Objective
Pregnancy interventions to limit gestational weight gain (GWG) have been proposed as a means of preventing hypertensive disorders of pregnancy (HDP); however, it is currently unclear whether GWG has a causal influence on the development of HDP. Thus, we aimed to determine whether GWG in early pregnancy is a risk factor for preeclampsia and gestational hypertension and whether GWG precedes the increases in blood pressure in normotensive women across pregnancy.
Study Design
We examined repeat antenatal clinic measurements of weight and blood pressure (median of 12 and 14 per woman, respectively) of 12,522 women in the Avon Longitudinal Study of Parents and Children.
Results
Greater prepregnancy weight was associated with an increased risk of gestational hypertension and preeclampsia per 10 kg of prepregnancy weight: odds ratio (OR), 1.80; 95% confidence interval (CI), 1.70–1.91 and OR, 1.71; 95% CI, 1.49–1.95, respectively, for women weighing 90 kg or less before pregnancy; OR, 1.24; 95% CI, 1.03–1.49 and OR, 1.61; 95% CI, 1.18–2.19 for women weighing more than 90 kg. Fully adjusted odds ratios for gestational hypertension and preeclampsia per 200 g per week GWG up to 18 weeks were OR, 1.26; 95% CI, 1.16–1.38 and OR, 1.31; 95% CI, 1.07–1.62. In normotensive women, GWG in early pregnancy was associated positively with blood pressure change in midpregnancy and negatively with blood pressure change in late pregnancy. In all gestational periods, GWG was positively associated with concurrent blood pressure change. However, there was no evidence that blood pressure changes in any period were associated with subsequent GWG.
Conclusion
These findings suggest that GWG in early pregnancy may be a potential target for interventions aimed at reducing the risk of HDP.
See Journal Club, page 391
The hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, remain a leading cause of maternal and perinatal mortality and morbidity worldwide and can affect up to 10% of pregnancies. At present, effective treatments are limited, and consequently, there is considerable interest in their prevention. Prepregnancy maternal adiposity is the strongest modifiable risk factor for HDP and thus provides a potential means of prevention; however, it is increasingly recognized that reducing overweight/obesity in all women of reproductive age is extremely difficult. As a result there has been increased interest in the extent to which gestational weight gain (GWG) may influence HDP and hence provide a potential target for interventions aimed at reducing its risk.
Several studies have shown that HDP are more likely to develop in women who have greater GWG ; however, most of these studies have important methodological limitations. The primary concern is that previous studies have related total GWG across pregnancy to the risk of HDP. This is problematic because women who develop HDP are more likely to experience edema during pregnancy than women who remain normotensive, and this in turn may result in greater GWG. Therefore, a positive association of total GWG with HDP could represent increased edema in women with HDP, causing greater weight gain, rather than greater GWG influencing increases in blood pressure. Furthermore, although a recent metaanalysis of interventions designed to limit GWG did show a reduction in HDP, this could be explained by the treatment of gestational diabetes mellitus that occurred in the 2 largest studies contributing to the metaanalysis.
Therefore, clarification of whether greater GWG precedes HDP and therefore could be a potential causal risk factor is urgently needed. The primary aim of this study was to examine whether GWG up to 18 weeks’ gestation is associated with the subsequent development of HDP. GWG prior to 18 weeks’ gestation, the time of the nadir in blood pressure, is unlikely to be affected by edema caused by HDP because it occurs before blood pressure begins to increase, and generally clinical edema does not occur until the second half of pregnancy.
To further examine whether GWG influences blood pressure in pregnancy, we also investigated whether greater GWG in different periods of pregnancy precedes greater increases in blood pressure. In this second analysis, we excluded women with HDP to exclude the possibility that the relationships are explained by changes in weight caused by HDP.
Materials and Methods
The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective birth cohort study investigating the health and development of children. The study has been described in full elsewhere and on the website (Available at: www.bris.ac.uk/alspac . Accessed March 20, 2013). Women with expected delivery dates between April 1, 1991, and Dec. 31, 1992, who were living in a defined area of Avon during their pregnancy were eligible for recruitment. Ethical approval was obtained from the ALSPAC Law and Ethics Committee and from the National Health Service local ethics committee.
A total of 14,541 women were enrolled, 13,678 women had a singleton live birth, and 13,461 of these had data abstracted from obstetric records. We excluded women who reported having a previous diagnosis of hypertension outside pregnancy (n = 445), leaving 13,016 women of whom 12,522 had at least 1 measurement of blood pressure and weight during pregnancy.
Antenatal blood pressure and weight measurements
All weight and blood pressure measurements (median [interquartile range] per woman: 12 [10–14] and 14 [11–16], respectively) taken routinely as part of antenatal care by midwives or obstetricians were abstracted from obstetric records by 6 trained research midwives. There was no between-midwife variation in the mean values of the data abstracted, and error rates were consistently less than 1% in repeated data entry checks.
Gestational age at delivery was calculated as the difference between the delivery date and the mother’s reported last menstrual period date or updated if ultrasound information was available, which led to a reassessment of gestation. At the time of recruitment, first-trimester ultrasound gestational age dating was not routine clinical practice, and the information abstracted from clinical records did not indicate which few women had their gestational age adjusted.
HDP was defined according to International Society for the Study of Hypertension in Pregnancy criteria of systolic blood pressure (SBP) of 140 mm Hg or greater or diastolic blood pressure (DBP) of 90 mmHg or greater, measured on 2 occasions after 20 weeks’ gestation for gestational hypertension and the same criteria in conjunction with proteinuria of at least 1+ on dipstick testing for preeclampsia.
Prepregnancy weight was obtained from the predicted weight at 0 weeks’ gestation from multilevel models based on the antenatal weight measurements (see the following text). This correlated highly with self-reported prepregnancy weight from a questionnaire administered during pregnancy (r = 0.94). Absolute weight gain was calculated by subtracting the predicted weight at 8 weeks (because there were few measurements prior to this time) from the predicted weight at 40 weeks’ gestation, using a multilevel model for weight change across pregnancy including women with term pregnancies (see the following text) and was then categorized according to Institute of Medicine (IOM) recommendations ( Appendix ; Supplementary Table 1 ). Consistent results to those presented here for associations of IOM categories with HDP were found if self-reported prepregnancy weight and the last antenatal weight measurement (in which this was after 37 weeks) were used to define absolute weight gain.
Maternal characteristics
Maternal age at delivery and offspring sex were abstracted from obstetric records. Maternal height, parity, highest educational qualification, and smoking status were obtained from questionnaires administered during early pregnancy. Prepregnancy body mass index (BMI) was calculated as predicted prepregnancy weight (kilograms)/self-reported height (meters) squared and classified according to the World Health Organization categories ( Supplementary Table 1 ). Smoking status was classed as never for women who did not smoke immediately prior to or during pregnancy, before pregnancy/first trimester for women who smoked only immediately prior to pregnancy or in the first 3 months of gestation, or throughout for women who continued to smoke after the first trimester.
Statistical analysis
IOM categories of GWG and risk of HDP
For women with complete data on IOM categories of GWG and covariates (n = 9596), we used a multinomial regression model to assess the risk of developing gestational hypertension and preeclampsia (with normotensive women as the comparison group) by the IOM category of GWG, adjusting for prepregnancy BMI, maternal age, parity, smoking, education, and sex of offspring.
Early pregnancy GWG and risk of HDP
Using all weight measurements up to 18 weeks’ gestation for women with at least 1 weight measurement prior to this time (n = 11,760), we developed a multilevel model for the change in weight with gestational age, using a linear slope. The model had 2 levels: measurement occasion (occasion level) within woman (individual level); and 2 individual-level random effects representing weight at 0 weeks (the intercept; referred to as prepregnancy weight) and average GWG per week up to 18 weeks. The individual-level random effects were then used as exposure variables in multinomial logistic regression models.
The outcome variable had 3 categories: normotensive (comparison group), gestational hypertension, and preeclampsia. We adjusted for maternal height, age, parity, smoking, education, and offspring sex, and to examine the exposure of GWG up to 18 weeks, we additionally adjusted for prepregnancy weight. We tested for nonlinearity in these associations using fractional polynomials, and any nonlinear relationships were approximated using linear splines. We also tested for an interaction between prepregnancy BMI category and GWG up to 18 weeks.
GWG and changes in blood pressure in normotensive women
We have previously fitted multilevel linear spline models for changes in SBP, DBP, and weight with gestational age separately. We combined these models to develop 2 bivariate multilevel linear spline models, the first including changes in SBP and weight in parallel and the second including changes in DBP and weight in parallel ( Supplementary material ).
This analysis was restricted to normotensive women who had a term pregnancy (≥37 weeks) (n = 9855). The model with SBP and weight as outcomes had 5 random-effect parameters for SBP: SBP at 8 weeks (baseline) and rate of SBP change at 8-18 weeks (early pregnancy), 18-29 weeks (midpregnancy), 29-36 weeks (late pregnancy), and 36 weeks onward (very late pregnancy) and 4 random-effect parameters for weight: weight at 0 weeks (prepregnancy weight) and rate of GWG at 0-18 weeks (early pregnancy), 18-29 weeks (midpregnancy), and 29 weeks onward (late pregnancy). The model with DBP and weight as outcomes had the equivalent random-effects parameters for DBP as for SBP and the same weight parameters. (Estimates of these parameters are shown in Supplementary Table 2.)
In the second stage, we used the bivariate multilevel models to derive associations of prepregnancy weight and GWG (exposures) with blood pressure change (outcome), adjusting for maternal height, age, parity, smoking, education, and offspring sex in model 1. In model 2 we additionally adjusted for baseline weight and SBP/DBP and GWG and SBP/DBP changes in periods of pregnancy prior to the exposure period. We then conceptualized GWG as the outcome with changes in blood pressure as a potential risk factor. We therefore derived associations of GWG in each period of gestation (outcome) with SBP/DBP at 8 weeks and SBP/DBP change in previous periods of gestation (exposure).
We adjusted for maternal characteristics in model 1. In model 2 we additionally adjusted for baseline weight and SBP/DBP, GWG, and the SBP/DBP change in all periods prior to the exposure period and GWG in the exposure period.
We completed sensitivity analyses, restricting to women who contributed at least 8 measurements of blood pressure and weight to the bivariate models (n = 6666), and second, restricting to women who contributed no more than 11 measurements (n = 6135). The findings were not meaningfully changed from those in the main analyses. We also performed a sensitivity analysis using an 8 week baseline for weight.
Statistical analyses were carried out using MLwiN version 2.25, STATA version 12.1 and runmlwin and reffadjust Stata commands (StataCorp, College Station, TX).
Results
The characteristics of women in the full dataset, and subsets with complete data for each analysis, by categories of HDP are shown in Table 1 , and distributions of prepregnancy BMI and early-pregnancy GWG are shown in Supplementary Figures 1 and 2 , respectively. Each subset had similar characteristics to the full dataset.
| Maternal characteristic | Full dataset (total n = 12,522) mean (SD) or % | Complete data for GWG at ≤18 weeks and HDP analysis (n = 9536), mean (SD) or % | Complete data for GWG and BP change analysis (n = 7975) mean (SD) or % | ||||
|---|---|---|---|---|---|---|---|
| Normotensive (n = 10,346) | Gestational hypertension (n = 1892) | Preeclampsia (n = 284) | Normotensive (n = 7869) | Gestational hypertension (n = 1466) | Preeclampsia (n = 201) | Normotensive (n = 7975) | |
| Height, cm | (n = 9085) | (n = 1674) | (n = 243) | ||||
| 163.81 (6.66) | 164.70 (6.95) | 162.97 (6.69) | 163.88 (6.61) | 164.71 (6.96) | 162.99 (6.71) | 163.94 (6.59) | |
| Age, y | (n = 10,346) | (n = 1892) | (n = 284) | ||||
| 15-19 | 5.08 | 3.96 | 8.10 | 3.24 | 2.52 | 3.48 | 3.60 |
| 20-24 | 19.04 | 21.93 | 26.41 | 16.02 | 19.37 | 28.36 | 16.20 |
| 25-29 | 38.49 | 39.11 | 34.86 | 39.69 | 40.72 | 35.32 | 39.44 |
| 30-34 | 27.94 | 24.68 | 17.96 | 30.73 | 27.08 | 20.40 | 30.39 |
| ≥35 | 9.44 | 10.31 | 12.68 | 10.32 | 10.30 | 12.44 | 10.37 |
| Parity | (n = 9610) | (n = 1758) | (n = 255) | ||||
| Nulliparous | 42.58 | 57.05 | 70.98 | 42.66 | 57.71 | 71.64 | 42.39 |
| Multiparous | 57.42 | 42.95 | 29.02 | 57.34 | 42.29 | 28.36 | 57.61 |
| Smoking in pregnancy | (n = 9713) | (n = 1771) | (n = 256) | ||||
| Never | 65.42 | 69.85 | 74.22 | 68.31 | 72.24 | 75.12 | 68.13 |
| Before pregnancy/first trimester | 13.60 | 14.85 | 16.41 | 12.99 | 14.05 | 17.91 | 13.25 |
| Throughout | 20.98 | 15.30 | 9.38 | 18.71 | 13.71 | 6.97 | 18.62 |
| Highest qualification | (n = 9253) | (n = 1707) | (n = 242) | ||||
| CSE/vocational | 30.41 | 29.23 | 28.10 | 28.20 | 27.49 | 27.36 | 28.30 |
| O level | 33.99 | 36.44 | 36.78 | 34.63 | 37.18 | 36.82 | 34.51 |
| A level | 22.72 | 21.32 | 23.55 | 23.79 | 22.17 | 24.38 | 23.59 |
| Degree | 12.88 | 13.01 | 11.57 | 13.38 | 13.17 | 11.44 | 13.61 |
| Offspring sex | (n = 10,346) | (n = 1892) | (n = 284) | ||||
| Male | 51.29 | 53.17 | 51.76 | 51.14 | 52.59 | 53.73 | 50.51 |
| Female | 48.71 | 46.83 | 48.24 | 48.86 | 47.41 | 46.27 | 49.49 |
| Prepregnancy weight, kg a | (n = 9855) | (n = 1795) | (n = 209) | ||||
| 59.19 (11.07) | 67.59 (15.70) | 67.76 (17.81) | 59.49 (10.65) | 67.32 (15.08) | 66.38 (16.41) | 59.25 (10.83) | |
| Average weight gain up to 18 wks, kg/wk a | (n = 9691) | (n = 1804) | (n = 265) | (n = 7186) | |||
| 0.290 (0.129) | 0.278 (0.148) | 0.284 (0.149) | 0.291 (0.131) | 0.282 (0.150) | 0.284 (0.143) | 0.292 (0.132) | |
| Total weight gain, kg a | (n = 9855) | (n = 1795) | (n = 209) | (n = 7549) | (n = 1399) | (n = 155) | |
| 13.86 (4.49) | 14.96 (5.20) | 16.65 (5.59) | 13.94 (4.46) | 14.98 (5.20) | 16.50 (5.77) | 13.94 (4.42) | |
a Prepregnancy weight is calculated from the predicted weight at 0 weeks’ gestation; average weight gain up to 18 weeks is calculated from the predicted rate of weight change between 0 and 18 weeks (for women who had a weight measurement prior to 18 weeks), and total weight gain is calculated as the predicted weight at 40 weeks’ gestation minus the predicted weight at 8 weeks’ gestation from univariate linear spline random effects models including each woman’s antenatal weight measurements.
Nulliparous women, nonsmokers, and women aged over 35 years were more likely to develop HDP ( Supplementary Table 3 ). Gaining more than the IOM recommended weight was associated with an increased risk of gestational hypertension and preeclampsia compared with gaining within the recommended range ( Figure ; odds ratio [OR], 1.51; 95% confidence interval [CI], 1.32–1.73 and OR, 2.14; 95% CI, 1.46–3.12, respectively). Also, lower than IOM-recommended GWG was associated with a reduced risk of gestational hypertension (OR, 0.75; 95% CI, 0.62–0.91) and preeclampsia (OR, 0.70; 95% CI, 0.38–1.27) compared with GWG within the recommended range (although the confidence interval was wide for preeclampsia and included the null).
Early-pregnancy GWG and risk of HDP
A higher prepregnancy weight was associated with an increased risk of developing gestational hypertension and preeclampsia ( Table 2 ). This association was nonlinear, with evidence of a stronger association between prepregnancy weight and gestational hypertension for women who weighed 90 kg or less than for those who weighed more than 90 kg before pregnancy, although associations with preeclampsia were similar in each group.
| Exposure variables b | Subgroup | Gestational hypertension | Preeclampsia | ||
|---|---|---|---|---|---|
| OR | 95% CI | OR | 95% CI | ||
| Prepregnancy weight (10 kg) | ≤90 kg prepregnancy weight | 1.80 | 1.70–1.91 | 1.71 | 1.49–1.95 |
| >90 kg prepregnancy weight | 1.24 | 1.03–1.49 | 1.61 | 1.18–2.19 | |
| GWG up to 18 weeks (200 g/wk) | All women | 1.27 | 1.16–1.38 | 1.31 | 1.07–1.61 |
a Both models are adjusted for maternal height (continuous; centered around the mean of 164 cm); age (reference, 25-29 years); parity (reference, nulliparous); smoking (reference, never smoked); education (reference, O level); and offspring sex (reference, male). The model with GWG up to 18 weeks as the exposure is additionally adjusted for prepregnancy weight (2 linear splines: ≤90 kg and >90 kg)
b Prepregnancy weight and GWG up to 18 weeks were obtained using the residuals from a linear multilevel model for weight change up to 18 weeks’ gestation. Because of strong evidence for nonlinear associations between prepregnancy weight and these outcomes, results are presented for subgroups of women in whom magnitudes of associations differ.
After adjustment for prepregnancy weight, greater early-pregnancy GWG was independently associated with an increased risk of developing gestational hypertension and preeclampsia (per 200 g/wk increase in GWG up to 18 weeks: OR, 1.26; 95% CI, 1.16–1.38 and OR, 1.31; 95% CI, 1.07–1.62, respectively).
These findings are further illustrated by Table 3 , which shows the predicted probabilities of developing gestational hypertension or preeclampsia for different prepregnancy weights and rates of early-pregnancy GWG. This shows clearly that, even among women with healthy prepregnancy weights (eg, 50 or 60 kg), those who gain more weight have important increases in the risk of gestational hypertension and preeclampsia. We found no evidence that associations of GWG up to 18 weeks with the risk of gestational hypertension and preeclampsia differed by prepregnancy BMI category ( P value for interaction = .18).
| Prepregnancy weight, kg | GWG up to 18 wks, g/wk | Probability of gestational hypertension, % (SE) | Probability of Preeclampsia, % (SE) |
|---|---|---|---|
| 50 | 200 | 11.5 (0.9) | 1.8 (0.4) |
| 400 | 14.1 (1.0) | 2.3 (0.5) | |
| 600 | 17.0 (1.4) | 2.9 (0.7) | |
| 60 | 200 | 19.4 (1.2) | 2.9 (0.5) |
| 400 | 23.2 (1.4) | 3.6 (0.6) | |
| 600 | 27.3 (2.0) | 4.4 (1.0) | |
| 70 | 200 | 30.7 (1.7) | 4.4 (0.8) |
| 400 | 35.4 (1.9) | 5.3 (1.0) | |
| 600 | 40.4 (2.6) | 6.2 (1.5) | |
| 80 | 200 | 44.2 (2.3) | 6.0 (1.2) |
| 400 | 49.3 (2.5) | 7.0 (1.5) | |
| 600 | 54.1 (3.2) | 7.9 (2.1) | |
| 90 | 200 | 57.9 (2.8) | 7.5 (1.8) |
| 400 | 62.3 (3.0) | 8.4 (2.1) | |
| 600 | 66.1 (3.6) | 9.2 (2.8) |
a Predicted probabilities are for a woman of average height (164 cm), age (25-29 years), nulliparous, having never smoked during pregnancy, O level educational qualification, and having a male offspring.
Associations of prepregnancy weight and GWG with subsequent blood pressure change in normotensive women
Analysis of the mean differences in SBP and DBP change for a 200 g/wk increase in GWG in the same and preceding period of gestation are shown in Table 4 . For completeness, associations of all possible combinations of prepregnancy weight and GWG in each gestational period with later SBP and DBP changes are also shown in Supplementary Tables 4 and 5 , respectively.
| Exposure Average weight change (200 g/wk) | Outcome Average SBP/DBP change (mm Hg/wk) in the same and subsequent periods of gestation | SBP change | DBP change | |||
|---|---|---|---|---|---|---|
| Mean difference | 95% CI | Mean Difference | 95% CI | |||
| Early pregnancy (0-18 wks) | Same period | Early pregnancy (8-18 wks) | 0.06 | (0.02–0.10) | 0.03 | (0.00–0.05) |
| Subsequent period | Midpregnancy (18-29 wks) | 0.04 | (0.00–0.07) | 0.03 | (0.00–0.05) | |
| Midpregnancy (18-29 wks) | Same period | Midpregnancy (18-29 wks) | 0.09 | (0.06–0.12) | 0.04 | (0.01–0.06) |
| Subsequent period | Late pregnancy (29-36 wks) | 0.00 | (–0.06 to 0.06) | 0.01 | (–0.03 to 0.06) | |
| Late pregnancy (≥29 wks) | Same period (2 parts) | Late pregnancy (29-36 wks) | 0.11 | (0.06–0.16) | 0.08 | (0.04–0.12) |
| Very late pregnancy (≥36 wks) | 0.14 | (0.03–0.25) | 0.10 | (0.01–0.18) | ||
a Adjusted for maternal height, age, parity, smoking, education, and offspring sex; prepregnancy weight; SBP/DBP at baseline; and weight and SBP/DBP change prior to the exposure period (equivalent to model 2 in Supplementary Tables 4 and 5 )
b Estimates were obtained from 2 bivariate multilevel spline models: one including all of the women’s weight and SBP measurements across pregnancy and the other including all of the women’s weight and DBP measurements across pregnancy, restricting to women who had normotensive pregnancies.
In each period of pregnancy, GWG was positively associated with the changes in SBP and DBP that occurred during the same gestational period ( Table 4 ). In addition, an increase in GWG in early pregnancy (up to 18 weeks) was associated with a greater increase in SBP and DBP in the subsequent period of gestation (midpregnancy: 18-29 weeks) ( Table 4 ). However, greater GWG in early pregnancy was also associated with a smaller increase in SBP and DBP in late pregnancy ( Supplementary Tables 4 and 5 ). GWG in midpregnancy (18-29 weeks) was not associated with SBP or DBP change in late pregnancy (29-36 weeks) ( Table 4 ).
Associations of blood pressure changes with subsequent GWG
To assess whether rises in blood pressure may precede increases in edema and thus weight gain, even in these normotensive women, we also examined associations of changes in SBP and DBP with subsequent GWG ( Table 5 ). All possible associations of baseline SBP and DBP and changes in SBP and DBP with GWG in later periods of gestation are shown in Supplementary Table 6 . In fully-adjusted models, there were no associations between SBP or DBP change and GWG in subsequent periods of pregnancy. There was evidence of positive associations between SBP and DBP at baseline and GWG in early pregnancy ( Supplementary Table 6 ). However, when we repeated the bivariate analyses with the baseline set at 8 weeks for weight, neither SBP nor DBP at baseline was associated with GWG in early pregnancy after adjustment for baseline weight (no other findings were changed in this sensitivity analysis).
| Exposure Average SBP/DBP change (mm Hg/wk) | Outcome Average weight change (200 g/wk) in the subsequent period of gestation | Mean difference | 95% CI | |
|---|---|---|---|---|
| SBP change | ||||
| Early pregnancy (8-18 wks) | Subsequent period | Midpregnancy (18-29 wks) | 0.06 | (–0.06 to 0.18) |
| Midpregnancy (18-29 wks) | Subsequent period | Late pregnancy (≥29 wks) | –0.01 | (–0.17 to 0.15) |
| DBP change | ||||
| Early pregnancy (8-18 wks) | Subsequent period | Midpregnancy (18-29 wks) | 0.02 | (–0.18 to 0.24) |
| Midpregnancy (18-29 wks) | Subsequent period | Late pregnancy (≥29 wks) | 0.14 | (–0.07 to 0.36) |
a Adjusted for maternal height, age, parity, smoking, education, and offspring sex; prepregnancy weight; SBP/DBP at baseline; weight; and SBP/DBP change in all periods of pregnancy prior to the exposure period and weight change in the exposure period (equivalent to model 2 in Supplementary Table 6 )
b Estimates were obtained from 2 bivariate multilevel spline models: one including all of the women’s weight and SBP measurements across pregnancy and the other including all of the women’s weight and DBP measurements across pregnancy, restricting to women who had normotensive pregnancies.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
