International gestational age-specific centiles for blood pressure in pregnancy from the INTERGROWTH-21st Project in 8 countries: A longitudinal cohort study
Authors: Green Lauren J. , Kennedy Stephen H. , Mackillop Lucy , Gerry Stephen , Purwar Manorama , Staines Urias Eleonora , Cheikh Ismail Leila , Barros Fernando , Victora Cesar , Carvalho Maria , Ohuma Eric , Jaffer Yasmin , Noble J. Alison , Gravett Michael , Pang Ruyan , Lambert Ann , Bertino Enrico , Papageorghiou Aris T. , Garza Cutberto , Bhutta Zulfiqar , Villar José , Watkinson Peter ,   for the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st)
Published: April 2021

Background
Gestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure.

Methods and findings
Secondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at <14 weeks, then every 5 ± 1 weeks until delivery.
We enrolled 4,607 (35%) women of 13,108 screened. The mean maternal age was 28·4 (standard deviation [SD] 3.9) years; 97% (4,204/4,321) of women were married or living with a partner, and 68% (2,955/4,321) were nulliparous. Their mean body mass index (BMI) was 23.3 (SD 3.0) kg/m2. Systolic blood pressure was lowest at 12 weeks: Median was 111.5 (95% CI 111.3 to 111.8) mmHg, rising to a median maximum of 119.6 (95% CI 118.9 to 120.3) mmHg at 40 weeks’ gestation, a difference of 8.1 (95% CI 7.4 to 8.8) mmHg. Median diastolic blood pressure decreased from 12 weeks: 69.1 (95% CI 68.9 to 69.3) mmHg to a minimum of 68.5 (95% CI 68.3 to 68.7) mmHg at 19+5 weeks’ gestation, a change of −0·6 (95% CI −0.8 to −0.4) mmHg. Diastolic blood pressure subsequently increased to a maximum of 76.3 (95% CI 75.9 to 76.8) mmHg at 40 weeks’ gestation. Systolic blood pressure fell by >14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study’s main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements.

Conclusions
Our findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.