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

Ayodeji A Sanusi; Justin Leach; Kim Boggess; Lorraine Dugoff; Baha Sibai; Kirsten Lawrence; Brenna L Hughes; Joseph Bell; Kjersti Aagaard; Rodney K Edwards; Kelly S Gibson; David M Haas; Lauren Plante; Torri D Metz; Brian Casey; Sean Esplin; Sherri Longo; Matthew K Hoffman; George R Saade; Kara K Hoppe; Janelle Foroutan; Methodius Tuuli; Michelle Y Owens; Hyagriv N Simhan; Heather Frey; Todd Rosen; Anna Palatnik; Susan Baker; Phyllis August; Uma M Reddy; Emily J Su; Iris Krishna; Nguyet A Nguyen; Mary E Norton; Daniel Skupski; Yasser Y El-Sayed; Dotun Ogunyemi; Zorina S Galis; Lorie Harper; Namasivayam Ambalavanan; Nancy L Geller; Hui-Chien Kuo; Rachel G Sinkey; Ronald Librizzi; Leonardo Pereira; Everett F Magann; Mounira Habli; Shauna Williams; Giancarlo Mari; Gabriella Pridjian; David S McKenna; Marc Parrish; Eugene Chang; Sarah Osmundson; JoAnne Quinones; Jeff M Szychowski; Alan T N Tita

doi:10.1097/AOG.0000000000005613

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

Obstet Gynecol. 2024 Jul 1;144(1):126-134. doi: 10.1097/AOG.0000000000005613. Epub 2024 May 23.

Authors

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 (available on 2025-07-01)
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.

Publication types

Randomized Controlled Trial
Multicenter Study
Comparative Study

MeSH terms

Administration, Oral
Adult
Antihypertensive Agents* / administration & dosage
Antihypertensive Agents* / adverse effects
Antihypertensive Agents* / therapeutic use
Chronic Disease
Female
Humans
Hypertension* / drug therapy
Hypertension, Pregnancy-Induced / drug therapy
Infant, Newborn
Infant, Small for Gestational Age
Labetalol* / administration & dosage
Labetalol* / adverse effects
Labetalol* / therapeutic use
Nifedipine* / administration & dosage
Nifedipine* / adverse effects
Nifedipine* / therapeutic use
Pre-Eclampsia / drug therapy
Pregnancy
Pregnancy Complications, Cardiovascular / drug therapy
Pregnancy Outcome*

Substances

Labetalol
Nifedipine
Antihypertensive Agents

Associated data

ClinicalTrials.gov/NCT02299414

Grants and funding

U01 HL120338/HL/NHLBI NIH HHS/United States