Keywords gestational hypertension - timing of delivery - preeclampsia - maternal hypertensive
disorders - adverse perinatal outcomes
Hypertensive disorders during pregnancy are characterized by elevated blood pressure
(BP) during the antenatal period and include gestational hypertension, chronic hypertension,
preeclampsia, preeclampsia superimposed on chronic hypertension, and eclampsia.[1 ] More than 10% of pregnancies are complicated by hypertensive disorders, with increasing
prevalence in the United States over recent years.[2 ]
[3 ]
[4 ] These disorders carry risks for both the mother and baby, and the only effective
treatment is delivery.[5 ] These disorders are accompanied by substantial maternal and neonatal morbidity and
mortality worldwide.[6 ] In high-income countries, 10 to 16% of maternal deaths during pregnancy can be attributed
to hypertensive disorders.[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
Gestational hypertension is defined as a systolic BP ≥140 and <160 mm Hg and/or a
diastolic BP of ≥90 and <110 mm Hg on two occasions at least 4-hour apart after 20
weeks' gestation, in a woman who was previously normotensive.[10 ] Women with gestational hypertension progress to mild preeclampsia at a rate of up
to 46% and to severe preeclampsia at 9.6%.[11 ] Controversy exists as to the optimal timing for the delivery of mothers with gestational
hypertension when aiming to balance the fetal benefits of expectant management with
the maternal and fetal risks associated with early delivery. For instance, the American
College of Obstetrics and Gynecology recommends delivery of pregnant women with uncomplicated
gestational hypertension at 370/7 weeks' gestation,[12 ] whereas the International Society for the Study of Hypertension in Pregnancy suggests
expectant management up to 396/7 weeks' gestation for pregnancies with well-controlled BP, if there is reassuring
evidence regarding fetal status and no signs of preeclampsia.[13 ] The objective of this study was to compare maternal and fetal outcomes for mothers
who delivered at 37 weeks versus those who delivered from 38 to 40 completed pregnancy
weeks.
Materials and Methods
This was a retrospective cohort study from a single tertiary care perinatal center
of women giving birth from October 1, 2020, to February 28, 2023. The study was based
at Cabell Huntington Hospital in Huntington, West Virginia, the perinatal teaching
hospital for the Marshall University Joan C. Edwards School of Medicine. An in-house
attending obstetrician and resident team were available 24 hours per day. Antepartum,
intrapartum, and postpartum patient information were collected following delivery
using the Cabell Huntington Hospital Clinical Data Warehouse. Of the 2,962 total deliveries,
586 were coded for the diagnosis of gestational hypertension. Obstetrical and neonatal
records were manually reviewed, and data extracted and recorded in a secure REDCap
database. For this study, gestational hypertension was defined as systolic BP ≥140
and <160 mm Hg and/or a diastolic BP of ≥90 and <110 mm Hg confirmed by two measurements
at least 4 hours apart after 20 weeks' gestation. All obstetricians used the same
definition of gestational hypertension. Only singleton pregnancies were included in
this study. Mothers with previously known chronic hypertension, nonthyroid autoimmune
disease, and those late to prenatal care (after 14 weeks) or with incomplete prenatal
records were excluded from this study. Neonates with genetic disorders and those requiring
prolonged hospital stays due to neonatal abstinence syndrome and congenital syphilis
were also excluded.
Maternal outcomes included preeclampsia, the need for antihypertensive medication,
hospital readmission within 14 days after discharge due to elevated BP or BP-related
complications, primary cesarean section, length of hospitalization, and other severe
hypertensive-related complications including placental abruption, eclampsia, severe
hypertension (BP ≥ 160/≥110 mm Hg), pulmonary edema, HELLP (Hemolysis, Elevated Liver
enzymes and Low Platelets) syndrome, renal insufficiency (creatinine > 1.1 mg/dL),
thrombocytopenia (platelet count < 100,000/mL), liver dysfunction (liver enzymes >2×
upper limits and/or severe right upper quadrant abdominal pain), visual disturbances,
severe headache unresponsive to medication, stroke, myocardial infarction, and death.
Neonatal outcomes included neonatal intensive care unit (NICU) admission, hospital
length of stay, respiratory support after NICU admission (high-flow nasal cannula,
nasal continuous positive airway pressure, synchronized inspiratory positive airway
pressure, RAM cannula, and/or mechanical ventilation), need for phototherapy, small
for gestational age (birth weight < 10%), exclusive breastfeeding at discharge, and
death.
The protocol for this study was approved by Marshall University's Institutional Review
Board (study protocol: 1910767-7). The need for informed consent was waived due to
the retrospective nature of the study.
Statistical Analysis
Categorical variables were compared by chi-square or Fisher's exact tests. Continuous
variables were analyzed using univariable linear and quantile regression. A two-tailed
p -value of <0.05 was considered significant for all tests. Statistical analysis was
performed using STATA (Statacorp. 2022 Stata Statistical Software: Release 17. College
Station, TX).
Results
A total of 2,962 pregnancies lasting between 370/7 and 406/7 weeks' gestation occurred during the study period. Of these, 586 were coded for the
diagnosis of gestational hypertension. After exclusions, gestational hypertension
was confirmed in 337 (11.4%) of these pregnancies: 194 in cohort 1 and 143 in cohort
2 ([Fig. 1 ]).
Fig. 1 Flowchart of study participants.
Maternal Characteristics
Maternal characteristics and demographics are shown in [Table 1 ]. Most mothers were Caucasian and were of similar age and body mass index at the
time of delivery. There were no statistical differences between the cohorts regarding
rates of gestational diabetes, type II diabetes, and thyroid disease. There was no
statistical difference between cohorts for the highest mean systolic BP or the highest
mean diastolic BP during hospital admission for delivery.
Table 1
Maternal characteristics
37 weeks' gestation
N = 194
38–40 weeks' gestation
N = 143
Difference (95% CI)
p -Value
Maternal age at delivery, mean (SD)
27 (5)
26 (5)
−1 (−2, 0)
0.151
Delivery body mass index, mean (SD)
37 (8)
36 (8)
−2 (−3, 0)
0.126
Systolic blood pressure at admission for delivery, mean (SD)
134 (12)
135 (12)
2 (−1, 4)
0.239
Diastolic blood pressures at admission for delivery, mean (SD)
82 (10)
84 (9)
2 (0, 4)
0.085
Highest systolic blood pressure during admission, mean (SD)
152 (14)
154 (16)
1 (−2, 5)
0.466
Highest diastolic blood pressure during admission, mean (SD)
90 (14)
87 (11)
−2 (−5, 1)
0.138
Public health insurance
99/194 (51%)
68/143 (48%)
−3% (−8, 2)
0.252
Race/ethnicity White alone, non-Hispanic
187/194 (96%)
134/143 (94%)
−3% (−8, 2)
0.252
Gestational diabetes
19/194 (10%)
13/143 (9%)
−1% (−7, 6)
0.828
Type II diabetes
3/194 (2%)
0/143 (0%)
−2% (−3, 0)
0.265
Thyroid disease
14/194 (7%)
7/143 (5%)
−2% (−7, 3)
0.384
Abbreviations: CI, confidence interval; SD, standard deviation.
Maternal Outcomes
There were no maternal deaths or instances of stroke, myocardial infarction, HELLP
(haemolysis, elevated liver enzymes, low platelet count) syndrome, eclampsia, or renal
insufficiency in either cohort. There were no statistical differences in maternal
onset of preeclampsia, need for antihypertensive medication, hospital readmission,
severe hypertensive-related complications, or length of hospitalization between cohorts
([Table 2 ]). The rate of cesarean section and primary cesarean section were similar between
the two cohorts ([Table 3 ]). However, repeat cesarean sections occurred at a significantly higher rate in cohort
1 (18 vs. 6%, p = 0.001).
Table 2
Maternal outcomes
37 weeks' gestation
N = 194
38–40 weeks' gestation
N = 143
Difference (95% CI)
p -Value
Cesarean section
60/194 (31%)
38/194 (27%)
−4% (−14,5)
0.384
Induction due to gestational hypertension
133/194 (69%)
62/143 (43%)
−26% (−40,15)
<0.001
Preeclampsia
24/194 (12%)
12/143 (8%)
−4% (−11,3)
0.242
Uncontrolled, severe range blood pressure during delivery (>160 systolic and/or >110
diastolic)
13/194 (7%)
4/143 (3%)
−4% (−8,1)
0.133
Required blood pressure medication during or after delivery
20/194 (10%)
16/143 (11%)
1% (−6,8)
0.796
Severe hypertension-related complication[a ]
Placental abruption
2/194 (1%)
1/143 (1%)
0% (−2,2)
1
Pulmonary edema
1/194 (1%)
0/143 (0%)
−1% (−2,1)
1
Thrombocytopenia[b ]
2/185 (1%)
1/141 (1%)
0% (−2,2)
0.264
Liver dysfunction[c ]
2/177 (1%)
2/121 (2%)
1% (−2,3)
0.070
Visual disturbances
5/194 (3%)
0/143 (0%)
−3% (−5,0)
0.075
Severe headache
1/194 (1%)
2/143 (1%)
1% (−1,3)
0.577
Length of stay in days, mean (SD)
3 (1)
3 (1)
0 (0,0)
0.047
Hospital readmission within 2 wk of delivery
7/194 (4%)
3/143 (2%)
−2% (−5,2)
0.527
Abbreviations: CI, confidence interval; HELLP, Hemolysis, Elevated Liver enzymes and
Low Platelets; SD, standard deviation.
a There were no instances of stroke, myocardial infarction, HELLP syndrome, eclampsia,
renal insufficiency (creatinine > 1.1 mg/dL), or death in either group.
b Thrombocytopenia is defined as platelets < 100,000/mL.
c Liver dysfunction is defined as aspartate aminotransferase and/or alanine aminotransferase
≥2× the upper limit of normal or severe right upper quadrant pain.
Table 3
Cesarean section rates
37 weeks' gestation
N = 194
38–40 weeks' gestation
N = 143
Difference (95% CI)
p -Value
Cesarean sections, total
60/194 (31%)
38/143 (27%)
−4% (−14, 5)
0.384
Primary cesarean section
26/194 (13%)
30/143 (21%)
8% (−1, 16)
0.065
Repeat cesarean section
34/194 (18%)
8/143 (6%)
−12% (−18, −5)
0.001
Cesarean indication
Failed induction
28/194 (14%)
23/143 (16%)
2% (−6, 9)
0.676
CPD
0/194 (0%)
1/143 (1%)
1% (−1, 2)
0.243
Fetal distress
1/194 (1%)
1/143 (1%)
0% (−2, 2)
0.828
Elective primary
3/194 (2%)
0/143 (0%)
−2% (−3, 0)
0.135
Elective repeat
25/194 (13%)
8/143 (6%)
−7% (−13, −1)
0.026
Breech presentation
1/194 (1%)
5/143 (3%)
3% (0, 6)
0.041
Other
2/194 (1%)
0/143 (0%)
−1% (−2, 0)
0.223
Abbreviations: CI, confidence interval; CPD, cephalopelvic disproportion.
Neonatal Characteristics and Outcomes
Neonatal characteristics and outcomes are shown in [Table 4 ]. The median gestational age in cohort 1 was 37.0 versus 39.0 weeks' gestation in
cohort 2. There was a similar percentage of male infants in each cohort. Infants in
cohort 1 required admission to the NICU at significantly higher rates (14 vs. 6%,
p = 0.025) and had a longer length of stay when admitted to the NICU (6 vs. 2 days,
p = 0.049) compared with those in cohort 2. Infants delivered at 37 weeks' gestation
also required more respiratory support and phototherapy and had lower rates of exclusive
breast feeding at discharge compared with those delivered at 38 to 40 weeks' gestation.
The percentage of small for gestational age infants was similar in both cohorts (4
vs. 3%, p -value = not significant).
Table 4
Neonatal outcomes
37 weeks' gestation
N = 194
38–40 weeks' gestation
N = 143
Difference (95% CI)
p -Value
Neonatal sex, male
111/194 (57%)
76/143 (53%)
−4% (−15, 7)
0.457
Gestational age, wk, median (IQR)
37.0 (37.0,37.1)
39.0 (39.0,39.4)
1.9 (1.6, 2.0)
<0.001
NICU admission
27/194 (14%)
9/143 (6%)
−8% (−14, −1)
0.025
Respiratory support
17/194 (9%)
2/143 (2%)
−12% (−18, −7)
<0.001
Exclusive breastfeeding at discharge
122/192 (64%)
106/142 (75%)
11% (1, 21)
0.093
Birth weight, g, mean (SD)
3,174 (394)
3,442 (409)
268 (181, 355)
<0.001
Small for gestational age, birth weight < 10th percentile
7/194 (4%)
4/143 (3%)
−1% (−5, 3)
0.687
NICU length of stay, d, median (IQR)
6 (3, 10)
2 (2, 4)
−4 (−8, 0)
0.049
Abbreviations: CI, confidence interval; IQR, interquartile range; NICU, neonatal intensive
care unit; SD, standard deviation.
Discussion
In the context of our routine clinical practice, we have been steadily concerned by
the rising frequency of admissions to the NICU of infants born at 37 weeks' gestational
age manifesting complications of late prematurity. Many of these infants are delivered
by induction of labor or repeat cesarean section solely for maternal gestational hypertension.
In parallel, we are also keenly aware of the sizable proportion of mothers with gestational
hypertension who delivered at 38 to 40 weeks and were discharged home with their babies
without any significant complications. The dichotomous impressions generated by these
trends were the impetus for our study.
In the following paragraphs, we will review some of the extant relevant studies addressing
similar objectives to those formulated herein. For example, our findings differ from
those of Koopmans et al who in a multicenter trial (HYPITAT) in Holland studied women
with either gestational hypertension or mild preeclampsia who presented between 36
and <42 weeks' gestation. The subjects in this trial were prospectively randomized
to either expectant management or induction of labor. They found that those allocated
to induction of labor had better maternal outcomes compared with those allocated to
expectant management (31 vs. 44%; p < 0.0001).[14 ] However, contrary to our study, Koopmans et al did not separate gestational hypertension
from mild preeclampsia, making it unclear whether these two different conditions result
in similar morbidities. In addition, while the Dutch study separated maternal morbidities
by individual weeks of delivery, they combined neonatal morbidities into a single
group with a median gestational age at induction of 38.7 weeks (range: 37.9–39.8),
which may be why they did not detect a difference in neonatal outcomes.[14 ]
A more recent multicenter, randomized trial by Magee et al randomized women with gestational
and chronic hypertension during pregnancy to be delivered at 380/7–3/7 weeks or receive “usual care at term.” They did not find any difference in maternal
or neonatal morbidities.[15 ] However, this study included mothers with both chronic and gestational hypertension,
most of whom were on antihypertensive medication during pregnancy (over 75% of mothers
in both groups). In addition, there was minimal difference between the median gestational
age at delivery between their groups (38.0 vs. 38.3) compared with our cohorts (37.0
vs. 39.0). Such differences likely account for our dissimilar results. Furthermore,
this prospective study did not examine whether further delaying delivery to 39 or
40 weeks would have detected a beneficial effect that was otherwise missed by the
study design or by restricting the delayed delivery planning to 38 weeks.
In contradistinction, our study findings concur with those of the large, multicenter
study by Cruz et al who demonstrated that induction of labor between 38 and 39 weeks'
balances the lowest maternal and neonatal morbidity and mortality.[16 ] To our knowledge, this is the first investigation that supports the results of Cruz
et al questioning the justification for induction of labor at 37 weeks for gestational
hypertension. However, given the limitations of our study, further research is still
needed to address this important question.
In addition to being a retrospective, small study undertaken at a single institution,
this study has other limitations. We could not ascertain the number of elevated BP
measurements used to diagnose gestational hypertension or the gestational age at which
the diagnosis was reached by the treating obstetrician. Multiple elevated BP readings
might have a different prognosis than a limited number, and time of gestational presentation
may also influence the risk of complications. Indeed, some of the mothers included
in both cohorts were not diagnosed with gestational hypertension until they presented
for delivery. The selection bias caused by including mothers diagnosed later in gestation
may have influenced our results. In addition, due to the relatively small cohort sizes,
we combined maternal morbidities in cohort 2 as 38 to 40 weeks, even though larger
sample sizes might have discerned differences between 38 to 39, 39 to 40, and 40 to
41 weeks as previously shown in larger studies.[14 ]
[16 ] Furthermore, the unique health characteristics of our patient population may limit
the applicability of our findings to other populations. The rate of gestational hypertension
found in our study population was 11.4%, which is slightly higher than that currently
reported in the literature. While this may partially be due to the increasing prevalence
of gestational hypertension nationally,[4 ] the maternal health characteristics of our region are likely to also contribute
to this discrepancy. West Virginia ranks second in maternal obesity, which has been
shown to have an increased risk of hypertensive disorders associated with pregnancy.[17 ] Lastly, we only examined short-term morbidities in this study; there are reports
assessing long-term neurodevelopmental delays in late preterm infants that could have
further supported expectant management over delivery at 37 weeks.[18 ]
[19 ]
[20 ]
Although our study had several limitations, one important strength was the systematic
detection of gestational hypertension utilizing the electronic hospital database followed
by extraction of all other clinical information for each of the cases from direct
chart review of maternal and neonatal hospital records. This approach allowed for
detailed monitoring of the progression of maternal disease to preeclampsia even beyond
delivery in both cohorts and to confirm that no pregnancies resulted in stillbirths
or maternal deaths.
While our study limitations render us unable to draw a conclusion regarding optimal
timing of delivery for mothers with gestational hypertension, our findings do suggest
that further investigation on this topic is warranted. We found that for women with
gestational hypertension, delivery at 38 to 40 weeks was not associated with increased
maternal morbidity but was associated with fewer neonatal complications and NICU admissions
when compared with delivery at 37 weeks. However, it is unclear if the timing of gestational
hypertension presentation influenced our results. As such, this study highlights the
need for a prospective multicenter randomized control trial to evaluate if delivery
induction beyond 37 weeks' gestation is a safe and beneficial option among women with
gestational hypertension diagnosed prior to this gestational age to balance maternal
and fetal risks.
