Estimation of Fetal Weight by MR Imaging to PREdict Neonatal MACROsomia (PREMACRO Study)

Fetal Macrosomia Clinical Trial

Official title:

Estimation of Fetal Weight by MR Imaging to PREdict Neonatal MACROsomia (PREMACRO Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02713568
• Other study ID #: CHUB-PREMACRO
• Status: Completed
• Phase: N/A
• Start date: March 8, 2016
• Est. completion date: March 10, 2020

Study information

• Verified date: August 2020
• Source: Brugmann University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Macrosomia and growth restriction are important causes of perinatal morbidity, at or near to term. However, clear identification of 'at risk' foetuses is difficult and clinical estimates of fetal weight are poor. Historically, ultrasound has been used as a second line in such cases but the accuracy of this imaging modality in the mid- to late third trimester is also limited.

Estimated fetal weight (EFW) is an important part of the clinical assessment and is used to guide obstetric interventions, when a fetus is small or large for dates. It frequently is the single most important component guiding interventions, such as induction of labour or Caesarean section.

Due to the imprecision of ultrasound-derived EFW, particularly in cases of suspected macrosomia in the 3rd trimester, the investigators believe that these estimates should not be used to make important obstetric decisions regarding mode and timing of delivery and that a more accurate method of assessment could produce better outcomes by restricting interventions to those foetuses at greatest risk. Some publications have already demonstrated that magnetic resonance (MR) imaging derived-EFW close to delivery, is more accurate than ultrasound

The goal of the present study is thus to compare the performance of magentic resonance imaging derived-EFW, versus ultrasound derived-EFW at 36 weeks of gestation, regarding the prediction of neonatal macrosomia.

Description:

Macrosomia and growth restriction are important causes of perinatal morbidity, at or near to term. However, clear identification of 'at risk' foetuses is difficult and clinical estimates of fetal weight are poor. Historically, ultrasound has been used as a second line in such cases but the accuracy of this imaging modality in the mid- to late third trimester is also limited.

Estimated fetal weight (EFW) is an important part of the clinical assessment and is used to guide obstetric interventions, when a fetus is small or large for dates. When a diagnosis of intra-uterine growth restriction (IUGR) is made, the decision-making process is complex, particularly at very early gestations and involves multiple different factors, including maternal status, cardiotocography, liquor volume and dopplers. However, a large body of research is now available to assist with the management of both early and late-onset intrauterine growth restriction (IUGR) but there is a paucity of evidence to guide clinical practice, once macrosomia has been diagnosed, therefore the EFW is frequently the single most important component guiding interventions, such as induction of labour or Caesarean section.

Fetal macrosomia is associated with a higher incidence of perinatal morbidity, including shoulder dystocia and brachial plexus injury in the fetus and anal sphincter tears, uterine atony and haemorrhage in the mother. A recent multicentre randomised controlled trial appears to confirm the advantages of a policy of induction of labour for suspected macrosomia, demonstrating a clear reduction in the rates of shoulder dystocia and composite perinatal morbidity. However, some earlier but lower quality, observational studies have questioned the benefit of EFW made by ultrasonography in the last trimester, for suspected macrosomia, demonstrating that this practice can increase the risk of caesarean and instrumental delivery, without reducing perinatal morbidity.

Despite this conflicting data and a lack of evidence to support routine third trimester ultrasound, the absence of specific guidance, coupled with concerns regarding perinatal outcomes,mean that obstetricians will increasingly request an ultrasound at around 34-36 weeks gestation to identify foetuses above the 90th or below the 10th centiles. This practice will inevitably lead to increased and potentially harmful interventions based on relatively inaccurate data.

Due to the imprecision of ultrasound-derived EFW, particularly in cases of suspected macrosomia in the 3rd trimester, the investigators believe that these estimates should not be used to make important obstetric decisions regarding mode and timing of delivery and that a more accurate method of assessment could produce better outcomes by restricting interventions to those foetuses at greatest risk. Some publications have already demonstrated that magnetic resonance (MR) imaging derived-EFW close to delivery, is more accurate than ultrasound, with a mean percentage error superior to that of ultrasound and a recent meta-analyses has confirmed this promising accuracy.

The goal of the present study is thus to compare the performance of magentic resonance imaging derived-EFW, versus ultrasound derived-EFW at 36 weeks of gestation, regarding the prediction of neonatal macrosomia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2413
• Est. completion date: March 10, 2020
• Est. primary completion date: March 10, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects is = 18 years of age and able to provide a written informed consent.

• Subject is a pregnant woman carrying a live singleton fetus at the 36+0-36+6 weeks scan, with no major abnormalities appearing during prenatal imaging with no major abnormalities appearing during prenatal imaging potentially affecting the correct use of the Hadlock formula for US-EFW. Conditions such as congenital diaphragmatic hernia with decreased abdominal circumference could be underestimated by the Hadlock USEFW. Another example is a massive sacro-coccygial teratomas.

• Subject is planning a delivery at our maternity at the University Hospital Brugmann, in Brussels, Belgium.

• Subject is known not to have any contra-indication to undergo an MR imaging examination.

Exclusion Criteria:

• Subject is known to have a contra-indication to undergo an MR imaging examination such as: Carrying a pacemaker or a metallic cardiac valve, having metallic material inside the head, having metallic fragments inside the eye following an accident, having any type of implant including ear implant, having a hip prosthesis

• Subject presenting with painful regular uterine contractions or history of ruptured membranes.

• Subjects who are unconscious, severely ill, mentally handicapped or under the age of 18 years.

• If birth occurs before MR and US evaluation.

• If patients delivers outside our local maternity unit.

• If the neonate's weigh is not measured within 6 hours after birth for any reason, including the need for emergency care immediately after delivery

Related Conditions & MeSH terms

• Fetal Macrosomia
• Fetal Weight

Intervention

Other:
• Ultrasound examination
Prenatal Ultrasound examinations will be carried out using transabdominal sonography only by experienced consultants in MFM. Ultrasound-Estimated Fetal Weight will be obtained between 36.0-36.6 weeks of gestation, according to Hadlock et al. Operators performing the Ultrasound-Estimated Fetal Weight will be blinded to the results of Magnetic Resonance-Estimated Fetal Weight. The participants, general practitioners, obstetricians and midwifes of the patients will be aware of the results of Ultrasound-Estimated Fetal Weight which will be used for clinical management. For the primary outcome measure, macrosomia during Ultrasound-Estimated Fetal Weight will be defined as = P95 based on Yudkin et al. For secondary outcome measures, it will be redefined as = P90 or = P99 based on Yudkin.
• Magnetic resonance examination
MRI will be performed the same day as the Ultrasound examination, using a clinical 1.5T whole-body unit. Operators performing Fetal Body Volume measurements will be blinded from Ultrasound-Estimated Fetal Weight results. Magnetic Resonance-Estimated Fetal Weight will be calculated using the equation 0,12+1,031*Fetal Body Volume = MR imaging weight (g) developed by Baker. General practitioners, obstetricians and midwifes of the patients will be blinded to the results of the Magnetic Resonance-Estimated Fetal Weight. For the primary outcome measure, macrosomia will be defined as = P95 based on Yudkin et al. For secondary outcome measures, it will be defined as = P90 or = P99.

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Brugmann University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (19)

Baker PN, Johnson IR, Gowland PA, Hykin J, Harvey PR, Freeman A, Adams V, Worthington BS, Mansfield P. Fetal weight estimation by echo-planar magnetic resonance imaging. Lancet. 1994 Mar 12;343(8898):644-5. — View Citation

Boulvain M, Senat MV, Perrotin F, Winer N, Beucher G, Subtil D, Bretelle F, Azria E, Hejaiej D, Vendittelli F, Capelle M, Langer B, Matis R, Connan L, Gillard P, Kirkpatrick C, Ceysens G, Faron G, Irion O, Rozenberg P; Groupe de Recherche en Obstétrique et Gynécologie (GROG). Induction of labour versus expectant management for large-for-date fetuses: a randomised controlled trial. Lancet. 2015 Jun 27;385(9987):2600-5. doi: 10.1016/S0140-6736(14)61904-8. Epub 2015 Apr 8. — View Citation

Bricker L, Neilson JP, Dowswell T. Routine ultrasound in late pregnancy (after 24 weeks' gestation). Cochrane Database Syst Rev. 2008 Oct 8;(4):CD001451. doi: 10.1002/14651858.CD001451.pub3. Review. Update in: Cochrane Database Syst Rev. 2015;6:CD001451. — View Citation

Bricker L, Neilson JP. Routine ultrasound in late pregnancy (after 24 weeks gestation). Cochrane Database Syst Rev. 2000;(2):CD001451. Review. Update in: Cochrane Database Syst Rev. 2007;(2):CD001451. Cochrane Database Syst Rev. 2008;(4):CD001451. — View Citation

DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988 Sep;44(3):837-45. — View Citation

DeVore GR. The importance of the cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol. 2015 Jul;213(1):5-15. doi: 10.1016/j.ajog.2015.05.024. Review. — View Citation

Gupta M, Hockley C, Quigley MA, Yeh P, Impey L. Antenatal and intrapartum prediction of shoulder dystocia. Eur J Obstet Gynecol Reprod Biol. 2010 Aug;151(2):134-9. doi: 10.1016/j.ejogrb.2010.03.025. Epub 2010 Apr 27. — View Citation

Hadlock FP, Harrist RB, Carpenter RJ, Deter RL, Park SK. Sonographic estimation of fetal weight. The value of femur length in addition to head and abdomen measurements. Radiology. 1984 Feb;150(2):535-40. — View Citation

Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study. Am J Obstet Gynecol. 1985 Feb 1;151(3):333-7. — View Citation

King JR, Korst LM, Miller DA, Ouzounian JG. Increased composite maternal and neonatal morbidity associated with ultrasonographically suspected fetal macrosomia. J Matern Fetal Neonatal Med. 2012 Oct;25(10):1953-9. doi: 10.3109/14767058.2012.674990. Epub 2012 Apr 17. — View Citation

Leisenring W, Alonzo T, Pepe MS. Comparisons of predictive values of binary medical diagnostic tests for paired designs. Biometrics. 2000 Jun;56(2):345-51. — View Citation

Malin GL, Bugg GJ, Takwoingi Y, Thornton JG, Jones NW. Antenatal magnetic resonance imaging versus ultrasound for predicting neonatal macrosomia: a systematic review and meta-analysis. BJOG. 2016 Jan;123(1):77-88. doi: 10.1111/1471-0528.13517. Epub 2015 Jul 29. Review. — View Citation

McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med. 1999 Apr 22;340(16):1234-8. — View Citation

Rouse DJ, Owen J, Goldenberg RL, Cliver SP. The effectiveness and costs of elective cesarean delivery for fetal macrosomia diagnosed by ultrasound. JAMA. 1996 Nov 13;276(18):1480-6. — View Citation

Sampson ML, Gounden V, van Deventer HE, Remaley AT. CUSUM-Logistic Regression analysis for the rapid detection of errors in clinical laboratory test results. Clin Biochem. 2016 Feb;49(3):201-7. doi: 10.1016/j.clinbiochem.2015.10.019. Epub 2015 Oct 30. — View Citation

Seravalli V, Baschat AA. A uniform management approach to optimize outcome in fetal growth restriction. Obstet Gynecol Clin North Am. 2015 Jun;42(2):275-88. doi: 10.1016/j.ogc.2015.01.005. Review. — View Citation

Wani S, Hall M, Wang AY, DiMaio CJ, Muthusamy VR, Keswani RN, Brauer BC, Easler JJ, Yen RD, El Hajj I, Fukami N, Ghassemi KF, Gonzalez S, Hosford L, Hollander TG, Wilson R, Kushnir VM, Ahmad J, Murad F, Prabhu A, Watson RR, Strand DS, Amateau SK, Attwell A, Shah RJ, Early D, Edmundowicz SA, Mullady D. Variation in learning curves and competence for ERCP among advanced endoscopy trainees by using cumulative sum analysis. Gastrointest Endosc. 2016 Apr;83(4):711-9.e11. doi: 10.1016/j.gie.2015.10.022. Epub 2015 Oct 26. — View Citation

Yudkin PL, Aboualfa M, Eyre JA, Redman CW, Wilkinson AR. New birthweight and head circumference centiles for gestational ages 24 to 42 weeks. Early Hum Dev. 1987 Jan;15(1):45-52. — View Citation

Zaretsky MV, Reichel TF, McIntire DD, Twickler DM. Comparison of magnetic resonance imaging to ultrasound in the estimation of birth weight at term. Am J Obstet Gynecol. 2003 Oct;189(4):1017-20. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Receiver Operating Curve (AUROC) for prediction of macrosomia (= P95)	AUROC for prediction of macrosomia (= P95 for gestational age; normal ranges of Yudkin et al.) with MR (4 mm ST (slice thickness)/ 20 mm gap) versus US using the Hadlock equation.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Area Under the Receiver Operating Curve (AUROC) for prediction of macrosomia (= P90)	AUROC for prediction of macrosomia (= P90 for gestational age) with magnetic resonnance (4 mm slice thickness/20 mm gap) versus ultrasound.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Area Under the Receiver Operating Curve (AUROC) for prediction of macrosomia (= P99)	AUROC for prediction of macrosomia (= P99 for gestational age) with Magnetic Resonance (4 mm slice thickness/ 20 mm gap) versus Ultrasound.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Area Under the Receiver Operating Curve (AUROC) for prediction of macrosomia (= P97)	AUROC for prediction of macrosomia (= P97 for gestational age) with Magnetic Resonance (4 mm slice thickness/ 20 mm gap) versus Ultrasound.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Area Under the Receiver Operating Curve (AUROC) for prediction of macrosomia (Abdominal Circumference)	AUROC for prediction of macrosomia with Abdominal Circumference = P90 for gestational age. Measured in cm with Ultrasound	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Area Under the Receiver Operating Curve (AUROC) for prediction of 'Small for gestational age' (SGA)	Measured with Magnetic Resonnace (4 mm slice thickness)/ 20 mm gap) versus ultrasound.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Comparative prediction rate for significant shoulder dystocia	Ability of Magnetic Resonnace-Estimated Fetal Weight (+/- pelvimetric measurements) vs. Ultrasound-Estimated Fetal Weigth in predicting significant shoulder dystocia. Significant shoulder dystocia is defined clinically as difficulty with delivery of the shoulders that was not resolved by the McRoberts' manoeuvre (flexion of the maternal thighs), usually combined with suprapubic pressure. Manoeuvres whose use suggested significant shoulder dystocia were those involving rotation of the fetus to displace the anterior shoulder impacted behind the maternal pubic bone (Woods, Rubin, or Jacquemier manoeuvres). The definition also included births with an interval of 60 s or more between delivery of the head and the body.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Comparative prediction rate for maternal morbidity	Ability of Magnetic Resonance-Estimated Fetal Weigth (+/- pelvimetric measurements) vs. Ultrasound-Estimated Fetal Weigth in predicting maternal morbidity, defined as caesarean section, operative vaginal delivery (vacuum or forceps), postpartum haemorrhage (1000 mL or more), blood transfusion, and anal sphincter tear.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Comparative prediction rate for neonatal morbidity	Ability of Magentic Resonance-Estimated Fetal Weigth (+/- pelvimetric measurements) vs. Ultrasound-Estimated Fetal Weigth in predicting neonatal morbidity, defined as arterial cord blood pH less than 7.10, Apgar score at 5 min less than 7, and admission to the neonatal intensive-care unit.	Between 36 weeks and 36 weeks + 6 days of gestation
Secondary	Comparative prediction rate for neonatal hyperbilirubinaemia	Ability of Magentic Resonance-Estimated Fetal Weigth (+/- pelvimetric measurements) vs. Ultrasound-Estimated Fetal Weigth in predicting neonatal hyperbilirubinaemia, defined as a maximum value exceeding 350 mmol/L of blood bilirubin.	Between 36 weeks and 36 weeks + 6 days of gestation