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.

The impact of CREBRF rs373863828 Pacific-variant on infant body composition.

In Maori and Pacific adults, the CREBRF rs373863828 minor (A) allele is associated with increased body mass index (BMI) but reduced incidence of type-2 and gestational diabetes mellitus. In this prospective cohort study of Maori and Pacific infants, nested within a nutritional intervention trial for pregnant women with obesity and without pregestational diabetes, we investigated whether the rs373863828 A allele is associated with differences in growth and body composition from birth to 12-18 months' corrected age. Infants with and without the variant allele were compared using generalised linear models adjusted for potential confounding by gestation length, sex, ethnicity and parity, and in a secondary analysis, additionally adjusted for gestational diabetes. Carriage of the rs373863828 A allele was not associated with altered growth and body composition from birth to 6 months. At 12-18 months, infants with the rs373863828 A allele had lower whole-body fat mass [FM 1.4 (0.7) vs. 1.7 (0.7) kg, aMD -0.4, 95% CI -0.7, 0.0, P = 0.05; FM index 2.2 (1.1) vs. 2.6 (1.0) kg/m2 aMD -0.6, 95% CI -1.2,0.0, P = 0.04]. However, this association was not significant after adjustment for gestational diabetes, suggesting that it may be mediated, at least in part, by the beneficial effect of CREBRF rs373863828 A allele on maternal glycemic status.

Use of healthcare resources and family planning methods 12 months after birth in women of South Auckland: The Healthy Mums and Babies (HUMBA) randomised trial.

AIM: To report the utilisation of healthcare and family planning methods by participants in the Healthy Mums and Babies (HUMBA) trial at 12 months postpartum. METHODS: Surveys on access to 1) healthcare, and 2) family planning methods were completed 1 year following birth by a sample of multi-ethnic women with obesity in South Auckland, New Zealand. RESULTS: One hundred and twenty-seven out of two hundred and thirty (55.2%) HUMBA participants completed the surveys. All babies and 99% of the mothers were enrolled with a general practitioner (GP) and over 60% also accessed community or hospital emergency departments. One hundred and twelve (88.2%) used Plunket as their Well Child provider. A discussion on family planning/contraception during or after pregnancy occurred for 123/127 (96.9%) but only 74/127 (58.3%) had family planning/contraception provided after birth. Of the 53 who did not have a family planning/contraception method arranged, 20 (37.7%) did not believe in them. Factors that participants felt would assist access to family planning/contraception services included home visits, weekend or after-hour clinics and a local or mobile clinic. CONCLUSIONS: In this South Auckland population, engagement with primary healthcare and Well Child health providers was almost universal. Family planning/contraception discussions during or after pregnancy were done well. However, provision of family planning/contraception services postpartum could be improved.

Modification of maternal late pregnancy sleep position: a survey evaluation of a New Zealand public health campaign.

INTRODUCTION: A 'Sleep-On-Side When Baby's Inside' public health campaign was initiated in New Zealand in 2018. This was in response to evidence that maternal supine going-to-sleep position was an independent risk factor for stillbirth from 28 weeks' gestation. We evaluated the success of the campaign on awareness and modification of late pregnancy going-to-sleep position through nationwide surveys. METHODS AND ANALYSIS: Two web-based cross-sectional surveys were conducted over 12 weeks in 2019-2020 in a sample of (1) pregnant women ≥28 weeks, primary outcome of going-to-sleep position; and (2) health professionals providing pregnancy care, primary outcome of knowledge of going-to-sleep position and late stillbirth risk. Univariable logistic regression was performed to identify factors associated with supine going-to-sleep position. DISCUSSION: The survey of pregnant women comprised 1633 eligible participants. Going-to-sleep position last night was supine (30, 1.8%), non-supine (1597, 97.2%) and no recall (16, 1.0%). Supine position had decreased from 3.9% in our previous New Zealand-wide study (2012-2015). Most women (1412, 86.5%) had received sleep-on-side advice with no major resultant worry (1276, 90.4%). Two-thirds (918, 65.0%) had changed their going-to-sleep position based on advice, with most (611 of 918, 66.5%) reporting little difficulty. Supine position was associated with Maori (OR 5.05, 95% CI 2.10 to 12.1) and Asian-non-Indian (OR 4.20, 95% CI 1.27 to 13.90) ethnicity; single (OR 10.98, 95% CI 4.25 to 28.42) and cohabitating relationship status (OR 2.69, 95% CI 1.09 to 6.61); hospital-based maternity provider (OR 2.55, 95% CI 1.07 to 6.10); education overseas (OR 3.92, 95% CI 1.09 to 14.09) and primary-secondary level (OR 2.80, 95% CI 1.32 to 6.08); and not receiving sleep-on-side advice (OR 6.70, 95% CI 3.23 to 13.92). The majority of health professionals (709 eligible participants) reported awareness of supine going-to-sleep position and late stillbirth risk (543, 76.6%). CONCLUSION: Most pregnant women had received and implemented sleep-on-side advice without major difficulty or concern. Some groups of women may need a tailored approach to acquisition of going-to-sleep position information.

Case-control study of prolactin and placental lactogen in SGA pregnancies.

Prolactin and placental lactogens increase during pregnancy and are involved with many aspects of maternal metabolic adaptation to pregnancy, likely to impact on fetal growth. The aim of this study was to determine whether maternal plasma prolactin or placental lactogen concentrations at 20 weeks of gestation were associated with later birth of small-for-gestational-age babies (SGA). In a nested case-control study, prolactin and placental lactogen in plasma samples obtained at 20 weeks of gestation were compared between 40 women who gave birth to SGA babies and 40 women with uncomplicated pregnancies and size appropriate-for-gestation-age (AGA) babies. Samples were collected as part of the 'screening of pregnancy endpoints' (SCOPE) prospective cohort study. SGA was defined as birthweight <10th customized birthweight centile (adjusted for maternal weight, height, ethnicity, parity, infant sex, and gestation age) in mothers who remained normotensive. No significant differences were observed in concentrations of prolactin or placental lactogen from women who gave birth to SGA babies compared with women with uncomplicated pregnancies. However, a sex-specific association was observed in SGA pregnancies, whereby lower maternal prolactin concentration at 20 weeks of gestation was observed in SGA pregnancies that were carrying a male fetus (132.0 ± 46.7 ng/mL vs 103.5 ± 38.3 ng/mL, mean ± s.d., P = 0.036 Student's t-test) compared to control pregnancies carrying a male fetus. Despite the implications of these lactogenic hormones in maternal metabolism, single measurements of either prolactin or placental lactogen at 20 weeks of gestation are unlikely to be useful biomarkers for SGA pregnancies. LAY SUMMARY: Early identification during pregnancy of small for gestational age (SGA) babies would enable interventions to lower risk of complications around birth (perinatal), but current detection rates of these at risk babies is low. Pregnancy hormones, prolactin and placental lactogen, are involved in metabolic changes that are required for the mother to support optimal growth and development of her offspring during pregnancy. The levels of these hormones may provide a measurable indicator (biomarker) to help identify these at risk pregnancies. Levels of these hormones were measured in samples from week 20 of gestation from women who went on to have SGA babies and control pregnancies where babies were born at a size appropriate for gestation age. Despite the implications of prolactin and placental lactogen in maternal metabolism, no significant differences were detected suggesting that single measures of either prolactin or placental lactogen at 20 weeks gestation are unlikely to be useful biomarker to help detect SGA pregnancies.

Detection of small for gestational age babies and perinatal outcomes following implementation of the Growth Assessment Protocol at a New Zealand tertiary facility: An observational intervention study.

BACKGROUND: Timely detection of small for gestational age (SGA) fetuses is important for reducing severe perinatal morbidity and mortality, and better tools are needed to detect SGA in maternity care. AIM: We evaluated the effect of the introduction of the Perinatal Institute's Growth Assessment Protocol (GAP) in the Counties Manukau Health region, South Auckland, New Zealand, on antenatal detection of SGA and maternal and perinatal outcomes. MATERIALS AND METHODS: Uncontrolled before and after study in women booked under hospital community midwife care with a singleton, non-anomalous pregnancy. Antenatal detection of SGA (birthweight <10th customised centile) was compared pre-GAP (2012, N = 1105) and post-GAP (2017, N = 1082). Composite adverse neonatal outcome was defined as neonatal unit admission >48 h, five-minute Apgar score <7, and/or any ventilation. Analyses were adjusted for maternal age, body mass index, deprivation, smoking and ethnicity. RESULTS: SGA rates were similar across epochs (13.8% vs 12.9%) but antenatal detection of SGA increased from 22.9% (35/153) to 57.9% (81/140) post-GAP (adjusted odds ratio (aOR) = 4.8, 95% CI 2.82-8.18). Rates of induction of labour and caesarean section increased between epochs but were similar in SGA, non-SGA, and detected and non-detected SGA subgroups. Among SGA babies, there was some evidence that antenatal detection of SGA may be associated with lower composite adverse neonatal outcome (detected SGA: aOR 0.44 95% CI 0.17-1.15; non-detected SGA: aOR = 1.81 95% CI 0.73-4.48; interaction P = 0.03). Pre-term birth did not appear to be influenced by GAP. CONCLUSION: Implementation of GAP was associated with a nearly five-fold increase in SGA detection without increasing obstetric intervention for SGA.

The Pacific-specific CREBRF rs373863828 allele protects against gestational diabetes mellitus in Maori and Pacific women with obesity.

AIMS/HYPOTHESIS: The CREBRF rs373863828 minor (A) allele is associated with increased BMI but reduced prevalence of type 2 diabetes in Maori and Pacific people. Given the shared aetiology of type 2 diabetes and gestational diabetes mellitus (GDM), we tested for an association between the CREBRF rs373863828 variant and GDM. METHODS: We conducted a prospective cohort study of Maori and Pacific women nested within a nutritional intervention study for pregnant women with obesity. Women were enrolled at 12-17 weeks' gestation and underwent anthropometry and collection of buffy coats for later genetic testing. GDM was diagnosed by 75 g OGTT at 24-28 weeks' gestation using the International Association of Diabetes and Pregnancy Study Groups criteria. Genotyping was performed by real-time PCR with a custom CREBRF rs373863828 probe-set. The association between CREBRF rs373863828 and GDM was analysed separately by ethnic group using logistic regression, with effect estimates combined in a meta-analysis. RESULTS: Of 112 Maori and Pacific pregnant women with obesity, 31 (28%) carried the CREBRF rs373863828 A allele (A/G or A/A) and 35 (31%) developed GDM. Women who carried the CREBRF rs373863828 A allele did not differ in BMI when compared with non-carriers (G/G). There was a fivefold reduction in the likelihood of GDM per CREBRF rs373863828 A allele (OR 0.19 [95% CI 0.05, 0.69], p = 0.01), independent of age, BMI and family history of diabetes (adjusted OR 0.13 [95% CI 0.03, 0.53], p = 0.004). GDM was diagnosed in 10% and 40% of women with and without the CREBRF rs373863828 A allele, respectively (no woman with the A/A genotype developed GDM). CONCLUSIONS/INTERPRETATION: The CREBRF rs373863828 (A) allele is associated with reduced likelihood of GDM in Maori and Pacific women with obesity and may improve GDM risk prediction. Graphical abstract.

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

BACKGROUND: Small-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. AIM: The 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 DESIGN: Women 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. SUBJECTS: Nulliparous women with singleton pregnancies. OUTCOME MEASURES: SGA (<10th customised birthweight centile). RESULTS: 5606 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 (ß 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. CONCLUSIONS: In 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.

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.

An analysis of omega-3 fatty acid status in a population of pregnant women with obesity, at higher risk of preterm birth.

An updated Cochrane Review showed that maternal supplementation with omega-3 fatty acids reduced preterm birth, offering a potential strategy for prevention. We hypothesised that pregnant women with obesity, at higher risk of preterm birth, would have low omega-3 fatty acid levels and may benefit from supplementation. Our study measured the omega-3 fatty acid levels of 142 participants from the Healthy Mums and Babies study, Counties Manukau, Auckland, New Zealand. Counties Manukau is a multi-ethnic community with high rates of socio-economic deprivation, obesity, and preterm birth. Red blood cell omega-3 fatty acid levels were measured from samples collected between 120 and 176 weeks' gestation. Contrary to our hypothesis, participants in our study had similar or higher levels of omega-3 fatty acids to those reported in pregnant populations in Australia, Norway, China, and Germany. Our findings emphasise the importance of testing omega-3 fatty acid status before supplementing groups at risk of preterm birth.

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.

How Do Home and Clinic Blood Pressure Readings Compare in Pregnancy?

Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure (BP) might improve the detection and management of hypertensive disorders of pregnancy, but few data are available, including regarding appropriate thresholds. This systematic review and individual patient data analysis aimed to assess the current evidence on differences between clinic and self-monitored BP through pregnancy. MEDLINE and 10 other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature on self-monitoring of BP during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic BP and demographic data. Twenty-one studies that utilized self-monitoring of BP during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from 7 plus 1 unpublished articles (8 studies; n=758) and 2 further studies published summary data. Analysis revealed a mean self-monitoring clinic difference of ≤1.2 mm Hg systolic BP throughout pregnancy although there was significant heterogeneity (difference in means, I2 >80% throughout pregnancy). Although the overall population difference was small, levels of white coat hypertension were high, particularly toward the end of pregnancy. The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds.

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

In our 'Primary Outcomes' we made a typographical error [1]; the mean weekly weight gain should read >0.27 kg instead of >0.22 kg. The 'Primary Outcomes' should read as follows.

Accuracy of point-of-care HbA1c testing in pregnant women.

BACKGROUND: In New Zealand, it is recommended that all pregnant women have a haemoglobin A1c (HbA1c) test performed with their booking antenatal bloods to identify previously unrecognised diabetes. However, screening rates in some groups are low. Use of a point-of-care device may improve compliance with screening. AIM: To assess the accuracy of the COBAS b101 point-of-care system referenced against a laboratory method, for measurement of HbA1c levels in pregnant women. MATERIALS AND METHODS: Convenience sample of 40 obese pregnant women enrolled in a clinical trial. HbA1c was assayed in paired capillary and venous whole blood samples using the COBAS b101 point-of-care system and Primus Ultra2 high performance liquid chromatography laboratory analyser, respectively. The accuracy of the point-of-care system was assessed by Bland-Altman analysis. RESULTS: The mean (SD) laboratory HbA1c was 35.9 (2.0) mmol/mol. The COBAS b101 point-of-care system, compared with the laboratory reference method, had a small negative bias for HbA1c (-1.0 mmol/mol, 95% CI -2.0 to -0.03, P = 0.03) and relatively wide 95% limits of agreement (-7.2 to 5.1 mmol/mol). CONCLUSION: In conclusion, we found that in pregnancy, the COBAS b101 point-of-care system has a small negative bias and modest point accuracy for HbA1c. When used to screen for previously unrecognised diabetes in pregnancy, appropriate COBAS b101 HbA1c point-of-care HbA1c thresholds for a negative and positive result are 7 mmol/mol below and 5 mmol/mol above the clinical threshold, respectively. Values between these limits should be confirmed by laboratory testing.

Maternal serum placental growth hormone, insulin-like growth factors and their binding proteins at 20 weeks' gestation in pregnancies complicated by gestational diabetes mellitus.

OBJECTIVE: To investigate whether maternal serum concentrations of placental growth hormone (GH-V), insulin-like growth factor (IGF) 1 and 2, and IGF binding proteins (IGFBP) 1 and 3 were altered in pregnancies complicated by gestational diabetes mellitus (GDM). METHOD: In a nested case-control study, GDM cases (n=28) and matched controls (n=28) were selected from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Maternal serum hormone concentrations at 20 weeks of gestation were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no significant difference in maternal serum GH-V concentration in the GDM group compared to the control group (1.64 ± 0.11 ng/ml vs. 1.38 ± 0.10 ng/ml, p=0.079). However, GDM cases who delivered large for gestational age (LGA) babies had significantly higher serum GH-V concentrations compared to non-diabetic control cases. Maternal IGF-1 concentrations in GDM pregnancies were significantly higher than in controls (275.7 ± 11.5 ng/ml vs. 218.5 ± 11.1 ng/ml, p <0.001). Maternal IGFBP-1 concentrations were significantly lower in GDM pregnancies than in controls (41.04 ± 3.42 ng/ml vs. 67.58 ± 6.17 ng/ml, p <0.001). There were no significant differences in serum IGF-2 and IGFBP-3 concentrations between groups. CONCLUSION: Concentrations of IGF-1 and IGFBP-1 in maternal serum were altered in GDM pregnancies compared to controls, suggesting that the IGF axis plays a role in the development of this condition. GH-V may be associated with macrosomia as increased maternal GH-V was observed in GDM cases who delivered LGA babies.

Maternal serum IGF-1, IGFBP-1 and 3, and placental growth hormone at 20weeks' gestation in pregnancies complicated by preeclampsia.

OBJECTIVE: To investigate whether maternal serum concentrations of placental growth hormone (GH-V), insulin-like growth factor (IGF) 1 and 2, and IGF binding proteins (IGFBP) 1 and 3 were altered in pregnancies complicated by later preeclampsia (PE). STUDY DESIGN: In a nested case-control study, PE cases (n=71) and matched controls (n=71) were selected from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Maternal serum hormone concentrations at 20weeks of gestation were determined by ELISA. RESULTS: We found that maternal serum GH-V concentration at 20weeks of gestation was unaltered in the PE group, compared to the control group (median, 1.78ng/ml vs. 1.65ng/ml, p=0.884). Maternal IGF-1 and IGFBP-3 concentrations and the IGF-1/IGFBP-3 ratio in PE pregnancies were significantly higher than in controls (median, 253.1ng/ml vs. 204.3ng/ml, p<0.0001; 8535ng/ml vs. 7711ng/ml, p=0.0023; 0.032vs. 0.026, p<0.0001, respectively), whereas maternal IGFBP-1 concentration was significantly lower in PE pregnancies than in controls (median, 34.85ng/ml vs. 48.92ng/ml, p=0.0006). CONCLUSION: Our findings suggest a potential role of IGFs and IGFBPs in the prediction of pregnancies complicated by PE. However, the maternal serum concentration of GH-V at 20weeks' gestation is unlikely to be useful in the early prediction of PE.

Survey of maternal sleep practices in late pregnancy in a multi-ethnic sample in South Auckland, New Zealand.

BACKGROUND: The Auckland Stillbirth study demonstrated a two-fold increased risk of late stillbirth for women who did not go to sleep on their left side. Two further studies have confirmed an increased risk of late stillbirth with supine sleep position. As sleep position is modifiable, we surveyed self-reported late pregnancy sleep position, knowledge about sleep position, and views about changing going-to-sleep position. METHODS: Participants in this 2014 survey were pregnant women (n = 377) in their third trimester from South Auckland, New Zealand, a multi-ethnic and predominantly low socio-economic population. An ethnically-representative sample was obtained using random sampling. Multivariable logistic regression was performed to identify factors independently associated with non-left sided going-to-sleep position in late pregnancy. RESULTS: Respondents were 28 to 42 weeks' gestation. Reported going-to-sleep position in the last week was left side (30%), right side (22%), supine (3%), either side (39%) and other (6%). Two thirds (68%) reported they had received advice about sleep position. Non-left sleepers were asked if they would be able to change to their left side if it was better for their baby; 87% reported they would have little or no difficulty changing. Women who reported a non-left going-to-sleep position were more likely to be of Maori (aOR 2.64 95% CI 1.23-5.66) or Pacific (aOR 2.91 95% CI 1.46-5.78) ethnicity; had a lower body mass index (BMI) (aOR 0.93 95% CI 0.89-0.96); and were less likely to sleep on the left-hand side of the bed (aOR 3.29 95% CI 2.03-5.32). CONCLUSIONS: Maternal going-to-sleep position in the last week was side-lying in 91% of participants. The majority had received advice to sleep on their side or avoid supine sleep position. Sleeping on the left-hand side of the bed was associated with going-to-sleep on the left side. Most non-left sleepers reported their sleeping position could be modified to the left side suggesting a public health intervention about sleep position is likely to be feasible in other multi-ethnic communities.

Maternal plasma miRNAs as biomarkers during mid-pregnancy to predict later spontaneous preterm birth: a pilot study.

More than 10% of babies are born too early resulting in over 15 million preterm births and more than one million new-born deaths globally. Although women with a previous spontaneous preterm birth (SPTB) are considered at high risk for recurrence, the majority occur in women without prior history. Prediction of SPTB risk allows for improved care and potential for targeting novel and existing therapeutics to prevent SPTB, which may result in improved outcomes for infant and mother. In this pilot study, a miRNA array was used to analyse plasma from healthy women in their first pregnancy at 20 weeks of gestation who then went on to deliver either at term or experience SPTB at 28-32 weeks. We identified specific miRNA expression profiles that differentiated between those mothers who delivered at term or delivered following SPTB. miR302b, miR1253 and a clustering of miR548 miRNAs were underexpressed in SPTB cases compared to term controls. Conversely, miR223 was elevated in mothers that later experienced a SPTB. The circulating miRNAs identified in the present study may therefore be attractive candidates as non-invasive biomarkers for the early prediction of SPTB. Further larger studies are now warranted to investigate the potential clinical utility of these markers.

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers.

OBJECTIVE: Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks' with ultrasound parameters at 20±1 weeks' gestation. METHODS: Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve. RESULTS: 633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks' clinical variables, 15±1 weeks' clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks' were: 0.63 (0.59-0.67), 0.64 (0.60-0.68) and 0.69 (0.66-0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57-0.66), 0.61 (0.56-0.66) and 0.68 (0.64-0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70-0.82), 0.80 (0.75-0.86) and 0.84 (0.78-0.89) with minimal change in the Training datasets. CONCLUSION: Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry.