The Association of Maternal Insurance Status on Maternal and Neonatal Outcomes in Women with Hypertensive Disorders of Pregnancy

doi:10.21203/rs.3.rs-2069400/v1

The objective of this study was to examine the association between maternal insurance status and maternal and neonatal adverse outcomes in women who had hypertensive disorders in pregnancy. A population-based retrospective cohort study was undertaken using the US Vital Statistics dataset on Period Linked Birth-Infant Data from 2016-2020. The study population was restricted to non-anomalous births from women whose pregnancies were complicated by hypertensive disorders. Insurance status was categorized as private, Medicaid, self-pay and other. The primary outcome was a composite of maternal adverse outcomes, which included admission to the intensive care unit, unplanned hysterectomy, maternal blood transfusion or uterine rupture. We examined the role of prenatal care in these relationships using a mediation analysis with Kotelchuck’s Adequacy of Prenatal Care Utilization Index. Multivariable logistic regression models were used to estimate the association between maternal insurance status and adverse outcomes (using adjusted odds ratios [aOR] and 99% confidence interval [CI]). Of the 18,999,865 live births in the five-year study, 1,655,007 (8.7%) met the inclusion criteria. The frequency of the composite maternal adverse outcome was 1.3%. The maternal composite occurred more frequently in women with Medicaid (aOR = 1.13, 99% CI: 1.08, 1.18) or self-pay (aOR = 1.43, 95% CI: 1.28, 1.59) when compared to private insurance. Adjusting for prenatal care slightly attenuated this association, but remained significant. Among women with hypertensive disorders in pregnancy, women with Medicaid insurance or self-pay were more likely to experience maternal and neonatal adverse outcomes than women with private insurance.

Hypertensive disorders in pregnancy, including chronic hypertension, gestational hypertension and preeclampsia/eclampsia complicate nearly 10% of all pregnancies in the United States.(1, 2) This rate has increased over the past decade and is projected to continue to do so.(3) Hypertensive disorders in pregnancy are associated with increased maternal and neonatal morbidity which have short and long term sequalae.(4–7) Identification of demographic factors that potentially increase the risk of these disorders is important so that prevention, diagnosis, and treatment may be optimized.

A variety of socio-economic factors have been examined for associations with the rate of hypertensive disorders in pregnancy. Educational status, income, and geographic location have all been found to be related with disparate rates of hypertensive disorders in pregnancy.(8–10) Insurance status may be an independent predictor of adverse outcomes in women with hypertensive disorders in pregnancy. While almost 50% of births in the United States are covered by Medicaid, 30% of households with income less than $25,000 are privately insured.(11) Single center studies have demonstrated an association between insurance status and hypertensive disorders in pregnancy.(12) The purpose of this study was to address this knowledge gap and provide nationwide data on the possible association between insurance status and the prevalence of adverse maternal and neonatal outcomes among pregnancies with hypertensive disorders.

The primary objective of this study was to examine the composite of adverse maternal outcomes (admission to the intensive care unit, unplanned hysterectomy, maternal blood transfusion, or uterine rupture) among women who deliver with hypertensive disorders of pregnancy stratified by insurance status. The secondary outcome was to examine a composite of adverse neonatal outcomes (five-minute Apgar score less than 7, admission to the neonatal intensive care unit, assisted ventilation for > 6 hours, or neonatal seizures). We also examine the role of prenatal care in these relationships. We hypothesized, among women with hypertensive disorders in pregnancy who delivered a viable neonate, the maternal and neonatal adverse outcomes would be elevated in women without private insurance.

Population and Study Design

This population-based retrospective cohort study utilized the U.S. Vital Statistics dataset on Period Linked Birth-Infant Death Data from 2016–2020. The study population was women with hypertensive disorders in pregnancy (chronic hypertension, gestational hypertension/preeclampsia, or eclampsia) who delivered livebirths with gestational ages between 23 and 40 weeks. Exclusion criteria included women with anomalous fetuses (anencephaly, spina bifida, cyanotic congenital heart disease, congenital diaphragmatic hernia, omphalocele, gastroschisis, or limb reduction defect), births outside of the hospital, births with no data on insurance status, births with missing data on birth weight, gestational age, prenatal care, or covariates including education, nativity, and race and ethnicity. Adequacy of prenatal care utilization was based on the Kotelchuck index.(13) This study was considered exempt by the institutional review board at the Warren Alpert School of Medicine at Brown University due to the publicly available nature of the dataset, which does not contain direct personal identifiers (IRB# 1746034-1). The STROBE guidelines for reporting observational studies were followed.(14)

Procedures

The exposure variable was maternal insurance status, defined as payer at delivery. The primary outcome was a composite of maternal adverse outcomes, including admission to the intensive care unit (ICU), unplanned hysterectomy, maternal blood transfusion, or uterine rupture. A secondary outcome was a composite of neonatal adverse outcomes, including: five-minute Apgar score less than 7, admission to the neonatal intensive care unit, assisted ventilation for > 6 hours, or neonatal seizures. If mothers or neonates suffered more than one adverse outcome they were counted only once in the composite. Additional outcomes including preterm birth, low birth weight, and small-for-gestational-age were examined. A preplanned mediation analysis based on the adequacy of prenatal care utilization index was also performed. The adequacy of prenatal care utilization index was dichotomized, whereby women with “Adequate” or “Adequate Plus” scores on the adequacy of prenatal care utilization index were categorized as “Adequate”, and women with “Intermediate” or “Inadequate” scores were categorized as “Inadequate”.

Statistical Analysis

Differences in demographics were stratified by insurance type Potential confounders were identified using a Directed Acyclic Graph and included maternal age, maternal nativity, maternal education, and maternal race and ethnicity. Multivariable logistic regression models were used to estimate the association between insurance status and the adverse outcomes. The results were presented as adjusted odds ratios (aOR) with 99% confidence interval (CI). The statistical analysis was conducted using R version 4.1.1, the “tidyverse” and “gtsummary” packages.

There were 18,999,865 live births that were recorded over the study period, with 1,655,007 (8.7%) meeting the inclusion criteria (Fig. 1). The most common indications for exclusion were no hypertensive disorders in pregnancy (90.6%), gestational age out of range (6.3%) and missing adequacy of prenatal care utilization index (3.2%).

Maternal demographic information, stratified by insurance status; private insurance, Medicaid, self-pay and other, are presented in Table 1. The rate of adverse maternal outcomes was highest in women with self-pay (1.9%) and lowest in women with private insurance (1.1%). Women with private insurance were more likely to be older, more highly educated, born in the United States, be of non-Hispanic white ethnicity, be married and not smoke during pregnancy.

Compared to women with private insurance, the odds of the composite maternal adverse outcome was higher in women with Medicaid (aOR = 1.13, 99% CI: 1.08, 1.18), self-pay (aOR = 1.43, 99% CI: 1.28, 1.59). Regression results from the analysis of the individual components of adverse maternal outcomes are displayed in the Supplemental Appendix eTable 1. The results from the mediation analysis are displayed in Table 2. Adjusting for adequacy of prenatal care utilization attenuated the association between insurance status and adverse maternal outcomes in women with Medicaid (aOR = 1.11, 99% CI: 1.07, 1.15) and self-pay (aOR = 1.36, 95% CI: 1.25, 1.47), but the results remained significant.

The composite of adverse neonatal outcomes occurred more frequently in Medicaid (aOR = 1.10, 99% CI: 1.09, 1.11), self-pay (aOR = 1.11, 99% CI: 1.08, 1.15) when compared to pregnancies covered by private insurance (Table 2). Regression results from the analysis of the individual components of adverse neonatal outcomes are displayed in the Supplemental Appendix eTable 1. The results from the mediation analysis are displayed in Table 2. Adjusting for adequacy of prenatal care utilization did not change the association between insurance status and adverse neonatal outcomes in women with Medicaid (aOR = 1.10, 99% CI: 1.09, 1.11) and self-pay (aOR = 1.11, 95% CI: 1.08, 1.14), but the results remained significant.

For the exploratory outcomes, preterm birth, low birth weight, and small-for-gestational-age occurred more frequently in Medicaid (aOR 1.06, 95%CI = 1.06–1.09) and self-pay (aOR 1.10, 95%CI = 1.06–1.14) cohorts (Table 3). The odds of delivering a small-for-gestational-age infant was higher in women with Medicaid (aOR = 1.10, 95% CI: 1.08, 1.12) and self-pay (aOR = 1.13, 95% CI: 1.09, 1.18) insurance.

This study demonstrated that, in pregnancies complicated by hypertensive disorders, women with Medicaid or self-pay insurance were at an increased risk of maternal and neonatal adverse outcomes. This association persisted in pregnancies that had adequate prenatal care.

Our data differs from a prior single center which did not demonstrate the increased rate of transfusion or admission to the intensive care unit amongst pregnancies covered by Medicaid insurance that was found here.(12) In this study, the high rate of composite neonatal adverse outcomes is in keeping with prior data demonstrating that pregnancies with hypertensive disorders increase the rate of preterm birth and neonatal complications.(15, 16) An increased rate of admission to the neonatal intensive care unit, but no difference in ventilation rates among Medicaid pregnancies is in keeping with prior research.(12) The mediation analysis demonstrating the persistence of the primary findings in pregnancies with adequate prenatal care raise questions regarding the quality-of-care patients with Medicaid or self-pay insurance receive compared to women with private insurance.

Strengths of this study include the use of a comprehensive, nationwide dataset. The contemporary component allows improved understanding of current obstetrical practice. Despite the American College of Obstetricians and Gynecologists recognizing the importance of the U.S. Vital Statistics dataset, research validating the accuracy of maternal outcomes is needed.(17, 18) In part due to this, hypertensive patients at 40-41 weeks EGA were excluded from the analysis, although this exclusion likely drove the results towards the null. The variable self-pay was unable to distinguish between patients without access to insurance and those choosing to go without. The modest odds ratios identified may constitute a pseudo epidemic.(19)

This analysis found that in pregnancies complicated by hypertensive disorders, private insurance was associated with lower rates of maternal and neonatal adverse outcomes. These results indicate the need for further exploration in to how to optimize outcomes for patients with Medicaid insurance.

What is Known About this Topic

1) Hypertensive disorders in pregnancy are associated with increased maternal and neonatal adverse outcomes.

2) A variety of socio-economic factors are related with disparate rates of hypertensive disorders in pregnancy.

What this Study Adds

1) in pregnancies complicated by hypertensive disorders, women with Medicaid or self-pay insurance were at an increased risk of maternal and neonatal adverse outcomes.

2) These findings persisted in pregnancies with adequate prenatal care.

The authors report no conflicts of interest.

There was no funding received for conducting this project.

Butwick AJ, Druzin ML, Shaw GM, Guo N. Evaluation of US State-Level Variation in Hypertensive Disorders of Pregnancy. JAMA Netw Open. 2020;3(10):e2018741.
Kuklina EV. Hypertension in Pregnancy in the US-One Step Closer to Better Ascertainment and Management. JAMA Netw Open. 2020;3(10):e2019364.
Cameron NA, Everitt I, Seegmiller LE, Yee LM, Grobman WA, Khan SS. Trends in the Incidence of New-Onset Hypertensive Disorders of Pregnancy Among Rural and Urban Areas in the United States, 2007 to 2019. J Am Heart Assoc. 2022;11(2):e023791.
Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin Summary, Number 222. Obstet Gynecol. 2020;135(6):1492-5.
Abdelazim IA, Bekmukhambetov Y, Aringazina R, Shikanova S, Amer OO, Zhurabekova G, et al. The outcome of hypertensive disorders with pregnancy. J Family Med Prim Care. 2020;9(3):1678-83.
Pauli JM, Repke JT. Preeclampsia: Short-term and Long-term Implications. Obstet Gynecol Clin North Am. 2015;42(2):299-313.
Wagner SM, Chen H-Y, Gupta M, Bicocca MJ, Mendez-Figueroa H, Chauhan SP. Association between time of delivery and composite adverse outcomes in pregnancies complicated by hypertensive disorders. Hypertension in Pregnancy. 2021;40(3):246-53.
Bartsch E, Medcalf KE, Park AL, Ray JG, High Risk of Pre-eclampsia Identification G. Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BMJ. 2016;353:i1753.
Sibai BM, Hauth J, Caritis S, Lindheimer MD, MacPherson C, Klebanoff M, et al. Hypertensive disorders in twin versus singleton gestations. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol. 2000;182(4):938-42.
Zhang S, Cardarelli K, Shim R, Ye J, Booker KL, Rust G. Racial disparities in economic and clinical outcomes of pregnancy among Medicaid recipients. Matern Child Health J. 2013;17(8):1518-25.
Cha AE, Cohen RA. Demographic Variation in Health Insurance Coverage:United States, 2020. Natl Health Stat Report. 2022(169):1-15.
Greiner KS, Speranza RJ, Rincón M, Beeraka SS, Burwick RM. Association between insurance type and pregnancy outcomes in women diagnosed with hypertensive disorders of pregnancy. J Matern Fetal Neonatal Med. 2020;33(8):1427-33.
Kotelchuck M. The Adequacy of Prenatal Care Utilization Index: its US distribution and association with low birthweight. Am J Public Health. 1994;84(9):1486-9.
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495-9.
Langenveld J, Ravelli AC, van Kaam AH, van der Ham DP, van Pampus MG, Porath M, et al. Neonatal outcome of pregnancies complicated by hypertensive disorders between 34 and 37 weeks of gestation: a 7 year retrospective analysis of a national registry. Am J Obstet Gynecol. 2011;205(6):540.e1-7.
Tsujimoto Y, Kataoka Y, Banno M, Taito S, Kokubo M, Masuzawa Y, et al. Association of low birthweight and premature birth with hypertensive disorders in pregnancy: a systematic review and meta-analysis. J Hypertens. 2022;40(2):205-12.
ACOG Committee Opinion No. 748: The Importance of Vital Records and Statistics for the Obstetrician-Gynecologist. Obstet Gynecol. 2018;132(2):e78-e81.
Schoendorf KC, Branum AM. The use of United States vital statistics in perinatal and obstetric research. Am J Obstet Gynecol. 2006;194(4):911-5.
Grimes DA, Schulz KF. False alarms and pseudo-epidemics: the limitations of observational epidemiology. Obstet Gynecol. 2012;120(4):920-7.

Table 1: Maternal Characteristics of the Study Sample of Women with Hypertensive Disorders in Pregnancy between 2016-2020.

Characteristic	Private insurance, N = 855,012¹	Medicaid, N = 701,962¹	Self-pay, N = 36,973¹	Other, N = 61,060¹
Gestational hypertension/Preeclampsia	661,169 (77%)	517,322 (74%)	28,576 (77%)	44,032 (72%)
Chronic hypertension	176,969 (21%)	168,857 (24%)	7,179 (19%)	14,603 (24%)
Eclampsia	22,341 (2.6%)	20,429 (2.9%)	1,451 (3.9%)	2,897 (4.7%)
Gestational diabetes	110,354 (13%)	93,453 (13%)	4,832 (13%)	7,751 (13%)
Chronic diabetes	24,076 (2.8%)	29,982 (4.3%)	1,164 (3.1%)	2,219 (3.6%)
Adverse maternal outcomes	9,756 (1.1%)	10,306 (1.5%)	710 (1.9%)	813 (1.3%)
Admission to intensive care unit	3,587 (0.4%)	4,065 (0.6%)	334 (0.9%)	298 (0.5%)
Unplanned hysterectomy	620 (<0.1%)	546 (<0.1%)	57 (0.2%)	46 (<0.1%)
Maternal blood transfusion	6,774 (0.8%)	6,632 (0.9%)	408 (1.1%)	550 (0.9%)
Ruptured uterus	243 (<0.1%)	302 (<0.1%)	24 (<0.1%)	29 (<0.1%)
Adverse neonatal outcomes	169,459 (20%)	157,194 (22%)	8,340 (23%)	12,508 (20%)
Five-minute APGAR <7	27,199 (3.2%)	27,399 (3.9%)	1,435 (3.9%)	2,330 (3.8%)
Admission to neonatal intensive care unit	158,334 (19%)	147,510 (21%)	7,867 (21%)	11,540 (19%)
Assisted ventilation for >6 hours	35,061 (4.1%)	29,375 (4.2%)	1,616 (4.4%)	2,457 (4.0%)
Neonatal seizures	426 (<0.1%)	410 (<0.1%)	24 (<0.1%)	38 (<0.1%)
Preterm birth	189,241 (22%)	174,362 (25%)	9,347 (25%)	13,677 (22%)
Low birthweight	149,704 (18%)	147,429 (21%)	7,969 (22%)	11,060 (18%)
Small-for-gestational-age	101,999 (12%)	108,301 (15%)	5,700 (15%)	7,838 (13%)
Maternal age
< 20	11,985 (1.4%)	56,387 (8.0%)	1,938 (5.2%)	2,462 (4.0%)
20-26	170,155 (20%)	253,720 (36%)	9,422 (25%)	20,605 (34%)
27-34	445,812 (52%)	269,863 (38%)	15,387 (42%)	26,156 (43%)
35+	227,060 (27%)	121,992 (17%)	10,226 (28%)	11,837 (19%)
Maternal education
Less than high school	19,249 (2.3%)	139,214 (20%)	11,416 (31%)	7,048 (12%)
High school or equivalent	127,515 (15%)	282,168 (40%)	10,867 (29%)	15,503 (25%)
Some college	172,976 (20%)	177,969 (25%)	5,345 (14%)	16,512 (27%)
College and above	535,272 (63%)	102,611 (15%)	9,345 (25%)	21,997 (36%)
Maternal nativity
Born in US	759,753 (89%)	579,321 (83%)	16,443 (44%)	49,625 (81%)
Born outside US	95,259 (11%)	122,641 (17%)	20,530 (56%)	11,435 (19%)
Maternal race and ethnicity
Non-Hispanic White	592,654 (69%)	260,765 (37%)	11,329 (31%)	30,557 (50%)
Non-Hispanic Black	99,082 (12%)	215,372 (31%)	6,436 (17%)	10,595 (17%)
Non-Hispanic American Indian/Alaska Native	3,662 (0.4%)	10,618 (1.5%)	217 (0.6%)	1,787 (2.9%)
Non-Hispanic Asian/Native Hawaiian or Pacific Islander	44,928 (5.3%)	16,936 (2.4%)	1,491 (4.0%)	2,432 (4.0%)
Non-Hispanic two or more races	17,594 (2.1%)	18,585 (2.6%)	463 (1.3%)	2,152 (3.5%)
Hispanic	97,092 (11%)	179,686 (26%)	17,037 (46%)	13,537 (22%)
Received at least one prenatal care visit	850,158 (99%)	686,723 (98%)	33,832 (92%)	60,010 (98%)
Adequacy of Prenatal Care Utilization Index
Adequate Plus	498,928 (58%)	340,030 (48%)	12,862 (35%)	28,790 (47%)
Adequate	256,686 (30%)	178,900 (25%)	8,667 (23%)	17,887 (29%)
Intermediate	41,192 (4.8%)	46,177 (6.6%)	2,887 (7.8%)	5,357 (8.8%)
Inadequate	58,206 (6.8%)	136,855 (19%)	12,557 (34%)	9,026 (15%)
Maternal marital status
Married	622,618 (78%)	204,684 (31%)	19,555 (55%)	39,224 (69%)
Unmarried	175,139 (22%)	454,131 (69%)	16,295 (45%)	17,628 (31%)
Unknown	57,255	43,147	1,123	4,208
Parity
1	794,969 (93%)	665,569 (95%)	35,079 (95%)	57,685 (94%)
2	57,670 (6.7%)	35,492 (5.1%)	1,787 (4.8%)	3,245 (5.3%)
3+	2,373 (0.3%)	901 (0.1%)	107 (0.3%)	130 (0.2%)
Smoked at least one cigarette during pregnancy	25,720 (3.0%)	83,711 (12%)	2,146 (5.9%)	3,278 (5.4%)
Unknown	4,744	6,882	311	416
Year of birth
2016	148,279 (17%)	121,873 (17%)	6,393 (17%)	11,136 (18%)
2017	154,526 (18%)	131,890 (19%)	7,079 (19%)	11,237 (18%)
2018	170,208 (20%)	139,990 (20%)	7,920 (21%)	12,313 (20%)
2019	185,443 (22%)	150,186 (21%)	8,057 (22%)	12,574 (21%)
2020	196,556 (23%)	158,023 (23%)	7,524 (20%)	13,800 (23%)
¹n (%)

Table 2. Results from regression analysis on the composite of adverse maternal outcomes and adverse neonatal outcomes.

	Unadjusted model			Multivariable model 1¹		Multivariable model 2²
Characteristic		OR³	99% CI⁴	OR³	99% CI⁴	OR³	99% CI⁴
Adverse maternal outcomes⁵
Insurance status
Private insurance		—	—	—	—	—	—
Medicaid		1.29	1.24, 1.34	1.13	1.08, 1.18	1.11	1.07, 1.15
Self-pay		1.70	1.53, 1.87	1.43	1.28, 1.59	1.36	1.25, 1.47
Other		1.17	1.06, 1.28	1.09	0.99, 1.20	1.07	0.99, 1.15
Adverse neonatal outcomes⁶
Private insurance		—	—	—	—	—	—
Medicaid		1.17	1.16, 1.18	1.10	1.09, 1.11	1.10	1.09, 1.11
Self-pay		1.18	1.14, 1.22	1.11	1.08, 1.15	1.11	1.08, 1.14
Other		1.04	1.01, 1.07	1.03	1.00, 1.06	1.03	1.01, 1.05

Notes: Bold indicates statistically significant results.

¹Multivariable model 1 was adjusted for the following potential covariates: maternal age, maternal nativity, maternal education, and maternal race and ethnicity

²Multivariable model 2 was the mediation analysis adjusted for all the potential covariates in multivariable model 1 in addition to the adequacy of prenatal care utilization index

³Odds ratio

⁴Confidence interval

⁵Includes any of the following outcomes: admission to the intensive care unit, unplanned hysterectomy, maternal blood transfusion, or uterine rupture

⁶Includes any of the following outcomes: five-minute APGAR score <7, admission to the neonatal intensive care unit, assisted ventilation for > 6 hours, or neonatal seizures

Table 3. Results from regression analysis on the exploratory analysis of the outcomes of preterm birth, low birth weight, and small-for-gestational-age.

	Unadjusted model			Multivariable model 1¹		Multivariable model 2²
Characteristic		OR³	99% CI⁴	OR³	99% CI⁴	OR³	99% CI⁴
Preterm birth⁵
Insurance status
Private insurance		—	—	—	—	—	—
Medicaid		1.16	1.15, 1.17	1.07	1.06, 1.09	1.09	1.08, 1.10
Self-pay		1.19	1.15, 1.23	1.11	1.07, 1.14	1.15	1.12, 1.18
Other		1.02	0.99, 1.04	0.99	0.97, 1.02	1.00	0.98, 1.02
Low birth weight⁶
Private insurance		—	—	—	—	—	—
Medicaid		1.25	1.24, 1.27	1.07	1.06, 1.08	1.07	1.06, 1.08
Self-pay		1.29	1.25, 1.34	1.13	1.09, 1.17	1.15	1.12, 1.18
Other		1.04	1.01, 1.07	0.98	0.95, 1.01	0.98	0.96, 1.01
Small-for-gestational-age⁷
Private insurance		—	—	—	—	—	—
Medicaid		1.35	1.33, 1.36	1.10	1.08, 1.12	1.09	1.08, 1.10
Self-pay		1.35	1.30, 1.40	1.13	1.09, 1.18	1.09	1.06, 1.13
Other		1.09	1.05, 1.12	0.99	0.96, 1.02	0.98	0.96, 1.00

Notes: Bold indicates statistically significant results.

¹Multivariable model 1 was adjusted for the following potential covariates: maternal age, maternal nativity, maternal education, and maternal race and ethnicity

²Multivariable model 2 was the mediation analysis adjusted for all the potential covariates in multivariable model 1 in addition to the adequacy of prenatal care utilization index

³Odds ratio

⁴Confidence interval

⁵Gestational age <37 weeks

⁶Birth weight <2,500 g

⁷<10^th percentile for US births

There is NO conflict of interest to disclose.

supplementaldata.docx

The Association of Maternal Insurance Status on Maternal and Neonatal Outcomes in Women with Hypertensive Disorders of Pregnancy

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Methods

Population and Study Design

Procedures

Statistical Analysis

Results

Discussion

Summary

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1