Doris M. Campbell

Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

Abstract Objective: To examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life. Design: Cohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure. Setting: Maternity services in the Grampian region of Scotland. Participants: Women selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970. Main outcome measures: Current vital and cardiovascular health status ascertained through postal questionnaire survey, clinical examination, linkage to hospital discharge, and mortality data. Results: There were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4). Conclusions: Hypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases. What is already known on this topic Much is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to women Retrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later life What this study adds Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertension Women who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart disease Long term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)

Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies

BackgroundThe increasing prevalence of obesity in young women is a major public health concern. These trends have a major impact on pregnancy outcomes in these women, which have been documented by several researchers. In a population based cohort study, using routinely collected data, this paper examines the effect of increasing Body Mass Index (BMI) on pregnancy outcomes in nulliparous women delivering singleton babies.MethodsThis was a retrospective cohort study, based on all nulliparous women delivering singleton babies in Aberdeen between 1976 and 2005. Women were categorized into five groups – underweight (BMI < 20 Kg/m2), normal (BMI 20 – 24.9 Kg/m2) overweight (BMI 25 – 29.9 Kg/m2), obese (BMI 30 – 34.9 Kg/m2) and morbidly obese (BMI > 35 Kg/m2). Obstetric and perinatal outcomes were compared by univariate and multivariate analyses.ResultsIn comparison with women of BMI 20 – 24.9, morbidly obese women faced the highest risk of pre-eclampsia {OR 7.2 (95% CI 4.7, 11.2)} and underweight women the lowest {OR 0.6 (95% CI 0.5, 0.7)}. Induced labour was highest in the morbidly obese {OR 1.8 (95% CI 1.3, 2.5)} and lowest in underweight women {OR 0.8 (95% CI 0.8, 0.9)}. Emergency Caesarean section rates were highest in the morbidly obese {OR 2.8 (95% CI 2.0, 3.9)}, and comparable in women with normal and low BMI. Obese women were more likely to have postpartum haemorrhage {OR 1.5 (95% CI 1.3, 1.7)} and preterm delivery (< 33 weeks) {OR 2.0 (95% CI 1.3, 2.9)}. Birthweights less than 2,500 g were more common in underweight women {OR 1.7 (95% OR 1.2, 2.0)}. The highest risk of birth weights > 4,000 g was in the morbidly obese {OR 2.1 (95% CI 1.3, 3.2)} and the lowest in underweight women {OR 0.5 (95% CI 0.4, 0.6)}.ConclusionIncreasing BMI is associated with increased incidence of pre-eclampsia, gestational hypertension, macrosomia, induction of labour and caesarean delivery; while underweight women had better pregnancy outcomes than women with normal BMI.

Diet in pregnancy and the offspring's blood pressure 40 years later

Objective To determine how diet of the mother in pregnancy influences the blood pressure of the offspring in adult life.

Pre‐eclampsia in second pregnancy

Summary. A total population of pregnant women from Aberdeen City District 1967–1978 has been studied. There were 29 851 pregnancies and 6637 women had a first recorded pregnancy between 1967 and 1978 and had two or more pregnancy events. As expected the incidence of pre‐eclampsia in a second pregnancy was less than that in a first pregnancy, but it was dependent on the outcome of the first pregnancy. If the first pregnancy was complicated by proteinuric pre‐eclampsia than the incidence of the condition in the second pregnancy was similar t o that in a first pregnancy, but women who were normotensive in the first pregnancy had a reduced incidence of the condition in the second pregnancy. The incidence of proteinuric pre‐eclampsia after early abortion <13 weeks), either spontaneous or induced was similar to the population incidence in a first pregnancy, but after a late spontaneous abortion the risk of proteinuric pre‐eclampsia was significantly reduced. Change of civil status of the offspring from first to second pregnancy did not affect the incidence of pre‐eclampsia in a second pregnancy. There was an effect of birthweight in that women who had proteinuric pre‐eclampsia in conjunction with a low‐birthweight baby (<2500g) in their first pregnancy had double the incidence of proteinuric pre‐eclampsia in their second pregnancy. Only a pregnancy of 37 weeks or more is likely to offer protection or ‘immunity’ to pre‐eclampsia in a second pregnancy and even then the effect is moderated by the development of pre‐eclampsia in the first pregnancy.

Taking folate in pregnancy and risk of maternal breast cancer

Taking folate before conception and then for the first three months of pregnancy reduces the risk of recurrence of neural tube defects,1 and fortification of food has been proposed. The effects of long term exposure to high concentrations of supplemental folate are unknown, and antimetabolite effects are theoretically possible.2 Data on the long term effects of increased folate intake in pregnancy are limited. We followed up a large trial of folate supplementation in pregnancy from the 1960s.3 4 We examined the association between folate status and death, and we also analysed the effects of folate supplementation. From June 1966 to June 1967, 3187 women were identified as potentially eligible for a trial of folate supplementation.3 4 At her booking visit, the mothers age, gestation, parity, weight, and blood pressure were recorded, and blood was taken to …

Folate in pregnancy and imprinted gene and repeat element methylation in the offspring

BACKGROUND Epigenetic regulation of imprinted genes and transposable elements has been implicated in human disease and may be affected by maternal diet. OBJECTIVE The objective was to determine the effect on offspring epigenetic status of nutritional and genetic factors that influence folate exposure in pregnancy. DESIGN We measured folate intake from diet, the use of folic acid supplements and the period of consumption, maternal and cord red blood cell (RBC) folate, and genotypes for 5 methylation cycle enzymes in a prospective cohort study of pregnancies in the United Kingdom between 2000 and 2006. We related these to offspring methylation status within 3 maternally methylated imprinted genes: paternally expressed gene 3 (PEG3), insulin-like growth factor 2 (IGF2), and small nuclear ribonucleoprotein polypeptide N, and the long interspersed nuclear element 1 (LINE-1) in genomic DNA extracted from whole blood in 913 pregnancies. RESULTS Supplement use after 12 wk of gestation was associated with a higher level of methylation in IGF2 (+0.7%; 95% CI: 0.02, 1.4; P = 0.044) and reduced methylation in both PEG3 (-0.5%; 95% CI: -0.9, -0.1; P = 0.018) and LINE-1 (-0.3%; 95% CI: -0.6, -0.04; P = 0.029). The same pattern was observed in relation to RBC folate in the cord blood at birth: IGF2 (P = 0.038), PEG3 (P < 0.001), and LINE-1 (P < 0.001). LINE-1 methylation was related to maternal RBC folate (P = 0.001) at 19 wk. No effect of supplement use up to 12 wk (current recommendation) was found. CONCLUSIONS Folic acid use after 12 wk of gestation influences offspring repeat element and imprinted gene methylation. We need to understand the consequences of these epigenetic effects.

Can obstetric complications explain the high levels of obstetric interventions and maternity service use among older women? A retrospective analysis of routinely collected data.

Objective To determine whether the higher levels of obstetric intervention and maternity service use among older women can be explained by obstetric complications.

Is birth weight determined genetically

Birthweight correlations were analysed among 505 intergenerational pairs of first births to women aged 18-25 identified from a large obstetric data bank. After standardisation for fetal sex, maternal height, gestational age, and proteinuric pre-eclampsia residual correlations of between 0.1402 and 0.1725 were found, suggesting only a small genetic effect. It is concluded that genetic factors play only a small part in determining birth weight.

First trimester maternal tobacco smoking habits and fetal growth

Rationale Maternal smoking in pregnancy is associated with reduced birth weight and childhood lung function. This study determined when maternal smoking first influences fetal growth and how this relates to childhood respiratory outcomes. Methods A longitudinal cohort of 1924 pregnant women was recruited. Fetal ultrasound measurements at 11 weeks (crown–rump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) and birth measurements were recorded. Childhood respiratory symptoms and spirometry were ascertained. Results Of the 1924 original study participants, fetal size was determined in 903 in the first trimester, 1544 in the second trimester and at term in 1737 infants. Maternal smoking when first pregnant was reported in 593 (31%) and was not associated with reduced CRL. There was an inverse exposure-response relationship between cigarette consumption and FL (mean reduction in lowest compared with highest tertile 0.91 cm, p=0.033). Birth weight and length of those born to mothers who did (n=331) and did not (n=56) reduce cigarette consumption were similar and reduced compared with 186 infants whose mothers quit during the first trimester (p≤0.020). Children of mothers who continued smoking had increased wheeze at age 2 years (OR 1.58, p=0.017) and GP visits with wheeze at age 5 years (OR 2.18, p=0.030) and mean reduction in forced expiratory volume in 1 s of 62 ml (p=0.014) compared with controls. Conclusions Maternal smoking is associated with reduced fetal measurements in the second and third trimesters but not in the first trimester. Mothers who do not quit smoking during the first trimester deliver smaller infants who go on to have adverse respiratory outcomes in childhood.

Diet in late pregnancy and glucose-insulin metabolism of the offspring 40 years later.

Objective To determine how diets of women in pregnancy influence the glucose‐insulin metabolism of their offspring in adult life.