Accuracy of antenatal ultrasound in predicting large-for-gestational-age babies: population-based cohort study.

BACKGROUND: Pregnancies with large-for-gestational-age fetuses are at increased risk of adverse maternal and neonatal outcomes. There is uncertainty about how to manage birth in such pregnancies. Current guidelines recommend a discussion with women of the pros and cons of options, including expectant management, induction of labor, and cesarean delivery. For women to make an informed decision about birth, antenatal detection of large for gestational age is essential. OBJECTIVE: To investigate the ability of antenatal ultrasound scans to predict large for gestational age at birth. STUDY DESIGN: In this retrospective cohort study, we analyzed data from a routinely collected database from the West Midlands, United Kingdom. We included pregnancies that had an antenatal ultrasound-estimated fetal weight between 35+0 and 38+0 weeks gestation for any indication and a subgroup where the reason for the scan was that the fetus was suspected to be big. Large for gestational age was defined as >90th customized GROW percentile for estimated fetal weight as well as neonatal weight. In addition, we tested the performance of an uncustomized standard, with Hadlock fetal weight >90th percentile and neonatal weight >4 kg. We calculated diagnostic characteristics for the whole population and groups with different maternal body mass indexes. RESULTS: The study cohort consisted of 26,527 pregnancies, which, on average, had a scan at 36+4 weeks gestation and delivered 20 days later at a median of 39+3 weeks (interquartile range 15). In total, 2241 (8.4%) of neonates were large for gestational age by customized percentiles, of which 1459 (65.1%) had a scan estimated fetal weight >90th percentile, with a false positive rate of 8.6% and a positive predictive value of 41.0%. In the subgroup of 912 (3.4%) pregnancies scanned for a suspected large fetus, 293 (32.1%) babies were large for gestational age at birth, giving a positive predictive value of 50.3%, with a sensitivity of 77.1% and false positive rate of 36.0%. When comparing subgroups from low (<18.5 kg/m2) to high body mass index (>30 kg/m2), sensitivity increased from 55.6% to 67.8%, false positive rate from 5.2% to 11.5%, and positive predictive value from 32.1% to 42.3%. A total of 2585 (9.7%) babies were macrosomic (birthweight >4 kg), and of these, 1058 (40.9%) were large for gestational age (>90th percentile) antenatally by Hadlock's growth standard, with a false positive rate of 4.9% and a positive predictive value 41.0%. Analysis within subgroups showed better performance by customized than uncustomized standards for low body mass index (<18.5; diagnostic odds ratio, 23.0 vs 6.4) and high body mass index (>30; diagnostic odds ratio, 16.2 vs 8.8). CONCLUSION: Late third-trimester ultrasound estimation of fetal weight for any indication has a good ability to identify and predict large for gestational age at birth and improves with the use of a customized standard. The detection rate is better when an ultrasound is performed for a suspected large fetus but at the risk of a higher false positive diagnosis. Our results provide information for women and clinicians to aid antenatal decision-making about the birth of a fetus suspected of being large for gestational age.

Stillbirth risk and smallness for gestational age according to Hadlock, INTERGROWTH-21st, WHO, and GROW fetal weight standards: analysis by maternal ethnicity and body mass index.

BACKGROUND: Appropriate growth charts are essential for fetal surveillance, to confirm that growth is proceeding normally and to identify pregnancies that are at risk. Many stillbirths are avoidable through antenatal detection of the small-for-gestational-age fetus. In the absence of an international consensus on which growth chart to use, it is essential that clinical practice reflects outcome-based evidence. OBJECTIVE: This study investigated the performance of 4 internationally used fetal weight standards and their ability to identify stillbirth risk in different ethnic and maternal size groups of a heterogeneous population. STUDY DESIGN: We analyzed routinely collected maternity data from more than 2.2 million pregnancies. Three population-based fetal weight standards (Hadlock, Intergrowth-21st, and World Health Organization) were compared with the customized GROW standard that was adjusted for maternal height, weight, parity, and ethnic origin. Small-for-gestational-age birthweight and stillbirth risk were determined for the 2 largest ethnic groups in our population (British European and South Asian), in 5 body mass index categories, and in 4 maternal size groups with normal body mass index (18.5-25.0 kg/m2). The differences in trend between stillbirth and small-for-gestational-age rates were assessed using the Clogg z test, and differences between stillbirths and body mass index groups were assessed using the chi-square trend test. RESULTS: Stillbirth rates (per 1000) were higher in South Asian pregnancies (5.51) than British-European pregnancies (3.89) (P<.01) and increased in both groups with increasing body mass index (P<.01). Small-for-gestational-age rates were 2 to 3-fold higher for South Asian babies than British European babies according to the population-average standards (Hadlock: 26.2% vs 12.2%; Intergrowth-21st: 12.1% vs 4.9%; World Health Organization: 32.2% vs 16.0%) but were similar by the customized GROW standard (14.0% vs 13.6%). Despite the wide variation, each standard's small-for-gestation-age cases had increased stillbirth risk compared with non-small-for-gestation-age cases, with the magnitude of risk inversely proportional to the rate of cases defined as small for gestational age. All standards had similar stillbirth risk when the small-for-gestation-age rate was fixed at 10% by varying their respective thresholds for defining small for gestational age. When analyzed across body mass index subgroups, the small-for-gestation-age rate according to the GROW standard increased with increasing stillbirth rate, whereas small-for-gestation-age rates according to Hadlock, Intergrowth-21st, and World Health Organization fetal weight standards declined with increasing body mass index, showing a difference in trend (P<.01) to stillbirth rates across body mass index groups. In the normal body mass index subgroup, stillbirth rates showed little variation across maternal size groups; this trend was followed by GROW-based small-for-gestation-age rates, whereas small-for-gestation-age rates defined by each population-average standard declined with increasing maternal size. CONCLUSION: Comparisons between population-average and customized fetal growth charts require examination of how well each standard identifies pregnancies at risk of adverse outcomes within subgroups of any heterogeneous population. In both ethnic groups studied, increasing maternal body mass index was accompanied by increasing stillbirth risk, and this trend was reflected in more pregnancies being identified as small for gestational age only by the customized standard. In contrast, small-for-gestation-age rates fell according to each population-average standard, thereby hiding the increased stillbirth risk associated with high maternal body mass index.

Fetal size vs growth: comparative analysis of 3 models of growth velocity based on third trimester estimated fetal weights for identifying stillbirth risk.

BACKGROUND: Fetal growth velocity is being recognized as an important parameter by which to monitor fetal wellbeing, in addition to assessment of fetal size. However, there are different models and standards in use by which velocity is being assessed. OBJECTIVE: We wanted to investigate 3 clinically applied methods of assessing growth velocity and their ability to identify stillbirth risk, in addition to that associated with small for gestational age. STUDY DESIGN: Retrospective analysis of prospectively recorded routine-care data of pregnancies with 2 or more third trimester scans in New Zealand. Results of the last 2 scans were used for the analysis. The models investigated to define slow growth were (1) 50+ centile drop between measurements, (2) 30+ centile drop, and (3) estimated fetal weight below a projected optimal weight range, based on predefined, scan interval specific cut-offs to define normal growth. Each method's ability to identify stillbirth risk was assessed against that associated with small-for-gestational age at last scan. RESULTS: The study cohort consisted of 71,576 pregnancies. The last 2 scans in each pregnancy were performed at an average of 32+1 and 35+6 weeks of gestation. The 3 models defined "slow growth" at the following differing rates: (1) 50-centile drop 0.9%, (2) 30-centile drop 5.1%, and (3) below projected optimal weight range 10.8%. Neither of the centile-based models identified at-risk cases that were not also small for gestational age at last scan. The projected weight range method identified an additional 79% of non-small-for-gestational-age cases as slow growth, and these were associated with a significantly increased stillbirth risk (relative risk, 2.0; 95% CI, 1.2-3.4). CONCLUSION: Centile-based methods fail to reflect adequacy of fetal weight gain at the extremes of the distribution. Guidelines endorsing such models might hinder the potential benefits of antenatal assessment of fetal growth velocity. A new, measurement-interval-specific projection model of expected fetal weight gain can identify fetuses that are not small for gestational age, yet at risk of stillbirth because of slow growth. The velocity between scans can be calculated using a freely available growth rate calculator (www.perinatal.org.uk/growthrate).

Prospective risk of stillbirth according to fetal size at term.

OBJECTIVES: Fetal growth and size are associated with stillbirth risk. We wanted to investigate the week by week predictive value of fetal size at term on the prospective risk of stillbirth. METHODS: Anonymised database from the UK GAP program, with 2,094,702 term (≥37 weeks) deliveries including 4,670 stillbirths. Prospective stillbirth risk was defined as fetal death in the current week divided by total undelivered pregnancies. The data were analysed in five centile bands for stillbirth risk and risk ratios (RR) for 38, 39, 40 and 41+ weeks, using appropriate for gestational age (AGA) at 37 weeks as reference. RESULTS: Baseline stillbirth risk at 37 weeks was 0.29 per 1,000 and rose to 1.39 at 41+ weeks, with RR increasing to 4.8. In the 3<10 centile band risk rose from 0.72 to 2.43 over the same period, with RR increasing from 2.5 to 8.4. In the <3 centile group, the stillbirth risk rose from 1.62 to 6.16 (RR (5.6 to 21.2). In the 97>90 centile band, risk increased from 0.40 to 1.50 (RR 1.4 to 5.2) and for >97 centiles, it rose from 0.80 to 2.13 (RR 2.8-7.3). CONCLUSIONS: Prospective risk of fetal death at term is related to fetal size. The information provided, together with other considerations and results of investigations where available, will help clinicians to determine the advice to give to mothers about the best timing for delivery, balancing the baby's risk of compromise with iatrogenic sequelae of early delivery.

Evaluating the Growth Assessment Protocol for stillbirth prevention: progress and challenges.

Many stillbirths are associated with fetal growth restriction, and are hence potentially avoidable. The Growth Assessment Protocol (GAP) is a multidisciplinary program with an evidence based care pathway, training in risk assessment, fetal growth surveillance with customised charts and rolling audit. Antenatal detection of small for gestational age (SGA) has become an indicator of quality of care. Evaluation is essential to understand the impact of such a prevention program. Randomised trials will not be effective if they cannot ensure proper implementation before assessment. Observational studies have allowed realistic evaluation in practice, with other factors excluded that may have influenced the outcome. An award winning 10 year study of stillbirth data in England has been able to assess the effect of GAP in isolation, and found a strong, causal association with improved antenatal detection of SGA babies, and the sustained decline in national stillbirth rates. The challenge now is to apply this program more widely in low and middle income settings where the main global burden of stillbirth is, and to adapt it to local needs and resources.

Customised birthweight standard for a Slovenian population.

Objective To produce a customised birthweight standard for Slovenia. Methods This retrospective study used a cohort from the National Perinatal Information System of Slovenia (NPIS). Prospectively collected information from pregnancies delivered in all of Slovenia's 14 maternal hospitals between 1st January 2003 and 31st December 2012 was included. Coefficients were derived using a backward stepwise multiple regression technique. Results A total of 126,627 consecutive deliveries with complete data were included in the multivariable analysis. Maternal height, weight in early pregnancy and parity as well as the baby's sex were identified as physiological variables, with coefficients comparable to findings in other countries. The expected 280-day birthweight, free from pathological influences, of a standard size mother (height 163 cm, weight 64 kg) in her first pregnancy was 3451.3 g. Pathological influences on birthweight within this population included low and high maternal age, low and high body mass index (BMI), smoking, pre-existing and gestational diabetes and pre-existing and gestational hypertension. Conclusion The analysis confirmed the main physiological variables that affect birthweight in studies from other countries, and was able to quantify additional pathological factors of maternal age and gestational diabetes. Development of a country-specific customised birthweight standard will aid clinicians in Slovenia with the distinction between normal and abnormal small-for-gestational age (SGA) fetuses, thus avoiding unnecessary interventions and improving identification of at risk pregnancies, and long-term outcomes for infants.

Customized vs INTERGROWTH-21st standards for the assessment of birthweight and stillbirth risk at term.

BACKGROUND: Fetal growth abnormalities are linked to stillbirth and other adverse pregnancy outcomes, and use of the correct birthweight standard is essential for accurate assessment of growth status and perinatal risk. OBJECTIVE: Two competing, conceptually opposite birthweight standards are currently being implemented internationally: customized gestation-related optimal weight (GROW) and INTERGROWTH-21st. We wanted to compare their performance when applied to a multiethnic international cohort, and evaluate their usefulness in the assessment of stillbirth risk at term. STUDY DESIGN: We analyzed routinely collected maternity data from 10 countries with a total of 1.25 million term pregnancies in their respective main ethnic groups. The 2 standards were applied to determine small for gestational age (SGA) and large for gestational age (LGA) rates, with associated relative risk and population-attributable risk of stillbirth. The customized standard (GROW) was based on the term optimal weight adjusted for maternal height, weight, parity, and ethnic origin, while INTERGROWTH-21st was a fixed standard derived from a multiethnic cohort of low-risk pregnancies. RESULTS: The customized standard showed an average SGA rate of 10.5% (range 10.1-12.7) and LGA rate of 9.5% (range 7.3-9.9) for the set of cohorts. In contrast, there was a wide variation in SGA and LGA rates with INTERGROWTH-21st, with an average SGA rate of 4.4% (range 3.1-16.8) and LGA rate of 20.6% (range 5.1-27.5). This variation in INTERGROWTH-21st SGA and LGA rates was correlated closely (R = ±0.98) to the birthweights predicted for the 10 country cohorts by the customized method to derive term optimal weight, suggesting that they were mostly due to physiological variation in birthweight. Of the 10.5% of cases defined as SGA according to the customized standard, 4.3% were also SGA by INTERGROWTH-21st and had a relative risk of 3.5 (95% confidence interval, 3.1-4.1) for stillbirth. A further 6.3% (60% of the whole customized SGA) were not SGA by INTERGROWTH-21st, and had a relative risk of 1.9 (95% confidence interval, 3.1-4.1) for stillbirth. An additional 0.2% of cases were SGA by INTERGROWTH-21st only, and had no increased risk of stillbirth. At the other end, customized assessment classified 9.5% of births as large for gestational age, most of which (9.0%) were also LGA by the INTERGROWTH-21st standard. INTERGROWTH-21st identified a further 11.6% as LGA, which, however, had a reduced risk of stillbirth (relative risk, 0.6; 95% confidence interval, 0.5-0.7). CONCLUSION: Customized assessment resulted in increased identification of small for gestational age and stillbirth risk, while the wide variation in SGA rates using the INTERGROWTH-21st standard appeared to mostly reflect differences in physiological pregnancy characteristics in the 10 maternity populations.

Customized GROW vs INTERGROWTH-21st birthweight standards to identify small for gestational age associated perinatal outcomes at term.

BACKGROUND: Fetal growth restriction is associated with stillbirth and other adverse pregnancy outcomes, and the use of the correct weight standard is an essential proxy indicator of growth status and perinatal risk. OBJECTIVE: This study aimed to assess the performance of two international birthweight standards for their ability to identify perinatal morbidity and mortality indicators associated with small for gestational age infants at term. STUDY DESIGN: This retrospective cohort study used data from a multicenter perinatal quality initiative, including a multiethnic dataset of 125,826 births from 2012 to 2017. Of the singleton term births, 92,622 had complete outcome data including stillbirth, neonatal death, 5-minute Apgar score <7, neonatal glucose instability and need for newborn transfer to a higher level of care or neonatal intensive care unit admission. The customized GROW and INTERGROWTH-21st birthweight standards were applied to determine small for gestational age (<10th percentile) according to their respective methods and formulae. The associations with adverse outcomes were expressed as relative risks with 95% confidence intervals and population attributable fractions. RESULTS: GROW and INTERGROWTH-21st classified 9578 (10.3%) and 4079 (4.4%) pregnancies as small for gestational age, respectively. For all of the outcomes assessed, GROW identified more small for gestational age infants with adverse outcomes than INTERGROWTH-21st, including more stillbirths, perinatal deaths, low Apgar scores, glucose instability, newborn seizure, and transfers to a higher level of care. Moreover, 13 of 27 stillbirths (48%) that were small for gestational age by either method were identified as small for gestational age by GROW but not by INTERGROWTH-21st. Similarly, additional cases of all other adverse outcome indicators were identified by GROW as small for gestational age, whereas INTERGROWTH-21st identified in only 1 category (glucose instability) 9 of 295 cases (3.1%), which were not identified as small for gestational age by GROW. CONCLUSION: Customized assessment using GROW resulted in increased identification of small for gestational age term infants that were at significantly increased risk of an array of adverse pregnancy outcomes.