Screening For Pregnancy Endpoints Research Articles

Maternal Plasma miRNAs as Early Biomarkers of Moderate-to-Late-Preterm Birth.

Globally, preterm birth (PTB) is a primary cause of mortality and morbidity in infants, with PTB rates increasing worldwide over the last two decades. Biomarkers for accurate early prediction of PTB before the clinical event do not currently exist. Given their roles in the development and progression of many disease states, there has been increasing interest in the utility of microRNAs (miRNAs) as early biomarkers for pregnancy-related disorders, including PTB. The present study was designed to examine potential differences in miRNA abundances in maternal plasma from mothers with infants born following a moderate to late (28-36 weeks' gestation, n = 54) spontaneous PTB (SPTB) compared to mothers with matched term infants (n = 54). Maternal plasma collected at 15 weeks' gestation were utilised from the Auckland and Adelaide cohorts from the Screening for Pregnancy Endpoints (SCOPE) study. miRNAs in plasma were quantified using the NanoString nCounter expression panel (800 miRNAs). The top four most abundant miRNAs were significantly decreased in the plasma of mothers in the SPTB group with results consistent across both cohorts and pathway analysis was undertaken to examine the biological processes linked to the dysregulated miRNAs. The top candidate miRNAs (miRs-451a, -223-3p, let-7a-5p, and -126-3p) were linked to gene pathways associated with inflammation, apoptosis, and mitochondrial biogenesis. Moreover, miRNAs were consistently less abundant in the plasma of mothers of preterm infants across both sites, suggesting potential global dysregulation in miRNA biogenesis. This was supported by a significant downregulation in expression of key genes that are involved in miRNA biogenesis (DROSHA, DICER, and AGO2) across both sites in the SPTB group. In summary, the present study has identified miRNAs in maternal plasma that may provide predictive utility as early biomarkers for the risk of later SPTB. Importantly, these observations were conserved across two independent cohorts. Further, our data provide evidence for a persistent decrease in miRNA abundance in mothers who later experienced an SPTB, which is likely to have widespread consequences for gene regulation and epigenetic processes.

FRI589 MicroRNAs In Maternal Plasma At 15 Weeks Gestation As Biomarkers For Later Preterm Birth: Evidence For Dysregulated Mirna Biogenesis And Implications For Pregnancy-related Endocrine Signaling Pathways

Abstract Disclosure: F. Ramzan: None. J. Rong: None. C. Roberts: None. J. O'Sullivan: None. J.K. Perry: None. R. Taylor: None. L. McCowan: None. M.H. Vickers: None. Introduction: Preterm birth (PTB) is a leading cause of morbidity and mortality in infants, with rates of PTB increasing globally over the last 20 years. MicroRNAs (miRNAs) have been reported to have widespread involvement in the development of and protection from many diseases, there is increasing interest in their potential role in the aetiology of a range of pregnancy-related disorders, including PTB. Objectives: To investigate differential miRNA abundances in mid-pregnancy plasma samples between mothers with term infants compared with moderate to late preterm infants (spontaneous PTB) and replication across independent cohorts. Method: The Auckland and Adelaide arms of the Screening for Pregnancy Endpoints (SCOPE) study were utilised. miRNAs in plasma at 15 weeks gestation from mothers of term and moderate to late preterm infants (n=54 per group) were quantified using the NanoString nCounter human v2 miRNA expression panel. Gene expression of key mediators of miRNA biogenesis, including Drosha, Dicer and Argonaut were quantified via RT-qPCR. In-silico analysis was performed to investigate the biological pathways associated with the dysregulated miRNAs. Results: Of the 800 miRNAs examined, the top four miRNAs identified were conserved across both cohorts and were significantly downregulated in the plasma of mothers who later experienced a PTB. The gene pathways associated with the top candidate miRNAs were linked to inflammatory processes, mitochondrial biogenesis, apoptosis and regulation of key pregnancy-related hormonal signaling pathways. Moreover, miRNAs were consistently downregulated in the PTB group concomitant with reduced gene expression of key miRNA biogenesis markers. Conclusions: We identified miRNAs in maternal plasma in mid-pregnancy that were highly predictive of later spontaneous PTB and, importantly, were conserved across two independent cohorts. Moreover, in addition to identifying potential early biomarkers for subsequent PTB, we provide evidence for persistent downregulation of miRNAs in those mothers who later delivered preterm, which is likely to have widespread effects on endocrine signaling pathways during pregnancy. Presentation: Friday, June 16, 2023

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

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. 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. 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). Cardio metabolic risk factors at the booking visit in the first pregnancy may be useful in identifying young women at risk of future CVD.

The Effect of Interactions between Folic Acid Supplementation and One Carbon Metabolism Gene Variants on Small-for-Gestational-Age Births in the Screening for Pregnancy Endpoints (SCOPE) Cohort Study.

Small-for-gestational-age (SGA) is associated with significant perinatal morbidity and mortality. Our aim was to investigate gene-nutrient interactions between maternal one-carbon single nucleotide polymorphisms (SNPs) and folic acid supplement (FAS) use, and their association with SGA. Nulliparous New Zealand women with singleton pregnancy were recruited as part of the Screening for Pregnancy Endpoints prospective cohort study. Data on FAS use was collected via face-to-face interview at 15 weeks’ gestation; participants were followed prospectively and birth outcome data collected within 72 h of delivery. Participants were genotyped for MTHFR 677, MTHFR 1298, MTHFD1 1958, MTR 2756, MTRR 66 and TCN2 776 SNPs. Genotype data for at least one SNP was available for 1873 (93%) of eligible participants. Analysis showed a significant SNP-FAS interaction for MTHFR 1298 (p = 0.020), MTHFR 677 (p = 0.019) and TCN2 776 (p = 0.017) in relation to SGA: MTHFR 1298 CC variant non-FAS users had an increased likelihood [Odds Ratio (OR) = 2.91 (95% Confidence Interval (CI) = 1.52, 5.60] compared with wild-type (MTHFR 1298 AA) FAS users. MTHFR 677 variant allele carrier (MTHFR 677 CT + MTHFR 677 TT) non-FAS users had an increased likelihood [OR = 1.87 (95% CI = 1.21, 2.88)] compared to wild-type (MTHFR 677 CC) FAS users. TCN2 776 variant (TCN2 776 GG) non-FAS users had an increased likelihood [OR = 2.16 (95% CI = 1.26, 3.71)] compared with wild type homozygote + heterozygote (TCN2 776 CC + TCN2 776 CG) FAS users. No significant interactions were observed for MTHFD1 1958, MTR 2756 or MTRR 66 (p > 0.05). We observed an overall pattern of FAS attenuating differences in the likelihood of SGA seen between genotype groups in FAS non-users. Future research should focus on how intake of other one-carbon nutrients might mediate these gene-nutrient interactions.

Folic acid supplementation is associated with size at birth in the Screening for Pregnancy Endpoints (SCOPE) international prospective cohort study

BackgroundSmall-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. AimThe aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters. Study designWomen were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 ± 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors. SubjectsNulliparous women with singleton pregnancies. Outcome measuresSGA (<10th customised birthweight centile). Results5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67–01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (β 2.56 (95% CI: 0.87–4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference. ConclusionsIn this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.

Sex- and growth-specific characteristics of small for gestational age infants: a prospective cohort study

BackgroundAsymmetric fetal growth and male sex are both associated with adverse neonatal outcome. However, less is known about the influence of asymmetric growth and fetal sex within SGA neonates, a group of infants already at increased risk for adverse neonatal outcomes. The aim of the present study was to provide insight into variance in risk factors for SGA in a fetal sex- and growth symmetry-specific way.MethodsFor this prospective, multicenter cohort study, data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 (11.3%) pregnancies were complicated with SGA and 3376 (60.0%) women had uncomplicated pregnancies. Association between risk factors for SGA, SGA subgroups, and uncomplicated pregnancies were assessed with multivariable analyses.ResultsPrevalence of asymmetric growth varied from 45.8% of SGA infants to 5.5% of infants with a customized birthweight > 90th percentile (p < 0.001). Significantly more SGA males had asymmetric growth compared to SGA female infants (51.2% vs 40.4%, p = 0.009). Maternal pre-pregnancy diet and BMI < 20 and ≥ 30 were significantly associated with symmetric SGA but not with asymmetric SGA. Asymmetric SGA infants had not only lower customized birthweight percentile (4.4 (SD 2.8) vs 5.0 (SD 3.0), p < 0.001), but also lower rates of stillbirth (p = 0.041) and less often Apgar scores < 7 (p = 0.060).ConclusionsAmong SGA infants, low customized birthweight percentiles and male sex are associated with asymmetric growth. Only symmetric SGA is significantly associated with maternal risk factors in early pregnancy. There is a substantial variance in risk factors and neonatal outcomes for SGA based on growth symmetry, implying a different pathogenesis.Trial registrationACTRN12607000551493

Childhood dietary patterns and body composition at age 6 years: the Children of SCOPE study.

Dietary patterns describe the quantity, variety, or combination of different foods and beverages in a diet and the frequency of habitual consumption. Better understanding of childhood dietary patterns and antenatal influences could inform intervention strategies to prevent childhood obesity. We derived empirical dietary patterns in 1142 children (average age 6.0 (0.2) years) in Auckland, New Zealand whose mothers had participated in the Screening for Pregnancy Endpoints (SCOPE) cohort study and explored associations with measures of body composition. Participants (Children of SCOPE) had their diet assessed by food frequency questionnaire (FFQ) and empirical dietary patterns were extracted using factor analysis. Three distinct dietary patterns were identified; 'Healthy', 'Traditional' and 'Junk'. Associations between dietary patterns and measures of childhood body composition (waist, hip, arm circumferences, body mass index (BMI), bioelectrical impedance analysis (BIA) derived body fat percentage, and sum of skinfold thicknesses (SST)) were assessed by linear regression, with adjustment for maternal influences. Children who had higher 'Junk' dietary pattern scores had 0.24cm greater arm (0.08 SD (95%CI 0.04, 0.13)) and 0.44cm hip (0.05 SD (95% CI 0.01, 0.10)) circumferences, 1.13cm greater SST (0.07 SD (95%CI 0.03, 0.12)) and were more likely to be obese (OR=1.74 (95%CI 1.07, 2.82)); those with higher 'Healthy' pattern scores were less likely to be obese (OR=0.62 (95%CI 0.39, 1.00)). In a large mother-child cohort, a dietary pattern characterised by high sugar and fat foods was associated with greater adiposity and obesity risk in children aged 6 years, while a 'Healthy' dietary pattern offered some protection against obesity. Targeting unhealthy dietary patterns could inform public health strategies to reduce the prevalence of childhood obesity.

Association between phospholipid metabolism in plasma and spontaneous preterm birth: a discovery lipidomic analysis in the cork pregnancy cohort

IntroductionPreterm birth (PTB) is defined as birth occurring before 37 weeks’ gestation, affects 5–9% of all pregnancies in developed countries, and is the leading cause of perinatal mortality. Spontaneous preterm birth (sPTB) accounts for 31–50% of all PTB, but the underlying pathophysiology is poorly understood.ObjectiveThis study aimed to decipher the lipidomics pathways involved in pathophysiology of sPTB.MethodsBlood samples were taken from SCreening fOr Pregnancy Endpoints (SCOPE), an international study that recruited 5628 nulliparous women, with a singleton low-risk pregnancy. Our analysis focused on plasma from SCOPE in Cork. Discovery profiling of the samples was undertaken using liquid chromatography-mass spectrometry Lipidomics, and features significantly altered between sPTB (n = 16) and Control (n = 32) groups were identified using empirical Bayes testing, adjusting for multiple comparisons.ResultsTwenty-six lipids showed lower levels in plasma of sPTB compared to controls (adjusted p < 0.05), including 20 glycerophospholipids (12 phosphatidylcholines, 7 phosphatidylethanolamines, 1 phosphatidylinositol) and 6 sphingolipids (2 ceramides and 4 sphingomyelines). In addition, a diaglyceride, DG (34:4), was detected in higher levels in sPTB compared to controls.ConclusionsWe report reduced levels of plasma phospholipids in sPTB. Phospholipid integrity is linked to biological membrane stability and inflammation, while storage and breakdown of lipids have previously been implicated in pregnancy complications. The contribution of phospholipids to sPTB as a cause or effect is still unclear; however, our results of differential plasma phospholipid expression represent another step in advancing our understanding of the aetiology of sPTB. Further work is needed to validate these findings in independent pregnancy cohorts.

Maternal and severe anaemia in delivering women is associated with risk of preterm and low birth weight: A cross sectional study from Jharkhand, India

Background and objectivesHaemoglobin content is the well accepted indicator for anaemia assessment. The high prevalence of anaemia, maternal health care issues and adverse delivery outcome in Jharkhand, we investigated whether delivering women with anaemia would present a modifiable risk of preterm (PTB) and low birth weight (LBW). MethodsA facility-based cross-sectional study involving pregnant women, with screening for pregnancy endpoints and haemoglobin assay, were conducted. Anaemia was classified according to World Health Organization's definition of anaemia in pregnancy. Confounding variables were adjusted in a logistic model. The adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were used for analyzing the association among maternal anaemia, PTB and LBW. ResultsWe observed a high prevalence of anaemia (78.45%) in delivering women, whereas high prevalence of preterm birth (34.75%) and LBW (32.81%) in delivering women overall. In the adjusted analysis, overall anaemia in pregnancy was strongly associated with preterm birth (OR, 3.42; 95% CI, 1.98–5.88; P ≤ .0001) as compared to LBW (OR, 1.12; 95% CI, 0.65–1.61; P = .0003). The risk of PTB and LBW were dependent on the stratification of the anaemia group, as the strongest association was observed in severe (OR, 4.86) followed by mild (OR, 3.66) and moderate (OR, 3.18) anaemia in PTB; whereas risk of LBW was found in severe (OR, 2.5) followed by moderate (OR, 1.11) and mild (OR, 0.57) anaemia. The risk of PTB and LBW across six pregnancy haemoglobin groups were compared, haemoglobin of 10–10.9 g/dl (OR, 1.25) and ≤ 8 g/dl (OR, 1.03) have shown association with PTB and LBW, respectively. However, high haemoglobin concentration was not associated with either PTB or LBW. ConclusionsAnaemia in delivering women was associated with an elevated risk of PTB and LBW and the risk increased with the severity of anaemia in pregnant women.

Relationships of maternal body mass index and plasma biomarkers with childhood body mass index and adiposity at 6years: The Children of SCOPE study.

Maternal obesity has been implicated in the origins of childhood obesity through a suboptimal environment in-utero. We examined relationships of maternal early pregnancy body mass index (BMI), overweight/obesity, and plasma biomarkers of obesity, inflammation, insulin resistance, and placental function with measures of childhood BMI and adiposity. BMI z-score, sum of skinfold thicknesses (SST), body fat percentage (BFP, by bioelectrical impedance), and waist, arm, and hip circumferences were measured in 1173 6-year-old children of nulliparous pregnant women in the Screening for Pregnancy Endpoints (SCOPE) study, New Zealand. Relationships of maternal early pregnancy (15weeks' gestation) BMI and biomarkers with these childhood anthropometric measures were assessed by linear regression, with appropriate adjustment. 28.1% of mothers were classified as overweight and 10.1% with obesity; compared with normal weight mothers, the BFP of their children were 5.3% higher (0.16 SD [95% CI, 0.04-0.29] p=.01) and 7.8% higher (0.27 [0.08-0.47] p=.006) with comparable values for BMI z-score and arm, waist, and hip circumferences. Early pregnancy maternal BMI and plasma placental growth factor (PlGF) were associated with higher child's SST, BMI z-score, hip circumference, and BFP. None of the metabolic or inflammatory maternal biomarkers were associated with childhood obesity. In this contemporary large prospective cohort study with extensive maternal/childhood phenotyping and a high prevalence of maternal overweight/obesity, we found independent relationships of maternal early pregnancy BMI with childhood BMI and adiposity; similar associations were observed with PlGF, which may imply a role for placenta function in the developmental programming of childhood obesity risk.

Social, biological, behavioural and psychological factors related to physical activity during early pregnancy in the Screening for Pregnancy Endpoints (Cork, Ireland) cohort study

ObjectiveThe aim of this study was to identify the social, biological, behavioural and psychological factors related to physical activity (PA) in early pregnancy.DesignThis is a secondary analysis of data from...

Paternal contributions to large-for-gestational-age term babies: findings from a multicenter prospective cohort study.

We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P<0.001) and were more likely to have been born macrosomic (P<0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P<0.001), 2.8 kg heavier (P<0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA.

Maternal Iodine Status and Associations with Birth Outcomes in Three Major Cities in the United Kingdom

Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine concentrations (UIC) and birth outcomes in three UK cities. Spot urines were collected from 541 women in London, Manchester and Leeds from 2004–2008 as part of the Screening for Pregnancy End points (SCOPE) study. UIC at 15 and 20 weeks’ gestation was estimated using inductively coupled plasma-mass spectrometry (ICP-MS). Associations were estimated between iodine status (UIC and iodine-to-creatinine ratio) and birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth. Median UIC was highest in Manchester (139 μg/L, 95% confidence intervals (CI): 126, 158) and London (130 μg/L, 95% CI: 114, 177) and lowest in Leeds (116 μg/L, 95% CI: 99, 135), but the proportion with UIC <50 µg/L was <20% in all three cities. No evidence of an association was observed between UIC and birth weight centile (−0.2% per 50 μg/L increase in UIC, 95% CI: −1.3, 0.8), nor with odds of spontaneous preterm birth (odds ratio = 1.00, 95% CI: 0.84, 1.20). Given the finding of iodine concentrations being insufficient according to World Health Organization (WHO) guidelines amongst pregnant women across all three cities, further studies may be needed to explore implications for maternal thyroid function and longer-term child health outcomes.

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

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. 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. 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. 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.

BackgroundObesity 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 findingsLow-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.ConclusionsWe 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.

Exploring the concept of functional vitamin D deficiency in pregnancy: impact of the interaction between 25-hydroxyvitamin D and parathyroid hormone on perinatal outcomes

Associations of vitamin D with perinatal outcomes are inconsistent and few studies have considered the wider calcium metabolic system. We aimed to explore functional vitamin D deficiency in pregnancy by investigating associations between vitamin D status, parathyroid hormone (PTH), and perinatal outcomes. SCOPE (Screening for Pregnancy Endpoints) Ireland is a prospective cohort study of low-risk, nulliparous pregnant women. We measured serum 25-hydroxyvitamin D [25(OH)D] and PTH at 15 wk of gestation in 1754 participants. Mean±SD 25(OH)D was 56.6±25.8 nmol/L (22.7±10.3ng/mL) and geometric mean (95% CI) PTH was 7.84 pg/mL (7.7, 8.0 pg/mL) [0.86 pmol/L (0.85, 0.88 pmol/L)]. PTH was elevated in 34.3% of women who had 25(OH)D <30nmol/L and in 13.9% of those with 25(OH)D ≥75 nmol/L. Whereas 17% had 25(OH)D <30 nmol/L, 5.5% had functional vitamin D deficiency, defined as 25(OH)D <30 nmol/L with elevated PTH. Elevated mean arterial pressure (MAP), gestational hypertension, pre-eclampsia, and small-for-gestational-age (SGA) birth were confirmed in 9.2%, 11.9%, 3.8%, and 10.6% of participants, respectively. In fully adjusted regression models, neither low 25(OH)D nor elevated PTH alone increased the risk of any individual outcome. The prevalence of elevated MAP (19.1% compared with 9.7%) and SGA (16.0% compared with 6.7%) were highest (P<0.05) in those with functional vitamin D deficiency compared with the reference group [25(OH)D ≥75 nmol/L and normal PTH]. The adjusted prevalence ratio (PR) and RR (95% CIs) for elevated MAP and SGA were 1.83 (1.02, 3.27) and 1.53 (0.80, 2.93), respectively. There was no effect of functional vitamin D deficiency on the risk of gestational hypertension (adjusted RR: 1.00; 95% CI: 0.60, 1.67) or pre-eclampsia (adjusted RR: 1.17; 95% CI: 0.32, 4.20). The concept of functional vitamin D deficiency, reflecting calcium metabolic stress, should be considered in studies of vitamin D in pregnancy. The SCOPE pregnancy cohort is registered at http://www.anzctr.org.au as ACTRN12607000551493.

126. Sex and growth specific characteristics of small for gestational age neonates: A prospective cohort study

Introduction Male bearing pregnancies and asymmetric fetal growth are associated with preeclampsia (PE). However, this has not been studied in small for gestational age (SGA) neonates, a group that is also associated with PE. Objective To provide insight regarding risk factors and differences in neonatal outcome for SGA neonates based on sex and growth symmetry. Methods Data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 pregnancies were complicated with SGA and 3376 women had uncomplicated pregnancies. SGA pregnancies were grouped based on fetal sex (male/female) and growth symmetry [ponderal index below (asymmetric) and above (symmetric) the 10th percentile for gestation]. Association between risk factors for SGA, SGA subgroups and uncomplicated pregnancies were assessed with multinominal analyses. Results Of all asymmetric neonates, 24.2% were SGA, while 7.4% of all symmetric neonates were SGA. Of all SGA neonates, 45.8% showed asymmetric growth, while 5.5% of neonates with a customised birthweight >90th percentile (p 90th percentile) umbilical Doppler resistance index (RI) at 20 weeks’ gestation was more common in SGA females (9.6% vs 17.8% p = 0.003) but did not differ between symmetric and asymmetric SGA neonates. The presence of abnormal uterine artery Doppler RI at 20 weeks’ gestation did not differ between SGA subgroups. In each SGA subgroup PE incidence was increased (28.2% in symmetric SGA, 26.1% in asymmetric SGA, 27.2% in SGA male and 25.3% in SGA female bearing pregnancies) compared to non-SGA pregnancies (4.2%). The incidence of PE did not differ between SGA subgroups. Discussion A quarter of asymmetric neonates are SGA. Asymmetric SGA associates with male neonates. In contrast with literature, PE was associated with both symmetric and asymmetric growth in SGA neonates.

Associations between maternal lifestyle factors and neonatal body composition in the screening for pregnancy endpoints (CORK) cohort study

Background A person's chronic disease risk can be influenced during their fetal development in ways that are likely mediated by their body composition at birth. A better understanding of how maternal lifestyle is related to newborn body composition could thus inform intervention efforts. Methods Using Cork participant data (n = 1754) from the Screening for Pregnancy Endpoints (SCOPE) cohort study (ECM5(10)05/02/08), we estimated how pre-pregnancy body size, gestational weight gain, exercise, alcohol, smoking and diet were related to neonatal fat and fat-free mass, as well as length and gestational age at birth, using quantile regression. Maternal factors were measured by a trained research midwife at 15 gestational weeks, in addition to a 3rd trimester weight measurement used to calculate weight gain. Infant body composition was measured using air-displacement plethysmography. Results Healthy (versus excess) gestational weight gain was associated with lower median fat-free mass (−112 g, 95%CI: −47 to −176) and fat mass (−33 g, 95%CI: −1 to −65) in the offspring and a 103 g decrease in the 95th centile of fat mass (95%CI: −33 to −174). Maternal normal weight status (versus obesity) was associated with lower median fat mass (−48 g, 95%CI: −12 to −84). At the highest centiles, fat mass was lower among infants of women who engaged in frequent moderate-intensity exercise early in the pregnancy (−92 g at the 95th centile, 95%CI: −168 to −16). No other lifestyle factors were strongly related to infant body composition. Conclusions These results suggest that supporting healthy maternal lifestyles could reduce the risk of excess fat accumulation in the offspring, without increasing the risk of low body fat, or adversely affecting fat-free mass development, length or gestational age.

Vitamin D levels in an Australian and New Zealand cohort and the association with pregnancy outcome

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

Antenatal risk factors associated with neonatal morbidity in large-for-gestational-age infants: an international prospective cohort study.

Large-for-gestational-age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal morbidity in large-for-gestational-age infants. Nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. We compared maternal and fetal factors between large-for-gestational-age infants (birthweight >90th customized centile) with and without neonatal morbidity, defined as admission to a neonatal intensive care unit or severe neonatal morbidity. Factors were selected based on a priori hypotheses of association and included maternal demography, anthropometric measures and self-reported physical activity (15 and 20weeks), fetal biometry (20weeks), and clinical information. Multivariable logistic regression was used to identify risk factors. Stratified analyses were performed by maternal obesity and physical activity. Among term pregnancies, prevalence of large-for-gestational-age infants was 9.3% (491/5255), with 11.8% (58/491) prevalence of neonatal morbidity. Random glucose at 20weeks (odds ratio 1.52; 95% confidence interval 1.17-1.97, per 1mmol/L increase) and no regular physical activity at 20weeks (odds ratio 3.93; 95% confidence interval 1.75-8.83) were associated with increased risk of neonatal morbidity after adjustment for birthweight, gestational age at delivery and gestational diabetes. The increased risk associated with higher glucose levels was not evident in women with regular physical activity or without obesity. Regular physical activity in mid-pregnancy is associated with lower risk for neonatal morbidity in large-for-gestational-age infants and seems to offer protection against the increased risk associated with higher maternal glucose levels.