Randomized Controlled Trial

. 2024 Jul 1;144(1):126-134.

doi: 10.1097/AOG.0000000000005613. Epub 2024 May 23.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension

Ayodeji A Sanusi^{1

2}, Justin Leach^{1

2}, Kim Boggess^{1

2}, Lorraine Dugoff^{1

2}, Baha Sibai^{1

2}, Kirsten Lawrence^{1

2}, Brenna L Hughes^{1

2}, Joseph Bell^{1

2}, Kjersti Aagaard^{1

2}, Rodney K Edwards^{1

2}, Kelly S Gibson^{1

2}, David M Haas^{1

2}, Lauren Plante^{1

2}, Torri D Metz^{1

2}, Brian Casey^{1

2}, Sean Esplin^{1

2}, Sherri Longo^{1

2}, Matthew K Hoffman^{1

2}, George R Saade^{1

2}, Kara K Hoppe^{1

2}, Janelle Foroutan^{1

2}, Methodius Tuuli^{1

2}, Michelle Y Owens^{1

2}, Hyagriv N Simhan^{1

2}, Heather Frey^{1

2}, Todd Rosen^{1

2}, Anna Palatnik^{1

2}, Susan Baker^{1

2}, Phyllis August^{1

2}, Uma M Reddy^{1

2}, Emily J Su^{1

2}, Iris Krishna^{1

2}, Nguyet A Nguyen^{1

2}, Mary E Norton^{1

2}, Daniel Skupski^{1

2}, Yasser Y El-Sayed^{1

2}, Dotun Ogunyemi^{1

2}, Zorina S Galis^{1

2}, Lorie Harper^{1

2}, Namasivayam Ambalavanan^{1

2}, Nancy L Geller^{1

2}, Hui-Chien Kuo^{1

2}, Rachel G Sinkey^{1

2}, Ronald Librizzi^{1

2}, Leonardo Pereira^{1

2}, Everett F Magann^{1

2}, Mounira Habli^{1

2}, Shauna Williams^{1

2}, Giancarlo Mari^{1

2}, Gabriella Pridjian^{1

2}, David S McKenna^{1

2}, Marc Parrish^{1

2}, Eugene Chang^{1

2}, Sarah Osmundson^{1

2}, JoAnne Quinones^{1

2}, Jeff M Szychowski^{1

2}, Alan T N Tita^{1

2}

Affiliations

¹ Departments of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, and University of South Alabama at Mobile, Mobile, Alabama, University of North Carolina at Chapel Hill, Chapel Hill, and Duke University, Durham, North Carolina, University of Pennsylvania and Drexel University College of Medicine, Philadelphia, and Magee Women's Hospital and University of Pittsburgh, Pittsburgh, Pennsylvania, University of Texas at Houston and the Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, and University of Texas Medical Branch, Galveston, Texas, Columbia University and Weill Cornell University, New York, and New York Presbyterian Queens Hospital, Flushing, New York, University of Oklahoma Health Sciences, Oklahoma City, Oklahoma, Indiana University, Indianapolis, Indiana, University of Utah and Intermountain Healthcare, Salt Lake City, Utah, UnityPoint Health-Meriter Hospital/Marshfield Clinic, Madison, Wisconsin, Washington University in St. Louis, St. Louis, Missouri, University of Mississippi Medical Center, Jackson, Mississippi, The Ohio State University, Columbus, Ohio, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, New Jersey, Medical College of Wisconsin, Milwaukee, Wisconsin, Yale University, New Haven, Connecticut, University of Colorado, Aurora, and Denver Health, Denver, Colorado, Emory University, Atlanta, Georgia.
² University of California San Francisco, San Francisco, and Stanford University, Stanford, California, and Arrowhead Regional Medical Center/Beaumont Hospital, Michigan, Detroit, Michigan; the Center for Women's Reproductive Health, the Department of Biostatistics and the Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama; St. Luke's University Health Network, Bethlehem, Pennsylvania; MetroHealth System, Cleveland, Ohio; Ochsner Baptist Medical Center, New Orleans, Louisiana; Christiana Care Health Services, Newark, Delaware; St. Peters University Hospital, New Brunswick, New Jersey; Zuckerberg San Francisco General Hospital, San Francisco, California; the Division of Cardiovascular Sciences and the Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and the Department of Women's Health, University of Texas at Austin, Austin, Texas.

PMID: 38949541
PMCID: PMC11219006
DOI: 10.1097/AOG.0000000000005613

Randomized Controlled Trial

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension

Ayodeji A Sanusi et al. Obstet Gynecol. 2024.

. 2024 Jul 1;144(1):126-134.

doi: 10.1097/AOG.0000000000005613. Epub 2024 May 23.

Authors

Affiliations

¹ Departments of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, and University of South Alabama at Mobile, Mobile, Alabama, University of North Carolina at Chapel Hill, Chapel Hill, and Duke University, Durham, North Carolina, University of Pennsylvania and Drexel University College of Medicine, Philadelphia, and Magee Women's Hospital and University of Pittsburgh, Pittsburgh, Pennsylvania, University of Texas at Houston and the Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, and University of Texas Medical Branch, Galveston, Texas, Columbia University and Weill Cornell University, New York, and New York Presbyterian Queens Hospital, Flushing, New York, University of Oklahoma Health Sciences, Oklahoma City, Oklahoma, Indiana University, Indianapolis, Indiana, University of Utah and Intermountain Healthcare, Salt Lake City, Utah, UnityPoint Health-Meriter Hospital/Marshfield Clinic, Madison, Wisconsin, Washington University in St. Louis, St. Louis, Missouri, University of Mississippi Medical Center, Jackson, Mississippi, The Ohio State University, Columbus, Ohio, Rutgers University-Robert Wood Johnson Medical School, New Brunswick, New Jersey, Medical College of Wisconsin, Milwaukee, Wisconsin, Yale University, New Haven, Connecticut, University of Colorado, Aurora, and Denver Health, Denver, Colorado, Emory University, Atlanta, Georgia.
² University of California San Francisco, San Francisco, and Stanford University, Stanford, California, and Arrowhead Regional Medical Center/Beaumont Hospital, Michigan, Detroit, Michigan; the Center for Women's Reproductive Health, the Department of Biostatistics and the Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama; St. Luke's University Health Network, Bethlehem, Pennsylvania; MetroHealth System, Cleveland, Ohio; Ochsner Baptist Medical Center, New Orleans, Louisiana; Christiana Care Health Services, Newark, Delaware; St. Peters University Hospital, New Brunswick, New Jersey; Zuckerberg San Francisco General Hospital, San Francisco, California; the Division of Cardiovascular Sciences and the Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and the Department of Women's Health, University of Texas at Austin, Austin, Texas.

PMID: 38949541
PMCID: PMC11219006
DOI: 10.1097/AOG.0000000000005613

Abstract

Objective: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial.

Methods: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding.

Results: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine.

Conclusion: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy.

Clinical trial registration: ClinicalTrials.gov, NCT02299414.

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Conflict of interest statement

Financial Disclosure Brenna L. Hughes reports receiving payment from UpToDate. Rodney K. Edwards' institution received payment from the Oklahoma Center for Advancement of Science and Technology and the Presbyterian Health Foundation. He received payment from the NIH through Oklahoma CTR grant for a pilot trial on warming preterm infants during delayed cord clamping. He received a Presbyterian Health Foundation grant for a pilot trial on omega-3 fatty acid supplementation effects on maternal triglycerides and fetal growth. He received an NIH grant for evaluation of atherogenic lipoproteins changes with immediate prepregnancy intervention and whether they were maintained during pregnancy. He received a grant from Cepheid for the clinical evaluation of the Xpert Xpress GBS test using vaginal/rectal swabs collected intrapartum. He was awarded an Oklahoma State DOH contract for support for patient-centered, comprehensive pregnancy care for women with substance use disorders. He received an NIH grant for a multicenter RCT of intensive glycemic targets in women with overweight and obesity with GDM. Lastly, he has a pending NIH grant for a multicenter RCT of prophylactic antibiotics for induction of labor in women with obesity. He has served on an expert witness case regarding a medical malpractice claim. Kelly S. Gibson's institution received an NHCID-MFMU network grant and Materna Medical research support (EASE). She received payment from NIH as a RADx grant reviewer and was an Ohio AIM grant recipient as an AIM webinar speaker. Rachel Sinkey received funding paid to her institution from the NIH and the American Heart Association. Kelly S. Gibson reports her institution received an NHCID-MFMU network grant and Materna Medical research support (EASE). She received payment as a NIH-RADx grant reviewer. Torri D. Metz received UpToDate royalties for two topics on trial of labor after cesarean. Her institution received payment from Pfizer, as she has been a site PI for a phase III respiratory syncytial virus (RSV) vaccine trial (institution received money to conduct study). Her institution also received payment for her to serve as a site PI for a COVID-19 vaccination trial in pregnancy. She has received payment from Pfizer as a site PI for a pharmacokinetic study of Paxlovid in pregnancy for mild-to-moderate COVID-19. Sean Esplin received payment from Laborie. Mary E. Norton received payment from Luna Genetics. Daniel Skupski received payment from Organon and Cooper Surgical. Leonardo Pereira's institution received payment from Johnson & Johnson/Janssen Pharmaceuticals for an FDA trial on alloimmunization management. Everett F. Magann is a co-author on and UpToDate chapter on amniotic fluid volume assessment. Heather Frey also received royalties for contributions to UpToDate on the topic of uterine rupture. Alan T.N. Tita's institution received funding from Pfizer. Torri D. Metz received UpToDate royalties for two topics on trial of labor after cesarean. Her institution received payment from Pfizer, as she has been a site PI for a phase III respiratory syncytial virus (RSV) vaccine trial, a COVID-19 vaccine trial in pregnancy, and pharmacokinetic study of Paxlovid in pregnancy for mild-to-moderate COVID-19 (institution received money to conduct studies). Kara K. Hoppe's institution received an NIH grant for a multicenter RCT of remote blood pressure monitoring with health coaching versus standard of care, HHS funding for a hypertension challenge initiative, Marani to study implementation of their remote patient monitoring platform for hypertensive patients in pregnancy and postpartum. Additionally, she received payment for the NIH as a grant reviewer and WisPQC for providing physician leadership for the state quality initiative on hypertension in pregnancy. Eugene Chang received payment from Roche diagnostics for research on sflt-1/plgf. Sherri Longo acknowledges the financial support received for the Prospect study and other NIH-funded studies including CHAP maternal follow-up and CSOAP follow-up. She is also an investigator for the Moms on the Bayou research project with Tulane University and is receiving funding from the NIH Maternal Health Research Center of Excellence awarded to a collaborative effort between Tulane University, Ochsner Health, and RHI. Alan T.N. Tita's institution received funding from Pfizer. The other authors did not report any potential conflicts of interest.

References

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Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension

Affiliations

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical