3rd Percentile Research Articles

Echocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or diagnosed with fetal growth restriction (FGR) are at increased risk of neonatal mortality as well as cardiovascular disease later in life. Previous studies based on smaller cohorts (n<200) of newborns with SGA and FGR (n<200) have demonstrated structural and morphological alterations in the heart compared to infants born appropriate for gestational age (AGA). However, to our knowledge no previous study has systematically investigated the effect of SGA and FGR on echocardiographic parameters in the infant heart. Purpose To investigate whether echocardiographic parameters differ among infants born SGA or with FGR, in comparison to infants born AGA. Methods This study is a population-based cohort study of infants (n>25,000) offering postnatal cardiac examination including transthoracic echocardiography (TTE) between 2016-2018. We compared left ventricular (LV) TTE parameters in infants born SGA (birthweight ≥3rd and <10th percentile, n=2,106) and with FGR (birthweight <3rd percentile, n=972) with infants born AGA (birthweight ≥10th and <90th percentile, n=20,468) using a multiple linear regression analysis. We have investigated LV volumes, systolic function, diastolic function, and LV structure. All analyses were adjusted for sex, gestational age at birth, weight, length, and age at cardiac examination. Results Infants born SGA had higher heart rates compared with infants born AGA. Both infants born SGA and infants with FGR had significantly smaller LV dimensions including septal and posterior wall thicknesses (IVSd and LVPWd), and LV internal diameters (LVIDd and LVIDs). Infants born SGA had smaller end-diastolic and end-systolic volumes compared with infants born AGA (Table 1). Infants born SGA or with FGR had significantly higher mitral valve early peak velocities, compared with infants born AGA, and infants born SGA showed increased mitral valve atrial peak velocities indicating altered diastolic function (Table 1). Conclusion Infants born with inadequate intrauterine growth had smaller LV dimensions compared with infants born AGA, even when adjusting for infant size and age. Infants born SGA and with FGR both exhibited altered diastolic function. Longitudinal studies of children with inadequate intrauterine growth are needed to determine the impact on adult cardiac health.

Electrocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or following fetal growth restriction (FGR) have an increased risk of neonatal mortality as well as cardiovascular disease later in life. Prenatal electrocardiograms (ECGs) in fetuses with FGR exhibit QT prolongation. However, neonatal alterations in the conduction system in infants born SGA or with FGR has not previously been assessed in a large cohort of infants. Purpose To investigate potential variations in electrocardiographic parameters between infants born SGA or diagnosed with FGR, in comparison to infants born appropriate for gestational age (AGA). Methods This study was based on data from a population-based cohort study of infants (n>25,000) with prenatal inclusion and postnatal cardiac examination including eight-lead ECG between 2016-2018. We conducted a multiple linear regression analysis to compare ECG parameters among infants with FGR (birthweight <3rd percentile, n=544) and SGA (birthweight ≥3rd and <10th percentile, n=1,384) to infants born AGA (birthweight ≥10th percentile and <90th percentile, n=14,076). Parameters of interest included: heart rate (HR), uncorrected and corrected (Bazzet and Fridericia) QT intervals, QRS duration, PR interval, QRS axis, maximum amplitudes of the R- and S-waves in V1 and V6. All analyses were adjusted for infant sex, gestational age at birth, and weight, length, and age at ECG examination. Results Infants born SGA or with FGR had higher HR and consequently shorter uncorrected QT intervals compared with infants born AGA (Table 1). Infants with FGR had significantly shorter corrected (Fridericias) QT intervals. Infants born SGA had smaller amplitudes of both the R- and S-wave in V6, and significantly larger amplitude of the S-wave in V1, compared with infants born AGA (Table 1). Conclusion ECGs from infants born SGA and infants with FGR differed from infants born AGA, including higher HRs and shorter uncorrected QT-intervals even after adjustments for infant size and age at the examination. Furthermore, we saw infants born SGA had reduced amplitudes of the S and R wave in the lateral lead (V6), and an increased amplitude of the S-wave in V1, compared with infants born AGA. Follow-up examinations of these infants could determine whether these alterations persist beyond the neonatal period, and to fully understand their implications of the cardiac function later in life.

Growth Status of Bangladeshi Children in Functional Constipation: Experience From A Tertiary Care Hospital

Background: Constipation is one of the common complaints of children with long-term hazardous consequences. It is a frequent cause of hospital visit in both primary and specialized care which needs proper evaluation and management. Recently in few studies, impairment of growth status has been reported as a result of functional constipation. But the relation is not well evaluated, especially in the pediatric population of our country. Aim: To assess the growth status of Bangladeshi children in functional constipation. Methods: This analytical study was conducted at the department of Pediatric Gastroenterology and Nutrition, BSMMU, Dhaka. A total 150 children aged 2-18 years were enrolled in this study. Children were divided into two groups, 75 having functional constipation (FC) and 75 healthy children with no constipation. Samples were collected randomly from pediatric out-patient department of BSMMU with consent of parents and child’s approval. Diagnosis of functional constipation was made by Rome IV criteria. Children with any red flag sign, chronic disease and on treatment of constipation were excluded from the study. Growth status (weight, height & BMI) was evaluated by using growth charts. Data collected in semi-structured questionnaire and analyzed by SPSS 23.0. Results: We evaluated 75 constipated children with the mean age of 7.61±3.50 years and 75 healthy children with the mean age of 7.40±3.88 years. The mean weight of children with functional constipation was 22.8±10.01 kg, mean height 117.7 ±18.4 cm and BMI 15.6±2.3 kg/m2. The mean weight of children with no constipation was 28.6± 13.72 kg, mean height 124.49±23.3 cm and BMI 18.11±2.9 kg/m2,demonstrated significant difference between two sets. In functional constipation group, on weight for age and height for age chart, 28% and 24% children were below the 3rd centile respectively and 18.6% children had BMI below 5th centile. All these parameters (weight, height, BMI) were statistically significant in compare to children without constipation and p value is <.05. Presenting features of functional constipation were anorexia (64%), abdominal pain (73.3%), hard stool (84%), blood mixed hard stool (13.3%) and nausea (34%). Conclusion: Growth impairment occurs in children with functional constipation in comparison to children without constipation. Children aged 2 to 18 years with functional constipation may have decelerated weight, height and BMI growth. And this observation needs further large-scale multicenter study for ensuring optimal growth of children with constipation. J Shaheed Suhrawardy Med Coll 2023; 15(1): 73-77

Reference Values for Handgrip Strength, Five Times Sit-to-stand, and Gait Speed in Patients on Hemodialysis.

Low levels of muscle strength and function predict adverse clinical outcomes in patients on hemodialysis; however, reference values remain lacking. We described reference values for handgrip strength, five times sit-to-stand (STS-5), and 4-m gait speed in a large-scale sample in patients on hemodialysis. Baseline data from the SARCopenia trajectories and associations with adverse clinical outcomes in patients on HemoDialysis (SARC-HD) study were analyzed. Muscle strength was evaluated using handgrip strength and the STS-5, whereas physical performance was evaluated using usual 4-m gait speed before a midweek dialysis session. Sex- and age-specific smoothed reference curves for each test at the 3rd, 15th, 50th, 85th, and 97th percentiles were constructed using generalized additive models for location shape and scale. Comparisons between sex and age were also performed. Data from 1004 patients (39% female; 19 to 96 years; 49% ≥ 60 years) were analyzed. Declines in muscle strength and physical performance were observed with advancing age in both sexes. However, among males, muscle strength and performance were similar between 18 and 49 years of age. Males exhibited substantially greater performance in handgrip strength (10.3 kg, 95% confidence interval (CI) 9.1 to 11.4) and 4-m gait speed (-0.10 seconds, 95% CI: -0.14 to -0.05) compared to females. Older patients, independent of sex, exhibited poorer performance on most tests. Lower handgrip strength in the arm with arteriovenous fistula was observed in both sexes (males -2.3 kg, 95% CI: -2.8 to -1.7; and females -2.1 kg, 95% CI: -2.6 to -1.6). Reference values obtained in this study may be used in clinical and research settings to identify patients on hemodialysis with low physical function according to sex and age. Future studies should test these reference values as potential predictors of adverse clinical outcomes.

Anthropometric indices growth references (length, Weight and Head Circumferences) of children aged 0–24 months in North-East of Iran by GAMLSS

BackgroundGrowth references play a crucial role in the screening, evaluation, and surveillance of children, aiding in the early identification of the requirement for diverse growth-promoting interventions. Variations in human growth across distinct ethnic cohorts arise from genetic disparities, lifestyle variances, nutritional diversity, and diverse social and environmental contexts. Consequently, the selection of growth references markedly influences the prevalence of developmental disorders and nutritional imbalances in children. The study aims to assess the growth percentile of children in the north-east of Iran and establish population-specific reference charts for length, weight, and head circumference spanning from birth to 24 months.MethodsThis cross-sectional population-based research conducted in the north-east of Iran, from 2016 to 2023. The Data extracted from the electronic health records of Mashhad University of Medical Sciences. All apparently healthy children aged from birth to 24 months who were measured at least once by health staff at the ages of birth,1,2,4,6,7,9,12,15,18,24 months were included. The target population of the study were 479,089 children (96.21%), encompassing 233,565 girls (48.75%) and 245,524 boys (51.25%). Gender-specific percentile curves for length, weight, and head circumference concerning age, as well as weight concerning length, were derived using the GAMLSS approach.ResultsFrom the anthropometric information of 479,089 children (245,524 boys and 233,565 girls), growth charts were constructed. In comparison to the standard WHO chart, Iranian neonates displayed lower weight across all percentiles during the first month after birth, exhibited decreased head circumference at the 3rd percentile, and boys showed reduced length across all percentiles. After this age, Iranian children demonstrated increased weight, length, and head circumference.ConclusionsThis research introduces the inaugural large-scale endeavor for indigenous reference charts. Through the noted distinctions from the international reference, the utilization of this novel resource offers the potential to enhance the surveillance of children’s growth within the area. Moreover, by accurately assessing growth anomalies such as underweight, stunting, and wasting, it expands the domain of impactful policies in this sphere. Simultaneously, it enables the exploration of the secular trend of children’s growth in the forthcoming years.

Evaluation of Anterior and Middle Brain Structures With Cerebrovascular Flow in Fetuses With Fetal Growth Restriction: A Prospective Study.

To investigate the adaptation of the anterior cerebral artery (ACA) in fetuses with fetal growth restriction (FGR) and assess if forebrain and midbrain structures are affected by vascular adaptations. A prospective case-control study involving normally developed fetuses and those with late-onset FGR (estimated fetal weight < 3rd percentile and/or abdominal circumference < 3rd percentile). Doppler indices of the middle cerebral artery (MCA), ACA and umbilical artery (UA) were determined between 32 + 0 and 37 + 0 weeks. Neurosonography assessed the depth of the insula, the sylvian fissure, and the antero-posterior diameter of the frontal lobes (FAPD). The cerebral-placental ratio (CPR) and cerebro-placental-uterine ratio (CPUR) were lower in FGR cases. ACA PI percentile values were significantly lower in the FGR group (p = 0.020). Sylvian fissure depth was significantly lower in FGR fetuses. The ACA may be the first cranial vascular structure affected in fetuses with FGR. This may be related to the impact on postnatal cognitive functions in FGR patients. NCT06215690.

Evaluation of Growth Characteristics and Final Heights of Cases Diagnosed with Noonan Syndrome on GH Treatment.

Proportional short stature is one of the most important features of Noonan Syndrome, and adult height often remains below the 3rd percentile. Although the pathophysiology of short stature in NS patients is not fully understood, it has been shown that GH treatment is beneficial in NS, and it significantly improves the height in respect to the results of short and long-term GH treatment. In this study, the efficacy of GH therapy was evaluated in children and adolescents with Noonan syndrome who attained final height. In this national cohort study, 67 cases with NS who reached final height from 14 centers were evaluated. A total of 53 cases (mean follow-up time 5.6 years) received GH treatment. Height SDS of the subjects who were started on GH tended to be shorter than those who did not receive GH (-3.26± 1.07 vs. -2.53 ±1.23) at initial presentation. The mean final height and final height SDS in girls using GH vs those not using GH were 150.1 cm and -2.17 SD vs 47.4 cm and-2.8 SD, respectively. The mean final height and final height SDS in boys using GH vs. not using GH were 162.48 ± 6.19 cm and -1.81 SD vs 157.46 ± 10.16 cm and -2.68 ± 1.42 SD, respectively. The Δheight SDS value of the cases was significantly higher in the group receiving GH than in those not receiving GH (1.36 ± 1.12 SD vs. -0.2 ± 1.24, p<0.001). Cardiac findings remained stable in two patients with hypertrophic cardiomyopathy who received GH treatment. No significant side effects were observed in the cases during follow-up. In patients with Noonan syndrome who reach their final height, a significant increase in height is observed with GH treatment, and an increase of approximately +1.4 SDS can be achieved. It has been concluded that GH treatment is safe and effective.

6805 Impact of Feeding Types on Catch-Up Growth in Early Infancy Among Small-for-Gestational-Age Infants: A Nationwide Korean Study

Abstract Disclosure: J. Choi: None. Y. Choe: None. S. Yang: None. Purpose: The study aimed to compare growth patterns and catch-up growth (CUG) in small-for-gestational-age (SGA) infants up to age four, based on feeding type during the first 4-6 months, using nationwide data. Methods: A total of 42,295 children born SGA (21,917 boys, 52.%) who underwent the first (4-6 month), 2nd (9-12 month), 3rd (18-24 month) and 5th (42-48 month) National Health Screening Program for Infants and Children (NHSPIC) under the National Health Insurance Service from 2007 to 2014 were included. The study population was categorized into two groups based on the primary milk feeding type recorded in the self-reported questionnaire during the first round of NHSPIC: the ”Breastfed”group, and the "Formula-fed" group. Catch-up growth (CUG) was defined as a Height Standard Deviation Score (Ht SDS) of 3rd percentile or above at the 5th NHSPIC visits. We used propensity scores to 1:1 match breastfed and formula-fed group based on sex, birth weight, cesarean section, socioeconomic status, residance. Multivariate logistic regression analysis was performed to evaluate the effect of milk feeding type on CUG at 4 years of age. Results: 49.1% of infants (n = 20,774) were breastfed and 50.9% (n = 21,521) were formula-fed. The median birth weight was 2.7 kg (interquartile range: 2.5-2.9 kg), and 98.7% of the children (n = 41,752) achieved CUG by the 5th NHSPIC round. Following propensity score matching, both groups included 19,308 infants. At four years of age, the breastfed group showed a lower likelihood of achieving CUG compared to the formula-fed group (aOR 0.794, 95% CI 0.665-0.948). During the 1st NHSPIC round, the breastfed group had a significantly lower weight Z-score (mean: -0.05, range: -0.64 to 0.41) than the formula-fed group (mean: 0.14, range: -0.42 to 0.78, p &amp;lt; 0.001). This trend was more pronounced from the 1st to 2nd round, with greater decreases in both weight and height Z-scores for the breastfed group (weight difference: -0.36, range: -0.74 to 0.02; height difference: -0.21, range: -0.62 to 0.20) compared to the formula-fed group (weight difference: -0.17, range: -0.53 to 0.20; height difference: -0.13, range: -0.53 to 0.28, p &amp;lt; 0.001). However, from the 2nd round, the breastfed group demonstrated faster gains in both weight and height (p &amp;lt; 0.001). Conclusion : In a study of Korean SGA infants, those breastfed during the first 4-6 months post-birth had lower CUG rates at four years compared to formula-fed infants. The breastfed group exhibited less weight and height gain, especially between the 1st and 2nd NHSPIC rounds, aligning with the initial phase of solid food introduction. These findings may suggest the need for enhanced nutritional supplementation for breastfed SGA infants. Further research is necessary to explore other factors that may impact growth during this critical developmental period. Presentation: 6/3/2024

6715 Short Adult Height in Childhood Cancer Survivors: Prevalence, Risk Factors, and Genetic Contribution

Abstract Disclosure: T. Yoshida: None. J. Baedke: None. F. Wang: None. W. Moon: None. Y. Sapkota: None. J. Miguel Martínez: None. T.E. Merchant: None. C.L. Wilson: None. K.K. Ness: None. M.M. Hudson: None. Y. Yasui: None. A. Delaney: None. Background: Survivors of childhood cancer are at elevated risk for short adult height (SAH) due to cancer and/or its treatment. In the general population, height is a highly polygenic trait; heritability is estimated to be 70-80%. However, the contribution of genetic factors to SAH among childhood cancer survivors is unknown. In addition, the contribution of chemotherapy agents to risk of SAH among survivors has not been established. We assessed: 1) prevalence of SAH; 2) contribution of genetic factors; and 3) impact of cancer therapy including chemotherapy, on SAH in a large cohort of childhood cancer survivors. Methods: Participants included 4461 childhood cancer survivors aged ≥18 years (female 47.5%, mean age 33.2 years old) with measured height information. SAH was defined as height &amp;lt;3rd percentile for age and sex based on the Centers for Disease Control growth charts. Cancer and treatment history were extracted from medical records. We calculated multi-ancestry height polygenic score (PGS) using the latest methodology developed from 5.4 million individuals of diverse ancestries with more than 1 million variants, where lower score associates with shorter height. With a random sample of 75% of survivors, we fit a multivariable logistic regression model for SAH with the PGS, chemotherapy exposures/doses, corticosteroid exposures/doses, and established risk factors for SAH (e.g., age at cancer diagnosis, radiotherapy exposure) as covariates (main model). The remaining 25% of survivors served for validation of the main model and for the calculation of the population attributable fractions (PAF) of the PGS and cancer treatments. Results: The prevalence of SAH was 8.9% among all survivors (9.3% in males; 8.5% in females) and differed widely by primary cancer diagnosis. SAH was associated with lower PGS [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.40-0.55 for a one standard deviation increase], alkylating agent exposure of &amp;gt;12000 mg/m2 (OR 2.19, 95% CI 1.41-3.38, vs. non-exposure), and spinal radiotherapy (OR 3.65, 95% CI 2.23-6.00, vs. non-exposure). Radiotherapy exposure to the hypothalamic-pituitary region and younger age at cancer diagnosis was also associated with SAH in a dose-response manner. The area under the ROC curve of the main model in the validation dataset was 0.80 (95% CI 0.74-0.87), suggesting good predictive ability for SAH by the model. The PAF of SAH calculated from the multiplicative logistic regression model of SAH was 85.7% for cancer treatments and 30.2% and 60.2% for having PGS below the median and the 90th percentile, respectively. Conclusions: Cancer treatments are the primary contributor to SAH risk among survivors with a PAF of 85.7%. Exposure to high-dose alkylating agents contributes to this along with radiotherapy. Inherited genetic factors also affect SAH among survivors but to a much lesser degree than cancer treatments. Presentation: 6/3/2024

7338 Temporal Trend of Age at Menarche in Korean Adolescents: A Population-based Study

Abstract Disclosure: H.Y. Kim: None. J. Kim: None. Background: The age at menarche has been decreasing worldwide. Previous studies in Korean adolescents also reported a downward trend of age at menarche. We investigated the current trends of age at menarche in Korean adolescents using nationally representative data. Methods: Data from the Korea National Health and Nutrition Examination Survey 2007-2021 were used in this study. A total of 50,730 females born between 1927 and 2004 with information on age at menarche were included in this study. The trend of age at menarche was analyzed according to 12 birth-year groups (with 5-year interval) using quantile regression analysis. Results: The mean age at menarche decreased over time, from 16.58±0.02 years for females born before 1950 to 12.45±0.04 years for females born between 2000 and 2004 (P &amp;lt;0.001). According to the percentiles group of age at menarche, the menarche age decreased by 0.073 years per year (95% confidence intervals [CIs], 0.072-0.074) in the 50th percentile group, 0.088 years per year (95% CI, 0.085-0.091) in the 97th percentile group, and 0.050 years per year (95% CI, 0.048-0.052) in the 3rd percentile group (P &amp;lt;0.001 for all). A decreasing trend of age at menarche was more prominent in the obese group (0.080 years per year, 95% CI, 0.078-0.082) compared to the non-obese group (0.069 years per year, 95% CI, 0.068-0.071) (P &amp;lt;0.001 for both). Conclusion: Ongoing downward trend in age at menarche was observed in Korean adolescents born until 2004, decreasing by 0.73 years per decade. A downward trend was faster in individuals in the higher percentile of age at menarche and in those with obesity. Presentation: 6/1/2024

Neonatal outcomes after in utero exposure to antipsychotics: a systematic review and meta-analysis.

Adverse neonatal outcomes following in utero antipsychotic exposure remain unclear. This systematic review and meta-analysis aimed to investigate associations between in utero first- and second-generation antipsychotic exposure and various neonatal outcomes. The primary outcome was small for gestational age. Secondary outcomes included other birth weight-related measures, prematurity and neonatal outcomes. MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrials.gov were searched for on 8th July 2023. Two reviewers independently selected studies reporting associations between exposure and neonatal outcomes (all designs were eligible, no language or time restriction) and extracted data. ROBINS-I was used for risk of bias assessment. Meta-analyses were performed. Measures of association were odds ratios and mean differences. Thirty-one observational studies were included. Regarding small for gestational age < 10th percentile, meta-analysis was only performed for second-generation antipsychotics and showed no evidence for an association (OR 1.31 [95%CI 0.83; 2.07]; I²=46%; phet=0.13, n = 4 studies). First-generation antipsychotics were associated with an increased risk of small for gestational age < 3rd percentile (OR 1.37 [95%CI 1.02; 1.83]; I²=60%; phet=0.04, n = 5) and a lower mean birthweight (MD -135g [95%CI -203; -66]; I²=53%; phet=0.07, n = 5). Second-generation antipsychotics were associated with large for gestational age > 97th percentile (OR 1.56 [95%CI 1.31; 1.87]; I²=4%; phet=0.37, n = 4) and Apgar score < 7 (OR 1.64 [95%CI 1.09; 2.47]; I²=47%; phet=0.13, n = 4). Both types of antipsychotics were associated with increased risks of preterm birth and neonatal hospitalization. Despite potential confounding in the studies, this systematic review and meta-analysis showed that newborns of mothers using antipsychotics during pregnancy are potentially at risk of adverse neonatal outcomes. Data sources: MEDLINE, EMBASE, CENTRAL, ICTRP, ClinicalTrials.gov. Prospero Registration Number CRD42023401805.

Coagulation profiles and percentiles in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: A step toward more accurate transfusion thresholds.

In the literature, there are no studies about the transfusion threshold for neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). In order to facilitate accurate interpretation of coagulation results in these neonates, we aimed to generate specific reference intervals in this specific population. This retrospective study included all HIE neonates admitted from 2014 to 2022 to undergo TH. All infants during TH underwent blood exams, including the coagulation profile. Our primary outcome was to assess the estimates of the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles for each parameter on admission (before transfusion). By the receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) and the best cut-off point were used to evaluate the ability of the prothrombin time expressed as international normalized ratio (PT-INR) to predict the risk of any bleeding. A total of 143 infants were included in this study. On admission, the median fibrinogen value was 205mg/dL, prothrombin time 18.6seconds, PT-INR 1.50, activated partial thromboplastin time 38.3seconds, thrombin time 18.6seconds, antithrombin 57.0%. The optimal cut-off of PT-INR in predicting the risk of any bleeding was greater than 1.84 (AUC.623, p=.024). For the first time, we proposed the percentiles of coagulation parameters in our cohort of neonates with HIE. Furthermore, we found that a PT-INR greater than 1.84 can significantly predict the risk of any bleeding. Further studies are needed to determine if a restrictive versus a liberal transfusion approach can be equally safer for these high-risk infants.

Metformin use and preeclampsia risk in women with diabetes: a two-country cohort analysis

BackgroundMetformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy.MethodsWe utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model.ResultsThe Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89–1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60–1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41–1.48]).ConclusionsIn this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes.

Insulin-like growth factor-1 deficiency caused by hepatocellular adenoma leads to growth arrest, primary amenorrhea and metabolic syndrome: a case report and 4 years follow up

BackgroundHepatocellular adenoma (HCA) is a rare benign neoplasm, seldom ascribed as the cause of endocrine and metabolic derangement. We herein report a case of primary amenorrhea, growth arrest and metabolic syndrome. En bloc resection of the tumor normalized all the disturbances.Case presentationA 16-year-old girl complained of primary amenorrhea and growth arrest for the past 2 years. Her height and weight were at the 3rd percentile, whereas waist circumference was at the 90th percentile for chronological age. She was hypertensive on admission. Plasma cholesterol, triglyceride and uric acid were elevated. Evaluation of GH/IGF-1 axis showed extremely low IGF-1 concentration, which was unresponsive to hGH stimulation. Computer tomography identified a huge liver mass (18.2 cm×13.7 cm×21 cm). The patient underwent an uneventful open right hepatic lobectomy. The tumor was en bloc resected. Immunohistochemistry indicated an unclassified HCA, which was confirmed by genetic screening. IGF-1 concentration, blood pressure, lipid profile and ovarian function were all normalized after surgery, and the girl had reduction in waist circumference and gain in height during the follow up.ConclusionWe provide evidence that liver-derived IGF-1 has a direct effect on skeletal and pubertal development, blood pressure, visceral adiposity and dyslipidemia independent of insulin resistance and obesity in the circumstance of undernutrition. Though rare, we propose the need to look into HCA cases for the existence of IGF-1 deficiency and its impact on metabolic derangement.

Cook’s balloon versus dinoprostone for Labour induction of term pregnancies with fetal GROWth restriction: study protocol for a randomised controlled trial in tertiary maternity hospitals in Spain (COLIGROW study)

IntroductionFetal growth restriction (FGR) affects about 3%–5% of term pregnancies. If prenatally detected and anterograde umbilical artery flow is preserved (stage I), it is recommended to deliver at term (≥...

Factors associated with the use of pharmacopuncture in addition to acupuncture in South Korea: An analysis of a nationally representative panel.

Pharmacopuncture is a widely used Korean medicine treatment, but its usage patterns and associated factors remain unclear. This study aimed to explore factors related to the use of pharmacopuncture alongside acupuncture and investigate the associated medical cost burden in South Korea. We analyzed the 2019 Korea Health Panel Annual Data, focusing on adult outpatients who received acupuncture alone or both acupuncture and pharmacopuncture (PA). We employed individual-level and visit-level approaches, using chi-square tests, t-tests, and binary logistic regression for analysis. Among 1280 patients, 10% were PA users. Logistic regression showed that PA use was significantly associated with being aged 30 to 49 (odd ratio [OR] = 2.531; P = .009), having an education level of elementary school or lower (OR = 2.571; P = .011), and being in the 2nd (OR = 1.914; P = .041) or 3rd income percentile (OR = 1.925; P = .020). Of 13,101 medical visits, 5.80% involved PA, with PA visits incurring significantly higher costs than acupuncture only visits (KRW 4438.33 vs 14,700.16; P < .001). Arthritis, shoulder disorders, and other joint conditions were more prevalent among PA visits (P < .001). This study reveals socioeconomic factors influencing pharmacopuncture use and highlights potential health inequalities in its access in South Korea. The higher costs associated with PA visits suggest a need for considering its inclusion in health insurance coverage. Future research should focus on the effectiveness, cost-effectiveness, and standardization of pharmacopuncture to address unmet healthcare needs and inform policy decisions.

Can the neutrophil-to-lymphocyte ratio be used as an early marker of small fetuses for gestational age? A prospective study.

Small-for-gestational-age (SGA) fetuses are at increased risk of mortality and morbidity, and less than 30% will be detected by any ultrasound scan within 4 weeks before delivery. Our aim was to evaluate the relationship between neutrophil/lymphocyte ratio (NLR) in the first trimester of pregnancy and SGA fetuses. We performed a prospective study between June 2021 and August 2022, to evaluate the relationship between the neutrophil to lymphocyte ratio in maternal blood in the first trimester of pregnancy, with the birth of an SGA fetus. One hundred ninety-four participants with singleton pregnancies between 11 + 1 and 13 + 6 weeks of gestation were recruited. Pregnancies affected with diagnosed fetal chromosomal abnormalities, or chronic pathologies were excluded. SGA was defined as birthweight less than the 10th centile (N = 42) and severe SGA as birthweight less than the 3rd centile for gestation (N = 10) according to a locally derived descriptive charts. The NLR value measured in the first trimester was compared between these two groups and controls. We found no statistically significant difference in NLR, (3.5 +/-1.2 vs. 3.4+/-1.2, p-value of 0.78) when comparing the SGA less than the 10th centile group to the control group. NLR was also not different between severe SGA and controls (3.6+/-1.4 vs. 3.4+/-1.2 p-value of 0.78). We found no association between first-trimester NLR ratio and SGA.

Comparison of SGA and Severe SGA rates using six size standards – Is there a difference?

BackgroundSmall for gestational age (SGA) neonates are known to be at an elevated risk for neonatal morbidity. Despite this, there is a growing array of proposed size standards for identifying SGA fetuses. Given the inherent differences in design, acquisition methods, and the characteristics of the populations they represent, the generalizability of these standards to diverse populations remains uncertain. IntroductionThis study aimed to assess variations in rates of SGA and severe SGA using six distinct size standards: Hadlock, Fetal Medicine Foundation (FMF), World Health Organization (WHO), Intergrowth-21 (IG-21), and two locally derived population-based size standards. The objective was to examine the differences in SGA and severe SGA rates among these size standards. MethodsA retrospective cohort study was conducted, encompassing all singleton deliveries in two tertiary referral hospital campuses with an annual birth count exceeding 10,000, from January 2019 to July 2022. SGA and severe SGA were defined as birthweights below the 10th or 3rd percentile, respectively, based on each growth standard. The study design included details on the setting, subjects (singleton deliveries), and the chosen size standards. Comparative analyses were performed to assess variations in SGA and severe SGA rates among these size standards. ResultsOur study analyzed 32,912 singleton deliveries. We found that the choice of growth standard significantly impacted the rates of both SGA and severe SGA infants. Notably, the WHO criteria identified 5,548 (16.9 %) fetuses as SGA, compared to only 1,716 (5.2 %) using the INTERGROWTH-21 standard (p < 0.001). Similarly, for severe SGA, the FMF charts classified 2098 (6.37 %) infants, significantly higher than the 320 (1 %) identified by Dolberg’s local population-based charts (p < 0.001). ConclusionOur study demonstrates a significant variety of SGA and severe SGA rates using different size standards. Therefore, the decision on the size standards in use is critical given the significant influence on clinical management. SynopsisThere are significant variations in SGA and Severe SGA rates depending on the chosen size standard.

Placental Element Content Assessed via Synchrotron-Based X-ray Fluorescence Microscopy Identifies Low Molybdenum Concentrations in Foetal Growth Restriction, Postdate Delivery and Stillbirth.

Placental health and foetal development are dependent upon element homeostasis. Analytical techniques such as mass spectroscopy can provide quantitative data on element concentrations in placental tissue but do not show spatial distribution or co-localisation of elements that may affect placental function. The present study used synchrotron-based X-ray fluorescence microscopy to elucidate element content and distribution in healthy and pathological placental tissue. The X-ray fluorescence microscopy (XFM) beamline at the Australian Synchrotron was used to image trace metal content of 19 placental sections from healthy term (n = 5, 37-39 weeks), foetal growth-restricted (n = 3, <32 weeks, birth weight <3rd centile), postdate (n = 7, >41 completed weeks), and stillbirth-complicated pregnancies (n = 4, 37-40 weeks). Samples were cryo-sectioned and freeze-dried. The concentration and distribution of fourteen elements were detected in all samples: arsenic, bromine, calcium, chlorine, copper, iron, molybdenum, phosphorous, potassium, rubidium, selenium, strontium, sulphur, and zinc. The elements zinc, calcium, phosphorous, and strontium were significantly increased in stillbirth placental tissue in comparison to healthy-term controls. Strontium, zinc, and calcium were found to co-localise in stillbirth tissue samples, and calcium and strontium concentrations were correlated in all placental groups. Molybdenum was significantly decreased in stillbirth, foetal growth-restricted, and postdate placental tissue in comparison to healthy-term samples (p < 0.0001). Synchrotron-based XFM reveals elemental distribution within biological samples such as the placenta, allowing for the co-localisation of metal deposits that may have a pathological role. Our pilot study further indicates low concentrations of placental molybdenum in pregnancies complicated by foetal growth restriction, postdate delivery, and stillbirth.

The current state of the problem, clinical-pathogenetic approaches to the diagnosis and management tactics of fetal growth restriction

Fetal growth restriction is a common complication of pregnancy with a complex etiology and limited possibilities of diagnosis and treatment. The relevance of this difficult obstetric problem is determined by various published diagnostic criteria, relatively low detection rates, and limited options for prevention and treatment.Fetal growth restriction is defined as the inability of the fetus to reach its genetically determined growth potential, most often due to abnormal placentation. Forms of fetal growth restriction with early or late onset are distinguished based on the gestational age determined during prenatal ultrasound diagnosis. According to most recommendations, the 32nd week of pregnancy is set as the cut-off point for distinguishing between early and late onset fetal growth restriction.The definition underlying this classification is based on differences between these two phenotypes of fetal growth restriction in severity, natural history, Doppler findings, association with hypertensive complications, placental features, and management. It is important to distinguish two separate conditions: fetal growth restriction and small-for-gestational fetus, which differ in short-term and long-term perinatal outcomes.A fetus is defined as small for gestational age if the estimated weight or weight of the fetus at birth is below the 10th percentile. Fetal growth restriction is diagnosed if the estimated fetal weight is below the 3rd percentile or a combination of pathological blood flow in the umbilical arteries and/or uterine arteries in fetuses with an estimated weight below the 10th percentile. It can also occur in fetuses and newborns with a body weight above the 10th percentile.The need to distinguish between fetal growth restriction and small-for-gestational-age fetus is related to the fact that fetal growth restriction is the main cause of stillbirth, neonatal death, higher perinatal morbidity, as well as increased risk of diseases in adulthood.The article analyzes the approaches to differentiating fetal growth restriction from small growth retardation in terms of fetal gestation period and further increasing the accuracy of diagnosis, as well as the modern concept of pathogenesis, with an emphasis on oxidant stress as a key molecular mechanism of adverse outcomes. Appropriate interventions during pregnancy to reduce perinatal complications should include antenatal monitoring and drug therapy.