Household solid waste combustion with wood increases particulate trace metal and lung deposited surface area emissions.

In households, municipal solid waste (MSW) is often burned along with wood to get rid of waste, to help in ignition or simply to reduce fuel costs. The aim of this study was to characterize the influence of household waste combustion, along with wood, on the physical and chemical properties of particulate emissions in a flue gas of a masonry heater. The MSW burning alongside wood increased average particulate matter (PM) mass (65%), lung deposited surface areas (LDSA, 15%), black carbon (BC, 65%) concentrations and the average particle size in the flue gas. The influence of MSW was smaller during ignition and burning phases, but especially during fuel additions, the mass, number, and LDSA concentrations increased significantly and their size distributions moved towards larger particles. For wood burning the trace metal emissions were relatively low, but significant increase (3.3-179 -fold increase over cycle) was seen when MSW was burned along the wood. High ratios were observed especially during fuel addition phases but, depending on compounds, also during ignition and burning end phases. The highest ratios were observed for chloride compounds (HCl, KCl, NaCl). The observed increase in light-absorbing particle, trace metal and BC concentrations in flue gas when adding wood with MSW are likely to have negative impacts on air quality, visibility, human health and climate. Furthermore, metals may also affect the condition and lifetime of the burning device due to corrosion.

Prognostic significance of extracellular matrix metalloproteinase inducer and matrix metalloproteinase 2 in epithelial ovarian cancer.

AIMS: We investigated the prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase 2 (MMP-2) in epithelial ovarian cancer as well as their relation to hyaluronan (HA) expression. METHODS: The expression of EMMPRIN and MMP-2 was analyzed immunohistochemically in 295 primary epithelial ovarian cancer patients and 67 metastases. RESULTS: A low membranous EMMPRIN expression was detected more often in serous tumors than in other types (p < 0.0005) and it was associated with tumors of advanced stage (p = 0.012) or with a large primary residual (p = 0.011). A low expression of MMP-2 in cancer cells was associated with a high histologic grade (grade 3) of the tumor (p = 0.005) and endometrioid type of tumors (p < 0.0005). Stromal MMP-2 expression was significantly associated with strong stromal HA expression (p = 0.002, r = 0.187). In univariate analysis, 10-year disease-related (DRS) and recurrence-free survivals were significantly better when MMP-2 expression in cancer cells was high (p = 0.0057 and p = 0.0467, respectively). DRS was also better when membranous EMMPRIN expression was high (p = 0.013). In multivariate analysis, strong MMP-2 in cancer cells (RR = 1.48, CI = 1.07-2.04, p = 0.017) indicated favorable DRS. CONCLUSION: Our results show that EMMPRIN and MMP-2 in cancer cells are significant indicators of a favorable prognosis of epithelial ovarian cancer.

Identification of novel dioxin-responsive genes by representational difference analysis.

Representational difference analysis (RDA) was employed on dioxin-stimulated Hepa-1 mouse hepatoma cells (human breast cancer) MCF-7 cells, mouse liver, and mouse thymocytes in order to identify novel responder genes to dioxin. In addition to several clones representing known dioxin-inducible genes, several clones were isolated that represented genes that were previously not known to be inducible by dioxin, including B94 (also known as tumour necrosis factor alpha-induced protein 2 (Tnfaip2), Seven in absentia homologue 2 (Siah2), the mouse homologue of Bob/Gpr15, and S-adenosyl-homocysteine hydrolase (Sahh, Ahcy). Induction of these genes by dioxin in Hepa-1 cells was rapid. Furthermore, induction occurred in the presence of the protein synthesis inhibitor cycloheximide, indicating that in each case induction is a primary response.

Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer.

OBJECTIVE: We investigated the expression of matrix metalloproteinase-9 (MMP-9) and its relation to clinicopathologic factors and survival and also to previously analyzed expressions of CD44 and hyaluronan in epithelial ovarian cancer. METHODS: The expression of MMP-9 was analyzed immunohistochemically in 292 primary tumors and their 31 metastases. RESULTS: A low proportion of strong MMP-9 expression in cancer cells and high stromal MMP-9 expression correlated with advanced stage of the tumor (p=0.003, p=0.02, respectively). Stromal MMP-9 expression significantly correlated with hyaluronan positivity (p<0.0005), whereas MMP-9 did not correlate with CD44. In univariate analysis, a longer 10-year disease-related survival (DRS) was found in patients with a high proportion of MMP-9 or strong MMP-9 expression in cancer cells (p=0.02, p=0.05, respectively). However, high stromal expression of MMP-9 indicated short DRS (p=0.01). In multivariate analysis of all patients, MMP-9 expressing cancer or stromal cells were not independent prognostic factors, while in FIGO stage I patients a high percentage of MMP-9 positive cancer cells was associated with long DRS (p=0.008). CONCLUSION: These data suggest that MMP-9 has a dual role in tumor progression, acting against tumor advancement when in tumor epithelium and promoting tumor progression while in the stroma.

Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity.

Identification of genes that are differentially expressed in rats bidirectionally selected for alcohol preference might reveal biological mechanisms underlying alcoholism or related phenotypes. Microarray analysis from medial prefrontal cortex (mPFC), a key brain region for drug reward, indicated increased expression of glutathione-S-transferases of the alpha (Gsta4) and mu (Gstm1-5) classes in ethanol-preferring AA rats compared with nonpreferring ANA rats. Real-time RT polymerase chain reaction (RT-PCR) analysis demonstrated approximately 2-fold higher Gsta4 transcript levels in several brain regions of ethanol-naive AA compared with ANA rats. Differences in mRNA levels were accompanied by differential levels of GSTA4 protein. We identified a novel haplotype variant in the rat Gsta4 gene, defined here as var3. Allele frequencies of var3 were markedly different between AA and ANA rats, 52% and 100%, respectively. Gsta4 expression was strongly correlated with the gene dose of var3, with approximately 60% of the variance in expression accounted for by genotype at this locus. The contribution of glutathione S-transferase expression to the ethanol-preferring phenotype is presently unclear. It could, however, underlie observed differences in life span between AA and ANA lines, prompting a utility of this animal model in aging research.

Prognostic significance of E-cadherin-catenin complex in epithelial ovarian cancer.

OBJECTIVE: To clarify the prognostic role of E-cadherin and beta- and gamma-catenins, and their relation to CD44 in epithelial ovarian carcinoma. METHODS: The expression of E-cadherin and beta- and gamma-catenins was analysed immunohistochemically in 305 primary epithelial ovarian cancers and 44 metastases, and related to CD44 expression, clinicopathological factors, and the patients' survival. RESULTS: Reduced cell surface expression of E-cadherin, beta-catenin, and gamma-catenin was particularly frequent in serous and endometrioid histological types. Reduced cell surface expression of E-cadherin and beta-catenin was also associated with poor differentiation. Nuclear positivity of beta-catenin was associated with high CD44 expression, endometrioid histology, and local stage of the tumour, whereas nuclear gamma-catenin expression was associated with serous histology and poor differentiation. In the univariate analysis, preserved cell surface beta-catenin expression in the whole study material and nuclear expression of beta- and gamma-catenins in the subgroup of endometrioid ovarian cancers were predictors of better 10 year disease related survival. Preserved cell surface expression of E-cadherin and beta-catenin predicted favourable recurrence-free survival. These statistical significances were not retained in multivariate analysis. CONCLUSIONS: The correlation between nuclear beta-catenin and CD44 indicates that beta-catenin may regulate the transcription of CD44 in epithelial ovarian cancer. E-cadherin-catenin complex members are associated with the prognosis of patients with epithelial ovarian cancer, but these univariate associations were not strong enough to compete for significance with the traditional clinicopathological factors.

Selenium in pregnancy: is selenium an active defective ion against environmental chemical stress?

Transportation of selenium from mother to fetus and its possible effects on mother's zinc, copper, cadmium, and mercury levels were studied together during the first trimester and at term in 216 mothers. Mothers came from three geographical places with different selenium intakes. The role of selenium as a biomarker for the vital function was estimated by studying the associations between tissue or blood selenium content and placental cytochrome P450 enzyme activities and the newborn's birth weight. Regardless of the selenium intake of the mothers, higher concentrations were found in the cord blood than in mother's blood reflecting active transportation of selenium to the fetus. Active smoking was associated with higher placental selenium concentrations like it is associated with higher placental zinc concentrations. When the cadmium concentrations were high in placenta, as in smokers, the transfer of selenium from blood to placenta was increased, decreasing the selenium levels in blood. On the other hand, the high selenium concentrations in blood were connected to lower cadmium concentrations in placenta also in nonsmokers. Selenium had correlations with copper and zinc. ECOD activity in placental tissue, mercury in mothers' hair, mothers' age, and selenium concentrations in cord blood and placental selenium all seem to have connections with xenobiotic-metabolizing enzymes linked effects among mothers. These data suggest that selenium has an active role in the mother's defense systems against the toxicity of environmental pollutants and the constituents of cigarette smoke.

Calcaneal ultrasound predicts early postmenopausal fractures as well as axial BMD. A prospective study of 422 women.

Low calcaneal ultrasound measurement (quantitative ultrasound, QUS) has been shown to predict fractures in elderly women. However, only a few studies have examined its ability to predict perimenopausal and early postmenopausal fractures. We conducted a prospective population-based cohort study to assess the capability of QUS as compared to axial BMD measurement to predict early postmenopausal fractures at that age. Four hundred and twenty-two women (mean age 59.6, range 53.7-65.3) from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) were randomly chosen to undergo a calcaneal ultrasound measurement. In all, 9.4% of these women were premenopausal at the time of measurement. Thirty-two follow-up fractures were reported during the mean follow-up of 2.6 years (SD 0.7). These were validated with patient record perusal. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were significantly lower among women with than without fracture ( P-values 0.028, 0.001 and 0.001, respectively). Mean T-score adapted from SI was -1.5 (95% CI -1.7 to -1.2) for fracture group and -1.0 (95% CI -1.1 to -0.9) for the non-fracture group. All QUS measurements predicted fractures even after adjusting for age, weight, height, previous fracture history, femoral neck BMD and use of hormone replacement therapy according to Cox regression. The adjusted hazard ratios (HR, 95% confidence interval) of a follow-up fracture for a 1 SD decrease were 1.80 (1.27-2.56), 1.72 (1.21-2.45) and 1.43 (1.01-2.03) for SOS, SI and BUA, respectively. Similarly, the adjusted HR for a 1 SD decrease of spinal BMD was 1.27 (0.85-1.94) and for that of femoral neck BMD 1.14 (0.78-1.70). In receiver operator analyses, the area under the curve (AUC) was greatest for QUS measurements: SOS (AUC=0.68), stiffness (AUC=0.67), BUA (AUC=0.62) and least for lumbar BMD (AUC=0.56), while and femoral neck BMD (AUC=0.59). The difference between AUCs was statistically significant between SI and lumbar BMD ( P=0.02, Duncan's P=0.07). We conclude that low calcaneal QUS predicts early postmenopausal fractures as well as or even better than axial BMD.

Interaction of nutritional calcium and HRT in prevention of postmenopausal bone loss: a prospective study.

The aim of this study was to investigate the interactive effects between nutritional calcium (Ca) intake and hormone replacement therapy (HRT) on bone loss. The study population, 937 peri- and postmenopausal women, was selected from a random sample (n = 2025) of the OSTPRE-study cohort (n = 13,100) in Kuopio, Finland. Of them, 545 women had never used HRT and 392 women reported its use during the follow-up period of 6 years. Women were divided in groups according to self-reported daily nutritional Ca intake (mg/day): <648 (1st), 648-927 (2nd), >927 (3rd). Bone mineral density of the lumbar spine and femoral neck was measured with dual X-ray absorptiometry at baseline in 1989-91 and at the 5-year follow-up in 1994-97. According to analysis of variance, there were no statistically significant differences in annual bone loss rate between Ca intake tertiles in HRT never users. In HRT users the annual bone loss at the femoral neck was significantly lower in the third tertile than in the second and first tertiles. In a linear regression model, Ca intake prevented femoral bone loss in HRT users (P < 0.001) but contrast had no effect in never users. At lumbar spine, the corresponding Ca effect was weak (P = 0.063). Adjustment for potentially modifying parameters did not change these effects. In addition, HRT prevented femoral bone loss only among women with the highest Ca intake. At the lumbar spine, the difference between HRT users/non-users was significant in all tertiles but was greater in the second and third tertiles than in the first. In conclusion, nutritional Ca intake may protect HRT users from bone loss and vice versa, low nutritional calcium intake may be a risk factor for non-response to HRT.

Changes in body weight and onset of hypertension in perimenopausal women.

We assessed the determinants of onset of hypertension in a large, prospective population-based study of perimenopausal women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The data collection started in 1989, when a baseline postal inquiry was sent to all women aged 47-56 years (n=14 220) residing in the Kuopio Province in Eastern Finland. Names, social security numbers and addresses were obtained from the Population Register Centre of Finland. A total of 11 798 women responded at baseline and at 5-year follow-up in 1994. After the exclusion of 1777 women with prevalent hypertension at baseline and women with missing height or weight information, the study population consisted of 9485 without established hypertension at baseline. New cases of established hypertension during the follow-up (n=908) were ascertained with the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). According to the National Health Insurance, the SII granted 90% reimbursement for drug costs in defined chronic illnesses necessitating continuous medication, like arterial hypertension. Weight and weight gain both raised the risk by 5% per kg (P<0.001). Weight gain of 4-6 kg increased the risk of hypertension 1.25 times and a gain of more than 7 kg 1.65 times compared with the control (zero) group. To conclude, the onset of hypertension in peri- and early postmenopausal women was related to an increase in body weight despite controlling for initial body weight, reported physical activity and use of HRT. Therefore, preventing weight gain by dietary means and exercise is of great importance at menopausal age.

Risk factors associated with peri- and postmenopausal bone loss: does HRT prevent weight loss-related bone loss?

In the present study we evaluated the risk factors associated with peri- and postmenopausal bone loss and the effect of hormone replacement therapy (HRT) on weight-loss-related bone loss. The study population, 940 peri- and postmenopausal women, was selected from a random sample (n = 2025) of the OSTPRE study cohort (n = 13 100) in Kuopio, Finland. Bone mineral density (BMD; g/cm(2)) at the lumbar spine and femoral neck, and body weight, were measured at baseline in 1989-91 and at 5-year follow-up in 1994-97 by trained personnel. Five hundred and forty-seven women had never used HRT and 393 women used part-time or continuous HRT during follow-up of 3.8-7.9 years (mean 5.8 years). Similarly, of the 172 weight losers, 97 had never used HRT while 75 used it during follow-up. According to multiple regression analysis on the total study population (n = 940), HRT use, years since menopause and weight increase significantly predicted lower annual bone loss at both the lumbar spine and femoral neck (p < 0.005). Low baseline weight and higher age predicted higher bone loss only at the lumbar spine (p < 0.001) and high grip strength predicted lower bone loss only at the femoral neck (p = 0.021). In a sub-analysis on weight losers, weight loss predicted greater bone loss in HRT non-users (p < 0.05), whereas this was not observed in HRT users. These results remained similar after adjustment for age, weight, height, calcium intake, duration of menopause, baseline BMD and bone-affecting diseases/medication. In conclusion, the transition to menopause, HRT and weight change are the most important determinants of bone loss at both the lumbar spine and femoral neck. Furthermore, HRT seems to be effective in prevention of weight loss related bone loss.

Relation of statin use and bone loss: a prospective population-based cohort study in early postmenopausal women.

Recent experimental and epidemiologic studies have suggested that the lipid-lowering drugs, statins, may have bone-protective effects. We studied the effects of statin use on the change in bone mineral density (BMD) in a prospective 4.5-year cohort study based on subjects from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study, Finland. Six hundred and twenty women aged 53-64 years were divided into four groups: 55 women reported continuous and 63 women occasional statin use during the follow-up; 142 non-users of statins reported hypercholesterolemia whereas 360 non-users did not. Spinal and femoral BMDs were measured by dual-energy X-ray densitometry in 1995-1996 and 1999-2000 and the BMD changes of the four groups were compared. Characteristics of the study population were obtained with postal inquiries. The mean annual spinal and femoral BMD changes of the study groups were 0.29% and -0.50% for the continuous statin users, 0.19% and -0.57% for the occasional statin users, 0.52% and -0.29% for the hypercholesterolemic non-users of statins, and 0.39% and -0.33% for the non-users of statins without hypercholesterolemia, ( p = 0.398 and p = 0.404) respectively. The corresponding BMD changes adjusted for age, years since menopause, body mass index, BMD at baseline, calcium intake, estrogen and cortisone therapy, duration of follow-up and statin use before the baseline were -0.20% and -0.47%, 0.19% and -0.54%, 0.54% and -0.32%, 0.47% and -0.33% ( p = 0.134 and p = 0.628), respectively. Our results suggest that statins do not protect from early postmenopausal bone loss. Randomized trials are needed to confirm these results.

Lifestyle and other factors predict ankle fractures in perimenopausal women: a population-based prospective cohort study.

The Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study examines the risk factors for fractures and low bone density in middle-aged women. In the present study we investigated lifestyle and other risk factors for ankle fracture. The study population consisted of 11,798 women, aged 47-56 years at baseline. During the 5 year follow-up, these women sustained 194 validated malleolar fractures, giving an incidence of 3.4 fractures/1000 person-years. Four independent predictors for malleolar fracture were detected: smoking; multipharmacy; fracture history; and overweight status. The hazard ratio (HR) for positive fracture history was 1.63 (p = 0.005). In women with a body mass index (BMI) of 25-30 kg/m(2) vs. those with a BMI <25 kg/m(2), HR was 1.69 (p = 0.003). Those who used three or more prescribed drugs had an HR of 2.03 (p = 0.0003) vs. those who used no drugs. Smoking had a dose-response effect, with HRs of 1.73 (p = 0.016) in those smoking 1-19 cigarettes/day, and 2.94 (p = 0.001) in those smoking > or =20 cigarettes/day. Lifestyle factors and fracture history appear to be important predictors of ankle fracture.

Need for maternal critical care in obstetrics: a population-based analysis.

The purpose of this study was to note potential obstetric risk factors leading to maternal intensive care and to estimate the frequency, costs and outcomes of management. In a cross-sectional study of intensive care admissions in Kuopio from March 1993 to October 2000, 22 consecutive obstetric patients admitted to a mixed medical-surgical intensive care unit were followed. We recorded demographics, admitting diagnoses, APACHE II score, clinical outcomes and treatment costs. The overall need for maternal intensive care was 0.9 per 1000 deliveries during the study period. The mean age (+/-SD) of the patients was 31.7 (+/-6.6) years and the APACHE II score 10.8 (+/-6.2). The most common admission diagnoses were obstetric haemorrhage (73%) and pre-eclampsia-related complications (32%). The duration of ICU stay was 5.8 days (range 1-31) and one of the 21 patients died in the intensive care unit (4.5%). The total cost of intensive care was in the order of USD 5000 per patient. Very few obstetric patients develop complications requiring intensive care. Although several risk factors associated with maternal intensive care were documented, most cases occurred in low-risk women, which implies that the risk is relevant to all pregnancies. Long-term morbidity was rare, and collectively the outcome of intensive care was good. Further research is needed to determine effective approaches in prevention, such as uterine artery embolization.

Identification of genes differentially induced by hypoxia in pancreatic cancer cells.

A hypoxic microenvironment is characteristic of many solid tumors, including pancreatic cancer, the fifth leading cause of cancer death in the United States. Hypoxia causes the stabilization of the HIF-1 (hypoxia-inducible factor-1) transcription factor and the induction of many genes that promote angiogenesis, tumor growth, and metastasis. We performed representational difference analysis (RDA) using mRNA extracted from hypoxic and normoxic Capan-2, a human pancreatic cancer cell line. cDNAs corresponding to hypoxia-inducible genes were cloned and sequenced. We identified GPI/NLK/AMF (glucose phosphate isomerase/neuroleukin/autocrine motility factor) as a hypoxic inducible gene. In addition, hexokinase II and DEC1/Stra13, genes known to be hypoxia inducible in other systems, were found to be hypoxia inducible in our pancreatic cancer system. We thus identified three genes that are induced by hypoxia in a human pancreatic cancer, including GPI/NLK/AMF, which was not previously known to be hypoxia inducible in any other system. These genes may provide new targets for diagnosis and treatment of pancreatic cancer.

Cytochrome P450 3A expression in the human fetal liver: evidence that CYP3A5 is expressed in only a limited number of fetal livers.

CYP3A is the major cytochrome P450 subfamily constitutively expressed in the human liver. CYP3A4 is the predominant hepatic P450 form in adults and it is expressed at high but very variable levels among individuals. The fetal liver contains mainly CYP3A7, while the presence of the other CYP3A enzymes in fetal liver has remained controversial. In this study, the relative levels of CYP3A4, CYP3A5 and CYP3A7 expression were determined in a panel of 9-11 fetal livers with a similar gestation age (9-12 weeks) and compared to adult livers. CYP3A7 was found to be the major CYP3A form in all the fetal liver samples. The abundance of CYP3A7 varied more at the mRNA (77-fold variation) than at the protein level (4.8-fold variation). CYP3A5 mRNA was also detected in all of the fetal liver samples, but the average level was 700-fold lower than that of CYP3A7. CYP3A5 protein was detected by immunoblot analysis in only 1 fetal liver out of the 9 investigated, the level of expression being moderately high in this sample. CYP3A4 mRNA was detected in only a subset of the fetal liver samples and its level was the lowest of the CYP3A forms. This is the first study to demonstrate the polymorphic expression of CYP3A5 and the variability of CYP3A7 expression in fetal liver and suggests that significant interindividual differences in the metabolism of xenobiotics may already exist at the prenatal stage. These differences may contribute to individual pharmacological and/or toxicological responses in the fetus.

Risk of obstetric cholestasis in sisters of index patients.

The aim of the present study was to evaluate the rate of intrahepatic cholestasis of pregnancy in first-degree relatives of index patients. Index patients (n=65) with singleton pregnancies complicated by intrahepatic cholestasis were identified among the women (n=11 984) who gave birth at Kuopio University Hospital in 1994-1998. The pregnancy histories of relatives of 56 index patients were reviewed and the rate of cholestasis in first-degree relatives was compared with that in the general obstetric population. Obstetric cholestasis was experienced by 9% of the parous sisters and 11% of the mothers of the index patients. The risk per delivery was 6% in the first-degree relatives. The rate in the general obstetric population was 0.54%. The odds ratios and 95% confidence intervals were 12.6 (5.6-28.1) for the sisters and 12.2 (6.2-24.2) for the mothers. Obstetric cholestasis clusters within some families and is under strong genetic influence, although the precise genetic pattern remains obscure. The sisters of index patients are at an increased risk of the disorder and may benefit from close obstetric care.

Hormone replacement therapy and risk of falling in early postmenopausal women - a population-based study.

OBJECTIVE: The purpose of this study was to examine the effect of hormone (oestrogen) replacement therapy (HRT) on the risk of falling among early postmenopausal women. METHODS: We assessed the incidence of falls in HRT users compared to non-users using population-based data from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study. The study group consisted of 9792 postmenopausal women who responded to the OSTPRE baseline and follow-up inquiries. RESULTS: A total of 3049 women reported sustaining a fall during the previous 12 months. The association between current continuous use of HRT and overall risk of falling was non-significant - 9% (P = 0.10). However, current continuous HRT use was associated with a decreased risk (- 30%) of non-slip falls (N = 1129) (P = 0.0001) but not with the risk (+ 9%) of slip falls (N = 1757) (P = 0.23). In early postmenopausal women (time since menopause < 5 years) the protective effect of current continuous HRT was strengthened: the risk of non-slip falls was 71% lower in HRT users than non-users (P = 0.0035) if menopause had occurred within the past 2.5 years, and 43% lower (P = 0.0015) if time since menopause was 2.5-5 years. CONCLUSION: Hormone replacement therapy may reduce the risk of non-slip falls in early postmenopausal women.

Weights of placentae from small-for-gestational age infants revisited.

The objective of the study was to investigate the association between placental weight and birthweight in appropriate (AGA) and small for gestational age (SGA) infants. Placental weight, birthweight and their ratio in chromosomally normal singleton pregnancies with SGA (n=1569) and AGA (n=15 047) infants were compared, and their determinants were studied by logistic regression. SGA infants had 24 per cent smaller placentae than AGA infants when gestational age was used as a covariate. Placental actual weight was also lower in SGA infants than in AGA infants of the same birthweight (P< 0.001). SGA infants had smaller placentae than the controls, suggesting that fetal growth depends on the actual weight of the placenta. Future studies should evaluate whether growth restriction could be reversed by therapeutic approaches increasing placental weight.