Pediatric paradox: heterogeneity in the birth cohort

Comparisons of birth-weight-specific infant mortality indicate that low-birth-weight African American infants have lower mortality than low-birth-weight European American infants despite higher infant mortality overall-the "pediatric paradox." One explanation is heterogeneity in birth weight. Analyses of African American and European American births suggest that birth cohorts consist of two heterogeneous subpopulations. One appears to account for normal births, whereas the other may consist of compromised births. Estimates of infant mortality indicate that the compromised subpopulation has higher overall mortality but lower birth-weight-specific mortality. We attribute lower birth-weight-specific infant mortality in the compromised subpopulation to higher rates of fetal loss. Compared to European American birth cohorts, African American birth cohorts have (1) higher birth-weight-specific mortality in the normal subpopulation, (2) larger compromised subpopulations, and (3) lower birth-weight-specific mortality in the compromised subpopulation. Consequently, the pediatric paradox is attributable to greater rates of compromised pregnancies and higher fetal losses among African Americans.     

Mortality rate of Japanese twins: Infant deaths of twins after birth to one year of age

Abstract

In twin individuals born in Japan in the first half of 1974, rates of infant mortality up to one year of age were computed according to sex and order of birth. The rates were 5.50 per cent for males and 3.81 per cent for females. A lower mortality rate for first‐born twins indicates a reduced viability for second‐born twins, even in MZ twins. The effect of maternal age, gestational age, and birth weight on the rates of infant mortality were also analyzed.     

Placental growth patterns affect birth weight for given placental weight

BACKGROUND: An important contributor to fetal growth is growth of the placenta, the fetus' sole source of nutrients and oxygen. Here we use placental growth measures (larger and smaller disk diameters, reflecting the laterally expanding chorionic plate, and disk thickness) to test the hypothesis that placental growth patterns, while associated with placental weight and birth weight, measure placental functional efficiency, and will have independent effects on the feto-placental weight ratio (FPR). METHODS: Placental measures were available from 23,313 participants in the Collaborative Perinatal Project delivered between 34 and 43 completed weeks. Continuous variables were analyzed by regression for associations with placental weight, birth weight, and FPR, to further explore effects of placental growth patterns on the FPR (lateral chorionic plate growth and chorionic disk thickness were grouped as low, normal, and high values). The relationships of the nine resultant combinations of placental growth categories to the FPR using birth weight adjusted for gestational age, infant gender, parity, and African American race were analyzed (ANOVA). RESULTS: As chorionic disk area and thickness increased, birth weight and placental weight increased, and the FPR decreased (each p < .0001) after adjustment for gestational age, parity, race, and infant gender. Small, thin placental disks had an adjusted FPR of 8.46; the largest, thickest placentas had an adjusted FPR of 6.33. The nine categories of FPRs were significantly different, consistent with chorionic plate area and disk thickness combining to determine the FPR. CONCLUSIONS: Patterns of placental growth, relating to different functional dimensions of the placenta, deliver a different birth weight for a given placental weight.     

Maternal Glomerular Filtration Rate in Pregnancy and Fetal Size

BackgroundThe relationship of maternal glomerular filtration rate (GFR) in pregnancy to fetal size needs to be better characterized as it impacts an ongoing debate about confounding effect of maternal GFR in investigations of important environmental contaminants. We aimed to characterize the size of the association between maternal GFR and infant birth weight.ResultsMaternal GFR-CG (β: 0.73 g/ml/min, p = 0.04) and GFR-MDRD (β: 0.83 g/ml/min, p = 0.04) were associated with infant birth weight in models adjusted for maternal weight in kilograms, preeclampsia, and gestational age at delivery (days). Partial correlation coefficients for the association between infant birth weight and GFR were 0.07 for both formulas. Although the birth weight-GFR association was stronger among the women with preeclampsia, the difference from women without preeclampsia was not statistically significant.ConclusionThese data support an association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations.     

Reexamination of interpregnancy intervals and subsequent birth outcomes: Evidence from U.S. linked birth/infant death records

Abstract

This study examines the net effects of the interpregnancy interval (time period from one birth to the next pregnancy) on the risks of preterm birth, intrauterine growth retardation, and infant mortality, for blacks and whites separately, using data from 1991 U.S. Linked Birth‐Infant Death files. Results show that short (less than 7 months) and long (61+ months) intervals between pregnancies raise the risk of preterm birth and intrauterine growth retardation for both race groups, though the increase in risk is generally less than 30 per cent. Short intervals also raise (slightly) the risk of infant mortality after controlling for birthweight and gestational age.     

Case fatality among infants with congenital malformations by lethality

OBJECTIVE: Infant mortality rates continue to show that congenital anomalies are the leading cause of infant death in the United States. However, studies of factors contributing to increased mortality across different types of congenital anomalies have been limited. The objective of this study was to assess whether the likelihood of infant mortality varied by maternal race and ethnic group while considering the severity of the birth defect. METHODS: A retrospective cohort analysis was conducted using data from Colorado's statewide, population-based birth defects surveillance system (CRCSN). The cohort included infants, born between 1995 and 2000 to Colorado resident mothers, who were diagnosed with major congenital malformations stratified by degree of lethality. Multiple logistic regression was performed for each level of lethality, and included the following potential explanatory variables: maternal race/ethnicity, clinical gestation, birth weight, maternal education level, maternal age, and sex of child. RESULTS: Within the low/very low lethality cohort, maternal race/ethnicity of Black/non-Hispanic was associated with increased risk of infant mortality, OR 2.81 (1.41-5.19), as were low and very low birth weight, OR 2.21 (1.12-4.04) and 19.31 (11.84-31.01), respectively. Maternal race/ethnicity was not a significant risk factor in either high or very high lethality groups; however, the interaction between birth weight and gestational age significantly increased the risk of mortality. CONCLUSIONS: Through the use of statewide, population-based birth defects surveillance data, a disparity in infant mortality has been identified in a specific subset of the population that could be investigated further and targeted for prevention activities.     

Serum zinc levels of cord blood: Relation to birth weight and gestational period

BackgroundZn-deficiency has been associated with numerous alterations during pregnancy including low birth weight; however, the research relating neonatal zinc status and birth weight has not produced reliable results.ObjectiveTo compare the serum Zn-levels of cord blood in healthy newborns and low birth weight newborns, and to assess a possible relationship between zinc concentration and neonatal birth weight and gestational age.Material and methods123 newborns divided in “study group” (n = 50) with <2500 g birth weight neonates and “control group” (n = 73) with ≥2500 g birth weight neonates were enrolled. Study group was subdivided according to gestational age in preterm (<37 weeks) and full-term (≥37 weeks). Serum cord blood samples were collected and the Zn-levels were analyzed using flame Atomic Absorption Spectrophotometry method and the result was expressed in μmol/L. The Zn-levels were compared between the groups (Mann–Whitney-U test) and the Zn-levels were correlated with the birth weight and gestational age (Spearman's rank correlations).ResultsStatistically significant low positive correlation between Zn-levels and birth weight (ρ = 0.283; p = 0.005) was found. No statistically significant difference between Zn-levels of study and control groups [17.00 ± 0.43 vs. 18.16 ± 0.32 (p = 0.053)] was found. Statistically significant low positive correlation between Zn-levels and gestational age (ρ = 0.351; p = 0.001) was found. No statistically significant difference between Zn-levels of preterm as compare to full-term newborns [16.33 ± 0.42 vs. 18.43 ± 0.93 (p = 0.079)] was found. Zn-level of preterm subgroup was significantly lower compared to control group (p = 0.001).ConclusionsDespite low birth weight preterm neonates had significantly lower serum zinc levels of cord blood than healthy term neonates, the correlation between cord blood zinc levels and birth weight and gestational age was lower. The results are not enough to relate the change in cord blood zinc concentration to the birth weight values or gestational period. In relation to complicated pregnancies, further studies regarding zinc levels in blood in our population are required.     

Twin differences in birth weight: the effects of genotype and prenatal environment on neonatal and post-neonatal mortality.

There is much evidence to suggest that both genes and prenatal environment influence life chances. However, recent within-twin estimates also raise questions about how the influence of genes and prenatal environment may vary across different subgroups of a population and over time. This paper explores such potential variation within the 1st year of life. Using data on twin births from the 1995-1997 Matched Multiple Birth Database and an analytic strategy based on the Weinberg assumption, this paper considers how associations between birth weight and infant mortality vary across identical and fraternal twins, gestational age, and time. Results suggest that the influence of genes and prenatal environment vary most significantly by gestational age. In pregnancies that lasted less than 37 weeks, within-twin variation in prenatal environment is able to account for negative associations between birth weight and infant mortality. However, in pregnancies that lasted 37 weeks or longer, underlying genetic variation across fraternal twins appears to be largely responsible for birth weight-mortality associations. Such distinct findings by gestation suggest that genes and prenatal environment may play varying roles in birth weight-mortality associations across different situations.     

Chronotype in very low birth weight adults – a sibling study

ABSTRACT

Chronotype is the temporal preference for activity and sleep during the 24 h day and is linked to mental and physical health, quality of life, and mortality. Later chronotypes, so-called “night owls”, consistently display poorer health outcomes than “larks”. Previous studies have suggested that preterm birth (<37 weeks of gestation) is associated with an earlier chronotype in children, adolescents, and young adults, but studies beyond this age are absent. Our aim was to determine if adults born preterm at very low birth weight (VLBW, ≤1500 g) display different chronotypes than their siblings. We studied VLBW adults, aged 29.9 years (SD 2.8), matched with same-sex term-born siblings as controls. A total of 123 participants, consisting of 53 sibling pairs and 17 unmatched participants, provided actigraphy-derived data on the timing, duration, and quality of sleep from 1640 nights (mean 13.3 per participant, SD 2.7). Mixed effects models provided estimates and significance tests. Compared to their siblings, VLBW adults displayed 27 min earlier sleep midpoint during free days (95% CI: 3 to 51 min, p =.029). This was also reflected in the timing of falling asleep, waking up, and sleep-debt corrected sleep midpoint. The findings were emphasized in VLBW participants born small for gestational age. VLBW adults displayed an earlier chronotype than their siblings still at age 30, which suggests that the earlier chronotype is an enduring individual trait not explained by shared family factors. This preference could provide protection from risks associated with preterm birth.     

高龄孕妇分娩新生儿出生体重及出院转归的影响因素分析

摘要 目的：探讨高龄孕妇分娩新生儿出生体重及出院转归的影响因素。方法：选择2021年01月到2022年01月与我院就诊的198例产妇作为研究对象,根据孕妇分娩时的年龄分为观察组和对照组,分娩时年龄满35周岁为高龄产妇组（98例）,分娩时年龄为20~34周岁为适龄组（100例）。比较适龄孕妇和高龄孕妇新生儿出生体重情况和新生儿住院时间,对高龄孕妇新生儿体重和新生儿出院转归影响因素进行Logistic单因素分析和多因素分析。结果：与适龄孕妇相比,高龄孕妇新生儿低出生体重儿、巨大儿发生率更高（P<0.05）,新生儿住院时间明显更长（P<0.05）。对高龄孕妇新生儿体重进行单因素分析结果显示,妊娠糖尿病、产检检查、分娩方式、是否使用催产素、分娩时麻醉方式和脐带情况与高龄孕妇新生儿体重无关（P>0.05）,孕妇年龄、孕前BMI、孕期体重增加情况、妊娠高血压、合并其他疾病状况、孕次、产次、羊水情况与高龄孕妇新生儿体重相关（P<0.05）。进行Logistic多因素回归分析结果显示,孕妇年龄、孕前BMI、孕期体重增加情况、孕次、产次、羊水情况是影响高龄孕妇新生儿出生体重的独立危险因素（P<0.05）。对新生儿出院转归情况进行单因素分析结果显示,胎次、开奶时间、喂养方式和有无接受治疗与新生儿出院转归无相关性（P>0.05）,胎龄、出生体重、Apgar评分、出生窒息史、有无伴发疾病与新生儿转归相关（P<0.05）。进行Logistic多因素分析结果显示,胎龄、出生体重、Apgar评分、出生窒息史、有无伴发病是影响新生儿出院转归的独立危险因素（P<0.05）。结论：孕妇年龄、孕前BMI、孕期体重增加情况、孕次、产次、羊水情况是影响高龄孕妇新生儿出生体重的独立危险因素。新生儿出院转归受到胎龄、出生体重、Apgar评分、出生窒息史、有无伴发病影响。     

Maternal Cadmium Levels during Pregnancy Associated with Lower Birth Weight in Infants in a North Carolina Cohort

Cadmium (Cd) is a ubiquitous environmental contaminant, a known carcinogen, and understudied as a developmental toxicant. In the present study, we examined the relationships between Cd levels during pregnancy and infant birth outcomes in a prospective pregnancy cohort in Durham, North Carolina. The study participants (n = 1027) had a mean Cd level of 0.46 µg/L with a range of <0.08 to 2.52 µg/L. Multivariable models were used to establish relationships between blood Cd tertiles and fetal growth parameters, namely birth weight, low birth weight, birth weight percentile by gestational age, small for gestational age, pre-term birth, length, and head circumference. In multivariable models, high maternal blood Cd levels (≥0.50 µg/L) during pregnancy were inversely associated with birth weight percentile by gestational age (p = 0.007) and associated with increased odds of infants being born small for gestational age (p<0.001). These observed effects were independent of cotinine-defined smoking status. The results from this study provide further evidence of health risks associated with early life exposure to Cd among a large pregnancy cohort.     

Birth-weight-specific infant and neonatal mortality: effects of heterogeneity in the birth cohort

Birth-weight-specific infant mortality is examined using a novel statistical procedure, parametric mixtures of logistic regressions. The results indicate that birth cohorts are composed of two or more subpopulations that are heterogeneous with respect to infant mortality. One subpopulation appears to account for the "normal" process of fetal development, while the other, which accounts for the majority of births at both low and high birth weights, may represent fetuses that were "disturbed" during development. Surprisingly, estimates of neonatal and infant mortality indicate that the "disturbed" subpopulation has lower birth-weight-specific mortality, although overall crude mortality rates are higher for this subpopulation. It is hypothesized that this is due to high rates of fetal loss among the "disturbed" subpopulation, resulting in a highly selected group at birth. The heterogeneity identified in the birth cohort could be responsible for recent decelerations in the decline in infant mortality, and might be the cause of unexplained ethnic differences in birth-weight-specific infant mortality. The novel statistical methodology developed here has broad application within human biology. In particular, it could be used in any context where parametric mixture modeling is applied, such as complex segregation analysis.     

Trends in All-Cause Mortality across Gestational Age in Days for Children Born at Term

Background

Term birth is a gestational age from 259 days to 293 days. However trends in mortality according to gestational ages in days have not yet been described in this time period.

Methods and Findings

Based on nation-wide registries, we conducted a population-based cohort study among all children born at term in Denmark from 1997 to 2004 to estimate differences in mortality across gestational ages in days among singletons born at term. We studied early-neonatal mortality, neonatal mortality, infant mortality, and five-year mortality. Children were followed from birth up to the last day of the defined mortality period or December 31, 2009. A total of 360,375 singletons born between 259 and 293 days of gestation were included in the study. Mortality decreased with increasing gestational age in days and the highest mortality was observed among children born at 37 week of gestation. A similar pattern was observed when analyses were restricted to children born to by mothers without pregnancy complications.

Conclusions

This study demonstrates heterogeneity in mortality rates even among singletons born at term. The highest mortality was observed among children born 37 weeks of gestation, which call for cautions when inducing labor in term pregnancies just reaching 37 weeks of gestation. The findings support that 37 weeks of gestation should be defined as early term.     

Gastroschisis, low maternal age, and fetal morbidity outcomes

OBJECTIVE: To determine if the risk for fetal growth inhibition among gastroschisis-afflicted fetuses is heightened among younger gravidas (teen mothers). METHOD: This was a retrospective cohort study on live-born infants with isolated gastroschisis delivered in New York State from 1983 through 1999. We compared infants of mature (>20 years) mothers with those of younger (<20 years) mothers with respect to the following indices of fetal morbidity outcomes: low birth weight and very low birth weight, preterm and very pre-term, and small for gestational age. We used adjusted odds ratios to approximate relative risks. RESULTS: A total of 368 infants with isolated gastroschisis were analyzed. The two groups differed in terms of mean gestational age at delivery [Mean + standard deviation(SD) for infants with gastroschisis born to mature mothers = 37.2 weeks +/- 2.8 versus 36.3 weeks + 3.6 for those of teenage mothers(p = 0.01)], as well as mean birth weight [mean birth weight +/- SD for infants with gastroschisis born to mature mothers = 2562.4 grams +548.8 versus 2367.9 grams +/- 645.2 for those of younger mothers (p = 0.004)]. Infants of teen mothers were about twice as likely to be of low birth weight (OR = 1.70; 95% CI = 1.05-2.77) and about three times as likely to be born very preterm when compared to those of mature mothers (OR = 2.80; 95% Cl = 1.02-8.00). No significant differences were observed with respect to very low birth weight, pre-term and small for gestational age. CONCLUSION: Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.     

Maternal, neonatal and community factors influencing neonatal mortality in Brazil

Child mortality (the mortality of children less than five years old) declined considerably in the developing world in the 1990s, but infant mortality declined less. The reductions in neonatal mortality were not impressive and, as a consequence, there is an increasing percentage of infant deaths in the neonatal period. Any further reduction in child mortality, therefore, requires an understanding of the determinants of neonatal mortality. 209,628 birth and 2581 neonatal death records for the 1998 birth cohort from the city of S?o Paulo, Brazil, were probabilistically matched. Data were from SINASC and SIM, Information Systems on Live Births and Deaths of Brazil. Logistic regression was used to find the association between neonatal mortality and the following risk factors: birth weight, gestational age, Apgar scores at 1 and 5 minutes, delivery mode, plurality, sex, maternal education, maternal age, number of prior losses, prenatal care, race, parity and community development. Infants of older mothers were less likely to die in the neonatal period. Caesarean delivery was not found to be associated with neonatal mortality. Low birth weight, pre-term birth and low Apgar scores were associated with neonatal death. Having a mother who lives in the highest developed community decreased the odds of neonatal death, suggesting that factors not measured in this study are behind such association. This result may also indicate that other factors over and above biological and more proximate factors could affect neonatal death.     

Perinatal mortality in term and preterm twin and singleton births.

Although, in general, twins have higher perinatal mortality rates than singletons, preterm twins have lower perinatal mortality rates than singletons of the same birth weight or gestational age. This study investigated the hypotheses that this paradoxical twin advantage: 1) is due to gestational age distribution differences between the singleton and twin populations, and 2) is due to increased likelihood of birth having occurred in a tertiary perinatal center. A pre-existing, time-limited data set of all births in the province of Ontario in odd years between 1979 and 1985 was chosen for this study because of the large sample size (n = 618,579). Multivariable logistic regression of the relationship between perinatal mortality and twin status was controlled for mother's age, hospital level and gestational age. Findings confirm the lower mortality of preterm twins. After controlling for level of hospital of birth this difference remained, suggesting that level of hospital of birth was not a major factor responsible for the twin advantage. Analyses in which gestational age was standardized indicate that, for those whose gestational age was less than 2 SD below the mean for their particular group (twin or singleton), twins were actually at higher risk than singletons. These results support hypothesis 1 and do not strongly support hypothesis 2. The results also support earlier authors' suggestions that the definition of term birth should be different for twins and singletons     

Increasing pre-term and low-birth-weight rates over time and their impact on infant mortality in south-east Brazil

This study investigates the possible effects of pre-term births and low birth weight on infant mortality rates (IMRs) over a 15-year period in Ribeir?o Preto, Brazil, based on surveys carried out in 1978/79 and 1994. The 1978/79 survey included 6750 births over a 12-month period and the 1994 survey 2846 births over a 4-month period. Infant deaths were retrieved monthly from the city register. Infant mortality rate decreased from 36.6 to 16.9 deaths per 1000 over 15 years. The decrease in IMR was larger in the 2500-2999 g group than in any other group. The observed falls in IMR were attributable to decreases in birth-weight-specific mortality rates. Likewise, there was a general decrease in IMR in mild, moderate and severe pre-term births. The incidence rate ratio of infant mortality between surveys was 0.46 (95% CI 0.34-0.63); it increased to 0.57 (95% CI 0.35-0.75) when adjusted for birth weight and other factors in the model and rose to 0.69 (95% CI 0.49-0.97) when adjusted for length of gestation and other variables. The increase in pre-term births and low birth weight may have had, at most, a marginal effect on the IMR. Progress in the care of newborns may have decreased the mortality risk, but even mild pre-term birth still has an impact on infant mortality. There is room for further improvement in IMR by tackling the high rates of pre-term birth.     

Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis

Background

Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach.

Methods and Findings

We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10⁻⁹), birth weight (p = 2.19 × 10⁻¹⁵), and gestational age (p = 1.51 × 10⁻⁷). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects.

Conclusions

Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.     

Quantification Methodology of “Health Human Resources” Related to “Health Technologies” Based on Indicators “RhSan”, “TechSan” and “RhTech”: Application to Senegal

ObjectivesAfter a century of spectacular advances, healthcare systems are facing unprecedented crisis, linked to shortage of health human resources and health technologies. In fact, availability of care depends on both technological and human resources of health. The objective of this study is to develop indicators that can measure qualitatively human resources and technologies of health in healthcare facilities, in order to assess availability of care in sub-Saharan African countries.Materials and MethodsRegarding “health technology” related to “medical devices”, an indicator called “TechSan” for “Technologies de Santé” was previously developed and published (Ndione FB et al. (2019) [6]). To address the deficiencies in usual indicators related to health human resources, a second indicator called “RhSan” for “Ressources humaines de santé” in French is proposed. This indicator assigns a weight to each health worker taking into account his specific “level of medical knowledge” and “experience”. In order to correlate “RhSan” with “TechSan”, a third indicator called “RhTech” is also developed to assess matches between “health technologies” and “health human resources” and establish realistic availability of care. These indicators have the advantage to be consolidated by specialty such as laboratory, imaging, surgery, and “mother and child care”.ResultsThe application of TechSan, RhSan and RhTech to data collected in Senegal in 2016, enabled to assess the distribution of “health technology” and “health human resources” in this country. They also permit the mapping of care availability per specialty in Senegal. The results show a strong oversupply of Dakar in terms of both human resources and technologies of health compared to other Senegalese regions. Oppositely, Sedhiou, Kaffrine, Matam and Kédougou are poorly endowed showing limits of the Senegalese health pyramid system.ConclusionTechSan, RhSan and RhTech can provide reliable decision-making tools in order to elaborate health policies in sub-Saharan African countries on more rigorous basis.