Small For Gestational Age Research Articles

Pregnancy outcomes by hyperemesis gravidarum severity and time of diagnosis: A retrospective cohort study.

With inconsistencies regarding the possible effect of hyperemesis gravidarum on the course of pregnancy, this research aimed to study the association between hyperemesis gravidarum and pregnancy outcomes, while also addressing the trimester of diagnosis and severity. A retrospective cohort study was performed, including all singleton deliveries of mothers from the largest health maintenance organization in the country, in a single tertiary hospital between 1991 and 2021. The incidence of adverse pregnancy outcomes was compared between pregnancies with and without hyperemesis gravidarum diagnosis. Multivariable generalized estimation equation binary models were used to study the association between maternal hyperemesis gravidarum, trimester of diagnosis and hyperemesis gravidarum severity and the studied outcomes. The study population included 232 476 pregnancies, of which 3227 (1.4%) were complicated with hyperemesis gravidarum. Women with hyperemesis gravidarum were more likely to deliver preterm (adj. OR = 1.33, 95% CI: 1.18-1.50), a newborn with low birthweight (adj. OR = 1.52, 95% CI: 1.16-1.98, only if diagnosed in the second trimester), and to have a cesarean delivery (adj. OR = 1.20, 95% CI: 1.09-1.32). They were less likely to deliver small gestational age newborn (adj. OR = 0.82, 95% CI: 0.69-0.99) and their offspring to experience perinatal mortality (adj. OR = 0.54, 95% CI: 0.31-0.93, among mild cases only). A dose-response association was observed between preterm birth and hyperemesis gravidarum (adj. OR = 1.26; 95% CI: 1.11-1.44, for mild cases and adj. OR = 2.04; 95% CI: 1.31-3.19, for severe cases). Hyperemesis gravidarum is associated with an increased risk for adverse pregnancy outcomes including mainly preterm delivery in a dose-response manner and when diagnosed during the second trimester.

Post‐term births as a risk factor for small for gestational age births and infant mortality in Brazil, Mexico, and Palestinian refugees: An analysis of electronic birth records

AbstractBackgroundPost‐term pregnancy, defined as reaching or exceeding 42 + 0 weeks of gestation, is known to be associated with unfavourable birth outcomes. High‐income countries have responded to this risk by widely adopting labour induction protocols in late‐term, but many low‐ and middle‐income countries have not. However, understanding underlying mechanisms linking post‐term births to adverse newborn and infant outcomes remains limited.ObjectiveTo investigate the (a) prevalence of post‐term, (b) the risk factors associated with post‐term (c) the association between post‐term births and the risk of small‐for‐gestational‐age (SGA) neonates and of infant mortality in middle‐income settings.MethodsWe used existing electronic datasets from the general population of Brazil, Mexico, and Palestinian refugees. Regression models were used to explore the associations between post‐term birth and SGA and infant mortality.ResultsWe analysed 21,335,033 live births in Brazil (2011–2018), 23,416,126 in Mexico (2008–2019), and 966,102 in Palestinian refugees (2010–2020) (N = 45,717,261). Post‐term deliveries accounted for 3.1% of births in Brazil, 1.2% in Mexico, and 2.1% in Palestinian refugees. Post‐term births had approximately three times the risk of resulting in SGA neonates compared to term births. Additionally, post‐term neonates exhibited a 15% to 40% increased risk of infant mortality compared to term infants. Notably, post‐term SGA neonates faced a significantly increased risk of infant mortality compared to term appropriate for gestational age neonates.ConclusionsThese findings emphasise the critical significance of implementing induction strategies to prevent post‐term pregnancies and mitigate the associated risks of SGA neonates and subsequent infant mortality. Moreover, the study highlights the importance of accurately determining gestational age and using INTERGROWTH‐21st charts to improve the identification of SGA cases, enabling targeted interventions. This is especially relevant because post‐term SGA neonates may not exhibit low birthweight (a commonly used risk marker) and, therefore, may miss out on required specialised attention.

Intravoxel incoherent motion MRI to assess feto-placental diffusion and perfusion properties in small fetuses.

To investigate the use of intravoxel incoherent motion (IVIM) to study microperfusion and microstructural characteristics of lungs, brain, and placenta in normal and small fetuses. We retrospectively enrolled 30 small fetuses and 82 normal pregnancies who underwent a 1.5-T MRI examination using an IVIM-DWI. Small fetuses were distinguished in small for gestational age (SGA) and "true" fetal growth restriction (FGR). ROIs were placed on the brain parenchyma, lungs, and fetal/maternal placental sides. Differences in perfusion fraction f, diffusion coefficient D, and pseudo-diffusion coefficient D* and their correlation with gestational age (GA) and birth weight (BW) were investigated. LUNG: f showed significantly lower values (p = 2·10-7) in small fetuses (SGA + FGR); f discriminates SGA and FGR from normal (p = 0.001; p = 1·10-6). f increases with GA (p < 0.0001) in the control group; a positive correlation was also obtained in small fetuses, although less significant. FGR showed lower f values than normal ones, in both the fetal (p = 1.4·10-7) and maternal side (p = 0.001); f discriminates between SGA and FGR (p = 0.03). In small fetuses (SGA + FGR), f correlates positively with BW. D values in supratentorial white matter (WM) were significantly higher compared to other regions, in both normal and small fetuses. Small fetuses showed higher D values in occipital WM and pons (p = 0.041; p = 0.027) than in normal. D correlates negatively with GA in the healthy group. No correlation between D and GA was found in SGA + FGR group. In our study, IVIM-MRI allowed us to detect microstructural and microperfusion changes in the placenta, brain, and lung of small fetuses, noninvasively.

Response to rhGH therapy in short children born at very low birth weight.

Although the clinical benefits of long-term rhGH therapy have been well demonstrated in children born small for gestational age (SGA), little is known about the outcomes of this therapy in children born with very low birth weight (VLBW). This study aimed to report the short and long-term response to rhGH therapy in a cohort of VLBW patients, comparing subgroups according to size, gestational age, and causal factors associated with VLBW. We describe 33 patients born at VLBW treated with rhGH; 16 also received GnRHa. Medical records were analyzed at baseline and after one year of rhGH treatment. Data on the adult height SDS from 23 patients were also collected. Growth velocities and height SDS changes were calculated, along with the differences between the observed and predicted growth velocities. The first-year growth velocity (7.5±2.1cm/y) was aligned with prediction models for SGA children. After one year of rhGH treatment, height SDS improved from -3.0±1.1 to -2.6±1.3, with no differences among subgroups. Among patients reaching adult height, 73.9% remained short (-2.5±1.3) after long-term therapy (6.7±3.3y). The initial height SDS, height SDS change in the first year of treatment, and target height SDS were key independent predictors of height gain. The response to rhGH treatment was suboptimal in the VLBW group, independent of the size, gestational age, or etiological diagnosis. However, adult height may be improved in patients receiving rhGH treatment. This underscores the need for tailored protocols and further investigations to optimize outcomes in this population.

3D scanner measuring preterm infants’ head circumference and cranial volume: validation in a simulated care setting

IntroductionWeekly head circumference (HC) measurements using a measuring tape is the current standard for longitudinal brain growth monitoring of preterm infants. The MONITOR3D (M3D) 3D scanner has been developed to measure both HC and cranial volume (CrV) of preterm infants within incubators. The M3D’s usability, accuracy and precision were validated in a simulated setting in a neonatal intensive care unit (NICU).Materials and methodsDuring a simulated routine care moment, NICU nurses conducted M3D scans of a preterm doll simulating an extreme low birthweight preterm (ELBW; BW &amp;lt; 1,000 g) infant, followed by manual HC measurements using a measuring tape. Usability was quantified by percentage of successful HC and CrV measurements from scans. HC and CrV were calculated by marking anatomical landmarks on the 3D image. Measurements were compared to the real, ground truth (GT) values of the doll’s head, defined by an accurate medical scanner. Measurement accuracy was assessed using mean or median absolute measurement error (ME), and precision by the spread of ME, represented by the 95% interval of the ME range. ME intervals were compared with preterm weekly growth increases to assess clinical usability.ResultsRegarding usability, 56 M3D scan sessions resulted in 25 successful (44.6%) HC and CrV measurements, with incomplete 3D data being the primary cause of unsuccessful scans. Accuracy of the measuring tape for HC was 0.2 cm (proportional 0.9% of GT), and precision was 1.6 cm (6.3%). M3D’s accuracy of HC was 0.4 cm (1.5%), and precision was 0.7 cm (2.9%). For CrV, M3D’s accuracy was 8.0 mL (3.8%) and precision 22.6 mL (10.8%).ConclusionThe M3D scanner is suitable for measuring HC and CrV in ELBW infants. However, current scan success rate is too low for practical usability. The M3D’s accuracy and precision are clinically sufficient, while the precision of the current measuring tape method is inadequate for preterm infants. This makes the M3D a promising alternative for HC, offering less disturbance to the infant. In the future, the M3D technique could facilitate the creation of CrV growth reference charts for ELBW infants, enhancing the accuracy of clinical growth monitoring for preterm infants.

Abstract 4137064: High Incidence of Adverse Neonatal Outcomes of Pregnancy in Women with Congenital Heart Disease

Background: Neonates born to women with congenital heart disease (CHD) are at high risk for adverse outcomes. We sought to describe these outcomes and maternal/pregnancy risk factors. Methods: We analyzed linked clinical, administrative, and birth certificate data in 3 geographic areas in Georgia, North Carolina and Utah from 2011 through 2014. Birth certificates provided neonatal, maternal and pregnancy characteristics. Maternal CHD was identified from linked clinical and administrative data and categorized as severe , shunt , valve , or shunt+valve . Neonatal outcomes of interest included preterm delivery (&lt;37 wk), low birth weight (&lt;2500 g) (LBW), small for gestational age (SGA), neonatal intensive care unit admission (NICU), a composite “any poor outcome” (one or more of preterm, SGA, or NICU), and CHD. Neonatal outcomes were summarized using descriptive statistics. Differences by maternal CHD severity were assessed using Kruskal-Wallis and Chi-square tests for continuous and categorical variables, respectively. Association of maternal/pregnancy characteristics and neonatal outcomes were assessed using generalized estimating equations with logit link function clustered on mother and adjusted for mother’s age, birth year, and state. Results: We identified 2,422 liveborn neonates (median gestational age 38 wks, weight 3155 g) born to 1,987 women with CHD (34% severe , 32% non-White, median age 28yrs). Overall, 19% were preterm, 18% LBW and 14% SGA; 25% required NICU and 40% experienced the composite adverse outcome (preterm, SGA, and/or NICU). CHD was present in 4.2%. Infants born to mothers with severe CHD (vs. combined non-severe) were more likely to have an adverse composite outcome [aOR 2.1 (1.7, 2.5)] and CHD [aOR 17.1 (9.3, 31.5)]. Black race [vs. White, aOR 1.8 (1.4, 2.3)], pregestational diabetes (DM) [vs. no, aOR 2.5 (1.3, 5.0)], gestational hypertension (GHTN) [vs. no, aOR 2.1 (1.5, 3.1)], prior preterm birth [vs. no, aOR 2.0 (1.3, 3.1)] and multiples [vs. singleton, aOR 6.7 (3.8, 11.6)] were associated with increased risk of composite adverse outcome. Conclusions: Forty percent of neonates born to women with CHD experienced an adverse neonatal outcome. Risk increased with maternal CHD severity, Black race, GHTN, DM, prior preterm birth, and multiple pregnancy. These findings highlight the need for heightened awareness and surveillance of these risk factors and expert preconception and pregnancy counseling for woman with CHD.

Effect of nutrition on the nutritional status in preterm infants with very low birth weight

Introduction. Postnatal growth retardation in premature infants with very low birth weight (VLBW) remains an unresolved problem. There are different approaches regarding the duration of use of breast milk fortifiers during breastfeeding and specialized formulas during formula feeding, as well as the timing of the appointment of complementary feeding. Objective: to evaluate the physical development and component body composition in VLBW infants, depending on nutritional support over the first year of life. Materials and methods. The study included ninety three VLBW premature infants of 2 to 11 months postnatal age (PNA). The main (1st) group included infants (n = 74) who received dietary correction depending on the nutritional status, while no such intervention was performed in the (2nd) comparison group (n = 19). Up to 64 weeks of postconceptional age (PCA), weight, body length, and head circumference were assessed using INTERGROWTH-21st international growth standards, then in the software “WHO Anthro (2009)”. Fat and fat-free (lean) mass were determined using the air plethysmography method (PEA POD, LMi, USA). Results. The analysis of the nutritional status revealed a moderate deviation, not exceeding 1 sigma, decrease in indices (Z-scores) of anthropometric indices in infants of the 1st and 2nd groups by PNA of 2–3 months. Further in infants of the 1st group on the background of prolonged use of fortified nutrition (breast milk fortifier or specialized formulas for preterm infants) and timely introduction of complementary foods, nutritional deficiencies throughout the first year of life in general were not revealed. In the 2nd group of infants without additional correction of nutrition by 4–5 months of age, the development of mild nutritional deficiency was noted by 6–7 months of age. By 6–7 months of age, it turned into moderate nutritional deficiency, which persisted until 8–9 months of age and then turned into mild nutritional deficiency. Analysis of the component body composition showed that during the observation period, the fat-free body mass (FFM) gain in infants in the 1st group was 3.40 kg, in Group 2 infants — 2.2 kg. At the same time, % body fat mass (FM) in infants in groups 1 and 2 had no significant differences (%FM 1 = 19.3 [15.3–22.5], %FM 2 = 19.9 [16.7–24.6], p = 0.769) and did not exceed the values characteristic of preterm infants. Conclusion. A comprehensive assessment of the nutritional status of VLBW infants during the first year of life allowed us to eva­luate the positive impact of long-term use of fortified diets and timely introduction of certain complementary foods. Optimization of nutrition made it possible to prevent the development of nutritional deficiency, which can have a significant positive impact on their further growth, development, and health status.

Abstract 4123182: Women with Severe Congenital Heart Disease Have Increased Risk of Fetal/Neonatal Death

Background: Women with congenital heart defects (CHD) now routinely survive to reproductive age. Offspring of these women have more complications, including but not limited to inherited CHD, prematurity, small for gestational age (SGA), and fetal/neonatal death. In the United States, pregnancy-related complications and death are more common in Black women and their offspring compared to White women and their offspring, and in those residing in rural areas compared to urban areas. Aims: This study evaluates fetal/neonatal outcomes among women with CHD covered by Georgia Medicaid at the time of pregnancy, looking for differences among racial, geographic, and CHD severity groups. Methods: This retrospective cohort study identified 4581 women with CHD aged 11-50 with 6522 pregnancies (28.5% with severe CHD, 50.9% Black, 23.2% rural) covered by Georgia Medicaid between 2008-2019. Fetal/neonatal death, defined as fetal death after 20 weeks gestation, stillbirth, or neonatal death, was examined by CHD severity, race, and rurality using chi-square analysis. Multivariate logistic regression models were conducted adjusting for age at first documented pregnancy, social deprivation index (SDI), number of pregnancies, and multiple gestations. Results: Of 6522 pregnancies, 3.0% resulted in fetal/neonatal death. Fetal/neonatal death was more common in women with severe CHD compared to those with non-severe CHD (4.1% severe vs. 2.6% non-severe [aOR 1.39, 95% CI 1.02-1.85, p = 0.0018]). No significant differences were revealed in fetal/neonatal death between racial (3.3% Black vs. 2.8% White) or geographic (2.9% rural vs. 3.1% urban) groups after controlling for other variables. Conclusions: Compared to reported fetal and neonatal death rates among all U.S. pregnancies in 2019, women with CHD experienced a higher rate of fetal/neonatal death. Fetal/neonatal death was even more prevalent for women with severe CHD (4.1%) versus women with non-severe CHD (2.6%). Women with CHD, especially those with severe disease, have a high risk of fetal/neonatal death and should be monitored closely throughout the course of pregnancy.

The association of Helicobacter pylori with adverse pregnancy outcomes in three European birth cohorts.

Helicobacter pylori is a prevalent infection that may complicate pregnancy, but evidence remains limited, controversial and may not apply to all pregnant women. This study aims to evaluate whether Helicobacter pylori is a risk factor for adverse pregnancy outcomes and to identify vulnerable subpopulations. Multiplex serology was utilized to measure blood levels of immunoglobulin G against eight Helicobacter pylori antigens in 1372 pregnant women from three European birth cohorts: BiB (United Kingdom), Rhea (Greece) and INMA (Spain). Outcomes of interest included gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth and small for gestational age neonates, as well as prenatal anxiety and depression. Adjusted logistic regression models were used to evaluate the association between Helicobacter pylori seropositivity (overall and by antigen) and antigen specific antibody levels with the outcomes. We examined effect modification of the associations by ethnicity. Helicobacter pylori seropositivity was detected in 18.8% (258/1372) of pregnant women. Preeclampsia was the least common outcome (26/830). Helicobacter pylori seropositivity was associated with the development of two or more adverse pregnancy outcomes (gestational hypertension, gestational diabetes, preterm birth, small gestational age and preeclampsia) [OR:1.32 (95% CI: 1.06-1.65), p-value: 0.01], especially in women with high antibody levels to OMP antigen [OR: 2.12 (95% CI: 1.62-2.76), p-value: 0.001]. Women with high antibody levels to Helicobacter pylori antigens GroEL and NapA were more likely to develop preeclampsia [OR: 2.34 (95% CI: 1.10-8.82), p-value: 0.03; OR: 4.09 (95% CI: 1.4-11.93), p-value 0.01)]. Helicobacter pylori seropositivity increased the odds of developing any hypertensive disorder during pregnancy among women of western ethnicity (948/1372) [OR:3.35 (95% CI: 1.29-8.74), p-value 0.03]. Our study suggests that Helicobacter pylori seropositivity is a risk factor for multiple adverse pregnancy outcomes and particularly in women of western origin for hypertensive disorders during pregnancy. Moreover, pathogen specific characteristics reflected in the antibody responses against OMP, GroEL and NapA seem to determine disease associations.

Metabolomic signatures associated with fetal growth restriction and small for gestational age: a systematic review.

The pathways involved in the pathophysiology of fetal growth restriction (FGR) and small for gestational age (SGA) are incompletely understood. We conduct a systematic review to identify metabolomic signatures in maternal and newborn tissues and body fluids samples associated with FGR/SGA. Here, we report that 825 non-duplicated metabolites were significantly altered across the 48 included studies using 10 different human biological samples, of which only 56 (17 amino acids, 12 acylcarnitines, 11 glycerophosphocholines, six fatty acids, two hydroxy acids, and eight other metabolites) were significantly and consistently up- or down-regulated in more than one study. Three amino acid metabolism-related pathways and one related with lipid metabolism are significantly associated with FGR and/or SGA: biosynthesis of unsaturated fatty acids in umbilical cord blood, and phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, and phenylalanine metabolism in newborn dried blood spot. Significantly enriched metabolic pathways were not identified in the remaining biological samples. Whether these metabolites are in the causal pathways or are biomarkers of fetal nutritional deficiency needs to be explored in large, well-phenotyped cohorts.

Motor outcomes in individuals born small for gestational age at term: a systematic review.

Being born small for gestational age (SGA) is a risk factor for motor difficulties. Previous reviews exploring this topic are mostly focused on children born preterm. We aimed to review the literature to determine the association between being born SGA at term and motor outcomes. PubMed and Embase were searched for relevant articles without any restrictions on publication year or participants' age. Inclusion criteria were SGA exposure at term (≥ 37 weeks of gestation), cohort studies or randomized controlled trials with motor outcome assessed by standardized motor tests with results reported as continuous scores (mean/median) compared with a control group. Exclusion criteria were abstracts, editorials and commentaries, articles in non-English language or no full text available. Reviews were screened for relevant articles. Quality of included studies was assessed by the Newcastle-Ottawa Scale. In total, 674 records were identified by the literature search and screened by two independent authors. Thirteen original articles were eligible and included in a qualitative synthesis, and five (38%) of these were included in a meta-analysis. Nine (69%) studies were from high-income countries. Most studies were carried out in early childhood, and only one study in adulthood. Seven (54%) articles reported that individuals born SGA at term had poorer scores on standardized motor tests compared with controls, while no differences were reported in five (38%) articles. One article did not report p-values, although the differences were comparable to the other studies. Group differences were of small to moderate effect size (0.19 to 0.65 standard deviation units). The pooled effect size was -0.43 (95% confidence interval: -0.60 to -0.25). Adjustment for covariates were reported in seven (54%) articles and did not change the results. Proportions of motor difficulties, reported in five (38%) articles, ranged from 8.9 to 50% in individuals born SGA from infancy to adolescence. This systematic review shows that being born SGA, also at term, may be a risk factor for poorer motor outcomes throughout childhood, confirmed by a meta-analysis in early childhood. Further research is needed to establish the risk of adult motor difficulties in individuals born SGA at term.

A Phase 2 Study of PEGylated Recombinant Human Growth Hormone for 52 Weeks in Short Children Born Small for Gestational Age in China.

Children born small for gestational age (SGA) are at increased risk of health issues. This study evaluated the efficacy, safety and optimal dose of PEGylated-recombinant human growth hormone (PEG-rhGH) in these children. In this multicentre, randomised, open-label, Phase 2 trial conducted at nine clinical sites in China, patients were randomised 1:1 to receive subcutaneous injections of PEG-rhGH at 0.1 mg/kg/week (low dose) or 0.2 mg/kg/week (high dose) for 52 weeks. Ninety-six children were born SGA. The primary endpoint was the change in height standard deviation score (HT-SDS) at Week 52. At Week 52, the change in HT-SDS in the high- and low-dose groups was 0.923 ± 0.352 (p < 0.0001) and 0.511 ± 0.336 (p < 0.0001), respectively (least-squares means difference, 0.410; 95% confidence interval 0.270-0.551; p < 0.0001). Height velocity (9.94 ± 1.55 vs. 8.37 ± 1.50 cm/year) was also significantly higher in the high-dose than in the low-dose group (p < 0.0001). Change in insulin-like growth factor (IGF)-1 SDS was 1.867 ± 1.747 and 1.168 ± 1.193 in the high- and low-dose groups, respectively (p = 0.0189). IGF-1/IGF binding protein-3 and bone maturity were improved in both groups at Week 52. Most treatment-emergent adverse events were mild to moderate; the safety profile was similar in both groups. PEG-rhGH at either dose for 52 weeks was effective and well tolerated in children born SGA. Patients in the high-dose group achieved greater improvement in HT-SDS than in the low-dose group. ClinicalTrials. gov identifier: NCT02375620.

Importance of Modifiable Factors to Infant Health in the Context of Prenatal Opioid Use Disorder.

The aim of the study is to estimate the contributions of common and modifiable risk factors to birth outcomes of individuals with prenatal opioid use disorder (OUD). We conducted an observational cohort study of all Wisconsin Medicaid-covered singleton live births from 2011-2019. Using Blinder-Oaxaca decomposition for continuous, and the Fairlie extension for categorical outcomes, we estimated the contributions of comorbidities, tobacco use, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) to birthweight for gestational age (BW-GA) percentile associated with prenatal OUD and the risk of small for gestational age (SGA), net of other factors. Among 216,684 births, the 5184 (2.4%) with OUD had greater prevalence of tobacco use, a lower average pre-pregnancy BMI (26.7 kg/m2, SD = 0.09 versus 28.4 kg/m2, SD = 0.02), and on average 2.0 pounds less GWG, when compared to those without OUD. The predicted mean BW-GA percentile among infants with OUD exposure was 11.2 (95% CI 10.5, 11.9) points lower than those without; 62.3% (95% CI 57.4, 67.1) of this difference could be explained by the variables included in the full model and the largest contribution of the explained portion came from the higher prevalence of tobacco use followed by the contributions of comorbidities, GWG, and pre-pregnancy BMI. More than half of the difference in BW-GA percentile, and risk of SGA associated with prenatal OUD, could be attributed to modifiable factors and not opioids. Moreover, potentially modifiable factors including tobacco use and measures reflecting nutritional status contributed to a majority of the explained portion.

Effects of rapid enteral feed advancement with early human milk fortification in very low birth weight preterm infants > 30 weeks gestation in a resource limited setting- a randomized controlled trial.

To study the effects of rapid enteral feed advancement with early feed fortification in stable very low birth weight (VLBW) infants >30 weeks gestation. Preterm infants (N = 92) were randomized to a) rapid feed advancement-early fortification - REF group (enteral feed advanced at 25-30 ml/kg/day, fortification at 50 ml/kg/day) or b) slow feed advancement-late fortification-SLF group (feed advanced at 15-20 ml/kg/day, fortification at 100 ml/kg/day). The primary outcome-time to regain birth weight was significantly lower in REF group (9 days vs 13 days, P = 0.02). REF group reached full enteral feeds earlier (6 days vs 9 days, P = 0.001), had lower rates of sepsis (13% vs 38%, P = 0.007) and shorter hospital stay (10 days vs 15 days, P = 0.01). At one year, the median Z-scores for weight [-1.5 vs -2.2, P < 0.001] and head circumference [1.1 vs 0, P < 0.001) were significantly higher in the REF group. In VLBW preterm infants >30 weeks, rapid feed advancement with early fortification resulted in early postnatal regain of birth weight with positive effects on growth at one year.

Association of maternal 25(OH)D levels during pregnancy with fetal birth weight and preschooler growth status: A retrospective birth cohort study.

There is limited and conflicting evidence available regarding the correlation between maternal vitamin D status and childhood overweight and body mass index (BMI). The aim of this study was to investigate the following: (1) potential association between maternal 25-hydroxyvitamin D (25(OH)D) levels and newborn growth status; (2) relationship between maternal 25OHD levels and BMI and the risk of overweight with preschoolers being overweight. A cohort of 3213 eligible singleton mother-infant pairs were used to investigate the possible associations between maternal 25(OH)D levels and fetal growth status. Data of 1767 available singleton mother-infant pairs and 6-year-old preschoolers was applied to analyze the potential correlations between maternal 25(OH)D status and risk of childhood overweight. Compared with sufficient 25(OH)D in pregnancy group (≥75 nmol/L), there were no correlations between the maternal 25(OH)D deficiency (<50 nmol/L) and large gestational age (LGA) (p = 0.465), small gestational age (SGA) (p = 0.607), lower birth weight (LBW) (p = 0.725) or fetal macrosomia (p = 0.535). Moreover, no significant associations between insufficient maternal 25(OH)D (50-75 nmol/L) and LGA (p = 0.505), SGA (p = 0.816), LBW (p = 0.816), or fetal macrosomia (p = 0.413) were observed. We found statistically significant disparities between the fetal birth weight and height (p < 0.001), weight (p < 0.001), head circumference (p = 0.001) of 6-years preschooler. No significant associations were found between the maternal 25(OH)D levels and BMI and risk of overweight at 6-year-old preschoolers. There were no apparent correlation found between maternal 25(OH)D concentrations and fetal birth status. There was no evidence found to suggest the effect of maternal 25(OH)D level on overweight at 6-year-old preschoolers.

Associations of maternal urinary nitrophenol concentrations with adverse birth outcomes and neurodevelopment delay at 4 years of age: The Japan environment and children's study

Maternal urinary nitrophenol concentrations are reportedly associated with preterm birth and foetal/offspring development delay, but the evidence is still inconclusive. We investigated the association between maternal urinary concentrations of 4-nitrophenol (4NP) and 3-methyl-4-nitrophenol (3M4NP) and adverse birth outcomes, as well as offspring neurodevelopment delay, defined using the Ages and Stages Questionnaires at 4 years of age, stratified by offspring sex. A total of 3650 non-hypertensive mothers with singleton births were enrolled from the Japan Environment and Children's Study. High 4NP (≥0.41 μg/L) and 3M4NP (≥0.29 μg/L) were defined as ≥ lowest concentration minimum reporting level. Four groups were created using these dichotomized 4NP and 3M4NP concentrations: ‘both low’, ‘either high/low’, and ‘both high’. Multivariable logistic regression models were used to estimate the adjusted odds ratios (aOR) and population attributable fraction (PAF). For 4NP and 3M4NP, 68.4% and 19.0% of participants had ’high’ urinary concentrations, respectively. Compared to ‘both low’, the overall analysis showed no significant associations between ‘both high’ and any of the outcomes. However, the stratified analysis showed that the aOR (95% confidence interval [CI]) and PAF (95% CI) for ‘both high’ regarding preterm birth (<37 weeks' gestation) were 2.7 (1.3, 5.7) and 16.3% (2.5%, 28.1%), respectively, in male offspring. Among female offspring, the aOR and PAF for the ‘both high’ regarding small-for-gestational-age (SGA)—defined as weight-for-gestational age <10 percentile based on the Japanese neonatal anthropometric charts—were 1.7 (1.0, 2.8) and 10.6% (−0.2%, 20.2%), respectively. Urinary 4NP and 3M4NP concentrations showed no association with low birth weight (<2500 g) and neurodevelopment delay.In conclusion, offspring sex-specific associations of maternal urinary nitrophenols with preterm birth and SGA were observed. Even slight elevations in their levels may explain a certain proportion of preterm birth and SGA. The exposure source, expressed by urinary nitrophenols, should be identified.

Low PAPPA and Its Association with Adverse Pregnancy Outcomes in Twin Pregnancies: A Systematic Review of the Literature and Meta-Analysis

Background: It is well established in the literature that pregnancy-associated plasma protein-A (PAPP-A) is linked to several adverse pregnancy outcomes, including pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB) in singleton pregnancies. However, data regarding such an association in twin pregnancies are lacking. The primary goal of this systematic review and meta-analysis was to assess the potential value of low PAPP-A levels in the prediction of the subsequent development of hypertensive disorders of pregnancy (HDPs), PTB, and small for gestational age (SGA)/FGR fetuses in twin pregnancies and investigate its association with the development of gestational diabetes, intrauterine death (IUD) of at least one twin, and birth weight discordance (BWD) among the fetuses. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 July 2024. All observational studies reporting low PAPP-A levels after the performance of the first-trimester combined test as part of the screening for chromosomal abnormalities with reported adverse pregnancy outcomes were included. Results: The current systematic review encompassed a total of 11 studies (among which 6 were included in the current meta-analysis) that enrolled a total of 3741 patients. Low PAPP-A levels were not associated with HDPs (OR 1.25, 95% CI 0.78, 2.02, I-square test: 13%). Low PAPP-A levels were positively associated with both the development of preterm birth prior to 32 (OR 2.85, 95% CI 1.70, 4.77, I-square test: 0%) and 34 weeks of gestational age (OR 2.09, 95% CI 1.34, 3.28, I-square test: 0%). Furthermore, low PAPP-A levels were positively associated with SGA/FGR (OR 1.58, 95% CI 1.04, 2.41, I-square test: 0%). Prediction intervals indicated that the sample size that was used did not suffice to support these findings in future studies. Conclusions: Our study indicated that low PAPP-A levels are correlated with an increased incidence of adverse perinatal outcomes in twin pregnancies. Identifying women at elevated risk for such adversities in twin pregnancies may facilitate appropriate management and potential interventions, but additional studies are required to identify the underlying mechanism linking PAPP-A with those obstetrical complications.

Metabolomic profiling of human feces and plasma from extrauterine growth restriction infants.

Extrauterine growth restriction (EUGR) affects a substantial proportion of preterm infants and may influence both short-term complications and long-term sequelae. While many preterm infants with EUGR are secondary to small for gestational age (SGA) or very low birth weight (VLBW), a subset of EUGR infants do not exhibit these conditions. The purpose of this study is to investigate the metabolic profiles and biomarkers of EUGR infants in the absence of SGA and VLBW. A total of 100 feces (n = 50) and plasma samples (n = 50) were collected from participants categorized as either EUGR (EUGR group) or non-EUGR (NonEUGR group) in the absence of SGA and VLBW. Metabolites were characterized via UPLC-MS/MS using the Discovery HD4® platform. Data normalization, partial least squares discriminant analysis (PLSDA), and KEGG enrichment analysis of metabolite profiles were performed using the MetaboAnalyst 6.0. The clinical characteristics of preterm infants differed significantly between the EUGR and NonEUGR groups at discharge, including length of stay, weight Z-score, weight, height Z-score, height, head circumference, and fat-free mass. The PLSDA model exhibited clustering within groups and separation between groups. A total of 58 and 71 differential metabolites were identified in feces and plasma samples, respectively. They were involved in pathways such as caffeine, galactose, glutathione, cysteine, and methionine metabolisms. In the feces sample, 1-palmitoyl-galactosylglycerol exhibited a significant negative correlation with the growth characteristics of preterm infants, while 1-palmitoyl-2-palmitoleoyl-GPC displayed the opposite pattern. In plasma samples, androsterone glucuronide displayed a significant positive correlation with the growth characteristics of preterm infants, whereas 2-methoxyhydroquinone sulfate generated an opposite pattern. Moreover, 2-oleoylglycerol and sphinganine-1-phosphate exhibited the highest area under the curve in feces and plasma samples, respectively, according to diagnostic ROC curves. Preterm infants with EUGR, in the absence of SGA and VLBW, exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol may hold promise as diagnostic markers for EUGR in the absence of SGA and VLBW. The objective of this study is to identify the differential metabolites in preterm infants with extrauterine growth restriction (EUGR) in the absence of small for gestational age (SGA) or very low birth weight (VLBW). Preterm infants with EUGR without SGA and VLBW exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol emerged as potential diagnostic biomarkers for EUGR. This study enhances our understanding of the metabolomic profile in preterm infants with EUGR without SGA or VLBW. Our findings will offer valuable evidence for improving nutritional management and shedding light on the associated pathophysiological mechanisms of EUGR.

Development and validation of an ultrasound-based estimated fetal weight reference for Chinese twin pregnancy: a retrospective cohort study

BackgroundFetal growth monitoring is important for twin pregnancies. However, there has been no clinically validated tool for monitoring fetal growth of twin pregnancies in China. This study aims to develop and validate a chorionicity-specific growth chart of ultrasound estimated fetal weight (EFW) for Chinese twin pregnancies.MethodsThis retrospective cohort study included all twin pregnancies who delivered two live fetuses with gestational age ≥ 34 weeks without severe obstetric complications at a tertiary hospital from January 2007 to March 2021. The participants were divided into a development set (delivered in or before December 2017) and a validation set (delivered in or after January 2018). Chorionicity-specific growth charts were created using the generalized additive models for location, scale, and shape (GAMLSS) based on the development set. The fetuses from the validation set were classified into three groups based on the last EFW: small-for-gestational-age (SGA) indicated by both the newly established twin charts and the Hadlock singleton chart currently used for twin pregnancies in China, suspected SGA indicated by only the singleton chart, and no SGA indicated by either chart. The incidence of neonatal outcomes among the three groups was then compared accordingly, including intensive care unit (NICU) stay length, respiratory diseases, and neurological disorders.ResultsThe development set included 883 twin pregnancies and a total of 6374 EFW measurements between 16 and 38 weeks of gestation, and the validation set included 801 twin pregnancies and 7630 EFW measurements. In the development set, monochorionic diamniotic (MCDA) twins had a significantly lower EFW compared to dichorionic diamniotic (DCDA) twins beginning at 26 weeks, with the difference gradually increasing thereafter, supporting the establishment of chorionicity-specific growth charts. Of the 1,602 twin neonates in the validation set, 103 (6.4%) were classified into the SGA group, 164 (10.2%) into the suspected SGA group, and 1335 (83.3%) into the no SGA group. The incidence of respiratory diseases and neurological disorders was comparable between the suspected SGA group and the no SGA group, but apparently higher in the SGA group. Meanwhile, NICU stay lengths were consistently longer for twins in the SGA group compared to the no SGA group (difference: 0.57, 95% CI: 0.31–0.83), with no significant differences observed between the suspected SGA and no SGA groups.ConclusionsThe fetal growth trajectories differed by chorionicity, with a lower EFW for MCDA twins beginning at 26 weeks. The establishment of chorionicity-specific growth chart could reduce overdiagnosis of SGA and improve fetal growth monitoring of twin pregnancies.

Analysis of the Association between In Vitro Fertilization/Assisted Conception and the Development of Retinopathy of Prematurity in Very-Low-Birth Weight Newborns.

The objective is to study to what extent the development of retinopathy of prematurity (ROP) is associated with assisted conception (AC) and in vitro fertilization (IVF) in a tertiary referral hospital. This study is a retrospective observational cohort study. Very-low-birth weight (VLBW) infants with gestational age (GA) <32 weeks or birth weight <1500 g were admitted to the neonatal unit of a tertiary care hospital between January 1, 2011, and December 31, 2021. The study determined the degree of ROP developed according to the type of fertilization used for conception. Main outcome measures were ROP prevalence in pregnancies obtained after IVF/intracytoplasmic sperm injection (ICSI) in the period from January 1, 2011, to December 31, 2021, in a tertiary hospital. Of the 408 infants included in the study sample, 105 (25.7%) were born following AC and 12.4% of these developed ROP. In our sample, the practice of IVF was not associated with an increase in the incidence of VLBW infants (R2 = 0.12; P = .29). Conception achieved via AC or IVF is not significantly associated with ROP in any degree of severity.