Abstract
Objective:
To investigate the optimal gestational age to deliver pregnant people with chronic hypertension (CHTN) to improve perinatal outcomes.
Methods:
We conducted a planned secondary analysis of a randomized controlled trial of CHTN treatment to different blood pressure goals. Participants with a term, singleton gestation were included. Pregnancies with fetal anomalies and those with a diagnosis of preeclampsia < 37 weeks were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit (ICU) admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar < 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios with 95% CIs are reported.
Results:
1,417 participants with mild CHTN were included; 305 (21.5%) with a new diagnosis in pregnancy and 1112 (78.5%) with known pre-existing HTN. Groups differed by body mass index and pre-existing diabetes. In adjusted models, there was not an association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI 1.40–5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI 1.27–3.08 in week 37 and 14.4% vs 7.7%, aOR 1.82, 95% CI 1.06–3.10 in week 38).
Conclusions:
Planned delivery in the early term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild CHTN should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.
Precis:
Planned early term delivery in individuals with mild chronic hypertension was not associated with a reduction in adverse maternal outcomes, but was associated with an increase in some neonatal complications.
Introduction
Chronic hypertension (CHTN) is a common underlying comorbidity encountered during pregnancy affecting approximately 2% of all pregnancies in the United States.1–3 Individuals with CHTN are at increased risk of adverse pregnancy and neonatal outcomes related predominantly to progression to preeclampsia and preterm birth. For those with ongoing pregnancies in the early term period, clinicians and patients must weigh appropriate timing of delivery to optimize both maternal and neonatal outcomes. The American College of Obstetricians and Gynecologists (ACOG) recommends delivery as early as 37w0d gestation to as late as 39w6d for chronic hypertension (CHTN).4
In uncomplicated pregnancies, induction of labor at 39 weeks’ gestation compared with expectant management does not increase the risk of adverse neonatal outcomes and decreases the risk of cesarean birth and development of hypertensive disorders of pregnancy.5 In patients with more complex pregnancies, induction of labor is often recommended earlier than 39 weeks’ gestation as the risks associated with ongoing pregnancy are greater than the risks of early term delivery.6 While some clinicians use factors such as severity of hypertensive disease and need for anti-hypertensive therapy to modify decision-making related to timing of delivery, there are limited data to guide these decisions.
A 2017 Cochrane review summarized existing data related to timing of delivery for pregnancies complicated by hypertensive disorders beyond 34 weeks’ gestation.7 When all hypertensive disorders were pooled for the analysis there were lower rates of maternal morbidity and mortality, but increased risk of neonatal intensive care unit (NICU) admission and respiratory distress syndrome (RDS) for neonates with earlier delivery. However, the authors noted a need for more studies specifically examining different types of hypertensive disorders and including both maternal and neonatal outcomes.
Our objective was to investigate the optimal gestational age to deliver pregnant people with mild CHTN by evaluating the association between planned delivery and maternal and neonatal outcomes by week of delivery compared with those expectantly managed.
Methods
This was a planned secondary analysis of the Chronic Hypertension in Pregnancy (CHAP) trial which was a randomized controlled trial of CHTN treatment to different blood pressure goals. Details of the parent study were previously published.8 For this planned secondary analysis, participants with a term (≥ 37w0d), living singleton gestation were included. Pregnancies with fetal anomalies and those with a diagnosis of preeclampsia < 37 weeks’ gestation were excluded. A diagnosis of preeclampsia prior to 37 weeks’ gestation was assumed for participants who had an indication for delivery of preeclampsia between 37w0d and 37w2d. IRB approval for this secondary analysis was obtained at all sites as part of the parent trial.
Patients who remained pregnant at the start of each gestational week were classified as undergoing planned delivery or expectant management. A classification of planned delivery was based on the recorded indication for delivery (either induction or cesarean without labor) and timing of delivery. Participants with specific indications for delivery and who underwent either induction of labor or cesarean without labor between 37w0d-37w2d, 38w0d-38w2d, or 39w0d-39w2d were classified as planned delivery in the corresponding gestational week. Indications in these data ranges that were classified as planned deliveries were chronic hypertension, fetal growth restriction, macrosomia, prior stillbirth, diabetes, maternal cardiac disease, positive fetal lung maturity, previa or elective. Patients who had a delivery in these date ranges with indications that included preeclampsia, oligohydramnios, or abruption beyond 37 weeks’ gestation were considered to have unplanned deliveries (e.g., were being expectantly managed) as individuals with these conditions are typically delivered at the time of diagnosis if the pregnancy is beyond 37 weeks’ gestation per ACOG recommendations.6 All others were classified as expectant management.
The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit (ICU) admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal composite outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar < 3 at 5 minutes, neonatal seizures, suspected sepsis. Secondary outcomes included intrapartum cesarean birth, and neonatal outcomes including length of stay, NICU admission, respiratory distress syndrome, transient tachypnea of the newborn, and hypoglycemia. Analyses to examine intrapartum cesarean birth excluded those with a scheduled repeat cesarean delivery who did not experience labor. All outcomes were obtained by medical record abstraction performed by trained perinatal research staff for 6 weeks after birth. All components of the primary maternal composite with the exception of hemorrhage requiring blood transfusion were also adjudicated by site investigators.
Baseline demographic and socioeconomic characteristics were collected including maternal age in years, pre-existing diabetes, body mass index (BMI) at parent study enrollment, race and ethnicity, marital status, education level, insurance type, tobacco use, aspirin use, new or pre-existing CHTN and medication use, and whether the participant was in the active (goal BP <140/90) or control (goal BP <160/105) arm of the parent CHAP trial. Race and ethnicity were recorded as part of the parent trial to ensure a diverse population, and for assessment of generalizability of the study findings.
In bivariate comparisons, those with a planned delivery were compared with those expectantly managed during each gestational week using Chi square or two sample t test as appropriate. Differences between groups at baseline with a P value <0.05 and covariates that were judged to be clinically important a priori were considered for inclusion in the multivariable logistic regression models for study outcomes. The model for neonatal length of stay was estimated with analysis of covariance (ANCOVA). An additional sensitivity analysis was performed excluding participants with pre-existing diabetes. Adjusted odds ratios with 95% CIs are reported. Multivariable modeling was not performed for outcomes with counts less than 5 in either group. Given some level of uncertainty in the assumptions for planned delivery based on timing and indication, we also performed a secondary analysis in which patients were simply classified into the gestational week in which they delivered regardless of whether delivery was planned to evaluate the consistency of the observed results.
No adjustments were made for multiple comparisons; thus, the results should be considered exploratory. All analyses were performed in SAS version 9.4 The principles of the STROBE guidelines for reporting of observational studies were followed.
Results
Of the 2,408 participants available from the CHAP trial cohort, 1,417 participants with mild CHTN at term were eligible for inclusion (Figure 1). Of the included participants, 305 (21.5%) had a new diagnosis of CHTN in pregnancy and 1,112 (78.5%) had known pre-existing HTN. At 38 weeks, there were 961 participants who were still pregnant and could be analyzed; this number decreased to 460 at the beginning of 39 weeks. Overall, 618 (43.6%) participants had planned deliveries across the analyzed time period and 378 (26.7%) were taking an antihypertensive medication (230 labetalol only, 133 extended-release nifedipine only and 15 taking both at delivery).
Figure 1.
Flow chart of participants including number per gestational weeks at delivery.
Participants with planned deliveries differed from those who were expectantly managed by some baseline characteristics in each gestational age week (Table 1). There were no differences at baseline in maternal age, education level, insurance status, aspirin use, or parent trial treatment group in any gestational age week.
Table 1.
Characteristics of Planned Delivery versus Expectant Management Groups for Each Gestational Age Week
| Characteristic | 37w0d-39w6d (n=1417) | 38w0d-39w6d (n=961) | 39w0d-39w6d (n=460) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Planned Delivery (n=165) | Expectant Management (n=1252) | P value* | Planned Delivery (n=160) | Expectant Management (n=801) | P value* | Planned Delivery (n=293) | Expectant Management (n=167) | P value* | |
| Maternal age in years | 33.1 ± 5.6 | 32.1 ± 5.5 | 0.04 | 32.0 ± 5.4 | 32.1 ± 5.5 | 0.84 | 31.7 ± 5.5 | 32.1 ± 5.7 | 0.51 |
| Pre-existing diabetes | 29 (17.5) | 154 (12.3) | 0.06 | 30 (18.8) | 76 (9.5) | <.001 | 30 (10.2) | 10 (6.0) | 0.12 |
| BMI at enrollment | 38.2 ± 8.7 | 37.4 ± 9.8 | 0.30 | 38.3 ± 9.3 | 37.0 ± 9.8 | 0.14 | 37.8 ± 10.4 | 36.9 ± 9.8 | 0.39 |
| Race and ethnicity | |||||||||
| Black, non-Hispanic | 47 (28.5) | 391 (31.2) | 0.40 | 56 (35.0) | 243 (30.3) | 0.02 | 86 (29.4) | 44 (26.3) | 0.84 |
| Hispanic | 83 (50.3) | 576 (46.0) | 58 (36.3) | 383 (47.8) | 145 (49.5) | 88 (52.7) | |||
| White, non-Hispanic | 32 (19.4) | 234 (18.7) | 41 (25.6) | 142 (17.7) | 49 (16.7) | 26 (15.6) | |||
| None of the above | 3 (1.8) | 51 (4.1) | 5 (3.1) | 33 (4.1) | 13 (4.4) | 9 (5.4) | |||
| Chronic hypertension type | |||||||||
| Newly diagnosed | 33 (20.0) | 272 (21.7) | 0.87 | 34 (21.3) | 181 (22.6) | 0.01 | 74 (25.3) | 38 (22.8) | 0.53 |
| Known, medication | 100 (60.6) | 738 (58.9) | 82 (51.3) | 479 (59.8) | 179 (61.1) | 100 (59.9) | |||
| Known, no medication | 32 (19.4) | 242 (19.3) | 44 (27.5) | 141 (17.6) | 40 (13.7) | 29 (17.4) | |||
| Married* | 84 (50.9) | 637 (50.9) | 0.97 | 101 (63.1) | 407 (50.8) | 0.003 | 124 (42.3) | 83 (49.7) | 0.14 |
| Maternal education* | |||||||||
| Less than high school | 13 (7.9) | 124 (9.9) | 0.34 | 20 (12.5) | 74 (9.2) | 0.16 | 27 (9.2) | 17 (10.2) | 0.61 |
| High school or equivalent | 43 (26.1) | 354 (28.3) | 33 (20.6) | 237 (29.6) | 87 (29.7) | 59 (35.3) | |||
| Some college | 31 (18.8) | 279 (22.3) | 36 (22.5) | 176 (22.0) | 67 (22.9) | 32 (19.2) | |||
| College graduate | 60 (36.4) | 381 (30.4) | 43 (26.9) | 250 (31.2) | 90 (30.7) | 50 (29.9) | |||
| Maternal insurance* | |||||||||
| Government/Medicaid | 82 (49.7) | 650 (51.9) | 0.56 | 83 (51.9) | 423 (52.8) | 0.94 | 160 (54.6) | 94 (56.3) | 0.89 |
| Private insurance | 75 (45.5) | 524 (41.9) | 64 (40.0) | 335 (41.8) | 118 (40.3) | 64 (38.3) | |||
| None or self-pay | 6 (3.6) | 63 (5.0) | 7 (4.4) | 41 (5.1) | 14 (4.8) | 9 (5.4) | |||
| Current tobacco use | 11 (6.7) | 71 (5.7) | 0.61 | 12 (7.5) | 42 (5.2) | 0.26 | 19 (6.5) | 6 (3.6) | 0.19 |
| Aspirin use at baseline | 80 (48.5) | 560 (44.7) | 0.36 | 76 (47.5) | 346 (43.2) | 0.32 | 136 (46.4) | 74 (44.3) | 0.66 |
| Parent trial treatment group | |||||||||
| Active (BP <140/90) | 92 (55.8) | 665 (53.1) | 0.52 | 82 (51.3) | 419 (52.3) | 0.81 | 151 (51.5) | 87 (52.1) | 0.91 |
| Control (BP <160/105) | 73 (44.2) | 587 (46.9) | 78 (48.7) | 382 (47.7) | 142 (48.5) | 80 (47.9) | |||
BMI is body mass index in kg/m2. BP is blood pressure in mmHg.
P value obtained for categorical outcomes using Chi square test. Two sample t-test used for maternal age and BMI at enrollment.
Missing data for 37w0d-39w6d cohort data – Marital status: 1 (<1%) in planned delivery group and 12 (1.0%) in the expectant group, education level: 18 (10.9%) in planned delivery group and 114 (9.1%) in expectant group, maternal insurance: 2 (1.2%) in planned delivery group and 15 (1.2%) in expectant group.
Missing data for 38w0d-39w6d subcohort – Marital status: 3 (1.9) in planned delivery group and 6 (<1) in the expectant group, education level: 28 (17.5) in planned delivery group and 64 (8.0) in expectant group, maternal insurance: 6 (3.8) in planned delivery group and 2 (<1) in expectant group.
Missing data for 39w0d-39w6d subcohort – Marital status: 3 (1.0) in planned delivery group and 1 (<1) in the expectant group, education level: 22 (7.5) in planned delivery group and 9 (5.4) in expectant group, maternal insurance: 1 (<1) in planned delivery group.
The overall rate of the primary maternal composite endpoint was 14.1% with 14 cases of serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit (ICU) admission, intubation, renal failure), 161 cases of preeclampsia with severe features, 51 cases of hemorrhage requiring blood transfusion, and 5 cases of abruption. The prevalence of maternal outcomes by planned delivery and expectant management groups is included in Table 2. In models adjusting for pre-existing diabetes and BMI, there was not a statistically significant association between planned delivery and the maternal composite outcome in any gestational age week compared with expectant management (Table 2).
Table 2.
Maternal and Neonatal Outcomes of those with Planned Delivery versus Expectant Management
| Outcome | 37w0d-39w6d (n=1417) | 38w0d-39w6d (n=961) | 39w0d-39w6d (n=460) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Planned Deliverya (n=165) | Expectant Management (n=1252) | baOR (95% CI) | Planned Deliveryc (n=160) | Expectant Management (n=801) | baOR (95% CI) | Planned Deliveryd (n=293) | Expectant Management (n=167) | baOR (95% CI) | |
| Maternal primary composite outcome and components of the outcome, n(%) | |||||||||
| Primary composite maternal outcome | 20 (12.1) | 180 (14.4) | 0.83 (0.50–1.36) | 14 (8.8) | 99 (12.4) | 0.65 (0.36–1.18) | 32 (10.9) | 17 (10.2) | 1.02 (0.54–1.91) |
| Serious maternal morbidity | 0 (0) | 14 (1.1) | N/Ae | 1 (<1) | 9 (1.1) | N/Ae | 5 (1.7) | 1 (<1) | N/Ae |
| Preeclampsia with severe features | 13 (7.9) | 148 (11.8) | 0.64 (0.35–1.16) | 11 (6.9) | 81 (10.1) | 0.63 (0.33–1.22) | 20 (6.8) | 16 (9.6) | 0.69 (0.35–1.38) |
| Hemorrhage requiring blood transfusion | 7 (4.2) | 44 (3.5) | 1.22 (0.54–2.77) | 4 (2.5) | 29 (3.6) | N/Ae | 17 (5.8) | 2 (1.2) | N/Ae |
| Placental abruption | 1 (<1) | 4 (<1) | N/Ae | 1 (<1) | 2 (<1) | N/Ae | 0 (0) | 1 (<1) | N/Ae |
| Primary composite neonatal outcome | 36 (21.8) | 192 (15.3) | 1.44 (0.96–2.17) | 24 (15.0) | 112 (14.0) | 1.01 (0.62–1.65) | 47 (16.0) | 22 (13.2) | 1.24 (0.72–2.15) |
| Secondary neonatal outcomes, n(%) | |||||||||
| Length of neonatal stay (Mean ± SD) | 1.5 ± 4.3 | 0.9 ± 3.9 | 0.48 (-0.15, 1.12) | 1.4 ± 4.7 | 0.7 ± 3.3 | 0.46 (-0.15, 1.07) | 0.7 ± 2.1 | 0.5 ± 1.6 | 0.16 (-0.21, 0.53) |
| NICU admission, n(%) | 37 (22.4) | 196 (15.7) | 1.51 (1.00–2.27) | 29 (18.1) | 98 (12.2) | 1.40 (0.88–2.24) | 43 (14.7) | 17 (10.2) | 1.47 (0.80–2.68) |
| RDS, n(%) | 13 (7.9) | 37 (3.0) | 2.70 (1.40–5.22) | 6 (3.8) | 12 (1.5) | 2.67 (0.98–7.28) | 7 (2.4) | 1 (<1) | N/Ae |
| TTN, n(%) | 8 (4.9) | 43 (3.4) | 1.41 (0.65–3.07) | 8 (5.0) | 23 (2.9) | 1.63 (0.71–3.75) | 10 (3.4) | 3 (1.8) | N/Ae |
| Hypoglycemia, n(%) | 32 (19.4) | 134 (10.7) | 1.97 (1.27–3.08) | 23 (14.4) | 62 (7.7) | 1.82 (1.06–3.10) | 16 (5.5) | 11 (6.6) | 0.51 (0.21–1.23) |
Planned delivery group included anyone with a scheduled induction of labor or cesarean without labor from 37w0d to 37w2d with indications of chronic hypertension, fetal growth restriction, macrosomia, prior stillbirth, diabetes, maternal cardiac disease, positive fetal lung maturity, previa or elective. Other participants who were still pregnant at or beyond 37w0d were considered expectantly managed.
Adjusted odds ratio with 95% confidence interval was obtained by multivariable logistic regression models for binary outcomes. Covariates included maternal BMI and pre-existing diabetes which were different between groups at baseline. The difference for length of neonatal stay between planned delivery and expected management with 95% confidence interval was estimated by analysis of covariance (ANCOVA).
Planned delivery group included anyone with a scheduled induction of labor or cesarean without labor from 38w0d to 38w2d with indications as detailed in footnote a. Other participants who were still pregnant at that time were considered expectantly managed.
Planned delivery group included anyone with a scheduled induction of labor or cesarean without labor from 39w0d to 39w2d with indications as detailed in footnote a. Other participants who were still pregnant at that time were considered expectantly managed.
N/A: Multivariable modeling was not performed if count less than 5
Bolded numbers are statistically significant results.
The rate of the primary neonatal composite endpoint was 16.1% with 4 cases of fetal death, 3 cases of neonatal death, 172 cases of respiratory support beyond oxygen mask, 6 cases of Apgar < 3 at 5 minutes, 23 cases of neonatal seizures, and 76 cases of suspected sepsis. The prevalence of neonatal outcomes by planned delivery and expectant management groups is included in Table 2. In adjusted models, there was not an association between planned delivery and the primary neonatal composite outcome in any gestational age week (Table 2).
In terms of the secondary outcomes, planned delivery was not associated with increased odds of intrapartum cesarean birth after excluding those with unlabored scheduled repeat cesarean deliveries (see Appendix 1, available online at http://links.lww.com/xxx). Planned delivery at 37 and 38 weeks was associated with adverse neonatal outcomes including RDS at 37 weeks and hypoglycemia at 37 and 38 weeks when compared with expectant management (Table 2). There was not an association between planned delivery and neonatal length of stay, NICU admission, proven neonatal sepsis, or TTN.
In a secondary analysis, simple comparisons were performed by gestational age week at delivery irrespective of planned delivery or expectant management. In these analyses, cesarean delivery, RDS and hypoglycemia were similarly more frequent with early term births. In addition, the maternal morbidity composite, the fetal and neonatal composite, length of stay and NICU admission were more frequent with early term births. Preeclampsia with severe features was more frequent in the group delivered 37w0d-37w6d compared with those delivered 39w0d-39w6d. Data are presented in Appendix 2, available online at http://links.lww.com/xxx. An additional sensitivity analysis was performed excluding participants with pre-existing diabetes. In this analysis, planned delivery remained associated with hypoglycemia at 37 weeks (see Appendix 3, available online at http://links.lww.com/xxx).
Discussion
In a cohort of individuals with mild CHTN, planned delivery in the early term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, early term delivery was associated with an increase in some neonatal complications including RDS and hypoglycemia. Delivery timing should weigh maternal and neonatal outcomes in each gestational week with recognition that many factors likely influence optimal delivery timing; however, in a stable patient with mild CHTN delivery at 39 weeks’ gestation may optimize outcomes.
Ram et al. compared outcomes with induction at 38 and 39 weeks of gestation versus expectant management in a cohort of 2,420 patients with CHTN; those who were induced were found to have lower (at 38 weeks) or similar (at 39 weeks) rates of cesarean delivery, and were less likely to experience disease progression to superimposed preeclampsia or eclampsia.9 The differences in results for maternal complications between the study by Ram et al. and our study may reflect that the prior study used any superimposed preeclampsia as the outcome. We focused on conditions anticipated to result in serious morbidity and only examined development of preeclampsia with severe features, not any preeclampsia. In addition, they only included an indication of CHTN in the planned induction group and we classified participants as a planned delivery for a number of standard indications. Some of the participants in our planned delivery group would have had an indication for delivery that would always necessitate a cesarean (eg. previa); although the number of participants with such an indication for cesarean at early term were small.
Harper and colleagues examined a similar question in a single center cohort of 683 individuals with CHTN.10 They found that planned delivery prior to 37 weeks’ gestation was associated with a composite adverse neonatal outcome that included stillbirth, neonatal death, cord pH < 7.0, 5-minute Apgar score of 3 or less, and neonatal seizures. They did not observe increased maternal risks until pregnancies were managed expectantly beyond 39 weeks’ gestation. These findings are similar to ours in terms of higher neonatal risks with earlier gestational age at delivery, although we did not examine gestational age windows prior to 37 weeks’ gestation.
There is an ongoing multicenter trial evaluating delivery of otherwise uncomplicated pregnancies with CHTN or gestational HTN at 38 weeks’ gestation versus expectant management to or beyond 40 weeks’ gestation called WILL (When to Induce Labour to Limit Risk in pregnancy hypertension): Protocol for a Multicentre Randomised Trial, registration SRCTN 77258279].11 The co-primary outcomes are maternal (severe hypertension, death, morbidity) and neonatal (NICU admission for >4 hours). Ultimately, randomized trial data will provide rigorous data to further guide clinical decision-making regarding timing of delivery.
Strengths of this study include rigorously collected data by trained perinatal research staff regarding baseline disease status and pregnancy outcomes. In addition, CHAP trial sites span many centers across the U.S. increasing generalizability. We took a nuanced approach and compared those with planned deliveries to those who were expectantly managed as this is the clinical scenario that practitioners face. We also included both maternal and neonatal outcomes, which are both important when weighing delivery timing with patients.
Limitations of this work include that we made assumptions when classifying patients as planned deliveries versus expectantly managed. This need arose from the way data were collected in the parent study, which noted only induction or scheduled cesarean without further information regarding whether it was scheduled in advance of the gestational week or prompted by a change in clinical status within the gestational week. We excluded people who developed superimposed preeclampsia prior to 37 weeks’ gestation as we assumed that people with preeclampsia would all be delivered early term based on ACOG guidelines; thus, the results are only generalizable to those who remain pregnant at term without superimposed preeclampsia. Our subgroups by gestational week were smaller than the overall cohort, which left us with insufficient sample size to examine some of the rare outcomes. There is also a possibility of type II error for the maternal outcomes as our sample size was limited to those in the parent trial, and while not statistically significant, the frequency of developing preeclampsia with severe features was lower in the planned delivery group compared with expectant management in weeks 37 and 38. Participants were not randomized to delivery timing. In addition, we do not have information about the nuanced decision making that occurred between the patient and clinician, which likely affected delivery timing in some cases. While we adjusted for pre-existing diabetes and BMI in multivariable models, there remains the possibility of residual confounding.
In conclusion, waiting for planned delivery until 39 weeks’ gestation, taking into consideration the overall clinical picture and potential need to deliver earlier when indicated, may optimize maternal and neonatal outcomes for individuals with mild CHTN. Further data from randomized controlled trials is needed to refine clinical guidance.
Supplementary Material
Funding:
This work is funded by the National Heart, Lung and Blood Institute (5U01HL1208336 and 5R01HL1208336). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Sinkey was supported by NHLBI K23159331 during the completion of this work.
Footnotes
The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.”
Financial Disclosure: Torri D. Metz reports personal fees from Pfizer for her role as a medical consultant for a SARS-CoV-2 vaccination in pregnancy study, grants from Pfizer for role as a site PI for SARS-CoV-2 vaccination in pregnancy study, and grants from Pfizer for role as a site PI for RSV vaccination in pregnancy study outside the submitted work. Sherri Longo reports that UAB received NIH funding for the CHAP trial and Ochsner was one of the sites participating in the trial. Ochsner received a subaward from UAB for participation in the trial. Ochsner is a subsite to UAB, who is in the MFMU network; therefore, they have participated in trials. They have participated in other studies with UAB, including the CSOAP trial. They have collaborated on studies with Tulane and have subawards. Kelly Gibson reports money was paid to her institution from NHLBI, NICHD, and Materna Medical. Lauren Plante reports receiving payment from Cambridge University Press and Taylor & Francis for textbook royalties. She also received an honorarium speaking fee from Monmouth Medical Center. Sean Esplin received payment from Laborie and Nemo Health. Heather Frey and Wendy Kinzler received payment from UptoDate. Todd Rosen’s institution received payment from Materna, Inc. and Myriad, Inc. Mary Norton received payment from Luna Genetics. Daniel Skupski received payment from Organon and Cooper Surgical. Leonardo Pereira’s institution received payment for a Johnson & Johnson clinical trial. He received payment from Prehevbrio - for serving on the data safety monitoring board for hepatitis vaccine in pregnancy. Namasivayam Ambalavanan received payment from Oak Hill Bio and for serving on the advisory board and holding intellectual property with AlveolusBio and Resbiotic. Alan T.N. Tita’s institution received payment from Pfizer. Everett Magann received payment from Up to Date for co-authorship of the Ultrasound Assessment of Amniotic Fluid Volume chapter. Lorraine Dugoff reports that money was paid to her institution from Myriad and Natera. Brenna L. Hughes reports receiving funding from UptoDate and Moderna. Eugene Chang reports money was paid to his institution from Roche Diagnostics and Roche. The other authors did not report any potential conflicts of interest.
Torri D. Metz, Deputy Editor (Obstetrics) of Obstetrics & Gynecology, was not involved in the review or decision to publish this article.
Each author has confirmed compliance with the journal’s requirements for authorship.
Presented at the Society for Maternal-Fetal Medicine Annual Meeting on February 14, 2024, in National Harbor, Maryland.
PEER REVIEW HISTORY
Received March 23, 2024. Received in revised form May 24, 2024. Accepted May 30, 2024. Peer reviews and author correspondence are available at http://links.lww.com/xxx.
Contributor Information
Torri D. Metz, Department of Obstetrics and Gynecology, University of Utah.
Hui-Chien Kuo, Department of Biostatistics, University of Alabama at Birmingham.
Lorie Harper, Department of Women’s Health, University of Texas at Austin.
Baha Sibai, Department of Obstetrics and Gynecology, University of Texas at Houston.
Sherri Longo, Ochsner Baptist Medical Center.
George R. Saade, Department of Obstetrics and Gynecology, University of Texas Medical Branch.
Lorraine Dugoff, Department of Obstetrics and Gynecology, University of Pennsylvania.
Kjersti Aagaard, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children’s Hospital.
Kim Boggess, Department of Obstetrics and Gynecology, University of North Carolina Chapel Hill, NC.
Kirsten Lawrence, Department of Obstetrics and Gynecology, Columbia University.
Brenna L. Hughes, Department of Obstetrics and Gynecology, Duke University.
Joseph Bell, St. Luke’s University Health Network.
Rodney K. Edwards, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences.
Kelly S. Gibson, MetroHealth System.
David M Haas, Department of Obstetrics and Gynecology, Indiana University.
Lauren Plante, Department of Obstetrics and Gynecology, Drexel University College of Medicine.
Brian Casey, Department of Obstetrics and Gynecology, University of Alabama at Birmingham.
Sean Esplin, Intermountain Healthcare, Utah.
Matthew K. Hoffman, Christiana Care Health Services.
Kara K. Hoppe, Department of Obstetrics and Gynecology, UnityPoint Health-Meriter Hospital/Marshfield Clinic.
Janelle Foroutan, St. Peters University Hospital.
Methodius Tuuli, Department of Obstetrics and Gynecology, Washington University.
Michelle Y. Owens, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS.
Hyagriv N. Simhan, Department of Obstetrics and Gynecology, Magee Women’s Hospital and University of Pittsburgh.
Heather Frey, Department of Obstetrics and Gynecology, Ohio State University.
Todd Rosen, Department of Obstetrics and Gynecology, Rutgers University-Robert Wood Johnson Medical School.
Anna Palatnik, Department of Obstetrics and Gynecology, Medical College of Wisconsin.
Susan Baker, Department of Obstetrics and Gynecology, University of South Alabama at Mobile.
Phyllis August, Weill Cornell University.
Uma M. Reddy, Department of Obstetrics and Gynecology, Yale University.
Wendy Kinzler, Department of Obstetrics and Gynecology, NYU Langone Hospital–Long Island.
Emily J. Su, Department of Obstetrics and Gynecology, University of Colorado.
Iris Krishna, Department of Obstetrics and Gynecology, Emory University.
Nguyet A. Nguyen, Department of Obstetrics and Gynecology, Denver Health.
Mary E. Norton, Department of Obstetrics and Gynecology, University of California San Francisco; Zuckerberg San Francisco General Hospital.
Daniel Skupski, Department of Obstetrics and Gynecology, New York Presbyterian Queens Hospital.
Yasser Y. El-Sayed, Department of Obstetrics and Gynecology, Stanford University.
Dotun Ogunyemi, Departments of Obstetrics and Gynecology Arrowhead Regional Medical Center / Beaumont Hospital, Michigan.
Ronald Librizzi, Virtua Health, Marlton, NJ, USA.
Leonardo Pereira, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon.
Everett F. Magann, Department of Obstetrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Mounira Habli, Fetal Care Center of Cincinnati, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Shauna Williams, Department of Obstetrics, Gynecology and Women’s Health, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, USA.
Giancarlo Mari, Obstetrics and Gynecology/Maternal-Fetal Medicine, The University of Tennessee Health Science Center, Memphis, USA.
Gabriella Pridjian, Department of Obstetrics & Gynecology, Tulane University, New Orleans, LA, 70112, USA.
David S. McKenna, Department of Obstetrics and Gynecology, Wright State University and Miami Valley Hospital, Dayton, Ohio, USA.
Marc Parrish, Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Eugene Chang, Medical University of South Carolina, Charleston, SC, USA.
Joanne Quiñones, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Lehigh Valley Health Network, Allentown, PA.
Zorina S. Galis, Division of Cardiovascular Sciences, NHLBI, Bethesda, MD.
Namasivayam Ambalavanan, University of Alabama at Birmingham Division of Neonatology, Department of Pediatrics and Center for Women’s Reproductive Health.
Rachel G. Sinkey, Department of Obstetrics and Gynecology and Center for Women’s Reproductive Health, University of Alabama at Birmingham.
Jeff M. Szychowski, Department of Biostatistics and Center for Women’s Reproductive Health, University of Alabama at Birmingham.
Alan T.N. Tita, Department of Obstetrics and Gynecology and Center for Women’s Reproductive Health, University of Alabama at Birmingham.
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