{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:22:08Z","timestamp":1790144528855,"version":"4.0.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"national institute on child health and human development","award":["R01HD082141"],"award-info":[{"award-number":["R01HD082141"]}]},{"DOI":"10.13039\/100005977","name":"Kaiser Permanente","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objective<\/jats:title><jats:p>To compare maternal and infant outcomes with different antihypertensive medications in pregnancy.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Design<\/jats:title><jats:p>Retrospective cohort study.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Setting<\/jats:title><jats:p>Kaiser Permanente, a large healthcare system in the United States.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Population<\/jats:title><jats:p>Women aged 15\u201349 years with a singleton birth from 2005\u20132014 treated for hypertension.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Methods<\/jats:title><jats:p>We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding.<\/jats:p><\/jats:sec><jats:sec id=\"sec006\"><jats:title>Main outcome measures<\/jats:title><jats:p>Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at &gt; 20 weeks.<\/jats:p><\/jats:sec><jats:sec id=\"sec007\"><jats:title>Results<\/jats:title><jats:p>Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight &lt; 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight &lt; 3<jats:sup>rd<\/jats:sup>percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other \u03b2-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication.<\/jats:p><\/jats:sec><jats:sec id=\"sec008\"><jats:title>Conclusions<\/jats:title><jats:p>Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0268284","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T17:24:04Z","timestamp":1652721844000},"page":"e0268284","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Maternal and neonatal outcomes of antihypertensive treatment in pregnancy: A retrospective cohort study"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6649-3659","authenticated-orcid":true,"given":"Sascha","family":"Dublin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abisola","family":"Idu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsay A.","family":"Avalos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Craig","family":"Cheetham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Easterling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L.","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerissa","family":"Nance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Bider-Canfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain S.","family":"Neugebauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-1649","authenticated-orcid":true,"given":"Kristi","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E.","family":"Badon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Shortreed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"issue":"34","key":"pone.0268284.ref001","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1093\/eurheartj\/ehy340","article-title":"2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy","volume":"39","author":"V Regitz-Zagrosek","year":"2018","journal-title":"Eur Heart J"},{"issue":"2","key":"pone.0268284.ref002","doi-asserted-by":"crossref","first-page":"134 e1","DOI":"10.1016\/j.ajog.2011.10.878","article-title":"Prevalence, trends, and outcomes of chronic hypertension: a nationwide sample of delivery admissions","volume":"206","author":"BT Bateman","year":"2012","journal-title":"Am J Obstet Gynecol"},{"issue":"4","key":"pone.0268284.ref003","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ajog.2012.11.011","article-title":"Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes","volume":"208","author":"H Orbach","year":"2013","journal-title":"Am J Obstet Gynecol"},{"issue":"5","key":"pone.0268284.ref004","first-page":"419","article-title":"Maternal complications in women with chronic hypertension: a population-based cohort study","volume":"84","author":"K Zetterstr\u00f6m","year":"2005","journal-title":"Acta obstetricia et gynecologica Scandinavica"},{"issue":"2","key":"pone.0268284.ref005","doi-asserted-by":"crossref","first-page":"e53844","DOI":"10.1371\/journal.pone.0053844","article-title":"Pregnancy outcomes of anti-hypertensives for women with chronic hypertension: a population-based study","volume":"8","author":"CY Su","year":"2013","journal-title":"PloS one"},{"issue":"1","key":"pone.0268284.ref006","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1097\/AOG.0000000000003020","article-title":"American College of Obstetricians and Gynecologists\u2019 Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 203: Chronic Hypertension in Pregnancy","volume":"133","year":"2019","journal-title":"Obstet Gynecol"},{"key":"pone.0268284.ref007","article-title":"Hypertension in pregnancy: diagnosis and management","author":"National Institute for Health and Care Excellence","year":"2019","journal-title":"NICE guideline [NG133]"},{"key":"pone.0268284.ref008","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.preghy.2018.05.004","article-title":"The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice","volume":"13","author":"MA Brown","year":"2018","journal-title":"Pregnancy hypertension"},{"key":"pone.0268284.ref009","first-page":"CD002252","article-title":"Antihypertensive drug therapy for mild to moderate hypertension during pregnancy","volume":"10","author":"E Abalos","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"issue":"4","key":"pone.0268284.ref010","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/10641955.2020.1791902","article-title":"Methyldopa versus labetalol or no medication for treatment of mild and moderate chronic hypertension during pregnancy: a randomized clinical trial","volume":"39","author":"M Rezk","year":"2020","journal-title":"Hypertens Pregnancy"},{"issue":"7","key":"pone.0268284.ref011","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1111\/1471-0528.13569","article-title":"Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial","volume":"123","author":"LA Magee","year":"2016","journal-title":"BJOG"},{"issue":"24","key":"pone.0268284.ref012","first-page":"2367","article-title":"Less-tight versus tight control of hypertension in pregnancy","volume":"372","author":"Chips Study Group","year":"2015","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0268284.ref013","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2012-001185","article-title":"beta-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study","volume":"2","author":"K Meidahl Petersen","year":"2012","journal-title":"BMJ Open"},{"issue":"1","key":"pone.0268284.ref014","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1161\/HYPERTENSIONAHA.117.09110","article-title":"Pregnancy Outcome After First Trimester Use of Methyldopa: A Prospective Cohort Study","volume":"70","author":"M Hoeltzenbein","year":"2017","journal-title":"Hypertension"},{"issue":"2","key":"pone.0268284.ref015","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/bdrb.20238","article-title":"Antihypertensive medication use during pregnancy and the risk of major congenital malformations or small-for-gestational-age newborns","volume":"89","author":"HR Nakhai-Pour","year":"2010","journal-title":"Birth Defects Res B Dev Reprod Toxicol"},{"issue":"1","key":"pone.0268284.ref016","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2393-1-6","article-title":"Use of antihypertensive medications in pregnancy and the risk of adverse perinatal outcomes: McMaster Outcome Study of Hypertension In Pregnancy 2 (MOS HIP 2)","volume":"1","author":"JG Ray","year":"2001","journal-title":"BMC Pregnancy Childbirth"},{"issue":"3","key":"pone.0268284.ref017","doi-asserted-by":"crossref","first-page":"37","DOI":"10.7812\/TPP\/12-031","article-title":"Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data","volume":"16","author":"C Koebnick","year":"2012","journal-title":"Perm J"},{"issue":"4","key":"pone.0268284.ref018","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1097\/AOG.0000000000002780","article-title":"One-Step Approach to Identifying Gestational Diabetes Mellitus: Association With Perinatal Outcomes","volume":"132","author":"G Pocobelli","year":"2018","journal-title":"Obstetrics and gynecology"},{"issue":"10","key":"pone.0268284.ref019","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1055\/s-0038-1675619","article-title":"Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study","volume":"36","author":"L Chen","year":"2019","journal-title":"Am J Perinatol"},{"issue":"1","key":"pone.0268284.ref020","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/AOG.0b013e318278ce86","article-title":"Prevalence, trends, and patterns of use of antidiabetic medications among pregnant women, 2001\u20132007","volume":"121","author":"JM Lawrence","year":"2013","journal-title":"Obstet Gynecol"},{"issue":"2","key":"pone.0268284.ref021","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/pds.3919","article-title":"Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies","volume":"25","author":"C Hansen","year":"2016","journal-title":"Pharmacoepidemiology and drug safety"},{"issue":"1","key":"pone.0268284.ref022","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/pds.3319","article-title":"Validity of health plan and birth certificate data for pregnancy research","volume":"22","author":"SE Andrade","year":"2013","journal-title":"Pharmacoepidemiology and drug safety"},{"issue":"1","key":"pone.0268284.ref023","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/pds.3728","article-title":"Linking mothers and infants within electronic health records: a comparison of deterministic and probabilistic algorithms","volume":"24","author":"E Baldwin","year":"2015","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"1","key":"pone.0268284.ref024","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ajog.2005.02.096","article-title":"The reporting of pre-existing maternal medical conditions and complications of pregnancy on birth certificates and in hospital discharge data","volume":"193","author":"MT Lydon-Rochelle","year":"2005","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"pone.0268284.ref025","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1365-3016.2005.00682.x","article-title":"Accuracy of reporting maternal in-hospital diagnoses and intrapartum procedures in Washington State linked birth records","volume":"19","author":"MT Lydon-Rochelle","year":"2005","journal-title":"Paediatr Perinat Epidemiol"},{"issue":"7","key":"pone.0268284.ref026","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/jech.2004.029496","article-title":"Estimating causal effects from epidemiological data","volume":"60","author":"MA Hern\u00e1n","year":"2006","journal-title":"Journal of epidemiology and community health"},{"key":"pone.0268284.ref027","volume-title":"Causal Inference: What If","author":"MA Hern\u00e1n","year":"2020","edition":"1"},{"issue":"8","key":"pone.0268284.ref028","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/aje\/kwv254","article-title":"Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available","volume":"183","author":"MA Hern\u00e1n","year":"2016","journal-title":"American journal of epidemiology"},{"issue":"4","key":"pone.0268284.ref029","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s40471-015-0053-5","article-title":"The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application","volume":"2","author":"JL Lund","year":"2015","journal-title":"Curr Epidemiol Rep"},{"key":"pone.0268284.ref030","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.preghy.2020.01.001","article-title":"Identifying hypertension in pregnancy using electronic medical records: The importance of blood pressure values","volume":"19","author":"L Chen","year":"2020","journal-title":"Pregnancy hypertension"},{"key":"pone.0268284.ref031","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2431-3-6","article-title":"A nearly continuous measure of birth weight for gestational age using a United States national reference","volume":"3","author":"E Oken","year":"2003","journal-title":"BMC Pediatr"},{"issue":"6","key":"pone.0268284.ref032","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/pds.3627","article-title":"Validity of maternal and infant outcomes within nationwide Medicaid data","volume":"23","author":"K Palmsten","year":"2014","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"1","key":"pone.0268284.ref033","first-page":"e1","article-title":"ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia","volume":"133","year":"2019","journal-title":"Obstet Gynecol"},{"key":"pone.0268284.ref034","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4899-4541-9","volume-title":"An Introduction to the Bootstrap","author":"B Efron","year":"1993"},{"issue":"30","key":"pone.0268284.ref035","doi-asserted-by":"crossref","first-page":"5642","DOI":"10.1002\/sim.7084","article-title":"Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis","volume":"35","author":"PC Austin","year":"2016","journal-title":"Stat Med"},{"issue":"5","key":"pone.0268284.ref036","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/00001648-200009000-00011","article-title":"Marginal structural models and causal inference in epidemiology","volume":"11","author":"JM Robins","year":"2000","journal-title":"Epidemiology"},{"key":"pone.0268284.ref037","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-1-4612-1284-3_2","volume-title":"Statistical Models in Epidemiology, the Environment, and Clinical Trials","author":"JM Robins","year":"2000"},{"issue":"25","key":"pone.0268284.ref038","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1002\/sim.3697","article-title":"Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples","volume":"28","author":"PC Austin","year":"2009","journal-title":"Stat Med"},{"issue":"28","key":"pone.0268284.ref039","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1002\/sim.6607","article-title":"Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies","volume":"34","author":"PC Austin","year":"2015","journal-title":"Statistics in medicine"},{"issue":"12","key":"pone.0268284.ref040","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1016\/j.ajpath.2018.08.011","article-title":"Human Placenta Expresses \u03b1(2)-Adrenergic Receptors and May Be Implicated in Pathogenesis of Preeclampsia and Fetal Growth Restriction","volume":"188","author":"HKB Motawea","year":"2018","journal-title":"Am J Pathol"},{"issue":"4","key":"pone.0268284.ref041","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.reprotox.2009.07.001","article-title":"Folic acid uptake by the human syncytiotrophoblast: interference by pharmacotherapy, drugs of abuse and pathological conditions","volume":"28","author":"E Keating","year":"2009","journal-title":"Reprod Toxicol"},{"issue":"4","key":"pone.0268284.ref042","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1161\/HYPERTENSIONAHA.119.14509","article-title":"Differential DNA Methylation in Placenta Associated With Maternal Blood Pressure During Pregnancy","volume":"75","author":"T Workalemahu","year":"2020","journal-title":"Hypertension (Dallas, Tex: 1979)"},{"issue":"1","key":"pone.0268284.ref043","doi-asserted-by":"crossref","DOI":"10.3390\/genes11010080","article-title":"Modulation of Placental Gene Expression in Small-for-Gestational-Age Infants","volume":"11","author":"JL O\u2019Callaghan","year":"2020","journal-title":"Genes (Basel)"},{"issue":"5","key":"pone.0268284.ref044","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1161\/HYPERTENSIONAHA.117.09972","article-title":"Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial","volume":"70","author":"LM Webster","year":"2017","journal-title":"Hypertension"},{"issue":"10203","key":"pone.0268284.ref045","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S0140-6736(19)31282-6","article-title":"Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial","volume":"394","author":"T Easterling","year":"2019","journal-title":"Lancet"},{"issue":"3","key":"pone.0268284.ref046","first-page":"211","article-title":"The short term effects of oral labetalol in patients with chronic renal disease and hypertension","volume":"6","author":"A Innes","year":"1992","journal-title":"J Hum Hypertens"},{"issue":"Suppl 2","key":"pone.0268284.ref047","doi-asserted-by":"crossref","first-page":"149s","DOI":"10.1111\/j.1365-2125.1979.tb04771.x","article-title":"A comparative study of methyldopa and labetalol in the treatment of hypertension","volume":"8","author":"GL Sanders","year":"1979","journal-title":"Br J Clin Pharmacol"},{"issue":"4a","key":"pone.0268284.ref048","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0002-9343(83)90140-7","article-title":"Treatment of severe hypertension with labetalol compared with methyldopa and furosemide. Results of a long-term, double-blind, multicenter trial","volume":"75","author":"JD Wallin","year":"1983","journal-title":"Am J Med"},{"issue":"11","key":"pone.0268284.ref049","doi-asserted-by":"crossref","first-page":"819","DOI":"10.7326\/M14-1884","article-title":"Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: U.S. Preventive Services Task Force recommendation statement","volume":"161","author":"ML LeFevre","year":"2014","journal-title":"Ann Intern Med"},{"issue":"5","key":"pone.0268284.ref050","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1097\/EDE.0000000000000699","article-title":"Nature as a Trialist?: Deconstructing the Analogy Between Mendelian Randomization and Randomized Trials","volume":"28","author":"SA Swanson","year":"2017","journal-title":"Epidemiology (Cambridge, Mass)"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0268284","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T17:35:01Z","timestamp":1700588101000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0268284"}},"subtitle":[],"editor":[{"given":"Zhong-Cheng","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,16]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0268284","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,16]]}}}