Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Fetal Gestational Age Estimation Using Ultrasonic Transverse Cerebellar Diameter in a Sub-Saharan African Population.

Background: To explore the relationship between fetal Transverse Cerebellar Diameter (TCD) and menstrual gestational age (GA) and to generate normative references (nomogram) of the fetal TCD in some pregnant women in Southwest Nigeria. Methods: Four hundred pregnant women with a singleton fetus between 14 and 38 weeks GA were enrolled. The TCD and other biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) as well as the cerebellar appearance were analyzed and correlated with the GA. Results: The mean TCD increased from 13.3 ± 0.3 mm at 14 weeks to 52.3 ± 3.3 mm at 38 weeks of pregnancy. A strong positive correlation was observed between TCD and GA, which was best represented by a linear regression equation: Predicted GA = 0.557 × TCD + 8.840. The regression analysis indicated a statistically significant strong positive relationship between TCD and GA (r = 0.972 and P < 0.001). The cerebellar appearance based on shape and echogenicity was graded into Grade I: 230 fetuses (57.5%); Grade II: 74 fetuses (18.5%) and Grade III: 96 fetuses (24.0%). Median GA and TCD were 21 weeks and 21.2 mm for Grade I; 29 weeks and 35.5 mm for Grade II; and 35 weeks and 48.1 mm for Grade III, respectively. Conclusion: The TCD increased in a linear fashion with advancing GA in the evaluated fetuses. The TCD is, therefore, a good marker for GA estimation. There is a gradual ultrasonographic change in fetal cerebellar appearance with advancing gestation.

Correlation of gestational age and age at death in sudden infant death syndrome: another pointer to the role of critical developmental period?

BACKGROUND: Filiano and Kinney proposed a triple-risk model for the sudden infant death syndrome (SIDS) that involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The primary evidence for the role of a critical developmental period in SIDS etiology is the peak of cases around the third month of life. Independently, several studies pointed to correlation between gestational age and age at death in SIDS, but used that to assess the SIDS risk for preterm infants, ignoring further ramifications. METHODS: We did a detailed analysis of CDC data spanning over two decades (1983-2011). We focused not only on the correlation between two age variables (gestational and age at death), but also on the possibility of misdiagnosis. Also, we attempted to account for potential biases in the data induced by the ICD-9/ICD-190 transition or the "Back to Sleep" campaign. RESULTS: The peak of deaths in the third month of life, that was the main argument for the role of the critical development period, wasn't unique to SIDS. However, we confirmed an almost linear and negative correlation between gestational age and the week of death due to SIDS. This pattern (slope of correlation < 0 and significance of correlation p < 0.05) is characteristic of SIDS among all diseases analyzed in the study. CONCLUSIONS: We interpret the results as the evidence of the role of the critical development period in SIDS etiology. Possibly more attention in the future research should be put to theories that are based on homeostatic control.

Comparisons of the Rates of Large-for-Gestational-Age Newborns between Women with Diet-Controlled Gestational Diabetes Mellitus and Those with Non-Gestational Diabetes Mellitus.

(1) Objectives: The primary objective is to compare the rate of large-for-gestational-age (LGA) between women with diet-controlled gestational diabetes mellitus (GDM) and those with non-GDM, and to assess whether or not diet-controlled GDM is an independent factor of LGA fetuses. The secondary objectives are to compare the rates of other common adverse pregnancy outcomes, such as preeclampsia, cesarean section rate, preterm birth, and low Apgar score, between pregnancies with diet-controlled GDM and non-GDM pregnancies. (2) Methods: A retrospective cohort study was conducted on singleton pregnancies, diagnosed with GDM and non-GDM between 24 and 28 weeks of gestation, based on a two-step screening test. The prospective database of the obstetric department was accessed to retrieve the records meeting the inclusion criteria, and full medical records were comprehensively reviewed. The patients were categorized into two groups, GDM (study group) and non-GDM (control group). The main outcome was the rate of LGA newborns, and the secondary outcomes included pregnancy-induced hypertension, preterm birth, cesarean rate, low Apgar scores, etc. (3) Results: Of 1364 recruited women, 1342 met the inclusion criteria, including 1177 cases in the non-GDM group and 165 (12.3%) in the GDM group. Maternal age and pre-pregnancy BMI were significantly higher in the GDM group. The rates of LGA newborns, PIH, and cesarean section were significantly higher in the GDM group (15.1% vs. 7.1%, p-value < 0.001; 7.8% vs. 2.6%, p-value = 0.004; and 54.5% vs. 41.5%, p-value = 0.002; respectively). On logistic regression analysis, GDM was not significantly associated with LGA (odds ratio 1.64, 95% CI: 0.97-2.77), while BMI and gender were still significantly associated with LGA. Likewise, GDM was not significantly associated with the rate of PIH (odds ratio: 1.7, 95% CI: 0.825-3.504), while BMI and maternal age were significantly associated with PIH, after controlling confounding factors. (4) Conclusions: The rates of LGA newborns, PIH, and cesarean section are significantly higher in women with diet-controlled GDM than those with non-GDM. Nevertheless, the rates of LGA newborns and PIH are not directly caused by GDM but mainly caused high pre-pregnancy BMI and advanced maternal age, which are more commonly encountered among women with GDM.

Understanding changes in echocardiographic parameters at different ages following fetal growth restriction: a systematic review and meta-analysis.

Fetal growth restriction (FGR) increases cardiovascular risk by cardiac remodeling and programming. This systematic review and meta-analysis across species examines the use of echocardiography in FGR offspring at different ages. PubMed and Embase.com were searched for animal and human studies reporting on echocardiographic parameters in placental insufficiency-induced FGR offspring. We included 6 animal and 49 human studies. While unable to perform a meta-analysis of animal studies due to insufficient number of studies per individual outcome, all studies showed left ventricular dysfunction. Our meta-analyses of human studies revealed a reduced left ventricular mass, interventricular septum thickness, mitral annular peak velocity, and mitral lateral early diastolic velocity at neonatal age. No echocardiographic differences during childhood were observed, although the small age range and number of studies limited these analyses. Only two studies at adult age were performed. Meta-regression on other influential factors was not possible due to underreporting. The few studies on myocardial strain analysis showed small changes in global longitudinal strain in FGR offspring. The quality of the human studies was considered low and the risk of bias in animal studies mostly unclear. Echocardiographymay offer a non-invasive tool to detect early signs of cardiovascular predisposition following FGR. Clinical implementation yet faces multiple challenges including identification of the most optimal timing and the exact relation to long-term cardiovascular function in which echocardiography alone might be limited to reflect a child's vascular status. Future research should focus on myocardial strain analysis and the combination of other (non-)imaging techniques for an improved risk estimation.

Correlations of Aflatoxin Exposure from Cooking Oil and Dietary Foods During Pregnancy with Birth Weight and Gestational Age at Birth in Guangxi, China.

Background: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth. Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis. Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r ≈0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ -0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth. Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.

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OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.

Utilizing daily excessive concentration hours to estimate small for gestational age infants attributable to fine particulate matter in Wuhan, China.

Limited studies in China have explored the association between gravidae exposure to PM2.5 and small for gestational age infants (SGA), yielding inconsistent results. This study in Wuhan utilized daily excessive concentration hours (DECH) as a novel measure to assess PM2.5's impact on SGA. Data on air pollutants and pregnant women were collected from the Wuhan Municipal Ecology and Environmental Bureau and Wuhan Children's Hospital, respectively. Logistic regression models were employed to evaluate the contribution of PM2.5-DECH and PM2.5-mean to SGA. Significant correlations were observed between PM2.5-mean and SGA during the second trimester [OR = 1.23 (95% CI: 1.14-1.32)] and the entire pregnancy [OR = 1.15 (95% CI: 1.07-1.24)]. Similar correlations were found between PM2.5-DECH and SGA. These findings suggest that increased PM2.5 exposure is associated with a higher risk of SGA, and DECH may be used as a prospective substitute indicator for daily average concentration in similar studies.

Tuberculosis in pregnancy and adverse neonatal outcomes in two peruvian hospitals.

Background: According to the World Health Organization, tuberculosis (TB) ranks among the top 10 causes of death worldwide. The significance of TB during pregnancy lies in its symptoms, which can be mistaken for physiological changes associated with pregnancy. This confusion can lead to maternal-perinatal complications. Objective: To evaluate the association between pulmonary TB in pregnancy and adverse neonatal outcomes in two Peruvian hospitals. Methods: This is a retrospective cohort study. The target population consisted of pregnant women with and without pulmonary TB whose deliveries were attended at two public hospitals, located in Lima, Peru. The adverse neonatal outcomes were prematurity, low birth weight (LBW), and being small for gestational age (SGA). Crude and adjusted relative risks (RRa) were calculated with their respective 95% confidence intervals (95%CI). Results: Information from 212 patients was analyzed; 48.1% had TB during pregnancy, and 23.1% had adverse neonatal outcomes (8%, 11.3%, and 12.3% for LBW, prematurity, and SGA, respectively). In the adjusted model, pregnant women with pulmonary TB had a 3.52 times higher risk of having a newborn with at least one of the adverse outcomes than those who were not exposed (aRR, 3.52; 95%CI: 1.93-6.68). Conclusion: Pulmonary TB in pregnancy was jointly and independently associated with adverse neonatal outcomes, including LBW, prematurity, and being SGA.

Cerebral Palsy and Motor Impairment after Extreme Prematurity: Prediction of Diagnoses at Ages 2 and 10 Years.

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. METHODS: Participants of the ELGAN Study were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at one visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during NICU stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.

Appendicular Muscle Mass Index as the Most Important Determinant of Bone Mineral Content and Density in Small for Gestational Age Children.

Preterm small for gestational age (SGA) children are at increased risk for low bone mineral content later in life; however, data on SGA children born at term are scarce. We included 44 SGA and 57 adequate for gestational age (AGA) children aged 6 to 11 years to compare bone mineral density (BMD) and bone mineral content (BMC) and to identify which anthropometric and biochemical values influence bone mineralization in these children. Fat mass, appendicular skeletal muscle mass index (ASMMI), BMC, and BMD were significantly lower in SGA children than in AGA (P ≤ .005). Appendicular muscle mass index correlated with BMC(TBLH,FN,L1-L4) and BMD(TBLH,FN,L1-L4) in both groups (r2 = 0.7, P < .05). In multivariate analysis, ASMMI was strongly associated with BMC and BMD in both groups. There were no differences in clinical biomarkers, calcium intake, and physical activity between the groups. Achieving adequate muscle mass contributes to adequate bone mineralization and a lower risk for low BMC and BMD in SGA children.

Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

Comparative analysis of foetal and neonatal growth curves.

INTRODUCTION: Our aim was to determine which foetal or neonatal growth curves discriminate the probability of dying of newborns with low birth weight for their gestational age (small for gestational age, SGA) and sex (weight < 10th percentile) and to establish the curves that are presumably most useful for monitoring growth through age 10 years. MATERIAL AND METHODS: The analysis included every neonate (15 122) managed in our hospital (2013-2022) and all neonates born preterm before 32 weeks (6913) registered in the SEN1500 database (2019-2022). We considered most useful those curves with the highest likelihood ratio (LR) for dying with or without a history of SGA in each subgroup of gestational ages. Theoretically, the optimal curves for monitoring growth would be those with a higher R2 in the quantile regression formulas for the 50th percentile. RESULTS: The growth curves exhibiting the strongest association between SGA and hospital mortality are the Intergrowth fetal curves and the Fenton neonatal curves in infants born preterm before 32 weeks. However, the optimal curves for premature babies and neonates overall were those of Olsen and Intergrowth. The most useful curves to monitor anthropometric values alone until age 10 years of age are the longitudinal Intergrowth curves followed by the WHO standards, but if a single reference is desired from birth through age 10 years, the best option is the Fenton curves followed by the WHO standards. CONCLUSIONS: The Intergrowth reference provides the most discriminating foetal growth curves. In neonatal clinical practice, the optimal references are the Fenton followed by the WHO charts.

The accuracy of sonographic fetal weight in very preterm infants (≤32 weeks).

OBJECTIVE: To examine the accuracy of sonographic fetal weight to predict birthweight in very preterm infants (<32 weeks), and to compare the accuracy of estimated fetal weight (EFW) between those small for gestational age (SGA) and those appropriate for gestational age (AGA). STUDY DESIGN: A retrospective study was conducted of data recorded between January 2010 and March 2023. Included were women with singleton livebirths at 23+0-31+6 weeks who had an EFW within one week from delivery. Mean percentage error, mean absolute percentage error, and underestimation and overestimation rates were calculated. We compared the accuracy of EFW between SGA and AGA infants. RESULTS: In total, 360 women were included. The mean absolute percentage error was 7.8 % (range 0 %-68.9 %); for 207 (57.5 %) infants the percentage error was within ±10 %. Overestimation error >10 % was observed in 102 (28.3 %) infants and errors >20 % in 34 (9.4 %). Among infants born in the periviable period (23+0 - 25+6 weeks; N = 56), the mean absolute percentage error was 9.8 % (range: 0 %-40.3 %); the value was within ±10 % for only 28 periviable infants (50 %) and exceeded 20 % for 16.1 %. Among SGA compared to AGA infants, the mean absolute percentage error was higher (11.1% vs. 6.6 %, p = 0.035). Overestimation error >10 % was more frequent among SGA than AGA infants (55 (49.1 %) vs. 47 (19.0 %), p < 0.001). In a multivariate logistic regression analysis, SGA status was independently associated with a higher mean percentage error (beta = 0.260, p < 0.001) and an increased risk of an error >10 % (odds ratio = 2.1, 95 % confidence interval 1.2-3.5, p = 0.008). CONCLUSIONS: Sonographic EFW is limited in assessing very preterm infants, particularly those who are SGA or born during the periviable period. These limitations should be considered regarding impending very preterm births and concerns about abnormal fetal growth.

Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden.

AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.

Birthweight trends and their explanatory factors in Hungary between 1999 and 2018: an analysis of the Hungarian Tauffer registry.

BACKGROUND: The increasing birthweight trend stopped and even reversed in several high income countries in the last 20 years, however the reason for these changes is not well characterized. We aimed to describe birthweight trends of term deliveries in Hungary between 1999 and 2018 and to investigate potential maternal and foetal variables that could drive these changes. METHODS: We analysed data from the Hungarian Tauffer registry, a compulsory anonymized data collection of each delivery. We included all singleton term deliveries in 1999-2018 (n = 1,591,932). We modelled birthweight trends separately in 1999-2008 and 2008-2018 in hierarchical multiple linear regression models adjusted for calendar year, newborn sex, maternal age, gestational age at delivery, and other important determinants. RESULTS: Median birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g in 2018. When we adjusted for gestational age at delivery the increase in the first period became more pronounced (5.4 g/year). During the second period, similar adjustment substantially decreased the rate of decline from 2.5 to 1.4 g/year. Further adjustment for maternal age halved the rate of increase to 2.4 g/year in the first period. During the second period, adjustment for maternal age had little effect on the estimate. CONCLUSIONS: Our findings of an increasing birthweight trend (mostly related to the aging of the mothers) in 1999-2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, the long-term effect cannot be predicted, as the trend is mostly explained by the shorter pregnancies.

Birthweights showed an increase followed by a decrease in several high income countries in the last 20 years, however the reasons for these changes is not well described. Thus, we aimed to investigate birthweight trends and their potential explanatory factors in Hungary between 1999 and 2018. We used registry data of all deliveries from Hungary in 1999­2018 (n = 1 591 932). Birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g until 2018. Maternal age explained approximately half of increase in the first period, while a substantial part of the decrease in the second period was explained by the presence of shorter pregnancies. The increasing birthweights in 1999­2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, its long-term consequences cannot be predicted, as the trend is mostly explained by the shorter pregnancies.

Gestational weight gain and pregnancy outcomes in Chinese women with type 2 diabetes mellitus: evidence from a tertiary hospital in Beijing.

Objective: To examine the effects of gestational weight gain on pregnancy outcomes and determine the optimal range of weight gain during pregnancy for Chinese women with type 2 diabetes mellitus. Methods: This retrospective cohort study included 691 Chinese women with type 2 diabetes mellitus from 2012 to 2020. The study utilized a statistical-based approach to determine the optimal range of gestational weight gain. Additionally, multivariate logistic regression analysis was conducted to assess the impact of gestational weight gain on pregnancy outcomes. Results: (1) In the obese subgroup, gestational weight gain below the recommendations was associated with decreased risks of large for gestational age (adjusted odds ratio [aOR] 0.19; 95% confidence interval [CI] 0.06-0.60) and macrosomia (aOR 0.18; 95% CI 0.05-0.69). In the normal weight subgroup, gestational weight gain below the recommendations of the Institute of Medicine was associated with decreased risks of preeclampsia (aOR 0.18; 95% CI 0.04-0.82) and neonatal hypoglycemia (aOR 0.38; 95% CI 0.15-0.97). (2) In the normal weight subgroup, gestational weight gain above the recommendations of the Institute of Medicine was associated with an increased risk of large for gestational age (aOR 4.56; 95% CI 1.54-13.46). In the obese subgroup, gestational weight gain above the recommendations was associated with an increased risk of preeclampsia (aOR 2.74; 95% CI 1.02, 7.38). (3) The optimal ranges of gestational weight gain, based on our study, were 9-16 kg for underweight women, 9.5-14 kg for normal weight women, 6.5-12 kg for overweight women, and 3-10 kg for obese women. (4) Using the optimal range of gestational weight gain identified in our study seemed to provide better prediction of adverse pregnancy outcomes. Conclusion: For Chinese women with type 2 diabetes, inappropriate gestational weight gain is associated with adverse pregnancy outcomes, and the optimal range of gestational weight gain may differ from the Institute of Medicine recommendations.

Application of 4 birthweight curves and local reference range at a University Hospital of Rio de Janeiro, Brazil.

BACKGROUND: Numerous fetal growth curves have been developed from various subpopulations and geographic locations worldwide. OBJECTIVE: To determine the birthweight standard at the Maternity School and compare it to currently used standards in the clinical practice services. STUDY DESIGN: Cross-sectional, observational, and descriptive study. Data from infants born between 2011 and 2016 were collected from the Maternity School Hospital of the Federal University of Rio de Janeiro to define the 10th, 25th, 50th, 75th, and 90th percentiles of the birthweight by gestational age. It was determined the performance of the INTERGROWTH-21st, Fenton, Alexander, and Lubchenco for the Maternity School standards. RESULTS: After the 33rd week of pregnancy, the INTERGROWTH standard was similar to the local standard for small-for-gestational-age infants and Fenton for large-for-gestational-age infants at Maternity School Hospital. The INTERGROWTH standard was found to be inadequate to classify small-for-gestational-age infants, which are babies at major risk for morbidity and mortality at the onset of the 33rd week of pregnancy. CONCLUSION: It was possible to define reference values for birthweight for the maternal school hospital considering at least 33 weeks of pregnancy with a 95% confidence interval. The comparison of the INTERGROWTH, Fenton, Alexander, and Lubchenko standards to the maternal school hospital curve showed that the Fenton curve was the most suitable for the diagnosis of small for gestational age.

Is Necrotizing Enterocolitis and Spontaneous Intestinal Perforation Part of Same Disease Spectrum - New Insights?

The diagnosis of NEC is based on the presence of pneumatosis, dilated bowel loops, portal venous gas, or pneumoperitoneum on the abdominal x-ray. Published studies suggest that the appearance of pneumatosis most likely depends on the gestational age, with a shift occurring between 27-28 weeks. For infants of gestational age under 27 weeks, pneumoperitoneum is the most likely presentation of bowel injury due to the thin bowel wall and the colonization of the gut with the non-gas-producing bacteria. Assessment of postoperative morbidity and white matter injury on the brain MRI at term equivalent age in a cohort of preterm infants failed to identify differences between SIP and NEC groups when confirmed by histology. These findings illustrate the difficulty in conclusively identifying cases as SIP or NEC, particularly when gestational age is considered and raise speculation that both conditions lie on the same spectrum of intestinal injury.