Abstract
Objective
To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy.
Study design
Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ2 tests, Fisher’s exact tests, and ANOVA.
Results
Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge.
Conclusions
This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively.
Hypertension (HTN) in infants has been increasingly recognized.1 HTN is reported to develop in ≤3% of infants admitted to the NICU, and the risk of HTN is directly related to the degree of prematurity.1-3 Common causes of HTN in infants include renovascular disease and renal parenchymal disease; coexisting conditions include antenatal steroid exposure, maternal HTN, umbilical artery catheter placement, and chronic lung disease.1 Furthermore, defining and managing HTN in infants is challenging because normative blood pressure data are limited, and few antihypertensive medications have been studied in infants.3 In many infants, no cause of HTN is identified. The blood pressure outcomes of these infants with idiopathic neonatal HTN is unclear.1-4 Robust, long-term outcome data on the resolution of idiopathic neonatal HTN and identification of risk factors for persistent HTN in infants are essential to optimize management, determine appropriate follow-up, and counsel families on expected clinical course.5
There have been no multicenter studies specifically investigating the course of idiopathic neonatal HTN or the need for antihypertensive therapy after discharge from the NICU. Most existing single-center studies report that most infants with idiopathic HTN improve over time and are able to discontinue antihypertensive therapy.4,6,7 However, these studies are limited by small sample sizes and short durations of follow-up4,6-8 We sought to describe the outcomes of infants with idiopathic HTN discharged from the NICU on antihypertensive therapy. Our primary hypothesis was that most infants discharged from the NICU with idiopathic HTN would have a normal blood pressure and no longer require antihypertensive medications by 1 year after NICU discharge.
Methods
Study Sample
We conducted a multicenter, retrospective cohort study at 14 centers in the Pediatric Nephrology Research Consortium. All centers obtained institutional review board approval for this study. We included all infants who (1) were discharged from NICUs on treatment with antihypertensives between May 1, 2012, and December 31, 2017, and (2) attended ≥1 follow-up outpatient appointment for HTN after discharge. Owing to management differences between centers, follow-up appointments could be conducted by pediatric nephrology, the NICU high-risk clinic, or pediatric cardiology. Infants with identified causes of neonatal HTN, including renal parenchymal disease, severe obstructive uropathy, renovascular abnormalities, cardiac disease, endocrine disease, neoplasia, and a history of closure of abdominal wall defect and malformation syndromes, were excluded. We included those with conditions associated with HTN such as bronchopulmonary dysplasia and corticosteroid exposure. Patients were followed until cessation of antihypertensive therapy or 2 years after NICU discharge, whichever came first.
Definitions and Outcomes
Demographic and clinical characteristics were documented. Self-reported maternal race and ethnicity were included as a variable because of the potential for difference in outcomes. Complications during the NICU stay were recorded through a review of the NICU discharge record. Maternal characteristics included age at delivery, HTN, pre-eclampsia, diabetes, prenatal care, and corticosteroids prior to delivery. Birth weight z-score for gestational age and sex were calculated post hoc.9 Small for gestational age status was calculated post hoc based on birth a weight of <10th percentile (z-score < −1.28).10 Criteria for the diagnosis of HTN and management approaches, including choice of medication and decision for initiation and discontinuation of antihypertensive therapy, were center specific and not standardized for this retrospective study.
The primary outcome was time to discontinuation of antihypertensive therapy. Because previous studies reported that most infants with idiopathic HTN do not require antihypertensive treatment beyond several months of age, we created 3 analytic groups a priori based on when antihypertensives were discontinued after NICU discharge: ≤6 months, >6 months to 1 year, and >1 year.7,8
Statistical Analysis
For descriptive statistics, categorical variables were summarized with frequency (percent) and compared between groups with the χ2 or Fisher’s exact tests depending on sample sizes. Categorical variables were analyzed when the sample size was ≥5 infants per group. Birth weight z-scores, which were normally distributed, were summarized with mean ± SD and compared between groups with 1-way ANOVA. All other continuous variables, which were non-normally distributed, were summarized with median (IQR) and compared with Kruskal-Wallis 1-way ANOVA on ranks. Multiple comparisons with Bonferroni adjustments were made to identify specific group differences when appropriate. In all analyses, a P value of <.05 was considered statistically significant. Analyses were performed using SPSS version 26.0 (IBM Corporation).
Results
Patient Characteristics
Data were collected and analyzed from a total of 118 infants at 14 North American pediatric centers (Figure 1, available at www.jpeds.com). Among the infants in the cohort, the median gestational age was 28.4 weeks (IQR, 5.0 weeks) and median birth weight was 1074 g (IQR, 760 g). Seventy infants (59.3%) were born at <29 weeks’ gestation, 33 (28.0%) were born between 29 and 36 weeks, and 15 (12.7%) were born at >36 weeks’ gestation. Seventy-eight infants (66.1%) were male, 62 (52.5%) were White, and 11 (9.3%) were Hispanic. Twelve infants (10.3%) were small for gestational age. Demographic and clinical characteristics of the infants and comparisons by primary outcome are shown in Table I.
Figure 1. Consort diagram.
134 subjects were enrolled in this retrospective cohort study. We excluded 9 infants who were not on antihypertensive therapy at the time of NICU discharge. Furthermore, we also excluded 5 infants who did not have follow-up after discharge. We further excluded 2 infants with errors in their date of birth or discharge date which made calculation of gestational age or chronologic age impossible. Therefore, 118 infants with sufficient data for analysis were included in this analysis.
Table I.
Comparison of demographic and clinical characteristics of study infants overall and by duration of antihypertensive treatment
| Characteristics variable | All infants | HTN meds | HTN meds | HTN meds | P value* |
|---|---|---|---|---|---|
| ≤6 mo | >6 mo-1 y | >1 y | |||
| No. | 118 | 48 | 39 | 31 | |
| Male sex, n (%) | 78 (66.1) | 33 (68.8) | 25 (64.1) | 20 (64.5) | .88 |
| Gestational age (wk), median (IQR) | 28.4 (5.0) | 28.4 (4.9) | 27.7 (4.6) | 28.6 (10.6) | .51 |
| Gestational age, wk | .36 | ||||
| 22-28 | 70 (59.3) | 27 (56.3) | 26 (66.7) | 17 (54.8) | |
| 29-36 | 33 (28.0) | 16 (33.3) | 10 (25.6) | 7 (22.6) | |
| >36 | 15 (12.7) | 5 (10.4) | 3 (7.7) | 7 (22.6) | |
| Corrected gestational age (wk) at discharge, median (IQR) | 42.4 (6.6) | 42.4 (6.1) | 41.6 (3.8) | 41.6 (16.6) | .13 |
| Birth weight (g), median (IQR)† | 1074 (760) | 1056 (767) | 1042 (636) | 1100 (2040) | .38 |
| Birth weight z-score, mean (SD)† | 0.00 (1.36) | 0.11 (1.74) | −0.22 (0.98) | 0.10 (1.04) | .49 |
| Small size for gestational age, n (%)† | 12 (10.3) | 6 (12.5) | 4 (10.5) | 2 (6.5) | .69 |
| APGAR at 1 minute, median (IQR)‡ | 5 (5) | 6 (5) | 4 (6) | 6 (6) | .15 |
| APGAR at 5 minutes, median (IQR)‡ | 8 (3) | 8 (3) | 7 (2) | 8 (3) | .53 |
| Race, n (%) | .99 | ||||
| White | 62 (52.5) | 21 (43.8) | 23 (59.0) | 18 (58.1) | |
| Black | 33 (28.0) | 16 (33.3) | 9 (23.1) | 8 (25.8) | |
| Hispanic | 3 (2.5) | 1 (2.1) | 1 (2.6) | 1 (3.2) | |
| Asian | 9 (7.6) | 4 (8.3) | 4 (10.3) | 1 (3.2) | |
| Hispanic ethnicity, n (%) | 11 (9.3) | 6 (12.5) | 2 (5.1) | 3 (9.7) | .52 |
| Multiple births, n (%) | .43 | ||||
| Single | 67 (56.8) | 30 (62.5) | 19 (48.7) | 18 (58.1) | |
| Multiple | 20 (16.9) | 9 (18.8) | 8 (20.5) | 3 (9.7) | |
| Unknown | 31 (26.3) | 9 (18.8) | 12 (30.8) | 10 (32.3) | |
| Neonatal course complications, n (%) | |||||
| Patent ductus arteriosus | 22 (18.6) | 8 (16.7) | 10 (25.6) | 4 (12.9) | .36 |
| Chronic lung disease | 4 (3.4) | 3 (6.3) | 1 (2.6) | 0 | .46 |
| Pulmonary HTN | 1 (0.8) | 1 (2.1) | 0 | 0 | .99 |
| Intraventricular hemorrhage | 13 (11.0) | 5 (10.4) | 4 (10.3) | 4 (12.9) | .94 |
| Severe IVH and PVL (grade 3, 4, and PVL) | 7 (5.9) | 3 (6.3) | 2 (5.1) | 2 (6.5) | .99 |
| Tracheostomy placement§ | 8 (7.0) | 1 (2.1) | 4 (10.5) | 3 (10.3) | .19 |
| Feeding tube placement¶ | 30 (25.4) | 13 (27.1) | 10 (25.6) | 7 (25.0) | .98 |
| History of AKI** | 19 (17.0) | 8 (17.0) | 6 (15.8) | 5 (18.5) | .99 |
| Respiratory support at follow-up** | 37 (33.0) | 15 (33.3) | 12 (30.8) | 10 (35.7) | .91 |
| Days with UAC, median (IQR)†† | 0 (4) | 0 (4) | 0 (5) | 0 (3) | .90 |
| Days with UVC, median (IQR)‡‡ | 0 (5) | 1 (6) | 0 (5) | 0 (3) | .75 |
| Imaging Results | |||||
| Abnormal renal ultrasound§§ | 29 (29.9) | 12 (29.3) | 10 (30.3) | 7 (30.4) | .99 |
| LVMI (g/height2.7), median (IQR)¶¶ | 82.6 (32.6) | 75.7 (39.6) | 84.6 (28.2) | 87.0 (54.5) | .91 |
| Discharge antihypertensive therapy class, n (%) | .76 | ||||
| ACE inhibitor | 22 (18.6) | 8 (16.7) | 5 (12.8) | 9 (29.0) | |
| Calcium channel blocker | 57 (48.3) | 22 (45.8) | 23 (59.0) | 12 (38.7) | |
| Diuretic | 16 (13.6) | 7 (14.6) | 4 (10.3) | 5 (16.1) | |
| Alpha- or beta-blocker | 2 (1.7) | 1 (2.1) | 1 (2.6) | 0 | |
| Clonidine | 2 (1.7) | 1 (2.1) | 1 (2.6) | 0 | |
| Multiple | 19 (16.1) | 9 (18.8) | 5 (12.8) | 5 (16.1) | |
| No. of antihypertensive therapy classes, n (%) | .68 | ||||
| 1 | 99 (83.9) | 39 (81.3) | 34 (87.2) | 26 (83.9) | |
| 2 | 16 (13.6) | 8 (16.7) | 5 (12.8) | 3 (9.7) | |
| 3 | 2 (1.7) | 1 (2.1) | 0 | 1 (3.2) | |
| 4 | 1 (0.8) | 0 | 0 | 1 (3.2) | |
| Multiple antihypertensive therapy classes, n (%) | 19 (16.1) | 9 (18.8) | 5 (12.8) | 5 (16.1) | .76 |
| Follow-up length (d), median (IQR) | 286 (312) | 136 (89) | 267 (105) | 529 (279) | na |
AKI, acute kidney injury; LVMI, left ventricular mass index; meds, medications; na, not applicable; PVL, periventricular leukomalacia; UAC, umbilical artery catheter; UVC, umbilical vein catheter.
P values for continuous variables are from 1-way ANOVA or Kruskal-Wallis ANOVA.
P values for categorical variables are from chi-square tests or Fisher’s exact tests.
Sample size for all infants is 118 unless otherwise indicated with superscriptsData only available for 117 infants.
Data only available for 108 infants.
Data only available for 114 infants.
Data only available for 115 infants.
Data only available for 112 infants.
Data only available for 81 infants.
Data only available for 80 infants.
Data only available for 97 infants.
Data only available for 53 infants.
Neonatal complications were common in the cohort, including 18.6% with patent ductus arteriosus. Renal ultrasound abnormalities were seen in 29.9% of infants, including mild pelvocaliectasis (n = 15), nephrocalcinosis (n = 6), and increased echogenicity (n = 3).
Length of Antihypertensive Therapy after NICU Discharge
Of the 118 infants in the cohort, 71 (60.2%) remained on antihypertensive therapy 6 months after NICU discharge. Median follow-up was 286 days (IQR, 312 days). At 1 year after NICU discharge, the number on antihypertensive therapy decreased to 31 (26.3%) and further to 8 (6.8%) at 2 years. There were no significant differences in the bivariable associations between infant characteristics and the length of antihypertensive therapy (Table I). There was no effect of antihypertensive medication class, number of antihypertensive classes prescribed, or the gestational age of infant on time to antihypertensive therapy discontinuation. Figure 2 displays the different types of antihypertensive medications received at each follow-up time point.
Figure 2.
Number of infants on specific antihypertensive medications at NICU discharge and at 6 months, 1 year, and 2 years after NICU discharge.
Antihypertensive Therapy Prescriptions
At the time of discharge, calcium channel blockers were the most prescribed antihypertensive (55.9%) and most infants were treated with one antihypertensive class (83.9%) (Table II, available at www.jpeds.com). Infants born at <29 weeks’ gestation were more likely to be discharged on multiple antihypertensive medication classes compared with infants born at 29-36 weeks’ gestation (22.9% vs 3.0%; P < .05). There were no other differences in antihypertensive medication class prescribed among the gestational age groups (Table III).
Table III.
Comparison of demographic and treatment characteristics of study infants by gestational age
| Variables | <29 wk | 29-36 wk | >36 wk | P value* |
|---|---|---|---|---|
| No. (% of 118) | 70 (59.3) | 33 (28.0) | 15 (12.7) | |
| Initial class of medication, n (%) | .03† | |||
| ACE inhibitor | 9 (12.9) | 8 (24.2) | 5 (33.3) | |
| Calcium channel blocker | 34 (48.6) | 18 (54.5) | 5 (33.3) | |
| Diuretic | 10 (14.3) | 5 (15.2) | 1 (6.7) | |
| Alpha- or beta-blocker | 0 | 1 (3.0) | 1 (6.7) | |
| Clonidine | 1 (1.4) | 0 | 1 (6.7) | |
| Multiple | 16 (22.9) | 1 (3.0) | 2 (13.3) | |
| No. of classes of medication, n (%) | .03† | |||
| 1 | 54 (77.1) | 32 (97.0) | 13 (86.7) | |
| 2 | 14 (20.0) | 1 (3.0) | 1 (6.7) | |
| 3 | 2 (2.9) | 0 | 0 | |
| 4 | 0 | 0 | 1 (6.7) | |
| Multiple antihypertensive therapy classes, n (%) | 16 (22.9) | 1 (3.0)‡ | 3 (13.3) | .02 |
| Remaining on antihypertensive therapy, n (%) | .36 | |||
| 6 mo | 27 (38.6) | 16 (48.5) | 5 (33.3) | |
| 1 y | 26 (37.1) | 10 (30.3) | 3 (20.0) | |
| 2 y | 17 (24.3) | 7 (21.2) | 7 (46.7) |
P values for categorical variables are from chi-square tests or Fisher’s exact tests.
After adjustment for multiple comparisons, there were no differences among the groups.
P < .05 vs gestational age 22-28 wk, Bonferroni multiple comparisons adjustment.
Calcium channel blockers were the most prescribed antihypertensive in infants at each follow-up time point, with 35 (49.3%) infants at 6 months, 12 (38.7%) at 1 year, and 4 (50.0%) at 2 years after NICU discharge. Nineteen infants (16.1%) were treated with multiple medications at discharge, 10 (14.1%) at 6 months, 5 (16.1%) at 1 year, and 2 (25.0%) at 2 years after NICU discharge. Other frequently prescribed antihypertensives included angiotensin-converting enzyme (ACE) inhibitors and diuretics (Figure 2).
Association of Maternal Characteristics with Length of Antihypertensive Therapy
Table IV shows maternal characteristics studied and comparisons between study groups for the 112 mothers of the 118 infants. There was a greater frequency of infants treated with antihypertensive therapy for between 6 months and 1 year born to mothers who received antenatal corticosteroid therapy compared with those treated with antihypertensive therapy >1 year group (69.4% vs 32.1%; P < .05). There were no other differences between the groups.
Table IV.
Comparison of demographic and clinical maternal characteristics overall and by duration of antihypertensive medication treatment
| Variables | All mothers | HTN meds | HTN meds | HTN meds | P value* |
|---|---|---|---|---|---|
| ≤6 mo | >6 mo-1 y | >1 y | |||
| Maternal prenatal care, n (%)† | .24 | ||||
| Had regular prenatal care | 74 (67.3) | 28 (60.9) | 25 (69.4) | 21 (75.0) | |
| No regular prenatal care | 11 (10.0) | 8 (17.4) | 1 (2.8) | 2 (7.1) | |
| Unknown | 25 (22.7) | 10 (21.7) | 10 (27.8) | 5 (17.9) | |
| Maternal antenatal steroid, n (%)‡ | .04 | ||||
| Yes | 59 (54.1) | 25 (55.6) | 25 (69.4) | 9 (32.1)§ | |
| No | 32 (29.4) | 12 (26.7) | 6 (16.7) | 14 (50.0) | |
| Unknown | 18 (16.5) | 8 (17.8) | 5 (13.9) | 5 (17.9) | |
| Maternal HTN, n (%)¶ | .81 | ||||
| Prepregnancy | 3 (2.7) | 1 (2.2) | 0 | 2 (6.7) | |
| Pregnancy only | 9 (8.1) | 3 (6.5) | 3 (8.6) | 3 (10.0) | |
| Both | 2 (1.8) | 0 | 1 (2.9) | 1 (3.3) | |
| None | 71 (64.0) | 31 (67.4) | 23 (65.7) | 17 (56.7) | |
| Unknown | 26 (23.4) | 11 (23.9) | 8 (22.9) | 7 (23.3) | |
| Maternal preeclampsia/eclampsia, n (%) | .92 | ||||
| Yes | 26 (23.2) | 9 (19.6) | 10 (27.8) | 7 (23.3) | |
| No | 71 (63.4) | 31 (67.4) | 21 (58.3) | 19 (63.3) | |
| Unknown | 15 (13.4) | 6 (13.0) | 5 (13.9) | 4 (13.3) | |
| Maternal diabetes, n (%) | .81 | ||||
| Prepregnancy type 1 | 5 (4.5) | 1 (2.2) | 3 (8.3) | 1 (3.3) | |
| Prepregnancy type 2 | 4 (3.6) | 1 (2.2) | 2 (5.6) | 1 (3.3) | |
| Gestational | 5 (4.5) | 1 (2.2) | 3 (8.3) | 1 (3.3) | |
| None | 76 (67.9) | 33 (71.7) | 22 (61.1) | 21 (70.0) | |
| Unknown | 22 (19.6) | 10 (21.7) | 6 (16.7) | 6 (20.0) | |
| Age at delivery (y), median (IQR)** | 26 (10) | 26 (10) | 27 (12) | 24 (10) | .14 |
P value for age at delivery is from Kruskal-Wallis ANOVA. Bonferroni multiple comparisons adjustment.
P values for categorical variables are from chi-square tests or Fisher’s exact tests.
Sample size for all mothers is 112 unless otherwise indicated with superscripts: Data only available for 110 mothers.
Data only available for 109 mothers.
P < .05, mothers of infants on HTN meds >1 y vs mothers of infants on HTN meds 6 mo-1 y.
Data only available for 111 mothers.
Data only available for 93 mothers.
Discussion
In this retrospective multicenter study of neonates with idiopathic HTN discharged from the NICU on antihypertensive therapy, we found that 60% of infants remained on antihypertensive therapy 6 months after NICU discharge, and >25% remained on therapy for ≥1 year after discharge. Although our findings are in concert with previous studies that most infants requiring antihypertensive medications at NICU discharge have declining antihypertensive needs over time, the duration of HTN treatment in our study is longer than previously reported.
More than one-half (60%) of patients in this study remained on antihypertensive therapy 6 months after NICU discharge. This number is higher than previously reported studies and may reflect changes in idiopathic HTN in infants. Seliem et al reported only 15% of infants receiving antihypertensive therapy at the age of 3-6 months.8 In a study of prematurely born infants with idiopathic HTN by Jenkins et al, the average treatment duration after NICU discharge was 5 months.4 We hypothesize that the longer duration of antihypertensive therapy in our study may be due to our study design, because patients were followed in pediatric subspecialty clinics after NICU discharge, and this cohort may represent infants with more severe or difficult-to-treat HTN. Another possible explanation is that our study may have included more premature infants with median gestational age of 28 weeks compared with 34 in previous studies.4,8 However, these differences are modest and gestational age was not associated with a longer duration of antihypertensive therapy.
Although studies have indicated the role of gestational age, respiratory disease, and many other neonatal and maternal factors as a cause of neonatal HTN, we did not see an association between these factors and duration of antihypertensive treatment in our study.1 We did find that maternal exposure to antenatal corticosteroids was associated with a shorter duration of antihypertensive treatment. Antenatal corticosteroid treatment is widely used to prevent respiratory distress syndrome and decrease the risk of intraventricular hemorrhage in preterm infants and is associated with higher blood pressures in newborns.1 In animal models, antenatal corticosteroid treatment result in more rapid glomerulogenesis, but with morphologic abnormalities and an overall decrease in nephron number.11-14 Maternal antenatal corticosteroids are also associated with poor cardiovascular outcomes throughout the life course.15 Our findings of a higher incidence of HTN and quicker resolution of antihypertensive therapy in those with maternal antenatal steroid exposure in the context of existing animal and human studies merit further evaluation with studies designed to specifically evaluate the kidney and cardiovascular implications of maternal antenatal corticosteroids exposure.
We report that, at time of discharge from NICU, calcium channel blocker therapy was the most prescribed class of antihypertensives (55.9%), followed by ACE inhibitors (28.8%). These findings resemble previous reports and practitioners’ experience that calcium channel blockers are overall well-tolerated and frequently used. Our report confirms a shift over time in prescribing practice, with previous studies in infants admitted to the NICU reporting direct vasodilators were most commonly used (64.2%), followed by ACE inhibitors (50.8%), calcium channel blockers (24%), and alpha- and beta-blockers (18.4%).16 We found a substantially lower use of ACE inhibitors compared with previous studies, particularly in infants born at <29 weeks’ gestation.1 Our finding agrees with a recent publication evaluating antihypertensive prescribing practice during NICU admission, which shows a similar decline in ACE inhibitor use.17 We suspect that this decline may be due to growing concern about ongoing postnatal glomerulogenesis, which could be impeded by ACE inhibition.18 There have been no randomized clinical trials of antihypertensive therapy in infants, and most recommendations are based on expert opinion and case series.
There are several limitations to this study. First, owing to the retrospective design, there may be inaccuracies in data collection of maternal and infant demographic characteristics, duration of HTN, and factors associated with HTN, most notably in the identification of potentially relevant exposures such as postnatal steroids and nephrotoxic medications. Comorbid diagnoses from the NICU admission (such as acute kidney injury and bronchopulmonary dysplasia) were taken from review of the NICU discharge summary therefore had to be both recognized and documented by providers caring for the patient. We also acknowledge that infants described as having idiopathic HTN may have HTN secondary to antenatal steroids or other factors not identified in our study. Second, sample sizes of the groups may have resulted in insufficient statistical power to detect differences for some factors. Third, infants were diagnosed and treated for HTN at 14 different institutions with differing clinical practices and standards of care. Therefore, selection bias and practice variation among providers are likely and, given the small numbers of infants from each site, we were unable to control for center-specific variations. Furthermore, these data are from 2012-2017, and it is possible that practice patterns of antihypertensive therapy may have shifted since then. Finally, given our inclusion criteria of only infants discharged from the NICU on antihypertensive therapies, we are unable to further characterize prevalence or characteristics of all infants with HTN or those who did not follow up after discharge. Despite these limitations, this multicenter retrospective study has several strengths, including the number of centers and detailed retrospective data including neonatal and maternal characteristics and robust longitudinal follow-up on antihypertensive therapy until 2 years of age in many infants.
In conclusion, we report that most infants treated for HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data raise questions about the etiology of idiopathic HTN. Further research is needed to better understand the natural history, clinical outcomes, and optimal management of idiopathic neonatal HTN.
Supplementary Material
Declaration of Competing Interest
M.S. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases T32DK007662 and National Center for Advancing Translational Sciences, Grant numbers: K12TR004415. The funding sources for this study had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
The authors declare no conflicts of interest.
Glossary
- ACE
Angiotensin-converting enzyme
- HTN
Hypertension
- NICU
Neonatal intensive care unit
Footnotes
Portions of this data were presented as a platform presentation at Pediatric Academic Society Meeting, April 24-May 19, 2019, Baltimore, MD.
Deidentified individual participant data will be made available to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal.
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