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Not yet recruitingNCT07846137OPHELIAUpdated Sep 29, 2026

The Ophthalmic Artery Doppler Evaluation Prior to Labor Induction and Adverse Intrapartum Fetal Outcomes

An interventional study of Ophthalmic Artery Doppler in Ophthalmic Artery, Labor and Delivery and Induction of Labor, sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Not yet recruiting. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
1,477
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
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Study summary

The ophthalmic artery Doppler has been recently proposed as a potential "soft marker" for placental insufficiency in retrospective and observational studies, with similar clinical significance with respect to Uterine Artery (UA) Doppler evaluation and it is currently being investigated as an adjunctive clinical instrument to predict pre-eclampsia (PE) occurrence. Placental insufficiency strictly correlates with intrapartum fetal adverse outcomes and a concomitant induction of labor, alone, may further increase the hypoxic stress on the fetus during labor. This can be reflected by cardiotocographic alterations during labor, ultimately leading to emergency cesarean deliveries or instrumental vaginal deliveries.

Despite great advancements in understanding various maternal-fetal pathologies, the investigators are still not able to properly detect fetuses that are at higher risk for intrapartum compromise among those receiving an induction of labor. Therefore, the aim of this prospective study is to investigate any potential association between altered ophthalmic artery Doppler PSV ratio measured before labor induction in at-term, pregnant patients with intra-partum fetal compromise. Furthermore, the investigators aim to also measure an additional parameter that is the optic nerve sheath diameter (ONSD) - an indirect measure of intracranial pressure - before and after the second stage of labour, with the aim of studying its physiology during and after delivery.

Read the detailed description

The ophthalmic artery (OA) Doppler has been recently proposed as a potential "soft marker" for placental insufficiency in retrospective and observational studies, with similar clinical significance with respect to Uterine Artery (UA) Doppler evaluation. It has been investigated in small-for-gestational-age (SGA) or fetal-growth-restricted (FGR) fetuses, as well as in low-risk pregnancies and at various gestational ages during pregnancy, showing to be predictive of impaired placentation, and, consequently, of pre-eclampsia occurrence.

The OA is the first branch of the internal carotid artery and its Doppler velocity waveform has two systolic peaks. The first systolic wave (PSV1) is created by cardiac systole, with the opening of the aortic valve and ejection of blood into the aorta, whilst the second systolic wave (PSV2) is a reflective wave formed by the systolic pulse wave reaching smaller, higher resistance arterioles and being reflected back towards the heart. At the level of the aortic arch, a fraction is diverted cranially to the cerebral circulation as a forward wave to create PSV2. In this way, PSV2 is most influenced by peripheral arterial compliance and resistance, whilst PSV1 is more affected by cardiac output. Therefore, an increase in the ratio of PSV2 to PSV1 (PSV ratio) could represent an increase in peripheral vascular resistance and/or a reduction in cardiac output, which are both indirect signs of placental dysfunction. The latter can be manifested during labor with well-established cardiotocographic patterns and induction of labor, alone, may enhance the intrapartum hypoxic stress on the fetus.

Furthermore, another parameter that is currently understudy is the Optic Nerve Sheath Diameter (ONSD). Recent evidence suggests that ONSD increases in pre-eclamptic patients, possibly reflecting a transient increase in intracranial pressure. However, evidence is scarce regarding its physiologic changes during and after labour. In understanding the potential mechanisms behind intrapartum fetal compromise in gravid, at-term patients undergoing labor induction, the hypothesis is that placental dysfunction, albeit not necessarily clinically manifest earlier in pregnancy, may play a role in fetal compromise during labor, especially in pregnancies undergoing induction of labor. Hence, investigating potential associations between a "soft marker" of placental insufficiency as Ophthalmic artery Doppler PSV ratio alterations and intrapartum fetal compromise would be paramount. Therefore the aim of this prospective interventional study is to investigate any association with altered OA PSV ratio and intrapartum fetal adverse outcomes in pregnant patients that reach term of pregnancy, undergoing induction of labor. In addition, the investigatos also aim to evaluate the ONSD before and after the second stage of labour in order to study its physiologic changes.

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Conditions studied

  • Ophthalmic Artery
  • Labor and Delivery
  • Induction of Labor
  • Intrapartum Fetal Distress
  • Optic Nerve Sheath Diameter Measurement
  • Doppler Ultrasound
  • Placental Insufficiency

Keywords

  • ophthalmic artery Doppler
  • induction of labor
  • intrapartu fetal compromise
  • placental insufficiency
  • optic nerve sheath diameter
  • ONSD
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Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Age ≥18 years
  • Pregnant patients after 37 weeks of gestation undergoing induction of labor
  • Ability to provide written informed consent

Exclusion criteria

Exclusion Criteria:

  • Age \<18 years
  • Known fetal malformations
  • Known fetal genetic syndromes
  • Multiple pregnancy
  • Known maculopathies
  • Inability or unwillingness to provide written informed consent
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Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1,477 participants (estimated)

Study arms

  • Experimental
    Ophthalmic Artery Doppler Assessment

    Pregnant patients after 37 weeks of gestation undergoing induction of labor. Before labor induction, participants will undergo maternal ophthalmic artery Doppler assessment and measurement of optic nerve sheath diameter (ONSD). ONSD will be measured again after delivery. Maternal, intrapartum, and neonatal outcomes will be collected.

    Diagnostic Test: Ophthalmic Artery Doppler

Interventions

  • Diagnostic testOphthalmic Artery Doppler

    Right before labour induction, once the patient is already admitted into the inpatient ward - as an elective admission for scheduled labour induction - we will perform an ultrasound by gently applying the probe onto the eyelid of the patient, using sterile gel. We will then measure both the Doppler velocity of the Ophthalmic Artery as well as the Optic Nerve Sheath Diameter (ONSD). The ONSD will then be measured again right after delivery following the exact same procedure.

    Also known as: Optic Nerve Sheath Diameter Assessment

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What researchers measure

Primary outcomes

  1. Occurrence of in-labor cesarean delivery due to fetal hypoxic stress, assessed in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Occurrence of cesarean delivery during labor due to fetal hypoxic stress, evaluated in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Time frame: From start of labor induction until delivery, up to 72 hours.

Secondary outcomes

  1. instrumental vaginal delivery for fetal hypoxic stress

    Occurrence of instrumental vaginal delivery due to fetal hypoxic stress, evaluated in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Time frame: From start of labor induction until delivery, up to 72 hours.

  2. Cesarean delivery for any indication

    Occurrence of cesarean delivery for any indication, evaluated in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Time frame: From start of labor induction until delivery, up to 72 hours.

  3. Cesarean delivery for clinical or subclinical chorioamnionitis

    Occurrence of cesarean delivery due to clinical or subclinical chorioamnionitis, evaluated in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Time frame: From start of labor induction until delivery, up to 72 hours.

  4. Umbilical arterial pH <7.0

    Occurrence of umbilical arterial cord blood pH \<7.0 at delivery, evaluated in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Time frame: At delivery

  5. 5-minute Apgar score <7

    Occurrence of an Apgar score \<7 at 5 minutes after birth, evaluated in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Time frame: 5 minutes after birth

  6. Neonatal Intensive Care Unit admission

    Occurrence of neonatal admission to the Neonatal Intensive Care Unit (NICU), evaluated in relation to maternal ophthalmic artery Doppler indices measured before induction of labor.

    Time frame: From birth until hospital discharge

Other outcomes

  1. Change in Optic Nerve Sheath Diameter (ONSD)

    Change in maternal optic nerve sheath diameter measured before labor induction and after delivery.

    Time frame: Before labor induction and up to 30 minutes after delivery

06

Study locations

No study locations are listed for this record.

07

References and documents

Publications

  • Singh SK, Bhatia K. Ultrasonographic Optic Nerve Sheath Diameter as a Surrogate Measure of Raised Intracranial Pressure in Severe Pregnancy-induced Hypertension Patients. Anesth Essays Res. 2018 Jan-Mar;12(1):42-46. doi: 10.4103/aer.AER_218_17. PubMed 29628552 ↗
  • Berty Gutierrez H, Carrera Gonzalez E. Usefulness of optic nerve sheath diameter measurement in hypertensive patients during pregnancy and the puerperium. J Matern Fetal Neonatal Med. 2023 Dec;36(1):2187253. doi: 10.1080/14767058.2023.2187253. PubMed 36889743 ↗
  • Rossi AC, Prefumo F. Antepartum and intrapartum risk factors for neonatal hypoxic-ischemic encephalopathy: a systematic review with meta-analysis. Curr Opin Obstet Gynecol. 2019 Dec;31(6):410-417. doi: 10.1097/GCO.0000000000000581. PubMed 31567446 ↗
  • Ghi T, Fieni S, Ramirez Zegarra R, Pereira S, Dall'Asta A, Chandraharan E. Relative uteroplacental insufficiency of labor. Acta Obstet Gynecol Scand. 2024 Oct;103(10):1910-1918. doi: 10.1111/aogs.14937. Epub 2024 Aug 6. PubMed 39107951 ↗
  • di Pasquo E, Giannubilo SR, Valentini B, Salvi S, Rullo R, Fruci S, Filippi E, Ornaghi S, Zullino S, Rossi F, Farsetti D, Di Martino DD, Vasapollo B, Locatelli A, De Santis M, Ciavattini A, Lanzone A, Mecacci F, Ferrazzi E, Valensise H, Ghi T. The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings. Am J Obstet Gynecol MFM. 2024 May;6(5):101368. doi: 10.1016/j.ajogmf.2024.101368. Epub 2024 Apr 3. PubMed 38574856 ↗
  • Ali S, Mukasa DC, Lukakamwa D, Nakayenga A, Namagero P, Biira J, Byamugisha J, Papageorghiou AT. Relationship of maternal ophthalmic artery Doppler with uterine artery Doppler, hemodynamic indices and gestational age: prospective MATERA study. Ultrasound Obstet Gynecol. 2025 Feb;65(2):163-172. doi: 10.1002/uog.29162. Epub 2025 Jan 20. PubMed 39831889 ↗
  • Gurgel Alves JA, Maia e Holanda Moura SB, Araujo Junior E, Tonni G, Martins WP, Da Silva Costa F. Predicting small for gestational age in the first trimester of pregnancy using maternal ophthalmic artery Doppler indices. J Matern Fetal Neonatal Med. 2016;29(7):1190-4. doi: 10.3109/14767058.2015.1040755. Epub 2015 Jun 1. PubMed 26030678 ↗
  • Arechvo A, Wright A, Nobile Recalde A, Liandro R, Charakida M, Nicolaides KH. Ophthalmic artery Doppler and biomarkers of impaired placentation at 36 weeks' gestation in pregnancies with small fetuses. Ultrasound Obstet Gynecol. 2024 Mar;63(3):358-364. doi: 10.1002/uog.27521. Epub 2024 Feb 10. PubMed 37902727 ↗
  • Cao L, He B, Zhou Y, Chen T, Gao Y, Yao B. Utility of uterine artery Doppler ultrasound imaging in predicting preeclampsia during pregnancy: a meta-analysis. Med Ultrason. 2024 Jun 21;26(2):197-204. doi: 10.11152/mu-4355. Epub 2024 Apr 15. PubMed 38805623 ↗
  • Abdel Azim S, Sarno M, Wright A, Vieira N, Charakida M, Nicolaides KH. Ophthalmic artery Doppler at 35-37 weeks' gestation in pregnancies with small or growth-restricted fetuses. Ultrasound Obstet Gynecol. 2022 Apr;59(4):483-489. doi: 10.1002/uog.24854. Epub 2022 Mar 4. PubMed 35000242 ↗
  • Nicolaides KH, Sarno M, Wright A. Ophthalmic artery Doppler in the prediction of preeclampsia. Am J Obstet Gynecol. 2022 Feb;226(2S):S1098-S1101. doi: 10.1016/j.ajog.2020.11.039. Epub 2021 Apr 24. PubMed 34292158 ↗
  • Kalafat E, Laoreti A, Khalil A, Da Silva Costa F, Thilaganathan B. Ophthalmic artery Doppler for prediction of pre-eclampsia: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018 Jun;51(6):731-737. doi: 10.1002/uog.19002. Epub 2018 May 3. PubMed 29330892 ↗
  • Sapantzoglou I, Wright A, Arozena MG, Campos RV, Charakida M, Nicolaides KH. Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 19-23 weeks' gestation. Ultrasound Obstet Gynecol. 2021 Jan;57(1):75-83. doi: 10.1002/uog.23528. Epub 2020 Dec 4. PubMed 33142353 ↗
  • Sarno M, Wright A, Vieira N, Sapantzoglou I, Charakida M, Nicolaides KH. Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 35-37 weeks' gestation. Ultrasound Obstet Gynecol. 2021 Apr;57(4):600-606. doi: 10.1002/uog.23517. Epub 2021 Mar 15. PubMed 33073902 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 16, 2026
  • Informed consent form · Feb 16, 2026
  • Informed consent form · Feb 16, 2026

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — There is no plan to make individual participant data (IPD) available.

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Registry details

Key details

Study ID
NCT07846137
Lead sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Responsible party
Ghi Tullio (Prof. Tullio Ghi, MD PhD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS) — Principal investigator
First posted
Sep 29, 2026
Start date
Sep 24, 2026 (estimated)
Primary completion
Apr 15, 2027 (estimated)
Completion
Apr 30, 2027 (estimated)
Last update
Sep 29, 2026

Study contacts

Tullio Ghi, MD PhD
Contact
tullio.ghi@unicatt.it
+393385070025
Alessandro Petrecca, MD
Contact
alessandro.petrecca@guest.policlinicogemelli.it
+393479212418
Tullio Ghi
principal investigator · Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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