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.

Impact of Gestational Diabetes Detection Thresholds on Infant Growth and Body Composition: A Prospective Cohort Study Within a Randomized Trial.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with offspring metabolic disease, including childhood obesity, but causal mediators remain to be established. We assessed the impact of lower versus higher thresholds for detection and treatment of GDM on infant risk factors for obesity, including body composition, growth, nutrition, and appetite. RESEARCH DESIGN AND METHODS: In this prospective cohort study within the Gestational Diabetes Mellitus Trial of Diagnostic Detection Thresholds (GEMS), pregnant women were randomly allocated to detection of GDM using the lower criteria of the International Association of Diabetes and Pregnancy Study Groups or higher New Zealand criteria (ACTRN12615000290594). Randomly selected control infants of women without GDM were compared with infants exposed to A) GDM by lower but not higher criteria, with usual treatment for diabetes in pregnancy; B) GDM by lower but not higher criteria, untreated; or C) GDM by higher criteria, treated. The primary outcome was whole-body fat mass at 5-6 months. RESULTS: There were 760 infants enrolled, and 432 were assessed for the primary outcome. Fat mass was not significantly different between control infants (2.05 kg) and exposure groups: A) GDM by lower but not higher criteria, treated (1.96 kg), adjusted mean difference (aMD) -0.09 (95% CI -0.29, 0.10); B) GDM by lower but not higher criteria, untreated (1.94 kg), aMD -0.15 (95% CI -0.35, 0.06); and C) GDM detected and treated using higher thresholds (1.87 kg), aMD -0.17 (95% CI -0.37, 0.03). CONCLUSIONS: GDM detected using lower but not higher criteria, was not associated with increased infant fat mass at 5-6 months, regardless of maternal treatment. GDM detected and treated using higher thresholds was also not associated with increased fat mass at 5-6 months.

A validation of placental pathology reports by ethnicity in New Zealand, through systematic analysis of histological slides.

INTRODUCTION: Reliability studies of placental examination have shown differing interobserver agreement for certain pathological features, a lack of uniform reporting criteria and variable experience among pathologists. In previous analyses we have shown that placental pathology differs by ethnicity. This validation study was performed to investigate whether bias related to ethnicity is a feature of placental pathology reporting in New Zealand (NZ). METHODS: 199 of 1726 eligible perinatal death cases between 2008 and 2017 were selected at random for this audit-type study, including 51 cases from South Asian, Maori and NZ European ethnicity and 46 cases from Pacific mothers. Stored histology slides were blinded and re-examined by an experienced perinatal pathologist, and linked to the corresponding original pathology report. Interobserver agreement (overall, by ethnicity and by gestational age) was described by proportional differences and kappa coefficients. RESULTS: Total interobserver agreement between original placental reporting and the validation review was 89.7 %, which differed by pathological feature. There was generally more underreporting than overreporting (3.6 % and 6.7 %, respectively). There was little disagreement by ethnicity (decidual vasculopathy [p = 0.03]), although there were more differences by gestational age (villous morphology [p < 0.01], chorioamnionitis [p = 0.03], high-grade villitis of unknown etiology [p < 0.01], and placental haemorrhage [p = 0.03]). DISCUSSION: No systematic bias in placental pathology reporting in NZ was identified by ethnicity or gestational age, as observed differences could be related to the underlying prevalence of pathology. We identified more underreporting than overreporting of pathology in the original reports, emphasizing the importance of placental investigation by specialised perinatal pathologists.

Does fetal size affect maternal perception of fetal movements? Evidence from an individual participant data meta-analysis.

INTRODUCTION: Maternal perception of fetal movements during pregnancy are reassuring; however, the perception of a reduction in movements are concerning to women and known to be associated with increased odds of late stillbirth. Prior to full term, little evidence exists to provide guidelines on how to proceed unless there is an immediate risk to the fetus. Increased strength of movement is the most commonly reported perception of women through to full term, but perception of movement is also hypothesized to be influenced by fetal size. The study aimed to assess the pattern of maternal perception of strength and frequency of fetal movement by gestation and customized birthweight quartile in ongoing pregnancies. A further aim was to assess the association of stillbirth to perception of fetal movements stratified by customized birthweight quartile. MATERIAL AND METHODS: This analysis was an individual participant data meta-analyses of five case-control studies investigating factors associated with stillbirth. The dataset included 851 cases of women with late stillbirth (>28 weeks' gestation) and 2257 women with ongoing pregnancies who then had a liveborn infant. RESULTS: The frequency of prioritized fetal movement from 28 weeks' gestation showed a similar pattern for each quartile of birthweight with increased strength being the predominant perception of fetal movement through to full term. The odds of stillbirth associated with reduced fetal movements was increased in all quartiles of customized birthweight centiles but was notably greater in babies in the lowest two quartiles (Q1: adjusted OR: 9.34, 95% CI: 5.43, 16.06 and Q2: adjusted OR: 6.11, 95% CI: 3.11, 11.99). The decreased odds associated with increased strength of movement was present for all customized birthweight quartiles (adjusted OR range: 0.25-0.56). CONCLUSIONS: Increased strength of fetal movements in late pregnancy is a positive finding irrespective of fetal size. However, reduced fetal movements are associated with stillbirth, and more so when the fetus is small.

An in-depth analysis of perinatal related mortality among women of South Asian ethnicity in Aotearoa New Zealand.

BACKGROUND: International and national New Zealand (NZ) research has identified women of South Asian ethnicity at increased risk of perinatal mortality, in particular stillbirth, with calls for increased perinatal research among this ethnic group. We aimed to analyse differences in pregnancy outcomes and associated risk factors between South Asian, Maori, Pacific and NZ European women in Aotearoa NZ, with a focus on women of South Asian ethnicity, to ultimately understand the distinctive pathways leading to adverse events. METHODS: Clinical data from perinatal deaths between 2008 and 2017 were provided by the NZ Perinatal and Maternal Mortality Review Committee, while national maternity and neonatal data, and singleton birth records from the same decade, were linked using the Statistics NZ Integrated Data Infrastructure for all births. Pregnancy outcomes and risk factors for stillbirth and neonatal death were compared between ethnicities with adjustment for pre-specified risk factors. RESULTS: Women of South Asian ethnicity were at increased risk of stillbirth (aOR 1.51, 95%CI 1.29-1.77), and neonatal death (aOR 1.51, 95%CI 1.17-1.92), compared with NZ European. The highest perinatal related mortality rates among South Asian women were between 20-23 weeks gestation (between 0.8 and 1.3/1,000 ongoing pregnancies; p < 0.01 compared with NZ European) and at term, although differences by ethnicity at term were not apparent until ≥ 41 weeks (p < 0.01). No major differences in commonly described risk factors for stillbirth and neonatal death were observed between ethnicities. Among perinatal deaths, South Asian women were overrepresented in a range of metabolic-related disorders, such as gestational diabetes, pre-existing thyroid disease, or maternal red blood cell disorders (all p < 0.05 compared with NZ European). CONCLUSIONS: Consistent with previous reports, women of South Asian ethnicity in Aotearoa NZ were at increased risk of stillbirth and neonatal death compared with NZ European women, although only at extremely preterm (< 24 weeks) and post-term (≥ 41 weeks) gestations. While there were no major differences in established risk factors for stillbirth and neonatal death by ethnicity, metabolic-related factors were more common among South Asian women, which may contribute to adverse pregnancy outcomes in this ethnic group.

Placental pathology findings in perinatal deaths from 28 weeks gestation in Aotearoa New Zealand.

INTRODUCTION: Women of South Asian ethnicity are overrepresented in adverse pregnancy outcome across high-income countries, including those related to placental dysfunction. It has been hypothesised that placental aging occurs at earlier gestation in South Asian pregnancies. We aimed to identify differences in placental pathology among perinatal deaths ≥28 weeks gestation, between South Asian, Maori and New Zealand (NZ) European women in Aotearoa NZ, with a focus on women of South Asian ethnicity. METHODS: Placental pathology reports and clinical data from perinatal deaths between 2008 and 2017 were provided by the NZ Perinatal and Maternal Mortality Review Committee, blinded, and analysed by an experienced perinatal pathologist using the Amsterdam Placental Workshop Group Consensus Statement criteria. RESULTS: 790 of 1161 placental pathology reports, 346 preterm (28+0 to 36+6 weeks) and 444 term (≥37+0 weeks) deaths, met the inclusion criteria. Among preterm deaths, South Asian women had higher rates of maternal vascular malperfusion compared with Maori (aOR 4.16, 95%CI 1.55-11.15) and NZ European (aOR 2.60, 95%CI 1.10-6.16). Among term deaths, South Asian women had higher rates of abnormal villous morphology compared with Maori (aOR 2.19, 95%CI 1.04-4.62) and NZ European (aOR 2.12, 95%CI 1.14-3.94), mostly due to increased rates of chorangiosis (36.7%, compared to 23.3% and 21.7%, respectively). DISCUSSION: Differences in placental pathology by ethnicity were observed among preterm and term perinatal deaths. While we suspect differing underlying causal pathways, these deaths may be associated with maternal diabetic and red blood cell disorders among South Asian women, leading to a hypoxic state in-utero.

Placental pathology findings amongst extremely preterm perinatal deaths in Aotearoa New Zealand.

INTRODUCTION: Women of South Asian ethnicity are overrepresented in adverse pregnancy outcomes across high-income countries, including placental dysfunction and antepartum haemorrhage. As the burden of mortality is highest for extremely preterm infants, we aimed to identify any differences in placental pathology among perinatal deaths from 20+0 to 27+6 weeks gestation between South Asian, Maori and New Zealand (NZ) European women in Aotearoa NZ, with a focus on women of South Asian ethnicity. METHODS: Placental pathology reports and clinical data from perinatal deaths between 2008 and 2017 were provided by the NZ Perinatal and Maternal Mortality Review Committee, blinded and analysed by an experienced perinatal pathologist using the Amsterdam Placental Workshop Group Consensus Statement criteria. South Asian ethnicity was classified as Indian, Fijian Indian, South African Indian, Sri Lankan, Pakistani and Bangladeshi. RESULTS: 886 of 1571 placental pathology reports met the inclusion criteria. Women of South Asian ethnicity were significantly more likely to show features of histologic chorioamnionitis (aOR 1.87, 95%CI 1.19-2.94) and chorionic vasculitis (aOR 1.92, 95%CI 1.13-3.29), than NZ European and Maori women respectively. 13 of 15 (87%) of South Asian mothers with a diabetic disorder were identified with chorioamnionitis, compared to 1 in 5 (20%) of Maori and 5 in 12 (41%) of NZ European women. Cord hyper-coiling was also more common among South Asian pregnancies, compared to NZ European (aOR 1.98, 95%CI 1.10-3.56). DISCUSSION: Differences in placental pathology by ethnicity were observed among extremely preterm perinatal deaths. Underlying metabolic disorders and an associated pro-inflammatory environment may play an important role in the causal pathway leading to these deaths in women of South Asian ethnicity.

Risk factors for late preterm and term stillbirth: A secondary analysis of an individual participant data meta-analysis.

OBJECTIVE: Identify independent and novel risk factors for late-preterm (28-36 weeks) and term (≥37 weeks) stillbirth and explore development of a risk-prediction model. DESIGN: Secondary analysis of an Individual Participant Data (IPD) meta-analysis investigating modifiable stillbirth risk factors. SETTING: An IPD database from five case-control studies in New Zealand, Australia, the UK and an international online study. POPULATION: Women with late-stillbirth (cases, n = 851), and ongoing singleton pregnancies from 28 weeks' gestation (controls, n = 2257). METHODS: Established and novel risk factors for late-preterm and term stillbirth underwent univariable and multivariable logistic regression modelling with multiple sensitivity analyses. Variables included maternal age, body mass index (BMI), parity, mental health, cigarette smoking, second-hand smoking, antenatal-care utilisation, and detailed fetal movement and sleep variables. MAIN OUTCOME MEASURES: Independent risk factors with adjusted odds ratios (aOR) for late-preterm and term stillbirth. RESULTS: After model building, 575 late-stillbirth cases and 1541 controls from three contributing case-control studies were included. Risk factor estimates from separate multivariable models of late-preterm and term stillbirth were compared. As these were similar, the final model combined all late-stillbirths. The single multivariable model confirmed established demographic risk factors, but additionally showed that fetal movement changes had both increased (decreased frequency) and reduced (hiccoughs, increasing strength, frequency or vigorous fetal movements) aOR of stillbirth. Poor antenatal-care utilisation increased risk while more-than-adequate care was protective. The area-under-the-curve was 0.84 (95% CI 0.82-0.86). CONCLUSIONS: Similarities in risk factors for late-preterm and term stillbirth suggest the same approach for risk-assessment can be applied. Detailed fetal movement assessment and inclusion of antenatal-care utilisation could be valuable in late-stillbirth risk assessment.

A comprehensive methodology report for maternity and perinatal mortality research in the New Zealand Integrated Data Infrastructure.

AIM: The highest quality perinatal data in New Zealand is collected and collated by the Perinatal and Maternal Mortality Review Committee (PMMRC) and is made available to a limited number of researchers. Therefore, maternity, and perinatal mortality studies are generally performed on Government-held data. This report offers an alternative approach with in-depth justification for the methodology, while simultaneously improving the understanding of the data sources. METHOD: A standardised method for creating a comprehensive maternity dataset within the Statistics New Zealand Integrated Data Infrastructure (IDI) was developed and a validation dataset was created to include all births between 2008 and 2017. RESULTS: A close approximation to the PMMRC annual report data was found, with 4.0% over-reporting of perinatal deaths and 0.05% over-reporting of live births in the IDI dataset. Several variables, including important pregnancy risk factors, were validated for use. Limitations to the datasets were explored and additional tables in the IDI were proposed, to include variables on pregnancy complications, ethnicity and country of birth, and socio-economic data. CONCLUSION: This methodological report describes an opportunity for standardised, high-quality maternity research in New Zealand using the IDI, including a variety of national data sources. Recommendations for further enhancement of these resources have been offered.

A screening test proposal for congenital defects based on maternal serum metabolomics profile.

BACKGROUND: Historically, noninvasive techniques are only able to identify chromosomal anomalies that accounted for <50% of all congenital defects; the other congenital defects are diagnosed via ultrasound evaluations in the later stages of pregnancy. Metabolomic analysis may provide an important improvement, potentially addressing the need for novel noninvasive and multicomprehensive early prenatal screening tools. A growing body of evidence outlines notable metabolic alterations in different biofluids derived from pregnant women carrying fetuses with malformations, suggesting that such an approach may allow the discovery of biomarkers common to most fetal malformations. In addition, metabolomic investigations are inexpensive, fast, and risk-free and often generate high performance screening tests that may allow early detection of a given pathology. OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of an ensemble machine learning model based on maternal serum metabolomic signatures for detecting fetal malformations, including both chromosomal anomalies and structural defects. STUDY DESIGN: This was a multicenter observational retrospective study that included 2 different arms. In the first arm, a total of 654 Italian pregnant women (334 cases with fetuses with malformations and 320 controls with normal developing fetuses) were enrolled and used to train an ensemble machine learning classification model based on serum metabolomics profiles. In the second arm, serum samples obtained from 1935 participants of the New Zealand Screening for Pregnancy Endpoints study were blindly analyzed and used as a validation cohort. Untargeted metabolomics analysis was performed via gas chromatography-mass spectrometry. Of note, 9 individual machine learning classification models were built and optimized via cross-validation (partial least squares-discriminant analysis, linear discriminant analysis, naïve Bayes, decision tree, random forest, k-nearest neighbor, artificial neural network, support vector machine, and logistic regression). An ensemble of the models was developed according to a voting scheme statistically weighted by the cross-validation accuracy and classification confidence of the individual models. This ensemble machine learning system was used to screen the validation cohort. RESULTS: Significant metabolic differences were detected in women carrying fetuses with malformations, who exhibited lower amounts of palmitic, myristic, and stearic acids; N-α-acetyllysine; glucose; L-acetylcarnitine; fructose; para-cresol; and xylose and higher levels of serine, alanine, urea, progesterone, and valine (P<.05), compared with controls. When applied to the validation cohort, the screening test showed a 99.4%±0.6% accuracy (specificity of 99.9%±0.1% [1892 of 1894 controls correctly identified] with a sensitivity of 78%±6% [32 of 41 fetal malformations correctly identified]). CONCLUSION: This study provided clinical validation of a metabolomics-based prenatal screening test to detect the presence of congenital defects. Further investigations are needed to enable the identification of the type of malformation and to confirm these findings on even larger study populations.

Grouping women of South Asian ethnicity for pregnancy research in New Zealand.

BACKGROUND: The New Zealand (NZ) Ministry of Health ethnicity data protocols recommend that people of South Asian (SAsian) ethnicity, other than Indian, are combined with people of Japanese and Korean ethnicity at the most commonly used level of aggregation in health research (level two). This may not work well for perinatal studies, as it has long been observed that women of Indian ethnicity have higher rates of adverse pregnancy outcomes, such as perinatal death. It is possible that women of other SAsian ethnicities share this risk. AIMS: This study was performed to identify appropriate groupings of women of SAsian ethnicity for perinatal research. MATERIALS AND METHODS: National maternity and neonatal data, and singleton birth records between 2008 and 2017 were linked using the Statistics NZ Integrated Data Infrastructure. Socio-demographic risk profiles and pregnancy outcomes were compared between 15 ethnic groups. Recommendations were made based on statistical analyses and cultural evaluation with members of the SAsian research community. RESULTS: Similarities were observed between women of Indian, Fijian Indian, South African Indian, Sri Lankan, Bangladeshi and Pakistani ethnicities. A lower-risk profile was seen among Japanese and Korean mothers. Risk profiles of women of combined Indian-Maori, Indian-Pacific and Indian-New Zealand European ethnicity more closely represented their corresponding non-Indian ethnicities. CONCLUSIONS: Based on these findings, we suggest a review of current NZ Ministry of Health ethnicity data protocols. We recommend that researchers understand the risk profiles of participants prior to aggregation of groups in research, to mitigate risks associated with masking differences.

Fetal movements: A framework for antenatal conversations.

BACKGROUND: Presentations for decreased fetal movements comprise a significant proportion of acute antenatal assessments. Decreased fetal movements are associated with increased likelihood of adverse pregnancy outcomes including stillbirth. Consensus-based guidelines recommend pregnant women routinely receive information about fetal movements, but practice is inconsistent, and the information shared is frequently not evidence-based. There are also knowledge gaps about the assessment and management of fetal movement concerns. Women have indicated that they would like more accurate information about what to expect regarding fetal movements. DISCUSSION: Historically, fetal movement information has focussed on movement counts. This is problematic, as the number of fetal movements perceived varies widely between pregnant women, and no set number of movements has been established as a reliable indicator of fetal wellbeing. Of late, maternity care providers have also advised women to observe their baby's movement pattern, and promptly present if they notice a change. However, normal fetal movement patterns are rarely defined. Recently, a body of research has emerged relating to maternal perception of fetal movement features such as strength, presence of hiccups, and diurnal pattern as indicators of fetal wellbeing in addition to frequency. CONCLUSION: Sharing comprehensive and gestation-appropriate information about fetal movements may be more satisfying for women, empowering women to identify for themselves when their baby is doing well, and importantly when additional assessment is needed. We propose a conversational approach to fetal movement information sharing, focusing on fetal movement strength, frequency, circadian pattern, and changes with normal fetal development, tailored to the individual.

Lower versus Higher Glycemic Criteria for Diagnosis of Gestational Diabetes.

BACKGROUND: Treatment of gestational diabetes improves maternal and infant health, although diagnostic criteria remain unclear. METHODS: We randomly assigned women at 24 to 32 weeks' gestation in a 1:1 ratio to be evaluated for gestational diabetes with the use of lower or higher glycemic criteria for diagnosis. The lower glycemic criterion was a fasting plasma glucose level of at least 92 mg per deciliter (≥5.1 mmol per liter), a 1-hour level of at least 180 mg per deciliter (≥10.0 mmol per liter), or a 2-hour level of at least 153 mg per deciliter (≥8.5 mmol per liter). The higher glycemic criterion was a fasting plasma glucose level of at least 99 mg per deciliter (≥5.5 mmol per liter) or a 2-hour level of at least 162 mg per deciliter (≥9.0 mmol per liter). The primary outcome was the birth of an infant who was large for gestational age (defined as a birth weight above the 90th percentile according to Fenton-World Health Organization standards). Secondary outcomes were maternal and infant health. RESULTS: A total of 4061 women underwent randomization. Gestational diabetes was diagnosed in 310 of 2022 women (15.3%) in the lower-glycemic-criteria group and in 124 of 2039 women (6.1%) in the higher-glycemic-criteria group. Among 2019 infants born to women in the lower-glycemic-criteria group, 178 (8.8%) were large for gestational age, and among 2031 infants born to women in the higher-glycemic-criteria group, 181 (8.9%) were large for gestational age (adjusted relative risk, 0.98; 95% confidence interval, 0.80 to 1.19; P = 0.82). Induction of labor, use of health services, use of pharmacologic agents, and neonatal hypoglycemia were more common in the lower-glycemic-criteria group than in the higher-glycemic-criteria group. The results for the other secondary outcomes were similar in the two trial groups, and there were no substantial between-group differences in adverse events. Among the women in both groups who had glucose test results that fell between the lower and higher glycemic criteria, those who were treated for gestational diabetes (195 women), as compared with those who were not (178 women), had maternal and infant health benefits, including fewer large-for-gestational-age infants. CONCLUSIONS: The use of lower glycemic criteria for the diagnosis of gestational diabetes did not result in a lower risk of a large-for-gestational-age infant than the use of higher glycemic criteria. (Funded by the Health Research Council of New Zealand and others; GEMS Australian New Zealand Clinical Trials Registry number, ACTRN12615000290594.).

Effect of the Growth Assessment Protocol on the DEtection of Small for GestatioNal age fetus: process evaluation from the DESiGN cluster randomised trial.

BACKGROUND: Reducing the rate of stillbirth is an international priority. At least half of babies stillborn in high-income countries are small for gestational-age (SGA). The Growth Assessment Protocol (GAP), a complex antenatal intervention that aims to increase the rate of antenatal detection of SGA, was evaluated in the DESiGN type 2 hybrid effectiveness-implementation cluster randomised trial (n = 13 clusters). In this paper, we present the trial process evaluation. METHODS: A mixed-methods process evaluation was conducted. Clinical leads and frontline healthcare professionals were interviewed to inform understanding of context (implementing and standard care sites) and GAP implementation (implementing sites). Thematic analysis of interview text used the context and implementation of complex interventions framework to understand acceptability, feasibility, and the impact of context. A review of implementing cluster clinical guidelines, training and maternity records was conducted to assess fidelity, dose and reach. RESULTS: Interviews were conducted with 28 clinical leads and 27 frontline healthcare professionals across 11 sites. Staff at implementing sites generally found GAP to be acceptable but raised issues of feasibility, caused by conflicting demands on resource, and variable beliefs among clinical leaders regarding the intervention value. GAP was implemented with variable fidelity (concordance of local guidelines to GAP was high at two sites, moderate at two and low at one site), all sites achieved the target to train > 75% staff using face-to-face methods, but only one site trained > 75% staff using e-learning methods; a median of 84% (range 78-87%) of women were correctly risk stratified at the five implementing sites. Most sites achieved high scores for reach (median 94%, range 62-98% of women had a customised growth chart), but generally, low scores for dose (median 31%, range 8-53% of low-risk women and median 5%, range 0-17% of high-risk women) were monitored for SGA as recommended. CONCLUSIONS: Implementation of GAP was generally acceptable to staff but with issues of feasibility that are likely to have contributed to variation in implementation strength. Leadership and resourcing are fundamental to effective implementation of clinical service changes, even when such changes are well aligned to policy mandated service-change priorities. TRIAL REGISTRATION: Primary registry and trial identifying number: ISRCTN 67698474. Registered 02/11/16. https://doi.org/10.1186/ISRCTN67698474 .

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474.

Relative importance of metabolic syndrome components for developing gestational diabetes.

PURPOSE: To assess the independent and joint contribution of the individual components of metabolic syndrome, and known risk factors for gestational diabetes (GDM), on risk of GDM. METHODS: Two thousand nine hundred and fifteen women from Australia and New Zealand, who participated in The Screening for Pregnancy Endpoints Study (SCOPE), were included. Using the SCOPE clinical data set and biomarkers obtained at 14-16 weeks' gestation, a logistic regression model was fitted to the binary outcome GDM, with individual metabolic syndrome components (waist circumference, blood pressure, glucose, HDL-C, triglycerides), recruitment site, and other established factors associated with GDM. Hierarchical partitioning was used to assess the relative contribution of each variable. RESULTS: Of the 2915 women, 103 women (3.5%) developed GDM. The deviance explained by the logistic regression model containing all variables was 18.65% and the AUC was 0.809. Seventy percent of the independent effect was accounted for by metabolic syndrome components. The highest independent relative contribution to GDM was circulating triglycerides (17 ± 3%), followed by waist circumference (13 ± 3%). Glucose and maternal BMI contributed 12 ± 2% and 12 ± 3%, respectively. The remaining factors had an independent relative contribution of < 10%. CONCLUSION: Triglyceride concentrations had the highest independent relative importance for risk of GDM. Increased focus for lowering triglycerides as an important risk factor for GDM is warranted.

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.

A better understanding of the association between maternal perception of foetal movements and late stillbirth-findings from an individual participant data meta-analysis.

BACKGROUND: Late stillbirth continues to affect 3-4/1000 pregnancies in high-resource settings, with even higher rates in low-resource settings. Reduced foetal movements are frequently reported by women prior to foetal death, but there remains a poor understanding of the reasons and how to deal with this symptom clinically, particularly during the preterm phase of gestation. We aimed to determine which women are at the greatest odds of stillbirth in relation to the maternal report of foetal movements in late pregnancy (≥ 28 weeks' gestation). METHODS: This is an individual participant data meta-analysis of all identified case-control studies of late stillbirth. Studies included in the IPD were two from New Zealand, one from Australia, one from the UK and an internet-based study based out of the USA. There were a total of 851 late stillbirths, and 2257 controls with ongoing pregnancies. RESULTS: Increasing strength of foetal movements was the most commonly reported (> 60%) pattern by women in late pregnancy, which were associated with a decreased odds of late stillbirth (adjusted odds ratio (aOR) = 0.20, 95% CI 0.15 to 0.27). Compared to no change in strength or frequency women reporting decreased frequency of movements in the last 2 weeks had increased odds of late stillbirth (aOR = 2.33, 95% CI 1.73 to 3.14). Interaction analysis showed increased strength of movements had a greater protective effect and decreased frequency of movements greater odds of late stillbirth at preterm gestations (28-36 weeks' gestation). Foetal hiccups (aOR = 0.45, 95% CI 0.36 to 0.58) and regular episodes of vigorous movement (aOR = 0.67, 95% CI 0.52 to 0.87) were associated with decreased odds of late stillbirth. A single episode of unusually vigorous movement was associated with increased odds (aOR = 2.86, 95% CI 2.01 to 4.07), which was higher in women at term. CONCLUSIONS: Reduced foetal movements are associated with late stillbirth, with the association strongest at preterm gestations. Foetal hiccups and multiple episodes of vigorous movements are reassuring at all gestations after 28 weeks' gestation, whereas a single episode of vigorous movement is associated with stillbirth at term.

The associations between maternal BMI and gestational weight gain and health outcomes in offspring at age 1 and 7 years.

In secondary analyses of a randomised controlled trial of exercise during pregnancy, we examined associations between mid-pregnancy maternal body mass index (BMI) and excessive gestational weight gain (GWG) with offspring health. Follow-up data were available on 57 mother-child pairs at 1-year and 52 pairs at 7-year follow-ups. Clinical assessments included body composition and fasting blood tests. At age 1 year, increased maternal BMI in mid-gestation was associated with greater weight standard deviation scores (SDS) in the offspring (p = 0.035), with no observed associations for excessive GWG. At age 7 years, greater maternal BMI was associated with increased weight SDS (p < 0.001), BMI SDS (p = 0.005), and total body fat percentage (p = 0.037) in their children. Irrespective of maternal BMI, children born to mothers with excessive GWG had greater abdominal adiposity (p = 0.043) and less favourable lipid profile (lower HDL-C and higher triglycerides). At 7 years, maternal BMI and excessive GWG had compounded adverse associations with offspring adiposity. Compared to offspring of mothers with overweight/obesity plus excessive GWG, children of normal-weight mothers with adequate and excessive GWG were 0.97 and 0.64 SDS lighter (p = 0.002 and p = 0.014, respectively), and 0.98 and 0.63 SDS leaner (p = 0.001 and p = 0.014, respectively). Both greater maternal BMI in mid-pregnancy and excessive GWG were independently associated with increased adiposity in offspring at 7 years.