Protocol for a 20-year follow-up after a randomized controlled trial of a Mediterranean diet in pregnancy: maternal and offspring risk factors for cardiovascular disease.

Background: An inadequate maternal diet during pregnancy can impair offspring health and may increase the risk of cardiovascular disease later in life. The purpose of the proposed study is to assess the risk factors associated with cardiovascular disease in both mothers and their offspring 20 years following their participation in a Mediterranean diet intervention trial during pregnancy. Methods: The "Cardiovascular Risk Reduction Diet In Pregnancy" (CARRDIP) study was a randomized controlled trial performed between 1999 and 2001. The participants were randomized to adhere to either a Mediterranean diet or their regular diet during pregnancy. An extensive amount of data such as diet information, ultrasound measurements, anthropometry, and biomarkers from these mothers during pregnancy and their offspring in the neonatal period were collected. The mother-offspring pairs (n = 269) from the CARRDIP study will be invited to participate in a clinical examination and blood sample collection. This follow-up study, conducted 20 years after the original CARRDIP study, will investigate cardiovascular risk factors in mothers and offspring. The primary outcome will be the blood pressure of the offspring. In addition, the study will explore various aspects of cardiovascular health, including metabolic and inflammatory status, clinical history, and body composition of the participants. Discussion: Previous studies investigating the effects of nutrition during pregnancy on maternal and offspring health have been either observational studies, animal studies, or randomized controlled trials with a follow-up period of less than 5 years. This project aims to study the long-term effects of dietary intervention during pregnancy on maternal and offspring cardiovascular risk markers. Clinical Trial Registration: Clinicaltrials.gov, identifier (NCT05030922).

Effects of antenatal diet and physical activity on maternal and fetal outcomes: individual patient data meta-analysis and health economic evaluation.

BACKGROUND: Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes. OBJECTIVES: To assess whether or not the effects of diet and lifestyle interventions vary in subgroups of women, based on maternal body mass index (BMI), age, parity, Caucasian ethnicity and underlying medical condition(s), by undertaking an individual patient data (IPD) meta-analysis. We also evaluated the association of gestational weight gain (GWG) with adverse pregnancy outcomes and assessed the cost-effectiveness of the interventions. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment database were searched from October 2013 to March 2015 (to update a previous search). REVIEW METHODS: Researchers from the International Weight Management in Pregnancy Collaborative Network shared the primary data. For each intervention type and outcome, we performed a two-step IPD random-effects meta-analysis, for all women (except underweight) combined and for each subgroup of interest, to obtain summary estimates of effects and 95% confidence intervals (CIs), and synthesised the differences in effects between subgroups. In the first stage, we fitted a linear regression adjusted for baseline (for continuous outcomes) or a logistic regression model (for binary outcomes) in each study separately; estimates were combined across studies using random-effects meta-analysis models. We quantified the relationship between weight gain and complications, and undertook a decision-analytic model-based economic evaluation to assess the cost-effectiveness of the interventions. RESULTS: Diet and lifestyle interventions reduced GWG by an average of 0.70 kg (95% CI -0.92 to -0.48 kg; 33 studies, 9320 women). The effects on composite maternal outcome [summary odds ratio (OR) 0.90, 95% CI 0.79 to 1.03; 24 studies, 8852 women] and composite fetal/neonatal outcome (summary OR 0.94, 95% CI 0.83 to 1.08; 18 studies, 7981 women) were not significant. The effect did not vary with baseline BMI, age, ethnicity, parity or underlying medical conditions for GWG, and composite maternal and fetal outcomes. Lifestyle interventions reduce Caesarean sections (OR 0.91, 95% CI 0.83 to 0.99), but not other individual maternal outcomes such as gestational diabetes mellitus (OR 0.89, 95% CI 0.72 to 1.10), pre-eclampsia or pregnancy-induced hypertension (OR 0.95, 95% CI 0.78 to 1.16) and preterm birth (OR 0.94, 95% CI 0.78 to 1.13). There was no significant effect on fetal outcomes. The interventions were not cost-effective. GWG, including adherence to the Institute of Medicine-recommended targets, was not associated with a reduction in complications. Predictors of GWG were maternal age (summary estimate -0.10 kg, 95% CI -0.14 to -0.06 kg) and multiparity (summary estimate -0.73 kg, 95% CI -1.24 to -0.23 kg). LIMITATIONS: The findings were limited by the lack of standardisation in the components of intervention, residual heterogeneity in effects across studies for most analyses and the unavailability of IPD in some studies. CONCLUSION: Diet and lifestyle interventions in pregnancy are clinically effective in reducing GWG irrespective of risk factors, with no effects on composite maternal and fetal outcomes. FUTURE WORK: The differential effects of lifestyle interventions on individual pregnancy outcomes need evaluation. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003804. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

How does the duration of active pushing in labor affect neonatal outcomes?

AIM: To assess the effect of time of active pushing (TAP) on neonatal outcome. MATERIALS AND METHODS: The study population (n=36,432) was taken from a Swedish randomized control trial on intrapartum monitoring, a European Union fetal electrocardiogram trial, and from Mölndal Hospital. After validation of acid-base samples and TAP, 22,812 cases were accepted for analysis. RESULTS: The median active TAP was 36 min for P0 and 13 min for P≥1 (P<0.001). After adjustments for parity, epidural, labor induction, birth weight, and gender, pushing for 15-29 min (n=6589) relative to pushing for <15 min (n=7264) increased the OR of a cord artery pH of <7.00 to 3.20 (95% CI 1.7-6.0), and that of a base deficit in extracellular fluid of >12 mmol/L to 3.5 (95% CI 1.3-9.0). The group with a cord artery pH of <7.00 had a longer TAP than the group with pH≥7.00: median (5th-95th percentile), 38 (9-107) min vs. 23 (5-87) min, P<0.001. The probability of a spontaneous vaginal delivery decreased significantly with every subsequent increase of 30 min in TAP (P<0.05). CONCLUSION: The risks of severe acidemia, metabolic acidosis, and deteriorated neonatal outcome gradually increased with the length of TAP (>15 min), while the probability of a spontaneous vaginal delivery decreased with the duration of pushing. We suggest active physiological evaluation of the labor progress together with continuous electronic fetal monitoring during pushing irrespective of guideline thresholds.

Intrapartum cardiotocography (CTG) and ST-analysis of labor in diabetic patients.

AIM: To determine the prevalence and types of intrapartum cardiotocography (CTG) patterns and investigate their relationship to moderate acidemia in term fetuses of diabetic mothers. Also, to assess if the combination of fetal electrocardiogram (FECG) and those CTG patterns strengthens the association with moderate acidemia. MATERIAL AND METHODS: The material for this study is obtained from the Swedish randomized control trial and the European Union ST-analysis trial. We developed an analytical model for CTG patterns based on the progress in CTG changes, in a longitudinal periodic manner. The model was then combined with information regarding changes in ST interval that indicate threatening asphyxia, and the findings were analyzed to determine correlation with the presence of moderate acidemia at birth. RESULTS: This study involved data of 413 diabetic mothers. A preterminal CTG was more common in the diabetes mellitus (DM) group (6/70, 8.6%) than in the gestational diabetes (GD) group (3/307, 1.0%; P=0.003). For diabetic mothers (i.e., DM+GD) with a normal CTG at the start of monitoring, the presence of FECG data indicating asphyxia significantly increased the likelihood of an umbilical artery pH<7.15 at birth [odds ratio (OR)=3.65, 95% confidence interval (CI)=1.33-10.05]. Among labors where the CTG was non-reassuring at the start of monitoring, no significant association was found between pH<7.15 and indication to intervene according to FECG information (OR=1.51, 95% CI=0.33-7.0). CONCLUSIONS: A preterminal CTG is more common in the fetuses of DM than GD mothers during labor. When CTG was normal at the start of recording, the addition of FECG information gave a significant add on information to predict moderate acidemia.

Evidence for impaired physiological decrease in the uteroplacental vascular resistance in pregnant women with familial hypercholesterolemia.

Abnormal hyperlipidemia characterizes pregnancy in familial hypercholesterolemia (FH), and is associated with vascular dysfunction. Hence, we compared blood flow in the feto- and uteroplacental circulation in FH and healthy reference women using Doppler velocimetry. The umbilical artery pulsatility index (PI) at gestational weeks 24 and 36, and the concomitant physiological decrease in PI, was similar in FH (n=10) and the reference group (n=143). The decrease in mean PI of both uterine arteries from week 24 to 36 was significant in the reference group, but not among the FH women. Plasma LDL-cholesterol measured between weeks 24 and 36 was not correlated with the decrease in umbilical PI in the FH group, or with the decrease in umbilical or mean uterine PI in the reference group. We conclude that pregnancy in FH might be associated with attenuated physiological decrease in mean PI of uterine arteries, possibly reflecting increased uteroplacental vascular resistance unrelated to plasma LDL-cholesterol levels.

Effect of a cholesterol-lowering diet during pregnancy on maternal and fetal Doppler velocimetry: the CARRDIP study.

OBJECTIVE: The purpose of this study was to evaluate the effect of a low-cholesterol low-saturated fat diet on Doppler indices in the fetus and mother. STUDY DESIGN: Two hundred ninety nonsmoking white women, aged 21-38 years, without previous pregnancy complications and carrying a single fetus were assigned randomly to continue their usual diet (control subjects; n = 149) or to adopt a low-cholesterol low-saturated fat diet (intervention group; n = 141) from gestational week 17-20 to birth. Doppler velocimetry of the umbilical artery and both uterine arteries were assessed at gestational weeks 24, 30, and 36. RESULTS: The physiologic gestational decrease in umbilical artery pulsatility index (PI) from week 24-30 was more pronounced in the intervention group, compared with the control group, with median values (interquartile range) of -0.17 (-0.29, -0.06) and -0.11 (-0.25, 0.01), respectively (P = .048). Assignment to the intervention diet did not influence the changes in mean PI value of the 2 uterine arteries (P = .3). The change in umbilical artery PI and mean PI value of the uterine arteries between weeks 24 and 36 were not significantly different between the 2 groups (P = 1.0 and .2 respectively). CONCLUSION: Our study shows that a cholesterol-lowering diet during pregnancy may modify fetoplacental circulation in mid pregnancy.

Altered hemostatic balance and endothelial activation in pregnant women with familial hypercholesterolemia.

INTRODUCTION: Patients with familial hypercholesterolemia (FH) are prone to premature cardiovascular disease. During pregnancy plasma lipids reach higher absolute values in FH than in healthy women. Pregnancy is associated with activation of coagulation and possibly also of vascular endothelium, which might further increase the risk of cardiovascular disease in FH. However, whether hemostatic and endothelial activation markers are increased in pregnant FH women compared with non-FH pregnancies, is unknown. MATERIALS AND METHODS: Activation markers of hemostasis and endothelium were analyzed in blood samples collected prospectively from 22 heterozygous FH women during pregnancy and compared with those of a reference group of 149 healthy, pregnant women. RESULTS: A procoagulant pattern was detected in both groups, but was more evident among FH women at least partly due to their enhanced thrombin generation, and because tissue factor pathway inhibitor type 1 increased in the reference group only. Furthermore, plasminogen activator inhibitor type 2 antigen increased more in FH than in the reference group. Whereas C-reactive protein, intercellular adhesion marker-1 and E-selectin did not change appreciably, vascular endothelial cell adhesion molecule 1 rose markedly in FH. CONCLUSION: Increased lipid levels as well as a net procoagulant activity and an enhanced endothelial activation possibly confer additional risks of cardiovascular disease among pregnant FH women.

Marked changes in plasma lipids and lipoproteins during pregnancy in women with familial hypercholesterolemia.

Serum lipids increase during pregnancy. However, data are scarce for lipid changes in pregnant women with heterozygous familiar hypercholesterolemia (FH). The purpose of the present study was to examine plasma lipids and lipoproteins during pregnancy in women with FH. In 22 pregnant women blood samples were collected at gestational weeks 17-20 (baseline), 24, 30 and 36. Total- and LDL cholesterol increased significantly between baseline and gestational week 36 by 29% and 30%, respectively, compared to 25% and 34% in a reference group of 149 healthy pregnant women. Notably, the plasma lipid concentrations in the FH women were much higher than in the reference women. Triglycerides increased (P<0.05) by 116% and 103%, in the FH group and reference group, respectively. HDL cholesterol was unchanged in both groups. Moreover, apolipoprotein B increased significantly during pregnancy in the FH women, whereas apolipoprotein A1 and lipoprotein (a) were unchanged. Pregnancy outcomes in the FH group did not differ significantly from those in the reference group. In conclusion, the relative increase in plasma lipids was similar in pregnant women with FH and in healthy women, but the absolute magnitude was considerably larger in pregnant FH women.

Effect of a cholesterol-lowering diet on maternal, cord, and neonatal lipids, and pregnancy outcome: a randomized clinical trial.

OBJECTIVE: We assessed the effect of a cholesterol-lowering diet on maternal, cord, and neonatal plasma lipids and pregnancy outcome. STUDY DESIGN: Nonsmoking white women with singleton pregnancies (n = 290), aged 21 to 38 years, and with no previous pregnancy-related complications, were randomized to either continue their usual diet or to adopt a diet that promoted fish, low-fat meats and dairy products, oils, whole grains, fruits, vegetables, and legumes from gestational week 17 to 20 to birth. RESULTS: Maternal total and low-density lipoprotein cholesterol levels were lowered in the intervention compared with the control group (P < .01). Lipid levels in cord blood and in neonates born to mothers in the intervention versus the control groups did not differ. In the intention-to-treat cohort 1 (0.7%) of 141 women in the intervention group versus 11 (7.4%) of 149 women in the control group delivered before 37 weeks (RR 0.10; 95% CI 0.01-0.77). The incidence of other pregnancy complications and birth weight was similar in both groups. CONCLUSION: A cholesterol-lowering diet may modify maternal lipid levels but not cord and neonatal lipids. The marked observed effect of this diet on the reduction of preterm delivery in low-risk pregnancies should encourage future larger studies to clarify the role of such a diet in the prevention of preterm birth.