Abstract
Background:
Race and ethnicity influence the distribution and severity of hypertensive disorders of pregnancy (HDP) in the U.S. population, although the impact of prior infant loss on this relationship requires further investigation.
Objectives:
The aim of this study was to assess the relationship between history of infant loss and the risk of HDP by maternal race and ethnicity.
Methods:
For this large cross-sectional study, data were analyzed from the National Center for Health Statistics Vital Statistics Natality Birth Data, 2014-2017. The primary outcome was HDP, and the primary predictor was infant loss after prior live birth. Maternal race/ethnicity was the secondary predictor categorized as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, Asian, or Other. Multiple logistic regression was used to assess the association between history of infant loss and HDP by race and ethnicity.
Results:
The 9,439,520 women included in this sample were 51% NHW, 15% NHB, 25% Hispanic, 6% Asian, and 3% Other with a mean age of 29.8±5.3 years. In adjusted analyses, infant loss after prior live birth was significantly associated with an 11% odds of HDP (OR 1.11, 95% CI 1.08, 1.13). Stratified by race, NHB (OR 1.28; 95% CI 1.21, 1.36) women had significantly higher odds of HDP, and Hispanic (OR 0.84, 95% CI 0.79, 0.90) and Asian (OR 0.85, 95% CI 0.75, 0.97) women had significantly lower odds compared to NHW women. Within races, all women with infant loss after prior live birth had significantly higher odds of HDP (p<0.001), except Other women (p=0.632).
Conclusions:
Infant loss after prior live birth was significantly associated with higher odds of HDP among NHB women after adjusting for covariates. Further research is warranted to assess underlying mechanisms associated with higher odds of HDP in NHB women.
Keywords: Infant Loss, Pregnancy, Hypertensive Disorders of Pregnancy, Prior Live Birth
Background
The rate of hypertensive disorders of pregnancy (HDP) is rising in the United States (U.S.), with up to 8% of pregnancies complicated by HDP.1-5 HDP encompasses gestational hypertension, preeclampsia, and eclampsia and increases the risk of various pregnancy complications including placental abruption, preterm birth, intrauterine growth restriction, postpartum hemorrhage, cesarean delivery, admission to neonatal intensive care unit, and perinatal death.2,5-7 A study conducted in 2017 found that within 12 months of delivery, the cost of preeclampsia alone in the U.S. healthcare system reached $2.18 billion.8 As the rate of HDP increases, these costs are expected to rise substantially.
Several studies have shown that race and ethnicity influence the distribution and severity of HDP in the U.S. population.2,4,5,7,10-13 Non-Hispanic Black (NHB) women have a significantly higher incidence of HDP compared to non-Hispanic White (NHW), Asian, and Hispanic women.5,7,9 Between 2014 and 2015, 9.8% of NHB women in the U.S. experienced maternal hypertension compared to 7.2% of NHW women and only 2.2% of Chinese women.7 The severity of preeclampsia also differs along racial and ethnic lines, with NHB women experiencing more severe hypertension during pregnancy, needing more treatments for severe-range blood pressure (i.e., 160/100 or higher), and experiencing a disproportionate number of maternal complications including stroke, heart failure, renal failure, and increased mortality compared to NHW women.5,11-13 Additionally, NHB women have higher rates of perinatal death and low birth weight infants when pregnancy is complicated by HDP.2,5,6
Multiple risk factors contribute to the development of HDP including prior pregnancy complicated by HDP, chronic hypertension, diabetes, autoimmune disease, history of thromboembolism, longer interpregnancy intervals, lower gestational age at first delivery, and prior small for gestational age infant(s).14-16 Additionally, multiple studies demonstrate a link between numerous lifetime maternal stressors, including perceived stress from prior infant loss, on the increased risk of developing HDP in subsequent pregnancies.17-19 Specifically, prior child loss may result in a 4-fold increased risk of HDP in a subsequent pregnancy, as the additional stress from infant loss may negatively alter placentation in the early gestational period due to the upregulation of pro-inflammatory cytokines.17-19 However, to our knowledge the impact of infant loss after a prior live birth on the development of HDP has not been investigated in regards to disparities by race and ethnicity. Therefore, we hypothesize that the risk of developing HDP after a prior infant loss will differ among racial and ethnic groups in a nationally representative sample of women.
Methods
Study Cohort
Natality data from the National Vital Statistics System (NVSS) of the National Center for Health Statistics provide demographic and health data for births occurring during the calendar year. The microdata are based on information abstracted from birth certificates filed in vital statistics offices of each state and the District of Columbia. This study used natality data between the years 2014 and 2017 within the United States. We compiled data files sequentially by birth year and extracted all available demographic and clinic variables based on the 2003 revision of the U.S. Standard Certificate of Live Birth (revised). Forty-seven states and the District of Columbia had implemented the revised birth certificate as of January 1, 2014. All states and territories had implemented the revised birth certificate as of January 1, 2016. The final analysis cohort was all live births with a reported maternal age between 18 and 44 years with a previous live birth. A total 9,646,873 live births were identified. After excluding individuals without reporting HDP, a prior live birth where an infant has died, and race/ethnicity, 9,439,520 were used for the analysis.20-21
Outcome
The primary outcome of interest was HDP, which was defined as having gestational hypertension, which included pregnancy induced hypertension (PIH) and preeclampsia, or eclampsia, hypertension during pregnancy. Individuals without definitive answers to these two variables were excluded.
Exposure
The primary predictor for this analysis was variable labeled “number of previous live births now dead”, which was defined as ‘yes’ with one or more infants dead from previous live births and “no” as zero death. This question assessed the total number of previous live-born infants now dead, where infants from current pregnancies and first born infants were excluded and all previous live-born infants who were not living were included.
The secondary predictor was maternal race/ethnicity, which was categorized as non-Hispanic White, non-Hispanic Black, Hispanic, Asian, and Other minority.
Covariates
Covariates included demographic, clinical, and risk variables. Demographic variables included maternal age (in years); education (grouped as less than high school, high school/some college, associate/bachelor’s degree, and grad/professional degree); marital status (grouped as married and unmarried); and insurance (grouped as Medicaid, private insurance, self-pay, and other). Clinical and risk variables included maternal pre-pregnancy Body Mass Index (BMI); cigarette smoking (dichotomized as yes vs. no); pre-pregnancy diabetes (dichotomized as yes vs. no); pre-pregnancy hypertension (dichotomized as yes vs. no); gestational diabetes (dichotomized as yes vs. no); prior cesarean delivery (dichotomized as yes vs. no), previous preterm birth (dichotomized as yes vs. no), months prenatal care began (grouped as 1st to 3rd month, 4th to 6th month, 7th to final month, and no prenatal care), number of prenatal visits, interval since last live birth (in months), and prior births now living.
Statistical Analysis
To analyze whether HDP was associated with infant loss after prior live birth, we fit a series of logistic regression models. We reported odds ratios (OR) instead of relative risk (RR) because the HDP incidence rate was 4.9% in our study; for less common events such as what was observed in our study (typically < 10%), odds is close to risk; therefore, this approach was appropriate for the analysis. First, we compared demographics, clinical, and risk factors across maternal race/ethnicity groups and infant loss after prior live birth, by using Chi-square test for categorical and ANOVA test for continuous variables. Secondly, univariate logistic models were developed to test the associations for HDP with infant loss and maternal race/ethnicity separately. Thirdly, we tested for significant interaction of prior live birth with infant loss and maternal race/ethnicity, and then constructed univariate and multivariable logistic models stratified by race/ethnicity, with the multivariable models adjusted for all demographic and clinical variables. We also ran the above models by using the two sub types of HDP (gestational hypertension and eclampsia) as outcomes separately. All p values were 2-sided and p<0.05 was considered statistically significant. Statistical analysis was performed with SAS version 9.4 (SAS Institute).
Ethics Approval
As this was a study involving secondary data analysis, ethics approval by an institution was not warranted.
Results
Table 1 shows the sample demographics by race and ethnicity. A total of 9,439,520 live births were included in the study. The racial/ethnic distribution included 51% NHW, 15% NHB, 25% Hispanic, 6% Asian, and 3% Other, with a mean age of 29.8±5.3 years. The majority of the women (63%) were married and had a high school or some college education (47.3%). Insurance status of this population shows 46.3% covered by Medicaid and 44.9% by private insurance. Approximately 5% of the study population reported previous preterm birth; nearly 2% reported pre-pregnancy hypertension; 4.7% reported gestational hypertension or preelampsia; and 0.2% reported eclampsia. Approximately 5% of the total population reported HDP, where 4.9% were NHW, 6.5% were NHB, 4.1% were Hispanic, 2.9% were Asian, and 5.5% were from Other race/ethnicity. 2.0% of the total population reported infant loss, with NHB women (3.3%) and women from Other race/ethnicity (2.5%) reporting more infant loss after a prior live birth than NHW (1.7%), Hispanic (1.8%), and Asian (1.3%) women.
Table 1:
Sample Demographics by Race and Ethnicity
| Total | NHW | NHB | Hispanic | Asian | Other | P- value |
|
|---|---|---|---|---|---|---|---|
| Count | 9,439,520 | 4,843,233 | 1,403,991 | 2,375,001 | 524,205 | 293,090 | |
| Mother’s Age (Mean±SD) | 29.8 ±5.3 | 30.2±5.1 | 28.8±5.5 | 29.3±5.6 | 32.6±4.6 | 28.6±5.4 | <0.001 |
| Education | <0.001 | ||||||
| Less than high school | 16.0% | 8.1% | 15.4% | 34.0% | 9.3% | 16.0% | |
| High school / some college | 47.3% | 43.6% | 61.8% | 49.6% | 26.4% | 58.4% | |
| Associate / Bachelor’s Degree | 26.5% | 34.4% | 17.7% | 13.4% | 39.5% | 20.0% | |
| Grad / Professional Degree | 10.2% | 13.9% | 5.1% | 3.0% | 24.8% | 5.6% | |
| Mother’s Marital Status | <0.001 | ||||||
| Married | 63.0% | 75.0% | 33.5% | 52.2% | 88.2% | 47.0% | |
| Insurance | <0.001 | ||||||
| Medicaid | 46.3% | 33.5% | 68.9% | 61.9% | 28.6% | 56.6% | |
| Private Insurance | 44.9% | 59.5% | 24.6% | 25.3% | 61.4% | 32.3% | |
| Self Pay | 4.6% | 3.5% | 3.1% | 7.7% | 6.8% | 2.7% | |
| Other | 4.1% | 3.6% | 3.5% | 5.2% | 3.2% | 8.5% | |
| Pre-Pregnancy BMI (kg/m2) (Mean±SD) | 27.2±6.7 | 26.7±6.6 | 29.1±7.5 | 27.9±6.3 | 23.8±4.5 | 28.4±7.2 | <0.001 |
| Cigarette Smoking | 8.6% | 12.5% | 7.8% | 2.0% | 0.7% | 15.4% | <0.001 |
| Previous Preterm Birth | 4.9% | 4.9% | 6.8% | 4.1% | 3.2% | 6.2% | <0.001 |
| Prior Cesarean Delivery | 24.7% | 23.7% | 26.2% | 25.3% | 27.7% | 23.2% | <0.001 |
| Months Prenatal Care Began (Mean±SD) | 2.9±1.6 | 2.8±1.4 | 3.2±1.8 | 3.0±1.7 | 2.8±1.5 | 3.2±1.8 | <0.001 |
| Months Prenatal Care Began Group | <0.001 | ||||||
| 1st to 3rd month | 75.9% | 81.1% | 65.1% | 71.6% | 80.0% | 68.0% | |
| 4th to 6th month | 17.7% | 14.3% | 24.5% | 20.9% | 15.0% | 21.9% | |
| 7th to final month | 4.6% | 3.4% | 7.1% | 5.3% | 4.3% | 7.4% | |
| No prenatal Care | 1.8% | 1.2% | 3.3% | 2.2% | 0.7% | 2.7% | |
| Number of Prenatal Visits (Mean±SD) | 11.1±4.2 | 11.5±4.0 | 10.2±4.7 | 10.8±4.2 | 11.3±3.9 | 10.2±4.6 | <0.001 |
| Number of Prenatal Visits Group | <0.001 | ||||||
| No visit | 1.8% | 1.2% | 3.3% | 2.2% | 0.7% | 2.7% | |
| 1-8 visits | 19.4% | 15.4% | 28.0% | 21.8% | 17.4% | 28.2% | |
| 9-12 visits | 47.1% | 48.1% | 42.3% | 47.2% | 52.3% | 42.5% | |
| 13-18 visits | 28.4% | 31.7% | 22.9% | 25.9% | 26.2% | 23.3% | |
| 19 or more visits | 3.4% | 3.6% | 3.5% | 3.0% | 3.3% | 3.3% | |
| Interval Since Last Live Birth in Months (Mean±SD) | 49.1±37.2 | 44.5±33.3 | 52.3±41.0 | 56.6±41.2 | 50.1±35.9 | 47.0±36.5 | <0.001 |
| Pre-Pregnancy Diabetes | 0.9% | 0.7% | 1.2% | 1.0% | 1.0% | 1.4% | <0.001 |
| Gestational Diabetes | 6.4% | 5.6% | 5.2% | 7.4% | 11.6% | 7.5% | <0.001 |
| Pre-Pregnancy HTN | 1.8% | 1.6% | 4.0% | 1.1% | 1.0% | 2.1% | <0.001 |
| Gestational HTN - PIH, Preeclampsia | 4.7% | 4.8% | 6.2% | 4.0% | 2.8% | 5.2% | <0.001 |
| HTN - Eclampsia | 0.2% | 0.2% | 0.4% | 0.2% | 0.1% | 0.4% | <0.001 |
| HDP | 4.9% | 4.9% | 6.5% | 4.1% | 2.9% | 5.5% | <0.001 |
| Prior Birth Now Living (Mean±SD) | 1.8±1.2 | 1.7±1.1 | 2.0±1.3 | 1.9±1.2 | 1.4±0.9 | 2.0±1.3 | <0.001 |
| Prior Infant Loss | 2.0% | 1.7% | 3.3% | 1.8% | 1.3% | 2.5% | <0.001 |
| Birth Cohort Group | <0.001 | ||||||
| 2014 | 24.5% | 24.7% | 24.2% | 24.3% | 23.8% | 24.0% | |
| 2015 | 25.1% | 25.2% | 24.8% | 25.2% | 24.3% | 24.8% | |
| 2016 | 25.5% | 25.4% | 25.2% | 25.6% | 26.1% | 25.5% | |
| 2017 | 25.0% | 24.8% | 25.7% | 25.0% | 25.7% | 25.6% |
Abbreviations: NHW=Non-Hispanic White; NHB=Non-Hispanic Black; SD=Standard Deviation; BMI=Body Mass Index; HTN=Hypertension; PIH=Pregnancy Induced Hypertension; HDP=Hypertensive Disorders of Pregnancy.
P value: Chi-square test for categorical variables and ANOVA test for continuous variables.
Table 2 shows logistic regression models of the relationship between infant loss after live birth and HDP as well the two sub types of HDP. In the unadjusted analyses, prior infant loss was significantly associated with 26% increased odds of HDP (OR 1.26; 95% CI 1.24, 1.29), 24% increased odds of gestational HTN (OR 1.24; 95% CI 1.21, 1.26), and 74% increased odds of eclampsia (OR 1.74; 95% CI 1.61, 1.88). After adjusting for covariates, the relationship and significance persisted with 11% higher odds of HDP with prior infant loss (OR 1.11; 95% CI 1.08, 1.13), 9% higher odds of gestational HTN with prior infant loss (OR 1.09; 95% CI 1.07, 1.12), and 33% higher odds of eclampsia with prior infant loss (OR 1.33; 95% CI 1.22, 1.45).
Table 2:
Logistic Regression Models Between Infant Loss afer Prior Live Birth and HDP (n=9,439,520)
| Unadjusted Model | Adjusted Model | ||
|---|---|---|---|
| Outcome | Predictor: Prior Infant Loss |
OR (95% CI) | OR (95% CI) |
| HDP | No | 1.00 (Ref) | 1.00 (Ref) |
| Yes | 1.26 (1.24, 1.29)*** | 1.11 (1.08, 1.13)*** | |
| Gestational HTN - PIH, Preeclampsia | No | 1.00 (Ref) | 1.00 (Ref) |
| Yes | 1.24 (1.21, 1.26)*** | 1.09 (1.07, 1.12)*** | |
| HTN - Eclampsia | No | 1.00 (Ref) | 1.00 (Ref) |
| Yes | 1.74 (1.61, 1.88)*** | 1.33 (1.22, 1.45)*** |
Significant at ***p<0.001, **p<0.01, *p<0.05. P value calculated by wald chi-square test.
Adjusted for covariates: mother’s age, education, marital status, race/ethnicity; insurance; cigarette smoking; pre-pregnancy body mass index; pre-pregnancy diabetes; pre-pregnancy hypertension; gestational diabetes; prior cesarean delivery; months prenatal care began; number of prenatal visits; interval since last live birth; and prior birth now living.
Abbreviation: HDP=Hypertensive Disorders of Pregnancy; HTN=Hypertension; PIH=Pregnancy Induced Hypertension; OR=Odds Ratio; 95% CI = 95% Confidence Interval
Table 3 shows the relationship between race and ethnicity and HDP for women with a history of prior infant loss. In the unadjusted model, NHB women had a 38% significantly increased odds of HDP (OR 1.38; 95% CI 1.32, 1.45) and Other women had an 11% significantly increased odds of HDP (OR 1.11; 95% CI 1.01, 1.23) with history of infant loss compared to NHW women with prior infant loss. Hispanic (OR 0.93; 95% CI 0.88,0.98) and Asian (OR 0.82; 95% CI 0.73, 0.92) women had significantly lower odds of HDP with history of infant loss compared to NHW women in unadjusted analyses. After adjusting for covariates, the significant relationship was maintained for NHB (OR 1.28; 95% CI 1.21, 1.36) women having increased odds of HDP after prior infant loss compared to NHW women, and for Asian (OR 0.85; 95% CI 0.75, 0.97) and Hispanic (OR 0.84; 95% CI 0.79, 0.90) women having significantly decreased odds. After adjusting for covariates, Other (OR 1.03; 95% CI 0.92, 1.15) women did not have a significant odds of HDP after prior infant loss.
Table 3:
Logistic Regression Models between Race/Ethnicity and HDP for Women with Infant Loss afer Prior Live Birth (n= 184,375)
| Unadjusted Model | Adjusted Model | |
|---|---|---|
| Predictor: Race & Ethnicity | OR (95% CI) | OR (95% CI) |
| NHW | 1.00 (Ref) | 1.00 (Ref) |
| NHB | 1.38 (1.32, 1.45)*** | 1.28 (1.21, 1.36)*** |
| Hispanic | 0.93 (0.88, 0.98)** | 0.84 (0.79, 0.90)*** |
| Asian | 0.82 (0.73, 0.92)** | 0.85 (0.75, 0.97)* |
| Other | 1.11 (1.01, 1.23)* | 1.03 (0.92, 1.15) |
Significant at ***p<0.001, **p<0.01, *p<0.05. P value calculated by wald chi-square test.
Adjusted for covariates: mother’s age, education, marital status; insurance; cigarette smoking; pre-pregnancy body mass index; pre-pregnancy diabetes; pre-pregnancy hypertension; gestational diabetes; prior cesarean delivery; months prenatal care began; number of prenatal visits; interval since last live birth; and prior birth now living.
Abbreviation: HDP=Hypertensive Disorders of Pregnancy; NHW=Non-Hispanic White; NHB=Non-Hispanic Black; OR=Odds Ratio; 95% CI=95% Confidence Interval.
Table 4 shows the logistic regression model between prior infant loss and HDP stratified by each racial/ethnic group. Women without prior infant loss were considered the reference group for their respective racial/ethnic category. In the unadjusted analysis, Asian women with a prior infant loss had 65% significantly higher odds of HDP compared to Asian women without a prior infant loss (OR 1.65; 95% CI 1.47, 1.85); Hispanic women with prior infant loss had statistically higher odds of HDP at 29% (OR 1.29; 95% CI 1.24, 1.35) compared to Hispanic women reporting no previous infant loss; NHB women with a prior infant loss had 20% significantly higher odds of HDP (OR 1.20; 95% CI 1.16, 1.24) compared to NHB women with no prior history of infant loss; and both NHW (OR 1.15; 95% CI 1.11, 1.18) and Other (OR 1.15; 95% CI 1.04, 1.27) women with a prior infant loss had 15% significantly higher odds of HDP compared to NHW and Other women without a prior infant loss. In the adjusted models, significantly higher odds of HDP with a history of prior infant loss persisted for NHW (OR 1.06; 95% CI 1.03, 1.10), NHB (OR 1.13; 95% CI 1.09, 1.18), Hispanic (OR 1.15; 95% CI 1.09, 1.20) and Asian (OR 1.39; 95% CI 1.22, 1.58) women compared to women of the same race/ethnicity without a prior infant loss; however, significance was not maintained in the adjusted model for Other minority women (OR 1.03; 95% CI 0.92, 1.15).
Table 4:
Logistic Regression Models between Infant Loss after Prior Live Birth and HDP Stratified by Race/Ethnicity Group (n= 9,439,520: NHW=4,843,233, NHB=1,403,991, Hispanic=2,375,001, Asian=524,205, Other=293,090)
| Unadjusted Model | Adjusted Model | ||
|---|---|---|---|
| Race & Ethnicity | Predictor | OR (95% CI) | OR (95% CI) |
| NHW | Infant Loss Yes | 1.15 (1.11, 1.18)*** | 1.06 (1.03, 1.10)*** |
| NHB | Infant Loss Yes | 1.20 (1.16, 1.24)*** | 1.13 (1.09, 1.18)*** |
| Hispanic | Infant Loss Yes | 1.29 (1.24, 1.35)*** | 1.15 (1.09, 1.20)*** |
| Asian | Infant Loss Yes | 1.65 (1.47, 1.85)*** | 1.39 (1.22, 1.58)*** |
| Other | Infant Loss Yes | 1.15 (1.04, 1.27)** | 1.03 (0.92, 1.15) |
Significance ***p<0.001, **p<0.01, *p<0.05. P value calculated by wald chi-square test.
Reference Groups: No prior infant loss within each racial/ethnic category.
Adjusted for covariates: mother’s age, education, marital status; insurance; cigarette smoking; pre-pregnancy body mass index; pre-pregnancy diabetes; pre-pregnancy hypertension; gestational diabetes; prior cesarean delivery; months prenatal care began; number of prenatal visits; interval since last live birth; and prior birth now living.
Abbreviation: HDP=Hypertensive Disorders of Pregnancy; NHW=Non-Hispanic White; NHB=Non-Hispanic Black; OR=Odds Ratio; 95% CI=95% Confidence Interval.
Comment
Principle Findings
In this nationally representative sample of women, infant loss after prior live birth was significantly associated with HDP in unadjusted and adjusted models. In unadjusted analyses among women with infant loss after prior live birth, NHB and Other women had significantly higher odds of HDP compared to NHW women, while Hispanic and Asian women had significantly lower odds compared to NHW women. These relationships were maintained after adjusting for confounding factors except among Other minority women. In unadjusted analyses among women within the same racial or ethnic groups, all women who reported infant loss after a prior live birth had significantly higher odds of HDP compared to women of the same race or ethnicity. After adjusting for covariates, these significant relationships persisted, except for Other women with infant loss compared to Other women without an infant loss. . Addiitonal research is warranted to further understand why NHB women have significantly higher odds of HDP after prior infant loss compared to NHW women, while Hispanic and Asian women have significantly lower odds of HDP.
Several mechanisms have been proposed to explain the racial disparities related to HDP, including differences in genetic factors, socioeconomic status, immigration status, access to healthcare, poor social environments, and increased prevalence of comorbid conditions such as cardiovascular disease among NHB women.5-7 Our findings are supported by evidence from previous studies demonstrating the relationship between race and HDP. In this study, NHB women had significantly higher odds of HDP with infant loss after prior live birth compared to NHW women. This result parallels findings in multiple studies which demonstrate racial disparities in the incidence and risk of HDP, with NHB women experiencing disproportionately higher rates of HDP than NHW women.5,7,9,11 Additionally, a nationally representative study of HDP conducted by Singh et al demonstrated that all Hispanic groups and certain groups of Asian women have significantly lower prevalence of HDP compared to NHW women, which aligns with the reported prevalence of HDP in our sample population. 7 Their study went on to find the risk of HDP in Chinese women was significantly lower compared to all other racial and ethnic groups.7 Another study showed East Asian women had the lowest risk of HDP compared to other racial and ethnic groups.4 After adjusting for covariates, our study found Asian and Hispanic women have similar odds for HDP after infant loss, although both racial/ethnic groups have lower odds compared to NHW, NHB, and Other women. While prior studies parallel our findings regarding racial and ethnic differences in HDP, they do not specifically analyze the impact of prior infant loss on these disparities.
Studying prior infant loss and odds of HDP together is necessary, as both variables may result in abnormal placental development resulting in numerous pregnancy complications and preterm birth. Similar to our findings, a study published in 2013 found that child loss six months before pregnancy was associated a four-fold increased risk of preeclampsia.17 The authors concluded that severe stress resulting from child loss may alter placentation in early pregnancy, resulting in an elevated risk of developing HDP.17 Yu et al studied the impact of lifetime stress, such as violence, family support, job stress, major events in the year prior to pregnancy, and chronic hypertension on the risk of preeclampsia.18 They found lifetime stress was significantly associated with an increased risk of preeclampsia (OR 2.1, 95% CI 1.6, 2.8), which was greatly elevated by the presence of chronic hypertension.18 Caplan et al also analyzed the impact of life stressors, such housing and financial security, occupation, abuse, discrimination, and depression, and found women with higher stress scores were more likely to develop gestational hypertension and preeclampsia, even after adjusting for parity, BMI, diabetes, smoking, and chronic hypertension.19 Multiple studies have also delved into the relationship between prior pregnancy loss and the increased risk of depression and anxiety in subsequent pregnancies.22-23 While these studies did not specifically evaluate the development of HDP in subsequent pregnancies, depression and anxiety increases overall maternal emotional stress, which has been associated with the development of preeclampsia.24-25 Elevated maternal stress has been found to increase pro-inflammatory cytokines which can negatively impact placenta formation, lead to the development of HDP, and result in fetal and neonatal complications, as studied extensively by Coussons-Read.26-28 These findings are in support of our study, demonstrating infant loss may contribute to depression, anxiety, elevated stress levels, and increased pro-inflammatory cytokine levels in the prenatal period and during a subsequent pregnancy, which may increase the overall risk of developing HDP.
Our findings impact clinical practice, as prior infant loss may trigger stress-response pathways including the upregulation of inflammatory cytokines, which can have harmful effects on placental and fetal development and subsequently increase the risk of HDP. While it is known that NHB women have increased odds of developing HDP due to numerous socioeconomic disparities, our findings suggest NHB women may be at an even increased odds of HDP when pregnancy is complicated by a prior infant loss. Therefore, care must be taken to identify higher-risk women who have experienced infant loss in the prenatal and early gestational periods, as they may benefit from additional support and monitoring to help prevent adverse pregnancy outcomes, including the development of HDP.
Limitations
Although this study included a nationally representative sample of women, there are limitations to interpreting the results. First, using a cross-sectional study design prevented determination of causality between infant loss after prior live birth and HDP. Future studies are needed to evaluate factors associated with the relationship between infant loss after prior live birth and HDP, including evaluation of inflammatory mediators, coping mechanisms, substance use, social support, income level, and zip code demographics of areas disproportionately impacted. Second, although pre-pregnancy hypertension was included in the covariate analysis, the variable of prior pregnancy complicated by HDP was not available in the National Vital Statistics natality data set and therefore represents a confounding factor. Studies have shown that prior preeclampsia remains a major risk factor for developing future preeclampsia.1,14-16 Third, we were not able to determine the temporal relationship beween HDP and prior infant loss; therefore, we cannot report on which event occurred first. Also, we were not able to assess whether the pregnancy in which the prior infant loss occurred was influenced by a concurrent HDP diagnosis. Fourth, we were not able to determine the etiology or age of infant loss. Despite these limitations, it is important to study these two pregnancy events together as both HDP and prior infant loss can be related to placental syndomes such as preterm birth and complications of prematurity. Additionally, prior infant loss is a major stressor for women and could trigger stress-related pathways that could increase the risk of HDP. Therefore, the findings of this study are important to provide evidence on the relationship between HDP and prior loss of an infant, so clinicians are aware and can determine appropriate management. Finally, five broad categories of race and ethnicity were used to aggregate data, which may conceal specific disparities in the relationship between infant loss after prior live birth and HDP in subpopulations within each racial or ethnic category. Further research should focus on understanding the underlying mechanisms associated with increased odds of HDP among women with prior infant loss in higher-risk populations.
Conclusions
In this cross sectional study of women stratified by race and ethnicity and adjusted for relevant covariates, infant loss after prior live birth was significantly associated with higher odds of HDP, especially for NHB women. These findings suggest the need for understanding the relationship between infant loss and HDP before and during pregnancy, especially among racial and ethnic minority women.
Acknowledgments
KW, JSW, AP, and LEE designed the study. AS identified the dataset, and EG and LEE acquired the data. JSW and LEE developed the analyses. EG analyzed the data. KW, JSW, and LEE interpreted the data. All authors critically revised the manuscript for important intellectual content and approved the final manuscript.
Funding
Effort for this study partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases K24Dk093699, R01DK118038, and R01DK120861 (PI: Leonard E. Egede, MD, MS).
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