Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction
Fetal growth restriction (FGR), when undetected antenatally, is the biggest risk factor for preventable stillbirth. Maternal circulating SPINT1 is reduced in pregnancies, which ultimately deliver small for gestational age (SGA) infants at term (birthweight < 10th centile), compared to appropriate...
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MDPI AG
2022-02-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/4/901 |
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| author | Ciara N. Murphy Catherine A. Cluver Susan P. Walker Emerson Keenan Roxanne Hastie Teresa M. MacDonald Natalie J. Hannan Fiona C. Brownfoot Ping Cannon Stephen Tong Tu’uhevaha J. Kaitu’u-Lino |
| author_facet | Ciara N. Murphy Catherine A. Cluver Susan P. Walker Emerson Keenan Roxanne Hastie Teresa M. MacDonald Natalie J. Hannan Fiona C. Brownfoot Ping Cannon Stephen Tong Tu’uhevaha J. Kaitu’u-Lino |
| author_sort | Ciara N. Murphy |
| collection | DOAJ |
| description | Fetal growth restriction (FGR), when undetected antenatally, is the biggest risk factor for preventable stillbirth. Maternal circulating SPINT1 is reduced in pregnancies, which ultimately deliver small for gestational age (SGA) infants at term (birthweight < 10th centile), compared to appropriate for gestational age (AGA) infants (birthweight ≥ 10th centile). SPINT1 is also reduced in FGR diagnosed before 34 weeks’ gestation. We hypothesised that circulating SPINT1 would be decreased in co-existing preterm preeclampsia and FGR. Plasma SPINT1 was measured in samples obtained from two double-blind, randomised therapeutic trials. In the Preeclampsia Intervention with Esomeprazole trial, circulating SPINT1 was decreased in women with preeclampsia who delivered SGA infants (<i>n</i> = 75, median = 18,857 pg/mL, IQR 10,782–29,890 pg/mL, <i>p</i> < 0.0001), relative to those delivering AGA (<i>n</i> = 22, median = 40,168 pg/mL, IQR 22,342–75,172 pg/mL). This was confirmed in the Preeclampsia Intervention 2 with metformin trial where levels of SPINT1 in maternal circulation were reduced in SGA pregnancies (<i>n</i> = 95, median = 57,764 pg/mL, IQR 42,212–91,356 pg/mL, <i>p</i> < 0.0001) compared to AGA controls (<i>n</i> = 40, median = 107,062 pg/mL, IQR 70,183–176,532 pg/mL). Placental Growth Factor (PlGF) and sFlt-1 were also measured. PlGF was significantly reduced in the SGA pregnancies, while ratios of sFlt-1/SPINT1 and sFlt1/PlGF were significantly increased. This is the first study to demonstrate significantly reduced SPINT1 in co-existing FGR and preeclamptic pregnancies. |
| first_indexed | 2024-03-09T21:41:48Z |
| format | Article |
| id | doaj.art-0f6180f16eee4205939ba631552b28cb |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T21:41:48Z |
| publishDate | 2022-02-01 |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-0f6180f16eee4205939ba631552b28cb2023-11-23T20:28:39ZengMDPI AGJournal of Clinical Medicine2077-03832022-02-0111490110.3390/jcm11040901Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth RestrictionCiara N. Murphy0Catherine A. Cluver1Susan P. Walker2Emerson Keenan3Roxanne Hastie4Teresa M. MacDonald5Natalie J. Hannan6Fiona C. Brownfoot7Ping Cannon8Stephen Tong9Tu’uhevaha J. Kaitu’u-Lino10Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaMercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, AustraliaFetal growth restriction (FGR), when undetected antenatally, is the biggest risk factor for preventable stillbirth. Maternal circulating SPINT1 is reduced in pregnancies, which ultimately deliver small for gestational age (SGA) infants at term (birthweight < 10th centile), compared to appropriate for gestational age (AGA) infants (birthweight ≥ 10th centile). SPINT1 is also reduced in FGR diagnosed before 34 weeks’ gestation. We hypothesised that circulating SPINT1 would be decreased in co-existing preterm preeclampsia and FGR. Plasma SPINT1 was measured in samples obtained from two double-blind, randomised therapeutic trials. In the Preeclampsia Intervention with Esomeprazole trial, circulating SPINT1 was decreased in women with preeclampsia who delivered SGA infants (<i>n</i> = 75, median = 18,857 pg/mL, IQR 10,782–29,890 pg/mL, <i>p</i> < 0.0001), relative to those delivering AGA (<i>n</i> = 22, median = 40,168 pg/mL, IQR 22,342–75,172 pg/mL). This was confirmed in the Preeclampsia Intervention 2 with metformin trial where levels of SPINT1 in maternal circulation were reduced in SGA pregnancies (<i>n</i> = 95, median = 57,764 pg/mL, IQR 42,212–91,356 pg/mL, <i>p</i> < 0.0001) compared to AGA controls (<i>n</i> = 40, median = 107,062 pg/mL, IQR 70,183–176,532 pg/mL). Placental Growth Factor (PlGF) and sFlt-1 were also measured. PlGF was significantly reduced in the SGA pregnancies, while ratios of sFlt-1/SPINT1 and sFlt1/PlGF were significantly increased. This is the first study to demonstrate significantly reduced SPINT1 in co-existing FGR and preeclamptic pregnancies.https://www.mdpi.com/2077-0383/11/4/901fetal growth restriction (FGR)intra-uterine growth restriction (IUGR)preeclampsiaSPINT1HAI-1stillbirth |
| spellingShingle | Ciara N. Murphy Catherine A. Cluver Susan P. Walker Emerson Keenan Roxanne Hastie Teresa M. MacDonald Natalie J. Hannan Fiona C. Brownfoot Ping Cannon Stephen Tong Tu’uhevaha J. Kaitu’u-Lino Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction Journal of Clinical Medicine fetal growth restriction (FGR) intra-uterine growth restriction (IUGR) preeclampsia SPINT1 HAI-1 stillbirth |
| title | Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction |
| title_full | Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction |
| title_fullStr | Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction |
| title_full_unstemmed | Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction |
| title_short | Circulating SPINT1 Is Reduced in a Preeclamptic Cohort with Co-Existing Fetal Growth Restriction |
| title_sort | circulating spint1 is reduced in a preeclamptic cohort with co existing fetal growth restriction |
| topic | fetal growth restriction (FGR) intra-uterine growth restriction (IUGR) preeclampsia SPINT1 HAI-1 stillbirth |
| url | https://www.mdpi.com/2077-0383/11/4/901 |
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