The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction

Groom, Katie; David, Anna L.

doi:10.1016/j.ajog.2017.11.565

Cited by 129 publications

(108 citation statements)

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“…In current practice, planned early birth is the only therapeutic option available that imposes further life‐long health risks. No current interventions alter fetal growth and wellbeing to allow safe prolongation of pregnancy, although a number of therapies are under investigation in a pipeline of preclinical and clinical studies aiming to modify the uteroplacental circulation and in utero environment . The most far advanced of these investigative therapies is the maternal administration of sildenafil citrate.…”

Section: Introductionmentioning

confidence: 99%

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early‐onset fetal growth restriction

Groom

McCowan

Mackay

et al. 2019

BJOG

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Objective To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction.Design A randomised placebo-controlled trial.Setting Thirteen maternal-fetal medicine units across New Zealand and Australia.Population Women with singleton pregnancies affected by fetal growth restriction at 22 +0 to 29 +6 weeks.Methods Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32 +0 weeks, birth or fetal death (whichever occurred first). Main Outcome MeasuresThe primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia.Results Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and newonset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75).Conclusions Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing.Keywords Fetal growth restriction, intrauterine growth restriction, pre-eclampsia, sildenafil, small for gestational age, uterine artery Doppler.Tweetable abstract Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

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Section: Introductionmentioning

confidence: 99%

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early‐onset fetal growth restriction

Groom

McCowan

Mackay

et al. 2019

BJOG

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“…Regarding primary prevention strategies, recent meta‐analyses have demonstrated that aspirin modestly reduces the risk of delivering an SGA infant in women at high risk, with most benefit derived by starting treatment before 16 weeks of gestation and using a dose of ≥100 mg (risk ratio 0.56–0.76) . Patient selection of those at increased risk was primarily based on an increased risk of developing a hypertensive pregnancy disorder rather than delivering an SGA infant . Currently, there are no effective interventions for the primary prevention of LGA available, except for the treatment of women with GDM that indirectly lowers the risk of LGA, such as diet .…”

Section: Discussionmentioning

confidence: 99%

“…69,70 Patient selection of those at increased risk was primarily based on an increased risk of developing a hypertensive pregnancy disorder rather than delivering an SGA infant. 71 Currently, there are no effective interventions for the primary prevention of LGA available, except for the treatment of women with GDM that indirectly lowers the risk of LGA, such as diet. 24 In summary, the application of the currently available prediction models for the risk of SGA or LGA, in settings in which models for the identification of 'vascular' (pre-eclampsia)-and 'metabolic' (GDM)related complications are already applied, are not likely to result in additional benefit regarding the overlap of predictors and preventive interventions.…”

Section: Discussionmentioning

confidence: 99%

External validation and clinical usefulness of first‐trimester prediction models for small‐ and large‐for‐gestational‐age infants: a prospective cohort study

Meertens

Smits

Kuijk

et al. 2019

BJOG

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Objective To assess the external validity of all published first‐trimester prediction models based on routinely collected maternal predictors for the risk of small‐ and large‐for‐gestational‐age ( SGA and LGA ) infants. Furthermore, the clinical potential of the best‐performing models was evaluated. Design Multicentre prospective cohort. Setting Thirty‐six midwifery practices and six hospitals (in the Netherlands). Population Pregnant women were recruited at <16 weeks of gestation between 1 July 2013 and 31 December 2015. Methods Prediction models were systematically selected from the literature. Information on predictors was obtained by a web‐based questionnaire. Birthweight centiles were corrected for gestational age, parity, fetal sex, and ethnicity. Main outcome measures Predictive performance was assessed by means of discrimination (C‐statistic) and calibration. Results The validation cohort consisted of 2582 pregnant women. The outcomes of SGA <10th percentile and LGA >90th percentile occurred in 203 and 224 women, respectively. The C‐statistics of the included models ranged from 0.52 to 0.64 for SGA ( n = 6), and from 0.60 to 0.69 for LGA ( n = 6). All models yielded higher C‐statistics for more severe cases of SGA (<5th percentile) and LGA (>95th percentile). Initial calibration showed poor‐to‐moderate agreement between the predicted probabilities and the observed outcomes, but this improved substantially after recalibration. Conclusion The clinical relevance of the models is limited because of their moderate predictive performance, and because the definitions of SGA and LGA do not exclude constitutionally small or large infants. As most clinically relevant fetal growth deviations are related to ‘vascular’ or ‘metabolic’ factors, models predicting hypertensive disorders and gestational diabetes are likely to be more specific. Tweetable abstract The clinical relevance of prediction models for the risk of small‐ and large‐for‐gestational‐age is limited.

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“…(7,8) In obstetrics, low-dose aspirin has been shown to be effective in preventing preterm preeclampsia, with delivery at <37 weeks' gestation, in women at risk. (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) The ASPRE (27) The latest systematic review and meta-analysis demonstrated that the reduction in the rate of preterm preeclampsia was confined to the subgroup in which aspirin was initiated at ≤16 weeks' gestation and at a daily dose of ≥100 mg (relative risk [RR], 0.33; 95% CI, 0.19-0.57). (20) Evidence suggests that pre-conception or early administration of low-dose aspirin might improve endometrial growth, placental vascularization and organogenesis.…”

Section: Introductionmentioning

confidence: 99%

Does low-dose aspirin initiated before 11 weeks’ gestation reduce the rate of preeclampsia?

Chaemsaithong

Cuenca-Gomez

Plana

et al. 2020

American Journal of Obstetrics and Gynecology

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Condensation: Aspirin given at <11 weeks' gestation in high risk women does not reduce the risk of preeclampsia and gestational hypertension but may reduce the risk of preterm delivery. Short title: Early aspirin administration and preeclampsia PROSPERO registration number: CRD42019125006 AJOG at a Glance: Why was this study conducted? • To perform a systematic review and meta-analysis to evaluate the effect of lowdose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction. Key findings • The administration of low-dose aspirin at <11 weeks' gestation in women with a history of recurrent pregnancy loss, women who had undergone in vitro fertilization or women with thrombophilia or antiphospholipid syndrome was associated with a non-significant decrease in the risk of preeclampsia, gestational hypertension, and any hypertensive disorder of pregnancy. • Early low-dose aspirin reduced the risk of preterm delivery but had no impact on the risk of fetal growth restriction. • Except for preterm delivery and any hypertensive disorder of pregnancy, sensitivity analysis demonstrated similar observations; confirming the robustness of our analysis. What does this add to what is known? • Administration of low-dose aspirin at <11 weeks' gestation to high risk women does not reduce the risk of preeclampsia, gestational hypertension, any hypertensive disorder of pregnancy and fetal growth restriction but might reduce the risk of preterm delivery at <37 weeks of gestation. ABSTRACT OBJECTIVE DATA: Pre-conception or early administration of low-dose aspirin might improve endometrial growth, placental vascularization and organogenesis. Most studies have evaluated the potential benefit of pre-conception or early administration of low-dose aspirin in women with a history of recurrent pregnancy loss, women who have undergone in vitro fertilization or women with thrombophilia or antiphospholipid syndrome. These women are at an increased risk of placenta-associated complications of pregnancy, including preeclampsia, preterm delivery and fetal growth restriction. STUDY: We performed a systematic review and meta-analysis to evaluate the effect of low-dose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction. STUDY APPRAISAL AND SYNTHESIS METHODS: We searched in MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.Gov and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) from 1985 to November 2018. Entry criteria were randomized controlled trials evaluating the effect of aspirin administered at <11 weeks' gestation in preventing preeclampsia and/or hypertensive disorders in pregnancy or improvi...

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The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction

Cited by 129 publications

References 125 publications

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early‐onset fetal growth restriction

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early‐onset fetal growth restriction

External validation and clinical usefulness of first‐trimester prediction models for small‐ and large‐for‐gestational‐age infants: a prospective cohort study

Does low-dose aspirin initiated before 11 weeks’ gestation reduce the rate of preeclampsia?

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