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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.)

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.)

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).)

Objectives: We aimed to assess women's perceptions on the long-term risks for cardiovascular disease (CVD) after major pregnancy complications., Methods: Women who experienced major pregnancy complications and those who experienced uncomplicated pregnancies were invited to participate in a qualitative study. Focus group discussions (FGDs) and self-administered questionnaires were used to explore: The knowledge of long-term sequelae after experiencing a major pregnancy complication; Importance of education on heart health; The practicality of referral to a clinic after pregnancy complications; Willingness for regular postpartum clinic visits after pregnancy complications. A thematic qualitative analysis was undertaken., Results: 26 women participated in four FGDs. The majority of women did not know of the association between major pregnancy complications and CVD. The main views expressed were: Women who experience pregnancy complications should receive education on improving heart health; An appointment for the first CVD risk screening visit needs to be made prior to discharge from the delivery suite; Women will benefit by having the option to select between a hospital and a general-practitioner based model of follow up., Conclusions: These views are important in developing postpartum strategies to reduce CVD risk among women who experience pregnancy complications., Competing Interests: No authors have competing interests.

Aims/hypothesis: The aim of this study was to determine whether presence of the metabolic syndrome in pregnancy associates with child telomere length or child anthropometry (weight, BMI) and BP, measured at 10 years of age., Methods: The Screening for Pregnancy Endpoints study (SCOPE) was a multicentre, international prospective cohort of nulliparous pregnant women recruited from Australia, New Zealand, Ireland and the UK (N = 5628). The current analysis is a 10 year follow-up of SCOPE pregnant women and their children, from the Australian cohort. Clinical data collected at 14-16 weeks' gestation during the SCOPE study were used to diagnose the metabolic syndrome using IDF criteria. Telomere length, a biomarker of ageing, was assessed by quantitative PCR from children's saliva collected at 10 years of age., Results: In women who completed follow-up (n = 255), 20% had the metabolic syndrome in pregnancy. After adjusting for a range of confounders, children of mothers who had the metabolic syndrome in pregnancy had 14% shorter telomeres than children of mothers without the metabolic syndrome in pregnancy (mean difference -0.36 [95% CI -0.74, 0.01]). Height- and weight-for-age, and BMI z scores were similar in children of mothers who did and did not have the metabolic syndrome during pregnancy., Conclusions/interpretation: Children of mothers who had the metabolic syndrome in pregnancy have shorter telomeres, a biomarker of accelerated ageing. These findings warrant further studies in larger cohorts of children, as well as investigations into whether telomere length measured in cord blood associates with telomere length in childhood.

Background: Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated., Methods and Findings: Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks' gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ≥80 cm, along with any 2 of the following: raised trigycerides (≥1.70 mmol/l [≥150 mg/dl]), reduced high-density lipoprotein cholesterol (<1.29 mmol/l [<50 mg/dl]), raised blood pressure (BP) (i.e., systolic BP ≥130 mm Hg or diastolic BP ≥85 mm Hg), or raised plasma glucose (≥5.6 mmol/l). Log-binomial regression analyses were used to examine the risk for each pregnancy outcome (GDM, PE, large for gestational age [LGA], small for gestational age [SGA], and spontaneous preterm birth [sPTB]) with each of the 5 individual components for MetS and as a composite measure (i.e., MetS, as defined by the IDF). The relative risks, adjusted for maternal BMI, age, study centre, ethnicity, socioeconomic index, physical activity, smoking status, depression status, and fetal sex, are reported. A total of 5,530 women were included, and 12.3% (n = 684) had MetS. Women with MetS were at an increased risk for PE by a factor of 1.63 (95% CI 1.23 to 2.15) and for GDM by 3.71 (95% CI 2.42 to 5.67). In absolute terms, for PE, women with MetS had an adjusted excess risk of 2.52% (95% CI 1.51% to 4.11%) and, for GDM, had an adjusted excess risk of 8.66% (95% CI 5.38% to 13.94%). Diagnosis of MetS was not associated with increased risk for LGA, SGA, or sPTB. Increasing BMI in combination with MetS increased the estimated probability for GDM and decreased the probability of an uncomplicated pregnancy. Limitations of this study are that there are several different definitions for MetS in the adult population, and as there are none for pregnancy, we cannot be sure that the IDF criteria are the most appropriate definition for pregnancy. Furthermore, MetS was assessed in the first trimester and may not reflect pre-pregnancy metabolic health status., Conclusions: We did not compare the impact of individual metabolic components with that of MetS as a composite, and therefore cannot conclude that MetS is better at identifying women at risk. However, more than half of the women who had MetS in early pregnancy developed a pregnancy complication compared with just over a third of women who did not have MetS. Furthermore, while increasing BMI increases the probability of GDM, the addition of MetS exacerbates this probability. Further studies are required to determine if individual MetS components act synergistically or independently., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: LCK is a minority shareholder in Metabolomic Diagnostics, an SME which has licensed IP pertaining to biomarkers predictive of pre-eclampsia which LCK invented. JEM receives a stipend as a specialty consulting editor for PLOS Medicine and serves on the journal's editorial board.

The intrarenal renin-angiotensin system (iRAS) is implicated in the pathogenesis of hypertension, chronic kidney disease and diabetic nephropathy. Urinary angiotensinogen (uAGT) levels reflect the activity of the iRAS and are altered in women with preeclampsia. Since Indigenous Australians suffer high rates and early onset of renal disease, we hypothesised that Indigenous Australian pregnant women, like non-Indigenous women with pregnancy complications, would have altered uAGT levels. The excretion of RAS proteins was measured in non-Indigenous and Indigenous Australian women with uncomplicated or complicated pregnancies (preeclampsia, diabetes/gestational diabetes, proteinuria/albuminuria, hypertension, small/large for gestational age, preterm birth), and in non-pregnant non-Indigenous women. Non-Indigenous pregnant women with uncomplicated pregnancies, had higher uAGT/creatinine levels than non-Indigenous non-pregnant women (P < 0.01), and levels increased as pregnancy progressed (P < 0.001). In non-Indigenous pregnant women with pregnancy complications, uAGT/creatinine was suppressed in the third trimester (P < 0.01). In Indigenous pregnant women with uncomplicated pregnancies, there was no change in uAGT/creatinine with gestational age and uAGT/creatinine was lower in the 2nd and 3rd trimesters than in non-Indigenous pregnant women with uncomplicated pregnancies (P < 0.03, P < 0.007, respectively). The uAGT/creatinine ratios of Indigenous women with uncomplicated or complicated pregnancies were the same. A decrease in uAGT/creatinine with advancing gestational age was associated with increased urinary albumin/creatinine, as is seen in preeclampsia, but it was not specific for this disorder. The reduced uAGT/creatinine in Indigenous pregnant women may reflect subclinical renal dysfunction which limits the ability of the kidney to maintain sodium balance and could indicate an increased risk of pregnancy complications and/or future renal disease., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

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 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., (© 2015 Royal College of Obstetricians and Gynaecologists.)

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.)

Background: Obesity has been associated with increased risk of antenatal depression, but little is known about this relationship. This study tested whether socio-economic status (SES) influences the relationship between obesity and antenatal depression., Methods: Data were taken from the Screening for Pregnancy Endpoints (SCOPE) cohort. BMI was calculated from measured height and weight at 15±1 weeks' gestation. Underweight women were excluded. SES was indicated by self-reported household income (dichotomised around the median: low SES ≤£45,000; high SES >£45,000). Antenatal depression was defined as scoring ≥13 on the Edinburgh Postnatal Depression Scale at both 15±1 and 20±1 weeks' gestation, to identify persistently elevated symptoms of depression., Results: Five thousand five hundred and twenty two women were included in these analyses and 5.5% had persistently elevated antenatal depression symptoms. There was a significant interaction between SES and BMI on the risk of antenatal depression (p=0.042). Among high SES women, obese women had approximately double the odds of antenatal depression than normal weight controls (AOR 2.11, 95%CI 1.16-3.83, p=0.014, adjusted for confounders). Among low SES women there was no association between obesity and antenatal depression. The interaction effect was robust to alternative indicators of SES in sensitivity analyses., Limitations: 1) Antenatal depression was assessed with a self-reported screening measure; and 2) potential mediators such as stigma and poor body-image could not be examined., Conclusions: Obesity was only associated with increased risk of antenatal depression among high SES women in this sample. Healthcare professionals should be aware that antenatal depression is more common among low SES women, regardless of BMI category., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: We sought to investigate the impact of introducing an antenatal asthma management service (AMS) on asthma control during pregnancy and subsequent perinatal outcomes., Study Design: Prospective, observational cohort study of pregnant asthmatic women attending a tertiary hospital antenatal clinic. Asthmatic women were recruited from the antenatal clinic and were followed prospectively with visits at 12, 20, 28 and 36 weeks gestation. A new nurse-led AMS was introduced offering asthma self-management education and support. Outcomes were compared between women recruited before and after the AMS was introduced (n=89 and 80, respectively) and included; prevalence of exacerbations during pregnancy, asthma control throughout pregnancy and perinatal outcomes, including preterm birth and small-for-gestational-age (SGA)., Results: The relative risk for exacerbations (0.69; CI: 0.33-1.42), loss of control (0.67; CI 0.46-0.99) and persistent uncontrolled asthma (0.48; CI 0.26-0.9) were all reduced with attendance to AMS during pregnancy. AMS was associated with non-statistically significant reductions in asthma exacerbations (19.1-15.0%; p=0.480) and uncontrolled asthma at ≥ 2 study visits (21.3-11.3%; p=0.078)., Conclusions: These findings demonstrate the potential impact of an AMS in improving asthma control during pregnancy, supporting the need for an adequately powered RCT to determine its clinical- and cost-effectiveness., (Copyright © 2015 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.)

Objectives: To compare the prevalence and predictors of alcohol use in multiple cohorts., Design: Cross-cohort comparison of retrospective and prospective studies., Setting: Population-based studies in Ireland, the UK, Australia and New Zealand., Participants: 17,244 women of predominantly Caucasian origin from two Irish retrospective studies (Growing up in Ireland (GUI) and Pregnancy Risk Assessment Monitoring System Ireland (PRAMS Ireland)), and one multicentre prospective international cohort, Screening for Pregnancy Endpoints (SCOPE) study., Primary and Secondary Outcome Measures: Prevalence of alcohol use pre-pregnancy and during pregnancy across cohorts. Sociodemographic factors associated with alcohol consumption in each cohort., Results: Alcohol consumption during pregnancy in Ireland ranged from 20% in GUI to 80% in SCOPE, and from 40% to 80% in Australia, New Zealand and the UK. Levels of exposure also varied substantially among drinkers in each cohort ranging from 70% consuming more than 1-2 units/week in the first trimester in SCOPE Ireland, to 46% and 15% in the retrospective studies. Smoking during pregnancy was the most consistent predictor of gestational alcohol use in all three cohorts, and smokers were 17% more likely to drink during pregnancy in SCOPE, relative risk (RR)=1.17 (95% CI 1.12 to 1.22), 50% more likely to drink during pregnancy in GUI, RR=1.50 (95% CI 1.36 to 1.65), and 42% more likely to drink in PRAMS, RR=1.42 (95% CI 1.18 to 1.70)., Conclusions: Our data suggest that alcohol use during pregnancy is prevalent and socially pervasive in the UK, Ireland, New Zealand and Australia. New policy and interventions are required to reduce alcohol prevalence both prior to and during pregnancy. Further research on biological markers and conventions for measuring alcohol use in pregnancy is required to improve the validity and reliability of prevalence estimates., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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.

Background: Pre-eclampsia, small-for-gestational-age infants, preterm birth and recurrent miscarriage complicate a significant number of pregnancies. The vascular endothelial growth factor (VEGF) family of angiogenic growth factors is implicated in the pathophysiology of these complications. We aimed to elucidate the role of these angiogenic factors in placentation and to evaluate the predictive value of their protein concentrations and genetic variations in pregnancy complications., Methods: We performed a systematic search of PubMed, and retrieved original articles. The search included a combination of terms such as VEGF-A, placental growth factor (PlGF), kinase insert domain receptor, fms-like-tyrosine-kinase receptor 1, soluble fms-like-tyrosine-kinase receptor 1, pre-eclampsia, small-for-gestational-age infants, preterm birth, recurrent miscarriage, placenta, prediction and polymorphisms., Results: This review summarizes the current knowledge of the roles of the VEGF family in early placentation and of the abnormalities in maternal plasma and placental expression of angiogenic proteins in adverse pregnancy outcomes compared with normal pregnancy. PlGF and sFLT-1 in combination with other clinical and biochemical markers in late first or second trimester appear to predict early-onset pre-eclampsia with a high sensitivity and specificity. However, VEGF family proteins do not have sufficient power to accurately predict late-onset pre-eclampsia, small-for-gestational age pregnancies or preterm birth. Functional polymorphisms in these angiogenic genes are implicated in pregnancy complications, but their contribution appears to be minor., Conclusions: Although the VEGF family has important roles in normal and complicated pregnancy, the current predictive value of the VEGF family as biomarkers appears to be limited to early-onset pre-eclampsia.

In healthy pregnancy reactive oxygen species and antioxidants remain in balance and DNA damage is repaired effectively. However, pregnancy is an inflammatory state exhibiting increased susceptibility to oxidative stress such that this balance can be easily disrupted. Increased DNA damage has been shown to be involved in many pathological states including pregnancy complications. Modern lifestyles including exposure to pollutants, poor diet, and lack of exercise cause excess inflammation, oxidative stress, and ultimately DNA damage. There is a growing body of literature providing evidence that these lifestyle changes are increasing our risk of infertility, miscarriage, and late-gestation pregnancy complications. Moreover, baseline DNA damage rises with age and couples in developed societies are delaying childbirth, placing them at further risk. In order to understand the effect of lifestyle and DNA damage on pregnancy health we require large prospective studies, with the collection of samples prior to conception and endpoints of time-to-pregnancy, early pregnancy loss, and late-gestation maternal and fetal health., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)

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.

Objective: To study plasma concentrations of endothelin (ET), lipidhydroperoxides (LOOH), glutathione peroxidase (GSHpx) and fibronectin in relation to abnormal umbilical artery velocimetry., Study Design: Plasma concentrations of ET, LOOH, GSHpx and fibronectin were measured in fetal and maternal venous blood in: (i) a control group (n=10); (ii) in pregnancies complicated by intrauterine growth retardation (IUGR) (n=6) or preeclampsia (n=5) with positive end diastolic flow; and in (iii) pregnancies complicated by absent or reversed end diastolic (ARED) flow in the umbilical artery (n=18). All children were delivered by primary caesarean section., Results: The significantly highest maternal and fetal ET concentrations were found in plasma collected in pregnancies complicated by ARED flow in the umbilical artery. Maternal fibronectin levels were significantly raised in the ARED flow group. Maternal plasma ET levels were lowest in pregnancies complicated by IUGR. The maternal and fetal plasma concentrations of LOOH and GSHpx did not differ significantly between the groups., Conclusion: Abnormal Doppler velocimetry, especially ARED flow is associated with elevated maternal and fetal plasma levels of ET. The exact mechanism causing the placental vasoconstriction is unknown yet, but oxidative stress seems not to be involved.

Objective: To assess the prevalence of haemostatic abnormalities in patients with an obstetric history of preeclampsia and/or fetal growth restriction and documented thrombophilia, and to evaluate the effects of low-molecular-weight heparin (LMWH) and aspirin on pregnancy outcome., Method: A total of 276 patients with a history of preeclampsia and/or fetal growth restriction were tested for the presence of coagulation abnormalities and anticardiolipin antibodies (ACA). Ninety patients with preeclampsia and 15 patients with isolated fetal growth restriction had haemostatic abnormalities. Twenty-six patients with coagulation abnormalities: protein S-deficiency, activated protein C (APC) resistance and/or > or =15 ACA GPL and/or MPL had a subsequent pregnancy and were treated with aspirin in combination with LMWH. Their pregnancy outcome was compared with all patients having a subsequent pregnancy from the same cohort without abnormalities, or <15 ACA GPL and/or MPL who received aspirin (n=19)., Results: In subsequent pregnancies birth weight of babies born to patients with an unequivocal coagulation abnormality (i.e., protein S-deficiency, APC resistance, or ACA titres > or =15 GPL and/or MPL), were higher than in the group with no disorders or <15 ACA GPL and/or MPL (P=0.019)., Conclusions: In this preliminary study, LMWH appears to have a favourable effect on the pregnancy outcome of women with a history of preeclampsia and/or fetal growth restriction and documented thrombophilia. Randomised trials are required.

The aim of the current study was to investigate the effects of psychosocial variables on well-being and on pregnancy-related complaints throughout pregnancy. Three hundred and ninety-six nulliparous women completed questionnaires on number of daily stressors, social support, gestational factors and mental and physical work load in each trimester of pregnancy. In addition, the following dependent measures were assessed: depression, anxiety, somatic complaints, and the pregnancy-related complaints fatigue, nausea and back pain. The independent variables predicted depression best (r2 = 42-44%), followed by anxiety (R2 = 13-20) and somatic complaints (R2 = 16-21%). Number of daily stressors explained most of the variance. Satisfaction with social support and maternal age were negatively correlated with depression. In contrast, pregnancy-related complaints could be less accurately predicted by psychosocial factors. The amount of explained variance for fatigue ranged between 6 and 10%, for nausea between 2 and 6%, and for back pain between 5 and 7% for the three trimesters. It is concluded that depressive symptoms during pregnancy are associated with negative psychosocial factors, particularly the number of daily stressors and low satisfaction with received social support. To a lesser degree, this is also the case with anxiety and somatic complaints. Pregnancy-related complaints, on the other hand, appear to be relatively independent of psychosocial conditions.

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]