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.

An Individual Participant Data Meta-analysis of Maternal Going-to-Sleep Position, Interactions with Fetal Vulnerability, and the Risk of Late Stillbirth.

BACKGROUND: Maternal supine going-to-sleep position has been associated with increased risk of late stillbirth (≥ 28 weeks), but it is unknown if the risk differs between right and left side, and if some pregnancies are more vulnerable. METHODS: Systematic searches were undertaken for an individual-level participant data (IPD) meta-analysis of case-control studies, prospective cohort studies and randomised trials undertaken up until 26 Jan, 2018, that reported data on maternal going-to-sleep position and stillbirth. Participant inclusion criteria included gestation ≥ 28 weeks', non-anomalous, singleton pregnancies. The primary outcome was stillbirth. A one-stage approach stratified by study and site was used for the meta-analysis. The interaction between supine going-to-sleep position and fetal vulnerability was assessed by bi-variable regression. The multivariable model was adjusted for a priori confounders. Registration number: PROSPERO, CRD42017047703. FINDINGS: Six case-control studies were identified, with data obtained from five (cases, n = 851; controls, n = 2257). No data was provided by a sixth study (cases, n = 100; controls, n = 200). Supine going-to-sleep position was associated with increased odds of late stillbirth (adjusted odds ratio [aOR] 2.63, 95% CI 1.72-4.04, p < 0.0001) compared with left side. Right side had similar odds to left (aOR 1.04, 95% CI 0.83-1.31, p = 0.75). There were no significant interactions between supine going-to-sleep position and assessed indicators of fetal vulnerability, including small-for-gestational-age infants (p = 0.32), maternal obesity (p = 0.08), and smoking (p = 0.86). The population attributable risk for supine going-to-sleep position was 5.8% (3.2-9.2). INTERPRETATION: This IPD meta-analysis confirms that supine going-to-sleep position is independently associated with late stillbirth. Going-to-sleep on left or right side appears equally safe. No significant interactions with our assessed indicators of fetal vulnerability were identified, therefore, supine going-to-sleep position can be considered a contributing factor for late stillbirth in all pregnancies. This finding could reduce late stillbirth by 5.8% if every pregnant woman ≥ 28 weeks' gestation settled to sleep on her side.

Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy.

Small for gestational age is usually defined as an infant with a birthweight <10th centile for a population or customized standard. Fetal growth restriction refers to a fetus that has failed to reach its biological growth potential because of placental dysfunction. Small-for-gestational-age babies make up 28-45% of nonanomalous stillbirths, and have a higher chance of neurodevelopmental delay, childhood and adult obesity, and metabolic disease. The majority of small-for-gestational-age babies are not recognized before birth. Improved identification, accompanied by surveillance and timely delivery, is associated with reduction in small-for-gestational-age stillbirths. Internationally and regionally, detection of small for gestational age and management of fetal growth problems vary considerably. The aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines; and identify future research priorities in this field. A search of MEDLINE, Google, and the International Guideline Library identified 6 national guidelines on management of pregnancies complicated by fetal growth restriction/small for gestational age published from 2010 onwards. There is general consensus between guidelines (at least 4 of 6 guidelines in agreement) in early pregnancy risk selection, and use of low-dose aspirin for women with major risk factors for placental insufficiency. All highlight the importance of smoking cessation to prevent small for gestational age. While there is consensus in recommending fundal height measurement in the third trimester, 3 specify the use of a customized growth chart, while 2 recommend McDonald rule. Routine third-trimester scanning is not recommended for small-for-gestational-age screening, while women with major risk factors should have serial scanning in the third trimester. Umbilical artery Doppler studies in suspected small-for-gestational-age pregnancies are universally advised, however there is inconsistency in the recommended frequency for growth scans after diagnosis of small for gestational age/fetal growth restriction (2-4 weekly). In late-onset fetal growth restriction (≥32 weeks) general consensus is to use cerebral Doppler studies to influence surveillance and/or delivery timing. Fetal surveillance methods (most recommend cardiotocography) and recommended timing of delivery vary. There is universal agreement on the use of corticosteroids before birth at <34 weeks, and general consensus on the use of magnesium sulfate for neuroprotection in early-onset fetal growth restriction (<32 weeks). Most guidelines advise using cardiotocography surveillance to plan delivery in fetal growth restriction <32 weeks. The recommended gestation at delivery for fetal growth restriction with absent and reversed end-diastolic velocity varies from 32 to ≥34 weeks and 30 to ≥34 weeks, respectively. Overall, where there is high-quality evidence from randomized controlled trials and meta-analyses, eg, use of umbilical artery Doppler and corticosteroids for delivery <34 weeks, there is a high degree of consistency between national small-for-gestational-age guidelines. This review discusses areas where there is potential for convergence between small-for-gestational-age guidelines based on existing randomized controlled trials of management of small-for-gestational-age pregnancies, and areas of controversy. Research priorities include assessing the utility of late third-trimester scanning to prevent major morbidity and mortality and to investigate the optimum timing of delivery in fetuses with late-onset fetal growth restriction and abnormal Doppler parameters. Prospective studies are needed to compare new international population ultrasound standards with those in current use.

INTERGROWTH-21st vs customized birthweight standards for identification of perinatal mortality and morbidity.

BACKGROUND: The recently published INTERGROWTH-21st Project international population standard for newborn size is intended for global use, but its ability to identify small infants at risk of adverse outcomes in a general obstetric population has not been reported. OBJECTIVE: The objective of the study was to compare adverse neonatal outcomes among small-for-gestational-age (SGA) infants between the INTERGROWTH-21st standard and a customized birthweight standard (accounting for maternal characteristics of height, weight, parity, and ethnicity). We hypothesized that in a multiethnic general obstetric population in Auckland, New Zealand, a customized birthweight standard would better identify SGA infants at-risk of neonatal morbidity/mortality and stillbirth than the INTERGROWTH-21st standard. STUDY DESIGN: Using prospectively gathered maternity data from a general obstetric population in Auckland, New Zealand, from 2006 to 2013 (n = 53,484 births at ≥ 33 weeks), infants were classified as SGA (birthweight < 10th centile) by INTERGROWTH-21st and customized standards. Infants were further categorized as SGA by both criteria, INTERGROWTH-21st only, customized only, or not SGA (met neither criteria). Composite adverse neonatal outcome was defined as neonatal death, neonatal intensive care admission > 48 hours, or ventilation > 4 hours or 5-minute Apgar score < 7. Relative risks for primary outcomes were estimated using modified Poisson regression, with the non-SGA group as the referent. RESULTS: Incidence of SGA was 4.5% by INTERGROWTH-21st and 11.6% by customized standard. Compared with those not SGA, infants identified as small for gestational age by both criteria had the highest risk of adverse neonatal outcome (relative risk [RR], 4.1, 95% confidence interval [CI], 3.7-4.6) and stillbirth (RR, 8.3, 95% CI, 5.1-13.4). Infants SGA by customized standard only (n = 4015) had an increased risk of adverse neonatal outcome (RR, 2.0, 95% CI, 1.8-2.2) and stillbirth (RR, 3.0, 95% CI, 1.7-5.3). Few infants were identified as SGA by INTERGROWTH-21st only (n = 172), and risks of adverse neonatal outcome and stillbirth were not increased. Findings were unchanged when analyses were limited to term infants (n = 50,739). The INTERGROWTH-21st standard identified more Indian (12.8%) and Asian (5.8%) but fewer European (3.0%) and Pacific (2.9%) infants as SGA (P < .01). Customized criteria identified more than 3 times as many SGA infants among Maori (14.5%), Pacific (13.5%), and European (11.2%) infants and twice as many among Asian (10.3%) infants (P<0.01) compared with INTERGROWTH-21st criteria. The majority of SGA infants by INTERGROWTH-21st only were born to Indian and Asian mothers (95.4%). CONCLUSIONS: In our general obstetric population, birthweight customization identified more SGA infants at risk of perinatal mortality and morbidity compared with the INTERGROWTH-21st standard. The INTERGROWTH-21st standard failed to detect many at-risk SGA infants, particularly among ethnic groups with larger maternal size while disproportionately identifying higher rates of SGA among those with smaller maternal size. Local validation is needed prior to implementation of the INTERGROWTH-21st standard to avoid misclassification of infant birth size.

Independent risk factors for infants who are small for gestational age by customised birthweight centiles in a multi-ethnic New Zealand population.

BACKGROUND: Infants born small for gestational age (SGA) by customised birthweight centiles are at increased risk of adverse outcomes compared with those SGA by population centiles. Risk factors for customised SGA have not previously been described in a general obstetric population. AIM: To determine independent risk factors for customised SGA in a multi-ethnic New Zealand population. METHODS: We performed a retrospective cohort analysis of prospectively recorded maternity data from 2006 to 2009 at National Women's Health, Auckland, New Zealand. After exclusion of infants with congenital anomalies and missing data, our final study population was 26,254 singleton pregnancies. Multivariable logistic regression analysis adjusted for ethnicity, body mass index, maternal age, parity, smoking status, social deprivation, hypertensive disease, antepartum haemorrhage (APH), diabetes and relevant pre-existing medical conditions. RESULTS: Independent risk factors for SGA included obesity (adjusted odds ratio 1.24 [95% CI 1.11-1.39] relative to normal weight), maternal age ≥ 35 years (1.16 [1.05-1.30] relative to 20-29 years), nulliparity (1.13 [1.04-1.24] relative to parity 1), cigarette smoking (2.01 [1.79-2.27]), gestational hypertension (1.46 [1.21-1.75]), pre-eclampsia (2.94 [2.49-3.48]), chronic hypertension (1.68 [1.34-2.09]), placental abruption (2.57 [1.74-3.78]) and APH of unknown origin (1.71 [1.45-2.00]). Gestational diabetes (0.80 [0.67-0.96]) and type 1 diabetes (0.26 [0.11-0.64]) were associated with reduced risk. CONCLUSIONS: We report independent pregnancy risk factors for customised SGA in a general obstetric population. In contrast to population SGA, obesity is associated with increased risk. Our findings may help identify pregnancies that require increased fetal growth surveillance.

Ethnicity, body mass index and risk of pre-eclampsia in a multiethnic New Zealand population.

BACKGROUND: Pre-eclampsia rates are reported to vary by ethnicity; however, few studies include body mass index (BMI). Increasing BMI has a dose-dependent relationship with pre-eclampsia, and rates of overweight and obesity as well as ratios of body fat to muscle mass differ between ethnicities. We hypothesised that after adjusting for confounders, including ethnic-specific BMI, ethnicity would not be an independent risk factor for pre-eclampsia. AIM: To assess independent pre-eclampsia risk factors in a multiethnic New Zealand population. METHODS: We performed a retrospective cohort analysis of prospectively recorded maternity data from 2006 to 2009 at National Women's Health, Auckland, New Zealand. After exclusion of infants with congenital anomalies and missing data, our final study population was 26 254 singleton pregnancies. Multivariable logistic regression analysis adjusted for ethnicity, BMI, maternal age, parity, smoking, social deprivation, diabetes, chronic hypertension and relevant pre-existing medical conditions was performed. RESULTS: Independent associations with pre-eclampsia were observed in Chinese (adjusted odds ratio (aOR) 0.56, [95% CI 0.41-0.76]) and Maori (aOR 1.51, [1.16-1.96]) compared with European women. Other independent risk factors for pre-eclampsia were overweight and obesity, nulliparity, type 1 diabetes, chronic hypertension and pre-existing medical conditions. CONCLUSIONS: Contrary to our hypothesis, we report an independent reduced risk of pre-eclampsia in Chinese and increased risk of pre-eclampsia in Maori women. Prospective studies are required to further explore these relationships. Other independent risk factors are consistent with international literature. Our findings may assist clinicians to stratify risk of pre-eclampsia in clinical practice.