In utero exposure to maternal smoking and women's risk of fetal loss in the Norwegian Mother and Child Cohort (MoBa).

BACKGROUND: Whether in utero exposure to tobacco smoke increases a woman's risk of fetal loss later in life is unknown, though data on childhood exposure suggest an association may exist. This study evaluated the association between in utero exposure to tobacco smoke and fetal loss in the Norwegian Mother and Child Cohort Study (MoBa), which enrolled ∼40% of the pregnant women in Norway from 1999 to 2008. METHODS: Information on exposure to tobacco smoke in utero, the woman's own smoking behavior during pregnancy and other factors was obtained by a questionnaire completed at ∼17 weeks of gestation. Subsequent late miscarriage (fetal death <20 weeks) and stillbirth (fetal death ≥ 20 weeks) were ascertained from the Norwegian Medical Birth Registry. This analysis included 76 357 pregnancies (MoBa data set version 4.301) delivered by the end of 2008; 59 late miscarriages and 270 stillbirths occurred. Cox proportional hazards models were fit for each outcome and for all fetal deaths combined. RESULTS: The adjusted hazard ratio (HR) of late miscarriage was 1.23 [95% confidence interval (CI), 0.72-2.12] in women with exposure to maternal tobacco smoke in utero when compared with non-exposed women. The corresponding adjusted HR for stillbirths was 1.11 (95% CI, 0.85-1.44) and for all fetal deaths combined, it was 1.12 (95% CI, 0.89-1.43). CONCLUSIONS: The relatively wide CI around the HR for miscarriage reflected the limited power to detect an association, due to enrollment around 17 weeks of gestation. However, for in utero exposure to tobacco smoke and risk of stillbirth later in life, where the study power was adequate, our data provided little support for an association.

Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults.

BACKGROUND: Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery. OBJECTIVES: To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted. SELECTION CRITERIA: Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention. DATA COLLECTION AND ANALYSIS: Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed. MAIN RESULTS: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. AUTHORS' CONCLUSIONS: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

Circulating lipopolysaccharides in the blood from "bioprotein" production workers.

BACKGROUND: Workers producing bacterial single-cell protein (BSCP), "bioprotein," are exposed to organic dust containing high levels of endoxins (lipopolysaccharides, LPS). Workers in this industry have complained of episodes of fever, fatigue, chest tightness, skin dryness and rubor. The aim of the present study was to quantify LPS and inflammatory mediators in plasma among the workers and non-exposed control subjects. METHODS: We included eight non-smoking production workers, aged 32-51 (median 38), and eight non-smoking, non-exposed controls, aged 30-51 (median 39). Airborne and plasma endotoxin concentrations were measured, as well as plasma hsCRP and different cytokines, chemokines and metalloproteinases. RESULTS: The workers who did not use personal respiratory protection were exposed to varying airborne levels of endotoxin, 430 (75-15 000) EU/m3 (median, range). The level of plasma LPS was significantly elevated (p = 0.01) among the workers compared to the non-exposed controls. The workers also had elevated levels of MCP-1 (p = 0.02), MIP-1alpha (p = 0.05) and MMP-3 (p = 0.04). IL-6 and hsCRP were also elevated among the exposed group, but not significantly (p = 0.10 and p = 0.07, respectively). CONCLUSIONS: In this study, we detected LPS in plasma of individuals exposed to high levels of LPS at their workplace. This finding is supported by elevated levels of several inflammatory cytokines among the workers, significantly exceeding that of the non-exposed control group. To the best of our knowledge, this is the first time that plasma LPS, together with increased inflammatory markers in plasma, has been detected in an occupational setting.

Response of circulating immune cells to major gunshot injury, haemorrhage, and acute surgery.

PURPOSE: The purpose of this study was to use an established porcine model to investigate the effects on immune function of severe gunshot injury. METHODS: Twelve pigs sustained two standardised rounds, one through right femur and one through left upper abdomen. First aid treatment and acute surgery was started immediately. Blood samples were drawn before shooting and after 75 min. Circulating neutrophils were isolated and reactive oxygen species (ROS) measured. Serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, and IL-10 were determined at 0, 75 min, as well as 2h after incubation with 1 microg/ml endotoxin in an ex vivo whole blood model. RESULTS: TNF-alpha, IL-1beta, and IL-6 significantly increased at 75 min. ROS in circulating granulocytes tended to increase (NS). Incubation with endotoxin led to a more than 100-fold increase of TNF-alpha pre-trauma, compared to a three-fold increase post-trauma (p<0.0001 between groups). A similar pattern was obtained for IL-1beta, and IL-6. IL-10 was below detection in all samples. The granulocytes maintained their ability to react to the protein kinase C activator phorbol myristate acetate (PMA) after trauma. CONCLUSION: Severe gunshot injury and peritraumatic stress rapidly activate circulating immune cells, but reduce their capacity to react to a subsequent challenge to endotoxin.

Tumour necrosis factor alpha and its promoter polymorphisms' role in the phenotypic expression of hemochromatosis.

BACKGROUND: The majority of hemochromatosis patients are homozygous for the HFE-C282Y mutation. However, less than half of C282Y homozygous subjects identified by population screening studies actually develop the disease. The cytokine TNF-alpha is implicated in the regulation of iron metabolism at different levels. Our aim was to study the role of TNF-alpha and its promoter polymorphisms in the phenotypic expression of hemochromatosis in individuals with and without the C282Y mutation. METHODS: We studied 4 groups of 10 subjects each: (1) C282Y homozygotes without clinical hemochromatosis; (2) C282Y homozygotes with hemochromatosis; (3) secondary hemochromatosis (without C282Y mutation); and (4) controls. Groups were age-matched and sex-matched. Peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) and the release of TNF-alpha was measured. Additionally, the G/A polymorphisms at position -238 and -308 of the TNF-alpha, gene were determined by PCR and RFLP analysis in 178 hemochromatosis patients and 41 controls. RESULTS: TNF-alpha production from PBMC at 8 and 24 h after increasing concentrations of LPS stimulation were similar in the four groups. The prevalence of TNF-alpha polymorphisms was similar in patients and controls. The prevalences of cirrhosis, siderosis, median s-ferritin and median ALT values were similar in patients with and without the TNF-alpha polymorphisms. CONCLUSIONS: Neither TNF-alpha, released from PBMC nor the presence of TNF-alpha polymorphisms seem to be associated with disease manifestation in hemochromatosis.

Familial fatal fetal cardiomyopathy with isolated myocardial calcifications: a new syndrome?

We describe three male sib fetuses with isolated myocardial calcifications resulting in intrauterine fetal death (IUFD) as early as the second trimester. No evidence for an underlying mitochondrial cytopathy, dystrophinopathy or myopathy was found. There were no signs of inflammation or a metabolic disorder, and the mother had no prenatal exposure of teratogenic drugs. Furthermore, no mutation in the Barth syndrome gene (G4.5) could be detected. Because isolated calcification of the heart and IUFD are not typical of any previously described inherited cardiomyopathy, it may represent a new familial fetal cardiomyopathy.

Non-mannose-capped lipoarabinomannan stimulates human peripheral monocytes to expression of the "early immediate genes" tissue factor and tumor necrosis factor-alpha.

In the present study, we have shown that stimulation of cryopreserved, human peripheral blood monocytes with the cell wall components from Gram-negative bacteria, lipopolysaccharide (LPS), and from rapid-growing Mycobacterium sp., non-mannose-capped lipoarabinomannan (AraLAM), both induce expression of the "early immediate genes" tissue factor (TF) and tumor necrosis factor-alpha (TNF-alpha). This was demonstrated both at the protein and the mRNA levels. Antibodies against the CD14 receptor could block the stimulating effects. AraLAM was a significantly weaker inducer than LPS, and we speculate that this may reside in the number of the fatty acids in the part of the molecule that interacts with the CD14/Toll-like receptors (TLR). Finally, both LPS and AraLAM activated the "early immediate genes" through translocation of the transcription factor proteins NF-kappaB/Rel and increasing the binding activity of AP-1.

A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy.

We recently described mutations of the neuronal sodium-channel alpha-subunit gene, SCN1A, on chromosome 2q24 in two families with generalized epilepsy with febrile seizures plus (GEFS+) type 2. To assess the contribution that SCN1A makes to other types of epilepsy, 226 patients with either juvenile myoclonic epilepsy, absence epilepsy, or febrile convulsions were screened by conformation-sensitive gel electrophoresis and manual sequencing of variants; the sample included 165 probands from multiplex families and 61 sporadic cases. The novel mutation W1204R was identified in a family with GEFS+. Seven other coding changes were observed; three of these are potential disease-causing mutations. Two common haplotypes, with frequencies of .67 and .33, were defined by five single-nucleotide polymorphisms (SNPs) spanning a 14-kb region of linkage disequilibrium. An SNP located 18 bp upstream of the splice-acceptor site for exon 3 was observed in 7 of the 226 patients but was not present in 185 controls, suggesting possible association with a disease mutation. This work has confirmed the role of SCN1A in GEFS+, by identification of a novel mutation in a previously undescribed family. Although a few candidate disease alleles were identified, the patient survey suggests that SCN1A is not a major contributor to idiopathic generalized epilepsy. The SCN1A haplotypes and SNPs identified here will be useful in future association and linkage studies.

Aspirin potentiates LPS-induced fibrin formation (FPA) and TNF-alpha-synthesis in whole blood.

The effect of aspirin on LPS-incubation of whole blood was investigated. Aspirin induced a concentration dependent increase (2.5-5-fold at 5 mM aspirin) in LPS-induced appearance of TNF-alpha and fibrinopeptide A (FPA) in plasma, despite the concomitant increase in the inhibitory cytokine IL-100. Aspirin substantially raised the levels of LPS-induced TF-mRNA and TNFalpha-mRNA in monocytes isolated from whole blood. The median ratio for TF-/beta-actin mRNA increased from 1.5 +/- 0.44 in the presence of LPS-alone, to 2.5 +/- 0.51 when 5 mM aspirin was added. The TNFalpha/beta-actin mRNA ratios were 1.8 +/- 0.4 and 5.5 +/- 2.7 respectively. Addition of exogenous PGE2 before incubation nearly abrogated the effect of aspirin on TNF-alpha, substantiating the role of PGE2 as a regulator of TNF-alpha synthesis, whereas the effect on FPA was small. Thus, in the presence of LPS in this whole blood model, aspirin apparently had a pro-inflammatory rather than an anti-inflammatory effect.

Maternal smoking and birthweight: effect modification of period, maternal age and paternal smoking.

OBJECTIVE: To study the effect on birthweight of maternal smoking, and its modification by study period, maternal age and paternal smoking. DESIGN: A retrospective questionnaire based national survey comprising a random sample (n=34,799) of all mothers giving birth in Norway 1970-91. Variables studied were parental smoking during pregnancy, birthweight, maternal age and infant's year of birth. RESULTS: The overall difference in mean birthweight between non-smoking and smoking mothers was 197 g. The difference in birthweight between non-smoking and smoking mothers increased with maternal age from 182 g (<20 years of age) to 232 g (35+ years of age). There was no significant effect of paternal smoking on birthweight when the mother was a non-smoker. When the mother was a smoker and the father was a non-smoker, the birthweight, adjusted for maternal age, was reduced by 153 g (p<0.005). However, when both parents smoked, the birthweight, adjusted for maternal age, was reduced by 201 g (p<0.0005). Even though the prevalence of paternal smoking decreased by 38% during the study period, there was no significant increase in overall mean birthweight. IMPLICATION AND RELEVANCE OF RESULTS: The negative effect of maternal smoking on birthweight appears to increase with maternal age. For a non-smoking pregnant woman to live with a smoking partner has little, if any, effect on birthweight. The negative effect of paternal smoking was only observed when the mother was smoking and might reflect two possible mechanisms: (1) that a smoking mother has a greater cigarette consumption when the partner also smokes, and (2) that a smoking mother is less concerned about passive smoking than a non-smoking mother.

OFD II, OFD VI, and Joubert syndrome manifestations in 2 sibs.

We present 2 sibs with manifestations of oral-facial-digital syndromes (OFD) and Joubert syndrome. The index patient was the 5th child of healthy nonconsanguineous Turkish parents. At birth this female patient had large hydrocephalus, hypertelorism, deep-set eyes, nystagmus, broad mouth, thick oral frenula, cleft palate, hamartomas of the tongue, postaxial polydactyly of fingers, normal toes, and hypotonia. Cranial MRI showed hydrocephalus and Dandy-Walker malformation. The child had no psychomotor development, was unable to swallow and had severe seizures. She died at 2 months of recurrent apneic episodes. At birth the brother of the index patient showed prominent forehead, broad, deep nasal bridge, cleft palate, multiple hamartomas of the tongue, irregular alveolar ridges, retrognathia, bilateral postaxial polydactyly of the hands and feet, and broad halluces. He had an abnormal breathing pattern with phases of tachypnea and apnea. Cranial MRI showed hydrocephalus, hypoplasia of the cerebellar vermis, Dandy-Walker malformation, and hypomyelination of the corpus callosum. Renal ultrasonography demonstrated multiple small cysts. Ocular fixation was absent and he had a mild nystagmus.

DNA damage induced by the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) in mammalian cells in vitro and in mice.

3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) formed during chlorination of water containing natural organic substances, is a very potent bacterial mutagen. Recently, tumours at multiple sites were reported in rats given MX-containing drinking water. We have investigated the genotoxicity of MX in mammalian cells exposed in vitro and in vivo using alkaline filter elution to detect DNA single-strand breaks and/or alkali-labile sites (SSBs). Concentrations as high as 100 and 300 microM MX were required to induce detectable levels of SSBs in the HL-60 cells. If MX treatment was carried out in the presence of DNA repair inhibitors (AraC plus hydroxyurea), the sensitivity of the assay to detect MX-induced SSBs was increased by a factor of 100. The presence of serum proteins during exposure resulted in a minor reduction of the MX-induced DNA damage in HL-60 cells at the lowest MX concentrations. In primary cultures of testicular cells as well as in resting human peripheral blood mononuclear cells (PBMC), a slightly increased level of SSBs was observed at MX-concentrations above 30 microM, this effect was not further increased by repair inhibitors. In LLC-PK1 renal proximal tubular epithelial cells and in growth stimulated human peripheral PBMC, increased SSBs were detected at MX concentrations as low as low as 3-10 microM and higher using repair inhibitors, and at 10 times higher concentrations without repair inhibitors. No dose dependent DNA damage was detected in the liver, kidney, spleen and colon of male B6C3F1 mice administrated high doses of MX (40 and 80 mg kg-1). Moderately increased and dose dependent SSBs were detected in the liver and kidney in the presence of DNA repair inhibitors during MX treatment, but no such increase was observed in the spleen and colon.

Secular trends in breastfeeding and parental smoking.

To explore the association between smoking and breastfeeding, we obtained data from a retrospective questionnaire-based national survey comprising a random sample (n = 34799) of all mothers giving birth in Norway 1970-91. Variables studied were postpartum smoking habits for both parents, duration of breastfeeding, infant's year of birth and parental age. The response rate was 70% (n = 24438). During the study period, the maternal postpartum smoking prevalence decreased from 38% to 26%. The proportion breastfeeding at 6 months increased from 15% to 44% among smokers, and from 30% to 72% among non-smokers. In spite of a considerable increase in breastfeeding both among smokers and non-smokers, the proportion of breastfeeding, non-smoking women at 6 months was twice that of smoking women during the whole period. Furthermore, the duration of breastfeeding was shorter among young mothers and when the fathers were smoking. There was epidemiological evidence that the effect on breastfeeding of smoking might represent both biological and social mechanisms.

Single-strand breaks, cell cycle arrest and apoptosis in HL-60 and LLCPK1 cells exposed to 1,2-dibromo-3-chloropropane.

We investigated 1,2-dibromo-3-chloropropane (DBCP)-induced DNA damage, cell cycle alterations and cell death in two cell lines, the human leukemia HL-60 and the pig kidney LLCPK1, both of which are derived from potential target sites for DBCP-induced toxicity. DBCP (30-300 micromol/L) caused a concentration-dependent increase in the levels of DNA single-strand breaks in both cell lines as well as in cultured human renal proximal tubular cells. After extended DBCP exposure in LLCPK1 cells (100 micromol/L, 30 h), the level of DNA breaks returned almost to control values. Incubation for 48 h showed a clear reduction of growth with DBCP concentrations as low as 10 micromol/L. Flow cytometric analysis showed that DBCP (1-10 micromol/L) exposure for 24 h caused an accumulation of LLCPK1 cells in the G2/M-phase. In HL-60 cells the accumulation in G2/M-phase was less marked, and at higher concentrations the cells accumulated in S-phase. Flow cytometric studies of HL-60 and LLCPK1 cells exposed to 100-500 micromol/L DBCP showed increased number of apoptotic cells/bodies with a lower DNA content than that of the G1 cells. Microscopic studies revealed that there were increased numbers of cells with nuclear condensation and fragmentation, indicating that apoptosis was the dominant mode of death in these cell lines, following exposure to DBCP. The characteristic ladder pattern of apoptotic cells was observed when DNA from DBCP-treated HL-60 cells and LLCPK1 cells was electrophoresed in agarose. The finding that DBCP can cause an accumulation of cells in G2/M-phase and induce apoptosis in vitro may be of importance for the development of DBCP-induced toxicity in vivo.

[Can we rely on self-reported smoking habits?]. / Kan vi stole på egenerklaerte røykevaner?

The reliability of self-reporting on smoking habits has been evaluated by comparing the reported smoking habits with the concentration of serum thiocyanate, which is higher in smokers than in non-smokers and increases with increasing cigarette consumption. When a smoker stops smoking, the level of serum thiocyanate decreases and falls to the level observed in non-smokers after about one month. When the questions asked about smoking were neutral, the reported smoking habits were generally reliable. However, in cases where the questions asked and the interview situation could be regarded as unpleasant, the reported smoking habits were not always correct. Some smokers underreported the number of cigarettes they smoked on a daily basis and some of them denied smoking altogether.

Smoking habits among pregnant women in Norway 1994-95.

AIMS: To investigate the smoking prevalence the last three months before pregnancy and at 18 weeks of gestation among women in Norway and to evaluate the impact of pre-pregnancy smoking habits, maternal age, level of education, civil status and parity on smoking cessation. MATERIAL AND METHODS: A prospective, multicenter survey. The study population included 4 766 pregnant women who attended a routine ultrasound examination at 18 weeks of pregnancy in six Norwegian hospitals during the period from September 1994 to March 1995. Smoking habits before and during pregnancy were recorded. RESULTS: The point prevalence of self-reported daily smoking among the women three months before the pregnancy was 34%. At 18 weeks of pregnancy, 21% of the women reported smoking daily (p<0.001). A multiple logistic regression analysis revealed that a low number of cigarettes smoked per day during the last three months before pregnancy was the best predictor for smoking cessation. Educational level, maternal age, parity and civil status were also statistically significant contributors to smoking cessation. Eighty percent of the women who were unable to stop smoking, reported a reduction in cigarette consumption. The mean number of cigarettes per day was reduced from 13.9 before pregnancy to 7.3 at 18 weeks of pregnancy (p<0.001). CONCLUSION: In a national survey, 21% of the pregnant women reported smoking daily in the second trimester. Thirty-eight percent of the women who were daily smokers before the pregnancy stopped smoking in early pregnancy. A low cigarette consumption prior to the pregnancy was the best predictor for smoking cessation.

Topographic analysis of proliferative activity in carotid endarterectomy specimens by immunocytochemical detection of the cell cycle-related antigen Ki-67.

BACKGROUND: On the basis of contradictory results found in animal experiments and coronary atherectomy tissue, there is an ongoing debate about the significance of cellular proliferation in human atherosclerosis. In the present prospective study, the cell cycle-related antigen Ki-67 was detected for topographic determination of cell turnover in distinct regions of human carotid endarterectomy specimens harvested en bloc by surgical biopsy. METHODS AND RESULTS: After en bloc resection, serial sections of 26 consecutive carotid lesions were analyzed by histomorphological examination and immunohistochemistry. Thereby, 319 high-power fields were attributed to separate plaque regions defined as follows: distal boundary of the lesion with normal intima, plaque shoulder, core region, and diffuse intimal thickening. Endothelial cells, smooth muscle cells, T cells, and macrophages were identified by immunostaining of factor VIII-related protein, alpha-actin, CD68, and CD45R0. An overall proliferation index of 0.49+/-1.05% was yielded by positive anti-Ki-67 immunolabeling, predominantly in macrophage-rich areas characterized by high cell density (>1000 cells/mm2) as well as in reparative sites in the perimeter of atheroma, intramural thrombosis, plaque hemorrhage, and neovascularization (P<.01). Few or no signs of proliferation activity were found in normal intima, in areas of dense alpha-actin positivity, or adjacent media. As shown by double immunostaining, macrophages and unspecified mesenchymal cells represented the prevailing proliferating cell type. CONCLUSIONS: Our results suggest that proliferation in advanced human carotid lesions is confined to the intima and focally concentrated in central plaque regions negative for alpha-actin. Furthermore, it apparently occurs primarily as part of inflammatory processes and structural repair predominantly involving macrophages, as well as unspecific mesenchymal cells.

The pregnant smoker's experience of ante-natal care--results from a qualitative study.

OBJECTIVES: 1) To obtain insight into pregnant smokers' experience of the information received from doctor and midwife at the ante-natal clinic. 2) To develop an understanding of pregnant women's own ideas of how health personnel can help them stop smoking. DESIGN: Qualitative study with strategic sampling. 33 pregnant smokers took part in an in-depth interview in the third trimester. SETTING: Home of patients, or surgeries in Hordaland county, Norway. PARTICIPANTS: Daily smokers during the last three months before conception, and still smoking in the 16th-18th week of pregnancy. RESULTS: Pregnant women lacking motivation to stop smoking seemed to be most satisfied with ante-natal care. The women interviewed saw doctors and midwives as responsible for raising the subject of smoking, and blamed them for disinterest. The findings suggest that pregnant smokers may be classified into four categories ("it could have been worse", "self-delusion", "self-confident", and "rational"), and that intervention should be tailored to meet each woman's perception of control over smoking behaviour.

Smoking habits among pregnant women in a Norwegian county 1987-1994.

BACKGROUND: The aim of the study was to investigate changes in smoking habits among pregnant women in the city of Trondheim and its surroundings. We also wanted to register the effect of a national campaign against smoking in pregnancy introduced in December 1989. MATERIAL AND METHODS: From 1987-1994 midwives interviewed 21 348 women in a non-selected population during a routine ultrasound examination at 18 weeks of pregnancy. Smoking habits and cigarette consumption were recorded. RESULTS: The point prevalence smoking rate among pregnant women decreased from 34% in 1987 to 22% in 1994 (p<0.001). A stratified analysis indicated that the reduction was not confounded by changes in age and parity over time. The mean number of cigarettes per pregnant smoker decreased from 8.6 cigarettes per day to 7.0 cigarettes per day during the study period (p<0.001). In 1987, 49% of the pregnant smokers consumed > or = 10 cigarettes compared with 35% in 1994 (p<0.001). The national campaign may have reinforced the on-going decline in smoking rate, but no significant effect was observed. CONCLUSIONS: The study demonstrated a statistically significant reduction in smoking prevalence among pregnant women in the study area. A similar decrease was not observed among women in the general population. No significant effect of the national campaign against smoking during pregnancy was observed.