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).

Assessment of fetal growth trajectory identifies infants at high risk of perinatal mortality.

OBJECTIVE: To analyze perinatal risks associated with three distinct scenarios of fetal growth trajectory in the latter half of pregnancy compared with a reference group. METHODS: This cohort study included women with a singleton pregnancy that delivered between 32 + 0 and 41 + 6 weeks' gestation and had two or more ultrasound scans, at least 4 weeks apart, from 18 + 0 weeks. We evaluated three different scenarios of fetal growth against a reference group, which comprised appropriate-for-gestational-age fetuses with appropriate forward-growth trajectory. The comparator growth trajectories were categorized as: Group 1, small-for-gestational-age (SGA) fetuses (estimated fetal weight (EFW) or abdominal circumference (AC) persistently < 10th centile) with appropriate forward growth; Group 2, fetuses with decreased growth trajectory (decrease of ≥ 50 centiles) and EFW or AC ≥ 10th centile (i.e. non-SGA) at their final ultrasound scan; and Group 3, fetuses with decreased growth trajectory and EFW or AC < 10th centile (i.e. SGA) at their final scan. The primary outcome was overall perinatal mortality (stillbirth or neonatal death). Secondary outcomes included stillbirth, delivery of a SGA infant, preterm birth, emergency Cesarean section for non-reassuring fetal status and composite severe neonatal morbidity. Associations were analyzed using logistic regression. RESULTS: The final study cohort comprised 5319 pregnancies. Compared to the reference group, the adjusted odds of perinatal mortality were increased significantly in Group 2 (adjusted odds ratio (aOR), 4.00 (95% CI, 1.36-11.22)) and Group 3 (aOR, 7.71 (95% CI, 2.39-24.91)). Only Group 3 had increased odds of stillbirth (aOR, 5.69 (95% CI, 1.55-20.93)). In contrast, infants in Group 1 did not have significantly increased odds of demise. The odds of a SGA infant at birth were increased in all three groups compared with the reference group, but was highest in Group 1 (aOR, 111.86 (95% CI, 62.58-199.95)) and Group 3 (aOR, 40.63 (95% CI, 29.01-56.92)). In both groups, more than 80% of infants were born SGA and nearly half had a birth weight < 3rd centile. Likewise, the odds of preterm birth were increased in all three groups compared with the reference group, being highest in Group 3, with an aOR of 4.27 (95% CI, 3.23-5.64). Lastly, the odds of composite severe neonatal morbidity were increased in Groups 1 and 3, whereas the odds of emergency Cesarean section for non-reassuring fetal status were increased only in Group 3. CONCLUSION: Assessing the fetal growth trajectory in the latter half of pregnancy can help identify infants at increased risk of perinatal mortality and birth weight < 3rd centile for gestation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Nurture growth: Ketogenic diet therapy and growth velocity in infants under 12 months with epilepsy - A systematic review and infant data study.

Ketogenic diet therapy (KDT) is well established for the treatment of early epileptic encephalopathies and specific aetiologies; however, the impact on growth in infancy remains controversial. Our aim was to examine the influence of early KDT on growth velocity and height percentiles completing two tasks. First, we systematically reviewed the literature on growth in infants younger than 12 months. Second, we analysed data from our prospective database, including infants <12 months (n = 63) treated with KDT. The literature review (n = 7) remains descriptive and includes growth percentiles and z-scores as growth velocity was not described. Studies up to 2010 used fasting, calorie restrictions, and ratios >3:1. In individual cases, significant growth delays were found; other authors did not find any changes in growth parameters. Study endpoints in our own cohort included z-scores of growth velocity, standard deviation (SD) of height, weight, BMI, deviation from individual height percentile, and daily macronutrient intake. The median z-score of growth velocity was 1.03 (first year of life). After three months, median daily intake of protein and energy was 1.68 g/kg and 85 kcal/kg. Until the age of one year, neither growth velocity nor individual growth percentiles decreased. Infants showed distinct growth improvements at three months, likely due to continuous nutritional monitoring and reduction in seizures. In the second year of life, z-scores of growth velocity decreased in patients still receiving KDT (from 1.03 at 12 months to -1.5 at 24 months). Furthermore, younger age at epilepsy onset and at KDT start correlated with slower growth velocities in the first year of life. With appropriate nutritional intake and monitoring, KDT does not reduce growth in the first year of life. Future directions might be to study the impact of KDT on growth velocity and growth hormones throughout childhood.

Role of surgery in the treatment of pediatric low-grade glioma with various degrees of brain stem involvement.

OBJECTIVE: Posterior fossa pediatric low-grade glioma involving the brainstem and cerebellar peduncles (BS-pLGG) are a subgroup with higher risks at surgery. We retrospectively analyzed the role of surgery in the interdisciplinary armamentarium of treatment options in our institutional series of BS-pLGG with various degrees of brainstem involvement. MATERIAL AND METHODS: We analyzed data of 52 children with BS-pLGG after surgical intervention for clinical/molecular characteristics, neurological outcome, factors influencing recurrence/progression pattern, and tumor volumetric analysis of exclusively surgically treated patients to calculate tumor growth velocity (TGV). Tumors were stratified according to primary tumor origin in four groups: (1) cerebellar peduncle, (2) 4th ventricle, (3) pons, (4) medulla oblongata. RESULTS: The mean FU was 6.44 years. Overall survival was 98%. The mean PFS was 34.07 months. Two patients had biopsies only. Fifty-two percent of patients underwent remission or remained in stable disease (SD) after initial surgery. Patients with progression underwent further 23 resections, 15 chemotherapies, 4 targeted treatments, and 2 proton radiations. TGV decreased after the 2nd surgery compared to TGV after the 1st surgery (p < 0.05). The resection rates were significantly higher in Groups 1 and 2 and lowest in medulla oblongata tumors (Group 4) (p < 0.05). More extended resections were achieved in tumors with KIAA1549::BRAF fusion (p = 0.021), which mostly occurred in favorable locations (Groups 1 and 2). Thirty-one patients showed postoperatively new neurological deficits. A total of 27/31 improved within 12 months. At the end of FU, 6% had moderate deficits, 52% had mild deficits not affecting activities, and 36% had none. Fifty percent of patients were free of disease or showed remission, 38% were in SD, and 10% showed progression. CONCLUSION: The first surgical intervention in BS-pLGG can control disease alone in overall 50% of cases, with rates differing greatly according to location (Groups 1 > 2 > 3 > 4), with acceptable low morbidity. The second look surgery is warranted except in medullary tumors. With multimodality treatments almost 90% of patients can obtain remission or stable disease after > 5 years of follow-up. An integrated multimodal and multidisciplinary approach aiming at minimal safe residual disease, combining surgery, chemo-, targeted therapy, and, as an exception, radiation therapy, is mandatory.

Does decreased fetal growth estimation in the appropriate for gestational age range affect delivery outcomes?

PURPOSE: To study the effect of decreased estimated fetal weight (EFW) percentiles in appropriate for gestational age fetuses. METHODS: This retrospective cohort study included women who had second and third trimester ultrasound examinations. Delivery and neonatal outcomes of pregnancies with decreased EFW of ≥ 30 percentiles in EFW between ultrasound examinations (decreased growth group) and those without such a decrease (control group) were compared. Deliveries with EFW or birthweight below the 10th percentile were excluded. RESULTS: Among 1610 deliveries, 57 were in the decreased growth group and 1553 in the control group. Maternal characteristics did not differ between the groups except for higher rate of nulliparity in the decreased growth group. We found similar rates of Category II/III monitoring, cesarean deliveries due to non-reassuring fetal heart rate and adverse neonatal outcomes. Neonatal birthweight was lower in the decreased growth group as compared to controls. CONCLUSIONS: This study did not find association between the group of appropriate for gestational age fetuses with decreased growth, with adverse outcomes.

Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction.

BACKGROUND: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. OBJECTIVE: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. STUDY DESIGN: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32+0 and 36+6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was <100 g/wk, irrespective of signs of cerebral blood flow redistribution. Infants with birthweight <0.65 multiple of the median were enrolled earlier, had the lowest fetal growth velocity, higher umbilical-cerebral ratio, and were more likely to have adverse perinatal outcome. A decreasing fetal growth velocity was observed in 163 (19%) women in whom the estimated fetal weight multiple of the median regression coefficient was <-0.025, and who had higher umbilical-cerebral ratio values and more frequent adverse perinatal outcome; 67 (41%; 8% of total group) of these women had negative growth velocity. Estimated fetal weight and umbilical-cerebral ratio at admission and fetal growth velocity combined by logistic regression had a higher association with adverse perinatal outcome than any of those parameters separately (relative risk, 3.3; 95% confidence interval, 2.3-4.8). CONCLUSION: In fetuses at risk of late preterm fetal growth restriction, reduced growth velocity is associated with an increased risk of adverse perinatal outcome, irrespective of signs of cerebral blood flow redistribution. Some fetuses showed negative growth velocity, suggesting catabolic metabolism.

Second-trimester growth velocities in twin and singleton pregnancies.

OBJECTIVE: Previous small studies used individualized growth assessment (IGA) to characterize prenatal growth velocities of singletons and twins. We aimed to compare second-trimester growth velocities of individual anatomical parameters between monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins and singleton fetuses in a larger study. METHODS: This was a study of a novel cohort of 222 MCDA twins and previously published cohorts of 40 DCDA twins and 118 singletons with serial ultrasound data. Fetal biometric measurements of biparietal diameter, head circumference, abdominal circumference and femur diaphysis length from prenatal ultrasound examinations were used to calculate second-trimester growth velocities using direct calculation or linear regression analysis. Linear fit was assessed based on the coefficient of determination (R2 ). Mean growth velocities and variances were compared among the three groups. RESULTS: The majority of cases underwent three second-trimester ultrasound examinations with fetal biometry available. All fetuses had linear growth, with R2 > 99% for all parameters. Only 1-2% of all MCDA and DCDA anatomical parameters had abnormal growth velocity scores outside the 95% reference range for singletons. There were no significant differences in mean growth velocity for any parameter between MCDA twins and singletons. Femur diaphysis length growth velocity was significantly lower in DCDA twins than in both MCDA twins and singletons. There were no other significant differences among the groups. CONCLUSIONS: Expanding on prior work using IGA, we found that second-trimester growth velocity of the four major anatomical parameters overall was similar between twins and singletons and between MCDA and DCDA twins, supporting the use of singleton-derived growth standards for IGA in twins. Twin growth potential appears to be similar to that of singletons in the second trimester, suggesting that subsequent growth divergence may be due to third-trimester physiological or pathological changes in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Predictive value of fetal growth trajectory from 20 weeks of gestation onwards for severe adverse perinatal outcome in low-risk population: secondary analysis of IRIS study.

OBJECTIVES: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. METHODS: This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. RESULTS: Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. CONCLUSIONS: In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Outcome-based comparative analysis of five fetal growth velocity models to define slow growth.

OBJECTIVE: Fetal growth surveillance includes assessment of size as well as rate of growth, and various definitions for slow growth have been adopted into clinical use. The aim of this study was to evaluate the effectiveness of different models to identify stillbirth risk, in addition to risk represented by the fetus being small-for-gestational age (SGA). METHODS: This was a retrospective analysis of a routinely collected and anonymized dataset of pregnancies that had two or more third-trimester ultrasound measurements of estimated fetal weight (EFW). SGA was defined as EFW < 10th customized centile, and slow growth was defined according to five published models in clinical use: (1) a fixed velocity limit of 20 g per day (FVL20 ); (2) a fixed > 50 centile drop, regardless of scan-measurement interval (FCD50 ); (3) a fixed > 30 centile drop, regardless of scan interval (FCD30 ); (4) growth trajectory slower than the third customized growth-centile limit (GCL3 ); and (5) EFW at second scan below the projected optimal weight range (POWR), based on partial receiver-operating-characteristics-curve-derived  cut-offs specific to the scan interval. RESULTS: The study cohort consisted of 164 718 pregnancies with 480 592 third-trimester ultrasound scans (mean ± SD, 2.9 ± 0.9). The last two scans in each pregnancy were performed at an average gestational age of 33 + 5 and 37 + 1 weeks. At the last scan, 12 858 (7.8%) EFWs were SGA, and of these, 9359 were also SGA at birth (positive predictive value, 72.8%). The rate at which slow growth was defined varied considerably (FVL20 , 12.7%; FCD50 , 0.7%; FCD30 , 4.6%; GCL3 , 19.8%; POWR, 10.1%), and there was varying overlap between cases identified as having slow growth and those identified as SGA at the last scan. Only the POWR method identified additional non-SGA pregnancies with slow growth (11 237/16 671 (67.4%)) that had significant stillbirth risk (relative risk, 1.58 (95% CI, 1.04-2.39)). These non-SGA cases resulting in stillbirth had a median EFW centile of 52.6 at the last scan and a median weight centile of 27.3 at birth. Subgroup analysis identified methodological problems with the fixed-velocity model because it assumes linear growth throughout gestation, and with the centile-based methods because the non-parametric distribution of centiles at the extremes does not reflect actual difference in weight gain. CONCLUSION: Comparative analysis of five clinically used methods to define slow fetal growth has shown that only the measurement-interval-specific POWR model can identify non-SGA fetuses with slow growth that are at increased risk of stillbirth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Implication of third-trimester screening accuracy for small-for-gestational age and additive value of third-trimester growth-trajectory indicators in predicting severe adverse perinatal outcome in low-risk population: pragmatic secondary analysis of IRIS study.

OBJECTIVES: To examine the implications of third-trimester small-for-gestational-age (SGA) screening accuracy on severe adverse perinatal outcome (SAPO) and obstetric intervention in a low-risk population. Furthermore, we aimed to explore the additive value of third-trimester sonographic growth-trajectory measurements in predicting SAPO and obstetric intervention. METHODS: This was a secondary analysis of a Dutch national multicenter stepped-wedge-cluster randomized trial among 11 820 low-risk pregnant women. Using multilevel multivariable logistic regression analysis, we compared SAPO and obstetric interventions in SGA neonates with and without SGA suspected prenatally (true positives and false negatives) and non-SGA neonates with and without SGA suspected prenatally (false positives and true negatives). In a subsample (n = 7989), we analyzed the associations of abdominal circumference (AC) and estimated fetal weight (EFW) < 10th centile (p10) and third-trimester growth-trajectory indicators AC and EFW crossing > 20 and AC crossing > 50 centiles and the lowest decile of AC growth-velocity Z-scores (ACGV < 10%) with SAPO and obstetric interventions. RESULTS: SGA infants, i.e. the true-positive and false-negative cases, had an increased risk of SAPO (adjusted odds ratio (aOR), 4.46 (95% CI, 2.28-8.75) and aOR 2.61 (95% CI, 1.74-3.89), respectively), and obstetric intervention (aOR for: induction of labor, 2.99 (95% CI, 2.15-4.17) and 1.38 (95% CI, 1.14-1.66); Cesarean section, 1.82 (95% CI, 1.25-2.66) and 1.27 (95% CI, 1.05-1.54); medically indicated preterm delivery, 2.67 (95% CI, 1.97-3.62) and 1.20 (95% CI, 1.03-1.40)). The false-positive cases did not differ from the true negatives for all outcomes, including obstetric intervention. Of the third-trimester growth-trajectory indicators, only ACGV < 10% was associated moderately with SAPO (aOR, 2.15 (95% CI, 1.17-3.97)), while AC and EFW crossing > 20 and AC crossing > 50 centiles were not. Both EFW < p10 alone (aOR, 1.95 (95% CI, 1.13-3.38)) and EFW < p10 combined with ACGV < 10% (aOR, 4.69 (95% CI, 1.99-11.07)) were associated with SAPO, and they performed equally well in predicting SAPO (area under the receiver-operating-characteristics curve, 0.71 (95% CI, 0.65-0.76) vs 0.72 (95% CI, 0.67-0.77), P = 0.51). CONCLUSION: Neonates who had been suspected falsely of being SGA during pregnancy had no higher rates of obstetric intervention than did those without suspicion of SGA prenatally. Our results do not support that third-trimester low fetal growth velocity (ACGV < 10%) may be of additive value for the identification of fetuses at risk of SAPO in populations remaining at low risk throughout pregnancy. AC and EFW crossing > 20 and AC crossing > 50 centiles performed poorly in identifying abnormal fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Evaluating preschool linear growth velocities: an interim reference illustrated in Nepal.

OBJECTIVE: An annualised linear growth velocity (LGV) reference can identify groups of children at risk of growing poorly. As a single velocity reference for all preschool ages does not exist, we present an interim tool, derived from published, normative growth studies, for detecting growth faltering, illustrating its use in Nepali preschoolers. DESIGN: The WHO Child Growth Velocity Standard was adapted to derive 12-month increments and conjoined to the Tanner-Whitehouse Height Velocity Reference data yielding contiguous preschool linear growth annualised velocities. Linear restricted cubic spline regressions were fit to generate sex-specific median and standard normal deviate velocities for ages 0 through 59 months. LGV Z-scores (LGVZ) were constructed, and growth faltering was defined as LGVZ < ­2. SETTING: Use of the reference was illustrated with data from Nepal's Tarai region. PARTICIPANTS: Children contributing the existing growth references and a cohort of 4276 Nepali children assessed from 2013 to 2016. RESULTS: Fitted, smoothed LGV reference curves displayed monotonically decreasing 12-month LGV, exemplified by male/female annual medians of 26·4/25·3, 12·1/12·7, 9·1/9·4, 7·7/7·8 and 7/7 cm/years, starting at 0, 12, 24, 36 and 48 months, respectively. Applying the referent, 31·1 %, 28·6 % and 29·3 % of Nepali children <6, 6­11 and 12­23 months of age, and ∼6 % of children 24­59 months, exhibited growth faltering. Under 24 months, faltering velocities were more prevalent in girls (34·4 %) than boys (25·3 %) (P < 0·05) but comparable (∼6 %) in older preschoolers. CONCLUSIONS: A LGV reference, concatenated from extant data, can identify preschool groups at-risk of growth faltering. Application and limitations are discussed.

The effects of gestational diabetes mellitus on fetal growth: is it different for low-risk and medium-high-risk pregnant women?

BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.

Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study.

PURPOSE: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control. METHODS: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing. RESULTS: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was -2.5 for girls and -3.2 for boys and decreased up to the age 5 years (-5.3 for girls; -4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward. CONCLUSION: This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.

Improving Underweight Mothers' Essential Newborn Care During Early Infancy: A Single-Blinded, Parallel-Randomized, Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of using a standardized Essential Newborn Care (ENC) module taught by pediatric residents on ENC skills and growth of offspring born to underweight primigravida mothers. STUDY DESIGN: This facility-based, single-blinded, parallel, randomized controlled trial was conducted between May 2018 and March 2019. Eighty-eight underweight primigravida mothers and their vaginally delivered offspring were blindly allocated into the intervention group (IG) or control group (CG). The IG mothers received education on ENC through pictorial aids, demonstrations, and practice sessions. All mothers received information from ongoing public health programs. A trained hospital nurse, blinded to the study, assessed the mothers' neonatal care skills on the second postnatal day. The infants were followed until 6 months. Weight, length, and head circumference were measured at birth and age 6 weeks, 10 weeks, 14 weeks, and 6 months (±1 week). RESULTS: Mothers in the IG had significantly better ENC skills in all domains (P < .001). Their infants had a statistically significant increase in weight (at 10 and 14 weeks and 6 months), length (at 14 weeks and 6 months), and head circumference (at 6 months). Infants' z-scores indicated significant improvements in anthropometry in the IG compared with the CG. At age 6 months, the number of infants with weight <3rd percentile decreased in the IG (from 20 of 44 to 5 of 41) and increased in the CG (from 17 of 44 to 22 of 42) compared with birth percentiles. CONCLUSIONS: An educational intervention to strengthen maternal ENC knowledge and skills soon after delivery improved physical growth in infants born to underweight primigravida mothers. TRIAL REGISTRATION: Clinical Trials Registry-India: CTRI/2018/04/013096.

Linear Growth Spurts are Preceded by Higher Weight Gain Velocity and Followed by Weight Slowdowns Among Rural Children in Burkina Faso: A Longitudinal Study.

BACKGROUND: The temporal relationship between length (linear) and weight (ponderal) growth in early life is important to support optimal nutrition program design. Studies based on measures of attained size have established that wasting often precedes stunting, but such studies do not capture responsiveness of growth to previous compared with current conditions. As a result, the temporality of linear and ponderal growth relationships remain unclear. OBJECTIVES: We used growth velocity indicators to assess the temporal bidirectional relationships between linear and ponderal growth in children. METHODS: Using monthly anthropometric measurements from 5039 Burkinabè children enrolled at 6 months of age and followed until 28 months from August 2014 to December 2016, we employed multilevel mixed-effects models to investigate concurrent and lagged associations between linear and ponderal growth velocity, controlling for time trends, seasonality, and morbidity. RESULTS: Faster ponderal growth is associated with faster concurrent and subsequent linear growth (0.21-0.72 increase in length velocity z-score per unit increase in weight velocity z-score), while faster linear growth is associated with slower future weight gain (0.009-0.02 decrease in weight velocity z-score per unit increase in length velocity z-score), especially among children 9-14 months. Ponderal growth slows around the same time as peaks in morbidity, followed roughly a month later by slower linear growth. CONCLUSIONS: Use of velocity measures to assess temporal dependencies between linear and ponderal growth demonstrate that the same growth-limiting conditions likely affect both length and weight velocity, that slow ponderal growth likely limits subsequent linear growth, and that linear growth spurts may not be accompanied by sufficient increases in dietary intake to avoid slowdowns in weight gain.

Comparing Attained Weight and Weight Velocity during the First 6 Months in Predicting Child Undernutrition and Mortality.

BACKGROUND: The first 6 mo of life are critical for subsequent risk of undernutrition and mortality. The predictive abilities of attained weight at the end of each month and monthly weight velocity for undernutrition and mortality need to be compared. OBJECTIVES: This study aimed to examine the predictive abilities of different weight metrics during the first 6 mo of life in predicting undernutrition and mortality. METHODS: This study used a cohort of infants in Tanzania. Weight and length were measured monthly from birth to 18 mo of age. Three weight metrics during the first 6 mo of life were considered as predictors, including attained weight-for-age z score (WAZ) at the end of each month, monthly change in WAZ, and monthly weight velocity z score (WVZ). Logistic models were used with undernutrition (at 6 or 12 mo) and mortality (over the first 18 mo) as outcomes. AUC values were compared across metrics. RESULTS: For predicting wasting at 6 mo, WVZ (AUC: 0.80) had a greater predictive ability than attained WAZ (AUC: 0.76) and change in WAZ (AUC: 0.71) during the second month of life. After 2 mo, attained WAZ (AUC: 0.81-0.89) had greater predictive abilities than WVZ (AUC: 0.71-0.77) and change in WAZ (AUC: 0.65-0.67). For predicting stunting at 6 mo, attained WAZ (AUC: 0.75-0.79) had consistently greater predictive abilities than WVZ (AUC: 0.56-0.66) and change in WAZ (AUC: 0.50-0.57). The weight metrics had similar abilities in predicting mortality, with the AUC rarely reaching >0.65. CONCLUSIONS: Attained weight at the end of each month had greater abilities than monthly weight velocity in the same month in predicting undernutrition. Attained weight remains a useful indicator for identifying infants at greater risk of undernutrition.

Fetal weight projection model to define growth velocity and validation against pregnancy outcome in a cohort of serially scanned pregnancies.

OBJECTIVE: Fetal growth assessment is central to good antenatal care, yet there is a lack of definition of normal and abnormal fetal growth rate which can identify pregnancies at risk of adverse outcome. The aim of this study was to develop and test a model for defining normal limits of growth velocity which are specific to the fetal weight measurement interval. METHODS: The cohort consisted of 102 138 singleton pregnancies which underwent at least two third-trimester measurements of ultrasound estimated fetal weight (EFW), usually carried out because routine early-pregnancy risk assessment had indicated an increased risk of fetal growth restriction. We projected the EFW from the first of each consecutive measurement pair along its own centile rank to the gestational age of the second scan. Normal growth was defined as the second EFW being within a weight range based on limits derived by partial receiver-operating-characteristics-curve (pROC) analyses for small-for-gestational-age (SGA; < 10th centile) and large-for-gestational-age (LGA; > 90th centile) birth weight. The limits were measurement-interval specific and calculated for a fixed false-positive rate (FPR) of 10%. The resultant normal, slow and accelerated growth rates calculated from consecutive EFW pairs were evaluated against the following predefined perinatal outcome measures: stillbirth, neonatal death, SGA and LGA at birth, 5-min Apgar score < 7 and admission to the neonatal intensive care unit. Slow growth based on the last two scans was compared with SGA fetal weight (EFW < 10th centile) at the last scan and association with stillbirth risk was assessed, expressed as relative risk (RR) with 95% CI. RESULTS: The optimal cut-off limits for normal growth rate between consecutive scans varied according to the length of the measurement interval, with an average of -8.0% for slow growth and + 9.3% for accelerated growth at a fixed FPR of 10%. Slow growth between random consecutive scan pairs was associated significantly with all predefined outcome measures including stillbirth (RR, 2.19; 95% CI, 1.84-2.53) and neonatal death (RR, 2.28; 95% CI, 1.60-3.13). Accelerated growth was associated with LGA at birth (RR, 2.15; 95% CI, 2.10-2.20), while normal growth was protective of all adverse outcome measures. Slow growth between the last two scans (which were performed at a median gestational age of 33 + 1 to 36 + 4 weeks) and SGA at the last scan were each predictors of stillbirth, and stillbirth risk was highest when both were present (RR, 2.65; 95% CI, 1.67-4.20). However, 66.2% of pregnancies with slow growth were not SGA at the last scan and these cases also had an increased risk of stillbirth (RR, 2.07; 95% CI, 1.40-3.05). CONCLUSION: Fetal growth velocity defined by projected, measurement-interval specific fetal weight limits is associated independently with perinatal outcome and should be used for antenatal surveillance in addition to assessment by fetal size. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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.

Growth Failure Prevalence in Neonates with Gastroschisis : A Statewide Cohort Study.

OBJECTIVES: To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis. STUDY DESIGN: This study included neonates with gastroschisis within sites in the University of California Fetal Consortium. The study's primary outcome was growth failure at hospital discharge, defined as a weight or length z score decrease >0.8 from birth. Regression analysis was performed to assess changes in z scores over time. RESULTS: Among 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35-37). Length of stay was 32 days (23-60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z scores at 14 days, 30 days, and discharge were less than birth (P < .01 for all). Weight and length z scores declined from birth to 30 days (-0.10 and -0.11 z score units/week, respectively, P < .001). Length growth failure at discharge was associated with weight and length z score changes over time (P < .05 for both). Lower gestational age was associated with weight growth failure (OR 0.70 for each gestational age week, 95% CI 0.55-0.89, P = .004). CONCLUSIONS: Growth failure, in particular linear growth failure, is common in infants with gastroschisis. These data suggest the need to improve nutritional management in these infants.

Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

BACKGROUND: Human growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth. OBJECTIVE: This study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks' gestation based on the same cohort that contributed to the INTERGROWTH-21st Fetal Growth Standards. STUDY DESIGN: This study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21st Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks' gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4-7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression. RESULTS: Peak velocity was observed at a similar gestational age: 16 and 17 weeks' gestation for head circumference (12.2 mm/wk), and 16 weeks' gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks' gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work. CONCLUSION: The fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21st Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21st tools at https://intergrowth21.tghn.org/standards-tools/.