The association of AGTR2 polymorphisms with preeclampsia and uterine artery bilateral notching is modulated by maternal BMI

On behalf of the SCOPE consortiumIntroductionThis study aimed to determine the association of AGTR1 and AGTR2 polymorphisms with preeclampsia and whether these are affected by environmental factors and fetal sex.MethodsOverall 3234 healthy nulliparous women, their partners and babies were recruited prospectively to the SCOPE study in Adelaide and Auckland. Data analyses were confined to 2121 Caucasian parent-infant trios, among whom 123 had preeclamptic pregnancies. 1185 uncomplicated pregnancies served as controls. DNA was extracted from buffy coats and genotyped by utilizing the Sequenom MassARRAY system. Doppler sonography on the uterine arteries was performed at 20 weeks' gestation.ResultsFour polymorphisms in AGTR1 and AGTR2 genes, including AGTR1 A1166C, AGTR2 C4599A, AGTR2 A1675G and AGTR2 T1134C, were selected and significant associations were predominately observed for AGTR2 C4599A. When the cohort was stratified by maternal BMI, in women with BMI ≥ 25 kg/m(2), the AGTR2 C4599A AA genotype in mothers and neonates was associated with an increased risk for preeclampsia compared with the CC genotype [adjusted OR 2.1 (95% CI 1.0-4.2) and adjusted OR 3.0 (95% CI 1.4-6.4), respectively]. In the same subset of women, paternal AGTR2 C4599A A allele was associated with an increased risk for preeclampsia and uterine artery bilateral notching at 20 weeks' gestation compared with the C allele [adjusted OR 1.9 (95% CI 1.1-3.3) and adjusted OR 2.1 (95% CI 1.3-3.4), respectively].ConclusionAGTR2 C4599A in mothers, fathers and babies was associated with preeclampsia and this association was only apparent in pregnancies in which the women had a BMI ≥ 25 kg/m(2), suggesting a gene-environment interaction.A. Zhou, G.A. Dekker, E.R. Lumbers, S.Y. Lee, S.D. Thompson, L.M.E. McCowan, C.T. Robert

Predicting preterm delivery: comparison of cervicovaginal interleukin (IL)-1 beta, IL-6 and IL-8 with fetal fibronectin and cervical dilatation

Objective: To compare the cervicovaginal cytokines IL-1 beta, IL-6 and IL-8 with fetal fibronectin (fFN) and cervical dilatation in the prediction of preterm delivery. Study design: Cervicovaginal cytokine concentration and fFN status were measured in 104 women with symptoms of preterm labour and intact membranes between 24(0) and 33(6) weeks and related to delivery within 2 and 7 days, Results: A group of 18% had cervical dilatation greater than or equal to 1 cm and 18% were positive for fFN. Preterm delivery within 2 and 7 days occurred in 5 and 12%, respectively. Only IL-6 demonstrated any ability to predict delivery within 2 and 7 days (area under the ROC curve = 0.63 and 0.75, respectively). Using 35 pg/ml (75th centile) as a cut-off, IL-6 had a sensitivity and specificity of 60 and 77% for predicting delivery within 2 days, and 62 and 80% for predicting delivery within 7 days. This is similar to the performance of cervical dilatation or fFN status. Conclusions: Measurement of cervicovaginal cytokines has limited ability to predict imminent delivery apart from cervicovaginal IL-6 concentrations, which, in this population, is equivalent to that of fFN status and cervical dilatation greater than or equal to 1 cm. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved

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

Published: 4 June 2020Small-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.Rhodi E. Bulloch, Clare R. Wall, Lesley M. E. McCowan, Rennae S. Taylor, Claire T. Roberts and John M. D. Thompso

A randomised controlled demonstration trial of multifaceted nutritional intervention and or probiotics: the healthy mums and babies (HUMBA) trial

Background: Maternal obesity is associated with adverse pregnancy outcomes and has lifelong negative implications for offspring health. The Institute of Medicine recommends limited gestational weight gain (GWG) in obese women for optimal maternal and infant outcomes. However, there is a gap regarding an effective and sustainable intervention strategy to achieve this goal. The aim of the healthy mums and babies (HUMBA) demonstration trial is to assess whether a multifaceted nutritional intervention and/or an oral probiotic treatment in obese pregnant women can reduce excessive GWG and optimise pregnancy outcomes. Methods and design: The study is a two by two factorial randomised controlled demonstration trial conducted in Counties Manukau health region, New Zealand, a multi-ethnic region with a high prevalence of obesity. A total of 220 non-diabetic obese women with a singleton pregnancy will be recruited between 120 and 176 weeks. At recruitment, women are randomised to receive either a culturally tailored multifaceted dietary intervention or routine dietary advice, and either an oral probiotic or placebo capsule. Randomisation is undertaken via a web-based protocol, randomize.net, with a 1:1 ratio using stratification by body mass index (BMI) category (BMI of 30-34.9 or BMI ≥35 kg/m2). The dietary intervention includes 4 customised nutrition education visits by a trained community health worker combined with motivational text messaging. Probiotic capsules consist of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 at a dose of 7 × 109 colony-forming units one per day until birth. Probiotic and placebo capsules are identically pre-packed and labelled by a third party, and are prescribed in a double blinded fashion. Research assessments are conducted at enrolment, 28 weeks, 36 weeks, at birth and at 5 months post-delivery. The primary outcomes for the study are proportion of women with excessive GWG and infant birthweight. Discussion: The HUMBA demonstration trial will assess the efficacy of a culturally tailored multifaceted dietary intervention and probiotic treatment in limiting excessive GWG and optimising birthweight in a multiethnic sample of obese pregnant women. If successful, either one or both of the interventions may be incorporated into future studies powered to investigate important pregnancy outcomes. Australian New Zealand Clinical Trials Registry registration number: Trial registration ACTRN12615000400561 , Universal Trial Number: U1111-1155-0409. Date registered: 29th April 2015.Karaponi Okesene-Gafa, Minglan Li, Rennae S. Taylor, John M. D. Thompson, Caroline A. Crowther, Christopher J. D. McKinlay and Lesley M. E. McCowa

Concentrations of activin A, inhibin A and follistatin in human amnion, choriodecidual and placental tissues at term and preterm

To investigate labour-associated changes in production of activin and related hormones by gestational tissues we prepared extracts from amnion, choriodecidual and placental tissues delivered at term before labour (TNL; n=15), at term after spontaneous labour (TSL; n=15) or preterm (PTD; n=31) and measured concentrations of inhibin A, activin A and follistatin by ELISA. Activin concentrations in placental tissues were significantly (Mann-Whitney U-test;

La gestion des données avec le logiciel V. M. S.

Objectives To compare pregnancy outcomes between women who stopped smoking in early pregnancy and those who either did not smoke in pregnancy or continued to smoke. Design Prospective cohort study. Setting Auckland, New Zealand and Adelaide, Australia. Participants 2504 nulliparous women participating in the Screening for Pregnancy Endpoints (SCOPE) study grouped by maternal smoking status at 15 (±1) week’s gestation. Main outcome measures Spontaneous preterm birth and small for gestational age infants (birth weight &lt;10th customised centile). We compared odds of these outcomes between stopped smokers and non-smokers, and between current smokers and stopped smokers, using logistic regression, adjusting for demographic and clinical risk factors. Results 80% (n=1992) of women were non-smokers, 10% (n=261) had stopped smoking, and 10% (n=251) were current smokers. We noted no differences in rates of spontaneous preterm birth (4%, n=88 v 4%, n=10; adjusted odds ratio 1.03, 95% confidence interval l0.49 to 2.18; P=0.66) or small for gestational age infants (10%, n=195 v 10%, n=27; 1.06, 0.67 to 1.68; P=0.8) between non-smokers and stopped smokers. Current smokers had higher rates of spontaneous preterm birth (10%, n=25 v 4%, n=10; 3.21, 1.42 to 7.23; P=0.006) and small for gestational age infants (17%, n=42 v 10%, n=27; 1.76, 1.03 to 3.02; P=0.03) than stopped smokers. Conclusion In women who stopped smoking before 15 weeks’ gestation, rates of spontaneous preterm birth and small for gestational age infants did not differ from those in non-smokers, indicating that these severe adverse effects of smoking may be reversible if smoking is stopped early in pregnancy. <br/

Effect of antenatal dietary interventions in maternal obesity on pregnancy weight-gain and birthweight: Healthy Mums and Babies (HUMBA) randomized trial

Background: Pregnancy interventions that improve maternal and infant outcomes are urgently needed in populations with high rates of obesity. We undertook the Healthy Mums and Babies (HUMBA) randomized controlled trial to assess the effect of dietary interventions and or probiotics in a multiethnic population of pregnant women with obesity, living in an area of high deprivation. Objectives: To determine whether a culturally tailored dietary intervention and or daily probiotic capsules in pregnant women with obesity reduces the co-primary outcomes of (1) excessive gestational weight gain (mean >0.27 kg/week) and (2) birthweight. Study Design: We conducted a 2 × 2 factorial, randomized controlled trial in women without diabetes at pregnancy booking, body mass index ≥30 kg/m2, and a singleton pregnancy. At 12+0 to 17+6 weeks' gestation, eligible women were randomized to a dietary intervention (4 tailored educational sessions at ≤28 weeks' gestation by a community health worker trained in key aspects of pregnancy nutrition plus text messaging until birth) or to routine dietary advice; and to daily capsules containing either (Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12, minimum 6.5 × 109 colony forming units), or placebo, until birth. Analysis was by intention to treat with adjustment for maternal baseline body mass index. Infant outcomes were additionally adjusted for ethnicity, sex, and gestational age at birth. Results: In total, 230 women were recruited between April 2015 and June 2017 (dietary intervention N = 116 vs routine dietary advice N = 114; probiotics N = 115 vs placebo N = 115). Baseline characteristics and demographic variables were similar across all groups. There was no significant difference between intervention groups, for the co-primary outcomes of (1) proportion of women with excessive gestational weight gain (dietary intervention vs routine advice: 79/107 [73.8%] vs 90/110 [81.8%], adjusted relative risk [relative risk, 0.92; 95% confidence interval, 0.80-1.05]; probiotics versus placebo: 89/108 [82.4%] and 80/109 [73.4%], relative risk, 1.14, 95% confidence interval, 0.99-1.31) or (2) birthweight (dietary intervention vs routine advice: 3575 vs 3612 g, adjusted mean difference, -24 g, 95% confidence interval, -146 to 97; probiotics vs placebo: 3685 vs 3504 g, adjusted mean difference, 107 g, 95% confidence interval, -14 to 228). Total maternal weight gain, a secondary outcome, was lower with dietary intervention compared with routine dietary advice (9.7 vs 11.4 kg, adjusted mean difference, -1.76, 95% confidence interval, -3.55 to 0.03). There were no significant differences between intervention groups in other secondary maternal or neonatal outcomes. Conclusion: Although dietary education and or probiotics did not alter rates of excessive gestational weight gain or birthweight in this multiethnic, high-deprivation population of pregnant women with obesity, dietary education was associated with a modest reduction in total weight gain with potential future benefit for the health of mothers and their offspring if sustained.Karaponi A.M. Okesene-Gafa, Minglan Li, Christopher J.D. McKinlay, Rennae S. Taylor, Elaine C. Rush, Clare R. Wall, Jess Wilson, Rinki Murphy, Rachael Taylor, John M.D. Thompson, Caroline A. Crowther, Lesley M.E. McCowa