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

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.

2018 ◽  
Vol 36 (03) ◽  
pp. 311-316 ◽  
Author(s):  
Nathanael Koelper ◽  
Mary Sammel ◽  
Lorraine Dugoff ◽  
Whitney Bender

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.


Cephalalgia ◽  
2021 ◽  
pp. 033310242110292
Author(s):  
Isabella Neri ◽  
Daniela Menichini ◽  
Francesca Monari ◽  
Ludovica Spanò Bascio ◽  
Federico Banchelli ◽  
...  

Objective This study aims to investigate pregnancy and perinatal outcomes in women with tension-type headache, migraine without aura and migraine with aura by comparing them to women without any headache disorders. Study design Prospective cohort study including singleton pregnancies attending the first trimester aneuploidy screening at the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results A total of 515 consecutive women were included and headache disorders were reported in 43.5% of them (224/515). Tension-type headache was diagnosed in 24.3% of the cases, while 14% suffered from migraine without aura and 5.2% from migraine with aura. Birthweight was significantly lower in women affected by migraine with aura respective to other groups, and a significantly higher rate of small for gestational age infants was found in tension-type headache (10.4%) and in migraine with aura (24.9%) groups respective to the others (p < 0.001). Moreover, the admission to the neonatal intensive care unit was significantly higher in all the headache groups (p = 0.012). Multivariate analysis showed that women presenting tension-type headache (OR 4.19, p = 0.004), migraine with aura (OR 5.37, p = 0.02), a uterine artery pulsatility index >90th centile (OR 3.66, p = 0.01), low multiple of the median (MoM) of Pregnancy-associated plasma protein-A (PAPP-A) (OR 0.48, p = 0.05) and high MoM of Inhibin-A (OR 3.24, p = 0.03) at first trimester, are independently associated with the delivery of small for gestational age infants when compared to women without headache disorders. Conclusion Migraine with aura and tension type headache expose women to an increased risk of delivering small for gestational age infants, in association with some utero-placenta markers evaluated at first trimester. These women with headache disorders have an additional indication to undergo first trimester aneuploidy screening and would possibly benefit from specific interventions.


2021 ◽  
Vol 10 (4) ◽  
pp. 643
Author(s):  
Veronica Giorgione ◽  
Corey Briffa ◽  
Carolina Di Fabrizio ◽  
Rohan Bhate ◽  
Asma Khalil

Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts (p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011990
Author(s):  
Liisa Karjalainen ◽  
Minna Tikkanen ◽  
Kirsi Rantanen ◽  
Karoliina Aarnio ◽  
Aino Korhonen ◽  
...  

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.


BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e049075
Author(s):  
Dionne V Gootjes ◽  
Anke G Posthumus ◽  
Vincent W V Jaddoe ◽  
Eric A P Steegers

ObjectiveTo study the associations between neighbourhood deprivation and fetal growth, including growth in the first trimester, and adverse pregnancy outcomes.DesignProspective cohort study.SettingThe Netherlands, Rotterdam.Participants8617 live singleton births from the Generation R cohort study.ExpositionLiving in a deprived neighbourhood.Main outcome measuresFetal growth trajectories of head circumference, weight and length.Secondary outcomes measuresSmall-for-gestational age (SGA) and preterm birth (PTB).ResultsNeighbourhood deprivation was not associated with first trimester growth. However, a higher neighbourhood status score (less deprivation) was associated with increased fetal growth in the second and third trimesters (eg, estimated fetal weight; adjusted regression coefficient 0.04, 95% CI 0.02 to 0.06). Less deprivation was also associated with decreased odds of SGA (adjusted OR 0.91, 95% CI 0.86 to 0.97, p=0.01) and PTB (adjusted OR 0.89, 95% CI 0.82 to 0.96, p=0.01).ConclusionsWe found an association between neighbourhood deprivation and fetal growth in the second and third trimester pregnancy, but not with first trimester growth. Less neighbourhood deprivation is associated with lower odds of adverse pregnancy outcomes. The associations remained after adjustment for individual-level risk factors. This supports the hypothesis that living in a deprived neighbourhood acts as an independent risk factor for fetal growth and adverse pregnancy outcomes, above and beyond individual risk factors.


Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1506-1513 ◽  
Author(s):  
Michael C. Honigberg ◽  
Hilde Kristin Refvik Riise ◽  
Anne Kjersti Daltveit ◽  
Grethe S. Tell ◽  
Gerhard Sulo ◽  
...  

Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84–2.35], P =0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50–2.68, P <0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery ( P interaction =0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.


BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e023529 ◽  
Author(s):  
Enny S Paixão ◽  
Oona M Campbell ◽  
Maria Gloria Teixeira ◽  
Maria CN Costa ◽  
Katie Harron ◽  
...  

ObjectivesDengue is the most common viral mosquito-borne disease, and women of reproductive age who live in or travel to endemic areas are at risk. Little is known about the effects of dengue during pregnancy on birth outcomes. The objective of this study is to examine the effect of maternal dengue severity on live birth outcomes.Design and settingWe conducted a population-based cohort study using routinely collected Brazilian data from 2006 to 2012.ParticipatingWe linked birth registration records and dengue registration records to identify women with and without dengue during pregnancy. Using multinomial logistic regression and Firth method, we estimated risk and ORs for preterm birth (<37 weeks’ gestation), low birth weight (<2500 g) and small for gestational age (<10thcentile). We also investigated the effect of time between the onset of the disease and each outcome.ResultsWe included 16 738 000 live births. Dengue haemorrhagic fever was associated with preterm birth (OR=2.4; 95% CI 1.3 to 4.4) and low birth weight (OR=2.1; 95% CI 1.1 to 4.0), but there was no evidence of effect for small for gestational age (OR=2.1; 95% CI 0.4 to 12.2). The magnitude of the effects was higher in the acute disease period.ConclusionThis study showed an increased risk of adverse birth outcomes in women with severe dengue during pregnancy. Medical intervention to mitigate maternal risk during severe acute dengue episodes may improve outcomes for infants born to exposed mothers.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3042 ◽  
Author(s):  
Isabelle Monier ◽  
Amandine Baptiste ◽  
Vassilis Tsatsaris ◽  
Marie-Victoire Senat ◽  
Jacques Jani ◽  
...  

Maternal 25-hydroxyvitamin D (25-OHD) deficiency during pregnancy may increase the risk of preterm and small-for-gestational age (SGA) birth, but studies report conflicting results. We used a multicenter prospective cohort of 2813 pregnant women assessed for 25-OHD levels in the first trimester of pregnancy to investigate the association between maternal 25-OHD concentrations and risks of preterm birth (<37 weeks) and SGA (birthweight <10th percentile). Odds ratios were adjusted (aOR) for potential cofounders overall and among women with light and dark skin separately, based on the Fitzpatrick scale. 25-OHD concentrations were <20 ng/mL for 45.1% of the cohort. A total of 6.7% of women had a preterm birth. The aOR for preterm birth associated with the 1st quartile of 25-OHD concentrations compared to the 4th quartile was 1.53 (95% confidence interval (CI): 0.97–2.43). In stratified analyses, an association was observed for women with darker skin (aOR = 2.89 (95% CI: 1.02–8.18)), and no association with lighter skin. A total of 11.9% of births were SGA and there was no association overall or by skin color. Our results do not provide support for an association between maternal first trimester 25-OHD deficiency and risk of preterm or SGA birth overall; the association with preterm birth risk among women with darker skin requires further investigation.


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