Comparing population-based fetal growth standards in a US cohort.

BACKGROUND: No fetal growth standard is currently endorsed for universal use in the United States. Newer standards improve upon the methodologic limitations of older studies; however, before adopting into practice, it is important to know how recent standards perform at identifying fetal undergrowth or overgrowth and at predicting subsequent neonatal morbidity or mortality in US populations. OBJECTIVE: To compare classification of estimated fetal weight that is <5th or 10th percentile or >90th percentile by 6 population-based fetal growth standards and the ability of these standards to predict a composite of neonatal morbidity and mortality. STUDY DESIGN: We used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be cohort, which recruited nulliparous women in the first trimester at 8 US clinical centers (2010-2014). Estimated fetal weight was obtained from ultrasounds at 16 to 21 and 22 to 29 weeks of gestation (N=9534 women). We calculated rates of fetal growth restriction (estimated fetal weight <5th and 10th percentiles; fetal growth restriction<5 and fetal growth restriction<10) and estimated fetal weight >90th percentile (estimated fetal weight>90) from 3 large prospective fetal growth cohorts with similar rigorous methodologies: INTERGROWTH-21, World Health Organization-sex-specific and combined, Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific and unified, and the historic Hadlock reference. To determine whether differential classification of fetal growth restriction or estimated fetal weight >90 among standards was clinically meaningful, we then compared area under the curve and sensitivity of each standard to predict small for gestational age or large for gestational age at birth, composite perinatal morbidity and mortality alone, and small for gestational age or large for gestational age with composite perinatal morbidity and mortality. RESULTS: The standards classified different proportions of fetal growth restriction and estimated fetal weight>90 for ultrasounds at 16 to 21 (visit 2) and 22 to 29 (visit 3) weeks of gestation. At visit 2, the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific, World Health Organization sex-specific and World Health Organization-combined identified similar rates of fetal growth restriction<10 (8.4%-8.5%) with the other 2 having lower rates, whereas Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific identified the highest rate of fetal growth restriction<5 (5.0%) compared with the other references. At visit 3, World Health Organization sex-specific classified 9.2% of fetuses as fetal growth restriction<10, whereas the other 5 classified a lower proportion as follows: World Health Organization-combined (8.4%), Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific (7.7%), INTERGROWTH (6.2%), Hadlock (6.1%), and Eunice Kennedy Shriver National Institute of Child Health and Human Development unified (5.1%). INTERGROWTH classified the highest (21.3%) as estimated fetal weight>90 whereas Hadlock classified the lowest (8.3%). When predicting composite perinatal morbidity and mortality in the setting of early-onset fetal growth restriction, World Health Organization had the highest area under the curve of 0.53 (95% confidence interval, 0.51-0.53) for fetal growth restriction<10 at 22 to 29 weeks of gestation, but the areas under the curve were similar among standards (0.52). Sensitivity was generally low across standards (22.7%-29.1%). When predicting small for gestational age birthweight with composite neonatal morbidity or mortality, for fetal growth restriction<10 at 22 to 29 weeks of gestation, World Health Organization sex-specific had the highest area under the curve (0.64; 95% confidence interval, 0.60-0.67) and INTERGROWTH had the lowest (area under the curve=0.58; 95% confidence interval 0.55-0.62), though all standards had low sensitivity (7.0%-9.6%). CONCLUSION: Despite classifying different proportions of fetuses as fetal growth restriction or estimated fetal weight>90, all standards performed similarly in predicting perinatal morbidity and mortality. Classification of different percentages of fetuses as fetal growth restriction or estimated fetal weight>90 among references may have clinical implications in the management of pregnancies, such as increased antenatal monitoring for fetal growth restriction or cesarean delivery for suspected large for gestational age. Our findings highlight the importance of knowing how standards perform in local populations, but more research is needed to determine if any standard performs better at identifying the risk of morbidity or mortality.

Role of coconut shell biochar and earthworm (Eudrilus euginea) in bioremediation and palak spinach (Spinacia oleracea L.) growth in cadmium-contaminated soil.

The contamination of soil with heavy metals is known to affect the yield the soil fertility, which in turn affects the growth of agricultural crops. This study investigates the role of coconut shell biochar (CSB) and earthworms (Eudrilus euginea) in the bioremediation and growth of Palak spinach (Spinacia oleracea L.) in cadmium (Cd) contaminated soil. The soils were amended with different combinations of CSB and earthworms and incubated for 35 days. Later, the soil samples were analyzed for the changes in the soil properties, soil enzyme activity, and heavy metal contents. It is observed that the treatments with both CSB and earthworms resulted in the improvement of soil properties and soil enzyme activity which was directly related to soil fertility. Meanwhile, the maximum removal of 94.38% of total Cd content in the soil was obtained for the soil sample contain both CSB and earthworms. The improved soil properties resulted in a higher germination percentage of Spinacia oleracea L. seeds in the Cd contaminated soil.

Dichorionic twin-specific vs singleton growth references for diagnosis of fetal growth restriction.

BACKGROUND: Fetal growth restriction is associated with an increased risk for adverse neonatal outcomes. The Hadlock singleton growth reference is widely used to determine the estimated fetal weight percentile for both twin and singleton gestations. The Eunice Kennedy Shriver National Institute of Child Health and Human Development's twin-specific growth reference accounts for the different growth trajectory that twins follow during gestation. There is a lack of research comparing these different growth references in their ability to identify fetal growth restriction that is associated with adverse neonatal outcomes in dichorionic twin gestations. OBJECTIVE: This study aimed to compare a twin-specific growth reference (the Eunice Kennedy Shriver National Institute of Child Health and Human Development's twin-specific growth reference) and a singleton growth reference (Hadlock) in their ability to identify fetal growth restriction associated with adverse neonatal outcomes in dichorionic twin gestations. STUDY DESIGN: This was a retrospective cohort study of dichorionic twin gestations at ≥32 weeks' gestation delivered at a single institution between 2004 and 2019 with the serial growth ultrasounds and neonatal outcomes data available for analysis. Using their last growth ultrasound before delivery, twins were classified into the following 3 categories: fetal growth restriction according to both the Hadlock and Eunice Kennedy Shriver National Institute of Child Health and Human Development references, fetal growth restriction according to the Hadlock reference only, and no fetal growth restriction according to either reference, with fetal growth restriction defined as an estimated fetal weight of <10th percentile for gestational age. Multivariable generalized linear mixed models were used to assess the adverse neonatal outcomes via pair-wise comparisons between the groups, with a random-effects component to account for twin-pair correlations. RESULTS: A total of 1460 dichorionic twin infants were included with 8.1% (n=118) of cases classified as fetal growth restricted by both the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Hadlock references, 8.8% (n=129) of cases classified as fetal growth restricted by the Hadlock reference only, and 83.1% (n=1213) of cases classified as no fetal growth restriction by either reference. Compared with twins with no fetal growth restriction by either reference, twins with fetal growth restriction by both references were more likely to experience mild (adjusted odds ratio, 2.38; confidence interval, 1.38-4.13) or severe (adjusted odds ratio, 2.82; confidence interval, 1.16-6.88) composite neonatal morbidity. Compared with twins with fetal growth restriction according to the Hadlock reference only, twins with fetal growth restriction according to both references were more likely to experience mild (adjusted odds ratio, 2.03; confidence interval, 1.00-4.14) but not severe (adjusted odds ratio, 3.70; confidence interval, 0.72-18.90) composite neonatal morbidity. Composite neonatal morbidity was not different between twins with fetal growth restriction according to the Hadlock reference only and those with no fetal growth restriction by either growth reference. CONCLUSION: The Eunice Kennedy Shriver National Institute of Child Health and Human Development's twin-specific growth reference better identifies the risk for adverse neonatal outcomes in dichorionic twin gestations diagnosed with fetal growth restriction. The use of the Hadlock singleton growth reference more than doubles the number of dichorionic twins identified with fetal growth restriction who seem to be at a low-risk for neonatal morbidity, leading to unnecessary maternal anxiety, increased antenatal testing, and possibly iatrogenic preterm delivery.

Oil supplementation improved growth and diet digestibility in goats and sheep fed fattening diet.

OBJECTIVE: This study evaluated the growth, digestibility and rumen fermentation between goats and sheep fed a fattening diet fortified with linseed oil. METHODS: Twelve 3 to 4 months old male goats and sheep were randomly allocated into two dietary treatment groups in a 2 (species)×2 (oil levels) factorial experiment. The treatments were: i) goats fed basal diet, ii) goats fed oil-supplemented diet, iii) sheep fed basal diet, and iv) sheep fed oil-supplemented diet. Each treatment group consisted of six animals. Animals in the basal diet group were fed with 30% alfalfa hay and 70% concentrates at a rate equivalent to 4% of their body weight. For the oil treatment group, linseed oil was added at 4% level (w:w) to the concentrate portion of the basal diet. Growth performance of the animals was determined fortnightly. Digestibility study was conducted during the final week of the feeding trial before the animals were slaughtered to obtain rumen fluid for rumen fermentation characteristics study. RESULTS: Sheep had higher (p<0.01) average daily weight gain (ADG) and better feed conversion ratio (FCR) than goats. Oil supplementation did not affect rumen fermentation in both species and improved ADG by about 29% and FCR by about 18% in both goats and sheep. The above enhancement is consistent with the higher dry matter and energy digestibility (p<0.05), as well as organic matter and neutral detergent fiber digestibility (p<0.01) in animals fed oil- supplemented diet. Sheep had higher total volatile fatty acid production and acetic acid proportion compared to goat. CONCLUSION: The findings of this study suggested that sheep performed better than goats when fed a fattening diet and oil supplementation at the inclusion rate of 4% provides a viable option to significantly enhance growth performance and FCR in fattening sheep and goats.

Estimating Gestational Age With Sonography: Regression-Derived Formula Versus the Fetal Biometric Average.

OBJECTIVES: To compare the accuracy of a new regression-derived formula developed from the National Fetal Growth Studies data to the common alternative method that uses the average of the gestational ages (GAs) calculated for each fetal biometric measurement (biparietal diameter, head circumference, abdominal circumference, and femur length). METHODS: This retrospective cross-sectional study identified nonanomalous singleton pregnancies that had a crown-rump length plus at least 1 additional sonographic examination with complete fetal biometric measurements. With the use of the crown-rump length to establish the referent estimated date of delivery, each method's (National Institute of Child Health and Human Development regression versus Hadlock average [Radiology 1984; 152:497-501]), error at every examination was computed. Error, defined as the difference between the crown-rump length-derived GA and each method's predicted GA (weeks), was compared in 3 GA intervals: 1 (14 weeks-20 weeks 6 days), 2 (21 weeks-28 weeks 6 days), and 3 (≥29 weeks). In addition, the proportion of each method's examinations that had errors outside prespecified (±) day ranges was computed by using odds ratios. RESULTS: A total of 16,904 sonograms were identified. The overall and prespecified GA range subset mean errors were significantly smaller for the regression compared to the average (P < .01), and the regression had significantly lower odds of observing examinations outside the specified range of error in GA intervals 2 (odds ratio, 1.15; 95% confidence interval, 1.01-1.31) and 3 (odds ratio, 1.24; 95% confidence interval, 1.17-1.32) than the average method. CONCLUSIONS: In a contemporary unselected population of women dated by a crown-rump length-derived GA, the National Institute of Child Health and Human Development regression formula produced fewer estimates outside a prespecified margin of error than the commonly used Hadlock average; the differences were most pronounced for GA estimates at 29 weeks and later.

Continuous culture techniques as simulators for standard cells: Jacques Monod's, Aron Novick's and Leo Szilard's quantitative approach to microbiology.

Continuous culture techniques were developed in the early twentieth century to replace cumbersome studies of cell growth in batch cultures. In contrast to batch cultures, they constituted an open concept, as cells are forced to proliferate by adding new medium while cell suspension is constantly removed. During the 1940s and 1950s new devices have been designed-called "automatic syringe mechanism," "turbidostat," "chemostat," "bactogen," and "microbial auxanometer"-which allowed increasingly accurate quantitative measurements of bacterial growth. With these devices cell growth came under the external control of the experimenters and thus accessible for developing a mathematical theory of growth kinetics-developed mainly by Jacques Monod, Aron Novick and Leo Szilard in the early 1950s and still in use today. The paper explores the development of continuous culture devices and claims that these devices are simulators for standard cells following specific requirements, in particular involving mathematical constraints in the design and setting of the devices as well as experiments. These requirements have led to contemporary designs of continuous culture techniques realizing a specific event-based flow algorithm able to simulate directed evolution and produce artificial cells and microorganisms. This current development is seen as an alternative approach to today's synthetic biology.

Chassis organism from Corynebacterium glutamicum--a top-down approach to identify and delete irrelevant gene clusters.

For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application.