IVF and stillbirth: a prospective follow-up study.

BACKGROUND: Previous studies have indicated that the risk of stillbirth is increased in singleton pregnancies achieved after assisted reproduction technology (ART). However, no previous study fully accounted for factors with potential influence on the risk of stillbirth. Further, whether fertility treatment, the possible reproductive pathology of the infertile couples or other characteristics related to being subfertile may explain a possible association with stillbirth remains unclear. This study compares the risk of stillbirth in women pregnant after fertility treatment (IVF/ICSI and non-IVF ART) and subfertile women with that in fertile women. METHODS: We used prospectively collected data from the Aarhus Birth Cohort, Denmark and included information about 20 166 singleton pregnancies (1989-2006). Outcome measure was stillbirth. RESULTS: The risk of stillbirth in women who conceived after IVF/ICSI was 16.2 per thousand ( per thousand) and in women who conceived after non-IVF ART 2.3 per thousand. In fertile and subfertile women, the risk of stillbirth was 3.7 per thousand and 5.4 per thousand, respectively. Compared with fertile women, women who conceived after IVF/ICSI had more than four times the risk of stillbirth [odds ratio (OR): 4.44, 95% confidence interval (CI): 2.38-8.28], and adjustments for maternal age, BMI, education, smoking habits and alcohol and coffee intake during pregnancy had only minor impact on the findings (OR: 4.08; 95% CI: 2.11-7.93). The risk of stillbirth in women who conceived after non-IVF ART and in women who conceived spontaneously with a waiting time to pregnancy of a year or more was not significantly different from the risk in women with a shorter time to pregnancy. CONCLUSIONS: Compared with fertile women, women who conceived by IVF/ICSI had an increased risk of stillbirth that was not explained by confounding. Our results indicate that the increased risk of stillbirth seen after fertility treatment is a result of the fertility treatment or unknown factors pertaining to couples who undergo IVF/ICSI.

Psychological stress during pregnancy and stillbirth: prospective study.

OBJECTIVE: To study the association between psychological stress during pregnancy and stillbirth. DESIGN: Prospective follow-up study. SETTING: Aarhus University Hospital, Skejby, Denmark,1989-98. POPULATION: A total of 19 282 singleton pregnancies in women with valid information about psychological stress during pregnancy. METHODS: Information about psychological stress during pregnancy was obtained from questionnaires and measured by the 12-item General Health Questionnaires (GHQ). A score was generated by the sum of all the answers, each contributing a value between 0 (low psychological stress) and 3 (high psychological stress). Women with an intermediate level of psychological stress (scores of 7-11) were considered the reference group. Scores of 0-6 were defined as a low level of psychological stress and scores of 12-36 as the highest level. The association between psychological stress and stillbirth was presented as relative risks with 95% CIs. Adjustment for potential confounding factors was carried out by logistic regression analyses. MAIN OUTCOME MEASURES: Stillbirth (delivery of a dead fetus at >28 weeks of gestation). RESULTS: There were 66 stillbirths (3.4 per thousand) in the population studied. Compared with women with an intermediate level of psychological stress during pregnancy, women with a high level of stress had 80% increased risk of stillbirth (relative risk = 1.8; 95% CI 1.1-3.2). Adjustment for maternal age, parity, maternal pre-pregnancy body mass index, smoking habits, alcohol and caffeine intake during pregnancy, education and cohabitation failed to change the result. The results remained essentially unchanged after exclusion of preterm deliveries. Exclusion of women with complications during pregnancy such as diabetes, hypertension, vaginal bleeding, immunisation and imminent preterm delivery failed to change the results. Likewise, restriction to women's first pregnancy in the cohort did not change the results. CONCLUSION: Psychological stress during pregnancy was associated with an increased risk of stillbirth.

Nicotine patches for pregnant smokers: a randomized controlled study.

OBJECTIVE: To assess the effect of nicotine patches on continine-validated smoking cessation in pregnant women and the effect of nicotine on birth weight and preterm delivery. METHODS: Pregnant women who smoked ten or more cigarettes after the first trimester (N = 250) were randomly assigned to receive nicotine patches (n = 124) or placebo patches (n = 126). Women randomized to nicotine were treated with 15-mg patches (16 hours/day) for 8 weeks, and 10-mg patches (16 hours/day) for 3 weeks. RESULTS: Overall, 26% stopped smoking and 14% were nonsmokers 1 year after delivery. There was no difference between nicotine and placebo groups. At the end of the intervention, the mean value of cotinine in saliva in women assigned to nicotine was 120 ng/mL and placebo 153 ng/mL (mean difference -33; 95% CI -72, 6 ng/mL). Mean birth weight difference was 186 g (95% CI 35, 336 g) higher in the nicotine than placebo group, and there was an insignificantly lower rate of low birth weight (under 2500 g) in the former group. There was no difference in the rate of preterm delivery between the two groups. CONCLUSION: Nicotine patches had no influence on smoking cessation during pregnancy, although they might increase birth weight in comparison with placebo.

[Is smoking during pregnancy a cause of premature delivery?]. / Er rygning under graviditet årsag til praeterm fødsel?

Preterm birth is an important determinant of perinatal mortality and morbidity. During the last ten years the rate of preterm birth has remained unchanged, and even though advances in neonatal intensive care have improved the chances of survival of the preterm child, the mortality remains high. In most cases the etiology is unknown, but several factors have been associated with preterm birth. However, most of these factors are not accessible for prevention. The search for preventable causes of preterm birth is therefore important. We reviewed English publications concerning smoking during pregnancy and preterm birth. We conclude that smokers have about a 50% higher risk of preterm birth compared to non-smokers. Furthermore, a dose response relationship seems to be present; the more the pregnant women smoke the higher the risk of preterm birth. If all pregnant women stopped smoking it can be estimated that between 5% and 20% of all preterm births could be avoided.

[Smoking among pregnant women and the significance of sociodemographic factors on smoking cessation]. / Rygevaner blandt gravide samt sociodemografiske faktorers betydning for rygeophør.

In order to describe smoking habits among pregnant women and predictors of smoking cessation all pregnant women attending routine antenatal care from 1989 to 1991 at the Department of Obstetrics, Aarhus University Hospital, were asked to fill in questionnaires. Information about smoking habits from 8806 women revealed that 44% smoked prior to pregnancy. One fifth of the smokers stopped smoking early in pregnancy, leaving 33% women smoking during pregnancy. The strongest predictor of smoking cessation was the number of cigarettes smoked prior to pregnancy, where those that smoked the least were most likely to give up smoking. Caffeine intake, parity, years of education, and partner's smoking habits were also associated with smoking cessation whereas social status, alcohol intake, marital status, and age of the women had no influence on smoking cessation. Thus, a strategy for a smoking cessation campaign among pregnant women could be directed towards women who smoke heavily prior to pregnancy and women with a high daily intake of caffeine.

[Smoking during pregnancy and preterm delivery]. / Rygning under graviditet og praeterm fødsel.

The purpose of the study was to evaluate the association between smoking during pregnancy and preterm birth. The overall rate of preterm delivery was 4.3%. Smokers had a 40% higher risk of preterm birth compared to non-smokers. A dose response relationship was found between smoking and risk of preterm birth. Adjustment for women's height, pre-pregnant weight, age of the mother, marital status, education, occupational status, and alcohol intake did not change the results. Among women with an intake of less than 400 mg of caffeine per day no difference in the risk of preterm birth between smokers and non-smokers was found. However, among women with an intake of more than 400 mg of caffeine per day, the risk of preterm birth was increased almost threefold among smokers compared to non-smokers. Furthermore, among women with a high intake of caffeine a dose response relationship was found between smoking and risk of preterm delivery.

[Strategies for smoking cessation among pregnant women]. / Strategier til rygeafvaenning blandt gravide kvinder.

Smoking during pregnancy is harmful to the health of the fetus and the newborn. Smoking increases the risk of low birthweight, preterm delivery and perinatal death. In developed countries smoking during pregnancy is regarded as the single most important risk factor for which it is possible to intervene. We reviewed the Scandinavian and English randomized controlled intervention studies directed towards smoking cessation during pregnancy. The intervention studies were classified according to the method of intervention namely antismoking advice, self-help manuals, measurements of smoking dependent chemical factors and multifactorial methods. We conclude that it is possible to reduce smoking during pregnancy only by an efficient and personal effort performed by a committed person towards each pregnant woman.

Gestational age, birth weight, and the risk of hyperkinetic disorder.

AIMS: To study the association between gestational age and birth weight and the risk of clinically verified hyperkinetic disorder. METHODS: Nested case-control study of 834 cases and 20 100 controls with incidence density sampling. RESULTS: Compared with children born at term, children born with gestational ages of 34-36 completed weeks had a 70% increased risk of hyperkinetic disorder (rate ratio (RR) 1.7, 95% confidence interval (CI) 1.2 to 2.5). Children with gestational ages below 34 completed weeks had an almost threefold increased risk (RR 2.7, 95% CI 1.8 to 4.1). Children born at term with birth weights of 1500-2499 g had a 90% increased risk of hyperkinetic disorder (RR 1.9, 95% CI 1.2 to 2.9), and children with birth weights of 2500-2999 g had a 50% increased risk (RR 1.5, 95% CI 1.2 to 1.8) compared with children born at term with birth weights above 2999 g. The results were adjusted for socioeconomic status of the parents, family history of psychiatric disorders, conduct disorders, comorbidity, and maternal smoking during pregnancy. Results related to birth weight were unchanged after adjusting for differences in gestational age. CONCLUSIONS: Children born preterm, also close to term, and children born at term with low birth weights (1500-2499 g) have an increased risk of clinically verified hyperkinetic disorder. These findings have important public health perspectives because the majority of preterm babies are born close to term.

The effect of induced arterial hypertension upon regional blood flow in subcutaneous tissue in patients with arterial insufficiency of the legs.

In nine patients with arterial insufficiency of the legs, the effect of induced arterial hypertension upon blood flow in subcutaneous tissue was correlated to the changes of blood flow in subcutaneous tissue during dependency. Arterial pressure was increased by constant intravenous infusion of angiotensin. Blood flow in subcutaneous tissue was measured 10 cm distal to the head of fibula, at the lateral malleolus, and at the base of the first toe by means of the xenon washout technique. It was found that in areas where blood flow decreased during dependency, blood flow decreased during angiotensin infusion. An increase in blood flow during angiotensin infusion was seen in areas where blood flow increased during dependency. It is concluded that the effect of angiotensin infusion on blood flow and of therapeutically induced hypertension can be predicted from the effect of orthostatic changes on blood flow. The results obtained support the hypothesis that the vessels behave as passive channels (i.e. blood flow depends mainly upon arterial perfusion pressure) in areas where the normal vasoconstrictor response to increased transmural pressure is abolished.

The effects of propanidid on arterial pressure, pulse rate, preganglionic sympathetic activity and barostatic reflexes in the cat.

We have studied the effects of propanidid on preganglionic cervical sympathetic nervous activity, arterial pressure, pulse rate and barostatic reflexes of the cat. Normal, hypertensive, baroreceptor denervated and decerebrate animals with sectioned vagal nerves were studied. On the basis of our findings it is concluded that propanidid exerts its depressant action on the cardiovascular system directly. Central circulatory control mechanisms are essentially unaffected. The depression of arterial pressure caused by propanidid is moderated by two compensatory mechanisms: normal barostatic reflexes causing an increased sympathetic tone in response to hypotension and a vagolytic action of propanidid.

The effects of althesin on arterial pressure, pulse rate preganglionic sympathetic activity and barostatic reflexes in cats.

We have studied the effects of Althesin on preganglionic cervical sympathetic nervous activity, arterial pressure, pulse rate and barostatic reflexes in cats. Normal, baroreceptor denervated and decerebrate animals were studied. On the basis of our finding it is concluded that Althesin severely depresses sympathetic nervous activity by action on the vasomotor centre. The depression of arterial pressure however was only moderate due to two compensatory mechanisms: a vagolytic action of Althesin and a peripheral vascular effect believed to be caused by an enhanced action of catecholamines caused by Althesin. Barostatic reflexes were found active under conditions where Althesin did not totally abolish sympathetic tone.

Cardiac effects of atropine and gallamine in patients receiving suxamethonium.

Eighty healthy patients were randomly allocated to four groups. Atropine 0.01 mg kg-1 i.v. (group I), gallamine 0.3 mg kg-1 i.v. (group II), atropine 0.01 mg kg-1 i.m. and gallamine 0.3 mg kg-1 i.v. (group III), or atropine 0.01 mg kg-1 i.v. and gallamine 0.3 mg kg-1 i.v. (group IV) were given before operation. After induction of anesthesia with thiopentone, suxamethonium 1 mg kg-1 was given i.v. The lungs were ventilated with halothane in nitrous oxide in oxygen. Five minutes later the same dose of suxamethonium was repeated. E.c.g. was monitored continuously. No serious bradycardia was observed following a second injection of suxamethonium in any group. The results suggest that thiopentone protects against suxamethonium-induced bradycardia during halothane anaesthesia.

Halothane anaesthesia ans suxamethonium II. The significance of preoperative gallamine administration.

Preoperative administration of gallamine was evaluated during inhalation anaesthesia with nitrous-oxide and halothane with two administrations of suxamethonium 1 mg/kg body weight, 5 min apart. Sixty healthy patients were randomly divided into three groups and preanaesthetic gallamine, 0.3, 0.4 or 0.5 mg/kg body weight, respectively was administered intravenously 3 min before induction, according to the allocation. Just before induction of anaesthesia the patients were examined for signs and symptoms of partial curarization. After induction of anaesthesia by nitrous-oxide-oxygen-halothane, suxamethonium 1 mg/kg was given intravenously. Exactly 5 min later the same dose was repeated. ECG was monitored continuously and serum potassium, Pao2 and Paco2 were measured at appropriate intervals. It was found that none of the examined doses of gallamine gave any reliable protection against serious bradyarrhythmias after repeated doses of suxamethonium. Furthermore the higher doses of gallamine caused an unacceptably high frequency of patients with tachycardia and signs and symptoms of partial curarization.

A prospective intervention study of stopping smoking in pregnancy in a routine antenatal care setting.

OBJECTIVES: To evaluate the effect of specific education of midwives on stopping smoking in pregnant women and to determine the effect of this programme on pregnancy outcome. DESIGN: A prospective intervention study. SETTING: Department of Gynaecology and Obstetrics, Aarhus University Hospital, Denmark. POPULATION AND METHODS: A group of midwives (9 out of 54) was taught the effects of smoking during pregnancy and instructed in various methods of educating women to stop smoking. All pregnant women who attended antenatal care from October 1994 to September 1995 were either in the intervention group (n = 527) or the control group (n = 2629). Pregnant women attending the specifically educated midwives were considered to be the intervention group. They were given individual advice about stopping smoking at the first antenatal visit at about 16 weeks of gestation and a leaflet on smoking and pregnancy. RESULTS: At the first antenatal visit at about 16 weeks of gestation, 22% of the pregnant women smoked. Between the first visit and the routine visit at 30 weeks of gestation 51 (2%) stopped smoking and 56 (2%) started smoking. No differences were found between the intervention group and the control group in the rate of stopping smoking, validated by cotinine measurements. Mean birthweight, mean gestational age and the proportion of preterm birth in the two groups were similar. CONCLUSION: Education of midwives and integration of advice about smoking cessation at a low cost in routine antenatal care failed to affect smoking habits among pregnant women.

Maternal smoking and gestational age in twin pregnancies.

BACKGROUND: A twin pregnancy imposes greater demands on maternal physiology and smoking may thus be associated theoretically with a greater risk of preterm delivery than in singleton pregnancies. POPULATION AND METHODS: From 1989 to 1996 all women who booked for antenatal care at the Department of Gynecology and Obstetrics, Aarhus University Hospital, Denmark were asked to fill in two questionnaires. Apart from smoking habits, these questionnaires provided information on medical and obstetric history together with information on sociodemographic and other lifestyle variables. Gestational age at delivery was calculated from ultrasonographically determined fetal biparietal diameter and information about the last menstrual period. Only women carrying twins were included in the present study (n=401). RESULTS: Mean gestational age was 5 days (95% CI 1-9 days) shorter among smokers compared with non-smokers. Among non-smokers mean gestational age was 261 days (+/-18), among women who smoked 1-9 and 10+ cigarettes per day 257 days (+/-23) and 255 days (+/-20), respectively. The overall risk of preterm delivery (< 37 weeks) and delivery before 34 completed weeks was 1.3 (95% CI 0.9-2.2) and 1.4 (95% CI 0.8-2.4), respectively. Primiparous women had shorter gestational age than did multiparous women. Still, among primiparous as well as among multiparous women gestational age decreased with smoking. Adjustment for maternal age, height and prepregnancy weight, alcohol and caffeine intake, marital status, education, occupational status, preterm birth in previous pregnancies, and in vitro fertilization in the present pregnancy did not change the results. CONCLUSIONS: Smoking has a substantial effect on mean gestational age in twin pregnancies, and a dose response like relationship is present.

Smoking during pregnancy and infantile colic.

OBJECTIVE: To evaluate the association between maternal smoking during pregnancy and infantile colic (IC). METHODS: A follow-up study of singleton infants delivered by Danish mothers at the Aarhus University Hospital from May 1991 to February 1992 and still living in the municipality of Aarhus at the age of 8 months was conducted. A total of 1820 mothers and their infants were included. Self-administered questionnaires were used to collect data on smoking, other lifestyle factors, and sociodemographic variables at 16 and 30 weeks of gestation and 8 months postpartum. IC was defined in the 8-month questionnaire and based on Wessel's criteria, except that we used only the crying criterion. RESULTS: IC was seen in 10.8% of all infants. We observed a twofold increased risk of IC among infants whose mothers smoked 15 or more cigarettes per day during their pregnancy(relative risk: 2.1; 95% confidence interval: 1.4-3.2) or in the postpartum period (relative risk: 2.0; 95% confidence interval: 1.3-3.1). Women who smoked continuously during pregnancy and the postpartum period had a relative risk of 1.5 (95% confidence interval: 1.1-2.0) of having a infant with IC compared with women who did not smoke during this period. Adjustment for maternal age, parity, marital status, alcohol intake, birth weight, gestational age, breastfeeding, caffeine intake postpartum, and paternal smoking did not change the effect measures. CONCLUSION: The results indicate that maternal smoking during pregnancy may increase the risk of IC.

Halothane anaesthesia and suxamethonium I: the significance of preoperative atropine administration. A double-blind study.

Preoperative administration of atropine was evaluated during induction of halothane anaesthesia with two administrations of suxamethonium 1 mg/kg body weight, 5 min apart. Sixty-eight healthy, adult patients were studied. They were divided into five groups according to dose and route of administration of atropine. ECG was continuously monitored. Serum potassium, pH, PaCO2, PaO2 and standard bicarbonate were measured at appropriate intervals. It was found that neither atropine 0.01 mg/kg body weight given intramuscularly 1 h beofre the anaesthesia nor atropine 0.01 mg/kg body weight given intravenously 5 min prior to induction protected against serious bradycardias (defined as heart rate below 20 beats per minute) following the second dose of suxamethonium. No serious brady-arrhythmias were seen in patients given either a combination of intramuscular and intravenous atropine in the above-mentioned doses or in patients given atropine 0.015 mg/kg body weight intravenously 5 minutes prior to induction. However, a decrease in heart rate to around 40-50 beats per minute occurred in some of these patients. Furthermore, these large doses of atropine caused an increase in heart rate during induction to more than 120 beats per minute in about 50% of the patients and to more than 140 beats per minute in about 25% of the patients. Our results suggest that preoperative administration of atropine does not protect against serious brady-arrhythmias following a second dose of suxamethonium, unless doses of atropine are used which cause tachycarida of considerable degree.