Influence of Gestational Age at Initiation of Antihypertensive Therapy
Authors: Pels Anouk , Mol Ben Willem J. , Singer Joel , Lee Terry , von Dadelszen Peter , Ganzevoort Wessel , Asztalos Elizabeth , Magee Laura A. , Gafni Amiram , Gruslin Andrée , Helewa Michael , Hutton Eileen , Lee Shoo , Logan Alexander , Menzies Jennifer , Moutquin Jean-Marie , Murphy Kellie , Rey Evelyne , Ross Sue , Sanchez Johanna , Thornton Jim G. , Welch Ross , Hoac Trinh , Kirton Joanne , Trigiani Katherine , Zahid Ainy , Bracken Michael B. , Crowley Patricia , Duley Lelia , Ehrenkranz Richard , Thorpe Kevin , Chan Sunny , Shi Michael , Yu Shelley , de Lourdes Martin Raquel , Bassi Maria Florencia , Caruso Mirta Clara , Lagunas Valeria , Vera Fernando , Mohedano de Duhalde Maria , Roque Alicia Beatriz , Roldan Patricia , Duhalde Esteban Marcos , Dip Viviana , Aguirre Jesus Daniel , Morales Elba Mirta Alicia , Abreo Griselda Itati , De Sagastizabal Teresa , Gomez Carolina , Rizzi Nadia , Arias Carlos , Bruno Ricardo Antonio , Mahomed Kassam , Drew Alison , Green Ann , Hoare Jane , Hague Bill , Coat Suzette , Crowther Caroline , Muller Peter , Trenowden Sophie , Walters Barry , Parker Claire , Graham Dorothy , Pennell Craig , Sung Eileen , Makris Angela , Lee Gaksoo , Thornton Charlene , Hennessy Annemarie , Farrell Louise , Sass Nelson , Korkes Henri , Ferreira Dayana Couto , Moreira de Sa Renato Augusto , Abreu Monique Schmidt Marques , Bornia Rita Guerios , da Silva Nancy Ribeiro , Cardoso Fernanda Freitas Oliveira , Marques Caio Coelho , Hornos Jorge , Davdt Ricardo Leal , Paula Letícia Germany , Zanella Pedro Luis , Inglis Gabrielle , Dillon Ruth , Docherty Ashley , Hutfield Anna , Still Keith , Lalji Sayrin , Van Tent Tamara , Hotz Chris , Messmer Tracy , Ray Joel G. , Berger Howard , De Souza Leanne , Lausman Andrea , Freire-Lizama Tatiana , Besel Kate , Gibson Paul , Ellsworth Greta , Miller Leslie , Hawkins T. Lee-Ann , Hladunewich Michelle , Rogowsky Anna , Hui Dini , Collins Virginia , Delisle Isabelle , Fanning Cora , Demianczuk Nestor , Khurana Rshmi , Sia Winnie , Marnoch Catherine , Young Carmen , Lux Cheryl , Perreault Sophie , Tremblay Valerie , Desindes Sophie , Côté Anne-Marie , Dagenais Veronique , Clark Heather , O’Shea Elaine , White Ruth Rennicks , Gandhi Shital , Martin Mary-Jean , Brush Cheryl , Seaward Gareth , Newstead-Angel Jill , Brandt Judy , Martel Jocelyne , Mytopher Kristine , Buschau Elise , Keely Erin , Waddell Patti , Shachkina Svetlana , Karovitch Alan , Anderson Robert , Koenig Nicole , Yong Theresa , Vasiliou Marie , Johnson Peri , Allan Beth , Natale Renato , Kennedy Laura , Opatrny Lucie , Lavigne Lorraine , Carson George , Kelly Sheila , Crane Joan , Hutchens Donna , Kusanovic Juan Pedro , Figueroa Christian , Neculman Karla Silva , Ortiz Juan Andres , Vargas Paula , Ferrand Pedro , Carrillo Jorge , Borrero Rodrigo Cifuentes , Gallo Dahiana Marcela , Moreno Luisa Fernanda , Kirss Fred , Rull Kristiina , Kirss Anne , Major Tamas , Fodor Andrea , Bartha Tunde , Hallak Mordechai , Aslih Nardin , Anabousi-Murra Saja , Pri-Or Ester , Harel Linda , Siev Sima , Hakim Marwan , Khoury Christina Simona , Hamati Najla , El-Zibdeh Mazen , Yousef Lama , Hughes Ruth , Leishman Di , Pullar Barbra , Farrant Matthew , Swiatkowska-Freund Malgorzata , Preis Krzysztof , Traczyk-Los Anette Aleksandra , Partyka Anna , Preis-Orlikowska Joanna , Lukaszuk Mariusz , Krasomski Grzegorz , Krekora Michael , Kedzierska-Markowicz Anna , Zych-Krekora Katarzyna , Breborowicz Grzegorz H. , Dera-Szymanowska Anna , Bakker Jannet , Akkermans Joost , van den Akker Eline , Logtenberg Sabine , Koenen Steven , de Reus Maartje , Borman David , Oudijk Martijn A. , Bolte Annemiek , Verfaille Viki , Graaf Bart , Porath Martina , Verhoeven Corine , Franssen Maureen T.M. , Ulkeman Lida , Hamming Ineke , Keurentjes Jose H.M. , van der Wal Ina , Bijvank S.W.A. Nij , Lutjes A.A. , Visser Henricus , Scheepers Hubertina Catharina Johanna , van Beek Erik , van Dam Coby , van den Berg-Swart Kathy , Pernet Paula , van der Goes Birgit , Schuitemaker Nico , Kleiverda Gunilla , van Alphen Marcel , Rosman Ageeth , Gaugler-Senden Ingrid , Linders Marieke , Nelson-Piercy Catherine , Briley Annette , Soh May Ching , Harding Kate , Tarft Hayley , Churchill David , Cheshire Katherine , Icke Julia , Ghosh Mausumi , Thornton James , Toomassi Yvonne , Barker Karen , Fisher Joanne , Grace Nicky , Green Amanda , Gower Joanne , Molnar Anna , Parameshwaran Shobhana , Simm Andrew , Bugg George , Davis Yvette , Desphande Ruta , Gunn Yvette , Houda Mohammed , Jones Nia , Waugh Jason , Allan Carly , Waring Gareth , Walkinshaw Steve A. , Pascall Angela , Clement-Jones Mark , Dower Michelle , Houghton Gillian , Longworth Heather , Purewal Tej , Tuffnell Derek , Farrar Diane , Syson Jennifer , Butterfield Gillian , Jones Vicky , Palethorpe Rebecca , Germaine Tracey , Habiba Marwan , Lee Debbie , Eniola Olufemi , Blake Lynne , Khan Jane , Cameron Helen M. , Hinshaw Kim , Bargh Amanda , Walton Eileen , Sorinola Olanrewaju , Guy Anna , D’Souza Zoe , Gabriel Rhiannon , Williams Jo , Hollands Heidi , Jibodu Olujimi , Collier Sara , Tottie Pauline , Oxby Claire , Dwyer James , Majoko Franz , Goldring Helen , Jones Sharon , Cresswell Janet , Underwood Louise , Kelly-Baxter Mary , Robinson Rebecca , Anumba Dilly , Chamberlain Anne , Pye Clare , Tower Clare , Woods Sue , Horrocks Lisa , Prichard Fiona , Moorhead Lynsey , Lee Sarah , Stephens Louise , Taylor Cara , Thomas Suzanne , Whitworth Melissa , Myers Jenny , Knox Ellen , Freitas Katie , Kilby Mark , Cotterill Amanda , Abdo Khalil , Rigby Katrina , Butler Julie , Crosfill Fiona , Hughes Sean , Prashar Sanjeev , Soydemir Fatimah , Ashworth Janet , Mycock Lorraine , Smith Jill , Ikomi Amaju , Goodsell Kerry , Byrne Jean , Masuku Maxwell , Pilcher Alice , Khandelwal Meena , Simpkins Gunda , Iavicoli Michelle , Kim Yon Sook , Fischer Richard , Perry Robin , Chang Eugene Y. , Saunders Tamara D. , Oswald Betty W. , Zaks Kristin D. , Rana Sarosh , McCullough Dawn , Sfakianaki Anna , Danton Cheryl , Kustan Erin , Coraluzzi Luisa , How Helen , Waldon Christina , Livingston Jeffrey , Jackson Sherry , Greene Lisa , Shah Dinesh , Tolosa Jorge E. , Rincon Monica , Pereira Leonardo , Lawrence Amy E. , Snyder Janice E. , Armstrong D. Michael , Blue Teresa , Hester Austin , Salisbury Kathryn 
Published: April 2018

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight <10th centile (
P
interaction
=0.005), but more preterm birth (
P
interaction
=0.043), and no effect on perinatal death or high-level neonatal care >48 hours (
P
interaction
=0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks (
P
interaction
=0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes.

Clinical Trial Registration—

URL:
https://www.isrctn.com
. Unique identifier: ISRCTN71416914.