Connecting the Dots: Exploring the Interplay Between Preeclampsia and Peripartum Cardiomyopathy.

Preeclampsia and peripartum cardiomyopathy (PPCM) are significant obstetric problems that can arise during or after pregnancy. Both are known to be causes of maternal mortality and morbidity. Several recent studies have suggested a link between preeclampsia and the pathophysiology of PPCM. However, the common thread that connects the two has yet to be thoroughly and fully articulated. Here, we investigate the complex dynamics of preeclampsia and PPCM in this review. Our analysis focuses mainly on inflammatory and immunological responses, endothelial dysfunction as a shared pathway, and potential genetic predisposition to both diseases. To begin, we will look at how excessive inflammatory and immunological responses can lead to clinical symptoms of both illnesses, emphasizing the role of proinflammatory cytokines and immune cells in modifying vascular and tissue responses. Second, we consider endothelial dysfunction to be a crucial point at which endothelial damage and activation contribute to pathogenesis through increased vascular permeability, vascular dysfunction, and thrombus formation. Finally, we examine recent information suggesting genetic predispositions to preeclampsia and PPCM, such as genetic variants in genes involved in the management of blood pressure, the inflammatory response, and heart structural integrity. With this synergistic study, we seek to encourage more research and creative therapy solutions by emphasizing the need for an interdisciplinary approach to understanding and managing the connection between preeclampsia and PPCM.

Randomised controlled trials of behavioural nudges delivered through text messages to increase influenza and COVID-19 vaccines among pregnant women (the EPIC study): study protocol.

BACKGROUND: Influenza and COVID-19 infections during pregnancy may have serious adverse consequences for women as well as their infants. However, uptake of influenza and COVID-19 vaccines during pregnancy remains suboptimal. This study aims to assess the effectiveness of a multi-component nudge intervention to improve influenza and COVID-19 vaccine uptake among pregnant women. METHODS: Pregnant women who receive antenatal care at five tertiary hospitals in South Australia, Western Australia and Victoria will be recruited to two separate randomised controlled trials (RCTs). Women will be eligible for the COVID-19 RCT is they have received two or less doses of a COVID-19 vaccine. Women will be eligible for the influenza RCT if they have not received the 2023 seasonal influenza vaccine. Vaccination status at all stages of the trial will be confirmed by the Australian Immunisation Register (AIR). Participants will be randomised (1:1) to standard care or intervention group (n = 1038 for each RCT). The nudge intervention in each RCT will comprise three SMS text message reminders with links to short educational videos from obstetricians, pregnant women and midwives and vaccine safety information. The primary outcome is at least one dose of a COVID-19 or influenza vaccine during pregnancy, as applicable. Logistic regression will compare the proportion vaccinated between groups. The effect of treatment will be described using odds ratio with a 95% CI. DISCUSSION: Behavioural nudges that facilitate individual choices within a complex context have been successfully used in other disciplines to stir preferred behaviour towards better health choices. If our text-based nudges prove to be successful in improving influenza and COVID-19 vaccine uptake among pregnant women, they can easily be implemented at a national level. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05613751. Registered on November 14, 2022.

Early pregnancy cardio metabolic risk factors and the prevalence of metabolic syndrome 10 years after the first pregnancy.

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.

Testing equivalence of two doses of intravenous iron to treat iron deficiency in pregnancy: A randomised controlled trial.

OBJECTIVE: To test the equivalence of two doses of intravenous iron (ferric carboxymaltose) in pregnancy. DESIGN: Parallel, two-arm equivalence randomised controlled trial with an equivalence margin of 5%. SETTING: Single centre in Australia. POPULATION: 278 pregnant women with iron deficiency. METHODS: Participants received either 500 mg (n = 152) or 1000 mg (n = 126) of intravenous ferric carboxymaltose in the second or third trimester. MAIN OUTCOME MEASURES: The proportion of participants requiring additional intravenous iron (500 mg) to achieve and maintain ferritin >30 microg/L (diagnostic threshold for iron deficiency) at 4 weeks post-infusion, and at 6 weeks, and 3-, 6- and 12-months postpartum. Secondary endpoints included repeat infusion rate, iron status, birth and safety outcomes. RESULTS: The two doses were not equivalent within a 5% margin at any time point. At 4 weeks post infusion, 26/73 (36%) participants required a repeat infusion in the 500-mg group compared with 5/67 (8%) in the 1000-mg group: difference in proportions, 0.283 (95% confidence interval [CI] 0.177-0.389). Overall, participants in the 500-mg arm received twice the repeat infusion rate (0.81 [SD = 0.824] versus 0.40 [SD = 0.69], rate ratio 2.05, 95% CI 1.45-2.91). CONCLUSIONS: Administration of 1000 mg ferric carboxymaltose in pregnancy maintains iron stores and reduces the need for repeat infusions. A 500- mg dose requires ongoing monitoring to ensure adequate iron stores are reached and sustained.

Pregnancy complications and cardiovascular disease risk perception: A qualitative study.

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.

INOVASIA Study: A Multicenter Randomized Clinical Trial of Pravastatin to Prevent Preeclampsia in High-Risk Patients.

OBJECTIVE: Our objective was to determine if treatment with pravastatin prevents preeclampsia in pregnant patients at risk of preeclampsia. MATERIAL AND METHODS: The study was performed in four major tertiary hospitals in Surabaya, Bandung, and Makassar between 2017 and 2021. Pregnant women at high risk of developing preeclampsia were recruited and randomized into an intervention group and control group. The control group received low-dose aspirin (80 mg) and calcium (1 g) daily, while the intervention group received additional pravastatin (20 mg twice daily) starting from 14 to 20 weeks' gestation until delivery. The pregnancy was followed until delivery, and the clinical data were collected. The primary outcome was the occurrence of preeclampsia. RESULT: A total of 173 people participated in this study, including 86 in the control group and 87 in the pravastatin group. The pravastatin group had a significantly lower rate of preterm preeclampsia (13.8 vs. 26.7%; p = 0.034; odds ratio [OR] = 0.034, 95% confidence interval [CI] = 0.202-0.905) and preterm birth (16.1 vs. 36%; p = 0.003; OR = 0.340, 95% CI = 0.165-0.7), mostly indicated preterm birth. Preeclampsia occurred later in the pravastatin group than in the control group (36.39 + 2.32 vs. 34.89 + 3.38 weeks, p = 0.048). Overall, the pravastatin group showed better perinatal outcomes. Neonates with low Apgar scores (<7) at 1 minute (5.7 vs. 25.6%, p = 0.000) and 5 minutes (2.3 vs. 25.6%, p = 0.028) were significantly less common in the pravastatin group. Additionally, the rate of low birthweight babies (<2,500 g) was lower in the pravastatin group (27.6 vs. 40.7%; p = 0.069). CONCLUSION: Pravastatin (20 mg bid) significantly reduces the risk of preterm preeclampsia and preterm birth in women at a high risk of developing preeclampsia. KEY POINTS: · This is an open-label multicenter RCT to evaluate pravastatin effect to prevent preeclampsia.. · Pravastatin significantly reduces the risk of preterm preeclampsia (PE) and preterm birth in high risk PE women.. · Pravastatin had a beneficial effect on perinatal outcomes, including Apgar scores and birth weight..

INOVASIA Study: A Randomized Open Controlled Trial to Evaluate Pravastatin to Prevent Preeclampsia and Its Effects on sFlt1/PlGF Levels.

OBJECTIVES: This study aimed to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing PE and the maternal and perinatal outcomes and the soluble fms-like tyrosine kinase 1/placental growth factor (sFlt1/PlGF) ratio. STUDY DESIGN: This is an open-labeled randomized controlled trial (RCT), a part of INOVASIA (Indonesia Pravastatin to Prevent Preeclampsia study) trial. Pregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery Doppler examination at 10 to 20 weeks' gestational age. The control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20-mg twice daily) starting from 14 to 20 weeks' gestation until delivery. Research blood samples were collected before the first dose of pravastatin and before delivery. The main outcome was the rate of maternal PE, maternal-perinatal outcomes, and sFlt-1, PlGF, sFlt-1/PlGF ratio, and soluble endoglin (sEng) levels. RESULTS: The rate of PE was (nonsignificantly) lower in the pravastatin group compared with the control group (17.5 vs. 35%). The pravastatin group also had a (nonsignificant) lower rate of severe PE, HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, acute kidney injury, and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly (p = 0.048) lower in the pravastatin group (n = 4) compared with the controls (n = 12). Neonates in the pravastatin group had significantly higher birth weights (2,931 ± 537 vs. 2,625 ± 872 g; p = 0.006), lower Apgar's scores < 7 (2.5 vs. 27.5%, p = 0.002), composite neonatal morbidity (0 vs. 20%, p = 0.005), and NICU admission rates (0 vs. 15%, p = 0.026). All biomarkers show a significant deterioration in the control group compared with nonsignificant changes in the pravastatin group. CONCLUSION: Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes by improving the angiogenic imbalance. KEY POINTS: · Prophylactic pravastatin was associated with a significantly lower rate of adverse perinatal outcome.. · The sFlt1/PlGF ratio stabilized in the pravastatin group compared with a deterioration in the control group.. · Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes..

The interaction between metabolic syndrome and physical activity, and risk for gestational diabetes mellitus.

AIMS: Metabolic syndrome (MetS) is a cluster of risk factors which increases risk of cardiometabolic diseases in the adult population and increases risk for pregnancy complications such as gestational diabetes mellitus (GDM). Epidemiological data indicate that moderate-to-high levels of physical activity reduces the risk for GDM. The study aims to determine whether the association between MetS and GDM is affected by physical activity. METHODS: We performed a prospective cohort study among 1373 pregnant nulliparous women in Adelaide, South Australia. At 9-16 weeks' gestation, demographic, lifestyle and self-reported frequencies of physical activity were obtained, and a non-fasting blood sample was taken for assessment of MetS, defined using the International Diabetes Federation criteria. GDM was diagnosed at 24-28 weeks' gestation using the World Health Organization classification. RESULTS: 1158 pregnant women were included: 107 (9%) women had MetS in early pregnancy, and 184 (16%) developed GDM. Having MetS increased the risk of developing GDM (37.4% vs. 13.7%, adjusted RR 2.5; 95% CI 1.7, 3.6). The interaction effect (RR; (95% CI) between MetS and physical activity was not significant (vigorous physical activity: 2.60; 0.46, 14.71) for ≥ 4 times per week; less vigorous activity; 0.77; 0.15, 4.02 for ≥ 4 times per week; stair climbing ≥ once day (1.16; 0.54, 2.51), all compared to no physical activity). CONCLUSIONS: Physical activity was not an effect modifier in the association between GDM and MetS. Information collected about the nature and extent of physical activity needs to be more detailed and granular to determine whether physical activity really has an effect.

The metabolic syndrome in pregnancy and its association with child telomere length.

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.

Mechanisms linking exposure to preeclampsia in utero and the risk for cardiovascular disease.

Preeclampsia (PE) is now recognised as a cardiovascular risk factor for women. Emerging evidence suggests that children exposed to PE in utero may also be at increased risk of cardiovascular disease (CVD) in later life. Individuals exposed to PE in utero have higher systolic and diastolic blood pressure and higher body mass index (BMI) compared to those not exposed to PE in utero. The aim of this review is to discuss the potential mechanisms driving the relationship between PE and offspring CVD. Exposure to an adverse intrauterine environment as a consequence of the pathophysiological changes that occur during a pregnancy complicated by PE is proposed as one mechanism that programs the fetus for future CVD risk. Consistent with this hypothesis, animal models of PE where progeny have been studied demonstrate causality for programming of offspring cardiovascular health by the preeclamptic environment. Shared alleles between mother and offspring, and shared lifestyle factors between mother and offspring provide alternate pathways explaining associations between PE and offspring CVD risk. In addition, adverse lifestyle habits can also act as second hits for those programmed for increased CVD risk. PE and CVD are both multifactorial diseases and, hence, identifying the relative contribution of PE to offspring risk for CVD is a very complex task. However, considering the emerging strong association between PE and CVD, those exposed to PE in utero may benefit from targeted primary CVD preventive strategies.

Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility.

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks' gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99-1.44)) or who had lower selenium concentrations (1.19 (1.01-1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06-2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.

Peripheral maternal haemodynamics across pregnancy in hypertensive disorders of pregnancy.

OBJECTIVES: Evaluating maternal haemodynamics across pregnancy in uncomplicated pregnancies and those complicated by hypertensive disorders of pregnancy (HDP). STUDY DESIGN: Prospective cohort study from 2015 to 2018 of healthy, nulliparous, singleton-bearing women. Maternal haemodynamics assessed by Uscom BP+ at 9-16 and 32-36 weeks' gestation in pregnancies complicated by HDP [preeclampsia with severe (sPE n = 12) and without severe clinical features (nsPE n = 49), gestational hypertension (GH n = 25), transient gestational hypertension (TGH n = 33)] were compared to uncomplicated pregnancies (n = 286) using mixed-effects linear modelling. MAIN OUTCOME MEASURES: Maternal haemodynamic adaptation in uncomplicated pregnancies and those complicated by HDP. RESULTS: Between the two measurements, haemodynamic adaptation in women with sPE and nsPE was significantly different compared to those with uncomplicated pregnancies. An additional increase was observed for peripheral systolic blood pressure [SBP; 14.3 mmHg, 8.6-20.1 (sPE)], peripheral diastolic blood pressure [DBP; 7.7 mmHg, 3.3-12.1 (sPE); 2.6 mmHg, 3.3-12.1 (nsPE)] peripheral mean arterial pressure [MAP; 10.6 mmHg, 5.8-15.5 (sPE); 3.4 mmHg, 0.8-6.0 (nsPE)], peripheral pulse pressure [PP; 6.6 mmHg, 2.1-11.1 (sPE)], central SBP [15.8 mmHg, 10.4-21.2 (sPE); 2.9 mmHg, 0.1-5.8 (nsPE)], central DBP [8.3 mmHg, 3.9-12.6 (sPE); 2.5 mmHg, 0.2-4.8 (nsPE), central MAP [10.8 mmHg, 6.4-15.2 (sPE); 2.6 mmHg, 0.3-5.0 (nsPE)] and central PP [7.6 mmHg, 3.9-11.3 (sPE)]. Augmentation index (AIx) decreased less (15.5%, 6.3-24.6 (sPE); 9.0%, 4.2-13.6 (nsPE)] compared to uncomplicated pregnancies. Haemodynamic adaptation across pregnancy in women with GH and TGH was not different from those with uncomplicated pregnancies. CONCLUSION: Women who develop preeclampsia show an altered, while those who develop GH or TGH demonstrate a comparable haemodynamic adaptation compared to uncomplicated pregnancies. TGH is not a benign condition.

Low Serum Levels of HtrA3 at 15 Weeks of Gestation Are Associated with Late-Onset Preeclampsia Development and Small for Gestational Age Birth.

OBJECTIVE: The aim of this study was to investigate the potential utility of serum HtrA1 and HtrA3, serine proteases that are highly expressed in the developing placenta, at 15 and 20 weeks of gestation for predicting later development of adverse pregnancy outcomes of preeclampsia (PE), gestational hypertension (GHT), preterm birth (PTB), and small for gestational age (SGA) birth. METHODS: This is a nested case control study of 665 samples (330 controls, 335 cases) from the Adelaide SCOPE cohort. The cases included were 92 PE, 71 GHT, 56 PTB, and 116 SGA. Samples were assessed by ELISA and data adjusted for maternal age, BMI, socioeconomic index, hCG, and smoking status. Multivariate logistic regression was performed with other biochemical and biophysical parameters available for these samples. RESULTS: HtrA1 did not differ between the controls and cases. In contrast, HtrA3 was significantly lower at 15 weeks in pregnancies that later developed late-onset PE (LPE) or resulted in SGA birth, with an area under the ROC curve (AUC) of 0.716 and 0.790, respectively. The combination of HtrA3 with PAPP-A, uterine, and umbilical Doppler improved the AUC to 0.755 for LPE and 0.844 for SGA. CONCLUSION: HtrA3 at 15 weeks is associated with, and may be useful for, the early detection of LPE development and SGA birth.

Effect of Birth Weight and Early Pregnancy BMI on Risk for Pregnancy Complications.

OBJECTIVE: This study investigated the influence of birth weight on the risk of pregnancy complications, including preeclampsia (PE), gestational hypertension (GH), small for gestational age (SGA) pregnancy, spontaneous preterm birth, and gestational diabetes mellitus (GDM), and assessed the effect of early pregnancy BMI on this relationship. METHODS: A total of 5,336 nulliparous women from the SCreening fOr Pregnancy Endpoints (SCOPE) study were included. Women's birth weights were self-reported and confirmed via medical records when possible. A birth weight of 3,000 to 3,499 g was considered the reference. RESULTS: After adjusting for confounders, birth weight < 2,500 g was associated with increased risk of GH (adjusted odds ratio [aOR] = 2.2, 95% CI = 1.3-3.7), PE (aOR = 1.7, 95% CI = 1.0-2.9), small for gestational age (aOR = 1.9, 95% CI = 1.1-3.2), and GDM (aOR = 2.4, 95% CI = 1.0-5.8) compared with the referent. Women born with birth weight < 2,500 g and who subsequently developed overweight or were diagnosed with obesity were at increased risk of GH (aOR = 2.2, 95% CI = 1.1-4.5), PE (aOR = 2.3, 95% CI = 1.2-4.5), and GDM (aOR = 3.2, 95% CI = 1.1-9.5) compared with women with birth weight ≥ 2,500 g and remained lean. CONCLUSIONS: Women who were born with a low birth weight are at increased risk of pregnancy complications. Those born small may have undergone "programming" in response to unfavorable intrauterine conditions. In such women, the physiological demands of pregnancy may act as a "second hit," leading to pregnancy complications.

Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes: A prospective cohort of nulliparous women.

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.

Pre-pregnancy fast food and fruit intake is associated with time to pregnancy.

STUDY QUESTION: Is preconception dietary intake associated with reduced fecundity as measured by a longer time to pregnancy (TTP)? SUMMARY ANSWER: Lower intake of fruit and higher intake of fast food in the preconception period were both associated with a longer TTP. WHAT IS KNOWN ALREADY: Several lifestyle factors, such as smoking and obesity, have consistently been associated with a longer TTP or infertility, but the role of preconception diet in women remains poorly studied. Healthier foods or dietary patterns have been associated with improved fertility, however, these studies focused on women already diagnosed with or receiving treatments for infertility, rather than in the general population. STUDY DESIGN, SIZE, DURATION: This was a multi-center pregnancy-based cohort study of 5628 nulliparous women with low-risk singleton pregnancies who participated in the Screening for Pregnancy Endpoints (SCOPE) study. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 5598 women were included. Data on retrospectively reported TTP and preconception dietary intake were collected during the first antenatal study visit (14-16 weeks' gestation). Dietary information for the 1 month prior to conception was obtained from food frequency questions for fruit, green leafy vegetables, fish and fast foods, by a research midwife. Use of any fertility treatments associated with the current pregnancy was documented (yes, n = 340, no, n = 5258). Accelerated failure time models with log normal distribution were conducted to estimate time ratios (TR) and 95% CIs. The impact of differences in dietary intake on infertility (TTP >12 months) was compared using a generalized linear model (Poisson distribution) with robust variance estimates, with resulting relative risks (RR) and 95% CIs. All analyses were controlled for a range of maternal and paternal confounders. Sensitivity analyses were conducted to explore potential biases common to TTP studies. MAIN RESULTS AND THE ROLE OF CHANCE: Lower intakes of fruit and higher intakes of fast food were both associated with modest increases in TTP and infertility. Absolute differences between the lowest and highest categories of intake for fruit and fast food were in the order of 0.6-0.9 months for TTP and 4-8% for infertility. Compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day (TR = 1.06, 95% CI: 0.97-1.15), 1-6 times/week (TR = 1.11, 95% CI: 1.01-1.22) or <1-3 times/month (TR = 1.19, 95% CI: 1.03-1.36), corresponded to 6, 11 and 19% increases in the median TTP (Ptrend = 0.007). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2-<4 times/week (TR = 0.89, 95% CI: 0.81-0.98), >0-<2 times/week (TR 0.79, 95% CI 0.69-0.89) or no fast food (TR = 0.76, 95% CI: 0.61-0.95), corresponded to an 11, 21 and 24% reduction in the median TTP (Ptrend <0.001). For infertility, compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day, 1-6 times/week or <1-3 times/month corresponded to a 7, 18 and 29% increase in risk of infertility (Ptrend = 0.043). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2-<4 times/week, >0-<2 times/week, or no fast food, corresponded to an 18, 34 and 41% reduced risk of infertility (Ptrend <0.001). Pre-pregnancy intake of green leafy vegetables or fish were not associated with TTP or infertility. Estimates remained stable across a range of sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: Collection of dietary data relied on retrospective recall and evaluated a limited range of foods. Paternal dietary data was not collected and the potential for residual confounding cannot be eliminated. Compared to prospective TTP studies, retrospective TTP studies are prone to a number of potential sources of bias. WIDER IMPLICATIONS OF THE FINDINGS: These findings underscore the importance of considering preconception diet for fecundity outcomes and preconception guidance. Further research is needed assessing a broader range of foods and food groups in the preconception period. STUDY FUNDING/COMPETING INTEREST(S): The SCOPE database is provided and maintained by MedSciNet AB (http://medscinet.com). The Australian SCOPE study was funded by the Premier's Science and Research Fund, South Australian Government (http://www.dfeest.sa.gov.au/science-research/premiers-research-and-industry-fund). The New Zealand SCOPE study was funded by the New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council (04/198); Evelyn Bond Fund, Auckland District Health Board Charitable Trust. The Irish SCOPE study was funded by the Health Research Board of Ireland (CSA/2007/2; http://www.hrb.ie). The UK SCOPE study was funded by National Health Service NEAT Grant (Neat Grant FSD025), Biotechnology and Biological Sciences Research council (www.bbsrc.ac.uk/funding; GT084) and University of Manchester Proof of Concept Funding (University of Manchester); Guy's and St. Thomas' Charity (King's College London) and Tommy's charity (http://www.tommys.org/; King's College London and University of Manchester); and Cerebra UK (www.cerebra.org.uk; University of Leeds). L.E.G. is supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (ID 1070421). L.J.M. is supported by a SACVRDP Fellowship; a program collaboratively funded by the National Heart Foundation, the South Australian Department of Health and the South Australian Health and Medical Research Institute. L.C.K. is supported by a Science Foundation Ireland Program Grant for INFANT (12/RC/2272). C.T.R. was supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (GNT1020749). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

The duration of sexual relationship and its effects on adverse pregnancy outcomes.

This study aims to determine if a short duration of sexual relationship is more common among women who experience adverse pregnancy outcomes including gestational hypertension (GHT), preeclampsia, small for gestational age (SGA) pregnancies and spontaneous preterm birth (sPTB) with or without abnormal uterine artery Doppler compared to women who have uncomplicated pregnancies. 5591 nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. The risk for pregnancy complications for women who had a duration of sexual relationship of ≤3 months, 4-6 months, 7-9 months, 10-12 months was compared with women who had a duration of sexual relationship of >12 months. Uterine artery Doppler was performed at 20 ±â€¯1 weeks' gestation. A short duration of sexual relationship (≤3 months) was more common among women with SGA in the presence of abnormal uterine artery Doppler [9.8% vs 3.0%, aOR (95% CI) 3.4 (1.6-7.08] compared to women who had uncomplicated pregnancies. A short duration of sexual relationship (≤3 months) was also more common among women who had abnormal uterine artery Doppler compared to those with normal uterine artery Doppler [6.1% vs 3.1%, aOR (95% CI) = 2.1 (1.4-3.2)]. A short duration of sexual relationship was not associated with preeclampsia after adjusting for confounders. A short duration of sexual relationship is more common among women who deliver SGA infants with features of placental insufficiency as indicated by abnormal uterine artery Doppler.

Urinary angiotensinogen excretion in Australian Indigenous and non-Indigenous pregnant women.

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.

Seasonality of hypertensive disorders of pregnancy - A South Australian population study.

OBJECTIVES: To investigate the seasonal variation of hypertensive disorders of pregnancy (HDP) in South Australia. STUDY DESIGN: Retrospective population study including all 107,846 liveborn singletons during 2007-2014 in South Australia. Seasonality in incidence of HDP in relation to estimated date of conception (eDoC) and date of birth (DoB) were examined using Fourier series analysis. MAIN OUTCOME MEASURES: Seasonality of HDP in relation to eDoC and DoB. RESULTS: During 2007-2014, the incidence of HDP was 7.1% (n = 7,612). Seasonal modeling showed a strong relationship between HDP and eDoC (p < .001) and DoB (p < .001). Unadjusted and adjusted models (adjusted for maternal age, body mass index, ethnicity, parity, type of health care, smoking and gestational diabetes mellitus) demonstrated the presence of a peak incidence (7.8%, 7.9% respectively) occurring among pregnancies with eDoC in late Spring (November) and a trough (6.4% and 6.3% respectively) among pregnancies with eDoC in late Autumn (May). Both unadjusted and adjusted seasonal modelling showed a peak incidence of HDP for pregnancies with DoB in August (8.0%, 8.1% respectively) and a nadir among pregnancies with eDoB in February (6.2%). CONCLUSION: The highest incidence of HDP was associated with pregnancies with eDoC during late spring and summer and birth in winter, while the lowest incidence of HDP was associated with pregnancies with eDoC during late autumn and early winter and birth in summer. Nutrient intake, in particular vitamin D, sunlight exposure and physical activity may affect maternal, fetal and placental adaptation to pregnancy and are potential contributors to the seasonal variation of HDP.