Could carbonic anhydrase IX predict fetal growth restriction in early onset preeclampsia?

Ozgen, Gulten; Dincgez, Burcu

doi:10.1590/1806-9282.20250838

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Original Article • Rev. Assoc. Med. Bras. 71 (11) • 2025 • https://doi.org/10.1590/1806-9282.20250838 linkcopy

Could carbonic anhydrase IX predict fetal growth restriction in early onset preeclampsia?

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE: Placental insufficiency, which plays a crucial role in both preeclampsia and fetal growth restriction, can cause oxidative stress and high reactive oxygen species production that could lead to hypoxia. Carbonic anhydrase IX is induced by hypoxia-inducible factor-1α, an important transcriptional regulator of genes involved in response to hypoxia. Considering this, we aimed to determine carbonic anhydrase IX levels in early preeclampsia with and without fetal growth restriction, and also to evaluate the predictive role of carbonic anhydrase IX for the development of fetal growth restriction in early onset preeclampsia.

METHODS: This prospective study included a total of 180 participants, who were divided into two groups—early onset preeclampsia (n=90) and control (n=90). Then, preeclamptic patients were followed and subgrouped as preeclampsia with fetal growth restriction (n=35) and without fetal growth restriction (n=55). Sociodemographic and obstetric characteristics and laboratory features including carbonic anhydrase IX were compared between groups.

RESULTS: Median carbonic anhydrase IX was higher in preeclampsia than controls [2.07 (0.78–5.48) vs. 1.32 (0.63–2.12), p<0.001]. Moreover, median carbonic anhydrase IX was higher in the preeclampsia with fetal growth restriction group as compared to the preeclampsia without fetal growth restriction group [2.76 (0.78–5.48) vs. 1.77 (0.89–5.14), p=0.018]. The carbonic anhydrase IX >1.83 pg/mL predicted fetal growth restriction with 77.14% sensitivity and 52.73% specificity (p=0.015, AUC=0.649) in the early onset preeclampsia.

CONCLUSION: Carbonic anhydrase IX could reflect the insufficiency of the placenta in early onset preeclampsia and fetal growth restriction, and it could be used in early onset preeclampsia patients for the prediction of fetal growth restriction.

KEYWORDS:
Carbonic anhydrase IX; Fetal growth restriction; Preeclampsia

	EOP (n=90)	Control (n=90)	p-value
Age (years)	27 (18–40)	27.5 (18–40)	0.444
BMI (kg/m²)	31.4 (23.8–48.3)	33 (21.3–46.9)	0.119
Gravida (n)	2 (1–7)	3 (1–6)	0.490
Parity (n)	2 (0–7)	2 (0–6)	0.637
Nulliparity (n, %)	3 (3.3%)	6 (6.7%)	0.497
Gestational age at sampling (week)	24 (22–26)	24 (22–26)	0.986
Systolic blood pressure (mmHg)	140 (140–200)	120 (110–130)	<0.001
Diastolic blood pressure (mmHg)	90 (90–110)	80 (60–90)	<0.001
Birth weight (gram)	1,955 (525–4,780)	3,305 (845–4,200)	<0.001
Birth week (week)	35 (24–39)	38 (28–41)	<0.001
Apgar score of first minute	7 (1–9)	8 (2–9)	<0.001
Apgar score of fifth minute	8 (2–10)	9 (1–10)	0.034
NICU requirement (n, %)	18 (20%)	8 (8.9%)	<0.001
Preterm birth (n, %)	61 (67.8%)	19 (21.1%)	<0.001
Cesarean section (n, %)	40 (44.4%)	17 (18.9%)	<0.001
Neonatal death (n, %)	5 (5.6%)	3 (3.3%)	0.469
Platelet (x10³/μL)	211 (109–417)	202.5 (125–361)	0.233
AST (IU/L)	21.5 (10–57)	19.5 (7–59)	0.062
ALT (IU/L)	12.5 (2–36)	12 (6–54)	0.439
Creatinine (mg/dL)	0.58 (0.43–1.40)	0.47 (0.4–0.87)	0.175
Maternal CAIX (pg/mL)	2.07 (0.78–5.48)	1.32 (0.63–2.12)	<0.001

	EOP with FGR (n=35)	EOP without FGR (n=55)	p-value
Age (years)	26 (19–39)	27 (18–40)	0.054
BMI (kg/m²)	30.9 (23.8–48.3)	33 (24–48.3)	0.410
Gravida (n)	2 (1–7)	2 (1–7)	0.487
Parity (n)	2 (0–7)	2 (0–5)	0.756
Nulliparity (n, %)	1 (2.9%)	2 (3.6%)	1.000
Gestational age at sampling (week)	24 (22–26)	24 (22–26)	0.616
Systolic blood pressure (mmHg)	150 (140–180)	140 (140–200)	0.192
Diastolic blood pressure (mmHg)	90 (90–110)	90 (90–110)	0.795
Birth weight (gram)	1,547±543.7	2,360±821.5	<0.001 *
Birth week (week)	34 (24–38)	36 (25–39)	0.011
Apgar score of first minute	6 (1–9)	8 (3–9)	<0.001
Apgar of score fifth minute	7 (2–10)	9 (4–10)	<0.001
NICU requirement (n, %)	11 (31.4%)	7 (12.7%)	0.031
Preterm birth (n, %)	29 (82.9%)	32 (58.2%)	0.015
Cesarean section (n, %)	20 (57.1%)	20 (36.4%)	<0.001
Neonatal death (n, %)	4 (11.4%)	1 (1.8%)	0.052
Platelet (x10³/μL)	220 (132–323)	206 (109–417)	0.665
AST (IU/L)	23 (12–42)	21 (10–57)	0.526
ALT (IU/L)	14 (6–36)	12 (2–28)	0.169
Creatinine (mg/dL)	0.58 (0.44–1.36)	0.58 (0.43–1.40)	0.960
Maternal CAIX (pg/mL)	2.76 (0.78–5.48)	1.77 (0.89–5.14)	0.018

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[TFN1] ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; CAIX: carbonic anhydrase IX; EOP: early onset preeclampsia; NICU: neonatal intensive care unit. Mann-Whitney-U test was used to compare variables between two groups for continuous variables and expressed as median (min–max) values. Significant p-values were expressed in bold.