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Objective: To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH).Design: Retrospective cohort study.Setting: Tertiary teaching hospital in Adelaide, Australia.Population: A total of 30 198 women delivering between 2002 and 2008.Methods: Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia.Main Outcome Measures: The primary outcome was PPH, defined as a recorded blood loss of ≥500 mL for vaginal deliveries and ≥1000 mL for caesarean sections. Secondary outcomes included severe PPH (≥1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records).Results: Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53; 95% confidence interval, 95% CI 1.25-1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04; 95% CI 0.89-1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84; 95% CI 1.39-2.44), as well as postpartum anaemia (aRR 1.80; 95% CI 1.46-2.22).Conclusions: Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH.Tweetable Abstract: Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage. [ABSTRACT FROM AUTHOR]

Objectives To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. Design Predictive test accuracy study. Setting Prospective multicentre cohort study Screening for Pregnancy Endpoints ( SCOPE). Methods Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor ( Pl GF), soluble endoglin and soluble fms-like tyrosine kinase-1 (s Flt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Main outcome measure Preterm pre-eclampsia (delivered before 37+0 weeks of gestation). Results Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls ( n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve ( AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of Pl GF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and Pl GF measurement. Conclusions Addition of plasma Pl GF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Anderson N, McCowan L, Fyfe E, Chan E, Taylor R, Stewart A, Dekker G, North R, on behalf of the SCOPE Consortium. The impact of maternal body mass index on the phenotype of pre-eclampsia: a prospective cohort study. BJOG 2012;119:589-595. Objective We hypothesised that among nulliparous women with pre-eclampsia, overweight or obese women would have a different phenotype of pre-eclampsia compared with normal weight women with pre-eclampsia. Specifically, they are more likely to develop term pre-eclampsia and less likely to have indicators of impaired placental perfusion, e.g. abnormal uterine artery Doppler or a small-for-gestational-age (SGA) infant. Design Prospective, multicentre, cohort SCOPE study ( n = 3170). Setting New Zealand and Australia. Population Nulliparous women who developed pre-eclampsia. Methods Participants were interviewed at 14-16 weeks of gestation, uterine artery Doppler studies were performed at 19-21 weeks and pregnancy outcome was tracked prospectively. Main outcome measures Rates of abnormal uterine artery Doppler indices, term/preterm birth and SGA infants were compared between normal, overweight and obese women with pre-eclampsia. Multivariable analysis was performed to examine the association between body mass index (BMI) and term pre-eclampsia. Results Of 178 women with pre-eclampsia, one underweight woman was excluded and 66 (37%) were normal weight, 52 (29%) were overweight and 59 (34%) were obese. Pre-eclampsia developed preterm in 26% of women and at term in 74% of women. There were no differences in the rates of term/preterm pre-eclampsia, abnormal uterine artery Doppler indices or SGA infants between BMI groups ( P > 0.10). No independent association between BMI and term pre-eclampsia was found ( P = 0.56). Conclusions Among women with pre-eclampsia, those who are overweight or obese in early pregnancy are not more likely to have term pre-eclampsia compared with women with a normal BMI. Overweight and obese women require vigilant surveillance for the development of preterm as well as term pre-eclampsia. [ABSTRACT FROM AUTHOR]

Objectives: To analyse risk factors of perinatal death, with an emphasis on potentially avoidable risk factors, and differences in the frequency of suboptimal care factors between maternity units with different levels of care. Methods: Six hundred and eight pregnancies (2001-2005) in South Australia resulting in perinatal death were described and compared to 86 623 live birth pregnancies. Results: Two hundred and seventy cases (44.4%) were found to have one or more avoidable maternal risk factors, 31 cases (5.1%) had a risk factor relating access to care, while 68 cases (11.2%) were associated with deficiencies in professional care. One hundred and four women (17.1% of cases) presented too late for timely medical care: 85% of these did have a sufficient number of antenatal visits. The following independent maternal risk factors for perinatal death were found: assisted reproductive technology (adjusted odds ratio (AOR) 3.16), preterm labour (AOR 22.05), antepartum haemorrhage (APH) abruption (AOR 6.40), APH other/unknown cause (AOR 2.19), intrauterine growth restriction (AOR 3.94), cervical incompetence (AOR 8.89), threatened miscarriage (AOR 1.89), pre-existing hypertension (AOR 1.72), psychiatric disorder (AOR 1.85) and minimal antenatal care (AOR 2.89). The most commonly found professional care deficiency in cases was the failure to act on or recognise high-risk pregnancies/complications, found in 49 cases (8.1%). Conclusion: Further improvements in perinatal mortality may be achieved by greater emphasis on the importance of antenatal care and educating women to recognise signs and symptoms that require professional assessment. Education of maternity care providers may benefit from a further focus on how to recognise and/or manage high-risk pregnancies. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare preterm delivery rates and neonatal morbidity/mortality rates for women with cervical incompetence with membranes at or beyond a dilated external cervical os that was treated with emergency cerclage, bed rest plus indomethacin, versus just bed rest.Study Design: Women with cervical incompetence with membranes at or beyond a dilated external cervical os, before 27 weeks of gestation, were treated with antibiotics and bed rest and randomly assigned for emergency cerclage and indomethacin or bed rest only.Results: Twenty-three women were included; 13 women were allocated randomly to the emergency cerclage and indomethacin group, and 10 women were allocated randomly to the bed rest-only group. Gestational age at time of randomization was 22.2 weeks in the emergency cerclage and indomethacin group and 23.0 weeks in the bed rest-only group. Mean interval from randomization until delivery was 54 days in the emergency cerclage and indomethacin group and 20 days in the bed rest-only group (P=.046). Mean gestational age at delivery was 29.9 weeks in the emergency cerclage and indomethacin group and 25.9 weeks in the bed rest-only group. Preterm delivery before 34 weeks of gestation was significantly lower in the emergency cerclage and indomethacin group, with 7 of 13 deliveries versus all 10 deliveries in the bed rest-only group (P=.02).Conclusions: Emergency cerclage, indomethacin, antibiotics, and bed rest reduce preterm delivery before 34 weeks compared with bed rest and antibiotics alone. [ABSTRACT FROM AUTHOR]

The objective of this study was to establish whether or not patients with unexplained recurrent abortion have an increased incidence of haemostatic or metabolic abnormalities. Fifty-two patients with a history of unexplained habitual abortion (two or more spontaneous abortions before 16 weeks' gestation) were tested for protein S, protein C and antithrombin (AT) III deficiency, activated protein C (aPC) resistance, hyperhomocysteinaemia and anticardiolipin antibodies (ACA). The control group consisted of 67 healthy women with a history of only uncomplicated pregnancies. Blood samples were taken for measuring protein S, protein C, AT III, ACA and activated protein C resistance and a methionine loading test was performed. Of the 46 patients tested for protein S deficiency, 8 (17.4%) were positive. Of the 43 patients tested, two (4.7%) were protein C deficient and none was AT III deficient. Of the 42 patients tested for ACA, eight (19.1%) had detectable antibodies. Of the 44 patients tested for aPC resistance, two (4.6%) were positive. Finally, 35 patients were tested for hyperhomocysteinaemia and six (17.1%) were positive. It was concluded that parous women with a history of unexplained recurrent abortion have an increased incidence of hyperhomocysteinaemia and a trend of increased incidence of ACA can be found. [ABSTRACT FROM PUBLISHER]

Background: We hypothesized that there is an influence of socioeconomic status (SES) on association between pregnancy complications and premature coronary artery disease (PCAD) risk., Materials and Methods: This project involved a data linkage approach merging three databases of South Australian cohorts using retrospective, age-matched case-control study design. Cases ( n  = 721), that is, women aged <60 years from Coronary Angiogram Database of South Australia (CADOSA) were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain prior pregnancy outcomes and SES. Controls ( n  = 194) were selected from North West Adelaide Health Study (NWAHS), comprising women who were healthy or had health conditions unrelated to CAD, age matched to CADOSA (±5 years), and linked to SAPSC to determine prior pregnancy outcomes and SES. This project performed comparative analysis of SES using socioeconomic indexes for areas-index of relative socioeconomic advantage and disadvantage (SEIFA-IRSAD) scores across three databases., Results: Findings revealed that SEIFA-IRSAD scores at the time of pregnancy ( p -value = 0.005) and increase in SEIFA-IRSAD scores over time ( p -value = 0.040) were significantly associated with PCAD. In addition, when models were adjusted for SEIFA-IRSAD scores at the time of pregnancy and age, risk factors including placenta-mediated pregnancy complications such as preterm birth (odds ratio [OR] = 4.77, 95% confidence interval [CI]: 1.74-13.03) and history of a miscarriage (OR = 2.14, 95% CI: 1.02-4.49), and cardiovascular disease (CVD) risk factors including smoking (OR = 8.60, 95% CI: 3.25-22.75) were significantly associated with PCAD. When the model was adjusted for change in SEIFA-IRSAD scores (from CADOSA/NWAHS to SAPSC) and age, pregnancy-mediated pregnancy complications including preterm birth (OR = 4.40, 95% CI: 1.61-12.05) and history of a miscarriage (OR = 2.09, 95% CI: 1.00-4.35), and CVD risk factor smoking (OR = 8.75, 95% CI: 3.32-23.07) were significantly associated with PCAD., Conclusion: SES at the time of pregnancy and change in SES were not associated with PCAD risk., Competing Interests: No competing financial interests exist., (© Adeel Khoja et al., 2024; Published by Mary Ann Liebert, Inc.)

Introduction: In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a "by-product" of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model., Materials and Methods: Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele's Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups., Results: The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; p  < 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; p  = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29  ±  80.76 mg vs. 550  ±  64.03 mg; p  < 0.001 and birth length: 14.43  ±  1.27 mm vs. 19.00  ±  1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29  ±  75.47 mg and 18.14  ±  1.34 mm, p  = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; p  = 0.794)., Conclusions: Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model.

Objectives: Evaluate the association between poor mental health and risk of developing gestational diabetes mellitus (GDM) in a cohort of women from a socioeconomically disadvantaged community., Methods: A total of 1363 nulliparous women with singleton pregnancies recruited to the Screening Tests to Predict Poor Outcomes of Pregnancy study in Adelaide, Australia. Women were assessed for mental health in the first trimester, including likelihood of depression, high functioning anxiety, perceived stress and risk of developing a mental health disorder. GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Socioeconomic status was measured using the New Zealand Socioeconomic Index (NZSEI)., Results: Complete mental health data was available for 1281 participants. There was no statistically significant difference in SEI, depression, risk of mental health issues, high functioning anxiety and perceived stress between women who developed GDM and those who did not. There was no difference in history of depression nor risk of developing a high mental health disorder in first trimester after adjusting for SEI, BMI in first trimester, smoking status in first trimester and maternal age between women with a GDM pregnancy and those who did not., Conclusions for Practice: There was no difference in markers of poor mental health in early pregnancy between women who subsequently did or did not develop GDM. Cohort participants were socioeconomically disadvantaged, potentially contributing to the lack of apparent differences in depression observed between groups. Socioeconomically disadvantaged women should be targeted in pre-conception planning to reduce risk of GDM., (© 2023. Crown.)

Background: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). Methods: This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case-control study design. Cases ( n  = 721) were ascertained from the Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain their prior pregnancy outcomes. Controls ( n  = 194) were selected from North West Adelaide Health Study (NWAHS) and comprised women who were healthy or had other health conditions unrelated to CAD, age-matched to CADOSA (±5 years), and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as >50% stenosis in one or more coronary arteries at coronary angiography. Results: Compared with women without a history of PCAD, women who were diagnosed with PCAD were more likely to have experienced the placenta-mediated pregnancy complications of preterm birth (adjusted odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.21-5.00) or low-birth weight (adjusted OR = 2.44, 95% CI: 1.22-4.88), or have been diagnosed with active asthma during pregnancy (adjusted OR = 3.52, 95% CI: 1.05-11.76). Conclusion: Placenta-mediated pregnancy complications should be recognized as clear risk markers for future PCAD.

Background: Breastfeeding is important for both mother and child in reducing risk of future cardiovascular disease. Therefore, it may be an effective method to improve cardio-metabolic health, particularly those who are exposed to pregnancy complications which increase later CVD risk for both mother and child. The aim of this study is to assess differences in cardiometabolic health at three years postpartum in mothers who breastfed for at least six months and their children compared to those who did not., Methods: Women and children from the Screening Tests to Predict Poor Outcomes of Pregnancy (STOP) study (2015-2017) were invited to attend a health check-up at three years postpartum. Women's breastfeeding status at least six months postpartum was ascertained through their child health record. Anthropometric and hemodynamic measurements were taken from women and their children. A fasting blood sample was taken from women to measure blood glucose and lipids., Results: A total of 160 woman-child dyads were assessed in this study. Women who breastfed for at least six months had significantly lower maternal BMI, systolic blood pressure, diastolic blood pressure, mean arterial pressure, central systolic blood pressure, and central diastolic blood pressure than those who did not and this did not change after adjusting for BMI and socioeconomic index in early pregnancy, prenatal smoking and maternal age in early pregnancy. Subgroup analysis on women who had one or more pregnancy complications during the index pregnancy (i.e. preeclampsia, gestational hypertension, delivery of a small for gestational age infant, delivery of a preterm infant, and/or gestational diabetes mellitus) demonstrated that women who breastfed for at least six months had significantly lower maternal systolic and diastolic blood pressures, serum insulin and triglycerides, and higher HDL cholesterol. There were no differences in child anthropometric or hemodynamic variables at three years of age between those children who had been breastfed for at least six months and those who had not., Conclusion: Breastfeeding for at least six months may reduce some maternal; cardiovascular risk factors in women at three years postpartum, in particular, in those who have experienced a complication of pregnancy., Trial Registration: ACTRN12614000985684 (12/09/2014)., (© 2023. The Author(s).)

Background: Certain maternal complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, birth of a growth restricted infant, idiopathic preterm labour, and placental abruption, are associated with a significantly increased risk of future maternal cardiovascular disease. In Australia, it is relatively unknown how many women with a history of complicated pregnancies are aware of their future cardiovascular disease risk., Aim: The aim of this study was to determine what percentage of women attending a cardiovascular disease prevention clinic in South Australia soon after a complicated pregnancy were aware of their increased risk of cardiovascular disease., Methods: This prospective observational study included 188 women attending a postpartum prevention clinic between 7th August 2018 and 10th February 2021. These women had experienced a serious maternal complication of pregnancy approximately seven months earlier. Women completed a self-administered health awareness survey immediately prior to their first clinic appointment to assess their awareness of their increased cardiovascular risk., Findings: Over two-thirds (69.1 %) of the women were unaware of the association between pregnancy complications and cardiovascular disease, and 6.4 % of the cohort did not realise they had experienced a complicated pregnancy. Almost 10 % of the cohort did not correctly identify the complication/s they had been diagnosed with during pregnancy., Conclusion: Awareness of the association between complications of pregnancy and future cardiovascular disease was low in our cohort of women who had experienced a complication of pregnancy only seven months earlier. This emphasises the need for improved education for and communication with women to assist in implementing preventative care strategies., (Copyright © 2023 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin resistance and gestational diabetes. We aimed to establish whether maternal one-carbon metabolism and hormones that regulate glucose homeostasis change in healthy pregnancies post-FA food fortification. Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood in women with uncomplicated pregnancies prior to (SCOPE: N = 604) and post (STOP: N = 711)-FA food fortification. FA food fortification resulted in 63% higher maternal folate. STOP women had lower hPL (33%) and GH2 (43%) after 10 weeks of gestation, but they had higher PRL (29%) and hPL (28%) after 16 weeks. FA supplementation during pregnancy increased maternal folate and reduced homocysteine but only in the SCOPE group, and it was associated with 54% higher PRL in SCOPE but 28% lower PRL in STOP. FA food fortification increased maternal folate status, but supplements no longer had an effect, thereby calling into question their utility. An altered secretion of hormones that regulate glucose homeostasis in pregnancy could place women post-fortification at an increased risk of insulin resistance and gestational diabetes, particularly for older women and those with obesity.

Background: We aimed to compare risk factors for CVD 10 years postpartum among women who had ≥ 1 compared to no cardio metabolic risk factor in early first pregnancy., Methods: Women of the SCOPE (Screening fOr Pregnancy Endpoints) study from Adelaide, South Australia were invited to participate in a cardiovascular risk assessment 10 years after the delivery of the first child. Data from 141 women who completed all the assessments are included in the analyses., Result: Compared to women who did not have any cardio metabolic risk factor at 15 ± 1 weeks' gestation during the first pregnancy, those who had ≥ 1 risk factor were 5.5 times more likely to have metabolic syndrome 10 years postpartum (aOR = 5.5, 95% CI 1.8-17.3, p = 0.004). Women who had ≥ 1cardio metabolic risk factor during the first pregnancy were more likely to be obese (p = 0.001), have high total cholesterol levels (p <0.001) or have increased insulin resistance (p <0.001) 10 years later compared to women who had no risk factor during the first pregnancy. 63.5% of the women with no cardio metabolic risk factor compared to 39% of women who had ≥ 1 risk factor in first pregnancy, had neither a complicated first pregnancy nor was diagnosed with MetS 10 years postpartum (p = 0.023)., Conclusion: Cardio metabolic risk factors at the booking visit in the first pregnancy may be useful in identifying young women at risk of future CVD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Andraweera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To test the equivalence of two doses of intravenous iron (ferric carboxymaltose) in pregnancy., Design: Parallel, two-arm equivalence randomised controlled trial with an equivalence margin of 5%., Setting: Single centre in Australia., Population: 278 pregnant women with iron deficiency., Methods: Participants received either 500 mg (n = 152) or 1000 mg (n = 126) of intravenous ferric carboxymaltose in the second or third trimester., Main Outcome Measures: The proportion of participants requiring additional intravenous iron (500 mg) to achieve and maintain ferritin >30 microg/L (diagnostic threshold for iron deficiency) at 4 weeks post-infusion, and at 6 weeks, and 3-, 6- and 12-months postpartum. Secondary endpoints included repeat infusion rate, iron status, birth and safety outcomes., Results: The two doses were not equivalent within a 5% margin at any time point. At 4 weeks post infusion, 26/73 (36%) participants required a repeat infusion in the 500-mg group compared with 5/67 (8%) in the 1000-mg group: difference in proportions, 0.283 (95% confidence interval [CI] 0.177-0.389). Overall, participants in the 500-mg arm received twice the repeat infusion rate (0.81 [SD = 0.824] versus 0.40 [SD = 0.69], rate ratio 2.05, 95% CI 1.45-2.91)., Conclusions: Administration of 1000 mg ferric carboxymaltose in pregnancy maintains iron stores and reduces the need for repeat infusions. A 500- mg dose requires ongoing monitoring to ensure adequate iron stores are reached and sustained., (© 2022 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO)., Methods: Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11-20 week's gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination)., Result: The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, p  = .013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), p  = .177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, p  = .006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 p  = .594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), p  = .044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), p  = .002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), p  = .402. Control: 3.38 (0.83) vs. 3.06 (0.74), p  = .287)., Conclusion: Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia.