Original Research

Gestation-Specific Vital Sign Reference

Ranges in Pregnancy
Lauren J. Green, BM, BSc, Lucy H. Mackillop, MA, Dario Salvi, PhD, Rebecca Pullon, DPhil,
Lise Loerup, PhD, Lionel Tarassenko, DPhil, Jude Mossop, BA(Hons), Clare Edwards, BSc, Stephen Gerry, MSc,
Jacqueline Birks, MSc, Rupert Gauntlett, MBChB, Kate Harding, FRCOG, Lucy C. Chappell, PhD,
and Peter J. Watkinson, MD

OBJECTIVE: To estimate normal ranges for maternal vital RESULTS: We screened 4,279 pregnant women, 1,041
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signs throughout pregnancy, which have not been well met eligibility criteria and chose to take part. Systolic and
defined in a large contemporary population. diastolic BP decreased slightly from 12 weeks of gesta-
METHODS: We conducted a three-center, prospective, tion: median or 50th centile (3rd–97th centile) 114
longitudinal cohort study in the United Kingdom from (95–138); 70 (56–87) mm Hg to reach minimums of 113
August 2012 to September 2017. We recruited women at (95–136); 69 (55–86) mm Hg at 18.6 and 19.2 weeks of
less than 20 weeks of gestation without significant gestation, respectively, a change (95% CI) of 21.0 (22 to
comorbidities with accurately dated singleton pregnan- 0); 21 (22 to 21) mm Hg. Systolic and diastolic BP then
cies. We measured participants’ blood pressure (BP), rose to a maximum median (3rd–97th centile) of 121
heart rate, respiratory rate, oxygen saturation and tem- (102–144); 78 (62–95) mm Hg at 40 weeks of gestation,
perature following standardized operating procedures at a difference (95% CI) of 7 (6–9) and9 (8–10) mm Hg,
4–6 weekly intervals throughout pregnancy. respectively. The median (3rd–97th centile) heart rate

From the Nuffield Department of Clinical Neurosciences, Nuffield Department of Women’s & Reproductive Health, the Department of Engineering Science, and the
Centre for Statistics in Medicine, University of Oxford, Oxford, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, Guy’s and St Thomas’ NHS
Foundation Trust, London, the Department of Women and Children’s Health, King’s College, London, and the Oxford National Institute for Health Research
Biomedical Research Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
The 4P Study is supported by the NIHR Biomedical Research Centre, Oxford and the NIHR Biomedical Research Centre of Guy’s and St Thomas’ NHS Foundation
Trust, London. Lise Loerup is funded by an RCUK Digital Economy Programme (grant number EP/G036861/1, Oxford Centre for Doctoral Training in Healthcare
Innovation) and the Clarendon Fund. Stephen Gerry is funded by an NIHR Doctoral Fellowship (DRF-2016-09-073). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the manuscript.
Presented at the UK Intensive Care Society State of the Art meeting, December 10–12, 2018, London, United Kingdom; and at the UK Obstetric Anesthetists’
Association meeting, November 7, 2018, London.
The authors thank the significant contribution toward data collection made by research midwives in Oxford (Fenella Roseman), London (Holly Lovell) and Newcastle
(Alison Kimber). Fiona Kumar contributed to the study design. The authors also thank Professor Stephen Kennedy for his review of the manuscript, and the whole
INTERBIO-21st Study team for their generosity in contributing maternal vital sign data to the 4P Study.
Each author has confirmed compliance with the journal’s requirements for authorship.
Corresponding author: Lauren J. Green, BM, BSc, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; email:
[email protected].
Financial Disclosure
Peter J. Watkinson and Lionel Tarassenko hold grants from the National Institute for Health Research (NIHR). Lauren J. Green, Lucy H. Mackillop, Lionel Tarassenko,
Peter J. Watkinson, Jude Mossop, Clare Edwards, Jacqueline Birks and Dario Salvi receive funding from NIHR Biomedical Research Centre, Oxford. Peter J. Watkinson
and Lucy H. Mackillop work part-time for Sensyne Health and have share options in Sensyne Health. Lise Loerup is currently an employee of Boston Consulting Group.
Lionel Tarassenko is a non-executive Director of Sensyne Health and holds share options in the company, and he is a non-executive Director of Oxehealth and holds shares
in the company. Sensyne Health markets the System for Electronic Notification and Documentation, which allows recording of adult vital signs and early warning score
calculation. It also markets an application for Gestational Diabetes management. Oxehealth markets a system to provide contact-free heart and breathing rate monitoring.
Neither company had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors did not report any
potential conflicts of interest.
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Obstetricians and Gynecologists. This is an open access
article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
ISSN: 0029-7844/20

VOL. 135, NO. 3, MARCH 2020 OBSTETRICS & GYNECOLOGY 653

was lowest at 12 weeks of gestation: 82 (63–105) beats practice. We included a pragmatic population, repre-
per minute (bpm), rising progressively to a maximum of sentative of women who would be monitored using
91 (68–115) bpm at 34.1 weeks. SpO2 decreased from 12 a modified obstetric early warning score system
weeks of gestation: median (3rd–97th centile) 98% (94– derived from the normal vital sign ranges obtained.
99%) to 97% (93–99%) at 40 weeks. The median (3rd– The primary objective of the Pregnancy Physiol-
97th centile) respiratory rate at 12 weeks of gestation ogy Pattern Prediction (4P) study was to develop
was 15 (9–22), which did not change with gestation. a database of prospective vital sign measurements
The median (3rd–97th centile) temperature at 12 weeks using standardized measurement techniques through-
of gestation was 36.7 (35.6–37.5)˚C, decreasing to
out pregnancy.26 Estimates of population distributions
a minimum of 36.5 (35.3–37.3)˚C at 33.4 weeks.
and associated centiles were derived from this data-
CONCLUSION: We present widely relevant, gestation- base. Secondary objectives of developing a centile-
specific reference ranges for detecting abnormal BP, based early warning score and investigating new pat-
heart rate, respiratory rate, oxygen saturation and tem- terns in vital sign data will be explored in further
perature during pregnancy. Our findings refute the
work.
existence of a clinically significant BP drop from 12
weeks of gestation. METHODS
CLINICAL TRIAL REGISTRATION: ISRCTN, ISRCTN10838017. This work is reported following the STROBE
(Obstet Gynecol 2020;135:653–64) (Strengthening the Reporting of Observational Stud-
DOI: 10.1097/AOG.0000000000003721 ies in Epidemiology) guidelines.27 We registered the
study (https://doi.org/10.1186/ISRCTN10838017).

S uccessive inquiries into maternal deaths call for an

evidence-based early warning score to facilitate
earlier recognition and treatment of the unwell preg-
Detailed methods are reported in the published pro-
tocol26 and in brief here. We conducted a multicenter,
longitudinal, observational, cohort study across three
nant woman.1–4 Recognition is complicated by the centers in the United Kingdom. We collected vital
normal physiologic changes in vital signs during preg- sign data during the antenatal, intrapartum, and post-
nancy.1 Changes in normal ranges for blood pressure natal periods. Here we present data from the antenatal
(BP) through pregnancy have been derived from rou- period.
tinely collected data—which may be biased by the rea- Recruitment commenced in August 2012, and
son for collection.5 Blood pressure trends without collection of vital sign data was completed in August
normal ranges have been investigated in smaller stud- 2017. The study started in Oxford as a substudy of the
ies.6 Substantially fewer data exist for heart rate,7–11 INTERBIO-21st Fetal Study, approved by Oxford
temperature,12,13 respiratory rate14,15 and oxygen sat- South Central C Research Ethics Committee
uration14,16 patterns during pregnancy. (REC):08/H0606/139),28,29 and then expanded to
Parameters recommended internationally for include two additional centers (Newcastle and Lon-
normal ranges of vital signs in pregnancy ([United don, South East Coast–Brighton and Sussex
Kingdom, Confidential Enquiry into Maternal and REC:14/LO/1312) continuing after completion of
Child Health1; Ireland, Irish Maternity Early Warn- INTERBIO-21st (December 2015).
ing System17; United States, National Partnership We approached women when they attended the
for Maternal Safety18]) and thresholds used for ultrasound department or antenatal clinic at three
modified obstetric early warning scores19–22 are university hospitals before 20 weeks of gestation.
not gestation-specific or evidence-based, but based Women were eligible if they were aged 16 years or
on expert opinion with wide local, national and older, with a singleton pregnancy, and fell within
international variation. category 1 of the American Society of Anesthesiolo-
Using robust estimates of the outer centiles of gists’ classification of physical status before pregnancy
vital sign distributions to generate early warning (“a normal healthy patient without any clinically
scores is reliable in nonpregnant adults.23,24 The important comorbidity and without clinically signifi-
approach may be particularly useful for pregnancy, cant past or present medical history”30). Gestational
where event rates are low. However, there are insuf- age was determined by ultrasound measurement of
ficient published data to generate evidence-based, ges- crown-rump length before 14 weeks of gestation. Full
tation-specific reference ranges for vital signs.25 eligibility criteria can be found in Appendix 1, avail-
A large-scale, contemporary prospective data set able online at http://links.lww.com/AOG/B746.
of vital signs in pregnancy is needed to provide The primary outcome was gestation-specific refer-
gestation-specific normal ranges for use in clinical ence ranges comprising centile distributions for vital

654 Green et al Vital Sign Reference Ranges for Pregnancy OBSTETRICS & GYNECOLOGY
 parameters: BP, heart rate, SpO2, temperature, and
respiratory rate. We measured all vital signs following
study standard operating procedures.26 Blood pressure
was measured with an automated BP monitor validated
for use in pregnancy (Microlife 3BT0-A (2)/WatchBP
Home). Heart rate and oxygen saturation were mea-
sured with a Bluetooth-enabled pulse oximeter (Wris-
tOx2 3150).
Temperature was measured with a tympanic
thermometer (Genius 2). Temperature was also mea-
sured with a Bluetooth enabled tympanic thermome-
ter (Fora IRb 20b) in the INTERBIO-21st subgroup.
Fig. 1. Flowchart of participants through the study. Respiratory rate was recorded using two different
Green. Vital Sign Reference Ranges for Pregnancy. Obstet Gynecol methods. Trained midwives observed chest wall
2020. movement over 15 seconds. From October 2015
onward, midwives also tapped in time with observed
signs through pregnancy. We conducted sensitivity respiratory rate for 1 minute using bespoke software
analyses to assess changes in performance of the sensors on an Android tablet. Research midwives entered
used to measure each vital sign over time. We assessed vital sign data (or in the case of Bluetooth-enabled
differences in methods for recording respiratory rate, devices, automatically transmitted) onto a study-
agreement between two thermometers used and the specific android tablet computer (Samsung Galaxy
effect of duplicate measurement. Tab 4.026).
We collected vital sign data at clinic visits every 4– We collected demographic information (age,
6 weeks31 throughout pregnancy for five physiologic height, weight, self-reported ethnicity, number of

Table 1. Baseline Maternal Characteristics

Study Center
Characteristic Oxford (n5779 [74.8]) London (n5105 [10.1]) Newcastle (n5157 [15.1]) Total (N51,041)

Age (y) 31.464.8 33.964.7 30.865.2 31.564.9

Weight (kg) 67.6613.0 69.9615.6 70.8616.2 68.3613.9
BMI (kg/m2) 24.664.3 25.465.4 2665.7 24.964.7
BMI category (kg/m2)
Normal (18.5–24.9) 467 (60.0) 63 (60.0) 81 (51.6) 611 (58.7)
Overweight (25.0–29.9) 220 (28.2) 22 (21.0) 43 (27.4) 285 (27.4)
Obese (30 or higher) 92 (11.8) 20 (19.0) 33 (21.0) 145 (13.9)
GA at first visit (wk) 12.662.5 14.462.4 15.261.0 13.162.4
Nulliparous 332 (42.6) 60 (57.1) 68 (43.3) 460 (44.2)
Ethnicity
White 668 (85.8) 71 (67.6) 150 (95.5) 889 (85.4)
Asian 34 (4.4) 13 (12.4) 5 (3.2) 52 (5.0)
African or Caribbean 6 (0.8) 17 (16.2) 0 (0) 23 (2.2)
Mixed 14 (1.8) 3 (2.9) 1 (0.6) 18 (1.7)
Other 57 (7.3) 1 (1.0) 1 (0.6) 59 (5.7)
Smoker 62 (8.0) 6 (5.7) 11 (7.0) 79 (7.6)
Anemia* 3 (0.4) 3 (2.9) 1 (0.6) 7 (0.7)
Pregestational diabetes 2 (0.3) 1 (1.0) 3 (1.9) 6 (0.6)
Preexisting hypertension† 16 (2.1) 0 (0) 1 (0.6) 17 (1.6)
Cardiac disease‡ 11 (1.4) 1 (1) 0 (0) 12 (1.2)
Preexisting renal disease 18 (2.3) 2 (1.9) 5 (3.2) 24 (2.3)
BMI, body mass index; GA, gestational age.
Data are mean6SD or n (%).
* Hb less than 110 g/L.
†
Unmedicated.
‡
Nonischemic noncongenital.

VOL. 135, NO. 3, MARCH 2020 Green et al Vital Sign Reference Ranges for Pregnancy 655
Table 2. Pregnancy Complications and Perinatal Outcomes

Study Center
Oxford (n5762 London (n596 Newcastle (n5146 Total
Complications and Outcomes [75.9]) [9.6]) [14.5]) (n51,004)

Gestational diabetes 26 (3.4) 4 (4.2) 8 (5.5) 38 (3.8)

Gestational hypertension 44 (5.8) 1 (1.0) 1 (0.7) 46 (4.6)
Preeclampsia 12 (1.6) 0 (0) 7 (4.8) 19 (1.9)
Severe preeclampsia, HELLP, eclampsia 2 (0.3) 0 (0) 3 (2.1) 5 (0.5)
Termination of pregnancy at less than 12 wk 0 (0) 0 (0) 0 (0) 0 (0)
Termination of pregnancy at more than 12 wk 3 (0.4) 0 (0) 0 (0) 3 (0.3)
Miscarriage at less than 12 wk 1 (0.1) 0 (0) 0 (0) 1 (0.1)
Late miscarriage 12–24 wk 8 (1) 1 (1.0) 0 (0) 9 (0.9)
Intrauterine death or stillbirth at more than 24 wk 3 (0.4) 0 (0) 0 (0) 3 (0.3)
Preterm delivery at less than 37 0/7 wk 50 (6.7) 4 (4.2) 13 (8.9) 67 (6.7)
Spontaneous vaginal birth 476 (63.6) 53 (56.4) 91 (64.5) 620 (59.6)
Assisted vaginal birth 133 (17.3) 14 (14.9) 11 (7.8) 158 (15.2)
Cesarean birth 138 (18.4) 28 (29.5) 39 (27.7) 205 (19.7)
Birth weight at 37 0/7 wk or more (g) 3,4096534 3,4426573 3,4506504 3,4186533
Term low birth weight (less than 2,500 g; 20/702 (2.8) 2/92 (2.2) 4/137 (2.9) 26/931 (2.8)
37 0/7 wk or more)
HELLP, hemolysis, elevated liver enzymes, low platelet count.
Data are n (%) or mean6SD.

previous pregnancies, smoking status), past medical participant inconvenience, duplicate measurements
and obstetric history, current health status, pregnancy- were reviewed by study statisticians to decide when
related health and current medications at the initial an adequate number of duplicate measurements had
assessment. At each follow-up appointment we col- been collected.
lected assessments of smoking status, current health Our sample size determination may be found in
status, pregnancy related health and current medica- Appendix 2 (available online at http://links.lww.com/
tions. We extracted medical and obstetric history AOG/B747) and the published protocol.26 In brief,
from the participants’ notes. a sample size of 1,000 women would achieve an SE
If participants did not respond to contact by of 0.05*SD at the 2.5 and 97.5 centiles, and even
research midwives during the study, they were treated greater precision at the less extreme centiles. Ade-
as withdrawn after the third failed contact attempt. quate precision was also met for any subgroup analy-
Data already collected from withdrawn participants sis; for example, a sample size of 300 women would
were included in the final analysis, unless explicitly achieve an SE of 0.1*SD at the 2.5 and 97.5 centiles.
requested otherwise. Vital sign data from all participants were included
Trained research midwives undertook all antena- in the primary analysis. We constructed smoothed
tal observations and extracted all hospital data fol- centiles for systolic and diastolic BP, heart rate, SpO2,
lowing study standard operating procedures. temperature and respiratory rate by gestational age.
Research midwife coordinators performed frequent We constructed gestation-specific reference ranges
site visits to carry out midwife training and address comprising smoothed centiles for vital sign distribu-
any recruitment and equipment issues. tion (3rd, 10th, 50th, 90th and 97th as used by the
Vital sign measurements taken for the study were World Health Organization Multicentre Growth Ref-
not included in the clinical record and were not erence Study,32,33 with corresponding 95% CIs) for all
communicated to the clinical team unless BP reached women. We presented centiles from 12 to 40 weeks of
predefined values (systolic 140 mm Hg or higher or gestation (because there were relatively few data at
diastolic 90 mm Hg or higher) according to study less than 12 and greater than 40 weeks of gestation)
standard operating procedures. for each vital sign graphically and tabulated at fort-
Duplicate measurements were recorded for a sub- nightly intervals, along with associated 95% CIs.
set of participant visits to document the effect of using We used statistical methods to generate gesta-
only the first recorded measurement for each vital tional age-specific centiles following those used in the
sign parameter (as in clinical practice). To minimize INTERGROWTH-21st Project for fetal growth.34–37

656 Green et al Vital Sign Reference Ranges for Pregnancy OBSTETRICS & GYNECOLOGY
Fig. 2. Smoothed centiles for systolic
blood pressure (upper line and cen-
tiles) and diastolic blood pressure
(lower line and centiles) in mm Hg.
Green. Vital Sign Reference Ranges for
Pregnancy. Obstet Gynecol 2020.

Once enrolled, we did not exclude women who devel- In this “restrictive” population, we excluded measures
oped conditions that might affect their vital signs (to from women who developed a severe maternal con-
generate a pragmatic, representative sample of preg- dition during pregnancy (severe preeclampsia; hemo-
nant women, maximizing the clinical applicability of lysis, elevated liver enzymes, and low platelet count
centiles generated). We explored different statistical [HELLP] syndrome; or eclampsia), from the time of
methods to achieve the best fit to the data (see Appen- diagnosis onward, in line with previous work.38 We
dix 2, http://links.lww.com/AOG/B747). conducted a post hoc analysis using these definitions
We expected some participants would become lost in comparison with the full “pragmatic” population.
to follow-up or have missing measures. We included To explore whether the small reduction in heart
these participants in the analysis, unless all data were rate near term resulted from women with higher heart
missing. We compared agreement between Fora and rates giving birth earlier, we conducted a post hoc
Genius thermometers using a Bland-Altman plot to analysis with all women who delivered at less than 37
assess whether it was possible to pool measures. We also weeks of gestation excluded. We undertook a prespe-
compared data from the counting and tapping methods cified subgroup analysis including only nulliparous
for recording respiratory rate before pooling. women. Participants provided informed written con-
We conducted sensitivity analyses to assess sent and could withdraw from the study at any time.
changes in sensor performance over time.
To explore whether limiting the population to RESULTS
those of optimal health would affect results, we We screened 4,279 women between August 1, 2012,
defined a “restrictive” population of women aged and December 28, 2016, of whom 1,054 agreed to
younger than 40 years with body mass indexes (BMIs, take part. Thirteen women subsequently withdrew
calculated as weight in kilograms divided by height in consent for any data to be used and were excluded
meters squared) between 18.5 and 29.9, who did not completely. This provided a total pragmatic study
smoke and did not have any medical comorbidities. cohort of 1,041 women who contributed antenatal

VOL. 135, NO. 3, MARCH 2020 Green et al Vital Sign Reference Ranges for Pregnancy 657
 Fig. 3. Smoothed centiles for heart
rate in beats per minute.
Green. Vital Sign Reference Ranges for
Pregnancy. Obstet Gynecol 2020.

vital sign data (Fig. 1). Delivery information was in 36% (2,125/5,890 from 477 women). Temperature
unavailable for 37 women, who were either lost to was recorded at 97% of visits (5,742/5,890), using
follow-up (15 women) or discontinued participation a Genius device at 93% (5,507/5,890for ad a Fora
(22 women) during the study period. Within this device at 55% of visits (3,225/5,890). An abnormal
group, 36 women provided data at 12 weeks of gesta- BP recording necessitating referral to the woman’s
tion, 24 at 24 weeks, 12 at 28 weeks, and two at 32 usual clinical team occurred at 0.2% of visits (11/
weeks, beyond which they no longer participated. 5,863 observations; 10/1,041 women).
Demographic characteristics of the study cohort Delivery information was available for 1,004
were similar across sites (Table 1). Mean (SD) gesta- women. Table 2 details pregnancy outcomes and peri-
tional age at the first antenatal visit was 13.2 (2.5) natal events within the study cohort.
weeks; maternal age 31.5 (4.9) years, BMI 24.9 (4.7), Systolic BP decreased from 12 weeks of gestation:
and 44.2% (460/1,041) were nulliparous. median, or 50th centile (3rd–97th centile) 114 (95–
The median number of visits per woman where 138) mm Hg to reach its nadir of 113 (95–136) mm
vital signs were taken was 6 (interquartile range 5–7). Hg at 18.6 weeks, a change (95% CI) of 21.0 (22 to 0)
In total, vital sign data were recorded at 5,890 visits. mm Hg. Systolic BP then rose progressively from 19
Most women, (982/1,041, 94%) missed no more than weeks of gestation to a maximum median of (3rd–
one expected visit, with 926/1,041 (89%) always 97th centile) 121 (102–144) mm Hg at 40 weeks, a dif-
achieving expected visits within 6 weeks of each other ference (95% CI) of 7 (6–9) mm Hg from minimum to
(for baseline characteristics of women with missing maximum systolic BP.
visits see Appendix 3, available online at http:// Diastolic BP decreased from 12 weeks of gesta-
links.lww.com/AOG/B748). Blood pressure was re- tion: median (3rd–97th centile) 70 (56–87) mm Hg to
corded at nearly every visit (5,863/5,890), SpO2 at its nadir of 69 (55–86) mm Hg at 19.2 weeks, a change
96% of visits (5,651/5,890) and respiratory rate at (95% CI) of 21 (22 to 21) mm Hg. Diastolic BP
91% of visits (5,370/5,890), using the tapping method subsequently increased to a maximum median of

658 Green et al Vital Sign Reference Ranges for Pregnancy OBSTETRICS & GYNECOLOGY
Fig. 4. Smoothed centiles for respi-
ratory rate from tapping technique.
Green. Vital Sign Reference Ranges for
Pregnancy. Obstet Gynecol 2020.

(3rd–97th centile) 78 (62–95) mm Hg at 40 weeks, SpO2 decreased from 12 weeks of gestation:

a difference (95% CI) of 9 (8–10) mm Hg from mini- median (3rd–97th centile) 98% (94–99%) to reach
mum to maximum diastolic BP. Figure 2 represents a minimum of 97% (93–99%) at 40 weeks, a change
smoothed gestation-specific centiles for systolic and (95% CI) of 21.0 (21 to 21)% (Fig. 5).
diastolic BP for the 3rd, 10th, 50th, 90th, and 97th Temperature measurements with both Fora and
centiles. Genius devices were recorded at 2,990 visits. The
The median (3rd–97th centile) heart rate was low- Bland-Altman plot showed wide limits of agreement,
est at 12 weeks of gestation—82 (63–105) beats around 2°C (Appendix 5, available online at http://
per minute (bpm). Median (3rd–97th centile) heart links.lww.com/AOG/B750). Therefore, it was not
rate rose progressively until 34.1 weeks of gestation appropriate to pool data from the two thermometers.
to a maximum of 91 (68–115) bpm, a difference (95% For the Genius device, median (3rd–97th centile) tem-
CI) of 9 (8–10) bpm. Heart rate then decreased perature decreased from its maximum at 12 weeks of
slightly to a median (3rd–97th centile) of 89 (65– gestation of 36.7 (35.6–37.5)°C to a minimum of 36.5
114) at 40 weeks, a difference (95% CI) of 22 (23 (35.3–37.3)°C at 33.4 weeks, a change (95% CI) of
to 0) bpm (Fig. 3). only 20.2 (20.2 to 20.1)°C. Temperature subse-
There was no significant change in respiratory quently plateaued until 40 weeks of gestation: median
rate with gestation irrespective of the method used. (3rd–97th centile) 36.6 (35.4–37.4)°C at 40 weeks (Fig.
Using the tapping technique, the median (3rd–97th 6). Results for the Fora device are shown in Appendix
centile) respiratory rate at 12 weeks of gestation was 4 (http://links.lww.com/AOG/B749).
15 (9–22) breaths per minute and 15 (9–23) breaths For each vital sign measured, gestation-specific
per minute at 40 weeks (Fig. 4). Figures and gestation- values for the smoothed centiles and a smoothed
specific values for respiratory rate from manual count- gestation-specific centile plot with associated 95%
ing are in Appendix 4, available online at http://links. CI can be found in Appendix 4 (http://links.lww.
lww.com/AOG/B749. com/AOG/B749). Duplicate measurements were

VOL. 135, NO. 3, MARCH 2020 Green et al Vital Sign Reference Ranges for Pregnancy 659
 Fig. 5. Smoothed centiles for oxygen
saturation in percentage.
Green. Vital Sign Reference Ranges for
Pregnancy. Obstet Gynecol 2020.

recorded for a subset of 273 participant visits DISCUSSION

(4.6%). There were no clinically meaningful differ- Our multicenter study includes longitudinal data from
ences between first and second measures of vital more than 1,041 women. From these data we pro-
signs in pregnancy, so duplicate readings were not duced evidence-based, gestation-specific centiles for
continued (Appendix 6, available online at http:// vital signs during pregnancy. Our findings refute
links.lww.com/AOG/B751). We found no evidence a large drop in BP during pregnancy after week 12,
of systematic sensor performance alteration over when women are usually first measured. Textbooks
time (see Appendix 7, available online at http://
suggest a 10–15-mm Hg drop in diastolic BP39–41 dur-
links.lww.com/AOG/B752).
ing pregnancy. Evidence supporting this BP drop
Applying the “restrictive” population definitions
came from small single center studies6,42–45 or larger
reduced the cohort to 595/1,041 women (Appendix 8,
birth cohorts from one geographical region46,47 com-
available online at http://links.lww.com/AOG/B753).
monly using routinely collected,6,44 nonstandardized
Although systolic and diastolic BP centiles were
numerically slightly lower in the restrictive cohort measurements42,45 with equipment not ratified for use
(higher BPs having been excluded) the relatively nar- in pregnancy.6,42–44,46–48 Our study concurs with
row CIs mainly overlapped. Centiles for other vital recent publications, including a recently published
signs were similar to the “pragmatic” cohort. systematic review7,25,49 that challenge this teaching,
Blood pressures from 460 nulliparous women were and strongly supports the resulting call to abandon
slightly higher than those from the 581 parous women this notion.50 Several studies suggest a drop occurs
(Appendix 9, available online at http://links.lww.com/ from prepregnancy levels in the first few weeks of
AOG/B754). Excluding women who delivered before pregnancy.8,48,51,52 However, preconception BPs are
37 weeks of gestation did not change the shape of the not normally available in clinical practice. Our find-
heart rate centiles (Appendix 10, available online at ings allow clinicians to recognize that relative hypo-
http://links.lww.com/AOG/B755). tension from the first BP in pregnancy may warrant

660 Green et al Vital Sign Reference Ranges for Pregnancy OBSTETRICS & GYNECOLOGY
Fig. 6. Smoothed centiles for tem-
perature (˚C) from a tympanic ther-
mometer.
Green. Vital Sign Reference Ranges for
Pregnancy. Obstet Gynecol 2020.

investigation. The third centile for systolic BP was our systolic BPs are similar, providing reassurance that
never less than 94 mm Hg and was greater than our BP ranges will be valid in routine clinical practice.
96 mm Hg after 30 weeks of gestation in all groups. It is commonly taught that heart rate increases by
These thresholds are above the less than 90 mm Hg 10–15 bpm from the first trimester onward.40,56 An
used to recognize sepsis in pregnancy53,54 and modi- increase in heart rate of 20–25% is reported by studies
fied obstetric early warning score charts trigger for which compare heart rate in pregnancy to prepreg-
escalation.1,17,18,55 The BP rise toward the end of nancy baseline.8,51,57 However, prepregnancy vital
pregnancy suggests gestational threshold adjustment sign data are not usually available. We demonstrated
could improve detection of deteriorating mothers. a smaller increase in heart rate of 9 bpm between 12
Before our study, the best evidence for longitudi- weeks of gestation and the third trimester. This is con-
nal reference ranges for BP in normal pregnancy sistent with our recent systematic review, that also
probably came from the Avon Longitudinal Study of highlighted that the outer centiles of heart rate in preg-
Parents and Children, a large, single-center cohort nancy have not been demonstrated in large modern
study using data from 20 years ago.5 The Avon Lon- studies.25 From 18 weeks of gestation, heart rates of
gitudinal Study of Parents and Children reported more than 100 bpm (more than 105 bpm from 28
a small (1.7 mm Hg) nadir of systolic BP at 17–18 weeks of gestation) occurred in more than 10% of
weeks of gestation, similar to the 1-mm Hg drop at observations taken in healthy pregnancy. However
18.6 weeks of gestation in our multicenter cohort. the 97th centile for heart rate increased from 105
The subtle nadir in diastolic BP was also similar in both bpm at 12 weeks of gestation to 115 at 36 weeks,
studies. The Avon Longitudinal Study of Parents and suggesting that a 120 bpm threshold for the high-
Children relied on BPs documented in women’s rou- risk threshold for modified obstetric early warning
tine obstetric records, rather than measuring BP with score escalation1,17,55 may be too high.
validated equipment following a standard operating Centiles for respiratory rate in pregnancy have
procedure. Despite this, the median and ranges of not been determined in a large modern cohort,

VOL. 135, NO. 3, MARCH 2020 Green et al Vital Sign Reference Ranges for Pregnancy 661
though our finding that respiratory rate does not similar BMI to previous U.K. findings.62 Women were
change with gestation is supported by a longitudinal predominantly of Caucasian ethnicity (85.2%), equiva-
study of 20 women.14 Our work shows that a respira- lent to the most recent England and Wales census data
tory rate of more than 22 breaths per minute (as used (86%).63 Our population therefore appears representa-
in the quick Sepsis Related Organ Failure Assessment tive and applicable to clinical practice. Extending to an
tool58) occurs in fewer than 3% of observations in international population would improve external valid-
normal pregnancy, suggesting this threshold could ity for other settings.
translate from other medical practice. Current moder- We present widely relevant, gestation-specific
ate and high-risk thresholds for respiratory rate of 21– reference ranges for systolic and diastolic BP, heart
24 and 25 breaths per minute or more (as advocated rate, respiratory rate, oxygen saturation and temper-
by the UK Sepsis Trust,54 the Irish Maternity Early ature. Our findings refute the idea that a clinically
Warning System17 and the Scottish Patient Safety Pro- significant first-to-mid trimester drop in BP is normal
gramme55) may more accurately detect women at risk and suggest evidence-based ranges for other vital
of sepsis than moderate1 and high-risk1,18 thresholds signs. These reference ranges can be used to facilitate
of more than 21–30 and more than 30 breaths early recognition of unwell pregnant women. The
per minute. differences from current accepted values used to
We identified a small drop in SpO2 during preg- detect deterioration in pregnant women emphasize
nancy. Previous small studies suggest a modest reduc- the need for robustly derived ranges for a modified
tion in SpO2 between the second and third trimester59 obstetric early warning score system.
and oxygen partial pressure (PaO2) across gestation.14
The lower thresholds of oxygen saturation have not
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664 Green et al Vital Sign Reference Ranges for Pregnancy OBSTETRICS & GYNECOLOGY