Jacob Alexander Lykke

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

OBJECTIVEnWe performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes.nnnSTUDY DESIGNnWe 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.nnnRESULTSnOf 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).nnnCONCLUSIONnAmong 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.

Angiogenic biomarkers in pregnancy: defining maternal and fetal health.

We review diagnostic and predictive roles of the angiogenic proteins placental growth factor, soluble fms‐like tyrosine kinase 1, and soluble endoglin in preeclampsia, and their association with future cardiovascular disease, diabetes, and breast cancer. Specific patterns of these proteins represent preeclamptic prediction markers and combined with maternal and clinical characteristics, the predictive values increase. Women experiencing preeclampsia have increased risks of developing cardiovascular diseases and diabetes, and a decreased risk of breast cancer. High placental growth factor concentrations have, in elderly patients, been shown to predict cardiovascular events. Diabetes is also a risk factor for future cardiovascular disease. Diabetic vascular complications are associated with increased soluble endoglin concentrations, and vascular endothelial growth factor concentrations are correlated to HbA1c and fasting glucose. Hence dysregulation in angiogenic proteins may link preeclampsia and cardiovascular diseases, targeting women who could in future benefit from prophylactic programs to possibly prevent, delay or reduce cardiovascular disease.

Parent-Offspring Conflict and the Persistence of Pregnancy-Induced Hypertension in Modern Humans

Preeclampsia is a major cause of perinatal mortality and disease affecting 5–10% of all pregnancies worldwide, but its etiology remains poorly understood despite considerable research effort. Parent-offspring conflict theory suggests that such hypertensive disorders of pregnancy may have evolved through the ability of fetal genes to increase maternal blood pressure as this enhances general nutrient supply. However, such mechanisms for inducing hypertension in pregnancy would need to incur sufficient offspring health benefits to compensate for the obvious risks for maternal and fetal health towards the end of pregnancy in order to explain why these disorders have not been removed by natural selection in our hunter-gatherer ancestors. We analyzed >750,000 live births in the Danish National Patient Registry and all registered medical diagnoses for up to 30 years after birth. We show that offspring exposed to pregnancy-induced hypertension (PIH) in trimester 1 had significantly reduced overall later-life disease risks, but increased risks when PIH exposure started or developed as preeclampsia in later trimesters. Similar patterns were found for first-year mortality. These results suggest that early PIH leading to improved postpartum survival and health represents a balanced compromise between the reproductive interests of parents and offspring, whereas later onset of PIH may reflect an unbalanced parent-offspring conflict at the detriment of maternal and offspring health.

Time from pre-eclampsia diagnosis to delivery affects future health prospects of children

Abstract Background and objectives Pre-eclampsia often has detrimental health effects for pregnant women and their fetuses, but whether exposure in the womb has long-term health-consequences for children as they grow up remains poorly understood. We assessed overall morbidity of children following exposure to either mild or severe pre-eclampsia up to 30 years after birth and related disease risks to duration of exposure, i.e. the time from diagnosis to delivery. Methodology We did a registry-based retrospective cohort study in Denmark covering the years 1979–2009, using the separate diagnoses of mild and severe pre-eclampsia and the duration of exposure as predictor variables for specific and overall risks of later disease. We analysed 3 537 525 diagnoses for 14 disease groups, accumulated by 758 524 singleton children, after subdividing deliveries in six gestational age categories, partialing out effects of eight potentially confounding factors. Results Exposure to mild pre-eclampsia appeared to have consistent negative effects on health later in life, although only a few specific disease cases remained significant after corrections for multiple testing. Morbidity risks associated with mild pre-eclampsia were of similar magnitude as those associated with severe pre-eclampsia. Apart from this overall trend in number of diagnoses incurred across disease groups, hazard ratios for several disorders also increased with the duration of exposure, including disorders related to the metabolic syndrome. Conclusions and implications Maternal pre-eclampsia has lasting effects on offspring health and differences between exposure to severe and mild pre-eclampsia appear to be less than previously assumed. Our results suggest that it would be prudent to include the long-term health prospects of children in the complex clinical management of mild pre-eclampsia.

Recurrence of hypertensive disorders of pregnancy

OBJECTIVEnWe performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes.nnnSTUDY DESIGNnWe 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.nnnRESULTSnOf 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).nnnCONCLUSIONnAmong 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.

OP0010. Optimizing time from diagnosis to delivery in preeclampsia based on the future health prospects of offspring

INTRODUCTIONnLimited data exist on long-term health-consequences of maternal preeclampsia for offspring.nnnOBJECTIVESnWe investigated long-term offspring morbidity following preeclampsia and related these data to the time from diagnosis to delivery.nnnMETHODSnWe performed a registry based retrospective cohort study in Denmark in the years 1977-2007. The primary exposure was preeclamptic days from diagnosis to delivery. We analyzed 6 gestational age groups separately. The outcomes were groups of later disease diagnoses in offspring.nnnRESULTSnWe included 758,524 singleton offspring who had accumulated 3,537,525 medical diagnoses. Offspring delivered by severely preeclamptic women between 28 and 33weeks had an increased risk of endocrine disorders (HR 1.46; 95% CI 1.09-1.96) compared to normotensive pregnancies, independent of days between diagnosis and delivery (HR 1.000; 95% CI 0.993-1.006). Offspring delivered by mildly preeclamptic women between 37 and 38 weeks had an increased risk of behavioral disorders (HR 1.19; 95% CI 1.05-1.37) and this risk was dependent on days since diagnosis (HR 1.006; 1.001-1.011). In general, after 37-38weeks, days from diagnosis to delivery increased the risk of later diagnoses in most disease groups.nnnCONCLUSIONnOffspring from preeclamptic pregnancies have increased risks of various later diseases. The time between diagnosis and delivery modified these risks only slightly, but it seems prudent not to prolong preeclamptic pregnancies after 38weeks.