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.

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.

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.

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.

Long-term Trends in Singleton Preterm Birth in South Australia From 1986 to 2014.

OBJECTIVE: To describe long-term trends in the prevalence of preterm birth and rates of preterm birth in singleton pregnancies complicated by hypertensive disorders of pregnancy, small for gestational age (SGA), and preterm prelabor rupture of membranes (PROM) in South Australia. METHODS: We conducted a retrospective population study including all singleton live births in the state of South Australia from 1986 to 2014. Long-term trends for preterm birth, hypertensive disorders of pregnancy, SGA, preterm PROM as well as stillbirth were assessed using joinpoint regression analyses. Trends in maternal age, body mass index (BMI), ethnic diversity, parity, and smoking over time were also assessed. RESULTS: From 1986 to 2014, with a total of 539,234 singleton births, the overall preterm birth rates increased from 5.1% to 7.1% (P<.001) and for iatrogenic preterm birth increased from 1.6% to 3.2% (P<.001). The incidence of hypertensive disorders of pregnancy decreased from 8.7% to 7.2%. Among pregnancies complicated by hypertensive disorders of pregnancy, the proportion of preterm birth increased (10.4-17.5%, P<.001). The incidence of SGA decreased from 11.1% to 8.0%. Among pregnancies complicated by SGA, the proportion of preterm birth increased (2.9-5.4%, P<.001). The incidence of preterm PROM increased from 1.4% to 2.2%. Among pregnancies complicated by preterm PROM, the proportion of preterm birth remained stable. Preterm stillbirth rates declined (4.23-2.32%, P<.001). Maternal age, BMI, and ethnic diversity have all increased since 1986, whereas maternal smoking has decreased. CONCLUSION: In South Australia, the preterm birth rate among singletons increased from 1986 to 2014 by 40%, with iatrogenic preterm birth being responsible for 80% of this increase. Incidence of hypertensive disorders of pregnancy and SGA declined. Among pregnancies complicated by hypertensive disorders of pregnancy and SGA, the proportions of preterm birth increased, indicating earlier interventions in these women. The diagnosis of preterm PROM increased from 1% to 2%, and greater than 80% of preterm PROM was associated with preterm birth after 1990. Increasing iatrogenic delivery may be attributable, in part, to changing maternal phenotype and to altered clinicians' behavior. However, improvements in fetal surveillance, particularly ultrasonography, and advanced neonatal care may underpin perinatal clinical decision-making and the likelihood of iatrogenic birth.

Seasonality of gestational diabetes mellitus: a South Australian population study.

OBJECTIVE: To investigate whether there is a seasonal variation in the incidence of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: This retrospective cohort study of 60 306 eligible South Australian live-born singletons during 2007-2011 recorded in the South Australian Perinatal Statistics Collection (SAPSC) examined the incidence of GDM in relation to estimated date of conception (eDoC). Fourier series analysis was used to model seasonal trends. RESULTS: During the study period, 3632 (6.0%) women were diagnosed with GDM. Seasonal modeling showed a strong relation between GDM and eDoC (p<0.001). Unadjusted and adjusted models (adjusted for maternal age, body mass index (BMI), parity, ethnicity, socioeconomic status, and chronic hypertension) demonstrated the presence of a peak incidence occurring among pregnancies with eDoC in winter (June/July/August), with a trough for eDoc in summer (December/January/February). As this was a retrospective study, we could only use variables that had been collected as part of the routine registration system, the SAPSC. CONCLUSIONS: This study is the first population-based study to demonstrate a seasonal variation for GDM. Several maternal lifestyle and psychosocial factors associated with seasonality and GDM may be influential in the pathophysiologic mechanisms of GDM. Ambient temperature, physical activity, nutrient intake, and vitamin D levels may affect maternal physiology, and fetal and placental development at the cellular level and contribute to the development of GDM. The mechanisms underlying these possible associations are not fully understood and warrant further investigation.

Sexual Dimorphism in Adverse Pregnancy Outcomes - A Retrospective Australian Population Study 1981-2011.

OBJECTIVES: Sexual inequality starts in utero. The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult. METHODS: Retrospective population-based study of 574,358 South Australian singleton live births during 1981-2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches. RESULTS: The traditional approach showed male predominance for PTB [20-24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274-1.445], spontaneous PTB [25-29 weeks: RR M/F 1.118, 95%-CI 1.044-1.197%], GDM [RR M/F 1.042, 95%-CI 1.011-1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034-1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044-1.105]. The FAR approach showed that males were at increased risk for PTB [20-24 weeks: RR M/F 1.273, 95%-CI 1.087-1.490], for spontaneous PTB [25-29 weeks: RR M/F 1.269, 95%-CI 1.143-1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044-1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25-29 weeks: RR M/F 0.857, 95%-CI 0.780-0.941] and PIHD associated with PTB [25-29 weeks: RR M/F 0.686, 95%-CI 0.581-0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25-29 weeks: RR M/F 0.779, 95%-CI 0.648-0.937]. CONCLUSIONS: This study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene expression and function are likely to play a key role. Further research on sex differences in placental function and maternal adaptation to pregnancy is required to delineate the causal molecular mechanisms in sex-specific pregnancy outcome. Identifying these mechanisms may inform fetal sex specific tailored antenatal and neonatal care.

Prevalence and predictors of alcohol use during pregnancy: findings from international multicentre cohort studies.

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.

Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study.

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78-1.0] and 0.78 [0.58-0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.

Association between maternal alcohol consumption in early pregnancy and pregnancy outcomes.

OBJECTIVE: To investigate the association between alcohol consumption and binge drinking before and during early pregnancy and adverse pregnancy outcomes. METHODS: We used data from 5,628 nulliparous pregnant participants recruited to the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study. Participants were interviewed at 15 weeks of gestation and information on alcohol intake before pregnancy and until the time of interview was obtained using a standardized questionnaire. Alcohol intake was classified as occasional (1-2 units per week), low (3-7 units per week), moderate (8-14 units per week), and heavy (greater than 14 units per week). Binge alcohol consumption was defined as consumption of 6 or more alcohol units in one session. RESULTS: Of the 5,628 participants, 1,090 (19%) reported occasional alcohol consumption, 1,383 (25%) low alcohol consumption, 625 (11%) moderate alcohol consumption, and 300 (5%) heavy alcohol consumption. Overall, 1,905 (34%) participants reported binge alcohol consumption in the 3 months before pregnancy, and 1,288 (23%) of these participants reported binge alcohol consumption during the first 15 weeks of pregnancy. Participants who consumed occasional to heavy amounts of alcohol in early pregnancy did not have altered odds of a small-for-gestational-age neonate, reduced birth weight, preeclampsia, or spontaneous preterm birth. Similarly, those who binge drank in early pregnancy did not have altered odds of these adverse pregnancy outcomes. CONCLUSION: Alcohol consumption in early pregnancy was prevalent in this nulliparous cohort. There was no association between alcohol consumption before 15 weeks of gestation and small for gestational age, reduced birth weight, preeclampsia, or spontaneous preterm birth. LEVEL OF EVIDENCE: : II.