Small For Gestational Age Infants Research Articles

Predictive factors of catch-up growth in term, small for gestational age infants: a two-year prospective observational study in Algeria.

Most small for gestational age (SGA) infants show catch-up growth but the minority who do not may benefit from growth-promoting treatment. We determined the prevalence of, and risk factors for, failure to show catch-up growth in term SGA infants. Prospective observational study of infants born at 37-42 weeks gestation between December 2012 and March 2014 with birth weight <10th percentile. Length, weight and head circumference were measured from birth to 2 years. Of 457 (3.9 %) term infants with SGA, 446 (97.6 %) were followed up until 2 years. At 24 months, supine length, weight and head circumference were ≥-2 standard deviation score (SDS) in 87.9 , 96.4 and 97.1 % subjects, with persistent short stature in 12.1 %. In a multivariate analysis, the independent predictors of failure to show catch-up growth at 24 months were: maternal height <150 cm, difference between mid-parental height and birth length of ≥2.2 SDS, height at 24 months <-2 SDS below mid-parental height SDS, history of SGA, ponderal index <3rd centile and duration of breast feeding <3 months. This study provides data concerning the epidemiology of SGA in Algeria and the factors associated with post-natal growth. Establishing which children remain short at 2 years has identified a cohort of patients requiring continuing follow up, with a view to instituting growth hormone therapy in selected cases. These results favour the setting up of an integrated national program to register SGA infants at birth, with re-evaluation at 2 years. (250 words).

Breast milk leptin concentrations and infant anthropometric indicators in SGA versus non-SGA breastfed infants born at term

Leptin concentrations in breast milk can influence metabolic programming during the first months of life. Small for gestational age (SGA) newborns show a peculiar growth pattern after birth, which can lead to adulthood diseases. This study aims to assess an association between leptin concentration in mature breast milk and the infant anthropometric indicators of the SGA and the non-SGA groups, in addition, to comparing the hormone level between these groups. A longitudinal study was performed with mother-infant pairs. The maternal sociodemographic information was collected in the first 48 h postpartum. Breast milk was collected at one month postpartum and leptin concentrations were obtained by immunoassays. The infant anthropometric measurements were collected at three and six months postpartum and included weight, height (to body mass index-BMI calculated), triceps skinfold (TSF), and subscapular skinfold (SSF). The BMI for age (BMI/A), TSF, and SSF were calculated by Z-score indicators. Data from 67 mother-infant pairs (n = 16 SGA and n = 51 non-SGA) were analyzed. In univariate analyses, the breast milk of the SGA group had lower leptin concentrations than the non-SGA group (p = 0.006), however, after adjustment, there was no difference between groups (p = 0.181). In the SGA group, there was a significant association between leptin concentrations and lower SSF at six months in infants, after adjustment (p = 0.003). In the non-SGA group, the breast milk leptin was associated with lower BMI/A at three and six months in infants, after adjustment (p = 0.002 and p = 0.010, respectively). The association between breast milk leptin concentrations with SSF in the SGA group and BMI/A in the non-SGA group suggests that leptin may be a modulating factor in infant growth in the first months of life.

Breastfeeding practices based on the gestational age and weight at birth in the first six months of life in a population-based cohort of infants from North India.

Short and long term benefits of early Initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) in the first six months of life are well established and recommended globally. However, reliable estimates of breastfeeding practices and impact of breastfeeding counselling interventions according to gestational age and weight at birth are not available in low and middle income countries. To assess the impact of breastfeeding counselling on EIBF and EBF during the first 6 months of life according to gestational age and weight at birth. We analysed the data collected from the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. Mothers were counselled on EIBF during third trimester of pregnancy. They were supported throughout the first 6 months to continue EBF by early problem identification, frequent home visits and assistance in expressing breastmilk when direct breastfeeding was not possible. Breastfeeding practices were ascertained through 24 h recalls at infant ages 1, 3 and 5 months for both the intervention and control groups by an independent outcome ascertainment team. The World Health Organization (WHO) definitions were used for classification of infant breastfeeding practices. Generalized linear models of the Poisson family with a log-link function were used to estimate the effect of interventions on breastfeeding practices. The relative measures of effect on breastfeeding practices were estimated in term appropriate for gestational age (T-AGA), term small for gestational age (T-SGA), preterm AGA (PT-AGA), preterm SGA (PT-SGA) infants. Amongst all infants irrespective of gestational age and weight at birth, EIBF was (51.7%) higher amongst the intervention group (IRR 1.38, 95% CI 1.28-1.48) compared with the control group. The proportion of exclusively breastfed infants at ages 1 month (IRR 1.37, 95% CI 1.28-1.48), 3 months (IRR 2.13, 95% CI 1.30-1.44) and 5 months (IRR 2.78, 95% CI 2.58-3.00) were higher in intervention group than control group. We identified significant interaction (p value for interaction <0.05) between intervention and infant size and gestation at birth on exclusive breastfeeding at 3 and 5 months of age. Subgroup analysis showed that the impact of the intervention was greater on exclusive breastfeeding in PT- SGA infants at 3 months (IRR 3.30, 95% CI 2.20-4.96) and 5 months of age (IRR 5.26, 95% CI 2.98-9.28). This is one of the first studies wherein impact of breastfeeding counselling interventions in the first 6 months of life was assessed according to infant size and gestation at birth wherein gestational age was reliably estimated. The impact of this intervention was higher in preterm and SGA babies compared to other infants. This finding is important as preterm and SGA infants have a higher burden of mortality and morbidity during early infancy. Intensive breastfeeding counselling to these vulnerable infants is likely to improve overall breastfeeding rates and reduce the adverse outcomes.Clinical Trial Registration: [http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339%26EncHid=%26userName=societyforappliedstudies], identifier [#CTRI/2017/06/008908].

Echocardiographic assessment of brain sparing in small-for-gestational age infants and association with neonatal outcomes

Brain sparing is an adaptive phenomenon (redistribution of blood flow to the brain) observed in fetuses exposed to chronic hypoxia, who are at risk of intrauterine growth restriction. Here, we assessed the blood flow distribution during the early neonatal period (< 7 days of life) using echocardiography, and evaluated the impact of brain-sparing on postnatal course and neurodevelopmental outcomes. This retrospective study included 42 small-for-gestational age (SGA) infants [further classified into asymmetric SGA (a-SGA, n = 21) and symmetric SGA (s-SGA, n = 21) groups according to their birth head circumference percentiles], and 1: 2 matched appropriate-for-gestational age (AGA) infants (n = 84) admitted to the neonatal intensive care unit. Left ventricular (LV) stroke volume, LV cardiac output (LVCO), upper body blood flow (UBBF), and UBBF/LVCO ratio (%) were significantly higher in both a-SGA and s-SGA infants than in AGA infants. Both a-SGA and s-SGA groups consisted predominantly of infants with higher UBBF/LVCO (%). A UBBF/LVCO ≥ 58.2% (3rd interquartile range) was associated with a later need for rehabilitative therapy after discharge. In summary, brain-sparing effect may continue during the early postnatal life in SGA infants, and may be a promising marker to detect future adverse neurodevelopmental outcomes.

Women's Economic Mobility and Small for Gestational Age Rates: The Effect of Paternal Early-Life Socioeconomic Position.

To determine whether paternal early-life socioeconomic position (defined by neighborhood income) modifies the association of maternal economic mobility and infant small for gestational age (weight for gestational age < 10th percentile, SGA) rates. Stratified and multilevel binomial regression analyses were executed on the Illinois transgenerational dataset of parents (born 1956-1976) and their infants (born 1989-1991) with appended U.S. census income information. Only Chicago-born women with an early-life residence in impoverished or affluent neighborhoods were studied. The incidence of impoverished-born women's upward economic mobility among births (n = 3777) with early-life low socioeconomic position (SEP) fathers was less than that of those (n = 576) with early-life high SEP fathers: 56% vs 71%, respectively, p < 0.01. The incidence of affluent-born women's downward economic mobility among births (n = 2370) with early-life low SEP fathers exceeded that of those (n = 3822) with early-life high SEP fathers: 79% vs 66%, respectively, p < 0.01. The adjusted RR of infant SGA for maternal upward (compared to lifelong impoverishment) economic mobility among fathers with early-life low and high SEP equaled 0.68 (0.56, 0.82) and 0.81 (0.47, 1.42), respectively. The adjusted RR of infant SGA for maternal downward (compared to lifelong residence in affluent neighborhoods) economic mobility among fathers with early-life low and high SEP were 1.37 (0.91, 2.05) and 1.17 (0.86, 1.59), respectively. Paternal early-life SEP is associated with maternal economic mobility (both upward and downward); however, it does not modify the relationship between maternal economic mobility and infant SGA rates.

Classification and Special Nutritional Needs of SGA Infants and Neonates of Multiple Pregnancies.

Data regarding the nutritional management of preterm small for gestational age (SGA) infants are scarce. In the recent report of ESPGHAN, the recommended energy for very preterm infants during hospitalization has been increased, yet this may not fit the needs of all preterm infants. It is important to distinguish fetal growth-restricted (FGR) infants from constitutional SGA infants, as well as preterm SGA from preterm AGA infants, since they may have different nutritional needs. Preterm FGR infants, and specifically infants < 29 weeks' gestation, accumulate nutrient deficits due to intrauterine malnutrition, prematurity, morbidities, delayed initiation of feeding, and feeding intolerance. Therefore, these infants may need more aggressive nutrition for optimal catch-up growth and neurologic development. However, a balance should be kept between optimal and excessive catch-up growth, since the combination of intrauterine malnutrition and excessive postnatal growth has been linked with later adverse metabolic consequences. Furthermore, multiple gestation is often complicated by FGR and prematurity. There is controversy in the definition of FGR in multiple gestations, and it should be noted that FGR in multiple gestation usually differs etiologically from FGR in singletons. The aim of this review is to summarize existing knowledge regarding the nutritional needs of preterm FGR and FGR infants of multiple gestation.

Factors associated with higher risk of small-for-gestational-age infants in women treated for gestational diabetes.

Previously, management of gestational diabetes (GDM) has focused largely on glycaemic control, with a view to reduce the occurrence of large-for-gestational-age (LGA) infants. However, tight glycaemic control in GDM is associated with a higher incidence of small-for-gestational-age (SGA) infants, which has been linked to higher rates of adverse outcomes. The aim was to characterise risk factors associated with having an SGA infant in women being treated for GDM. This was a retrospective observational cohort study of 308 women with GDM. Women were split into groups based on their infant's size at delivery (SGA, appropriate-for-gestational-age (AGA) or LGA). Literature review and expert opinion helped to determine several predictors of women with GDM delivering an SGA infant, and statistical analysis was used to produce odds ratios (OR) for these predictors. The sample included primiparous women with a mean pre-pregnancy body mass index (BMI) of 25.72 (standard deviation: 5.75). Metabolic risk factors associated with delivering an SGA infant included a lower pre-pregnancy BMI (adjusted OR 1.13, P = 0.04, 95% confidence interval (CI): 1.01-1.26), a lower fasting blood glucose level (BGL) (adjusted OR: 3.21, P = 0.01, 95% CI: 1.30-7.93) and growth that was high risk for SGA at baseline ultrasound scan (USS) (adjusted OR: 7.43, P < 0.001, 95% CI: 2.93-18.79). The combined clinical picture of lower pre-pregnancy BMI, fasting BGL and baseline USS growth measurements may indicate a need for less aggressive glucose management in women with GDM to prevent SGA infants.

Neonatal mortality in small for gestational age infants based on reference local newborn curve at secondary and tertiary hospitals in Indonesia

BackgroundSmall for gestational (SGA) infants during the neonatal period have risks of mortality and sequelae for survival. Two - third of neonatal mortality occurs in the first weeks of life. Prevalence of SGA depends on the newbon curve used. Objectives of the study were to know the conditions that posed the risk of early neonatal and neonatal mortality, to identify preterm/full-term and SGA/appropriate gestational age (AGA) infants with cumulative mortality incident (CMI), to compare 5- year-period of early and neonatal mortality, and to investigate CMI on neonatal mortality of four categories during 5-year-period.MethodsA retrospective cohort study on all live births, during 1998–2017, was conducted in Sleman and Sardjito hospitals, Yogyakarta, Indonesia. Based on the reference local curve, the eligible subjects were categorized into SGA and AGA infants. The analyses were based on preterm/full-term and SGA/AGA, thus resulting in 4 categories: preterm-SGA, preterm-AGA, full-term-SGA and full-term-AGA. Analysis was made with Unadjusted Hazard Ratio (HR) by Simple Cox Regression and Adjusted HR was calculated by Multiple Cox Regression, survival analysis to calculate CMI, and analysis mortality for 5-year period ( 1998–2002, 2003–2007, 2008–2012, 2013–2017).ResultThere were 35,649 live births eligible for the study. Respiratory distress was the highest risk with HR 9,46, followed by asphyxia with HR 5,08, mother’s death with HR 227, extra-health facility with HR 1,97, symmetrical SGA with HR 1,97, preterm-AGA with HR 1,75, low birth weight (LBW) with HR 1,64, primary health facility with HR 1,33, and boys with HR 1,16 consecutively. Early neonatal mortality in 4 categories by survival analysis revealed the highest CMI in preterm SGA. Similar result was found in neonatal mortality. Analysis of 5-year period unveiled the highest CMI during 1998–2002. The highest CMI based on the four categories, however, was found in preterm-SGA.ConclusionRespiratory distress posed the highest HR in early and neonatal mortality. Survival analysis showing the highest CMI on early and neonatal mortality was identified in preterm-SGA. The 5 - year - period of neonatal mortality showed the highest CMI during 1998–2002 period, whereas based on 4 SGA categories, preterm-SGA demonstrated the highest CMI.

Association of Maternal Asthma and Total Serum Immunoglobulin E levels with Obstetric Complications: The Japan Environment and Children's Study.

To evaluate the association between maternal asthma (MA) and obstetric complications, while considering subdivided total serum immunoglobulin E (IgE) levels. Data of the participants enrolled in the Japan Environment and Children's Study between 2011 and 2014 were analyzed. In total, 77,131 women with singleton live births at and after 22weeks of gestation were included. MA was defined based on a self-administered questionnaire. Women with MA were stratified based on the quartile of total serum IgE levels during pregnancy as follows: low IgE levels (< 52.40IU/mL), moderate IgE levels (52.40-331.00IU/mL), and high IgE levels (> 331.00IU/mL). The adjusted odds ratios (aORs) for preterm births (PTB), small for gestational age (SGA) infants, gestational diabetes mellitus, and hypertensive disorders of pregnancy (HDP) were calculated using multivariable logistic regression, while considering women without MA as reference and maternal socioeconomic factors as confounders. The aORs for SGA infants and HDP in women with MA and high total serum IgE levels were 1.26 (95% confidence interval [CI], 1.05-1.50) and 1.33 (95% CI, 1.06-1.66), respectively. The aOR for SGA infants among women with MA and moderate total serum IgE levels was 0.85 (95% CI, 0.73-0.99). The aOR for PTB among women with MA and low total serum IgE levels was 1.26 (95% CI, 1.04-1.52). MA with subdivided total serum IgE levels was associated with obstetric complications. Total serum IgE level may be a potential prognostic marker to predict obstetric complications in pregnancies with MA.

Pregnancy Outcome of Confined Placental Mosaicism: Meta-analysis of Cohort Studies

ABSTRACT Confined placental mosaicism (CPM) is a condition in which there is chromosomal abnormality in the placenta that is not present in the fetus. Confined placental mosaicism has historically been most often identified following a first-trimester chorionic villus sampling (CVS), in which there are 2 different cell lines in the placenta but a normal karyotype in the fetus based on amniocentesis or neonatal blood. As the outcome for CPM pregnancies is still debated, including the potential for adverse pregnancy and postnatal outcomes, this study aimed to evaluate the rates of adverse neonatal and obstetrical outcomes in CPM-diagnosed pregnancies, as compared with unaffected matched controls. This meta-analysis was performed in accordance with an a priori designed protocol and was registered with the PROSPERO (International Prospective Register of Systematic Reviews) database. A search of EMBASE and MEDLINE databases from 1980 to February 2022 was performed. Included articles were published in the English language and were observational studies including singleton CPM-diagnosed pregnancies (whose controls were unaffected and with normal karyotype). Excluded were all reviews, case reports, and congress abstracts. In addition, high-risk or positive cell-free DNA screening (cfDNA) cases followed by diploid amniotic cells were excluded (because of the different methodology, which may have an effect on the analysis). Because of the paucity of data regarding mosaicism in submicroscopic copy number variants, these abnormalities were also excluded from the analysis. Primary outcomes included the occurrence of the following: termination of pregnancy, major fetal defects (as defined by the Centers for Disease Control and Prevention), small for gestational age (SGA) neonate with birth weight (BW) &lt;10th centile and neonatal SGA with BW less than the third centile, preterm birth (PTB), hypertensive disorders, admission to a neonatal intensive care unit, intrauterine fetal demise at &lt;24 weeks' gestation, and &gt;24 weeks' gestation stillbirth. All other abnormal pregnancy outcomes were searched for, including PTB, obstetrical cholestasis, amniotic infection, gestational diabetes, cesarean delivery, amniotic infection, preterm prelabor rupture of membranes, and neonatal mortality or morbidity. Of 310 retrieved articles, 80 studies were assessed for eligibility, and 8 retrospective matched cohort studies were included. The results of the meta-analysis showed that women with CPM had a higher risk of adverse pregnancy outcomes than those without CPM. The most common adverse outcomes were fetal growth restriction (FGR), PTB, and stillbirth. The risk of FGR was significantly higher in women with CPM, with an odds ratio (OR) of 3.60 (95% confidence interval [CI], 2.40–5.39). Similarly, the risk of PTB was higher in women with CPM, with an OR of 2.64 (95% CI, 1.90–3.67), and the risk of stillbirth was also increased, with an OR of 2.58 (95% CI, 1.51–4.42). Scarcity of reporting for other obstetrical neonatal and obstetrical outcomes hindered further conclusions. In subgroup analysis, the risk of delivering an SGA infant was 3-fold higher for CPM when trisomy 16 was excluded and 11-fold higher for trisomy 16 specifically compared with unaffected controls. The authors acknowledge that the meta-analysis has several limitations, including the heterogeneity of the included studies, the lack of information on the specific type and extent of CPM in each case, and the potential for publication bias. Nevertheless, the study provides valuable insights into the pregnancy outcomes of women with CPM and highlights the need for further research to improve our understanding of this condition. Overall, this meta-analysis suggests that women with CPM are at increased risk of adverse pregnancy outcomes, particularly FGR, PTB, and stillbirth. The findings highlight the importance of early detection of CPM and close monitoring of pregnancies in women with this condition. The study also emphasizes the need for further research to better understand the underlying mechanisms of CPM and to identify effective interventions to improve pregnancy outcomes in affected women.

Preexisting Cerebrovascular Disease in Pregnancy: a Case Series on Pregnancy Outcomes (S3.004)

<h3>Objective:</h3> To characterize adverse pregnancy outcomes (APO) in patients with preexisting cerebrovascular disease (CVD). <h3>Background:</h3> Detailed data are lacking regarding APO in pregnant patients with CVD, limiting neurologists’ ability to counsel patients. <h3>Design/Methods:</h3> We reviewed medical records of 35 patients with CVD evaluated in a neuro-obstetrics subspecialty clinic embedded within a high risk maternal-fetal medicine practice between August 2019 and December 2021. Patients were referred for neurological evaluation during or prior to pregnancy. We described subsequent maternal and fetal APO, including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), pre term birth (PTB), fetal growth restriction (FGR), and small for gestational age infant (SGA), as well as delivery mode, postpartum readmissions and recurrent acute CVD. <h3>Results:</h3> A total of 35 patients were included (6 TIA, 14 ischemic stroke, 1 subarachnoid hemorrhage, 1 intracerebral hemorrhage, 5 cerebral venous thrombosis, 3 unruptured aneurysm, 2 arteriovenous malformation, 1 cervical artery dissection, 2 reversible cerebral vasoconstriction syndrome [RCVS]). Average age at delivery was 33 years, and most patients (91%) had vascular risk factors including obesity (23%), chronic hypertension (20%), diabetes mellitus (11%), history of prior APO (26%), and migraine (57%). All patients with prior TIA, ischemic stroke, or cerebral venous thrombosis received antithrombotics during pregnancy. Overall, APO occurred in 44% of pregnancies, and included PTB (28%), HDP (19%), GDM (14%), FGR (8%), and SGA (8%). Cesarean deliveries occurred in 42% of pregnancies, all for obstetric indications. Two patients were readmitted postpartum, one for neurological symptoms (headache) with normal brain imaging, and one for an obstetrical complication. One patient experienced recurrent postpartum CVD (RCVS), without readmission. <h3>Conclusions:</h3> In patients with CVD history, APO were common but recurrent acute CVD was rare. Patients with prior CVD may be at high risk for APO due to underlying vascular risk factors rather than specific CVD diagnosis. <b>Disclosure:</b> Ms. Wyckoff has nothing to disclose. Dr. Mammadli has nothing to disclose. Dr. Booker has nothing to disclose. Dr. D’Alton has a non-compensated relationship as a Advisory Board with Merck for Mothers that is relevant to AAN interests or activities. Dr. LaSala has nothing to disclose. Stephanie Purisch has nothing to disclose. Prof. Valeri has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for McLean Hospital. Prof. Valeri has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA. The institution of Prof. Valeri has received research support from National Institute of Health. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edwards Scientific. Dr. Willey has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for RECARDIO. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbott. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of the American College of Cardiology. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Uptodate. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as a Review chapter author, MKSAP 16-20 with American College of Physicians. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Argionis and Associates LLC. The institution of Dr. Miller has received research support from National Institutes of Health.

Aligning theory with practice: Child health programmes in Malaysia, a Narrative Review.

The Malaysian healthcare system, particularly for maternal and child health, has been well recognised to provide high-quality services and be at par with systems in other developed countries. Current health programmes and technological advancements effectively detect vulnerable groups of children, such as small-for-gestational-age (SGA) infants, antenatally. However, the postnatal care for SGA infants is not clearly evaluated, as this group of children is mostly classified as healthy in many medical contexts, especially in primary care settings. Available health programmes and healthcare service delivery must be continuously evaluated by implementing beneficial and relevant evidence-based theories. Articles, reports and guidelines used in providing mother and child health services in Malaysia published since 2000 were reviewed. There was no specific monitoring strategy used for SGA infants without critical health issues in early childhood, as they were commonly treated as healthy infants. Several challenges in aligning theory with the current practice of healthcare service delivery and recommendations for dealing with such challenges were identified. The alignment of theory with the current practice of service delivery should be tailored to the needs and demands parallel to the dynamic change in populations in the urbanisation era.

Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition.

Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. We longitudinally assessed PGRN concentrations in infants born appropriate (AGA) or small for gestational age (SGA), the latter being at risk for obesity and type 2 diabetes, especially if they experience an excessive postnatal catch-up in weight and are formula-fed (FF). The study population consisted of 183 infants who were exclusively breast-fed [(BF), AGA, n = 66; SGA, n = 40], or FF (AGA, n = 31; SGA, n = 46) over the first 4 months. Assessments included auxology, fasting glucose, insulin, IGF-1, high-molecular-weight adiponectin, PGRN and body composition (by DXA), at birth, and at age 4 and 12 months. PGRN levels were low at birth and unaffected by prenatal growth. PGRN increased at 4 and 12 months, although to a lesser extent in SGA infants, and was unrelated to the mode of feeding. PGRN correlated with markers of adiposity, inflammation and insulin resistance in both AGA and SGA infants, especially in those FF. The attenuated increase of PGRN levels in SGA infants over the first year of life, along with the association to markers of unhealthy metabolic profile, might point to a role of PGRN in future disease risks. Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. In healthy infants, PGRN concentrations are low at birth and experience a significant and progressive increase up to age 12 months, which is less marked in infants born small for gestational age (SGA) and is unrelated to the mode of feeding. Circulating PGRN is related to markers of adiposity, inflammation, and insulin sensitivity, especially in formula-fed SGA infants. PGRN may play a role in the metabolic adaptations of SGA infants during early life, potentially contributing to the risk for obesity and type 2 diabetes in this population.

Early childhood parent-reported speech problems in small and large for gestational age term-born and preterm-born infants: a cohort study

Objective(1) To assess if preterm and term small for gestational age (SGA) or large for gestational age (LGA) infants have more parent-reported speech problems in early childhood compared with infants...

Gestational age assessed by optical skin reflection in low-birth-weight newborns: Applications in classification at birth.

A new medical device was previously developed to estimate gestational age (GA) at birth by processing a machine learning algorithm on the light scatter signal acquired on the newborn's skin. The study aims to validate GA calculated by the new device (test), comparing the result with the best available GA in newborns with low birth weight (LBW). We conducted a multicenter, non-randomized, and single-blinded clinical trial in three urban referral centers for perinatal care in Brazil and Mozambique. LBW newborns with a GA over 24 weeks and weighing between 500 and 2,500 g were recruited in the first 24 h of life. All pregnancies had a GA calculated by obstetric ultrasound before 24 weeks or by reliable last menstrual period (LMP). The primary endpoint was the agreement between the GA calculated by the new device (test) and the best available clinical GA, with 95% confidence limits. In addition, we assessed the accuracy of using the test in the classification of preterm and SGA. Prematurity was childbirth before 37 gestational weeks. The growth standard curve was Intergrowth-21st, with the 10th percentile being the limit for classifying SGA. Among 305 evaluated newborns, 234 (76.7%) were premature, and 139 (45.6%) were SGA. The intraclass correlation coefficient between GA by the test and reference GA was 0.829 (95% CI: 0.785-0.863). However, the new device (test) underestimated the reference GA by an average of 2.8 days (95% limits of agreement: -40.6 to 31.2 days). Its use in classifying preterm or term newborns revealed an accuracy of 78.4% (95% CI: 73.3-81.6), with high sensitivity (96.2%; 95% CI: 92.8-98.2). The accuracy of classifying SGA newborns using GA calculated by the test was 62.3% (95% CI: 56.6-67.8). The new device (test) was able to assess GA at birth in LBW newborns, with a high agreement with the best available GA as a reference. The GA estimated by the device (test), when used to classify newborns on the first day of life, was useful in identifying premature infants but not when applied to identify SGA infants, considering current algohrithm. Nonetheless, the new device (test) has the potential to provide important information in places where the GA is unknown or inaccurate.

Placental morphological features of small for gestational age preterm neonates born to mothers with pregnancy-induced hypertension.

Small for gestational age (SGA) neonates are often born to mothers with pregnancy-induced hypertension (PIH). Here, we aimed to explore the morphometric characteristics of the placenta during the perinatal period associated with SGA risk in mothers with PIH and identify the risk factors related to SGA. The medical records of 134 neonates born between 28- and 32-weeks' gestation to PIH mothers were retrospectively analyzed. Placental morphology and umbilical cord (UC) length were compared between the SGA and appropriate for gestational age (AGA) groups. The placenta of the SGA group had a shorter major (15.00 vs. 18.00 cm; z = -6.04, p < 0.01) and minor placenta axes (13.00 vs. 15.00 cm; z = -4.59, p < 0.01), lower weight (300.00 vs. 420.00 g; z = -7.21, p < 0.01), smaller volume (282.00 vs. 396.00 cm3; z = -5.00, p < 0.01), and smaller area (141.00 vs. 212.00 cm2; z = -5.96, p < 0.01) than the AGA group. The UC was significantly shorter (39.00 vs. 44.00 cm; z = -3.68, p < 0.01). Short placental major axis [p = 0.03; odds ratio (OR): 2.16; 95% confidence interval (CI): 1.84 - 2.63] and low placental weight (p < 0.01; OR: 2.68; 95% CI: 2.66 - 2.70) were independent risk factors for SGA in premature newborns of PIH mothers. A major axis shorter than 15.5 cm or placental weight lower than 347.50 g at birth was related to a greater risk of SGA infants born to PIH mothers. As a predictor in prenatal ultrasound, the major axis is more helpful for precise prenatal pre-evaluation of vulnerable SGA preterm neonates with PIH mothers.

Invited Commentary: Beyond Barker-Mothers Are the Ones at Risk.

Dr. David Barker hypothesized that low birth weight (LBW) is the result of inadequate fetal nutrition, leading to increased risk ofcardiovascular disease (CVD) in the offspring. This hypothesis has stimulated thousands of reports on low birth weight (LBW) and CVD risk. One problem with this association is that many LBW infants are small because they are preterm, not growth-restricted. A second problem is that maternal CVD risk factors confound the association. In an accompanying article, Lu et al. (Am J Epidemiol. 2023;192(6):866-877) address both concerns. Using population data from Sweden and Denmark, the authors estimated CVD incidence among offspring born small for gestational age (SGA). The smallest 3% had a CVD hazard ratio of 1.44 (95% confidence interval: 1.38, 1.51). Even this moderate risk mostly evaporated in sibship analysis, which controlled for unmeasured maternal CVD risk factors (hazard ratio = 1.11, 95% confidence interval: 0.99, 1.25). The risk highlighted by Barker is negligible, especially when compared with a more urgent health issue-cardiovascular risk in women with pregnancy complications. Mothers of SGA infants have up to a 3-fold CVD risk, and mothers with preeclampsia and preterm delivery have up to a 9-fold risk. Pregnancy complications thus provide an early marker of a woman's propensity to develop CVD, and perhaps an opportunity for early intervention. From a public health perspective, Barker's hypothesis about CVD risk in LBW offspring is less compelling than the question of CVD risk among mothers with pregnancy complications. This article is part of a Special Collection on ABC.

Serum PCSK9 levels in infants with deviant birth weight: a biomarker of the lipoprotein metabolism

Objective Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9), a modulator of low-density lipoprotein (LDL) cholesterol metabolism, has been reported to be a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. In the current study, we sought to investigate potential differences in serum PCSK9 levels between infants with deviant birth weight and controls. Methods We enrolled 82 infants, classified into 33 small (SGA), 32 appropriate (AGA), and 17 large for gestation (LGA) infants. Serum PCSK9 was measured on routine blood analysis within the first postnatal 48 h. Results PCSK9 was significantly higher in SGA as compared to AGA and LGA infants [322 (236–431) as compared to 263 (217–302) and 218 (194–291) ng/ml respectively, p = .011]. In comparison to term AGA infants, PCSK9 was significantly elevated in preterm AGA and SGA infants. We also found a significantly higher level of PCSK9 in term female SGA infants as compared to term male SGA infants [325 (293–377) as compared to 174 (163–216) ng/ml, p = .011]. PCSK9 was significantly correlated with gestational age (R = –0.404, p < .001), birth weight (R = –0.419, p < .001), total cholesterol (R = 0.248, p = .028) and LDL cholesterol (R = 0.370, p = .001). SGA status (OR 2.56, p = .004, 95% CI 1.83–4.28) and prematurity (OR 3.10, p = .001, 95% CI 1.39–4.82) were strongly related to serum PCSK9 levels. Conclusion PCSK9 levels were significantly associated with total and LDL cholesterol. Moreover, PCSK9 levels were higher in preterm and SGA infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk. Highlights What’s already known? Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9) is a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. Infants that were born with a deviant birth weight have a unique lipoprotein metabolism profile. What this study adds? Serum PCSK9 levels were significantly associated with total and LDL cholesterol. PCSK9 levels were higher in preterm and small for gestation infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk.

Definitions matter: detection rates and perinatal outcome for infants classified prenatally as having late fetal growth restriction using SMFM biometric vs ISUOG/Delphi consensus criteria.

Fetal growth restriction (FGR) is often secondary to placental dysfunction and is suspected prenatally based on biometric or circulatory abnormalities detected on ultrasound. The aims of this study were to compare the screening performance of the Society for Maternal-Fetal Medicine (SMFM) biometric criteria (estimated fetal weight (EFW) or abdominal circumference (AC) < 10th centile) with that of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)-endorsed Delphi consensus criteria for late FGR for delivery of a small-for-gestational-age (SGA) infant at term, emergency Cesarean section (CS) for non-reassuring fetal status (NRFS), perinatal mortality and composite severe neonatal morbidity. We classified retrospectively non-anomalous singleton infants as having late FGR (diagnosed ≥ 32 weeks) according to SMFM and ISUOG/Delphi criteria in a cohort of women who had been referred to the Mater Mother's Hospital, Brisbane, Australia and who delivered at term between January 2014 and December 2020. The study outcomes were delivery of a SGA infant (birth weight (BW) < 10th or < 3rd centile), emergency CS for NRFS, perinatal mortality (defined as stillbirth or neonatal death within 28 days of a live birth) and a composite of severe neonatal morbidity. We assessed the screening performance of various ultrasound variables by calculating the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, false-positive and false-negative rates, positive likelihood ratio (LR+) and negative likelihood ratio. The SMFM and ISUOG/Delphi consensus criteria collectively classified 1030 cases as having late FGR. Of these, 400 cases were classified by both SMFM and ISUOG/Delphi criteria, whilst 548 cases were classified using only SMFM criteria and 82 cases were classified only by ISUOG/Delphi criteria. Prenatal detection of late FGR by SMFM and ISUOG/Delphi criteria was associated with increased odds of delivery of an infant with BW < 10th centile (SMFM: adjusted odds ratio (aOR), 133.0 (95% CI, 94.7-186.6); ISUOG/Delphi: aOR, 69.5 (95% CI, 49.1-98.2)) or BW < 3rd centile (SMFM: aOR, 348.7 (95% CI, 242.6-501.2); ISUOG/Delphi: aOR, 215.4 (95% CI, 148.4-312.7)). Compared with the SMFM criteria, the ISUOG/Delphi criteria were associated with lower odds (aOR, 0.5 (95% CI, 0.3-0.8)) of predicting a SGA infant with BW < 10th centile, but higher odds of predicting emergency CS for NRFS (aOR, 2.30 (95% CI, 1.14-4.66)) and composite neonatal morbidity (aOR, 1.22 (95% CI, 1.05-1.41)). Both SMFM and ISUOG/Delphi criteria were associated with high LR+, specificity, PPV and NPV for the prediction of infants with BW < 10th and BW < 3rd centile. However, both methods functioned much less efficiently for the prediction of composite severe neonatal morbidity or emergency CS for NRFS, with LR+ < 10. The SMFM biometric criteria alone, particularly AC < 3rd centile, had the highest LR+ values for the prediction of perinatal mortality. Both the SMFM and ISUOG/Delphi criteria had strong screening potential for the detection of infants with BW < 10th or < 3rd centile but not for adverse neonatal outcome. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The Association between Early Menarche and Small for Gestational Age Birth.

In the U.S., approximately 11% of infants are born small for gestational age (SGA). While there are many known behavioral risk factors for SGA births, there are still many factors yet to be explored. The purpose of this study was to investigate the maternal early menarche (< 12 years old)- SGA birth association. Data were retrieved from the 2011-2017 National Survey of Family Growth, and multivariate logistic regression was used to evaluate the association. Approximately 4% of mothers reported having an SGA infant and 24% of mothers reported early age at menarche. After controlling for maternal age, race/ethnicity, and annual household income, early menarche was associated with 3% increased odds of SGA, although this finding was not statistically significant (adjusted odds ratio: 1.03, 95% CI: 0.70, 1.53). Additional research is needed on the long-term birth outcomes and health consequences of early menarche.