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ABSTRACT: Observational (non-experimental) studies of the association between infant feeding and subsequent child or adult behaviour are prone to residual confounding by subtle differences in psychological attributes and interactional styles of mothers who breast feed vs. those who formula-feed. We followed up 13,889 6.5-year-old Belarusian children who participated in a large cluster-randomised trial of a breast-feeding promotion intervention. Behaviour was evaluated using the Strengths and Difficulties Questionnaire (SDQ), completed independently by the children's parents and teachers. We compared the results of experimental (intention-to-treat, ITT) and observational analyses (based on feeding actually received), both adjusted for clustering. Observational analyses were additionally adjusted for geographical region, urban vs. rural residence, child's sex, age at follow-up, birthweight, and maternal and paternal education. No differences between the randomised experimental vs. control groups were observed in ITT analyses. In contrast, small but statistically significant associations with weaning prior to 3 months were observed for parent and teacher SDQ scores on total difficulties, conduct problems and hyperactivity, even after multivariable adjustment. The absence of associations based on ITT analyses, in contrast with the significant associations based on observed breast-feeding duration, strongly suggests that the latter are biased by residual confounding.
Paediatric and Perinatal Epidemiology 11/2011; 25(6):500-6. · 2.31 Impact Factor
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ABSTRACT: Immaturity among individuals transferred from pediatric to adult-oriented care at a young age may leave them vulnerable to higher graft failure risks than in individuals transferred older. We sought to determine the impact of age at transfer on renal allograft failure rates. We evaluated graft failure rates among 440 kidney recipients recorded in the UNOS database (1987-2007), who had been transferred from pediatric to adult care. Transfers were identified using the center codes recorded at yearly data collection. Failure rates for those transferred early (<21 yr old) were compared with rates for those transferred late (≥21 yr old); time-dependent Cox models were used to estimate the additional risk of graft failure associated with early vs. late transfer. The age-standardized failure rate was 12.9 per 100 person-years among those transferred early, and 8.7 per 100 person-years among those transferred late. Compared with individuals the same age who had transferred late, graft failure rates were 58% higher ([95% confidence interval: 7%, 134%], p = 0.02) among those who had transferred early. Younger age at transfer to adult care is associated with higher graft failure rates. Transfer to adult-oriented care at <21 yr of age should be undertaken with caution.
Pediatric Transplantation 08/2011; 15(7):750-9. · 1.48 Impact Factor
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ABSTRACT: To assess risk factors for postpartum hemorrhage (PPH) and the extent to which changes in those risk factors may explain the rising incidence of PPH recently reported from industrialized countries.
We carried out a hospital-based cohort study of 103 726 consecutive deliveries from January 1, 1978, to January 31, 2007, from the computerized medical records of a tertiary-care university maternity hospital in Montreal. We examined adjusted odds ratios for any PPH (estimated blood loss > 500 mL for vaginal deliveries, > 1000 mL for Caesarean sections), severe PPH (estimated blood loss ≥ 1500 mL), and PPH accompanied by blood transfusion and/or hysterectomy.
Major independent risk factors for PPH included primiparity, prior Caesarean section, placenta previa or low-lying placenta, marginal umbilical cord insertion in the placenta, transverse lie, labour induction and augmentation, uterine or cervical trauma at delivery, gestational age < 32 weeks, and birth weight ≥ 4500 g. An overall increase in rate of PPH over the study period (OR 1.029; 95% CI 1.024 to 1.034 per year) disappeared (OR 0.995; 95% CI 0.988 to 1.001 per year) after inclusion of maternal age, parity, prior Caesarean section, labour induction and augmentation, placenta previa or low-lying placenta, and abnormal placenta, with most of the reduction attributable to rises in previous Caesarean section and labour augmentation.
Labour induction, augmentation of labour, and prior Caesarean section are significantly associated with the risk of PPH, and their increase over the study period largely explains the observed rise in PPH.
Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 08/2011; 33(8):810-9.
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American journal of epidemiology 03/2011; · 5.59 Impact Factor
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ABSTRACT: Infants who receive prolonged and exclusive breastfeeding grow more slowly during the first year of life than those who do not. However, infant feeding and growth are dynamic processes in which feeding may affect growth, and prior growth and size may also influence subsequent feeding decisions. The authors carried out an observational analysis of 17,046 Belarusian infants who were recruited between June 1996 and December 1997 and who participated in a cluster-randomized trial of a breastfeeding promotion intervention. To assess the effects of infant size on subsequent feeding, the authors restricted the analysis to infants breastfed (or exclusively breastfed) at the beginning of each follow-up interval and examined associations between weight or length at the beginning of the interval and weaning or discontinuation of exclusive breastfeeding by the end of the interval. Smaller size (especially weight for age) was strongly and statistically significantly associated with increased risks of subsequent weaning and of discontinuing exclusive breastfeeding (adjusted odds ratios = 1.2-1.6), especially between 2 and 6 months, even after adjusment for potential confounding factors and clustered measurement. The authors speculate that similar dynamic processes involving infant crying, other signs of hunger, and supplementation/weaning undermine causal inferences about the "effect" of prolonged and exclusive breastfeeding on slower infant growth.
American journal of epidemiology 03/2011; 173(9):978-83. · 5.59 Impact Factor
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Michael S Kramer,
John Lydon,
Louise Séguin,
Lise Goulet,
Susan R Kahn,
Helen McNamara,
Jacques Genest,
Shakti Sharma,
Michael J Meaney,
Michael Libman, Mourad Dahhou,
Robert W Platt
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ABSTRACT: During pregnancy, most maternal corticotrophin-releasing hormone (CRH) is secreted by the placenta, not the hypothalamus. Second trimester maternal CRH concentration is robustly associated with the subsequent risk of preterm birth, and it is often assumed that physiological and/or psychological stress stimulates placental CRH release. Evidence supporting the latter assumption is weak, however, and other factors affecting maternal CRH have received little attention from investigators. We carried out a case-control study nested within a large, multicentre prospective cohort of pregnant women to examine potential 'upstream' factors associated with maternal CRH concentration measured at 24-26 weeks of gestation. The predictors studied included maternal age, parity, birthplace (as a proxy for ethnic origin), pre-pregnancy body mass index, height, smoking, bacterial vaginosis and vaginal fetal fibronectin (FFN) concentration. Women with high (above the median) plasma CRH concentration were significantly less likely to have been born in Sub-Saharan Africa or the Caribbean, less likely to be overweight or obese, and more likely to be smokers. Associations with maternal birthplace and BMI persisted in logistic regression analyses controlling for potential confounding variables and when restricted to term controls. A strong (but imprecise and statistically non-significant) association was also observed with high vaginal FFN concentration. Further studies are indicated both in animal models and human populations to better understand the biochemical and physiological pathways to CRH secretion and their aetiological role, if any, in preterm birth.
Paediatric and Perinatal Epidemiology 07/2010; 24(4):390-7. · 2.31 Impact Factor
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Me-Linh Luong,
Michael Libman, Mourad Dahhou,
Moy Fong Chen,
Susan R Kahn,
Lise Goulet,
Louise Séguin,
John Lydon,
Helen McNamara,
Robert W Platt,
Michael S Kramer
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ABSTRACT: Vaginal douching and bacterial vaginosis (BV) are independently associated with spontaneous preterm birth. Because the interrelationships among these variables remain unclear, we sought to examine the associations in a prospective study.
We conducted a nested case-control study within a prospectively recruited cohort of pregnant women. We prospectively collected demographic and health status data, data on pre-pregnancy vaginal douching, vaginal smears for bacterial vaginosis as defined by Nugent's criteria, fetal fibronectin at 26 weeks of pregnancy, and placental pathology at delivery. Spontaneous preterm births before 37 weeks' gestation were selected as cases. All spontaneous births occurring after 37 weeks were potential control subjects. To limit costs, some tests were performed only in selected control subjects.
Preterm birth occurred in 207 of 5092 women (4.1%). In bivariate analysis, BV was not associated with preterm birth (OR 1.2; 95% CI 0.5 to 2.4). Vaginal douching was significantly associated with bacterial vaginosis (P < 0.05) and preterm birth (P < 0.05). On multivariate analysis, vaginal douching was no longer associated with preterm birth, but a significant association with early preterm birth < 34 weeks (OR, 6.9; 95% CI 1.7 to 28.2) and preterm birth due to preterm labour (OR 3.0; 95% CI 1.1 to 8.5) persisted after controlling for the presence of bacterial vaginosis and placental inflammation.
Vaginal douching and bacterial vaginosis were not associated with spontaneous preterm birth overall. However, vaginal douching appears to be an independent and potentially modifiable risk factor for early preterm birth (32-34 weeks), although the mechanism remains unclear.
Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 04/2010; 32(4):313-20.
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ABSTRACT: It has been hypothesised that dehydration in infancy could permanently increase sodium retention, raising blood pressure in later life. In this study, the association between gastrointestinal tract infection in infancy, a clinically relevant exposure often accompanied by dehydration, and raised blood pressure in childhood was investigated.
Data from a cohort study nested within a cluster-randomised trial of breastfeeding promotion in the Republic of Belarus were analysed. 17 046 healthy breastfed infants were enrolled from 31 maternity hospitals. 13 889 (81.5%) children were followed-up at 6.5 years. Exposure measures were any gastrointestinal infection in infancy (to 1 year) and hospitalisations for gastrointestinal infection in infancy and in childhood (1-6.5 years). The outcomes were systolic and diastolic blood pressure at age 6.5 years.
The prevalence of any gastrointestinal infection in infancy, and of hospitalisation for gastrointestinal infection in infancy or childhood, was 11.4%, 3.2% and 6.0%, respectively. No associations were observed between systolic blood pressure and any gastrointestinal infection (mean difference in those with minus those without infection -0.04 mm Hg; 95% CI -0.52 to 0.43) or hospitalisation for gastrointestinal infection (difference=-0.22 mm Hg; -1.07 to 0.64) in infancy. Nor were associations observed between diastolic blood pressure and any gastrointestinal infection during infancy or hospitalisation for gastrointestinal infection during infancy or childhood.
No evidence was found to prove that hospitalisation for gastrointestinal infection in infancy or childhood leads to raised blood pressure at age 6.5 years in a developed country setting.
Journal of epidemiology and community health 11/2009; 64(12):1068-73. · 3.04 Impact Factor
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Michael S Kramer,
Lidia Matush,
Natalia Bogdanovich,
Frances Aboud,
Bruce Mazer,
Eric Fombonne,
Jean-Paul Collet,
Ellen Hodnett,
Elena Mironova,
Sergei Igumnov,
Beverley Chalmers, Mourad Dahhou,
Robert W Platt
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ABSTRACT: Despite the current World Health Organization recommendation that infants be exclusively breastfed for 6 mo, this practice remains unusual in both developed and developing countries.
The objective was to compare health and development outcomes at age 6.5 y in children who were exclusively breastfed for 3 mo (EBF3) or for 6 mo (EBF6); in the EBF3 group, the children continued partial breastfeeding for > or =6 mo.
This was a prospective cohort study nested within a large, cluster-randomized trial of a breastfeeding promotion intervention in the Republic of Belarus. Outcomes compared at 6.5 y included anthropometric measurements, systolic and diastolic blood pressure, intelligence quotient, teachers' ratings of academic performance, parent- and teacher-rated behavior, atopic symptoms, allergen skin-prick tests, and dental caries. All statistical analyses were adjusted for cluster- and individual-level covariates and for clustering of outcomes within the clinics at which the children were examined.
The 2427 EBF3 and 524 EBF6 children who were followed up represented 84.7% and 89.4%, respectively, of those followed for the first year of life. The only significant differences observed between the 2 groups were in mean body mass index, triceps skinfold thickness, and hip circumference, all of which were higher in the EBF6 group.
We observed no demonstrable beneficial or adverse long-term effects on child health of exclusive breastfeeding for 6 mo. Higher adiposity measures in the EBF6 group probably reflect reverse causality rather than a causal effect of prolonged exclusive breastfeeding. Established benefits appear to be limited to the period of exclusive breastfeeding.
American Journal of Clinical Nutrition 09/2009; 90(4):1070-4. · 6.67 Impact Factor
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Michael S Kramer,
Susan R Kahn,
Robert W Platt,
Jacques Genest,
Moy Fong Chen,
Lise Goulet,
Louise Séguin,
John Lydon,
Helen McNamara,
Michael Libman, Mourad Dahhou,
Julie Lamoureux,
Kristin Skogstrand,
Poul Thorsen
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ABSTRACT: Most previous studies of maternal cytokines and preterm birth have analyzed immunologic biomarkers after the onset of labor or membrane rupture; fewer have examined the systemic (blood) immune response prior to labor onset. We carried out a case-control study nested in a large (n=5337) prospective, multi-center cohort. Cohort women had an interview, examination, and venipuncture at 24-26 weeks. Frozen plasma samples in women with spontaneous preterm birth (n=207) and approximately 2 term controls per case (n=444) were analyzed using Luminex multianalyte profiling technology. Fresh placentas were fixed, stained, and blindly assessed for histologic evidence of infection/inflammation, decidual vasculopathy, and infarction, and vaginal swabs were analyzed for bacterial vaginosis and fetal fibronectin concentration. High maternal matrix metalloproteinase-9 (MMP-9) concentration, but none of the other cytokines or C-reactive protein (CRP), was significantly associated with spontaneous preterm birth [adjusted OR=1.7 (1.1-2.4)] and showed a dose-response relation across quartiles. No association was observed, however, between maternal MMP-9 and placental infection/inflammation, bacterial vaginosis, or vaginal fetal fibronectin concentration. Our results require confirmation in future studies but suggest that a systemic immune response implicating MMP-9 may have an etiologic role in spontaneous preterm birth.
Cytokine 09/2009; 49(1):10-4. · 3.02 Impact Factor
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Michael S. Kramer,
Susan R. Kahn,
Robert W. Platt,
Jacques Genest,
Rima Rozen,
Moy Fong Chen,
Lise Goulet,
Louise Séguin,
Clément Dassa,
John Lydon,
Helen McNamara, Mourad Dahhou,
Julie Lamoureux,
Rhobert W. Evans
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ABSTRACT: Background: Neither macro- nor micronutrient supplements have been clearly demonstrated to reduce the risk of preterm birth. However, there has been little attention to carotenoids, tocopherols, and long-chain fatty acids other than n-3 polyunsaturates.
Methods: We conducted a case-control study nested in a large (n = 5337) prospective, multicenter cohort. All cohort women had an interview, examination, and venipuncture at 24-26 weeks' gestation. Frozen plasma samples in spontaneous preterm births (n = 207) and approximately 2-term controls per case (n = 443) were analyzed for carotenoids, retinol, tocopherols, and long-chain fatty acids. Fresh placentas were fixed, stained, and assessed (without knowledge of pregnancy outcome) for histologic evidence of infection or inflammation, decidual vasculopathy, and infarction.
Results: High (above the median) plasma concentrations of α- and β-carotene, α- and β-cryptoxanthin, and lycopene were all associated with reductions in risk of spontaneous preterm birth, with evidence of dose-response effects across quartiles. Modest increases in risk were observed with elevated total monounsaturated, total polyunsaturated, and total n-6 polyunsaturated long-chain fatty acids concentrations. Paradoxically, a high γ-tocopherol concentration was associated with increased preterm birth risk (adjusted odds ratio = 1.8 [95% confidence interval = 1.2-2.6]). Only one of the studied micronutrients (lutein) was independently associated with a reduced risk of decidual vasculopathy (0.5 [0.3-0.9]).
Conclusions: Carotenoids and long-chain fatty acids warrant further investigation in in vitro, animal, and human studies of preterm birth.
Epidemiology 08/2009; 20(5):707-713. · 5.57 Impact Factor
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Michael S Kramer,
Russell Wilkins,
Lise Goulet,
Louise Séguin,
John Lydon,
Susan R Kahn,
Helen McNamara,
Clément Dassa, Mourad Dahhou,
André Masse,
Louise Miner,
Guylaine Asselin,
Henriette Gauthier,
Antoinette Ghanem,
Alice Benjamin,
Robert W Platt
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ABSTRACT: Selective study participation can theoretically lead to selection bias. We explored this issue in the context of a multicentre cohort study of socio-economic disparities in preterm birth. Women with singleton pregnancies were recruited from four large Montreal maternity hospitals and invited to return for an interview, vaginal examination and venepuncture at 24-26 weeks of gestation. We compared the observed preterm birth rate (ultrasound confirmed) among the 5146 cohort women to that expected based on all 108 724 Montreal Census Metropolitan Area (CMA) singleton births for 1998-2000. The observed preterm birth rate in the study cohort was 5.1%, compared with 6.3% in the CMA (P < 0.001) (unadjusted morbidity ratio [95% CI] = 0.80 [0.71, 0.90]). Within each stratum of maternal education and neighbourhood income (the latter based on postal code matched links to the 2001 Canadian census), cohort women had substantially lower rates of preterm birth than women from the CMA. No significant association between socio-economic status (SES) and preterm birth was observed in the study cohort, except among 'indicated' (non-spontaneous) cases. The association between neighbourhood income and preterm birth was biased to the null in the study cohort, with adjusted odds ratios in the poorest vs. richest quintiles of 1.01 [0.63, 1.64] in the cohort vs. 1.28 [1.18, 1.39] in the CMA, although no such bias was observed for the association with maternal education assessed at the individual level. We speculate that the lower-than-expected preterm birth rate and attenuated association between neighbourhood income and preterm birth may be related to selective participation by women more psychologically invested in their pregnancies. Investigators should consider the potential for biased associations in pregnancy/birth cohort studies, especially associations based on SES or race/ethnicity, and carry out sensitivity analyses to gauge their effects.
Paediatric and Perinatal Epidemiology 08/2009; 23(4):301-9. · 2.31 Impact Factor
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Michael S Kramer,
John Lydon,
Louise Séguin,
Lise Goulet,
Susan R Kahn,
Helen McNamara,
Jacques Genest,
Clément Dassa,
Moy Fong Chen,
Shakti Sharma,
Michael J Meaney,
Steven Thomson,
Stan Van Uum,
Gideon Koren, Mourad Dahhou,
Julie Lamoureux,
Robert W Platt
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ABSTRACT: The authors investigated a large number of stressors and measures of psychological distress in a multicenter, prospective cohort study of spontaneous preterm birth among 5,337 Montreal (Canada)-area women who delivered from October 1999 to April 2004. In addition, a nested case-control analysis (207 cases, 444 controls) was used to explore potential biologic pathways by analyzing maternal plasma corticotrophin-releasing hormone (CRH), placental histopathology, and (in a subset) maternal hair cortisol. Among the large number of stress and distress measures studied, only pregnancy-related anxiety was consistently and independently associated with spontaneous preterm birth (for values above the median, adjusted odds ratio = 1.8 (95% confidence interval: 1.3, 2.4)), with a dose-response relation across quartiles. The maternal plasma CRH concentration was significantly higher in cases than in controls in crude analyses but not after adjustment (for concentrations above the median, adjusted odds ratio = 1.1 (95% confidence interval: 0.8, 1.6)). In the subgroup (n = 117) of participants with a sufficient maternal hair sample, hair cortisol was positively associated with gestational age. Neither maternal plasma CRH, hair cortisol, nor placental histopathologic features of infection/inflammation, infarction, or maternal vasculopathy were significantly associated with pregnancy-related anxiety or any other stress or distress measure. The biologic pathways underlying stress-induced preterm birth remain poorly understood.
American journal of epidemiology 05/2009; 169(11):1319-26. · 5.59 Impact Factor
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Michael S Kramer,
Susan R Kahn,
Rima Rozen,
Rhobert Evans,
Robert W Platt,
Moy Fong Chen,
Lise Goulet,
Louise Séguin,
Clément Dassa,
John Lydon,
Helen McNamara, Mourad Dahhou,
Jacques Genest
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ABSTRACT: Mothers who give birth to preterm infants are at increased risk of mortality from coronary heart disease and stroke, but the biological pathways underlying these associations have not been explored.
We carried out a case-control study nested in a large (n = 5337) prospective, multicentre cohort. All cohort women had an interview, examination and venipuncture at 24-26 weeks. Frozen plasma samples in spontaneous preterm births (n = 207) and 444 term controls were analysed for plasma homocysteine, folate, cholesterol (total, low-density lipoprotein and high-density lipoprotein) and thrombin-antithrombin (TAT) complexes. DNA was extracted and analysed for seven gene polymorphisms involved in thrombophilia or folate or homocysteine metabolism. Fresh placentas were fixed, stained and blindly assessed for histologic evidence of infarction and decidual vasculopathy.
High (above the median) plasma homocysteine and HDL cholesterol were significantly and independently associated with the risk of spontaneous preterm birth [adjusted odds ratios (OR)s = 1.9 (95% 1.1-3.3) and 0.5 (0.3-0.9), respectively]. A higher proportion of women with high homocysteine concentrations had decidual vasculopathy [(13.0 vs 6.8%; OR = 1.9 (1.1-3.5)], although the positive association between decidual vasculopathy and preterm birth did not achieve statistical significance [OR = 1.5 (0.9-2.7)]. No significant associations were observed with the DNA polymorphisms or with plasma TAT or folate levels.
Similar vasculopathic risk factors may underlie preterm birth and adult coronary heart disease and stroke.
International Journal of Epidemiology 04/2009; 38(3):715-23. · 6.41 Impact Factor
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BMJ (Clinical research ed.). 02/2009; 339:b2900.
