Neonatal respiratory distress syndrome (RDS), also known as hyaline membrane disease, is a leading cause of neonatal mortality in the US, which affects 1% of all newborns and 10% of preterm babies [1, 2]. It is also one of the most common causes of admission to neonatal intensive care unit [3]. Preeclampsia (PE) is a common pregnancy complication that affects an estimated 5% of pregnancies across the world [4]. It is a significant cause of low birth weight and preterm delivery, which are risk factors for RDS [5]. However, in the literature, the relationship between PE and RDS remains controversial [6–9].
The occurrences of both PE and RDS vary among difference races. Literature shows that Black or Asian infants have lower incidence rates of RDS compared to White infants [10–13]. Disproportional occurrence of PE among race groups was also noticed, as non-Hispanic Black infants are more severely affected compared to White infants [14, 15]. Therefore, building on the existing literature, we hypothesized that the effect of PE on RDS would be differentiated by race. Meanwhile, we are also interested in the effect of being Hispanic on RDS incidence among subgroups of Hispanic by race. Hispanics in the US are generally studied as a single ethnic group, but it is a culturally heterogeneous group, by country of origin or generation of immigration. This study aims to explore the modification effect of race on PE and ethnicity leading to RDS. We included full-term infants in the analysis besides preterm newborns and found some differences between the two subgroups.
De-identified birth records data from 2011 to 2020 provided by the Florida Bureau of Vital Statistics were used in this study. The Institutional Review Board (IRB) of Florida International University as well as the Florida Department of Health IRB reviewed this study and deemed it exempt. Informed consent to participate in the study have been obtained from participants (or their parent or legal guardian in the case of children under 16). Both PE and RDS were recorded in the dataset as Yes/No. Due to the small size of American Indian or Alaskan Native (AIAN), and other Pacific islander (NPI) in the data, race was categorized as White, Black, Asian or Pacific islander, and others (including other races, AIAN and multiple races). Ethnicity was defined as non-Hispanic/Hispanic. Covariates include demographic variables (maternal age, education level, ethnicity), behavior variables [tobacco and alcohol usage during pregnancy, prenatal care, and WIC (women, infants and children) program status], pregnancy-related variables (gestational weeks, birth weight, birth route, plurality, infant sex), and mother’s medical information (body mass index, history of diabetes, gestational diabetes, history of preterm birth, and premature rupture of membrane).
Births from mothers with eclampsia were excluded from the sample. A total of 2,219,144 infants, including 12,577 (0.57%) cases born with RDS (Table 1) were included in the study. Infants born to preeclamptic women had 2.63 times the odds of developing RDS compared to those born to non-preeclamptic women [odds ratio (OR) = 2.63, 95% confidence interval (CI) 2.50–2.76]. Compared to their White counterparts, Black race (OR = 1.64, 95% CI 1.58–1.70) was associated with higher odds of having RDS and Asian American race (OR = 0.89, 95% CI 0.79–0.99) was associated with lower odds of RDS. Being Hispanic (OR = 0.93, 95% CI 0.88–0.97) was also associated with lower odds of having RDS (Table 1).
Table 1.
Baseline descriptive statistics for Florida birth records from 2011 to 2020
| Variables | Respiratory distress syndrome |
Odds ratioa (95% CI) | |
|---|---|---|---|
| No (n = 2,206,567), n (%) | Yes (n = 12,577), n (%) | ||
|
| |||
| Preeclampsia | |||
| No | 2,071,643 (93.89) | 10,738 (85.38) | Reference |
| Yes | 134,924 (6.11) | 1839 (14.62) | 2.63 (2.50–2.76) |
| Mother’s age (y) | |||
| 18–35 | 1,788,828 (81.07) | 9779 (77.75) | Reference |
| < 18 | 31,285 (1.42) | 185 (1.47) | 1.08 (0.93–1.25) |
| > 35 | 386,454 (17.51) | 2613 (20.78) | 1.24 (1.18–1.29) |
| Mother’s educational level | |||
| ≥ High school graduate | 1,932,284 (87.57) | 10,525 (83.68) | Reference |
| < High school graduate | 274,283 (12.43) | 2052 (16.32) | 1.37 (1.31–1.44) |
| Mother’s race | |||
| White | 1,576,416 (71.44) | 7897 (62.79) | Reference |
| Black | 491,463 (22.27) | 4034 (32.07) | 1.64 (1.58–1.70) |
| Asian and Pacific islander | 69,106 (3.13) | 307 (2.44) | 0.89 (0.79–0.99) |
| Other | 69,582 (3.15) | 339 (2.70) | 0.97 (0.87–1.08) |
| Mother’s ethnicity | |||
| Non-hispanic | 1,461,282 (66.22) | 8437 (67.08) | Reference |
| Hispanic | 745,285 (33.78) | 4140 (32.92) | 0.93 (0.88–0.97) |
| WIC nutrition | |||
| No | 1,157,293 (52.45) | 6012 (47.8) | Reference |
| Yes | 1,049,274 (47.55) | 6565 (52.20) | 1.20 (1.16–1.25) |
| Tobacco use by mother | |||
| No | 2,098,393 (95.10) | 11,821 (93.99) | Reference |
| Yes | 108,174 (4.90) | 756 (6.01) | 1.24 (1.15–1.33) |
| Prenatal care received | |||
| Yes | 2,174,307 (98.54) | 12,094 (96.16) | Reference |
| No | 32,260 (1.46) | 483 (3.84) | 2.69 (2.45–2.95) |
| Mother’s history of diabetes | |||
| No | 2,187,918 (99.15) | 12,299 (97.79) | Reference |
| Yes | 18,649 (0.85) | 278 (2.21) | 2.65 (2.35–2.98) |
| Gestational diabetes | |||
| No | 2,089,199 (94.68) | 11,467 (91.17) | Reference |
| Yes | 117,368 (5.32) | 1110 (8.83) | 1.72 (1.62–1.83) |
| Alcohol use | |||
| No | 2,195,348 (99.49) | 12,467 (99.13) | Reference |
| Yes | 11,219 (0.51) | 110 (0.87) | 1.74 (1.43–2.09) |
| Mother’s history of preterm birth | |||
| No | 2,172,389 (98.45) | 11,813 (93.93) | Reference |
| Yes | 34,178 (1.55) | 764 (6.07) | 4.11 (3.82–4.42) |
| BMI | |||
| < 30 | 1,695,737 (76.85) | 8999 (71.55) | Reference |
| ≥ 30 | 510,830 (23.15) | 3578 (28.45) | 1.32 (1.27–1.37) |
| Premature rupture of membrane before labor | |||
| No | 2,133,645 (96.7) | 11,204 (89.08) | Reference |
| Yes | 72,922 (3.30) | 1373 (10.92) | 3.59 (3.39–3.79) |
| Birth route | |||
| No cesarean | 1,389,553 (62.97) | 4821 (38.33) | Reference |
| Cesarean | 817,014 (37.03) | 7756 (61.67) | 2.74 (2.64–2.84) |
| Plurality | |||
| Singleton | 2,137,044 (96.85) | 10,832 (86.13) | Reference |
| Twin | 67,378 (3.05) | 1617 (12.86) | 4.74 (4.49–4.99) |
| Multiples (3–5) | 2145 (0.10) | 128 (1.02) | 11.79 (9.80–14.04) |
| Infant sex | |||
| Female | 1,077,618 (48.84) | 5305 (42.18) | Reference |
| Male | 1,128,949 (51.16) | 7272 (57.82) | 1.31 (1.26–1.36) |
| Infant’s weight (g) | |||
| ≥ 2500 | 2,025,173 (91.78) | 6335 (50.37) | Reference |
| < 2500 | 181,394 (8.22) | 6242 (49.63) | 11.00 (10.62–11.40) |
| Infant gestation week (wk) | |||
| ≥ 37 | 1,991,265 (90.24) | 5334 (42.41) | Reference |
| 34–37 | 155,143 (7.03) | 2729 (21.70) | 6.57 (6.27–6.88) |
| < 34 | 60,159 (2.73) | 4514 (35.89) | 28.01 (26.90–29.19) |
CI confidence interval, BMI body mass index, WIC women, infants and children.
Odds ratio for univariate logistic analysis
Table 2 shows the adjusted odds ratios (aOR) and 95% CI of having RDS after controlling for potential confounders. Gestational subgroup analyses were conducted for preterm (< 37 gestational weeks) and full-term infants (≥ 37 gestational weeks) separately. Three important interactions were identified in the models. The two subgroups showed different patterns on the interactions.
Table 2.
Odds ratio of respiratory distress syndrome occurrence from multivariable models
| Variables | Model Aa (full sample) | Model Ba (preterm) | Model Ca (full-term) |
|---|---|---|---|
|
| |||
| Interactions | |||
| Race:ethnicity | |||
| Black:Hispanic | 2.12 (1.94–2.31)* | 1.90 (1.70–2.13)* | 2.40 (2.11–2.73)* |
| Asian:Hispanic | 3.44 (2.16–5.46)* | 2.16 (1.03–4.54)* | 5.35 (3.00–9.55)* |
| Others:Hispanic | 1.31 (1.02–1.68)* | 1.30 (0.93–1.82) | 1.32 (0.90–1.92) |
| Preeclampsia:race | |||
| Preeclampsia:Black | 0.80 (0.71–0.89)* | 0.91 (0.80–1.03) | 0.71 (0.58–0.88)* |
| Preeclampsia:Asian | 0.85 (0.58–1.23) | 1.07 (0.70–1.64) | 0.48 (0.20–1.19) |
| Preeclampsia:others | 0.99 (0.72–1.35) | 1.11 (0.77–1.61) | 0.84 (0.45–1.56) |
| Preeclampsia:PRoM | |||
| Preeclampsia:mother having PRoM | 0.73 (0.59–0.89)* | 0.63 (0.50–0.79)* | 1.65 (1.02–2.65)* |
| Preeclampsia:gestational week | |||
| Preeclampsia:< 34 wk | 0.68 (0.60–0.77)* | NA | NA |
| Preeclampsia:34–37 wk | 0.67 (0.58–0.76)* | NA | NA |
| Main effects | |||
| Preeclampsia | |||
| No | Reference | Reference | Reference |
| Yes | 1.78 (1.62–1.97)* | 1.15 (1.06–1.24)* | 1.75 (1.56–1.96)* |
| Mother’s race | |||
| White | Reference | Reference | Reference |
| Black | 0.94 (0.89–0.99)* | 0.89 (0.83–0.95)* | 1.05 (0.97–1.14) |
| Asian and Pacific islander | 0.80 (0.70–0.91)* | 0.76 (0.63–0.91)* | 0.80 (0.67–0.96)* |
| Other | 0.85 (0.74–0.98)* | 0.82 (0.68–0.99)* | 0.88 (0.72–1.06) |
| Mother’s ethnicity | |||
| Non-hispanic | Reference | Reference | Reference |
| Hispanic | 0.79 (0.75–0.83)* | 0.87 (0.81–0.92)* | 0.71 (0.66–0.76)* |
| Tobacco use by mother | |||
| No | Reference | Reference | Reference |
| Yes | 0.92 (0.85–0.99)* | 0.81 (0.73–0.90)* | 1.02 (0.91–1.15) |
| PRoM | |||
| No | Reference | Reference | Reference |
| Yes | 1.38 (1.30–1.47)* | 1.59 (1.49–1.71)* | 1.13 (0.94–1.35) |
| Infant gestation week (wk) | |||
| ≥ 37 | Reference | Reference | Reference |
| 34–37 | 4.37 (4.11–4.64)* | NA | NA |
| < 34 | 12.93 (12.02–13.91)* | NA | NA |
PRoM premature rupture of membrane before labor, BMI body mass index, WIC women, infants and children, NA not available.
Models were adjusted by maternal age, education level, BMI, prenatal care status, alcohol use during pregnancy, WIC program status, birth route, plurality, infant’s weight, sex, maternal history of diabetes, history of preterm birth, gestational diabetes.
P < 0.05
Interaction between race and PE was detected in full-sample (PE:Black, aOR = 0.80, 95% CI 0.71–0.89) and the full-term group (PE:Black, aOR = 0.71, 95% CI 0.58–0.88). In other words, the adverse effect of PE was significantly lessened by Black race among full-term infants but not preterm infants. While controlling for other covariates for full-term infants, the risk of RDS increased by 75% for infants from non-Hispanic White mothers having maternal PE compared to non-Hispanic Whites without PE, and the increased risk was damped to 30% for infants from mothers with PE among non-Hispanic Black race, compared with the same reference group (Table 3). For preterm infants, the corresponding two ratios of having RDS for the same group comparisons were 1.15 and 0.93, respectively (Table 3). As RDS among full-term and preterm infants are majorly caused by different factors [16], the differences seen in the current study are expected. The mechanisms underlying such disparities are currently unclear. Lower serum level of surfactant protein A (SP-A) is associated with RDS incidence and severity. Some previous studies revealed that SP-A and/or SP-B genetic variants may be associated with race differences of RDS incidence among Black and White races, and specific genotypes appear to be a protective factor for Blacks but not for Whites [17, 18]. Additionally, a lower serum level of SP-A was associated with early-onset PE [19]. These concurrent associations suggest a possible explanation for the racial difference of the association between race and PE. However, further biological studies are needed to clarify the patterns.
Table 3.
Respiratory distress syndrome occurrence risk for race/eth- nicity/preeclampsia groups
| Variables | Full sample | Preterm | Full-term |
|---|---|---|---|
|
| |||
| White | |||
| Non-Hispanic, non-preelamp- tic | Reference | Reference | Reference |
| Non-Hispanic, preelamptic | 1.78 | 1.15 | 1.75 |
| Hispanic, non-preelamptic | 0.79 | 0.87 | 0.71 |
| Hispanic, preelamptic | 1.41 | 1.00 | 1.24 |
| Black | |||
| Non-Hispanic, non-preelamp- tic | 0.94 | 0.89 | 1.05 |
| Non-Hispanic, preelamptic | 1.34 | 0.93 | 1.30 |
| Hispanic, non-preelamptic | 1.57 | 1.47 | 1.79 |
| Hispanic, preelamptic | 2.24 | 1.54 | 2.22 |
| Asian | |||
| Non-Hispanic, non-preelamp- tic | 0.80 | 0.76 | 0.80 |
| Non-Hispanic, preelamptic | 1.21 | 0.94 | 0.67 |
| Hispanic, non-preelamptic | 2.17 | 1.43 | 3.04 |
| Hispanic, preelamptic | 3.29 | 1.76 | 2.55 |
| Others | |||
| Non-Hispanic, non-preelamp- tic | 0.85 | 0.82 | 0.88 |
| Non-Hispanic, preelamptic | 1.50 | 1.05 | 0.85 |
| Hispanic, non-preelamptic | 0.88 | 0.93 | 0.82 |
| Hispanic, preelamptic | 1.55 | 1.18 | 1.21 |
Black and Asian races modified the effect of maternal Hispanic ethnicity on neonatal RDS for the full-sample as well as the preterm and full-term subgroups. The modification was smaller in the preterm group (Black:Hispanic, aOR = 1.90, 95% CI 1.70–2.13; Asian:Hispanic, aOR = 2.16, 95% CI 1.03–4.54) compared to the full-term group (Black:Hispanic, aOR = 2.40, 95% CI 2.11–2.73; Asian:Hispanic, aOR = 5.35, 95% CI 3.00–9.55). Even though being Hispanic White was associated with lower risk of neonatal RDS compared to non-Hispanic White group, self-identification as Hispanic was associated with higher risk of RDS for Black race or Asian race. With other covariates controlled for, preterm infants born to Hispanic Black or Hispanic Asian mothers were 1.47 and 1.43 times as likely to have RDS compared to those of non-Hispanic White mothers, respectively (Table 3). For full-term infants, the respective odds were 1.79 and 3.04 for the same comparison groups. A possible reason for the racial differences observed is that Hispanic Whites may be more acculturated compared to the other groups. That means some unmeasured social determinants may be different here, such as socioeconomic status, language barriers to medical treatment/care, or cultural beliefs or practices [20]. Because of this, it is important to investigate racial differences among Hispanic subgroups, and this is the first study to do so for the risk of RDS. Besides the modification effect of race on PE and ethnicity, the interaction between PE and premature rupture of membrane before labor (PRoM) was noticed. PRoM lessens the risk of RDS for the preterm group (aOR = 0.63, 95% CI 0.50–0.79) but increases the risk for the full-term group (aOR = 1.65, 95% CI 1.02–2.65).
Our findings identified preterm newborns from Hispanic Black/Hispanic Asian women with PE, full-term infants from preeclamptic non-Hispanic White women or from Hispanic Black/Hispanic Asian women regardless their PE condition as potentially vulnerable subgroups of acquiring RDS in their term group. Health care institutions should take the disparity observed here into consideration when providing prenatal care or preventative treatments. Special interventions for the identified vulnerable subgroups should be developed and evaluated. For example, provide culturally tailored materials about the risk and prevention strategies of PE; enhance clinical-community partnerships that help screen and support social determinants of health among Hispanic Black/Asian mothers, such as social isolation, parental education, and financial stress; increase their access to high-quality healthcare, and prepare for appropriate follow-up of these high-risk newborns.
This study has some limitations. Gestational hypertension was not separated from PE, and the severity of RDS and the onset stage of PE were not included in the analysis because of the restriction of data. Additional analysis with these features considered might be promising.
Funding
This work is supported by the National Heart Lung and Blood Institute (No. K01 HL146944), the National Institute on Minority Health and Health Disparities of the National Institutes of Health (No. U54MD012393), FIU-RCMI and the FL-DOH.
Footnotes
Conflict of interest No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflict of interest to declare.
Ethical approval The Institutional Review Board (IRB) of Florida International University as well as the Florida Department of Health IRB reviewed this study and deemed it exempt. Informed consent to participate in the study have been obtained from participants (or their parent or legal guardian in the case of children under 16).
Data availability
The datasets generated during and/or analyzed during the current study are not publicly available due to the Florida Department of Health Data Use agreement restriction but are available from the Florida Department of Health, Bureau of Vital Statistics on reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are not publicly available due to the Florida Department of Health Data Use agreement restriction but are available from the Florida Department of Health, Bureau of Vital Statistics on reasonable request.