Association of Fetal Fraction of Cell-Free DNA and Hypertensive Disorders of Pregnancy

2018 ◽  
Vol 36 (03) ◽  
pp. 311-316 ◽  
Author(s):  
Nathanael Koelper ◽  
Mary Sammel ◽  
Lorraine Dugoff ◽  
Whitney Bender
Keyword(s):  
Multinomial Logistic Regression ◽  
First Trimester ◽  
Chronic Hypertension ◽  
Hypertensive Disorders Of Pregnancy ◽  
Cell Free Dna ◽  
Free Dna ◽  
Hypertensive Disorders ◽  
Increased Risk ◽  
The Relationship ◽  
Fetal Fraction

Objective The objective of this study is to examine the relationship between fetal fraction and hypertensive disorders of pregnancy. Study Design This is a retrospective cohort study of women with singleton pregnancies who had cell-free DNA (cfDNA) screening at 10 to 20 weeks of gestation. The primary outcome was the development of gestational hypertension (gHTN), preeclampsia (PEC), and PEC with severe features. Multinomial logistic regression was performed to assess the relationship between fetal fraction and pregnancy outcomes of interest while controlling for potential confounders. Results Among 2,701 women meeting inclusion criteria, 387 (14.3%) were diagnosed with hypertensive disorders of pregnancy. First-trimester fetal fraction was significantly lower in women diagnosed with hypertensive disorders of pregnancy (10.9 vs. 12.4, p < 0.0001). An increased risk of gHTN and PEC, PEC with severe features with delivery > 34 weeks, and PEC with severe features with delivery ≤ 34 weeks was seen with lower first-trimester fetal fractions (odds ratio [OR]: 0.55, 95% confidence interval [CI] [0.36–0.83], p = 0.005; OR: 0.59, 95% CI [0.35–0.99], p = 0.048; and OR: 0.27, 95% CI [0.08–0.96], p = 0.044). The relationship between fetal fraction and hypertensive disorders of pregnancy was not statistically significant after adjusting for maternal age, race, body mass index, and chronic hypertension. Conclusion Fetal fraction of cfDNA at 10 to 20 weeks of gestation was not associated with the development of hypertensive disorders of pregnancy.

High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy Outcomes

2019 ◽  
Vol 37 (01) ◽  
pp. 008-013 ◽  
Author(s):  
Lydia L. Shook ◽  
Mark A. Clapp ◽  
Penelope S. Roberts ◽  
Sarah N. Bernstein ◽  
Ilona T. Goldfarb
Keyword(s):  
Preterm Birth ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
First Trimester ◽  
Hypertensive Disorders Of Pregnancy ◽  
Aneuploidy Screening ◽  
Hypertensive Disorders ◽  
Increased Risk ◽  
Adverse Pregnancy ◽  
Fetal Fraction

Abstract Objective To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. Study Design This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th–95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Results A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant <fifth percentile, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.1–4.8, p = 0.039). There was no significant association between high FF and either preterm birth or hypertensive disorders of pregnancy. Conclusion Women with a high FF in the first trimester are at increased risk of delivering a small for gestational age infant <fifth percentile. Further investigation into the clinical implications of a high FF is warranted.

Low Fetal Fraction and Birth Weight in Women with Negative First-Trimester Cell-Free DNA Screening

2019 ◽  
Vol 37 (01) ◽  
pp. 086-091
Author(s):  
Mark A. Clapp ◽  
Margaret Berry ◽  
Lydia L. Shook ◽  
Penelope S. Roberts ◽  
Ilona T. Goldfarb ◽  
...  
Keyword(s):  
Birth Weight ◽  
First Trimester ◽  
Cell Free Dna ◽  
Free Dna ◽  
Increased Risk ◽  
Trimester Screening ◽  
Future Work ◽  
Primary Variable ◽  
Cfdna Screening ◽  
Fetal Fraction

Abstract Objective To determine the association between low fetal fraction and birth weight among women with a negative cell-free DNA (cfDNA) result for common aneuploidies in the first trimester. Study Design This is a retrospective cohort of women who delivered a singleton between July 2016 and June 2018 at a single institution and had normal cfDNA testing in the first trimester. The primary variable of interest was “low fetal fraction,” which was defined as fetal fractions less than 5th percentile among all fetal fractions in the cohort (fetal fraction < 5.34%). The primary outcomes were birth weight ≤ 5th and ≤ 10th percentiles. Multivariable logistic regressions assessed for the association between low fetal fraction and birth weight. Results A total of 7,478 women delivered a singleton at ≥24 weeks' gestation, of which 2,387 (32%) underwent genetic screening through cfDNA; the majority were in the first trimester (n = 2,052 [86%]). 2,035 met the inclusion criteria. Birth weight ≤ 5th percentile was significantly higher in the low fetal fraction group (6.9 vs. 3.2%; p = 0.04). A low fetal fraction was associated with higher odds of an infant with a low birth weight: adjusted odds ratio (aOR) of 2.32 (95% CI 1.15–4.67) for birth weight ≤ 10th percentile (p = 0.02) and aOR of 3.73 (95% CI 1.40–9.03) for birth weight ≤ 5th percentile (p = 0.004). Conclusion Low fetal fractions of ≤ 5th percentile were associated with an increased risk of birth weights ≤ 5th and ≤ 10th percentiles in women with negative cfDNA screening in the first trimester. Future work is needed to further investigate this relationship and to determine the potential clinical implications, such as third-trimester screening for growth restriction in women with low fetal fractions and negative cfDNA screening results.

Stroke in Pregnancy and Puerperium: Validated Incidence Trends With Risk Factor Analysis in Finland 1987–2016

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011990
Author(s):  
Liisa Karjalainen ◽  
Minna Tikkanen ◽  
Kirsi Rantanen ◽  
Karoliina Aarnio ◽  
Aino Korhonen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Postpartum Period ◽  
First Trimester ◽  
Class Iii ◽  
Hypertensive Disorders Of Pregnancy ◽  
Risk Factor Management ◽  
Incidence Trends ◽  
Hypertensive Disorders ◽  
Increased Risk

Objective:To investigate whether previously reported increasing incidence of pregnancy-associated stroke (PAS) is observed in chart-validated register data in Finland. In an exploratory analysis, we studied risk factors for PAS.Methods:We performed a retrospective population-based cohort study and nested case-control study in Finland 1987-2016. The Medical Birth Register (MBR) was linked with the Hospital Discharge Register to identify women with incident stroke (ischemic stroke, cerebral venous thrombosis, intracerebral or subarachnoid hemorrhage) during pregnancy or puerperium. Cases were verified from patient records. Incidence of PAS over the study period, in 5-year age groups and pregnancy/postpartum period were calculated per number of deliveries. Three matched controls were selected for each case from MBR to compare risk factors.Results:After chart review, 29.6% (257/868) of cases were PAS. The incidence of PAS was 14.5 (95%CI: 12.8-16.3) per 100,000 deliveries. Incidence increased from 11.1 to 25.2 per 100,000 deliveries from 1987-1991 to 2012-2016 (p<0.0001). Incidence increased by age from 9.8 to 29.9 per 100,000 deliveries from ages 20-24 to ages >40 (p<0.0001). During early postpartum period, incidence was 5-fold greater compared to the first trimester. Maternal mortality was 6.6%. In the multivariable adjusted model, smoking beyond 12 gestational weeks (odds ratio [OR] 1.8, 95%CI: 1.2-2.7), migraine (OR 16.3, 95%CI: 5.3-49.8), and hypertensive disorders of pregnancy (OR 4.0, 95%CI: 2.5-6.3) were the most important risk factors for PAS.Conclusion:PAS incidence is increasing stressing the importance of careful pregnancy surveillance and risk factor management, particularly in older expectant mothers and extending to puerperium.Classification of Evidence:This study provides Class III evidence that smoking beyond 12 gestational weeks, migraine and hypertensive disorders of pregnancy are associated with an increased risk of PAS.

scholarly journals Noninvasive Fetal Genotyping by Droplet Digital PCR to Identify Maternally Inherited Monogenic Diabetes Variants

2020 ◽  
Vol 66 (7) ◽  
pp. 958-965 ◽  
Author(s):  
Richard C Caswell ◽  
Tristan Snowsill ◽  
Jayne A L Houghton ◽  
Ali J Chakera ◽  
Maggie H Shepherd ◽  
...  
Keyword(s):  
At Risk ◽  
Digital Pcr ◽  
Monogenic Diabetes ◽  
Droplet Digital Pcr ◽  
High Birth Weight ◽  
Cell Free Dna ◽  
Pathogenic Variants ◽  
Free Dna ◽  
Increased Risk ◽  
Fetal Fraction

Abstract Background Babies of women with heterozygous pathogenic glucokinase (GCK) variants causing mild fasting hyperglycemia are at risk of macrosomia if they do not inherit the variant. Conversely, babies who inherit a pathogenic hepatocyte nuclear factor 4α (HNF4A) diabetes variant are at increased risk of high birth weight. Noninvasive fetal genotyping for maternal pathogenic variants would inform pregnancy management. Methods Droplet digital PCR was used to quantify reference and variant alleles in cell-free DNA extracted from blood from 38 pregnant women heterozygous for a GCK or HNF4A variant and to determine fetal fraction by measurement of informative maternal and paternal variants. Droplet numbers positive for the reference/alternate allele together with the fetal fraction were used in a Bayesian analysis to derive probability for the fetal genotype. The babies’ genotypes were ascertained postnatally by Sanger sequencing. Results Droplet digital PCR assays for GCK or HNF4A variants were validated for testing in all 38 pregnancies. Fetal fraction of ≥2% was demonstrated in at least 1 cell-free DNA sample from 33 pregnancies. A threshold of ≥0.95 for calling homozygous reference genotypes and ≤0.05 for heterozygous fetal genotypes allowed correct genotype calls for all 33 pregnancies with no false-positive results. In 30 of 33 pregnancies, a result was obtained from a single blood sample. Conclusions This assay can be used to identify pregnancies at risk of macrosomia due to maternal monogenic diabetes variants.

scholarly journals Association between fetal fraction on cell‐free DNA testing and first‐trimester markers for pre‐eclampsia

2018 ◽  
Vol 52 (6) ◽  
pp. 722-727 ◽  
Author(s):  
D. L. Rolnik ◽  
F. da Silva Costa ◽  
T. J. Lee ◽  
M. Schmid ◽  
A. C. McLennan
Keyword(s):  
First Trimester ◽  
Dna Testing ◽  
Cell Free Dna ◽  
Free Dna ◽  
Fetal Fraction

scholarly journals Sequential measurement of the neurosensory retina in hypertensive disorders of pregnancy: a model of microvascular injury in hypertensive emergency

2021 ◽  
Author(s):  
Robert J. Herman ◽  
Anshula Ambasta ◽  
R. Geoff Williams ◽  
Kelly B. Zarnke ◽  
Fiona E. Costello ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Laboratory ◽  
Normal Pregnancy ◽  
Macular Thickness ◽  
Chronic Hypertension ◽  
Hypertensive Disorders Of Pregnancy ◽  
Laboratory Findings ◽  
Response Data ◽  
Hypertensive Disorders ◽  
The Relationship

AbstractOptical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP.

Abstract MP63: Established Cardiovascular Disease Risk Factors Mediate The Relationship Between Hypertensive Disorders In First Pregnancy And Maternal Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Jennifer J Stuart ◽  
Lauren J Tanz ◽  
Eric B Rimm ◽  
Donna Spiegelman ◽  
Stacey A Missmer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Chronic Hypertension ◽  
Cvd Risk Factors ◽  
First Birth ◽  
Cvd Risk ◽  
Hypertensive Disorders ◽  
Increased Risk ◽  
History Of ◽  
The Relationship

Introduction: Women with a history of hypertensive disorders in pregnancy (HDP; gestational hypertension [GHTN] or preeclampsia) have an increased risk of CVD risk factors and events compared to women with normotensive pregnancies. However, the extent to which the relationship between HDP and CVD events is mediated by established CVD risk factors is less clear. Hypothesis: We hypothesized that a large proportion of the HDP-CVD relationship would be mediated by subsequent CVD risk factors — chronic hypertension (CHTN), type 2 diabetes (T2D), hypercholesterolemia, and BMI. Methods: Parous women free of prior CVD events, CHTN, T2D, and hypercholesterolemia at first birth in the Nurses’ Health Study II comprised the analytic sample (n=57,974). Pregnancy history was retrospectively reported in 2009. Women were followed for confirmed CVD events (coronary heart disease [non-fatal or fatal MI, fatal CHD] or stroke [non-fatal or fatal]) from first birth through 2015. Potential mediators were self-reported on biennial questionnaires. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the relationship between HDP in first pregnancy (preeclampsia or GHTN vs. normotension [ref]) and CVD, adjusting for age, race/ethnicity, parental education, family history of CVD before age 60, and pre-pregnancy risk factors (e.g., smoking, diet, and BMI). To evaluate the proportion of the HDP-CVD association that was jointly mediated by the CVD risk factors we used the difference method, comparing a model including these four factors to a model without them. Results: Nine percent of women (n=5,306) had a history of HDP in first pregnancy (preeclampsia: 6.3%; GHTN: 2.9%). CVD events occurred in 650 women with normotension in first pregnancy, 30 with GHTN, and 81 with preeclampsia. Adjusting for pre-pregnancy confounders, women with HDP in first pregnancy had a 63% higher rate of incident CVD (CI: 1.33-2.00) compared to women with normotension in first pregnancy; in particular, the strongest association was observed between preeclampsia and CHD (HR=2.18, CI: 1.62-2.93). The overall HDP-CVD association was largely mediated by the group of four CVD risk factors (HDP: proportion mediation [PM]=65%, CI: 35-87; preeclampsia: PM=57%, CI: 21-87; GHTN: PM=99%, CI: inestimable). All CVD risk factors contributed to mediation, but chronic hypertension accounted for the largest proportion. Conclusions: While approximately 40% of the association between preeclampsia and CVD remained unexplained, almost all the increased risk of CVD conferred by a history of GHTN was jointly accounted for by the development of established risk factors postpartum. Screening for CHTN, T2D, hypercholesterolemia, and overweight/obesity after pregnancy may be especially helpful in CVD prevention among women with a history of HDP.

scholarly journals Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e018313 ◽  
Author(s):  
Gillian M Maher ◽  
Gerard W O’Keeffe ◽  
Louise C Kenny ◽  
Patricia M Kearney ◽  
Ted G Dinan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Neurodevelopmental Disorders ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Chronic Hypertension ◽  
Hypertensive Disorders Of Pregnancy ◽  
Hypertensive Disorders ◽  
Increased Risk ◽  
Meta Analyses ◽  
The Impact

IntroductionHypertensive disorders of pregnancy (HDPs), that is chronic hypertension, gestational hypertension, pre-eclampsia (de novo or superimposed on chronic hypertension) and white coat hypertension, affect approximately 5%–15% of pregnancies. HDP exposure has been linked to an increased risk of autism spectrum disorder, attention deficit/hyperactivity disorder and other neurodevelopmental disorders in children. However, findings are inconsistent, and a clear consensus on the impact of HDPs on the risk of neurodevelopmental disorders is needed. Therefore, we aim to synthesise the published literature on the relationship between HDPs and the risk of neurodevelopmental disorders in the form of a systematic review and meta-analysis.Methods and analysisWe will include cohort, case–control and cross-sectional studies in which diagnosis of an HDP was reported, and neurodevelopmental disorders were the outcome of interest based on a preprepared protocol. A systematic search of PubMed, CINAHL, Embase, PsycINFO and Web of Science will be conducted in accordance with a detailed search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction using a standardised data collection form and assess study quality using a bias classification tool. Meta-analyses will be performed to calculate overall pooled estimates using the generic inverse variance method. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses.Ethics and disseminationThis proposed systematic review and meta-analysis is based on published data, therefore, does not require ethics approval. Findings will be presented at scientific conferences and disseminated through publication in a peer-reviewed journal.RegistrationCRD42017068258.

scholarly journals Preeclampsia and Cardiovascular Disease in a Large UK Pregnancy Cohort of Linked Electronic Health Records

Circulation ◽  
2019 ◽  
Vol 140 (13) ◽  
pp. 1050-1060 ◽  
Author(s):  
Lydia J. Leon ◽  
Fergus P. McCarthy ◽  
Kenan Direk ◽  
Arturo Gonzalez-Izquierdo ◽  
David Prieto-Merino ◽  
...  
Keyword(s):  
Electronic Health Records ◽  
Cumulative Incidence ◽  
Chronic Hypertension ◽  
Cardiovascular Disorders ◽  
Hypertensive Disorders Of Pregnancy ◽  
Health Records ◽  
Hypertensive Disorders ◽  
Increased Risk ◽  
Electronic Health ◽  
The Impact

Background: The associations between pregnancy hypertensive disorders and common cardiovascular disorders have not been investigated at scale in a contemporaneous population. We aimed to investigate the association between preeclampsia, hypertensive disorders of pregnancy, and subsequent diagnosis of 12 different cardiovascular disorders. Methods: We used linked electronic health records from 1997 to 2016 to recreate a UK population-based cohort of 1.3 million women, mean age at delivery 28 years, with nearly 1.9 million completed pregnancies. We used multivariable Cox models to determine the associations between hypertensive disorders of pregnancy, and preeclampsia alone (term and preterm), with 12 cardiovascular disorders in addition to chronic hypertension. We estimated the cumulative incidence of a composite end point of any cardiovascular disorder according to preeclampsia exposure. Results: During the 20-year study period, 18 624 incident cardiovascular disorders were observed, 65% of which had occurred in women under 40 years. Compared to women without hypertension in pregnancy, women who had 1 or more pregnancies affected by preeclampsia had a hazard ratio of 1.9 (95% confidence interval 1.53–2.35) for any stroke, 1.67 (1.54–1.81) for cardiac atherosclerotic events, 1.82 (1.34–2.46) for peripheral events, 2.13 (1.64–2.76) for heart failure, 1.73 (1.38–2.16) for atrial fibrillation, 2.12 (1.49–2.99) for cardiovascular deaths, and 4.47 (4.32–4.62) for chronic hypertension. Differences in cumulative incidence curves, according to preeclampsia status, were apparent within 1 year of the first index pregnancy. Similar patterns of association were observed for hypertensive disorders of pregnancy, while preterm preeclampsia conferred slightly further elevated risks. Conclusions: Hypertensive disorders of pregnancy, including preeclampsia, have a similar pattern of increased risk across all 12 cardiovascular disorders and chronic hypertension, and the impact was evident soon after pregnancy. Hypertensive disorders of pregnancy should be considered as a natural screening tool for cardiovascular events, enabling cardiovascular risk prevention through national initiatives.

scholarly journals Not all low fetal fraction cell‐free DNA screening failures are at increased risk for aneuploidy

2021 ◽  
Author(s):  
Samantha Caldwell ◽  
Eyad Almasri ◽  
Lindsey Schmidt ◽  
Chen Xu ◽  
Brittany Dyr ◽  
...  
Keyword(s):  
Cell Free Dna ◽  
Free Dna ◽  
Increased Risk ◽  
Fetal Fraction
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