Impact of lifestyle intervention for obese women during pregnancy on maternal metabolic and inflammatory markers.

BACKGROUND: Offspring of obese mothers have increased risk of developing obesity and related short- and long-term disease. The cause is multifactorial and may partly be explained by the unfavorable intrauterine environment. Intervention during pregnancy leading to a healthier lifestyle among obese may alter this. OBJECTIVE: To assess the effect of lifestyle intervention on markers of maternal metabolism and inflammation in 'the TOP (Treatment of Obese Pregnant Women) study', a randomized controlled trial. METHODS: In the TOP-study 425 participants with body mass index ⩾30 kg/m2 were randomized to intervention with dietary advices and physical activity assessed by pedometer (PA+D), physical activity assessed by pedometer (PA) or control (C). Of 389 participants completing the study 376 had available blood samples. Serum was analyzed for insulin, c-peptide, lipid profile, leptin, high-sensitivity CRP (hsCRP) and Soluble urokinase Plasminogen Activator Receptor (suPAR), in week 18-20 and 28-30, and simultaneously a 2-h oral glucose-tolerance-test was performed. Diet was assessed in gestational week 11-14 and 36-37 using a validated 360-item Food Frequency Questionnaire. RESULTS: Median levels of hsCRP in gestational week 28-30 were lower in each of the intervention groups (8.3 mg/l in PA+D group, P=0.03; and 8.8 mg/l in PA group, P=0.02) versus the control group (11.5 mg/l). Obtaining 11 000 steps per day as aimed for resulted in a 21% lower hsCRP compared to non-compliant women. Women reporting high carbohydrate intake had around 30% higher hsCRP concentrations in late gestation than women reporting the lowest intake. There were no differences in lipid profile or any of the metabolic markers in gestational week 28-30 when comparing the intervention and control groups. CONCLUSIONS: Lifestyle intervention in obese women can reduce hsCRP representing a marker of inflammation during pregnancy. The effect may partly be mediated by more physical activity and partly by changes in intake of carbohydrates and the glycaemic load.

Risk of a venous thromboembolic episode due to caesarean section and BMI: a study in northern Denmark covering 2000-2010.

BMI significantly influences the risk of venous thromboembolism after emergency caesarean delivery compared with vaginal delivery.

Randomised trial of cervical cerclage, with and without occlusion, for the prevention of preterm birth in women suspected for cervical insufficiency.

OBJECTIVE: To evaluate the effect of cerclage, with and without cervical occlusion. DESIGN: Multicentre, stratified, randomised controlled trial. SETTING: Hospital-based multicentre study with 18 tertiary centres from nine countries. POPULATION: Women with a history of cervical insufficiency (prophylactic trial) and women with a short cervix (therapeutic trial) were recruited from August 2006 to August 2011. METHODS: A centralised telephone randomisation service with a computer system was used to randomise women to cervical cerclage with or without cervical occlusion. Only the analyst performing the interim analyses was blinded. MAIN OUTCOME MEASURES: The take-home baby rate (number of infants discharged alive from the hospital), gestational age at delivery, and the number of days in the neonatal intensive care unit (NICU). RESULTS: Women (n = 309) were stratified into the prophylactic trial (n = 213) or the therapeutic trial (n = 96). The trial stopped early due to slow recruitment and an interim analysis showing no benefit of occlusion. Final analysis comprised 197 women in the prophylactic trial and 87 women in the therapeutic trial. No added effect of cervical occlusion was found in terms of the take-home baby rate in the prophylactic trial (92 versus 90%, RR 1.03, 95% CI 0.94-1.12) or in the therapeutic trial (81 versus 85%, RR 0.96, 95% CI 0.79-1.16). No effect of cervical occlusion was found in terms of gestational age at delivery and number of days the neonate spent in the NICU. Cervical occlusion was associated with no harm. CONCLUSIONS: Cervical occlusion with cerclage had no significant additional effect.

Physical activity during pregnancy in normal-weight and obese women: compliance using pedometer assessment.

The objectives of this prospective study were to compare physical activity in 70 normal-weight women with a body mass index (BMI) 20-25 kg/m(2), and 70 obese with a BMI ≥ 30 kg/m(2), before and during pregnancy, and to compare compliance using the pedometer. Physical activity before pregnancy was assessed by questionnaires and during pregnancy by a pedometer worn on 7 consecutive days every 4th week. Obese women were less physically active than normal-weight women both before (p <0.05) and during pregnancy (p <0.0012). Both the compliance and the physical activity gradually declined during gestation. The change in physical activity could be described by a significant interaction between BMI group, gestational age (p <0.007) and the day of the week (p <0.001) when using ANOVA and interaction analysis. Maternal weight gain was larger in the normal-weight than in the obese women, but lower in the non-compliant obese women compared with the compliant (p <0.05).

Prolonged labour as indication for emergency caesarean section: a quality assurance analysis by criterion-based audit at two Tanzanian rural hospitals.

OBJECTIVE: To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour. DESIGN: A quality assurance analysis of a retrospective criterion-based audit supplemented by in-depth interviews with hospital staff. SETTING: Two Tanzanian rural mission hospitals. POPULATION: Audit of 144 cases of women undergoing caesarean sections for prolonged labour; in addition, eight staff members were interviewed. METHODS: Criteria of realistic best practice were established, and the case files were audited and compared with these. Hospital staff were interviewed about what they felt might be the causes for the audit findings. MAIN OUTCOME MEASURES: Prevalence of suboptimal management and themes emerging from an analysis of the transcripts. RESULTS: Suboptimal management was identified in most cases. Non-invasive interventions to potentially avoid operative delivery were inadequately used. When deciding on caesarean section, in 26% of the cases labour was not prolonged, and in 16% the membranes were still intact. Of the women with genuine prolonged labour, caesarean sections were performed with a fully dilated cervix in 36% of the cases. Vacuum extraction was not considered. Amongst the hospital staff interviewed, the awareness of evidence-based guidelines was poor. Word of mouth, personal experience, and fear, especially of HIV transmission, influenced management decisions. CONCLUSION: The lack of use and awareness of evidence-based guidelines led to misinterpretation of clinical signs, fear of simple interventions, and an excessive rate of emergency caesarean sections.

Parity and risk of diabetes in a Danish nationwide birth cohort.

AIMS: The purpose was to elucidate the association between parity and the incidence of diabetes using national register data. METHODS: The study population consisted of all Danish women with a singleton delivery in 1982/1983 (n = 100,669), who subsequently had 74,966 deliveries. The included women were followed up via registries until the end of 2006 for subsequent deliveries, diagnosis of diabetes and death/emigration. RESULTS: A total of 2021 cases (2.0%) were diagnosed with diabetes in connection with hospitalization or outpatient treatment during follow-up. Analyses were adjusted for fetal weight and duration of gestation, both at index pregnancy. Cox regression analysis with parity as a time-varying exposure, stratified in two age groups, showed an association between parity and risk of a diagnosis of diabetes. In women <33 years of age, parity 2, 3 and 4 + were associated with an increased risk of being diagnosed with diabetes compared with parity 1 [relative risks: 1.6 (95% confidence interval 1.1-2.3), 2.8 (1.8-4.3) and 2.5 (1.3-4.8), respectively]. Among women >33 years of age, parity 2 was associated with a significantly lower risk of diabetes diagnosis compared with parity 1, whereas parity 4 + was associated with a significantly higher risk of diabetes diagnosis compared with parity 1. CONCLUSIONS: The study shows that the risk of diabetes diagnosis increases with parity in young Danish women. This may support a causal association between diabetes and parity.

Defects on endoanal ultrasound and anal incontinence after primary repair of fourth-degree anal sphincter rupture: a study of the anal sphincter complex and puborectal muscle.

OBJECTIVES: To perform three-dimensional endoanal ultrasound (EAUS) after primary repair of fourth-degree anal sphincter rupture (ASR) and correlate the sonographic defects with anal incontinence (AI); to measure the axial and sagittal thickness and angle of the puborectal muscle (PRM) as well as the length of the anal canal, and then correlate these measures with AI; and to assess the interobserver measurement agreement between an inexperienced and an experienced sonologist. METHODS: EAUS was offered to 84 consecutive women, who were asked to answer a validated questionnaire after fourth-degree ASR. AI was graded according to the Wexner score and EAUS defects were graded according to the Starck score. RESULTS: Sixty-one women (73%) answered the questionnaire. The median (range) follow-up time was 5.1 (1.3-8.7) years. Thirty-three (54%) of these women underwent EAUS and were included in the study. There was no difference in the incontinence scores between women who underwent EAUS and those who did not. Eleven of the women who underwent EAUS (33%) were continent, 22 women (67%) had flatus incontinence at least once a month, of whom 12 also had incontinence for liquid stool and two had incontinence for solid stool. The median Wexner score was 2 (range, 0-12). Five of the patients (15%) had no ultrasound defects. All of the patients with Wexner scores > or = 4 had a Starck score of > or = 10. No association between ultrasound defects and AI was demonstrated, however, the angle of the PRM and parity were associated with Starck score. No clear association between the measurements of the PRM and AI was shown. The experienced observer detected more of the small defects than did the inexperienced observer. CONCLUSION: In a 1-9-year follow-up period after primary suture of fourth-degree ASR, the frequency of AI was high, at 67%. No clear association was seen between AI and sphincter defects detected on ultrasonography. There was an association between the angle of the PRM and the extent of ultrasound defects.

Cervical occlusion in women with cervical insufficiency: protocol for a randomised, controlled trial with cerclage, with and without cervical occlusion.

OBJECTIVE: To evaluate the effect of double cerclage compared with a single cerclage. DESIGN: Randomised, controlled multicentre trial. SETTING: Ten different countries are participating with both secondary and tertiary centres. The countries participating are Denmark, Sweden, Germany, United Kingdom, Spain, South Africa, Australia and India. This gives both a broad spectrum of diversity global and local. We expect a total of 242 women enrolled per year. POPULATION: Prophylactic study: 1. History of cervical incompetence/insufficiency. (Delivery 15 to <36 weeks.) 2. Congenital short cervix (secondary to maternal administration of diethyl stilbestrol) or traumatic/surgical damage rendering the vaginal approach difficult (e.g. conisation). 3. Cervical suture applied in previous pregnancy, successful outcome. 4. Previous failed cerclage. Therapeutic study: 5. Secondary cerclage: Short cervix, without the membranes being exposed to the vagina. 6. Tertiary cerclage: Short cervix, membranes exposed to the vagina. Observational study: Eligible women who refuse to be randomised will participate in an observational study. 7. Repeat/requested cervical occlusion. METHODS: The women will be randomised between a single (vaginal or abdominal) and a double cerclage. The cervical cerclage (McDonald or Shirodkar) as well as the abdominal suture will be performed with the same material and technique normally used by the participating department. Those randomised to the double cerclage will have their external os closed with a continuous nylon 2-0/3-0 suture, in addition to the standard single cerclage. Local guidelines concerning antibiotics, Heparin, bed rest, tocolytics etc. are followed and recorded in the follow-up form. MAIN OUTCOME MEASURES: Primary endpoint is take home baby rate. The secondary endpoints are gestational age at delivery, incidence of preterm birth (<34+0 days) and number of days in neonatal unit.

Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil.

OBJECTIVE: To examine the effect of fish oil supplementation on duration of pregnancy, conditional on the woman's habitual fish intake. DESIGN: Multicentre 1:1 randomised clinical trial of effect of fish oil in a high-risk population of pregnant women in whom habitual fish intake was assessed at randomisation. SETTING: Nineteen university delivery wards in seven European countries. SUBJECTS: Pregnant women with preterm delivery, intrauterine growth retardation (IUGR), or pregnancy-induced hypertension (PIH) in a previous pregnancy (group 1, n=495); with twin pregnancies (group 2, n=367); or with suspicion of IUGR or threatening preeclampsia in the current pregnancy (group 3, n=106). Women were stratified into low, middle, or high fish consumers. METHODS: The intervention group received fish oil capsules providing 2.7 g long-chain n-3 fatty acids per day (n-3 poly unsaturated fatty acids (PUFA)) from around week 20 (groups 1 and 2) or 6.3 g n-3 PUFA from week 33 (group 3). The control regimen was capsules with olive oil. Effect on timing of spontaneous delivery was examined by Cox regression, assuming elective delivery (occurring in 40%) as a censoring event. Analyses of effect of fish oil were intention to treat, and all analyses were adjusted for maternal smoking, age, and parity. RESULTS: In group 1, fish oil reduced the hazard rate of spontaneous delivery (HR) by 44% (95% confidence interval 14-64%) and 39% (16-56%) in low and middle fish consumers, respectively, with no detectable effect (-56 to 33%) in high fish consumers. In groups 2 and 3, no significant effect of fish oil was detected in any of the sub-strata defined by baseline fish consumption. CONCLUSIONS: In pregnant women with previous pregnancy complications, fish oil supplementation delayed onset of delivery in low and middle, but not in high, fish consumers. SPONSORSHIP: March of Dimes Birth Defects Foundation, Concerted Action (ERB-BMH1-CT92-1906) and PECO (ERB-CIPD-CT94-0235) programmes of the European Commission, and the Danish National Research Foundation. Lube Ltd donated the oil capsules.

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.

Stress and salivary cortisol during pregnancy.

The purpose of this study was to determine whether exposure to stressful life events was associated with changes in levels of circulating cortisol during pregnancy in a population of 603 pregnant women. The participating pregnant women filled out a questionnaire and collected a morning and evening sample of saliva in early pregnancy (median 14th gestational week) and in late pregnancy (median and 30th gestational week). They were asked to report the number of life events experienced during first and second trimester, respectively, and were asked to rate the intensity of the experienced events. Complications related to the pregnancy such as vaginal bleeding and suspected growth retardation were registered and the women were asked about concerns about their pregnancy. The salivary samples were analyzed for cortisol and the levels were higher in late than in early pregnancy. In late pregnancy women exposed to more than one life event or were concerned about pregnancy complications during second trimester had a higher evening cortisol level, whereas morning values were unaffected. After adjustment for smoking women who experienced more than one very stressful life event had 27% higher evening cortisol concentrations (95% confidence intervals: 1-59%). Women with worries about pregnancy complications had 27% (95% confidence intervals: 2-57%) higher levels. In early pregnancy women reporting stressful life events did not have higher evening cortisol levels, but tended to have a blunted morning HPA response. In conclusion, we found differences in the associations between chronic stress in early and late pregnancy and cortisol levels indicating that the response to chronic stress is dependent on the stage of the pregnancy.

Pre-eclampsia and febrile convulsions.

An association between pre-eclampsia and febrile convulsions has been reported, but the association may not be causal. We compared the risk of febrile convulsions in 14 974 children who had been exposed to pre-eclampsia in fetal life with that of 39 210 unexposed children. Children exposed to pre-eclampsia had a slightly increased risk of febrile convulsions, but the association was apparently caused by a shorter gestation in pre-eclamptic women.

An increasing proportion of infants weigh more than 4000 grams at birth.

BACKGROUND: To investigate how mean birthweight has changed in the past decade, and to describe changes in the proportion of infants with a birthweight above 4000 grams (g). METHODS: We analyzed data on 43,561 singleton infants born between 1990 and 1999 at Aarhus University Hospital, Denmark. Information on birthweight, gestational age, stillbirths, malformations, mode of delivery, prelabor intervention, and maternal diabetes was obtained from birth registration forms. RESULTS: For all infants mean birthweight increased by 45 g (95% CI: 20-70 g) from 3474 g in 1990 to 3519 g in 1999. For infants born at term the mean increase was 62 g (95% CI: 41-83 g). During the same period the percentage of infants born with a birthweight above 4000 g increased from 16.7% in 1990 to 20.0% in 1999 (p<0.05). Simultaneously we found a decrease in gestational age and an increase in the frequency of induction of labor. There was a statistically significantly higher risk of giving birth to an infant with a birthweight above 4000 g throughout the decade, when gestational age and prelabor intervention was taken into account. CONCLUSIONS: In Denmark mean birthweight has risen during the past decade independently of gestational age and prelabor intervention. Simultaneously the risk of having a baby with a birthweight above 4000 g has increased. Further studies on potential risk factors for birth of large infants are needed.

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.

[Does alcohol increase the risk of preterm delivery?]. / Øger alkohol risikoen for praeterm fodsel?

INTRODUCTION: The aim was to assess the association between alcohol intake during pregnancy and preterm delivery. MATERIALS AND METHODS: Women attending routine antenatal care at Aarhus University Hospital, Denmark, from 1989-1991 and 1992-1996 were eligible for the study. Our analyses included 18,228 singleton pregnancies. We obtained prospective information on alcohol intake at about 16 and 30 weeks of gestation, other lifestyle factors, maternal characteristics, and obstetrical risk factors from questionnaires completed by the women and hospital files. RESULTS: For women with an alcohol intake of 1-2, 3-4, 5-9, and > or = 10 drinks/week, the risk ratio (RR) of preterm delivery was 0.91 (95% CI: 0.76-1.08), 0.86 (0.64-1.15), 0.89 (0.52-1.52), and 2.93 (1.52-5.63) respectively, compared with an intake of < 1 drink/week at about 16 weeks of gestation, and 0.69 (0.56-0.86), 0.82 (0.60-1.13), 0.97 (0.58-1.64), and 3.56 (1.78-7.13) at about 30 weeks. Adjustment for smoking habits, caffeine intake, age, height, prepregnant weight, marital status, occupational status, education, parity, chronic diseases, previous preterm delivery, mode of initiation of labour, and sex of the child did not alter the conclusions, nor did restriction of the highest intake group to women drinking 10-14 drinks/week (RR = 3.41 (1.71-6.81) at 16 weeks and RR = 3.47 (1.64-7.35) at 30 weeks). DISCUSSION: The association between alcohol intake and preterm delivery appeared to be J-shaped, with a threshold for adverse effect at a level of about 10-14 drinks/week.

Exposure to tobacco smoke in utero and the risk of stillbirth and death in the first year of life.

The authors examined the association between exposure to tobacco smoke in utero and the risk of stillbirth and infant death in a cohort of 25,102 singleton children of pregnant women scheduled to deliver at Aarhus University Hospital, Aarhus, Denmark, from September 1989 to August 1996. Exposure to tobacco smoke in utero was associated with an increased risk of stillbirth (odds ratio = 2.0, 95% confidence interval: 1.4, 2.9), and infant mortality was almost doubled in children born to women who had smoked during pregnancy compared with children of nonsmokers (odds ratio = 1.8, 95% confidence interval: 1.3, 2.6). Among children of women who stopped smoking during the first trimester, stillbirth and infant mortality was comparable with that in children of women who had been nonsmokers from the beginning of pregnancy. Conclusions were not changed after adjustment in a logistic regression model for the sex of the child; parity; or maternal age, height, weight, marital status, years of education, occupational status, and alcohol and caffeine intake during pregnancy. Approximately 25% of all stillbirths and 20% of all infant deaths in a population with 30% pregnant smokers could be avoided if all pregnant smokers stopped smoking by the sixteenth week of gestation.

Association between raised serum relaxin levels during the eighteenth gestational week and very preterm delivery.

OBJECTIVE: Our aim was to evaluate a possible association between serum relaxin levels in the 18th gestational week and preterm delivery. STUDY DESIGN: We conducted a nested case-control study that was based on serum samples obtained in the 18th week of gestation from 1545 unselected healthy primiparous women. Eleven case subjects were delivered very early (9 spontaneously, 2 by indicated cesarean delivery) and 42 moderately early (41 spontaneously, 1 by indicated cesarean delivery); 123 control subjects (121 having spontaneous labor, 2 undergoing indicated cesarean delivery) were randomly selected among the women with delivery at term. RESULTS: The serum relaxin concentration during the 18th gestational week was 63% higher among subjects with very preterm deliveries than among control subjects (P = .01, Mann-Whitney test). High relaxin levels during the 18th gestational week were associated with an increased risk of very preterm delivery (odds ratio, 11.3; 95% confidence interval, 2.14-59.1) and spontaneous very preterm delivery (odds ratio, 5.5; 95% confidence interval, 1.3-23). There was a negative correlation for case subjects and control subjects between serum relaxin concentrations during the 18th gestational week and gestational age at delivery (P < .05). CONCLUSION: Serum relaxin may be an independent predictor when identification of women at risk of very preterm delivery is attempted in the 18th gestational week.