Inter-Pregnancy Weight Change and the Risk of Recurrent Pregnancy Complications.

Women with specific adverse pregnancy outcomes in their first pregnancy may be receptive to inter-pregnancy weight management guidance aimed at preventing these complications reoccurring in subsequent pregnancies. Thus the association between inter-pregnancy weight change and the risk of recurrent pregnancy complications at the second pregnancy was investigated in a retrospective cohort study of 24,520 women with their first-ever and second consecutive deliveries in Aberdeen using logistic regression. Compared with women who were weight stable, weight loss (>2BMI units) between pregnancies was associated with an increased risk of recurrent small for gestational age (SGA) birth and elective Cesarean-section, and was protective against recurrent pre-eclampsia, placental oversize and large for gestational age (LGA) birth. Conversely weight gain (>2BMI units) between pregnancies increased the risk of recurrent gestational hypertension, placental oversize and LGA birth and was protective against recurrent low placental weight and SGA birth. The relationships between weight gain, and placental and birth weight extremes were evident only in women with a healthy weight at first pregnancy (BMI<25units), while that between weight gain and the increased risk of recurrent gestational hypertension was largely independent of first pregnancy BMI. No relationship was detected between inter-pregnancy weight change and the risk of recurrent spontaneous preterm delivery, labour induction, instrumental delivery, emergency Cesarean-section or postpartum hemorrhage. Therefor inter-pregnancy weight change impacts the risk of recurrent hypertensive disorders, SGA and LGA birth and women with a prior history of these specific conditions may benefit from targeted nutritional advice to either lose or gain weight after their first pregnancy.

Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis.

OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION: Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension.

Inter-pregnancy weight change impacts placental weight and is associated with the risk of adverse pregnancy outcomes in the second pregnancy.

BACKGROUND: The inter-pregnancy period is considered a teachable moment when women are receptive to weight- management guidance aimed at optimising pregnancy outcome in subsequent pregnancies. In population based studies inter-pregnancy weight change is associated with several adverse pregnancy outcomes but the impact on placental size is unknown. METHODS: The association between inter-pregnancy weight change and the primary risk of adverse pregnancy outcomes in the second pregnancy was investigated in 12,740 women with first two consecutive deliveries at a single hospital using logistic regression. RESULTS: Compared with women who were weight stable, weight loss (>1BMI unit) between pregnancies was associated with an increased risk of spontaneous preterm delivery, low placental weight and small for gestational age (SGA) birth, while weight gain (>3BMI units) increased the risk of pre-eclampsia, gestational hypertension, emergency caesarean section, placental oversize and large for gestational age (LGA) birth at the second pregnancy. The relationship between weight gain and pre-eclampsia risk was evident in women who were overweight at first pregnancy only (BMI ≥25 units), while that between weight loss and preterm delivery was confined to women with a healthy weight at first pregnancy (BMI <25 units). In contrast, the association between weight loss and SGA was independent of first pregnancy BMI. A higher percentage of women who were obese at first pregnancy were likely to experience a large weight gain (P < 0.01) or weight loss (P < 0.001) between consecutive pregnancies compared with the normal BMI reference group. CONCLUSION: Inter-pregnancy weight change in either direction increases the risk of a number of contrasting pregnancy complications, including extremes of placental weight. The placenta may lie on the causal pathway between BMI change and the risk of LGA or SGA birth.

DNA methyltransferase candidate polymorphisms, imprinting methylation, and birth outcome.

BACKGROUND: Birth weight and prematurity are important obstetric outcomes linked to lifelong health. We studied a large birth cohort to look for evidence of epigenetic involvement in birth outcomes. METHODS: We investigated the association between birth weight, length, placental weight and duration of gestation and four candidate variants in 1,236 mothers and 1,073 newborns; DNMT1 (rs2162560), DNMT3A (rs734693), DNMT3B (rs2424913) and DNMT3L (rs7354779). We measured methylation of LINE1 and the imprinted genes, PEG3, SNRPN, and IGF2, in cord blood. RESULTS: The minor DNMT3L allele in the baby was associated with higher birth weight (+54 95% CI 10,99 g; p = 0.016), birth length (+0.23 95% CI 0.04,0.42 cm; p = 0.017), placental weight, (+18 95% CI 3,33 g; p = 0.017), and reduced risk of being in the lowest birth weight decile (p = 0.018) or requiring neonatal care (p = 0.039). The DNMT3B minor allele in the mother was associated with an increased risk of prematurity (p = 0.001). Placental size was related to PEG3 (p<0.001) and IGF2 (p<0.001) methylation. Birth weight was related to LINE1 and IGF2 methylation but only at p = 0.052. The risk of requiring neonatal treatment was related to LINE1 (p = 0.010) and SNRPN (p = 0.001) methylation. PEG3 methylation was influenced by baby DNMT3A genotype (p = 0.012) and LINE1 by baby 3B genotype (p = 0.044). Maternal DNMT3L genotype was related to IGF2 methylation in the cord blood but this effect was only seen in carriers of the minor frequency allele (p = 0.050). CONCLUSIONS: The results here suggest that epigenetic processes are linked birth outcome and health in early life. Our emerging understanding of the role of epigenetics in health and biological function across the lifecourse suggests that these early epigenetic events could have longer term implications.

Outcomes of pregnancy in women using illegal drugs and in women who smoke cigarettes.

OBJECTIVE: To compare obstetric outcomes in women using illegal drugs with women who smoke cigarettes. DESIGN: Retrospective cohort study. SETTING: Aberdeen, UK. POPULATION: All deliveries in Aberdeen in women using illegal drugs and women who smoked cigarettes during 1997-2007. MATERIAL AND METHODS: The women who used illegal drugs were identified from a database of affected pregnant women in Aberdeen. The Aberdeen Maternity and Neonatal Databank was used to identify women who smoke cigarettes and to obtain pregnancy outcome information. Sociodemographic characteristics, maternal and perinatal outcomes were compared using chi-squared test, independent sample t-test and logistic regression analysis. MAIN OUTCOME MEASURES: Preterm delivery, low birthweight (standardized birthweight score <-2) and admission to the neonatal unit. RESULTS: Of the 561 illegal drug users, 96% were also cigarette smokers. Compared with women who smoke cigarettes with no reported illegal drug use, they were significantly more likely to have a preterm delivery [adjusted odds ratio (aOR) 1.6 (95% confidence interval (CI) 1.3-2.1)], low birthweight baby [aOR 1.9 (95%CI 1.4-2.6)], baby admitted to the neonatal unit [aOR 13.3 (95%CI 10.9-16.3)], deep vein thrombosis [aOR (95%CI 8.8-50.8)] and antepartum hemorrhage [aOR (95%CI 1.2-2.1)]. They were less likely to be at the extremes of age, or to develop pregnancy-induced hypertension [aOR 0.3 (95%CI 0.2-0.4)]. CONCLUSION: Illegal drug use in pregnancy appears to increase the risk of adverse outcomes, over and above that related to cigarette smoking, but appears to be associated with lower prevalence of gestational hypertension.

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.

Vitamin D in pregnancy at high latitude in Scotland.

The aims of the present study were to determine compliance with current advice on vitamin D and to assess the influence of season, dietary intake, supplement use and deprivation on vitamin D status in pregnant mothers and newborns in the north of Scotland where sunlight exposure is low. Pregnant women (n 1205) and their singleton newborns were studied in the Aberdeen Maternity Hospital (latitude 57°N) between 2000 and 2006. Plasma 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were measured at 19 weeks of gestation in mothers and at delivery in newborns. During pregnancy, 21·0 (95 % CI 18·5, 23·5) % of women took vitamin D supplements. The median intake was 5 µg/d and only 0·6 (95 % CI 0·1, 1·0) % took the recommended 10 µg/d. Supplement use, adjusted for season, dietary intake and deprivation, significantly increased maternal 25-hydroxyvitamin D (25(OH)D) by 10·5 (95 % CI 5·7, 15·2) nmol/l (P< 0·001); however, there was no significant effect on cord 25(OH)D (1·4 (95 % CI - 1·8, 4·5) nmol/l). The biggest influence on both maternal and cord 25(OH)D was season of birth (P< 0·001). Compared with the least deprived women (top three deciles), the most deprived pregnancies (bottom three deciles) were characterised by a significantly lower seasonally adjusted 25(OH)D ( - 11·6 (95 % CI - 7·5, - 15·7) nmol/l in the mother and - 5·8 (95 % CI - 2·3, - 9·4) nmol/l in the cord), and a lower level of supplement use (10 (95 % CI 4, 17) v. 23 (95 % CI 20, 26) %). More should be done to promote vitamin D supplement use in pregnancy but the critical importance of endogenous vitamin D synthesis, and known adaptations of fat metabolism specific to pregnancy, suggest that safe sun advice may be a useful additional strategy, even at high latitude.

Inherited predisposition to spontaneous preterm delivery.

OBJECTIVE: To assess inherited predisposition to spontaneous preterm delivery. METHODS: In this retrospective cohort study, intergenerational data on deliveries in mother-daughter pairs were analyzed from the Aberdeen Maternity Neonatal Databank using multilevel logistic regression. The study included an exposed cohort of all women born spontaneously preterm or whose mothers had experienced at least one spontaneous preterm delivery (at 24-37 weeks of gestation). The unexposed cohort included women who were born at term (after 37 weeks of gestation) or those whose mothers had never experienced any spontaneous preterm deliveries (24-37 weeks of gestation). The primary outcome was spontaneous preterm delivery in the daughters' pregnancies. Results are shown as adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We identified 22,343 pregnancies occurring in 13,845 daughters born to 11,576 mothers. Women who were born spontaneously preterm had significantly higher odds of delivering preterm babies (OR 1.49, 95% CI 1.12-1.99). A stronger association was seen when the analysis was restricted to nulliparous women who had been born spontaneously preterm (OR 1.60, 95% CI 1.16-2.21). Other predictors of a woman having a spontaneous preterm delivery were age at delivery younger than 20 years (OR 1.67, 95% CI 1.43-1.94), lower socioeconomic status (OR 1.22, 95% CI 1.04-1.44), smoking more than 10 cigarettes per day (OR 1.47, 95% CI 1.27-1.71), body mass index 19 kg/m or less (OR 1.48, 95% CI 1.24-1.77), previous preterm delivery (OR 2.51, 95% CI 1.71-3.66). The risk of a woman delivering spontaneously preterm was increased even if her mother had a history of spontaneous preterm delivery in any other pregnancy (OR 1.35, 95% CI 1.12-1.63). The absolute risk of spontaneously delivering preterm in women who were born preterm was 9% as opposed to 6.2% in those who were born full-term. This gives an increase in risk of spontaneous preterm birth of 2.8% in women who were born spontaneously preterm. CONCLUSION: Women born spontaneously preterm or with siblings delivered in a similar manner have an increased risk of spontaneous preterm delivery in their own pregnancies. LEVEL OF EVIDENCE: II.

Diet and deprivation in pregnancy.

Deprivation is associated with poor pregnancy outcome but the role of nutrition as a mediating factor is not well understood. We carried out a prospective cohort study of 1461 singleton pregnancies in Aberdeen, UK during 2000-6. We measured nutrient intake and supplement use, B vitamin and homocysteine status, birth weight, gestational age, neonatal treatment and socio-economic deprivation status. Women in the most deprived deciles were approximately 6 years younger and half as likely to take folic acid supplements periconceptually as the least deprived mothers. Deprivation was associated with low blood folate, high homocysteine and diets low in protein, fibre and many of the vitamins and minerals. The diets of the more deprived women were also characterised by low intakes of fruit, vegetables and oily fish and higher intakes of processed meat, fried potatoes, crisps and snacks. Deprivation was related to preterm birth (OR 1.14 (95 % CI 1.03, 1.25); P = 0.009) and whether the baby required neonatal treatment (OR 1.07 (95 % CI 1.01, 1.14); P = 0.028). Low birth weight was more common in women consuming diets low in vitamin C (OR 0.79 (95 % CI 0.64, 0.97); P = 0.028), riboflavin (OR 0.77 (95 % CI 0.63, 0.93); P = 0.008), pantothenic acid (OR 0.79 (95 % CI 0.65, 0.97); P = 0.023) and sugars (OR 0.78 (95 % CI 0.64, 0.96); P = 0.017) even after adjustment for deprivation index, smoking, marital status and parity. Deprivation in pregnancy is associated with diets poor in specific nutrients and poor diet appears to contribute to inequalities in pregnancy outcome. Improving the nutrient intake of disadvantaged women of childbearing age may potentially improve pregnancy outcome.

Pre-eclampsia in the second pregnancy: does previous outcome matter?

OBJECTIVE: To assess the effect of initial pregnancy outcome and gestational age on the risk of pre-eclampsia in the second pregnancy. STUDY DESIGN: We conducted an observational study using routinely collected data from the Aberdeen Maternity and Neonatal Databank between 1986 and 2006. Cases were women who developed pre-eclampsia in their second pregnancy and controls were normotensive in their second pregnancy. Crude and adjusted odds ratios were produced for each of the risk factors using logistic regression. RESULTS: Inter-pregnancy intervals of 6 years or more were associated with increased incidence of pre-eclampsia (19.4% vs. 14.7%). A change of partner had a protective effect while an increase in BMI increased the risk of pre-eclampsia. A history of pre-eclampsia was associated with 5 times higher risk {adjusted O.R. 5.12 (95% C.I. 4.42-6.48)} of pre-eclampsia in the second pregnancy. Compared to a term delivery, a previous second trimester pregnancy loss was associated with a 4 times higher risk {adjusted O.R. 4.22 (95% C.I. 2.54-7.03)} of pre-eclampsia in the next pregnancy. Previous very preterm and preterm births were associated with adjusted odds ratios of 2.32 (95% C.I. 1.62-3.32) and 1.62 (95% C.I. 1.46-1.72) respectively. The risk of pre-eclampsia was no higher in women with a previous history of fetal death after 20 weeks than those with a previous live birth, after adjusting for pre-eclampsia in the first pregnancy. CONCLUSION: Only initial deliveries beyond 37 weeks, irrespective of outcome, were protective against pre-eclampsia in the second pregnancy.

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

BACKGROUND: The 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. METHODS: This 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. RESULTS: In 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)}. CONCLUSION: Increasing 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.

The influence of birth weight and genetic factors on lipid levels: a study in adult twins.

Twins can be used to investigate the biological basis for observed associations between birth weight and later disease risk, as they experience in utero growth restriction compared with singletons, which can differ in magnitude within twin pairs despite partial or total genetic identity. In the present study, sixty monozygotic and seventy-one dizygotic same-sex twin pairs aged 19-50 years and eighty-nine singleton controls matched for age, gestational age, sex, maternal age and parity were recruited from an obstetric database. Associations between fasting lipid levels and birth weight were assessed by linear regression with adjustment for possible confounding factors. Twins were significantly lighter at birth but were not significantly different in adult height, weight or lipid levels from the singleton controls. There was a significant inverse association between birth weight and both total and LDL-cholesterol levels among singleton controls (-0.53 mmol/l per kg (95 % CI -0.97, -0.09), P = 0.02 and -0.39 mmol/l per kg (95 % CI -0.76, -0.02), P = 0.04, respectively), but there was no significant association between birth weight and lipid levels in either unpaired or within-pair analysis of twins. The results suggest that the in utero growth restriction and early catch-up growth experienced by twins does not increase the risk of an atherogenic lipid profile in adult life.

Maternal intake of antioxidant vitamins in pregnancy in relation to maternal and fetal plasma levels at delivery.

The aim of the present study was to test the hypothesis that maternal intake of antioxidant vitamins is associated with maternal and cord plasma levels at delivery. Women were recruited in early pregnancy in Aberdeen Maternity Hospital and habitual diet during pregnancy was assessed by a food-frequency questionnaire mailed at 34 weeks gestation. Blood samples were taken at recruitment (n 1149) and maternal (n 1149) and cord blood samples (n 747) taken at delivery for analyses of vitamins A, C, E and beta-carotene. Maternal plasma levels of vitamin E and beta-carotene at delivery were significantly higher than levels in early pregnancy while levels of vitamins A and C were significantly lower. Positive correlations were observed for maternal levels of all the vitamins between early pregnancy and delivery. At delivery, maternal plasma concentrations of vitamins A, E and beta-carotene were significantly higher than cord levels, while maternal levels of vitamin C were significantly lower. There were significant correlations between maternal and cord plasma concentrations for beta-carotene and vitamin C but not for vitamins A or E. Maternal dietary intakes were positively correlated with maternal plasma levels of vitamins C, E and beta-carotene in early pregnancy, with maternal plasma levels of beta-carotene and vitamin C at delivery and with cord plasma levels of beta-carotene and vitamin C. The results from the present study show that, in this population, maternal diet influences cord plasma levels of beta-carotene and vitamin C, but not vitamins A and E.

The incidence of severe complications of preeclampsia.

OBJECTIVES: To examine the incidence of life-threatening (near-miss) complications, including hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome occurring in women with preeclampsia in the Grampian region of Scotland between 1981 and 2000. SUBJECTS AND METHODS: All women who were resident in a geographically determined region (the Grampian region of Scotland) and who developed moderate to severe preeclampsia in the time period 1981 to 2000 were identified from the Aberdeen Maternity and Neonatal Databank. All complications occurring antepartum, intrapartum, or postpartum in these pregnancies were listed as International Classification of Diseases (ICD) codes and significant complications were identified from these. The cases of HELLP syndrome were identified by case note review. Data were analyzed using Statistical Package for Social Scientists (SPSS). RESULTS: A total of 4188 cases of preeclampsia were identified over the 20-year period. Six percent (approx. 1 in 16) of preeclamptics developed one or more major systemic complications. The incidence of placental abruption and eclampsia was 2.8% and 1.65%, respectively. Hematological complications were most common, with reduced platelets accounting for about half of these cases; although, a definite diagnosis of HELLP syndrome could only be made in 13 cases over 20 years. After adjusting for gestational age, a woman was 1.14 times more likely to have a caesarean delivery (95% C.I. 1.08, 1.20) if she had complicated preeclampsia. She was also more likely to have a stillbirth [Odds Ratio (O.R.) = 1.45 (95% C.I. (confidence interval) 1.02, 2.29)] or a neonatal death [O.R. = 2.25 (95% C.I. 1.12, 4.260]. CONCLUSIONS: There has been a gradual decline in the rate of preeclampsia in the Grampian region of Scotland over the time period 1986 to 2000; although, the percentage of pre-eclamptics who developed one or more complications has not decreased appreciably. In fact, the incidence of eclampsia and placental abruption has increased in the most recent five years. The presence of complications in preeclampsia is associated with a poor neonatal outcome.

Size at birth, fasting glucose and insulin levels and insulin resistance in adult twins.

Studies in singletons have found an association between birthweight and Type 2 diabetes in adult life. The aim of this study was to investigate whether this association could also be seen in twins. 59 monozygotic (MZ) and 69 dizygotic (DZ) same-sex twin pairs aged 19-50 years and 89 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from a local obstetric database. Associations between adult glucose, HbA(1)C and insulin levels and insulin resistance and birthweight were assessed by linear regression with adjustment for confounding variables. Twins were significantly lighter at birth than singleton controls, but there were no significant differences in adult weight, glucose, HbA(1)C and insulin levels or insulin resistance between twins and controls. The relationship between birthweight and fasting glucose and insulin levels, and insulin resistance was not significantly different from zero in either twins or controls, but birthweight was significantly negatively associated with HbA(1)C only in controls. There was no evidence of a difference between MZ and DZ twins in unpaired or within-pair analysis. These results provide little evidence that low birthweight in twins increases the risk of impaired glucose-insulin metabolism in young adults or that genetic factors can account for the association observed in singletons.

Antenatal factors in the development of the lumbar vertebral canal: a magnetic resonance imaging study.

STUDY DESIGN: The lumbar vertebral canal was measured in two cohorts of 10-year-old children (n = 161) using magnetic resonance imaging (MRI) and compared with obstetric records. OBJECTIVE: To investigate whether there are identifiable obstetric factors that determine the size of the lumbar vertebral canal. SUMMARY OF BACKGROUND DATA: The most rapid period growth for the lumbar vertebral canal is between 12 and 32 weeks in utero, with the midsagittal diameter of L1-L4 already 70% of adult dimension at birth. Therefore, adverse antenatal factors during this critical growth period may be expected to affect the size of the canal. METHODS: The canal size was measured from axial MRI sections taken through each lumbar vertebra (L1-L5) at the pedicular level of 84 children. Relations with obstetric data, prospectively collected in a neonatal database, were sought. The relation of low birthweight and canal size was further investigated in a second cohort of children (n = 77). RESULTS: The canal size, particularly the midsagittal diameter and the cross-sectional area, was found to be significantly reduced by low birthweight (with growth retardation in utero being a more important factor than length of gestation), low placenta weight, and lower socioeconomic class. Smoking during pregnancy significantly reduced the perimeter at L3 (P = 0.032) and L5 (P = 0.031), and also the cross-sectional area at L3 (P = 0.030) and L5 (P = 0.016). CONCLUSIONS: This study showed that, for this group of children, the size of the lumbar vertebral canal was reduced by low birthweight, with maternal smoking as an added adverse factor. Therefore, good antenatal care and maternal education may help to reduce the risk of spinal stenosis in adult life.

Blood pressure in relation to birth weight in twins and singleton controls matched for gestational age.

Associations between adult blood pressure and birth weight were investigated in 122 same-sex twin pairs aged 18-50 years and 86 singleton controls matched according to maternal age and parity, gender, gestational age, and current age who were recruited via an obstetric database in Aberdeen, Scotland, in 1999. Twins weighed on average 425 g less than controls at birth (p < 0.001) but did not differ significantly in adult height or systolic or diastolic blood pressure from the controls. Among controls, the differences in systolic and diastolic blood pressure per kg of difference in birth weight, adjusted for gender, gestational age, current age, body mass index, smoking, physical activity level, and alcohol intake, were -4.3 (95% confidence interval (CI): -12.8, 4.3) and -6.1 (95% CI: -10.8, -1.5) mmHg/kg, respectively. In unpaired analysis among all twins, the equivalent values were -0.1 (95% CI: -4.0, 3.8) mmHg/kg for systolic pressure and -0.4 (95% CI: -2.9, 2.2) mmHg/kg for diastolic pressure, while in within-pair analysis the values were -0.9 (95% CI: -6.4, 4.6) mmHg/kg for systolic pressure and -0.2 (95% CI: -4.1, 3.7) mmHg/kg for diastolic pressure. The results suggest that in-utero growth restriction in twins is not a major determinant of their blood pressure as adults.

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

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.