Perinatal death in a term fetal growth restriction randomized controlled trial: the paradox of prior risk and consent

IntroductionFetal growth restriction (FGR) is a serious pregnancy complication, associated with increased rates of perinatal death and morbidity among survivors. Most commonly FGR results from placental insufficiency, where the placenta fails to deliver the oxygen and nutrients required for normal fetal growth. This leads to fetal oxidative stress, resulting in organ damage through lipid peroxidation. The early developing brain is particularly susceptible, such that FGR is associated with poorer neurodevelopment, witnessed as cognitive and behavioural dysfunction, and cerebral palsy. Promisingly, melatonin, a lipid soluble antioxidant is neuroprotective in animal models of FGR. We present a protocol outlining a randomised, placebo-controlled trial to explore whether antenatal maternal melatonin supplementation in pregnancies with severe, early-onset FGR can improve neurodevelopment among survivors at 2 years of age.Methods and analysesWe will recruit 336 women with a singleton pregnancy complicated by FGR between 23+0 and 31+6 weeks gestation. Participants will be randomised, stratified by gestational age, to either 30 mg melatonin per day or a visually identical placebo, continued until birth. Measures of maternal and fetal health will be collected until birth. Timing of birth will be determined by the treating clinical team in discussion with the woman. Neonatal and infant neurodevelopmental assessments will be undertaken, consisting of brain MRI at term corrected age, general movements assessment at term and 3 months’ corrected age, and Bayley Scales of Infant & Toddler Development-III and Infant Toddler Social Emotional Assessment at 2.5 years corrected age. Analyses will be on intention to treat. The primary outcome is a difference of 5 points in the cognitive domain of the Bayley-III. Secondary outcomes address maternal and fetal safety.Ethics and disseminationThis trial has Monash Health Human Research and Ethics committee approval (17-0000-583A). Findings will be disseminated through peer-reviewed publications, conference presentations and to participants.Trial registration numberACTRN12617001515381; Pre-results

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The role of sildenafil citrate in the treatment of fetal growth restriction: a randomized controlled trial

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20191929 ◽

2019 ◽

Vol 8 (5) ◽

pp. 1840

Author(s):

Ahmed Abdelshafy ◽

Khaled Ibrahim Abdullah ◽

Sherif Ashoush ◽

Heba E. Hosni

Keyword(s):

Middle Cerebral Artery ◽

Fetal Growth ◽

Cerebral Artery ◽

Fetal Growth Restriction ◽

Umbilical Artery ◽

Controlled Trial ◽

Maternity Hospital ◽

Growth Restriction ◽

Sildenafil Citrate ◽

Doppler Velocity

Background: This study was aimed to evaluate the effect of sildenafil citrate on Doppler velocity indices in patients with fetal growth restriction (FGR) associated with impaired placental circulation.Methods: A double-blinded, parallel group randomized clinical trial (clinicaltrials.gov NCT02590536) was conducted in Ain Shams Maternity Hospital, in the period between October 2015 and June 2017. Ninety pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were randomized to either sildenafil citrate 25 mg orally every 8 hours or placebo visually-identical placebo tablets with the same regimen. The primary outcome of the study was the change in umbilical artery and fetal middle cerebral artery indices.Results: There was a significant improvement in umbilical and middle cerebral artery indices after sildenafil administration p<0.001. Present study observed that, sildenafil group, in comparison to placebo, has a significantly higher mean neonatal birth weight. 1783±241g vs 1570±455g (p<0.001). There was a significantly higher mean gestational age at delivery in women in sildenafil group 35.3±1.67 weeks, whereas it was lower in the placebo group 33.5±1.7 weeks. The side effects as headache, palpitation and facial flushing were significantly higher in sildenafil group compared to placebo group.Conclusions: The use sildenafil citrate in pregnancies with fetal growth restriction (FGR) improved the feto-placental Doppler indices (pulsatility index of umbilical artery and middle cerebral artery) and improved neonatal outcomes.

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Effect of supplementation of complex milk lipids in pregnancy on fetal growth: results from the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.1080/14767058.2019.1683539 ◽

2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Tom Norris ◽

Renato Souza ◽

Yinyin Xia ◽

Ting Zhang ◽

Angela Rowan ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Fetal Growth ◽

Controlled Trial ◽

Randomized Controlled ◽

Complex Lipids ◽

Milk Lipids ◽

Complex Milk Lipids ◽

In Pregnancy

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Selective Fetal Growth Restriction in Dichorionic Twin Pregnancies: Diagnosis, Natural History, and Perinatal Outcome

Journal of Clinical Medicine ◽

10.3390/jcm9051404 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1404 ◽

Cited By ~ 1

Author(s):

Nikolaos Antonakopoulos ◽

Petra Pateisky ◽

Becky Liu ◽

Erkan Kalafat ◽

Baskaran Thilaganathan ◽

...

Keyword(s):

Natural History ◽

Disease Progression ◽

Diagnostic Criteria ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Perinatal Death ◽

First Trimester ◽

Growth Restriction ◽

Progression Rate ◽

Delphi Consensus

This study aims to evaluate the natural history, disease progression, and outcomes in dichorionic twins with selective fetal growth restriction (sFGR) according to different diagnostic criteria and time of onset. Dichorionic twins seen from the first trimester were included. sFGR was classified according to the Delphi consensus, and was compared to the outcomes of those classified by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) diagnostic criteria. Early sFGR occurred before 32-weeks, and late sFGR after 32-weeks. Disease progression, neonatal outcomes such as gestation at delivery, birthweight, neonatal unit (NNU) admission, and morbidities were compared. One-hundred twenty-three of 1053 dichorionic twins had sFGR, where 8.4% were classified as early sFGR, and 3.3% were late sFGR. Disease progression was seen in 36%, with a longer progression time (5 vs. 1 week) and higher progression rate (40% vs. 26%) in early sFGR. Perinatal death was significantly higher in the sFGR than the non-sFGR group (24 vs. 16 per 1000 births, p = 0.018), and those with early sFGR had more NNU admissions than late sFGR (p = 0.005). The ISUOG diagnostic criteria yielded a higher number of sFGR than the Delphi criteria, but similar outcomes. sFGR have worse perinatal outcomes, with early onset being more prevalent. Use of the Delphi diagnostic criteria can reduce over-diagnosis of sFGR and avoid unnecessary intervention.

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5: Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a prior history (the eppi trial): an open-label international multicentre randomized controlled trial

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2016.11.006 ◽

2017 ◽

Vol 216 (1) ◽

pp. S4 ◽

Cited By ~ 4

Author(s):

Katie Groom ◽

Lesley McCowan ◽

Laura MacKay ◽

Joanne Said ◽

Stefan Kane ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Intrauterine Growth Restriction ◽

Controlled Trial ◽

Growth Restriction ◽

Prior History ◽

Open Label ◽

Intrauterine Growth ◽

Randomized Controlled

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Umbilical Artery Half-Peak Systolic Velocity Deceleration Time in Fetal Growth Restriction

Fetal Diagnosis and Therapy ◽

10.1159/000442049 ◽

2015 ◽

Vol 40 (2) ◽

pp. 128-134 ◽

Cited By ~ 1

Author(s):

Juan Carlos Bustos ◽

Vivian Gonzalez ◽

Waldo Sepulveda

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Perinatal Outcome ◽

Umbilical Artery ◽

Perinatal Death ◽

Peak Systolic Velocity ◽

Growth Restriction ◽

Ultrasound Evaluation ◽

Diastolic Velocity ◽

Deceleration Time

Objective: To study the umbilical artery (UA) half-peak systolic velocity deceleration time (hPSV-DT) in pregnancies complicated by fetal growth restriction (FGR). Methods: The study included 266 singleton, high-risk pregnancies with an estimated fetal weight <10th percentile, which were examined between 24 and 40 weeks' gestation and delivered within a week from the last ultrasound evaluation. UA hPSV-DT was measured with Doppler ultrasound in the same wave used to measure the pulsatility index. UA hPSV-DT values were correlated with perinatal outcome. Results: UA hPSV-DT <5th percentile was found in 87 and 98% of fetuses with moderate and severe FGR, respectively. 94% of fetuses with a UA hPSV-DT <90 ms had poor perinatal outcome including perinatal death or prolonged admission to the neonatal intensive care unit. None of the fetuses had a UA hPSV-DT <70 ms. Perinatal death occurred in 39 fetuses; UA hPSV-DT was abnormal in all of them, with 95% of these fetuses having values of ≤120 ms. In the group of fetuses with absent/reverse end-diastolic velocity in the UA, the perinatal mortality rate was 51% for those with a UA hPSV-DT ≤90 ms and only 23% for those having a UA hPSV-DT >90 ms (p < 0.01). Conclusions: UA hPSV-DT seems to be a useful technique in the evaluation of pregnancies at risk for FGR and perinatal death. Additionally, hPSV-DT was shown to be a good predictor of perinatal death, with values of <90 ms corresponding to imminent risk of intrauterine demise and values of <70 ms being likely to be incompatible with intrauterine life.

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