Hindawi

International Journal of Hypertension

Volume 2019, Article ID 4108271, 9 pages
https://doi.org/10.1155/2019/4108271

Research Article
Early- and Late-Onset Preeclampsia: A Comprehensive Cohort
Study of Laboratory and Clinical Findings according to the New
ISHHP Criteria

Anna Wójtowicz ,1 Małgorzata Zembala-Szczerba,1 Dorota Babczyk,1

Monika Kołodziejczyk-Pietruszka,1 Olga Lewaczyńska,2 and Hubert Huras1
1
Department of Obstetrics & Perinatology, Jagiellonian University Medical College, Ul. Kopernika 23, 31-501 Kraków, Poland
2
Department of Neonatology, Jagiellonian University Medical College, Ul. Kopernika 23, 31-501 Kraków, Poland

Correspondence should be addressed to Anna Wójtowicz; [email protected]

Received 29 November 2018; Revised 5 July 2019; Accepted 21 August 2019; Published 17 September 2019

Guest Editor: Srijit Das

Copyright © 2019 Anna Wójtowicz et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Recently, the diagnostic criteria of preeclampsia have been changed. No studies are available in the literature that analyzed in detail
the differences between early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP), taking into account the International
Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. Thus, we sought to retrospectively investigate in detail the
differences in clinical and laboratory outcomes between EOP and LOP diagnosed according to the ISSHP criteria. A retrospective
cohort study was conducted in 214 women with singleton pregnancies and preeclampsia admitted to the Department of Obstetrics
and Perinatology of the University Hospital in Kraków, Poland, from 2013 to 2017 (113 (52.8%) women with EOP and 101 (47.2%)
women with LOP). Electronic medical records were reviewed for demographics and medical history, laboratory tests, and delivery
and neonatal data. Patients with preeclampsia accounted for 1.7% of the women who delivered during the study period. The EOP
and LOP groups did not differ in the distribution of risk factors for preeclampsia. The most common risk factor was primiparity,
which was observed in 72.0% of cases. Regarding the ISSHP diagnostic criteria, the two groups differed in the incidence of fetal
growth restriction (p � 0.0009), hemolysis (p � 0.0416), and neurological complications (p � 00342), which were found more
often in the EOP group. In addition, the EOP group had more frequent occurrence of severe cardiorespiratory (p < 0.0001) and
hematological (p � 0.0127) complications, adverse fetoplacental conditions (p < 0.0001), and severe fetoplacental complications
(p � 0.0003). Children born to women with EOP had lower Apgar scores (p < 0.001) and higher rates of intraventricular
hemorrhage (p < 0.0001), respiratory disorders requiring mechanical ventilation (p < 0.0001), and early (p � 0.0004) and late
sepsis (p � 0.002). EOP differed from LOP in terms of maternal and perinatal adverse outcomes. The observed higher rates of
fetoplacental adverse conditions and severe complications indicate a significant contribution of impaired placentation to the
etiopathogenesis of EOP.

1. Introduction disorders of pregnancy. There are some differences between

the two leading institutions dealing with the issue of hy-
Preeclampsia is a hypertensive disorder specific to pregnancy. pertension in pregnancy, namely, American College of
Over the last decades, the incidence of preeclampsia has in- Obstetricians and Gynecologists (ACOG) and International
creased in some regions worldwide [1]. It complicates up to 5% Society for the Study of Hypertension in Pregnancy (ISSHP)
of all pregnancies [2, 3] and is associated with serious maternal [7–9], which can lead to differences in their observed rates of
complications such as death, stroke, or liver rupture [4–6]. adverse maternal and fetal outcomes. In recent years, both
However, there has never been a consensus on the ACOG and ISSHP have modified the diagnostic criteria for
classification and diagnostic criteria for the hypertensive preeclampsia [7–9]. They have excluded the dependence of
2 International Journal of Hypertension

preeclampsia diagnosis on proteinuria. In 2013, ACOG Preeclampsia was diagnosed according to the criteria
published a report on hypertension in pregnancy, with fetal given in Table 1.
growth restriction (FGR) being eliminated from the con- Diagnostic criteria for severe preeclampsia included the
sideration of preeclampsia [7]. In 2014, a revised statement occurrence of severe uncontrolled hypertension (>160/
from the ISSHP was published [8, 9]. In this statement, 110 mmHg) and any severe neurological, cardiorespiratory,
uteroplacental dysfunction manifesting as FGR is considered hematological, renal, hepatic, or fetoplacental complications
one of the preeclampsia diagnostic criteria. Furthermore, the [8, 9]. Resistant preeclampsia was defined as the need for
end-organ dysfunction of preeclampsia, referred to as ad- three antihypertensive medications for blood pressure
verse conditions and severe complications, has been dis- control at ≥20 weeks of gestation [9].
tinguished. Adverse conditions consist of maternal HELLP was diagnosed if the platelet count is <10 × 109/L,
symptoms and abnormal laboratory and fetal monitoring alanine aminotransaminase (ALT) or aspartate amino-
results that may herald the development of severe maternal transferase (AST) >70 IU/L, and lactate dehydrogenase
or fetal complications. In turn, severe maternal or fetal (LDH) >600 IU/L [10].
complications of preeclampsia are the features that warrant In our center, all women with preeclampsia are referred
delivery. Depending on time, the condition is classified as to the hospital. When possible, on admission to the hospital
early-onset preeclampsia (EOP), which requires delivery with informed consent, a blood sample was collected to
before 34 weeks’ gestation, or late-onset preeclampsia assess blood count, platelet count, and serum levels of
(LOP), with delivery at or after 34 weeks or later [7–11]. creatinine, blood urea nitrogen, uric acid, and liver enzymes,
Although the diagnostic criteria for EOP and LOP are and a urine sample was collected and analyzed for pro-
the same, there are some uncertainties about the maternal teinuria. Depending on the clinical condition of the patient,
and fetal outcomes [12, 13]. It is thought that EOP poses a 24-hour urine collection was performed if possible to assess
high risk to both mother and fetus [14, 15], whereas LOP the level of proteinuria. The number of women in whom
may present with less severe clinical symptoms [16]. Many specific measurements have been performed is given in the
studies have explored the clinical and laboratory findings in tables. Moreover, fetal well-being was evaluated through an
EOP and LOP. However, they mainly have focused on the ultrasound examination to determine the estimated fetal
risk factors and selected maternal and neonatal clinical weight, Doppler flow in the umbilical artery (UA) and
outcomes as well as selected laboratory findings [17–26]. middle cerebral artery (MCA), cerebroplacental ratio (CPR),
Moreover, previous studies utilized the diagnostic criteria of and nonstress cardiotocographic test (NST). We considered
preeclampsia given several years ago. the pulsatility index (PI) in the UA and MCA as well as
Therefore, this study aimed to evaluate the differences in cerebroplacental ratio (CPR � MCA PI/UA PI).
clinical and laboratory findings between patients with EOP Blood pressure was measured at least four times per day,
and LOP and to assess whether both forms of the disease met and blood samples were collected 1-2 times per week. Fetal
the same ISSHP diagnostic criteria. well-being was assessed based on fetal heart rate monitoring
or NST. Ultrasound examination was performed at least
once per week and in cases of Doppler abnormalities, every
2. Materials and Methods three days.
This retrospective cohort study included women with Patients were treated with the antihypertensive drug,
pregnancies and preeclampsia admitted to the Department including methyldopa as the first-line therapy. For emer-
of Obstetrics and Perinatology of the University Hospital in gency treatment of preeclampsia, labetalol and/or oral ni-
Kraków, Poland, from 2013 to 2017. Preeclampsia was di- fedipine were administered. Magnesium sulfate was
agnosed based on the International Society for the Study of administered for neuroprotection and prevention of sei-
Hypertension in Pregnancy (ISSHP) guidelines [8, 9]. The zures. Steroid therapy was given for lung maturation be-
initial study population consisted of 231 patients with tween 24 + 0 and 34 + 0 weeks of gestation.
preeclampsia, accounting for 1.7% of the 13,716 patients Delivery was indicated in the event of preeclampsia after
who delivered at our institution from 2013 to 2017. EOP was 37 weeks; placental abruption; progressive maternal renal,
diagnosed in 120 patients (52%), and 111 patients (48%) liver, neurological, or hematological dysfunction; inability to
were diagnosed with LOP. Multiple pregnancies, which control maternal blood pressure despite antihypertensive
occurred at similar frequencies in the two groups (5.8% and medication; or nonreassuring cardiotocography or ultra-
9.0%, respectively), were excluded from further analyses, and sound-based concerns for fetal well-being or stillbirth.
113 women with EOP and 101 women with LOP were The institutional review board waived the requirement
enrolled. for ethical approval for this analysis since the laboratory and
sonographic evaluations were performed as an integral part
of the routine clinical care, for which informed consent had
2.1. Management of Pregnancy Complicated by Preeclampsia been obtained from the women. Data were anonymized.

2.1.1. Definitions. Gestational age was determined based on

the date of the last menstrual period and/or the measure- 2.2. Statistical Analysis. Patient characteristics are described
ment of the crown-rump length in the first trimester of as means with standard deviation for normally distributed
pregnancy. numerical data and as percentages for categorical variables.
International Journal of Hypertension 3

Table 1: Diagnostic criteria for preeclampsia [8].

Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg that are noted
Blood pressure twice within 6 hours after 20 weeks of gestation in women with normal blood pressure before
conception or in women with previous chronic hypertensive disorders
And coexistence of one or more of the following new-onset conditions
Spot urine protein/creatinine >30 mg/mmol (0.3 mg/mg) or >300 mg/day or at least 1 g/L (“2+”)
Proteinuria
on dipstick testing
(1) Renal insufficiency (creatinine >90 μmol/L; 1.02 mg/dL)
(2) Liver involvement (doubling of serum transaminases and/or severe right upper quadrant
pain)
Other maternal organ dysfunctions (3) Neurological complications (eclampsia, altered mental status, blindness, stroke, or more
commonly hyperreflexia when accompanied by clonus and severe headaches when
accompanied by hyperreflexia and persistent visual scotomata)
(4) Hematological complications (platelet count <150,000/dL, DIC, and hemolysis)
Uteroplacental dysfunction Fetal growth restriction
DIC, disseminated intravascular coagulation.

Differences were analyzed by Student’s t-test for normally Table 2: The distribution of selected maternal risk factors for
distributed data and the Mann–Whitney U-test for non- preeclampsia in women with singleton pregnancy and early- or
normally distributed data. Chi-square and Fisher’s exact tests late-onset preeclampsia.
were used for comparisons of categorical variables. In all an- EOP LOP Total
alyses, p values <0.05 were considered statistically significant. Risk factors for preeclampsia
(n � 113) (n � 101) (n � 214)
Primiparity, n (%) 83 (73.4) 71 (70.3) 154 (72.0)
3. Results Multiparity (>3), n (%) 3 (2.6) 5 (5.0) 8 (3.7)
Previous preeclamptic
2 (1.7) 2 (2.0) 4 (1.8)
The groups did not differ in terms of distribution of risk pregnancy, n (%)
factors for preeclampsia (Table 2). The most common risk Chronic hypertension, n (%) 20 (17.7) 14 (14.0) 34 (15.8)
factor was primiparity, which was present in 72.0% of the Chronic renal disease, n (%) 4 (3.5) 2 (2.0) 6 (2.8)
History of thrombophilia, n (%) 2 (1.7) 1 (1.0) 3 (1.4)
patients. Considering the applied diagnostic criteria, the
In vitro fertilization, n (%) 2 (1.7) 3 (3.0) 5 (2.3)
groups differed in the incidence of neurological complica- Family history of Data not Data not Data not
tions (p � 0.0342), hemolysis (p � 0.0416), and FGR preeclampsia, n (%) available available available
(p � 0.0009) (Table 3). Type 1 or type 2 diabetes
On average, preeclampsia was diagnosed at week 30 in 7 (6.2) 8 (8.0) 15 (7.0)
mellitus, n (%)
the EOP group and at week 36 in the LOP group. Admission- Obesity, BMI >30 kg/m2, n (%) 13 (11.5) 12 (12.0) 25 (11.7)
to-delivery interval was longer in the EOP group Systemic lupus
1 (0.9) 0 (0.0) 1 (0.4)
(8 ± 8.55 days) than in the LOP group (4 ± 5.5 days, erythematosus, n (%)
p � 0.0002); however, there was no difference in the de- Maternal age ≥40 years, n (%) 9 (8.0) 4 (4.0) 13 (6.0)
livery-to-discharge interval (Table 4). BMI, body mass index; EOP, early-onset preeclampsia; LOP, late-onset
Compared to the LOP group, the EOP group had a preeclampsia.
higher proportion of women with severe preeclampsia
(96.4% vs. 87.0%, p � 0.0412), higher mean systolic level of proteinuria (4.21 g vs. 2.32 g, p � 0.007) (Figure 1),
(178 mmHg vs. 168 mmHg, p � 0.005) and diastolic blood higher daily protein loss (6.35 g vs. 3.82 g, p � 0.008), and
pressure (109 mmHg vs. 104 mmHg, p � 0.026) on admis- more frequent daily protein loss ≥10 g (22.3% vs. 11.6%,
sion, as well as resistant hypertension (30.0% vs. 2.0%; p � 0.0122) (Table 6). In addition, the EOP group dem-
p < 0.0001), placental abruption (16.8% vs. 4.0%, p � 0.004), onstrated a higher blood urea nitrogen (5.31 vs. 4.88,
diagnosis of genitourinary infection (27.4% vs. 15%, p � 0.021) (Figure 2) and serum creatinine concentration
p � 0.0385), and the need for albumin transfusion (19.4% vs. (72.3 vs. 63.0 IU, p � 0.001) (Figure 3 and Table 6).
8.0%, p � 0.019) (Table 4). There were significant differences The mean gestational age at birth and mean birth weight
regarding the frequency of severe cardiorespiratory were significantly lower in the EOP group than in the LOP
(p < 0.0001) and hematological complications (p � 0.0127) group (p < 0.001) (Table 7). The indication for delivery was
(Table 5). There was one maternal death at 28 weeks of intrauterine fetal distress in 69.0% of cases in the EOP group
gestation because of pulmonary embolism as well as one case and in 33.0% of cases in the LOP group (p < 0.001) (Table 6).
of hysterectomy due to placental abruption and uterine The study groups also differed in the prevalence of CPR
atony. Furthermore, complications in puerperium occurred below the 5th percentile (70.0% vs. 32.0%, p � 0.001) and
more frequently in the EOP group than in the LOP group abnormal MCA flow rate, defined as PI <5th percentile
(56.0% vs. 41.6%, p � 0.0375). (46.0% vs. 11.0%, p < 0.001). Moreover, compared to the
All women had significant proteinuria, but patients in LOP group, the EOP group had higher rates of FGR, defined
the EOP group were characterized by a significantly higher as birth weight <10th (p � 0.001), 5th (p � 0.006), and 3rd
4 International Journal of Hypertension

Table 3: The revised ISSHP criteria of preeclampsia [8, 9] in women with singleton pregnancy and early- or late-onset preeclampsia.
EOP LOP Total
Criterion p
(n � 113) (n � 101) (n � 214)
Proteinuria 113 (100.0) 101 (100.0) 214 (100.0) ns
Renal insufficiency
11 (9.7) 6 (6.0) 17 (7.9) ns
(creatinine >90 μmol/L), n (%)
Liver involvement, n (%) 15 (13.3) 8 (7.9) 23 (10.7) ns
Neurological complications, n (%) 20 (17.7) 8 (8.0) 28 (13.0) 0.0342
Hematological complications, n (%) 50 (44.2) 35 (34.6) 85 (39.7) ns
(i) Thrombocytopenia, n (%) 37 (74) 29 (82.8) 66 (77.6) ns
(ii) DIC, n (%) 0 (0.0) 2 (5.8) 2 (2.4) ns
(iii) Hemolysis, n (%) 13 (26) 4 (11.4) 17 (20.0) 0.0416
FGR, n (%) 80 (70.7) 49 (48.5) 129 (60.3) 0.0009
DIC, disseminated intravascular coagulation; EOP, early-onset preeclampsia; FGR, fetal growth restriction; ISSHP, International Society for the Study of
Hypertension in Pregnancy; LOP, late-onset preeclampsia; ns, nonstatistically significant.

Table 4: Characteristics and occurrence of adverse maternal outcomes in women with early-onset and late-onset preeclampsia.
EOP (n � 113) LOP (n � 101) Total (n � 214) p
30.7 ± 5.5 30.1 ± 5.3 30.43 ± 5.4
Maternal age at EDD, years ± SD (range) ns
(19.00–48.00) (19.00–47.00) (19.00–48.00)
Gestational age at inclusion, weeks ± SD (range) 30.0 ± 2.5 (22.0–33.0) 36.2 ± 1.4 (34.0–39.3) 33.1 ± 1.6 (22.0–39.3) 0.00001
Systolic blood pressure on admission, mmHg ± SD
178 ± 18 (140–240) 168 ± 18 (120–230) 173 ± 18 (120–240) 0.005
(range)
Diastolic blood pressure on admission, mmHg ± SD
109 ± 12 (90–150) 104 ± 11 (70–145) 106 ± 11 (70–150) 0.026
(range)
Antihypertensive drug administration, n (%)
Methyldopa 106 (93.8) 90 (90.0) 196 (94.8) ns
Calcium channel blocker 46 (40.7) 29 (29.0) 75 (35.0) ns
Beta-blocker 65 (57.5) 26 (26.0) 91 (42.5) <0.001
Resistant hypertension, n (%) 34 (30.0) 2 (2.0) 36 (16.8) <0.0001
MgSO4 administered, n (%) 65 (57.5) 30 (30.0) 85 (45.8) <0.001
Admission-to-delivery interval, days ± SD (range) 6.8 ± 6.8 (1–30) 6 ± 8.5 (1–53) 6 ± 7.0 (1–53) 0.021
Gestational age at delivery, weeks ± SD (range) 30.6 ± 2.2 (23.0–33.8) 36.6 ± 1.4 (34.0–39.5) 33.9 ± 1.9 (23.0–39.5) <0.0001
Delivery-to-discharge interval, days ± SD (range) 6.7 ± 3.5 (3–24) 6.4 ± 3.6 (3–30) 6.5 ± 3 (3–30) ns
Severe preeclampsia, n (%) 109 (96.4) 87 (87.0) 196 (91.5) 0.0412
HELLP, n (%) 5 (4.4) 4 (4.0) 9 (4.2) ns
Eclampsia before delivery, n (%) 0 (0.0) 2 (2.0) 2 (0.9) ns
Postpartum eclampsia, n (%) 17 (15.0) 7 (7.0) 24 (11.2) ns
Placental abruption, n (%) 19 (16.8) 4 (4.0) 23 (10.7) 0.004
Hemorrhage, n (%) 3 (2.6%) 1 (1.0) 4 (1.8) ns
Blood transfusion, n (%) 12 (10.6) 7 (7.0) 19 (8.8) ns
Albumin transfusion, n (%) 22 (19.4) 8 (8.0) 30 (14.0) 0.019
Anemia, n (%) 50 (44.2) 40 (40.0) 90 (42.0) ns
Pulmonary edema, n (%) 5 (4.4) 0 (0.0) 5 (2.3) ns
Hysterectomy, n (%) 0 (0.0) 1 (1.0) 1 (0.4) ns
Maternal death, n (%) 1 (0.8) 0 1 (0.4) ns
DIC, n (%) 0 (0.0) 2 (2.0) 2 (0.9) ns
ICU, n (%) 22 (19.4) 6 (6.0) 28 (13.0) 0.02
Uterine contraction disorders, n (%) 3 (2.6) 1 (1.0) 4 (1.8) ns
Thrombosis, n (%) 2 (1.7) 4 (4.0) 6 (2.8) ns
Healing disorders of the scar, n (%) 3 (2.6) 6 (6.0) 9 (4.2) ns
Genitourinary infection, n (%) 31 (27.4) 15 (15.0) 46 (21.5) 0.0385
DIC, disseminated intravascular coagulation; EDD, estimated date of delivery; EOP, early-onset preeclampsia; HELLP, hemolysis, elevated liver enzymes, low
platelets; ICU, intensive care unit; LOP, late-onset preeclampsia; ns, nonstatistically significant; SD, standard deviation.

(p � 0.002) percentiles, and lower Apgar scores in the 1st, 95% CI � 3.11 – 18.53). Therefore, fetoplacental adverse
3rd, and 5th minute (all p < 0.001) (Table 7 and Figure 4). The conditions and severe complications were more frequent in
risk of birth of a child with an Apgar score <7/10 in the first the EOP group (Table 6).
minute instead of 10/10 was 7.59 times greater among pa- Early preeclampsia was also associated with a higher risk
tients with EOP than among patients with LOP (RR � 7.59, of perinatal mortality (RR � 1.90, 95% CI: 1.20–3.01). In the
International Journal of Hypertension 5

Table 5: Adverse conditions and severe complications in women with early-onset and late-onset preeclampsia.
EOP (n � 113) LOP (n � 101) p
Organ system
affected Adverse Severe Adverse Adverse Severe
Severe complications
conditions complications conditions conditions complications
CNS, n (%) 3 (2.6) 17 (15.0) 1 (1.0) 7 (7.0) ns ns
Cardiorespiratory, n (%) 2 (1.7) 34 (30.0) 1 (1.0) 2 (2.0) ns <0.0001
Hematological, n (%) 37 (32.7) 24 (21.2) 29 (29.0) 9 (9.0) ns 0.0127
Renal, n (%) 15 (13.2) 2 (1.7) 8 (8.0) 1 (1.0) ns ns
Hepatic, n (%) 15 (13.2) 0 (0.0) 8 (8.0) 0 (0.0) ns ns
Fetoplacental, n (%) 87 (77.0) 21 (18.5) 42 (42.0) 3 (3.0) <0.0001 0.0003
CNS, central nervous system; EOP, early-onset preeclampsia; LOP, late-onset preeclampsia; ns, nonstatistically significant.

25 population [27] but lower than that reported in another report

[17]. This relatively low prevalence of preeclampsia may be
20 because our department is a tertiary referral center and admits
mainly pregnant women at risk of giving birth before 32 weeks
Proteinuria (g/L)

of gestation as well as the most severe cases, which accounted

15 for 96.4% of patients in the EOP group and 87% of patients in
the LOP group (p � 0.0412). On the other hand, such a low
10 percentage of pregnancies complicated by preeclampsia may
result from ethnic conditions. It has been shown that there is a
5
higher percentage of preeclampsia in the African American
race than in the Chinese population [27]. The Polish population
and our cohort are characterized by the fact that they are
0 homogeneous of the Caucasian race. Another explanation may
20 22 24 26 28 30 32 34 36 38 40 be that, in Poland, women are covered by medical care before
Gestational age (weeks)
the 10th week of pregnancy, and medical appointments are held
LOP at least every 4 weeks. Another issue is the possibility of di-
EOP versity in diet and vitamin supplementation.
Figure 1: Proteinuria in women with early- and late-onset pre- The exact cause of preeclampsia is unknown, but ma-
eclampsia. EOP, early-onset preeclampsia; LOP, late-onset ternal and placental factors are considered to be involved in
preeclampsia. the etiology of the disease. It has been suggested that EOP is
more strongly associated with internal placental factors
EOP group, 22 (17.6%) women delivered at <28 weeks of [28, 29], whereas the late-onset form may be primarily due
gestation. There was one intrauterine death at 24 weeks of to predisposing maternal factors. Although the present
gestation, and 13 neonates (11.5%) died during the first study did not find any differences between the two groups
month, of which 10 were born at ≤28 weeks and 3 after with respect to risk factors for preeclampsia, a previous
28 weeks of gestation. All children born at <28 weeks of study by Lisonkova and Joseph [17] found that older
pregnancy developed respiratory distress syndrome and maternal age, unmarried status, and male sex of infant are
needed mechanical ventilation. Compared to the LOP typical to EOP and LOP, whereas African American race,
group, the EOP group also had higher rates of in- chronic hypertension, and congenital anomalies are
traventricular hemorrhage (27.4% vs. 1.0%, p < 0.0001), strongly associated with EOP [17]. Moreover, in the study
fresh frozen plasma transfusion (p � 0.0002), and early by Aksornphusitaphong and Phupong [15], history of
(p � 0.0004) and late sepsis (p � 0.002) (Table 7). chronic hypertension was significantly associated with
increased risk for only EOP, whereas a family history of
4. Discussion chronic hypertension was associated with increased risk for
only LOP. It is worth mentioning that patients in the
To the best of our knowledge, this is among the first studies studied population were predominantly primipara, which
that compared the clinical and laboratory outcomes between is known to be a major risk factor for preeclampsia [7].
EOP and LOP, which were diagnosed according to the new It is thought that EOP may have a more severe course
ISHPP criteria. This comprehensive cohort study demon- than LOP [8]. The incidence of placental abruption, overall
strates that EOP and LOP do not meet the same diagnostic mortality, and FGR have been shown to depend on the
criteria. Early-onset preeclampsia poses a high risk of ma- severity and duration of preeclampsia [30–34]. Our study
ternal neurological, cardiorespiratory, and hematological did identify differences in the frequency of neurological
complications as well as adverse fetoplacental conditions complications and severe cardiorespiratory and hemato-
and complications. logical complications between the EOP and LOP groups.
The incidence of preeclampsia in our department was 1.7%, These findings are different from those of the studies by
which is consistent with the observation in the Chinese Pettit et al. [13] and Madazil et al. [19].
6 International Journal of Hypertension

Table 6: Laboratory measurements in women with early-onset and late-onset preeclampsia.

EOP (n)∗ , mean ± SD LOP (n)∗ , mean ± SD p
(n � 80) (n � 58)
Proteinuria (g/L) 0.007
4.21 ± 6.84 2.32 ± 3.61
Proteinuria, n (%) (91) (78)
≤5 g/day, n (%) 53 (58.2) 59 (75.6) ns
5.1–9.9 g/day, n (%) 16 (17.6) 10 (12.8) ns
≥10 g/day, n (%) 22 (24.2) 9 (11.6) 0.0122
(n � 91) (n � 78)
24-hour urine proteinuria (g/24 h) 0.008
6.35 ± 8.23 3.82 ± 4.36
(n � 75) (n � 62)
Blood urea nitrogen (mmol/L) 0.021
5.31 ± 1.93 4.88 ± 3.14
(n � 30) (n � 25)
Uric acid (µmol/L) ns
418.1 ± 107.6 389.6 ± 82.3
(n � 78) (n � 56)
Creatinine (µmol/L) 0.001
72.3 ± 31.2 63.0 ± 34.4
(n � 16) (n � 15)
Creatinine clearance (ml/min) ns
102.8 ± 48.0 127.8 ± 74.1
(n � 71) (n � 48)
Total serum protein (g/L) ns
55.8 ± 6.0 57.7 ± 7.21
(n � 50) (n � 30)
Albumin (g/L) ns
29.2 ± 4.28 31.5 ± 6.74
(n � 113) (n � 92)
Hemoglobin (g/L) ns
12.3 ± 1.49 12.3 ± 1.33
(n � 113) (n � 92)
Hematocrit (%) ns
35.6 ± 4.3 35.8 ± 3.7
(n � 113) (n � 92)
Erythrocytes (×109/L) ns
4.05 ± 0.47 4.04 ± 0.42
(n � 113) (n � 92)
Platelet (×109/L) ns
184.0 ± 72.8 178.0 ± 68.9
(n � 73) (n � 50)
Alanine aminotransaminase (U/L) ns
43.4 ± 48.2 70.9 ± 141.0
(n � 73) (n � 50)
Aspartate aminotransferase (U/L) ns
44.8 ± 53.3 65.2 ± 134.9
∗
The values in ( ) indicate number of performed measurements; EOP, early-onset preeclampsia; LOP, late-onset preeclampsia; ns, nonstatistically significant;
SD, standard deviation.

14 350

12 300
Blood urea nitrogen (mmol/L)

10 250
Creatinine (μmol/L)

8 200

6 150

4 100

2 50

0 0
20 22 24 26 28 30 32 34 36 38 40 20 22 24 26 28 30 32 34 36 38 40
Gestational age (weeks) Gestational age (weeks)

LOP LOP
EOP EOP
Figure 2: Blood urea nitrogen of women with early- and late-onset Figure 3: Creatinine of women with early- and late-onset pre-
preeclampsia. EOP, early-onset preeclampsia; LOP, late-onset eclampsia. EOP, early-onset preeclampsia; LOP, late-onset
preeclampsia. preeclampsia.
International Journal of Hypertension 7

Table 7: Fetal factors associated with early- and late-onset preeclampsia.

EOP (n � 113) LOP (n � 101) Total (n � 214) p
Gestational age at delivery, weeks ± SD (range) 30.6 ± 2.2 (23.0–33.8) 36.6 ± 1.4 (34.0–39.5) 33.9 ± 1.9 (23.0–39.5) <0.0001
Birth weight (g), mean ± SD (range) 1358 ± 497 (460–3450) 2511 ± 689 (1010–4320) 1934 ± 592 (460–4320) <0.001
Fetal sex
Female, n (%) 63 (56.0) 53 (52.0) 116 (54.0) ns
Male, n (%) 50 (44.0) 48 (48.0) 98 (46.0) ns
Intrauterine fetal distress, n (%) 78 (69.0) 33 (33.0) 111 (51.8) <0.001
UA PI >95th percentile, n (%) 27 (23.9) 15 (15.0) 42 (19.6) ns
MCA PI <5th percentile, n (%) 52 (46.0) 11 (11.0) 63 (29.4) <0.001
CPR <5th percentile, n (%) 79 (70.0) 32 (32.0) 111 (51.8) 0.001
FGR <10th percentile, n (%) 80 (70.7) 49 (49.0) 129 (60.2) 0.0015
FGR <5th percentile, n (%) 71 (62.8) 46 (46.0) 117 (54.6) 0.006
FGR <3rd percentile, n (%) 66 (58.4) 37 (37.0) 103 (48.1) 0.002
Apgar score at 1 min, mean ± SD (range) 6.7 ± 1.9 (1–10) 9.1 ± 1.4 (1–10) 7.9 ± 1.5 (1–10) <0.001
Apgar score at 3 min, mean ± SD (range) 7.4 ± 1.7 (1–10) 9.6 ± 0.7 (7–10) 8.5 ± 1.4 (1–10) <0.001
Apgar score at 5 min, mean ± SD (range) 7.8 ± 1.3 (4–10) 9.8 ± 0.6 (7–10) 8.8 ± 1.3 (4–10) <0.001
Apgar score <7 at 1 min, n (%) 51 (45.0) 4 (4.0) 55 (25.7) <0.001
Apgar score <7 at 3 min, n (%) 27 (23.9) 2 (2.0) 29 (13.5) <0.001
Apgar score <7 at 5 min, n (%) 19 (16.8) 0 (0.0) 19 (8.8) <0.001
Intrauterine fetal death, n (%) 1 (0.9) 0 (0.0) 1 (0.4) ns
IVH, n (%) 31 (27.4) 1 (1.0) 32 (14.9) <0.0001
FFP transfusion, n (%) 15 (13.3) 0 (0.0) 15 (7.0) 0.0002
Mechanical ventilation 33 (29.2) 1 (1.0) 34 (15.9) <0.0001
Infection complications, n (%)
Early sepsis 18 (16.0) 1 (1.0) 19 (8.8) 0.0004
Late sepsis 20 (17.7) 2 (2.0) 22 (10.2) 0.0021
Retinopathy, n (%) 2 (1.8) 0 (0.0) 2 (0.9) ns
NEC, n (%) 3 (2.6) 0 (0.0) 3 (1.4) ns
Fetal death, n (%) 13 (11.5) 0 (0.0) 13 (6.0) 0.0008
Born ≤28 weeks 10 (8.8) 0 (0.0) 0.0058
Born >28 weeks 3 (2.6) 0 (0.0) ns
CPR, cerebroplacental ratio; FFP, fresh frozen plasma; FGR, fetal growth restriction; IVH, intraventricular hemorrhage; MCA, middle cerebral artery; NEC,
necrotizing enterocolitis; ns, nonstatistically significant; PI, pulsatility index; RDS, respiratory distress syndrome; SD, standard deviation; UA, umbilical
artery; EOP, early-onset preeclampsia; LOP, late-onset preeclampsia.

Interestingly, in our observation, the EOP group had by preeclampsia, which is consistent with the study of Madazil
higher serum levels of renal biomarkers than the LOP group, et al. [19], which reported a rate of 59.1%. Furthermore, in the
but no differences were found between the groups in terms present study, the incidence of fetal growth restriction
of adverse renal conditions and severe complications. reached as much as 70.7% in pregnancies with EOP. This
However, renal function can be impaired throughout pre- finding is consistent with the report of Lisonkova and Joseph
eclampsia as a result of glomerular endotheliosis, leading to a [17], but not with other observations [18]. Interestingly, the
decrease in the glomerular filtration rate [35]. In the present studied groups did not differ in terms of the frequency of flow
study, the groups differed in terms of proteinuria, blood urea disturbances in the UA, but in the EOP group, there were
nitrogen, and serum creatinine levels, which are represen- more frequent flow disturbances in the MCA. CPR <5th
tative of renal function in pregnancy. In contrast to our percentile also occurred more frequently in the EOP group.
study, Weitzner et al. [25] did not show differences in Both our study and Sibai’s study [30] showed a 100% mor-
creatinine levels. Furthermore, the increased serum level of tality rate in children born before 28 weeks of pregnancy.
uric acid has been shown to correlate with the severity of Compared to other papers, the major strength of the
glomerular endotheliosis [36]. However, in our study, the present work is that it contains a detailed, extensive analysis of
groups did not differ in terms of uric acid concentration, in clinical and laboratory factors that could be collected from the
contrast to a previous report by Li et al. comparing EOP and medical records. However, our study also has several limi-
LOP in patients with severe hypertension [18]. tations. First, it is a retrospective observational study with a
In our observation, EOP was strongly associated with relatively small sample size. Moreover, in some cases, due to
adverse fetoplacental conditions and severe complications. the severity of the disease, it became necessary to terminate
The cause of impaired fetoplacental function may be the the pregnancy within a short period of time, which did not
abnormal invasion of trophoblasts and remodeling of the permit further laboratory testing. Finally, the hospital where
spiral arteries, which can result in limited blood flow and lead the study was conducted is a tertiary referral center, wherein
to growth restriction and fetal distress symptoms. In our the most severe cases from the region of south-eastern Poland
study, FGR occurred in 60.2% of all pregnancies complicated are treated; hence, it could affect the results.
8 International Journal of Hypertension

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