Fetal cranial growth trajectories are associated with growth and neurodevelopment at 2 years of age: INTERBIO-21st Fetal Study.
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SUBMITTER: Villar J
PROVIDER: S-EPMC7613323 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
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Fetal cranial growth trajectories are associated with growth and neurodevelopment at 2 years of age: INTERBIO-21st Fetal Study.
Villar José J Gunier Robert B RB Tshivuila-Matala Chrystelle O O COO Rauch Stephen A SA Nosten Francois F Ochieng Roseline R Restrepo-Méndez María C MC McGready Rose R Barros Fernando C FC Fernandes Michelle M Carrara Verena I VI Victora Cesar G CG Munim Shama S Craik Rachel R Barsosio Hellen C HC Carvalho Maria M Berkley James A JA Cheikh Ismail Leila L Norris Shane A SA Ohuma Eric O EO Stein Alan A Lambert Ann A Winsey Adele A Uauy Ricardo R Eskenazi Brenda B Bhutta Zulfiqar A ZA Papageorghiou Aris T AT Kennedy Stephen H SH
Nature medicine 20210318 4
Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections)<sup>1</sup> and preventive interventions (for example, multiple-micronutrient supplementation)<sup>2</sup> that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood<sup>3</sup>. In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites w ...[more]
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Project description:BackgroundBeing born small for gestational age (SGA, <10th percentile) is a risk factor for worse neurodevelopmental outcomes. However, this group is a heterogeneous mix of healthy and growth-restricted babies, and not all will experience poor outcomes. We sought to determine whether fetal growth trajectories can distinguish who will have the worst neurodevelopmental outcomes in childhood among babies born SGA.MethodsThe present analysis was conducted in Generation R, a population-based cohort in Rotterdam, the Netherlands (N = 5,487). Using group-based trajectory modeling, we identified fetal growth trajectories for weight among babies born SGA. These were based on standard deviation scores of ultrasound measures from mid-pregnancy and late pregnancy in combination with birth weight. We compared child nonverbal intelligence quotient (IQ) and attention deficit hyperactivity disorder (ADHD) symptoms at age 6 between SGA babies within each growth trajectory to babies born non-SGA.ResultsAmong SGA individuals (n = 656), we identified three distinct fetal growth trajectories for weight. Children who were consistently small from mid-pregnancy (n = 64) had the lowest IQ (7 points lower compared to non-SGA babies, 95% confidence interval [CI] = -11.0, -3.5) and slightly more ADHD symptoms. Children from the trajectory that started larger but were smaller at birth showed no differences in outcomes compared to children born non-SGA.ConclusionsAmong SGA children, those who were smaller beginning in mid-pregnancy exhibited the worst neurodevelopmental outcomes at age 6. Fetal growth trajectories may help identify SGA babies who go on to have poor neurodevelopmental outcomes.
| S-EPMC8338787 | biostudies-literature
Project description:We sought to evaluate the relationships between fetal growth restriction (FGR) (both severe and less severe) and assessments of cognitive, academic, and adaptive behavior brain function at age 10 years. At age 10 years, the Extremely Low Gestational Age Newborns Cohort Study assessed the cognitive function, academic achievement, social-communicative function, psychiatric symptoms, and overall quality of life of 889 children born before 28 weeks' gestation. A pediatric epileptologist also interviewed parents as part of a seizure evaluation. The 52 children whose birth weight z scores were <-2 were classified as having severe FGR, and the 113 whose birth weight z scores were between -2 and -1 were considered to have less severe FGR. The more severe the growth restriction in utero, the lower the level of function on multiple cognitive and academic achievement assessments performed at age 10 years. Growth-restricted children were also more likely than their extremely preterm peers to have social awareness impairments, autistic mannerisms, autism spectrum diagnoses, difficulty with semantics and speech coherence, and diminished social and psychosocial functioning. They also more frequently had phobias, obsessions, and compulsions (according to teacher, but not parent, report). Among children born extremely preterm, those with severe FGR appear to be at increased risk of multiple cognitive and behavioral dysfunctions at age 10 years, raising the possibility that whatever adversely affected their intrauterine growth also adversely affected multiple domains of cognitive and neurobehavioral development.
| S-EPMC5654396 | biostudies-literature
Project description:ImportanceThe etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures.ObjectiveTo examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years.Design, setting, and participantsThe INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020.Exposures/interventionsPreterm-birth phenotypes.Main outcomes and measuresInfant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool.ResultsA total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype.Conclusions and relevanceResults of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.
| S-EPMC7922239 | biostudies-literature
Project description:BackgroundBabies born large-for-gestational age have an increased risk of adverse health outcomes, including birth injuries, childhood obesity, and cardiometabolic disorders. However, little work has been done to characterize patterns of fetal growth among large-for-gestational age births, which may further elucidate high- and low-risk subgroups.ObjectiveThis study aimed to identify subgroups of large-for-gestational age births based on trajectories of fetal growth derived from prenatal ultrasound measurements and explore differences in sociodemographic, pregnancy, and birth outcome characteristics across subgroups.Study designThis study identified and described trajectories of fetal growth among large-for-gestational age births (n=235) in the LIFECODES Fetal Growth Study. Ultrasound measurements of fetal growth in middle to late pregnancy were abstracted from health records. Group-based multi-trajectory modeling was applied to measurements of head circumference, abdominal circumference, and femur length z-scores to identify multivariate trajectories of fetal growth. Moreover, sociodemographic variables, pregnancy characteristics, and birth outcomes based on trajectory membership were summarized.ResultsThis study identified 4 multivariate trajectories of fetal growth among large-for-gestational age births: catch-up growth (n=28), proportional abdominal circumference-to-femur length growth (n=67), disproportional abdominal circumference-to-femur length growth (n=96), and consistently large (n=44). Fetuses in the "catch-up growth" group exhibited small relative sizes in midpregnancy (ie, below average head circumference, abdominal circumference, and femur length z-scores) and large relative sizes in late pregnancy. Growth among these births was driven by increases in relative abdominal circumference and head circumference sizes. Participants who delivered births assigned to this group were less likely to have normal glucose control (40% vs 65%-75%) and more likely to have pregestational diabetes mellitus (36% vs 10%-17%) than other large-for-gestational age subgroups. In addition, the babies in this trajectory group were more likely to have macrosomia (86% vs 67%-73%) and to be admitted to the neonatal intensive care unit (32% vs 14%-21%) than other large-for-gestational age subgroups. In contrast, babies in the "consistently large" group had the largest relative size for all growth parameters throughout gestation and experienced a lower risk of adverse birth outcomes than other large-for-gestational age subgroups.ConclusionThis study characterized several trajectories of fetal growth among large-for-gestational age births, which were related to different pregnancy characteristics and the distribution of adverse birth outcomes. Although the number of individuals within some trajectories was small, a subgroup that exhibited a catch-up growth phenotype during gestation was identified, which may be uniquely associated with exposure to pregestational diabetes mellitus and a higher risk of admission to the neonatal intensive care unit. These results have highlighted that the risk of adverse outcomes may not be evenly distributed across all large-for-gestational age births.
| S-EPMC9974610 | biostudies-literature
Project description:PurposeTo evaluate the contribution of genetic and early life environmental factors, as reflected by fetal anthropometric growth trajectories, toward the development of myopia during childhood and adolescence.MethodsThis analysis included 498 singleton Caucasian participants from the Raine Study, a pregnancy cohort study based in Western Australia. Serial fetal biometric measurements of these participants were collected via ultrasound scans performed at 18, 24, 28, 34, and 38 weeks' gestation. At a 20-year follow-up, the participants underwent a comprehensive ophthalmic examination, including cycloplegic autorefraction and ocular biometry measurements. Using a group-based trajectory modeling approach, we identified groups of participants with similar growth trajectories based on measurements of fetal head circumference (HC), abdominal circumference, femur length (FL), and estimated fetal weight (EFW). Differences between trajectory groups with respect to prevalence of myopia, axial length (AL), and corneal radius of curvature measured at the 20-year follow-up were evaluated via logistic regression and analysis of variance.ResultsPrevalence of myopia was highest among participants with consistently short or consistently long FLs (P = 0.04). There was also a trend toward increased prevalence with larger HC in late gestation, although not at a statistically significant level. Trajectory groups reflecting faster HC, FL, or EFW growth correlated with significantly flatter corneas (P = 0.03, P = 0.04, and P = 0.01, respectively) and a general, but not statistically significant, increase in AL.ConclusionsEnvironmental or genetic factors influencing intrauterine skeletal growth may concurrently affect ocular development, with effects persisting into adulthood.
| S-EPMC7774062 | biostudies-literature
Project description:BackgroundObesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment.MethodsIn the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m2, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto-placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants' health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis.FindingsFrom Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20-25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto-placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group.InterpretationEarly pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity.FundingBill & Melinda Gates Foundation.
| S-EPMC9622423 | biostudies-literature
Project description:Three recently completed longitudinal cohort studies have developed intrauterine fetal growth charts, one in the United States and two international. This expert review compares and contrasts the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies, INTERGROWTH-21st and World Health Organization Multicentre Growth Reference Study conclusions in light of differences in aims, sampling frames, and analytical approaches. An area of controversy is whether a single growth reference is representative of growth, regardless of ethnic or country origin. The INTERGROWTH and World Health Organization Fetal studies used a similar approach as the World Health Organization Multicentre Growth Reference Study for infants and children, the aim of which was to create a single international reference for the best physiological growth for children aged 0-5 years. INTERGROWTH made the same assumption (ie, that there would be no differences internationally among countries or racial/ethnic groups in fetal growth when conditions were optimal). INTERGROWTH found differences in crown-rump length and head circumference among countries but interpreted the differences as not meaningful and presented a pooled standard. The World Health Organization Multicentre Growth Reference Study was designed to create a pooled reference, although they evaluated for and presented country differences, along with discussion of the implications. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Study was designed to assess whether racial/ethnic-specific fetal growth standards were needed, in recognition of the fact that fetal size is commonly estimated from dimensions (head circumference, abdominal circumference, and femur length) in which there are known differences in children and adults of differing racial/ethnic groups. A pooled standard would be derived if no racial/ethnic differences were found. Highly statistically significant racial/ethnic differences in fetal growth were found resulting in the publication of racial/ethnic-specific derived standards. Despite all 3 studies including low-risk status women, the percentiles for fetal dimensions and estimated fetal weight varied among the studies. Specifically, at 39 weeks, the 50th percentile for estimated fetal weight was 3502 g for whites, 3330 g for Hispanics, 3263 g for Asians, and 3256 for blacks in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study, compared with 3186 g for INTERGROWTH and 3403 g for World Health Organization Multicentre Growth Reference Study. When applying these standards to a clinical population, it is important to be aware that different percentages of small- and large-for-gestational-age fetuses will be identified. Also, it may be necessary to use more restrictive cut points, such as the 2.5th or 97.5th, for small-for-gestational-age or large-for-gestational-age fetuses, respectively. Ideally, a comparison of diagnostic accuracy, or misclassification rates, of small-for-gestational-age and large-for-gestational-age fetuses in relation to morbidity and mortality using different criteria is necessary to make recommendations and remains an important data gap. Identification of the appropriate percentile cutoffs in relation to neonatal morbidity and mortality is needed in local populations, depending on which fetal growth chart is used. On a final point, assessment of fetal growth with a one-time measurement remains standard clinical practice, despite recognition that a single measurement can indicate only size. Ultimately, it is knowledge about fetal growth in addition to other factors and clinical judgment that should trigger intervention.
| S-EPMC5807181 | biostudies-literature
Project description:BackgroundFaltering postnatal growth in preterm babies is associated with adverse neurodevelopment. However, which growth reference is most helpful for predicting neurodevelopment is unknown. We examined associations between faltering growth and developmental delay in extremely low birthweight (ELBW) infants.MethodsWe categorized faltering growth (z-score decrease ≥0.8 for weight/length, >1 for head circumference) between birth, 4 weeks, 36 weeks' postmenstrual age and 2 years' corrected age using fetal (Fenton, UK-WHO and Olsen) and healthy preterm (INTERGROWTH-21st) references. Associations between faltering growth and developmental delay were examined using binary logistic regression and area under the receiver operating curve (AUC).ResultsIn 327 infants, Olsen charts identified the highest prevalence of faltering growth (weight 37%, length 63%, head 45%). Agreement in classification was higher amongst fetal references (kappa coefficient, ĸ = 0.46-0.94) than between INTERGROWTH-21st and fetal references (ĸ = 0.10-0.81). Faltering growth in all measures between 4-36 weeks (odds ratio, OR 2.0-4.7) compared with other time intervals (OR 1.7-2.7) were more strongly associated with developmental delay, particularly motor delay (OR 2.0-4.7). All growth references were poorly predictive of developmental delay at 2 years (AUC ≤ 0.62).ConclusionsFaltering postnatal growth in ELBW infants is associated with, but is poorly predictive of, developmental delay at 2 years.ImpactIn babies born preterm, different growth references result in wide variation in categorization of faltering postnatal growth. Faltering growth in weight, length, and head circumference from 4 weeks to 36 weeks' postmenstrual age are associated with developmental delay at 2 years' corrected age, particularly motor delay. However, postnatal growth is a poor predictor of later developmental delay in extremely low birthweight infants irrespective of the growth reference used.
| S-EPMC11343699 | biostudies-literature
Project description:BackgroundThe International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Project is a population-based, longitudinal study describing early growth and development in an optimally healthy cohort of 4607 mothers and newborns. At 24 months, children are assessed for neurodevelopmental outcomes with the INTERGROWTH-21st Neurodevelopment Package. This paper describes neurodevelopment tools for preschoolers and the systematic approach leading to the development of the Package.MethodsAn advisory panel shortlisted project-specific criteria (such as multi-dimensional assessments and suitability for international populations) to be fulfilled by a neurodevelopment instrument. A literature review of well-established tools for preschoolers revealed 47 candidates, none of which fulfilled all the project's criteria. A multi-dimensional assessment was, therefore, compiled using a package-based approach by: (i) categorizing desired outcomes into domains, (ii) devising domain-specific criteria for tool selection, and (iii) selecting the most appropriate measure for each domain.ResultsThe Package measures vision (Cardiff tests); cortical auditory processing (auditory evoked potentials to a novelty oddball paradigm); and cognition, language skills, behavior, motor skills and attention (the INTERGROWTH-21st Neurodevelopment Assessment) in 35-45 minutes. Sleep-wake patterns (actigraphy) are also assessed. Tablet-based applications with integrated quality checks and automated, wireless electroencephalography make the Package easy to administer in the field by non-specialist staff. The Package is in use in Brazil, India, Italy, Kenya and the United Kingdom.ConclusionsThe INTERGROWTH-21st Neurodevelopment Package is a multi-dimensional instrument measuring early child development (ECD). Its developmental approach may be useful to those involved in large-scale ECD research and surveillance efforts.
| S-EPMC4244160 | biostudies-literature
Project description:ImportancePreterm birth and low birth weight are associated with brain developmental and neurocognitive outcomes in childhood; however, not much is known about the specific critical periods in fetal life and infancy for these outcomes.ObjectiveTo examine the associations of fetal and infant growth patterns with brain morphology in children at school age.Design, setting, and participantsThis population-based, prospective cohort study was conducted from February 1 to April 16, 2021, as a part of the Generation R Study in Rotterdam, the Netherlands. The study included 3098 singleton children born between April 1, 2002, and January 31, 2006.ExposuresFetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD scores greater than 0.67 between time points. Infant measurements also included peak weight velocity, and age and body mass index reached at adiposity peak.Main outcomes and measuresBrain structure, including global and regional brain volumes, was quantified by magnetic resonance imaging at age 10 years.ResultsThe study evaluated 3098 children (mean [SD] age at follow-up, 10.1 [0.6] years; 1557 girls [50.3%]; and 1753 Dutch [57.8%]). One SD score-higher weight gain until the second and third trimesters, birth, and 6, 12, and 24 months was associated with larger total brain volume independently of growth during any other age windows (second trimester: 5.7 cm3; 95% CI, 1.2-10.2 cm3; third trimester: 15.3 cm3; 95% CI, 11.0-19.6 cm3; birth: 20.8 cm3; 95% CI, 16.4-25.1 cm3; 6 months: 15.6 cm3; 95% CI, 11.2-19.9 cm3; 12 months: 11.3 cm3; 95% CI, 7.0-15.6 cm3; and 24 months: 11.1 cm3; 95% CI, 6.8-15.4 cm3). Compared with children with normal fetal and infant growth, those with fetal and infant growth deceleration had the smallest total brain volume (-32.5 cm3; 95% CI, -53.2 to -11.9 cm3). Children with fetal weight deceleration followed by infant catch-up growth had similar brain volumes as children with normal growth. Higher peak weight velocity and body mass index reached at adiposity peak were associated with larger brain volumes. Similar results were observed for cerebral and cerebellar gray and white matter volumes.Conclusions and relevanceThis cohort study's findings suggest that both fetal and infant weight growth might be critical for cerebral and cerebellar brain volumes during childhood. Whether these associations link to neurocognitive outcomes should be further studied.
| S-EPMC8662367 | biostudies-literature