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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.)

Purpose: Pregnancy complications affect over one quarter of Australian pregnancies, and this group of mothers is vulnerable and more likely to experience adverse cardiometabolic health outcomes in the postpartum period. Metabolic syndrome is common in this population and may be associated with postpartum mental health issues. However, this relationship remains poorly understood. To compare the differences in psychosocial parameters and mental health outcomes between women with metabolic syndrome and women without metabolic syndrome 6 months after a complicated pregnancy., Methods: This study is prospective registry analysis of women attending a postpartum healthy lifestyle clinic 6 months following a complicated pregnancy. Mental health measures included 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalised Anxiety Disorder questionnaire (GAD-7), self-reported diagnosed history of depression, anxiety and/or other psychiatric condition, and current psychotropic medication use., Results: Women with metabolic syndrome reported significantly more subjective mental health concerns, were more likely to have a history of depression and other psychiatric diagnoses and were more likely prescribed psychotropic medications. However, there were no significant differences in PHQ-9 and GAD-7 scores., Conclusion: Amongst new mothers who experienced complications of pregnancy, those with metabolic syndrome represent a particularly vulnerable group with regards to psychosocial disadvantage and mental health outcomes. These vulnerabilities may not be apparent when using common standardised cross-sectional mental health screening tools such as PHQ-9 and GAD-7., (© 2022. The Author(s).)

Maternal micronutrient deficiencies in pregnancy can have profound effects on fetal development and pregnancy outcome. Plasma trace minerals including copper, zinc, selenium and iron have been shown to be extremely important in supporting reproduction. We sought to determine whether there is an association between maternal trace mineral status in early pregnancy and pregnancy complications using a prospective cohort study of 1065 pregnant Australian women who were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) study in Adelaide. Copper, zinc, selenium and iron present in the plasma were measured using mass spectrometry in samples collected at 15±1 weeks' gestation. After adjusting for covariates, women with lower plasma copper (<27.9μmol/L and 27.9-32.5μmol/L) had decreased risk for any pregnancy complication when compared with women with high plasma copper (>32.5μmol/L) (aRR=0.87; 95% CI=0.76, 0.99 and aRR=0.88; 95% CI=0.78, 1.00, respectively). This was also observed when adjusting for plasma zinc and selenium status (<27.9μmol/L: aRR=0.81; 95% CI=0.69, 0.96 and 27.9-32.5μmol/L: aRR=0.84; 95% CI=0.72, 0.98). Combined low copper and zinc status was also associated with a reduced risk of any pregnancy complication as compared with high copper and zinc status (aRR=0.80; 95% CI=0.70, 0.93). These results provide justification for further work into elucidating the mechanistic role of trace elements in early pregnancy, as well as their interactions in supporting successful pregnancy outcomes., (Crown Copyright © 2017. Published by Elsevier GmbH. All rights reserved.)

Objective: To review the management and outcomes of Intrahepatic Cholestasis of Pregnancy (ICP) in South Australia (SA) over the past decade., Design: Retrospective cohort review., Setting: Public clinics at two teaching hospitals in SA., Population: All pregnancies associated with ICP (defined as pruritus with serum bile acids≥10μmol/L) managed 2001-2010., Methods: Identification of subjects (laboratory database), detailed chart-review to ascertain demographics, maternal/perinatal outcomes and associated pregnancy comorbidities, analysis of mild/severe disease cohorts, comparison with normal population data, using Student's t-test or Mann-Whitney U test as appropriate for continuous variables, and Pearson's chi-square test or Fisher's exact test for categorical variables. Unadjusted odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in comparison with the general pregnant population for clinically significant outcomes., Results: 320 women (359 pregnancies) were diagnosed with ICP over the 10-years: incidence 0.6%/year. Within the cohort, the incidences of gestational diabetes (12.5%; OR 3.06, 95% CI 2.23-4.18), pre-eclampsia (10.3%; OR 75.84, 95% CI 52.91-178.70), and spontaneous preterm labour (23.1%; OR 2.05, 95% CI 1.41-2.98) were much higher than in the general SA pregnant population. Pregnancies with severe ICP (serum bile acids≥40μmol/L) had ICP diagnosed earlier (231 vs 248 days, P<0.001), and ended earlier (256 vs 260 days, P<0.001) with lower birthweights (2827g vs 3093g, P <0.001) than those with mild ICP. Neonates of severe ICP mothers were more likely to require special-care-nursery admission, but perinatal complication rates did not differ. There were no stillbirths., Conclusion: This large Australian retrospective cohort study confirms generally favourable outcomes associated with ICP, mild or severe, with no stillbirths, likely secondary to proactive medical management. A high proportion of pregnancies were also affected by gestational diabetes, pre-eclampsia, and/or spontaneous pre-term labour compared with the general population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine the impact of self-reported maternal depression/anxiety on asthma control during pregnancy., Method: Pregnant women with a doctor diagnosis of asthma (n = 189) were prospectively recruited at their antenatal booking visit, and the presence of maternal depression and anxiety was identified using self-report and routine questionnaire assessments. Data on exacerbations and asthma control were collected during gestation. Asthma control was assessed using the Juniper Asthma Control Questionnaire (ACQ) and women were classified as having recurrent uncontrolled asthma if their ACQ score was >1.5 during two or more consecutive study visits. Exacerbations were defined as events that led to increased treatment requirements, and doctor or hospital visits., Results: There were 85 women with self-reported depression/anxiety and 104 women without self-reported depression/anxiety. The presence of depression/anxiety was associated with an increased likelihood (adjusted hazard ratio (HR) 1.67: 95% confidence interval (CI) 1.03-2.72) and incidence (adjusted incidence rate ratio (IRR) 1.71: 95% CI 1.13-2.58) of uncontrolled asthma during pregnancy, as well as an increased risk of recurrent uncontrolled asthma during 2 or more study visits (adjusted relative risk (RR) 1.98: 95% CI 1.00-3.91). No impact of depression/anxiety was observed with respect to the likelihood (adjusted HR 0.70: 95% CI 0.35-1.41) or incidence of exacerbations during pregnancy (adjusted IRR 0.66: 95% CI 0.35-1.26)., Conclusions: This study provides evidence that the presence of maternal depression/anxiety is associated with an increased likelihood and incidence of uncontrolled asthma during pregnancy. Given the high prevalence of co-morbid depression/anxiety among asthmatics, further research investigating such associations is urgently required.

Objective: To examine the patterns and predictors of inter-pregnancy body mass index (BMI) change and its impact on perinatal outcomes in the second pregnancy., Design: Retrospective cohort study., Setting: Tertiary teaching hospital in Adelaide, Australia., Population: Women with their first and second consecutive, singleton deliveries occurring between 2000 and 2012 (N=5371)., Methods: Inter-pregnancy weight change calculated based on difference between BMI at respective antenatal booking visits. Association between inter-pregnancy weight change and perinatal outcomes investigated using multivariate generalised linear models, with stratification according to initial maternal BMI category in first pregnancy., Main Outcome Measures: Gestational diabetes (GDM); pregnancy induced hypertensive disorders; small-for-gestational age (SGA); preterm birth; large-for-gestational age (LGA) and macrosomia (>4500g)., Results: On average, women with a normal BMI gained 1kg/m(2) between first and second pregnancies, while women who were overweight or obese gained 1.37kg/m(2). Among women with a normal BMI in their first pregnancy, a BMI increase of ≥4kg/m(2) was associated with increased risk of developing GDM (aRR 1.97; 95% CI 1.22-3.19), a macrosomic (aRR 4.06; 95% CI 2.25-7.34) or LGA infant (aRR 1.31 0.96-1.78) in the second pregnancy, while a reduction in BMI (≤-2kg/m(2)) was associated with an increased risk of SGA (aRR 1.94; 1.19-3.16). Among women who were overweight or obese in their first pregnancy, a BMI increase of ≥2-4 and ≥4kg/m(2) was associated with increased risks of developing GDM in the second pregnancy (aRR 1.39; 95% CI 1.01-1.91 and aRR 1.64 95% CI 1.16-2.31; ptrend<0.001), while no associations were observed for a BMI increase and risk of a macrosomic, SGA, or LGA infant. In contrast, reduction in BMI (≤-2kg/m(2)) was associated with a reduced risk of GDM (aRR 0.58 95% CI 0.37-0.90) and SGA (aRR 0.47; 95% CI 0.25-0.87)., Conclusion: Increases in BMI between pregnancies is associated with an increased risk for perinatal complications, even in normal-weight women, while a reduction in BMI is associated with improved perinatal outcomes among women who are overweight/obese. Inter-pregnancy weight control is an important target to reduce the risk of an adverse perinatal outcome in a subsequent pregnancy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Being born small for gestational age (SGA) increases the risk for adverse perinatal outcomes and later life vascular and metabolic disorders. The insulin family plays a vital role in intrauterine growth. We investigated the association of functional SNPs in insulin (INS), insulin receptor (INSR) and insulin receptor substrate 2 (IRS2) with small for gestational age (SGA) pregnancies, uterine and umbilical artery Doppler and plasma insulin level. We conducted a nested case-control study of 1401 nulliparous Caucasian women, their partners and babies (216 SGA and 1185 uncomplicated). SGA was defined as a birthweight less than the 10th customized birthweight percentile adjusted for maternal height, weight, parity, ethnicity, gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 ± 1 week gestation. The SNPs in the parent infant trios were genotyped using Sequenom MassARRAY. Plasma insulin was measured by double antibody RIA in 188 healthy non-pregnant adults to assess correlations between SNP genotypes and circulating insulin. Paternal [odds ratio (OR) (95% CI) = 2.2 (1.3-3.9), P = 0.005] and infant [OR (95% CI) = 3.3 (1.7-6.2), P = 0.0001] INSR rs2059806 AA genotype was associated with SGA. Infant INSR rs2059806 A allele was associated with abnormal umbilical artery Doppler [OR (95% CI) = 1.3(1.0-1.7), P = 0.04]. INSR rs2059806 AA homozygous individuals had lower plasma insulin compared with heterozygotes (P = 0.03) and GG homozygotes (P = 0.03). The INSR rs2059806 SNP previously associated with adult vascular and metabolic diseases is also associated with SGA pregnancies. This polymorphism may associate with the risk of vascular and metabolic disorders across the life course., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Excessive gestational weight gain (GWG) is associated with adverse maternal and child outcomes and contributes to obesity in women. Our aim was to identify early pregnancy factors associated with excessive GWG, in a contemporary nulliparous cohort., Methods: Participants in the SCOPE study were classified into GWG categories ("not excessive" versus "excessive") based on pregravid body mass index (BMI) using 2009 Institute of Medicine (IOM) guidelines. Maternal characteristics and pregnancy risk factors at 14-16 weeks were compared between categories and multivariable analysis controlled for confounding factors., Results: Of 1950 women, 17% gained weight within the recommended range, 74% had excessive and 9% inadequate GWG. Women with excessive GWG were more likely to be overweight (adjOR 2.9 (95% CI 2.2-3.8)) or obese (adjOR 2.5 (95% CI 1.8-3.5)) before pregnancy compared to women with a normal BMI. Other factors independently associated with excessive GWG included recruitment in Ireland, younger maternal age, increasing maternal birthweight, cessation of smoking by 14-16 weeks, increased nightly sleep duration, high seafood diet, recent immigrant, limiting behaviour, and decreasing exercise by 14-16 weeks. Fertility treatment was protective., Conclusions: Identification of potentially modifiable risk factors for excessive GWG provides opportunities for intervention studies to improve pregnancy outcome and prevent maternal obesity.

Objective: To identify factors at 15 and 20 weeks' gestation associated with a subsequent uncomplicated pregnancy., Design: Prospective international multicentre observational cohort study., Setting: Auckland, New Zealand and Adelaide, Australia (exploration and local replication dataset) and Manchester, Leeds, and London, United Kingdom, and Cork, Republic of Ireland (external confirmation dataset)., Participants: 5628 healthy nulliparous women with a singleton pregnancy., Main Outcome Measure: Uncomplicated pregnancy, defined as a normotensive pregnancy delivered at >37 weeks' gestation, resulting in a liveborn baby not small for gestational age, and the absence of any other significant pregnancy complications. In a stepwise logistic regression the comparison group was women with a complicated pregnancy., Results: Of the 5628 women, 3452 (61.3%) had an uncomplicated pregnancy. Factors that reduced the likelihood of an uncomplicated pregnancy included increased body mass index (relative risk 0.74, 95% confidence intervals 0.65 to 0.84), misuse of drugs in the first trimester (0.90, 0.84 to 0.97), mean diastolic blood pressure (for each 5 mm Hg increase 0.92, 0.91 to 0.94), and mean systolic blood pressure (for each 5 mm Hg increase 0.95, 0.94 to 0.96). Beneficial factors were prepregnancy fruit intake at least three times daily (1.09, 1.01 to 1.18) and being in paid employment (per eight hours' increase 1.02, 1.01 to 1.04). Detrimental factors not amenable to alteration were a history of hypertension while using oral contraception, socioeconomic index, family history of any hypertensive complications in pregnancy, vaginal bleeding during pregnancy, and increasing uterine artery resistance index. Smoking in pregnancy was noted to be a detrimental factor in the initial two datasets but did not remain in the final model., Conclusions: This study identified factors associated with normal pregnancy through adoption of a novel hypothesis generating approach, which has shifted the emphasis away from adverse outcomes towards uncomplicated pregnancies. Although confirmation in other cohorts is necessary, this study implies that individually targeted lifestyle interventions (normalising maternal weight, increasing prepregnancy fruit intake, reducing blood pressure, stopping misuse of drugs) may increase the likelihood of normal pregnancy outcomes., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12607000551493.

Objective: Excessive gestational weight gain (GWG) is an important contributing factor to the obesity epidemic in women and is associated with pregnancy complications. We investigated the relationship between GWG and caesarean delivery in labour, large for gestational age (LGA), small for gestational age (SGA) infants and pregnancy-induced hypertension by maternal pre-pregnancy body mass index (BMI) in a contemporary nulliparous cohort., Study Design: Using 2009 Institute of Medicine guidelines, participants in the SCOPE study (from Cork, Ireland, Auckland, New Zealand and Adelaide, Australia) were classified into GWG categories (low, normal and high) according to pre-pregnancy BMI. Maternal characteristics and pregnancy outcomes were compared between weight gain categories. SGA and LGA were defined as <10th and >90th customised birthweight centile. Multivariable analysis adjusted for confounding factors that impact on GWG including BMI., Results: Of 1950 participants, 17.2% (n=335) achieved the recommended GWG, 8.6% (n=167) had low and 74.3% (n=1448) had high GWG. Women with high GWG had increased rates of LGA infants [adjusted OR 4.45 (95% CI 2.49-7.99)] and caesarean delivery in labour [aOR 1.46 (1.03-2.07)]. SGA was increased in women with low GWG [aOR 1.79 (1.06-3.00)]., Conclusion: Three quarters of participants had high GWG, which was associated with an independent risk of LGA infants and caesarean in labour. Low GWG was associated with SGA infants. These adverse outcomes are potentially modifiable by achievement of normal GWG, which should be an important focus of antenatal care., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs.

Aim: Previous studies have proposed a link between the presence of specific single nucleotide polymorphisms (SNPs) and cerebral palsy and the majority of these associations remain to be confirmed or rejected by prospective studies with sufficient statistical power. Prior studies have also given little attention to the interaction of genomic characteristics and clinical risk factors., Methods: This paper describes the design of a prospective case-control study to test these genetic associations in conjunction with more stringent data collection in respect to clinical features associated with pregnancy, particularly maternal infection. Here we consider the ethical requirements, our hypothesis that genetic susceptibility modifies the risk of cerebral palsy in the presence of perinatal environmental triggers, a priori primary and secondary aims, power calculations, participant recruitment strategies, data linkage, sampling methods of genetic material and subsequent SNP analysis, collection of clinical data and the proposed final statistical analysis., (© 2010 The Authors. Journal of Paediatrics and Child Health © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Objective: The purpose of this study was to investigate associations between fetal inherited thrombophilia and adverse pregnancy outcomes, including pregnancy-induced hypertensive disorders (PIHD), antepartum hemorrhage (APH), small-for-gestational age <10th percentile (SGA), and preterm birth (PTB)., Study Design: Seven hundred and seventeen cases and 609 controls were genotyped for Factor V Leiden (FVL, G1691A), Prothrombin gene mutation (PGM, G20210A), and Methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C using DNA from newborn screening cards., Results: For babies born <28 weeks' gestation, PGM was associated with an increased risk of SGA (OR 6.40, 95%CI 1.66-24.71) and APH with SGA (OR 6.35, 95%CI 1.63-24.75). Homozygous MTHFR A1298C was associated with an increased risk of SGA for babies born 28-31 weeks gestation (OR 4.00, 95%CI 1.04-15.37), and with APH and SGA for babies born <32 weeks' gestation (OR 3.57, 95%CI 1.09-11.66). Homozygous MTHFR C677T was associated with a reduced risk of PTB and SGA (OR 0.52, 95%CI 0.28-0.96) for babies born 32 to 36 weeks' gestation. Homozygous FVL decreased the risk of PTB <32 weeks' gestation (OR 0.55, 95%CI 0.31-0.98)., Conclusion: Fetal thrombophilic polymorphisms may be related to adverse pregnancy outcomes, in particular SGA.

Background: Pregnant women with chronic hypertension and thrombophilia have an increased risk for preeclampsia and/or intrauterine growth restriction (IUGR). Ketanserin lowers blood pressure and inhibits serotonin-induced platelet aggregation., Cases: A 38-year-old woman with chronic hypertension had a first pregnancy with severe hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. A second pregnancy with prophylactic oral ketanserin and low-dose aspirin was uneventful. The third pregnancy without oral ketanserin was again complicated by severe superimposed preeclampsia and IUGR. During this pregnancy a prothrombin mutation was found. A 37-year-old woman with chronic hypertension developed severe early-onset superimposed preeclampsia in her first pregnancy. In the 3 consecutive pregnancies, she was treated with low-molecular-weight heparin because of a factor XII deficiency. Only the pregnancy with the use of prophylactic oral ketanserin was uncomplicated., Conclusion: Clinical trials are warranted to analyze the role of oral ketanserin in preventing preeclampsia and IUGR.

Preeclampsia (PE) and gestational hypertension (GH) are pregnancy-specific diseases that occur in around 10% of pregnancies worldwide. Increasing evidence suggests that women whose pregnancies were complicated by PE or GH, and their offspring, are at increased risk of cardiovascular disease (CVD) later in life. We hypothesised that PE and GH would associate with CVD risk factors 8–10 years after the first pregnancy in the mother and child and that differences in cardiovascular risk profile would be seen between 8- and 10-year-old male and female children. This is a follow-up study of the Adelaide SCOPE pregnancy cohort where 1164 nulliparous women and their babies were recruited between 2005 and 2008. Haemodynamic function was assessed using non-invasive USCOMBP+ and USCOM1A devices. Microvascular function was assessed by post-occlusive reactive hyperaemia. Of the 273 mother–child pairs followed up, 38 women had PE and 20 had GH during pregnancy. Augmentation index (Aix) and suprasystolic pulse pressure (ssPP) were increased, whereas measures of microvascular function were decreased in children who were born to PE compared to uncomplicated pregnancies. Female children had decreased Aix and ssPP compared to male children after in utero exposure to PE. Women who developed GH during their first pregnancy had increased systolic, diastolic and mean arterial pressures compared to women who had uncomplicated pregnancy. Our data suggest that GH is associated with increased cardiovascular risk in women 8–10 years after first pregnancy and PE is associated with increased offspring risk at 8–10 years of age, highlighting differences between these two hypertensive disorders of pregnancy. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms and pre‐ and peri‐conception folic acid (FA) supplementation and dietary data were used to identify one‐carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 μg daily FA at 15‐week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 μg (5.4%) (P <.0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L−1 vs. 31.9 ± 11.2, P =.007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre‐ and early‐pregnancy dietary factors, are independent risk factors for pregnancy complications. [ABSTRACT FROM AUTHOR]

Background: For pregnant women with a known cardiac condition or those who develop cardiac disease during pregnancy, there is an increased risk of complications during pregnancy, to both mother and foetus. To reduce this risk, best practice guidelines have been developed and available in South Australia for several years. Measuring clinical practice against the guideline recommendations verifies real-life practice and an essential part of any clinical practice quality improvement project by identifying gaps. This study is the first report on adherence to statewide perinatal guidelines for these women in South Australia. Objectives: To evaluate adherence to evidence-based clinical practice perinatal guidelines To identify predictors of adherence. Make comparisons across three practice settings examined. Design: A retrospective cross-sectional observational design that analysed data from medical records. Setting: Three SA Health public metropolitan, university-affiliated teaching hospitals with an obstetric service within a ten-year timeframe (2003–2013). Participants: 271 admissions of women who were categorised as 'pre-existent' or 'newly acquired' cardiac condition during their pregnancy. Outcome measures: Adherence to guidelines was measured using a purposefully designed scoring system across the three sites. The researcher chose a minimum acceptable score of 17 applicable to the 'newly acquired' group and 35 for the 'pre-existent' group. Results: Overall adherence to the perinatal guidelines for the combined groups (n = 271) reported a mean score of 16.3, SD ± 6.7, with a median score of 17. Women in the 'newly acquired' group scored less compared to women in the 'pre-existent' group (Estimate -2.3, CI -3.9,-0.7). Variance in adherence was observed across the three hospitals (P value <0.0001). The most significant predictor of adherence to guidelines was pre-pregnancy cardiac consultation which increased the likelihood of preconception care by Odds ratio 18.5 (95%, CI 2, 168). Similarly, compliance with mental health screening was associated with improved adherence to antenatal assessments (OR: 11.3(95% CI 4.7, 27.3). Conclusion: There was overall suboptimal adherence to the statewide guidelines for women with cardiac conditions in pregnancy. The variance in the level of adherence across the three hospitals correlated with the exposure to higher acuity cases, and that appropriate up- referral to a higher acuity hospital was intrinsically linked to better adherence. Recommendations include preconception counselling, and to ensure that all health practitioners have the skills, sufficient training and time to complete a comprehensive initial antenatal assessment Trial registration: ACTRN12617000417381 [ABSTRACT FROM AUTHOR]

Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide, affecting 2–8% of all pregnancies. Studies suggest a link between complement activation and preeclampsia. The complement system plays an essential role in the innate immunity, leading to opsonization, inflammation, and elimination of potential pathogens. The complement system also provides a link between innate and adaptive immunity and clearance of immune complexes and apoptotic cells. During pregnancy there is increased activity of the complement system systemically. However, locally at the placenta, complement inhibition is crucial for the maintenance of a normal pregnancy. Inappropriate or excessive activation of the complement system at the placenta is likely involved in placental dysfunction, and is in turn associated with pregnancy complications like preeclampsia. Therefore, modulation of the complement system could be a potential therapeutic target to prevent pregnancy complications such as preeclampsia. This review, based on a systematic literature search, gives an overview of the complement system and its activation locally in the placenta and systemically during healthy pregnancies and during complicated pregnancies, with a focus on preeclampsia. Furthermore, this review describes results of animal and human studies with a focus on the complement system in pregnancy, and the role of the complement system in placental dysfunction. Various clinical and animal studies provide evidence that dysregulation of the complement system is associated with placental dysfunction and therefore with preeclampsia. Several drugs are used for prevention and treatment of preeclampsia in humans and animal models, and some of these drugs work through complement modulation. Therefore, this review further discusses these studies examining pharmaceutical interventions as treatment for preeclampsia. These observations will help direct research to generate new target options for prevention and treatment of preeclampsia, which include direct and indirect modulation of the complement system. [ABSTRACT FROM AUTHOR]

Background: The long‐acting oxytocic agent; carbetocin, has been consistently shown to reduce the need for additional uterotonics at caesarean section, but not postpartum haemorrhage (PPH). While promising, current evidence is limited by heterogenicity in study design and findings. Aims: To examine whether carbetocin confers clinical or economic benefit compared to oxytocin at caesarean section in an all‐risk Australian population. Materials and Methods: A retrospective cohort study was undertaken of all singleton caesarean sections at a public tertiary hospital from 2008 to 2010 (n = 2499). From 1 January 2008 to 24 March 2009 all women received prophylactic oxytocin 5–10 units slow push intravenously at delivery, after which all patients received 100 μg intravenous carbetocin. Outcomes were PPH (≥1000 mL) and the requirement of secondary uterotonics. A post hoc cost analysis was also performed. Results: A total of 1467 and 1024 patients received carbetocin and oxytocin, respectively. Incidence of PPH ≥1000 mL was 7.8% for carbetocin compared to and 9.7% for oxytocin (odds ratio (OR) 0.79, 95% CI 0.59–1.05). Moderate blood loss >500 mL was significantly reduced with carbetocin; occurring in 27.3% versus 39.4% (OR 0.57, 95% CI 0.49–0.68). There was a 20.0% reduction in secondary uterotonic treatment with carbetocin (OR 0.42, 95% CI 0.35–0.49). Average drug costs were lower with oxytocin at $4.74 versus $36.42/patient. However, the 1.9% reduction in PPH with carbetocin resulted in a $63.46 reduction in cost per patient, with a cost‐effectiveness ratio of $1667 to prevent one case of PPH ≥1000 mL. Conclusions: Carbetocin reduced moderate blood loss >500 mL, but not PPH ≥1000 mL. Carbetocin conferred a 20% reduction in secondary uterotonic treatment, as well as lowering direct medical costs. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To investigate the risk of pregnancy complications in women with and without polycystic ovary syndrome after consideration of lifestyle factors. Design: Prospective cohort. Patients and measurements: Participants (n = 5628) were apparently healthy nulliparous women with singleton pregnancies from the Screening for Pregnancy Endpoints study in New Zealand, Australia, United Kingdom and Ireland. Multivariable regression models were performed assessing the association of self‐reported polycystic ovary syndrome status with pregnancy complications with consideration of lifestyle factors at the 15th week of gestation. Results: Women with polycystic ovary syndrome (n = 354) were older, had a higher socio‐economic index and body mass index and were less likely to consume alcohol and smoke but more likely to do vigorous exercise and take multivitamins. In univariable analysis, polycystic ovary syndrome was associated with increased risk of gestational diabetes (OR: 2.2, 95% CI: 1.2, 4.0). In multivariable models, polycystic ovary syndrome was only significantly associated with decreased risk of large for gestational age (OR: 0.62, 95% CI: 0.40, 0.98) with a population attributable risk of 0.22%. None of the other outcomes were attributable to polycystic ovary syndrome status. Conclusions: Polycystic ovary syndrome is associated with a lower risk of large for gestational age infants. In this low‐risk population, the risk of pregnancy complications was not increased in women with polycystic ovary syndrome who were following a healthy lifestyle. Further studies are warranted assessing the contribution of lifestyle factors to the risk of pregnancy complications in higher risk groups of women with and without polycystic ovary syndrome. [ABSTRACT FROM AUTHOR]

Acute fatty liver of pregnancy (AFLP) is a rare, often autosomal recessive disorder with a major risk for maternal and perinatal mortality and morbidity. In order to achieve a more favorable outcome, awareness of its clinical signs and symptoms and early recognition are of pivotal importance. Over a 5-year period, 18 patients were diagnosed with AFLP (one twin, 19 babies). The most common sign and symptoms were jaundice, hypoglycemia, nausea and vomiting, encephalopathy, and hypertension. Abnormal laboratory test results included elevated total/conjugated (direct) bilirubin, AST, ALT, PT, APTT, creatinine, leukocyte count, and hypoalbuminemia. Maternal and fetal mortality rate was high: 66.7% resulted in a maternal death and 57.9% in an intrauterine fetal demise (IUFD). The number of complications was found to correlate with maternal death (p = .042). Surviving AFLP patients had ≤3 complications, while patients with >3 complications on presentation had a high risk of maternal death (OR = 5.0; 95% CI: 0.55-45.4). The presence of hypertension significantly increased the risk of maternal death (OR: 24.5; 95% CI: 1.1-542.8; p = .01). The risk of IUFD was primarily related to gestational age at delivery and birth weight. The high rate of jaundice as presenting symptom of AFLP suggests that Indonesian primary maternity care providers may often miss its important earlier signs and symptoms, in particular de novo onset of nausea and vomiting in late pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To compare the level of serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1), and neonatal outcome in early onset preeclampsia (EO-PE), late onset preeclampsia (LO-PE), and normal pregnancy (NP).Methods: In this prospective observational case control study, HO-1 and sFlt-1 levels were measured in blood samples within 24 h of hospital admission. Preeclampsia cases were divided into two groups based on gestational age at delivery: EO-PE (<34 weeks) and LO-PE (≥34 weeks). A total of 45 patients were involved in this study.Result: Maternal serum level of sFlt-1 was higher in EO-PE than LO-PE and NP groups (mean ± SD; 14.50 ± 17.12 ng/ml vs 5.20 ± 6.69 ng/ml vs 2.72 ± 1.2 ng/ml [p = 0.020]. Maternal serum level of HO-1 was not different between EO-PE, LO-PE, and NP groups (p = 0.681). Birthweights were significantly lower in the EO-PE group compared with the LO-PE and NP groups (1580 ± 536 g vs 2635 ± 578 g vs 3010 ± 371 g [p = 0.000]). The rate of small for gestational age infant (26.7% vs 6.7% vs 0%; p = 0.046) and perinatal death (20% vs 0 vs 0; p = 0.037) was also significantly higher in EO-PE compared to LO-PE and NP. The maternal sFlt-1 level was negatively correlated with birthweight (p = 0.006; CC = -0.445).Conclusion: This study did not find a correlation between maternal HO-1 levels and sFlt-1 levels. Maternal serum sFLt-1 levels in preeclampsia were higher in EO-PE and were associated with a worse perinatal outcome. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between maternal age and spontaneous breech presentation.Material and Methods: Fifteen-year observational study over (2001-2015). All consecutive singleton births delivered at the Centre Hospitalier Universitaire Sud Reunion's maternity. The only single exclusion criterion was uterine malformations (N = 123) women.Results: Of the 60,963 singleton births, there was a linear association (χ2 for linear trend, p< 0.0001) between maternal age and spontaneous breech presentation. Overall rate of breech presentation was 2.7% in deliveries over 32 weeks gestation, while it was 1.9% in women aged 15 to 19 years and 4.0% in women aged 45+, with a linear progression for each 5-year age category. This linearity remained significant controlling for early prematurity (<33 weeks) and severe fetal malformations (χ2 for linear trend = 64, p < 0.0001). Controlling in a multiple logistic regression model for other major risk factors gestational age, female sex, primiparity, maternal age remained significantly an independent risk factor, p < 0.0001.Conclusion: Maternal age (x) is an independent factor for breech presentation in singleton pregnancies after 32 weeks gestation with a linear association that may be approximated at y = 0.1x. (y: incidence, percent). [ABSTRACT FROM AUTHOR]

Introduction: The aim of this paper was to provide an in-depth analysis of all stillbirth causation over a period of 10 years in a busy maternity unit located in a socioeconomically disadvantaged urban area, with an emphasis on overlapping pathology.Materials and Methods: A retrospective analysis of all structurally normal stillbirths in singleton pregnancies born during 2002-2012. The PSANZ stillbirth classification was used; per stillbirth subgroup main risk factors were evaluated.Results: Out of 130 cases, 43% showed overlapping pathologies. In the remaining 74 (56%) cases, the following single pathologies were found: IUGR 20 (15%), infection 12 (9%), abruption 8 (6%), placental thrombotic pathology 8 (6%), miscellaneous 6 stillbirths (5%), and 20 cases (15%) unexplained. Smoking was a risk factor for stillbirth associated with abruption (OR 3.639), infection (OR 2.271), and thrombotic pathology (OR 2.168). Drug use had an association with (placental) infection (OR 3.598). Obesity showed a significant association with IUGR (OR 3.782) and abruption (OR 9.040). Thrombophilia risk analysis for the overall group of stillbirths showed significant results for Protein S (OR 8.889) and homocysteine >90th centile (OR 2.087).Conclusions: Overlapping pathology was identified in 43% of stillbirths. Infection, IUGR, and abruption were the most important single cause of stillbirth. [ABSTRACT FROM AUTHOR]

Eclampsia (together with epilepsy) being the first disease ever written down since the beginning of writings in mankind 5000 years ago, we will make a brief presentation of the different major steps in comprehension of Pre -eclampsia. 1) 1840. Rayer, description of proteinuria in eclampsia, 2) 1897 Vaquez, discovery of gestational hypertension in eclamptic women, 3) In the 1970′s, description of the “double” trophoblastic invasion existing only in humans (Brosens & Pijnenborg,), 4) between the 1970′s and the 1990′s, description of preeclampsia being a couple disease. The “paternity problem” (and therefore irruption of immunology), 5) at the end of the 1980′s, a major step forward: Preeclampsia being a global endothelial cell disease (glomeruloendotheliosis, hepatic or cerebral endotheliosis, HELLP, eclampsia), inflammation (J.Roberts. C Redman, R Taylor), 6) End of the 1990′s: Consensus for a distinction between early onset preeclampsia EOP and late onset LOP (34 weeks gestation), EOP being rather a problem of implantation of the trophoblast (and the placenta), LOP being rather a pre-existing maternal problem (obesity, diabetes, coagulopathies etc…). LOP is predominant everywhere on this planet, but enormously predominant in developed countries: 90% of cases. This feature is very different in countries where women have their first child very young (88% of world births), where the fatal EOP (early onset) occurs in more than 30% of cases. 7) What could be the common factor which could explain the maternal global endotheliosis in EOP and LOP? Discussion about the inositol phospho glycans P type. [ABSTRACT FROM AUTHOR]

Anxiety and health related Quality of Life (HRQoL) have emerged as important mental health measures in obstetric care. Few studies have systematically examined the longitudinal trajectories of anxiety and HRQoL in pregnancy. Using a linear growth modeling strategy, we analyzed the course of State-Trait Anxiety Inventory (STAI)- and Short Form (36) Health Survey (SF-36) scores between the 12th and the 36th week of gestation, in a sample of 355 women. We additionally analyzed the impact of depressive symptoms and a chronic medical condition (asthma), on STAI and SF-36 trajectory curves. STAI scores remained stable throughout pregnancy. A previous history of anxiety increased the overall STAI scores. Asthma and depressive symptoms scores had no impact on the STAI trajectory. Physical SF-36 scores decreased over the course of pregnancy, whereas mental SF-36 trended towards improvement. Asthma reduced physical SF-36 overall. While high depressive symptoms decreased the overall mental SF-36, they were also significantly associated with mental SF-36 improvements over time. Anxiety symptoms are stable during pregnancy and are not modulated by depressive symptoms or asthma. Physical HRQoL declines in pregnancy. In contrast, mental HRQoL appears to improve, particularly in women with high initial levels of depressive symptoms. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the FTO rs9939609 single nucleotide polymorphism (SNP), which is a risk factor for obesity and vascular diseases, is also associated with pregnancy complications including pre-eclampsia, gestational hypertension, small for gestational age pregnancy (SGA), and spontaneous preterm birth (sPTB).Methods: A case-control study of 1,741 nulliparous Caucasian women, their partners, and infants was conducted. DNA was extracted from peripheral blood or saliva from parents and cord blood from infants and genotyped using the Sequenom MassARRAY system.Results: The prevalence of maternal and infant AA genotype of FTO rs9939609 was increased in the SGA group compared with the uncomplicated pregnancy group (19.2% vs. 13.4%, OR = 1.7, 95% CI = 1.1-2.6, P = 0.02 and 24.6% vs. 12.5%, OR = 2.7, 95% CI = 1.6-4.6, P = 0.0002). The prevalence of maternal and infant AA genotype of FTO rs9939609 was also increased in the sPTB group compared with the uncomplicated pregnancy group (20.8% vs. 13.4%, OR = 2.1, 95% CI = 1.2-3.8, P = 0.009 and 20.0% vs. 12.5%, OR = 2.4, 95% CI = 1.0-5.3, P = 0.03).Conclusions: The maternal and infant AA genotype of the obesity associated FTO rs9939609 SNP associates with increased risk for SGA and sPTB. This SNP may be important in predicting the risk of these pregnancy complications and subsequent vascular diseases. [ABSTRACT FROM AUTHOR]

Objective: Small for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants. Methods: 5628 participants from SCOPE, a prospective study of nulliparous pregnant women, were interviewed at 15±1 weeks’ gestation. Fetal anthropometry, uterine and umbilical Doppler studies were performed at 20±1 weeks’. The cohort was divided into training (n = 3735) and validation datasets (n = 1871). All-SGA (birthweight <10th customised centile), Normotensive-SGA (SGA with normotensive mother) and Hypertensive-SGA (SGA with mother who developed hypertension) were the primary outcomes. Multivariable analysis was performed using stepwise logistic regression firstly using clinical variables and then with clinical and ultrasound variables. Receiver operator curves were constructed and areas under the curve (AUC) calculated. Results: 633 infants (11.3%) in the whole cohort were SGA; 465 (8.3%) Normotensive-SGA and 165 (3.0%) Hypertensive-SGA. In the training dataset risk factors for All-SGA at 15±1 weeks’ included: family history of coronary heart disease, maternal birthweight <3000 g and 3000 g to 3499 g compared with ≥3500 g, >12 months to conceive, university student, cigarette smoking, proteinuria, daily vigorous exercise and diastolic blood pressure ≥80. Recreational walking ≥4 times weekly, rhesus negative blood group and increasing random glucose were protective. AUC for clinical risk factors was 0.63. Fetal abdominal or head circumference z scores <10th centile and increasing uterine artery Doppler resistance at 20±1 weeks’ were associated with increased risk. Addition of these parameters increased the AUC to 0.69. Clinical predictors of Normotensive and Hypertensive-SGA were sub-groups of All-SGA predictors and were quite different. The combined clinical and ultrasound AUC for Normotensive and Hypertensive-SGA were 0.69 and 0.82 respectively. Conclusion: Predictors for SGA of relevance to clinical practice were identified. The identity and predictive potential differed in normotensive women and those who developed hypertension. [ABSTRACT FROM AUTHOR]

Good clinical practice recommends folic acid supplementation 1 month prior to pregnancy and during the first trimester to prevent congenital malformations. However, high rates of fetal growth and development in later pregnancy may increase the demand for folate. Folate and vitamins B12 and B6 are required for DNA synthesis and cell growth, and are involved in homocysteine metabolism. The primary aim of this study was to determine if maternal folate, vitamin B12, vitamin B6 and homocysteine concentrations at 18-20 weeks gestation are associated with subsequent adverse pregnancy outcomes, including pre-eclampsia and intrauterine growth restriction (IUGR). The secondary aim was to investigate maternal B vitamin concentrations with DNA damage markers in maternal lymphocytes. A prospective observational study was conducted at the Women's and Children's Hospital, Adelaide, South Australia. One hundred and thirty-seven subjects were identified prior to 20 weeks gestation as at high or low risk for subsequent adverse pregnancy outcome by senior obstetricians. Clinical status, dietary information, circulating micronutrients and genome damage biomarkers were assessed at 18-20 weeks gestation. Women who developed IUGR had reduced red blood cell (RBC) folate ( P < 0.001) and increased plasma homocysteine concentrations ( P < 0.001) compared with controls. Maternal DNA damage, represented by micronucleus frequency and nucleoplasmic bridges in lymphocytes, was positively correlated with homocysteine (r = 0.179, P = 0.038 and r = 0.171, P = 0.047, respectively). Multivariate regression analysis revealed RBC folate was a strong predictor of IUGR ( P = 0.006). This study suggests that low maternal RBC folate and high homocysteine values in mid pregnancy are associated with subsequent reduced fetal growth. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of polymorphisms in the vascular endothelial growth factor (VEGF) family genes ( VEGFA rs699947, VEGFA rs3025039, PGF rs1042886, KDR rs2071559 and KDR rs2305948) with preeclampsia in Sinhalese women in Sri-Lanka. Methods: We conducted a case-control study where 175 nulliparous Sinhalese women with preeclampsia and 171 normotensive women matched for age, ethnicity, parity and BMI were recruited in tertiary care maternity hospitals in Sri-Lanka. Preeclampsia was diagnosed using international guidelines. DNA extracted from peripheral venous blood and was genotyped using the Sequenom MassARRAY system. χ2-test was used to compare the distribution of allele and genotype frequencies between the cases and the control subjects. Results: The frequency of PGF rs1042886 variant allele (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-2.1) and dominant genotype model (aOR 1.6, 95% CI 1.0-2.4) were increased in preeclamptic women compared to controls. VEGFA rs699947, VEGFA rs3025039, KDR rs2071559, and KDR rs2305948 polymorphisms were not associated with preeclampsia. Conclusion: Maternal PGF rs1042886 polymorphism is associated with preeclampsia in Sinhalese women in Sri-Lanka. [ABSTRACT FROM AUTHOR]

Objective. To describe patterns of vaginal bleeding in the first 20 weeks of pregnancy and evaluate the association between patterns of bleeding and risk of subsequent pre-eclampsia in nulliparous women. Design. Cohort study. Setting. Participating centres of the Screening for Pregnancy Endpoints (SCOPE) study in Auckland (New Zealand), Adelaide (Australia), Manchester and London (UK) and Cork (Ireland). Population. Healthy nulliparous women ( n= 3431). Methods. Logistic regression was used to assess the association between bleeding characteristics and pre-eclampsia while controlling for known determinants of pre-eclampsia. Main outcome measures. Preeclampsia, defined as gestational hypertension with proteinuria or any multi-system complication of preeclampsia. Four bleeding variables were evaluated: any bleeding during the first 20 weeks; maximal bleeding intensity; duration of bleeding; and number of bleeding episodes. Results. Of the 3431 women enrolled, 780 (23%) experienced vaginal bleeding during the first 20 weeks of pregnancy. Risk of pre-eclampsia was not associated with the presence or absence of bleeding (adjusted odds ratio (ORa) 0.96, 95% confidence interval (95% CI) 0.67-1.38). Analyses confined to women with vaginal bleeding showed that any bleeding episode of five or more consecutive days, compared with shorter episodes, increased risk of pre-eclampsia approximately twofold (ORa 2.15, 95% CI 1.01-4.57), as did multiple compared with single episodes of bleeding (ORa 2.33, 95% CI 1.16-4.67). Conclusions. Bleeding is a common complication during the first 20 weeks of nulliparous pregnancy, and the presence or absence of vaginal bleeding is not a determinant of subsequent pre-eclampsia. Among women with vaginal bleeding, consideration of the bleeding pattern, in terms of intensity, duration and frequency, appears to be informative with respect to pre-eclampsia risk. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancies complicated by preeclampsia and small-for-gestational-age (SGA) infants share placental vascular abnormalities and both disorders confer increased risk of later life coronary artery disease. Kinase insert domain receptor (KDR) is the main receptor for vascular endothelial growth factor A, a potent angiogenic factor which regulates the development of the placental vasculature. Two polymorphisms in KDR (-604T/C and Val297Ile) are known to be associated with coronary artery disease. We investigated the association of these polymorphisms with preeclampsia, gestational hypertension, and SGA infants. Method: Nulliparous pregnant women, their partners, and infants were recruited to a prospective cohort study (n = 1169). Doppler ultrasound of the uterine and umbilical arteries was performed at 20 weeks of gestation. Preeclampsia, gestational hypertension, and SGA were defined according to international guidelines. DNA extracted from peripheral venous or cord blood was genotyped using the Sequenom MassARRAY system. Multivariable logistic regression was used to compare the odds for the pregnancy complications between the genotype groups adjusting for potential confounders. Results: Among 937 Caucasian pregnancies, 427 (45.6%) were uncomplicated, 75 (8.0%) developed preeclampsia, 102 (10.9%) developed gestational hypertension, and 72 (7.7%) had SGA infants in the absence of maternal hypertensive disease. Paternal and neonatal KDR-604T/C was associated with preeclampsia (adjusted odds ratio [aOR] 1.6, 95% confidence interval [CI] 1.0-3.0 and aOR 2.2, 95% CI 1.0-4.4), SGA (aOR 1.9, 95% CI 1.1-3.3 and aOR 2.2, 95% CI 1.2-3.9), and SGA with abnormal Doppler (aOR 2.7, 95% CI 1.2-5.9 and aOR 3.2, 95% CI 1.2-5.9). Conclusion: Paternal and neonatal carriage of the KDR-604T/C polymorphism is associated with the risk of preeclampsia and SGA infants. [ABSTRACT FROM PUBLISHER]

Objective. To investigate the roles of inherited polymorphisms in the MBL2 gene and exposure to viral infection in the development of a range of adverse pregnancy outcomes, including birthweight <10th percentile (small-for-gestational age, SGA), antepartum hemorrhage (APH), pregnancy-induced hypertensive disorders (PIHD), and preterm birth (PTB). Methods. This was a case--control study using DNA from newborn screening cards of 717 cases (babies with at least one of the adverse pregnancy outcomes listed above) and 609 controls, to screen for six polymorphisms within the MBL2 gene. These combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL2 levels. Results. Significant associations were found between variant MBL2 haplotypes and SGA (LYPA <32 weeks OR 5.37, 95%% CI 1.50--17.27), antepartum hemorrhage (LYPA <37 weeks OR 2.29, 95%% CI 1.25--4.18), and PIHD (LYQC <32 weeks (OR 17.89, 95%% CI 2.20--139.57). Evidence of exposure to infection increased the effect of these associations, (SGA OR 17.00, 95%% CI 1.03--252.48; APH OR 5.67, 95%% CI 1.73--18.84; PIHD OR 23.80, 95%% CI 1.08--1414.76), while no evidence of exposure to infection demonstrated no associations. PTB was significantly associated with the defective HYPD haplotype with evidence of exposure to infection (OR 6.14, 95%% CI 1.21--29.89). Conclusions. This research suggests that the combination of fetal MBL2 haplotypes and exposure to in utero viral infection increases the risk of adverse pregnancy outcomes, including PTB, antepartum hemorrhage, small-for-gestational age and PIHD. [ABSTRACT FROM AUTHOR]

Abstract: Developed countries represent 20% of the population in the world, but only 12% of human births annually, while 98% of medical publications are issued from these areas. What we can read on preeclampsia is correct, but only for 12% of human pregnancies! In addition, reproductive patterns in the developed world, but only for the last three decades, are different from elsewhere and during the first 70 years of the 20th century. A major difference is in the number of children in families but also, and mainly, in the ages at first pregnancies in primiparae (approaching now 30 years in many developed countries). This is probably why current epidemiological data seem different than that of the 20th century. The purpose of this article is to analyse to what extent the ‘primipaternity model’ may give clues for the comprehension of epidemiological descriptions past and present—and, indeed, it works in many respects. However, it is evident also that a proportion of preeclampsia cases cannot be explained by paternity patterns, and vascular disease predisposition in women (diabetes, obesity, thrombophilias, etc.) evidently comes into play. For these latter, maternal age is also strongly associated with these complications. Here, we reflect on what can be respective parts of the disease in preeclamptic couples, and on preeclampsia as a marker of subjects susceptible to vascular disease. [Copyright &y& Elsevier]

Objective . Tumor necrosis factor-alpha (TNF-α) is thought to play a role in immune activation in preeclampsia. The objective of this study was to establish if soluble TNF-receptor I (sTNF-rI) levels relate to the onset and severity of preeclampsia. Methods . Maternal plasma sTNF-rI levels were studied throughout pregnancy in 68 women with a history of severe preeclampsia or intra-uterine growth restriction (IUGR), and primigravidas with chronic hypertension. Data are presented as mean (SD) in ng/ml. Results . In the second trimester there was a significant difference in sTNF-rI levels between preeclamptic pregnancies with and without IUGR (means 1.33 (0.20) and 1.11 (0.15) respectively, p < 0.005). In severe preeclampsia with delivery before 34 weeks of gestation, sTNF-rI levels were higher than in mild preeclampsia in the second and third trimesters (means 1.40 (0.16) vs. 1.16 (0.19), p < 0.02 and 1.82 (0.47) vs. 1.42 (0.22), p < 0.05, respectively). Conclusion . sTNF-rI levels were higher in preeclampsia with fetal involvement, suggesting that increased TNF-α production in preeclampsia is related to impaired placentation rather than to the maternal syndrome. [ABSTRACT FROM AUTHOR]

The etiology of preeclampsia is unknown. At present, 4 hypotheses are the subject of extensive investigation, as follows: (1) Placental ischemia-Increased trophoblast deportation, as a consequence of ischemia, may inflict endothelial cell dysfunction. (2) Very low-density lipoprotein versus toxicity-preventing activity-In compensation for increased energy demand during pregnancy, nonesterified fatty acids are mobilized. In women with low albumin concentrations, transporting extra nonesterified fatty acids from adipose tissues to the liver is likely to reduce albumin's antitoxic activity to a point at which very-low density lipoprotein toxicity is expressed. (3) Immune maladaptation-Interaction between decidual leukocytes and invading cytotrophoblast cells is essential for normal trophoblast invasion and development. Immune maladaptation may cause shallow invasion of spiral arteries by endovascular cytotrophoblast cells and endothelial cell dysfunction mediated by an increased decidual release of cytokines, proteolytic enzymes, and free radical species. (4) Genetic imprinting-Development of preeclampsia-eclampsia may be based on a single recessive gene or a dominant gene with incomplete penetrance. Penetrance may be dependent on fetal genotype. The possibility of genetic imprinting should be considered in future genetic investigations of preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to assess the incidence of hyperhomocysteinemia in patients with a history of preeclampsia or fetal growth restriction, to evaluate the effects of vitamin supplementation on the methionine loading test, and to study the course of subsequent pregnancies in women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction.Study Design: A total of 207 consecutive patients with a history of preeclampsia or fetal growth restriction was tested for hyperhomocysteinemia. Thirty-seven were found to be positive and were treated with folic acid and vitamin B6, and 27 had a second methionine loading test after vitamin supplementation. Fourteen patients became pregnant again while receiving vitamins and aspirin.Results: All patients who underwent a methionine loading test after vitamin supplementation had a completely normalized methionine loading test. Of the 14 pregnancies in women receiving vitamins and aspirin, 7 were complicated by preeclampsia. Birth weights were 2867 +/- 648 g compared with 1088 +/- 570 g in the previous pregnancies.Conclusions: Vitamin B6 and folic acid correct the methionine loading test in patients with hyperhomocysteinemia. Perinatal outcome in patients with a history of preeclampsia or fetal growth restriction and hyperhomocysteinemia appears to be favorable. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are at increased susceptibility to vitamin D deficiency. Hence, there is continuing interest in determining how vitamin D influences pregnancy health. We aimed to compare vitamin D status in two distinct populations of pregnant women in Australia and New Zealand and to investigate the relationship between vitamin D status and pregnancy outcome. This included evaluating possible effect measure modifications according to fetal sex.Methods: Serum 25-hydroxy vitamin D (25(OH)D) was measured at 15 ± 1 weeks' gestation in 2800 women from Adelaide and Auckland who participated in the multi-centre, prospective cohort SCreening fOr Pregnancy Endpoints (SCOPE) study.Results: Mean serum 25(OH)D in all women was 68.1 ± 27.1 nmol/L and 28% (n = 772) were considered vitamin D deficient (< 50 nmol/L). Serum 25(OH)D was lower in the women recruited in Adelaide when compared to the women recruited in Auckland and remained lower after adjusting for covariates including maternal body mass index and socioeconomic index (Adelaide: 58.4 ± 50.3 vs. Auckland: 70.2 ± 54.5 nmol/L, P < 0.001). A 53% decreased risk for gestational diabetes mellitus (GDM) was observed with high (> 81 nmol/L) "standardised" vitamin D status when compared to moderate-high (63-81 nmol/L, aRR, 0.47; 95% CI: 0.23, 0.96). Marginal sex-specific differences occurred between vitamin D status and GDM: women carrying a female fetus had a 56% decreased risk for GDM in those with low-moderate levels of standardised vitamin D (44-63 nmol/L) compared to moderate-high levels (aRR: 0.44; 95% CI: 0.20, 0.97), whilst in women carrying a male fetus, a 55% decreased risk of GDM was found with high standardised vitamin D when compared to moderately-high vitamin D, but this was not statistically significant (aRR: 0.45; 95% CI: 0.15, 1.38).Conclusions: High serum 25(OH)D at 15 ± 1 weeks' gestation was shown to be protective against the development of GDM. A possible association between fetal sex, vitamin D status and GDM provides further questions and encourages continual research and discussion into the role of vitamin D in pregnancy, particularly in vitamin D replete populations. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study on the risks of spontaneous preterm birth and of having a small for gestational age infant in pregnant women who stopped smoking by 15 weeks of gestation. The study recruited healthy nulliparous women to the Screening for Pregnancy Endpoints (SCOPE) study in Auckland, New Zealand and Adelaide, South Australia between November 2004 and July 2007. It showed no significant differences in adverse pregnancy outcomes between women in their 15 weeks of gestation who stopped smoking and those who do not smoke. However, women who smoked during pregnancy had higher rates of preterm birth and small for gestational age infants.

Objectives: This study was undertaken to test novel genetic polymorphisms involved in 1-carbon metabolism for a potential association with increased risk of developing pregnancy complications associated with uteroplacental insufficiency. Study Design: This was a prospective cohort study consisting of 50 women at low risk and 93 women at high risk for having a pregnancy complication develop. Maternal and fetal DNA samples were genotyped for methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A. A chi squared or χ2 analysis was used to compare genotypes and pregnancy outcome, 1-way analysis of variance and linear regression were used to compare genotype with continuous variables. Results: The fetal MTR 2756 G allele was associated with uteroplacental insufficiency (P = .022, likelihood ratio = 10.4) and maternal homocysteine (P = .017). The maternal MTR A2756G polymorphism was associated with uteroplacental insufficiency (P = .049, likelihood ratio = 6.0), but only in mothers not supplementing with high-dose B-vitamins. The maternal MTHFD1 AA genotype was associated with intrauterine growth restriction (P = .047, likelihood ratio = 5.8). Conclusion: This study suggests the maternal and fetal MTR 2756 G allele is an important risk factor in the development of uteroplacental insufficiency. In addition, the maternal MTHFD1 1958 AA genotype may be associated with intrauterine growth restriction. [Copyright &y& Elsevier]

Hypertensive disorders of pregnancy (HDP: pregnancy-induced hypertension, preeclampsia, eclampsia) affect approximately 10% of human births. Women are at increased risk for HDP during their first conception; and/or when the conception is with a new partner (new paternity); when conception occurs very shortly after the beginning of their sexual relationship. A primary cause of preeclampsia is the defect of the normal human-specific deep endovascular invasion of trophoblast, which is a consequence of the nutritional demands of growth of the human fetal brain. The occurrence of preeclampsia represents a reproductive disadvantage unique to humans compared with other mammals. As such, it may have played a significant role in shaping human reproduction and, therefore, human sexuality. This deep implantation/preeclampsia phenomenon may explain many anthropological mysteries of human sexuality that do not exist in other mammalian species (and primates). These include: very low fertility rate, concealed ovulation, all year long ‘apparent-waste-of-efficiency’ sexuality, absence of sperm competition in human females at the time of conception, and the unexplained testicle size in human males compared with relevant primates. Further, this deep trophoblastic implantation (and its failure in preeclampsia) in humans might be a decisive condition of hominization between great apes and all the other Homo genuses. This frontier might even have occurred inside these Homo lineages: because of their relatively small brains, the first species of Homo might not have presented the deep trophoblastic invasion described in Homo sapiens. [Copyright &y& Elsevier]